Kerksick et al. Journal of the International Society of Sports Nutrition (2018) 15:38
https://doi.org/10.1186/s12970-018-0242-y

REVIEW

Open Access

ISSN exercise & sports nutrition review
update: research & recommendations
Chad M. Kerksick1* , Colin D. Wilborn2, Michael D. Roberts3, Abbie Smith-Ryan4, Susan M. Kleiner5, Ralf Jäger6,
Rick Collins7, Mathew Cooke8, Jaci N. Davis2, Elfego Galvan9, Mike Greenwood10, Lonnie M. Lowery11,
Robert Wildman12, Jose Antonio13 and Richard B. Kreider10*

Abstract
Background: Sports nutrition is a constantly evolving field with hundreds of research papers published annually. In
the year 2017 alone, 2082 articles were published under the key words ‘sport nutrition’. Consequently, staying current
with the relevant literature is often difficult.
Methods: This paper is an ongoing update of the sports nutrition review article originally published as the lead paper
to launch the Journal of the International Society of Sports Nutrition in 2004 and updated in 2010. It presents a wellreferenced overview of the current state of the science related to optimization of training and performanceenhancement through exercise training and nutrition. Notably, due to the accelerated pace and size at which
the literature base in this research area grows, the topics discussed will focus on muscle hypertrophy andperformance enhancement. As such, this paper provides an overview of: 1.) How ergogenic aids and dietary
supplements are defined in terms of governmental regulation and oversight; 2.) How dietary supplements arelegally regulated in the United States; 3.) How to evaluate the scientific merit of nutritional supplements; 4.)General nutritional strategies to optimize performance and enhance recovery; and, 5.) An overview of our current
understanding of nutritional approaches to augment skeletal muscle hypertrophy and the potential ergogenic value ofvarious dietary and supplemental approaches.
Conclusions: This updated review is to provide ISSN members and individuals interested in sports nutrition
with information that can be implemented in educational, research or practical settings and serve as a foundational
basis for determining the efficacy and safety of many common sport nutrition products and their ingredients.
Keywords: Sports nutrition, Performance nutrition, Position stand, Review, Recommendations, Efficacy, Double-blind,
Randomized, Placebo-controlled, Dietary supplements, Ergogenic aids, Weight gain, Hypertrophy, Strength, Capacity,
Power

Background
Evaluating the scientific merit of articles and advertisements about exercise and nutrition products is a key
skill that all sports nutrition professionals must possess.
To assist members and other advocates of theInternational Society of Sports Nutrition (ISSN) in
keeping up to date about the latest findings in sports
nutrition, the ISSN Exercise & Sports Nutrition* Correspondence: ckerksick@lindenwood.edu; rbkreider@tamu.edu
1
Exercise and Performance Nutrition Laboratory, School of Health Sciences,
Lindenwood University, St. Charles, MO, USA
10
Exercise & Sports Nutrition Lab, Human Clinical Research Facility, Texas
A&M University, College Station, TX, USA
Full list of author information is available at the end of the article

Review: Research & Recommendations has been updated. The initial version of this paper was the firstpublication used to help launch the Journal of theInternational Society of Sports Nutrition (JISSN, originally called the Sports Nutrition Review Journal).
This paper provides a definition of ergogenic aids
and dietary supplements and discusses how dietary
supplements are legally regulated. Other sections
highlight how to evaluate the scientific merit of nutritional supplements and provide general nutritional
strategies to optimize performance and enhance recovery. Finally, a brief overview of the efficacy surrounding many supplements commonly touted to© The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, andreproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Kerksick et al. Journal of the International Society of Sports Nutrition (2018) 15:38

promote skeletal muscle hypertrophy and improve physical performance is provided. Based upon the available scientific literature testing the efficacy and safety of thenutritional supplements discussed herein, all nutritional
supplements discussed in this paper have been placed into
three categories based upon the quality and quantity ofscientific support available:A) Strong Evidence to Support Efficacy and Apparently
SafeB) Limited or Mixed Evidence to Support Efficacy
C) Little to No Evidence to Support Efficacy and/or
SafetySince the last published version of this document in2010 [1], the general approach to categorization has notchanged, but several new supplements have been introduced to the market and are subsequently reviewed inthis article. In this respect, many supplements have had
additional studies published that has led to some supplements being placed into a different category or removed
from the review altogether. We understand and expectthat some individuals may not agree with our interpretations of the literature or what category we have assigned
a particular supplement, but it is important to appreciatethat some classifications may change over time as more
research becomes available.
Definition of an ergogenic aid

An ergogenic aid is any training technique, mechanicaldevice, nutritional ingredient or practice, pharmacologicalmethod, or psychological technique that can improve
exercise performance capacity or enhance training adaptations [2–4]. Ergogenic aids may help prepare an individual
to exercise, improve exercise efficiency, enhance recovery
from exercise, or assist in injury prevention during intense
training. Although this definition seems rather straightforward, there is considerable debate regarding the ergogenic
value of various nutritional supplements. A consensus
exists to suggest that a nutritional supplement is ergogenic
if peer-reviewed studies demonstrate the supplement
significantly enhances exercise performance following
weeks to months of ingestion (e.g., promotes increases inmaximal strength, running speed, and/or work during agiven exercise task). On the other hand, a supplement
may also have ergogenic value if it acutely enhances theability of an athlete to perform an exercise task orenhances recovery from a single exercise bout. The ISSN
has adopted a broader view regarding the ergogenic valueof supplements. While the muscle building and performance enhancing effects of a supplement on a single boutof exercise may lead to eventual ergogenic effects or optimized training adaptations, our view is that such evidence
does not warrant “Excellent Evidence to Support Efficacy”

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if there is a lack of long-term efficacy data. Herein, we haveadopted the view that a supplement is clearly ergogenic if
most of human studies support the ingredient as being
effective in promoting further increases in muscle hypertrophy or performance with exercise training. Conversely,
supplements that fall short of this standard and are only
supported by preclinical data (e.g., cell culture or rodent
studies) are grouped into other categories.

Definition and regulation of dietary supplements
The Dietary Supplement Health and Education Act (DSHEA)
and the safety of dietary supplements

Congress passed the Dietary Supplement Health and Education Act of 1994 (DSHEA), placing dietary supplements
in a special category of “foods”. In October 1994, President
Clinton signed DSHEA into law. This statute was enacted
amid claims that the Food and Drug Administration (FDA)
was distorting the then-existing provisions of the Food,
Drug, and Cosmetic Act (FDCA) to improperly deprive thepublic of safe and popular dietary supplement products.
The law defines a “dietary supplement” as a product thatis intended to supplement the diet and contains a “dietary
ingredient”. By definition, “dietary ingredients” in theseproducts may include vitamins, minerals, herbs or otherbotanicals, amino acids, and substances such as enzymes,organ tissues, and glandular extracts. Further, dietary ingredients may also include extracts, metabolites, or concentrates of those substances. Dietary supplements may befound in many forms such as tablets, capsules, softgels, gelcaps, liquids, or powders, but may only be intended for oral
ingestion. Dietary supplements cannot be marketed or promoted for sublingual, intranasal, transdermal, injected, orin any other route of administration except oral ingestion.
A supplement can be in other forms, such as a bar, as longas the information on its label does not represent the product as a conventional food or a sole item of a meal or diet.
Indeed, DSHEA clearly defines “dietary supplements”
and “dietary ingredients,” it sets certain criteria for “newdietary ingredients,” and the law prevents the FDA fromoverreaching. Additionally, and contrary to widespread
opinion, DSHEA did not leave the industry unregulated.
The dietary supplement industry is in fact regulated by
the FDA as a result of DSHEA. The law ensures the authority of the FDA to provide legitimate protections forthe public health. The Federal Trade Commission (FTC)also continues to have jurisdiction over the marketingclaims that dietary supplement manufacturers or companies make about their products. The FDA and FTC operate
in a cooperative fashion to regulate the dietary supplement industry. In this respect, the extent to which information is shared and jurisdiction between these twoentities overlaps with regard to marketing and advertisingdietary supplements continues to increase.

Kerksick et al. Journal of the International Society of Sports Nutrition (2018) 15:38

In the United States, dietary supplements are classified
as food products, not drugs, and there is generally no
mandate to register products with the FDA or obtain FDA
approval before producing or selling supplements to consumers. However, if a dietary supplement manufacturer ismaking a claim about their product, the company must
submit the claims to FDA within 30 days of marketing the
product. Compare this, for example, with Canada where
under the Natural Health Product (NHP) Regulations
enacted in 2004 supplements must be reviewed, approved,
and registered with Health Canada. The rationale for the
U.S. model is based on a presumed long history of safe use;
hence there is no need to require additional safety data.
DSHEA also requires supplement marketers to include
on any label displaying structure/function claims (i.e.,
claims that the product affects the structure or function of
the body) the mandatory FDA disclaimer “This statement
has not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure,or prevent any disease.” Opponents of dietary supplements
often cite this statement as evidence that the FDA does
not review or approve dietary supplements. However, most
dietary ingredients have been “grandfathered in” as
DSHEA-compliant ingredients due to a long history of safe
use, and those products containing new ingredients mustbe submitted by a notification to the FDA for a safety review prior to being brought to market. Although many
dietary ingredients have been introduced into dietary supplements since October 1994 and have not been submitted
to the FDA for a safety review, nutritional supplementation
writ large is generally safe. In this regard, while there areover 50,000 dietary supplements registered with the Officeof Dietary Supplement’s “Dietary Supplement Label Database”, a 2013 Annual Report (released in 2015) of theAmerican Association of Poison Control Centers revealed
zero fatalities occurred due to dietary supplements
compared to 1692 deaths due to drugs [5]. Perhaps morealarming is a 2015 report by the Centers for Disease
Control suggesting 2,287,273 emergency room visits were
due to prescription drug-related events which dwarfs the3266 emergency room visits due to dietary supplements(adjusted from 23,000 visits after excluding cases of older
adults choking on pills, allergic reactions, unsupervisedchildren consuming too many vitamins, and persons consuming ingredients not defined by DSHEA as a dietary
supplement) [5]. Furthermore, a recent Healthcare Costand Utilization Project Statistical Brief by Lucado et al. [6]reported approximately one in six Americans sufferedfrom food borne illnesses in 2010, and food borne illnesses
were associated with over 3.7 million treat-and-release
emergency department visits, 1.3 million inpatient hospital
stays, and 3000 deaths. Notwithstanding, there have beencase reports of liver and kidney toxicity potentially causedby supplements containing herbal extracts [7] as well as

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overdoses associated with pure caffeine anhydrous ingestion [8]. Collectively, the aforementioned statistics and casereports demonstrate that while generally safe, as with foodor prescription drug consumption, dietary supplement
consumption can lead to adverse events in spite of DSHEA
and current FDA regulations described below.
New dietary ingredients

Recognizing that new and untested dietary supplement
products may pose unknown health issues, DSHEA distinguishes between products containing dietary ingredientsthat were already on the market and products containing
new dietary ingredients that were not marketed prior to
the enactment of the law. A “new dietary ingredient”(NDI) is defined as a dietary ingredient that was not marketed in the United States before October 15, 1994.
DSHEA grants the FDA greater control over supplements
containing NDIs. A product containing an NDI is deemed
adulterated and subject to FDA enforcement sanctions unless it meets one of two exemption criteria: either (1) the
supplement in question contains “only dietary ingredients
which have been present in the food supply as an article
used for food in a form in which the food has not beenchemically altered”; or (2) there is a “history of use or otherevidence of safety” provided by the manufacturer or distributor to the FDA at least 75 days before introducing the
product into interstate commerce. The first criterion is silent as to how and by whom presence in the food supply
as food articles without chemical alteration is to be established. The second criterion—applicable only to new dietary ingredients that have not been present in the foodsupply—requires manufacturers and distributors of the
product to take certain actions. Those actions include submitting, at least 75 days before the product is introduced
into interstate commerce, information that is the basis onwhich a product containing the new dietary ingredient is“reasonably expected to be safe.” That information would
include: (1) the name of the new dietary ingredient and, if
it is an herb or botanical, the Latin binomial name; (2) adescription of the dietary supplement that contains the
new dietary ingredient, including (a) the level of the new
dietary ingredient in the product, (b) conditions of use of
the product stated in the labeling, or if no conditions ofuse are stated, the ordinary conditions of use, and (c) ahistory of use or other evidence of safety establishing thatthe dietary ingredient, when used under the conditions
recommended or suggested in the labeling of the dietary
supplement, is reasonably expected to be safe.
In July 2011, the FDA released a Draft Guidance forIndustry, entitled “Dietary Supplements: New Dietary
Ingredient Notifications and Related Issues.” While a
guidance does not carry the authority or the enforceability of a law or regulation, the FDA’s NDI draft guidance
represented the agency’s current thinking on the topic.

Kerksick et al. Journal of the International Society of Sports Nutrition (2018) 15:38

The guidance prompted great controversy, and FDA
agreed to issue a revised draft guidance to address someof the issues raised by industry. In August 2016, FDA released a revised Draft Guidance that replaced the 2011
Draft Guidance. The purpose of the 2016 Draft Guidance was to help manufacturers and distributors decide
whether to submit a premarket safety notification to
FDA, help prepare NDI notifications in a manner thatallows FDA to review and respond more efficiently andquickly, and to improve the quality of NDI notifications.
The 2016 Draft Guidance has been criticized by industry
and trade associations for its lack of clarity and otherproblems. Some of these issues include the lack of clarity
regarding Pre-DSHEA, (Grandfathered), ingredients and
FDA requiring an NDI notification even if anothermanufacturer has submitted a notification.
The lack of clarity surrounding the “new” Draft Guidance has led to many NDI notifications being rejected by
FDA for lack of safety data and other issues. Other companies have opted to utilize the “Self-Affirmed Generally
Recognized as Safe (GRAS)” route in order to “bypass” theNDI notification process. Self-Affirmed GRAS is when acompany has a team of scientific experts evaluate the safetyof their ingredient. There is no requirement that the safety
dossier be submitted to FDA but is used by the company
as an internal document that may be relied upon if theingredient is challenged by the FDA. FDA has expressed
its concern with this practice and does not encourage dietary supplement manufacturers to use Self-Affirmed GRAS
to avoid submitting NDI notifications. In any event, thelikelihood of another revised Draft Guidance from FDA
becoming available in the future is high, and possibly more
enforcement actions taken against companies that market
an NDI without submitting a notification.
Adverse event reporting

In response to growing criticism of the dietary supplement
industry, the 109th Congress passed the first mandatory
Adverse Event Reporting (AER) legislation for the dietary
supplement industry. In December 2006, President Bushsigned into law the Dietary Supplement and Nonprescription Drug Consumer Protection Act, which took effect on
December 22, 2007. After much debate in Congress andinput from the FDA, the American Medical Association(AMA), many of the major supplement trade associations,and a host of others all agreed that the legislation was necessary and the final version was approved by all. In short,the Act requires that all “serious adverse events” regarding
dietary supplements be reported to the Secretary of Healthand Human Services. The law strengthens the regulatory
structure for dietary supplements and builds greater consumer confidence, as consumers have a right to expectthat if they report a serious adverse event to a dietary
supplement marketer the FDA will be advised about it.

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An adverse event is any health-related event associatedwith the use of a dietary supplement that is adverse. A
serious adverse event is an adverse event that (A) results in(i) death, (ii) a life-threatening experience, (iii) inpatient
hospitalization, (iv) a persistent or significant disability or
incapacity, or (v) a congenital anomaly or birth defect; or(B) requires, based on reasonable medical judgment, a
medical or surgical intervention to prevent an outcome
described under subparagraph (A). Once it is determinedthat a serious adverse event has occurred, the manufacturer, packer, or distributor (responsible person) of a dietary
supplement whose name appears on the label of the
supplement shall submit to the Secretary of Health andHuman Services any report received of the serious adverse
event accompanied by a copy of the label on or within theretail packaging of the dietary supplement. The responsible
person has 15 business days to submit the report to FDA
after being notified of the serious adverse event. Following
the initial report, the responsible person must submit
follow-up reports of new medical information that theyreceive for one-year.

Adulterated supplements

The FDA has various options to protect consumers fromunsafe supplements. The Secretary of the Department of
Health and Human Services (which falls under FDA oversight) has the power to declare a dangerous supplement tobe an “imminent hazard” to public health or safety and
immediately suspend sales of the product. The FDA also
has the authority to protect consumers from dietary
supplements that do not present an imminent hazard to
the public but do present certain risks of illness or injury
to consumers. The law prohibits introducing adulterated
products into interstate commerce. A supplement shall bedeemed adulterated if it presents “a significant or unreasonable risk of illness or injury”. The standard does not
require proof that consumers have actually been harmed
or even that a product will harm anyone. It was under thisprovision that the FDA concluded that dietary supplements
containing ephedra, androstenedione, and DMAA presented an unreasonable risk. Most recently, FDA imposed
an importation ban on the botanical Mitragyna speciose,better known as Kratom. In 2016, FDA issued Import Alert#54–15, which allows for detention without physical examination of dietary supplements and bulk dietary ingredientsthat are, or contain, Kratom. Criminal penalties are present
for a conviction of introducing adulterated supplement
products into interstate commerce. While the harms associated with dietary supplements may pale in comparison to
those linked to prescription drugs, recent pronouncementsfrom the U.S. Department of Justice confirm that the
supplement industry is being watched vigilantly to protect
the health and safety of the American public.

Kerksick et al. Journal of the International Society of Sports Nutrition (2018) 15:38

Good manufacturing practices

When DSHEA was passed in 1994, it contained aprovision requiring that the FDA establish and enforce
current Good Manufacturing Practices (cGMPs) for dietary supplements. However, it was not until 2007 that thecGMPs were finally approved, and not until 2010 that thecGMPs applied across the industry, to large and small
companies alike. The adherence to cGMPs has helped
protect against contamination issues and should serve toimprove consumer confidence in dietary supplements.
The market improved as companies became compliant
with cGMPs, as these regulations imposed more stringent
requirements such as Vendor Certification, Document
Control Procedures, and Identity Testing. These compliance criteria addressed the problems that had damaged
the reputation of the industry with a focus on quality control, record keeping, and documentation.
However, it does appear that some within the industry
continue to struggle with compliance. In Fiscal Year 2017,it was reported that approximately 23.48% of the FDA’s
656 total cGMP inspections resulted in citations for failingto establish specifications for the identity, purity, strength,
and composition of dietary supplements. Further, 18.47%
of those inspected were cited for failing to establish and/or follow written procedures for quality control operations. Undoubtedly, relying on certificates of analysis fromthe raw materials supplier without further testing, or failing to conduct identity testing of a finished product, canresult in the creation of a product that contains something
it should not contain such as synthetic chemicals or evenpharmaceutical drugs. All members of the industry needto ensure compliance with cGMPs.
Marketing claims

According to the 1990 Nutrition Labeling and Education
Act (NLEA), the FDA can review and approve healthclaims (claims describing the relationship between a foodsubstance and a reduced risk of a disease or health-related
condition) for dietary ingredients and foods. However,since the law was passed it has only approved a few claims.
The delay in reviewing health claims of dietary supplement
ingredients resulted in a lawsuit, Pearson v. Shalala, filed
in 1995. After years of litigation, in 1999 the U.S. Court ofAppeals for the District of Columbia Circuit ruled that
qualified health claims may be made about dietary supplements with approval by FDA, as long as the statements aretruthful and based on adequate science. Supplement or
food companies wishing to make health claims or qualified
health claims about supplements can submit research
evidence to the FDA for review.
The FTC also regulates the supplement industry. Unsubstantiated claims invite enforcement by the FTC (alongwith the FDA, state district attorney offices, groups likethe Better Business Bureau, and plaintiff’s lawyers who file

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class action lawsuits). The FTC has typically applied a substantiation standard of “competent and reliable scientificevidence” to claims about the benefits and safety of dietary
supplements. FTC case law defines “competent and reliable
scientific evidence” as “tests, analyses, research, studies, orother evidence based on the expertise of professionals in
the relevant area, that has been conducted and evaluatedin an objective manner by persons qualified to do so, using
procedures generally accepted in the profession to yieldaccurate and reliable results.” The FTC has claimed that
this involves providing at least two clinical trials showing
efficacy of the actual product, within a population ofsubjects relevant to the target market, supporting thestructure/function claims that are made. While the exact
requirements are still evolving, the FTC has acted against
several supplement companies for misleading advertisements and/or structure/function claims.
A safer industry ahead

As demonstrated, while some argue that the dietary
supplement industry is “unregulated” and/or may havesuggestions for additional regulation, manufacturers anddistributors of dietary supplements must adhere to several
federal regulations before a product can go to market. Further, before marketing products, they must have evidence
that their supplements are generally safe to meet all therequirements of DSHEA and FDA regulations. For thisreason, over the last 20 years, many established supplement companies have employed research and development directors who help educate the public about
nutrition and exercise, provide input on product development, conduct preliminary research on products, and/or
assist in coordinating research trials conducted by independent research teams (e.g., university-based researchers
or clinical research sites). These companies also consult
with marketing and legal teams with the responsibility toensure structure/function claims do not misrepresent results of research findings. This has increased job opportunities for sports nutrition specialists as well as enhanced
external funding opportunities for research groups interested in exercise and nutrition research.
While some companies have falsely attributed researchon different dietary ingredients or dietary supplements totheir own products, suppressed negative research findings,
and/or exaggerated results from research studies, thetrend in the sports nutrition industry has been to developscientifically sound supplements. This trend toward
greater research support is the result of: (1) attempts tohonestly and accurately inform the public about results;(2) efforts to obtain data to support safety and efficacy on
products for the FDA and the FTC; and/or, (3) endeavors
to provide scientific evidence to support advertising claims
and increase sales. While the push for more research isdue in part to greater scrutiny from the FDA and FTC, itKerksick et al. Journal of the International Society of Sports Nutrition (2018) 15:38

is also in response to an increasingly competitive marketplace where established safety and efficacy attracts moreconsumer loyalty and helps ensure a longer lifespan forthe product in commerce. Companies that adhere to these
ethical standards tend to prosper while those that do notwill typically struggle to comply with FDA and FTC guidelines resulting in a loss of consumer confidence and an
early demise for the product.
Product development and quality assurance

A common question posed by athletes, parents, and professionals surrounding dietary supplements relates to how
they are manufactured and perceived supplement quality.
In several cases, established companies who develop dietary
supplements have research teams who scour the medical
and scientific literature looking for potentially effective
nutrients. These research teams often attend scientificmeetings and review the latest patents, research abstracts
presented at scientific meetings, and research publications.
Leading companies invest in basic research on nutrients
before developing their supplement formulations and often
consult with leading researchers to discuss ideas about dietary supplements and their potential for commercialization.
Other companies wait until research has been presented inpatents, research abstracts, or publications before developing nutritional formulations featuring the nutrient. Upon
identification of new nutrients or potential formulations,the next step is to contact raw ingredient suppliers to see if
the nutrient is available, if it is affordable, how much of it
can be sourced and what is the available purity. Sometimes,
companies develop and pursue patents involving new processing and purification processes because the nutrient has
not yet been extracted in a pure form or is not available inlarge quantities. Reputable raw material manufacturers
conduct extensive tests to examine purity of their raw ingredients. When working on a new ingredient, companies
often conduct series of toxicity studies on the new nutrient
once a purified source has been identified. The company
would then compile a safety dossier and communicate it to
the FDA as a New Dietary Ingredient submission, with thehopes of it being allowed for lawful sale.
When a powdered formulation is designed, the list of ingredients and raw materials are typically sent to a flavoringhouse and packaging company to identify the best way toflavor and package the supplement. In the nutrition industry, several main flavoring houses and packaging companies
exist who make many dietary supplements for supplementcompanies. Most reputable dietary supplement manufacturers submit their production facilities to inspection fromthe FDA and adhere to GMP, which represent industry
standards for good manufacturing of dietary supplements.
Some companies also submit their products for independent testing by third-party companies to certify that theirproducts meet label claims and that the product is free ofPage 6 of 57

various banned ingredients. For example, the certification
service offered by NSF International includes product testing, GMP inspections, ongoing monitoring and use of the
NSF Mark indicating products comply with inspection
standards, and screening for contaminants. More recently,
companies have subjected their products for testing by
third party companies to inspect for banned or unwanted
substances. These types of tests help ensure that the dietary
supplement made available to athletes do not contained
substances banned by the International Olympic Committee or other athletic governing bodies (e.g., NFL, NCAA,MLB, NHL, etc.). While third-party testing does not guarantee that a supplement is void of banned substances, thelikelihood is reduced (e.g., Banned Substances Control
Group, Informed Choice, NSF, etc.). Moreover, consumers
can request copies of results of these tests and each product that has gone through testing and earned certification
can be researched online to help athletes, coaches and support staff understand which products should be considered. In many situations, companies who are not willing toprovide copies of test results or certificates of analysis
should be viewed with caution, particularly for individuals
whose eligibility to participate might be compromised if atainted product is consumed.
Evaluation of nutrition ergogenic aids

The ISSN recommends that potential consumers undertake a systematic process of evaluating the validity and scientific merit of claims made when assessing the ergogenic
value of a dietary supplement [1, 4]. This can be accomplished by examining the theoretical rationale behind the
supplement and determining whether there is any wellcontrolled data showing the supplement is effective. Supplements based on sound scientific rationale with direct,
supportive research showing effectiveness may be worth
trying or recommending. However, those based on unsound scientific results or offer little to no data supporting
the ergogenic value of the actual supplement/technique
may not be worthwhile. Sports nutrition specialists should
be a resource to help their clients interpret the scientificand medical research that may impact their welfare andhelp them train more effectively. The following are recommended questions to ask when evaluating the potential
ergogenic value of a supplement.
Does the theory make sense?

Most supplements that have been marketed to improvehealth or exercise performance are based on theoreticalapplications derived from basic science or clinical researchstudies. Based on these preliminary studies, a dietary
approach or supplement is often marketed to people
proclaiming the benefits observed in these basic researchstudies. Although the theory may appear relevant, criticalanalysis of this process often reveals flaws in the scientificKerksick et al. Journal of the International Society of Sports Nutrition (2018) 15:38

logic or that the claims made do not quite match up withthe cited literature. By evaluating the literature one candiscern whether or not a dietary approach or supplement
has been based on sound scientific evidence. To do so, one
is recommended to first read reviews about the training
method, nutrient, or supplement from researchers who
have been intimately involved in the available research andconsult reliable references about nutritional and herbal
supplements [1, 9]. To aid in this endeavour, the ISSN has
published position statement on topics related to creatine[10], protein [11], beta-alanine [12], nutrient timing [13],caffeine [14], HMB [15], meal frequency [16], energy drinks[17], and diets and body composition [18]. Each of these
documents would be excellent resources for any of these
topics. In addition, other review articles and consensus
statements have been published by other researchers andresearch groups that evaluate dietary supplements, offer
recommendations on interpreting the literature, anddiscuss the available findings for several ingredients thatare discussed in this document [19–21]. We also advise
consumers to conduct a search on the nutrient, key ingredients or the supplement itself on the National Library ofMedicine’s Pub Med Online (https://www.ncbi.nlm.nih.gov/pubmed/). A quick look at these references will often
help determine if the theoretical impetus for supplementing with an ingredient is plausible or not. Proponents ofergogenic aids often overstate claims made about training
devices and dietary supplements while opponents of ergogenic aids and dietary supplements are often either unaware or are ignorant of research supporting their use.
Sports nutrition specialists have the responsibility to know
the literature and search available databases to evaluate
the level of merit surrounding a proposed ergogenic aid.
Is the supplement legal and safe?

An initial question that should be asked is whether the
supplement is legal and/or safe. Some athletic associations
have banned the use of various nutritional supplements(e.g., prohormones, ephedra that contains ephedrine,“muscle building” supplements, etc.) and many professional
sports organization have now written language into theircollective bargaining agreements that products made available by the team must be NSF certified as safe for sport.
Obviously, if the supplement is banned, the sports nutrition
specialist should discourage its use. In addition, many supplements lack appropriate long-term safety data. People
who consider taking nutritional supplements should bewell aware of the potential side effects so they can make an
informed decision whether to use a supplement. Additionally, they should consult with a knowledgeable physician tosee if any underlying medical problems exist that may
contraindicate its use. When evaluating the safety of a supplement, it is suggested to determine if any side effects
have been reported in the scientific or medical literature. In

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particular, we suggest determining how long a particularsupplement has been studied, the dosages evaluated, andwhether any side effects were observed. We also recommend consulting the Physician’s Desk Reference (PDR) for
nutritional supplements and herbal supplements to see if
any side effects have been reported and/or if there are any
known drug interactions. If no side effects have been reported in the scientific/medical literature, we generally willview the supplement as safe for the length of time and dosages evaluated. Unfortunately, many available supplements
have not had basic safety studies completed that replicate
the length of time and dosages being used.

Is there any scientific evidence supporting the ergogenic value?

The next question to ask is whether any well-controlled
data are available showing effectiveness of the proposed
ergogenic aid in athletic populations or people regularly
involved in exercise training. The first place to look is thelist of references cited in marketing material supporting
their claims. Are the abstracts or articles cited just generalreferences or specific studies that have evaluated theefficacy of the nutrients included in the formulation or of
the actual supplement? From there, one can criticallyevaluate the cited abstracts and articles by asking a seriesof questions: Are the studies basic research done in animals/clinicalpopulations or have the studies been conducted onathletes/trained subjects? For perspective, studies
reporting improved performance in rats or anindividual diagnosed with type 2 diabetes may beinsightful, but research conducted on non-diabetic
athletes is much more practical and relevant.
 Were the studies well controlled? For ergogenic aid
research, the gold standard study design is arandomized, double-blind, placebo controlled
clinical trial. This means that neither the researcher
nor the subject is aware which group received the
supplement or the placebo during the study and thatthe subjects were randomly assigned into theplacebo or supplement group. An additional elementof rigor is called a cross-over design, where eachsubject, at different times (separated by an interval
known as a “washout period”), is exposed to each of
the treatments. While utilization of a cross-overdesign is not always feasible, it reduces the elementof variability within a participant and subsequently,
increases the strength of study’s findings. At times,
supplement claims have been based on poorly
designed studies (i.e., small groups of subjects, nocontrol group, use of unreliable tests, etc.) or
testimonials which make interpretation moredifficult. Well-controlled clinical trials provide

Kerksick et al. Journal of the International Society of Sports Nutrition (2018) 15:38

stronger evidence as to the potential ergogenic value
and importantly how the findings can best be used.
 Do the studies report statistically significant results
or are claims being made on non-significant meansor trends? Appropriate statistical analysis of research
results allows for an unbiased interpretation of data.
Although studies reporting statistical trends may beof interest and lead researchers to conduct additional
research, studies reporting statistically significant
results are obviously more convincing. With this said,
it is important for people to understand that
oftentimes the potential effect a dietary supplement ordiet regimen may have above and beyond the effectseen from the exercise bout or an accepted dietary
approach is quite small. In addition, many studies
examining a biochemical or molecular biology
mechanism can require invasive sampling techniquesor the study population being recruited is unique(very highly trained) resulting in a small number ofstudy participants. When viewed together, thecombination of these two considerations can result instatistical outcomes that do not reach statisticalsignificance even though large mean changes wereobserved. In these situations, the reporting ofconfidence intervals on the mean change, individual
responses from all participants to the investigatedtreatment and/or effect sizes are additional pieces of
information that can allow for a more accurateinterpretation. In all such cases, additional research iswarranted to further examine the potential ergogenic
aid before conclusions can be made.
 Do the results of the cited studies match the claims
made about the supplement or do they accurately
portray the response of the supplement against an
appropriate placebo or control group? It is not
unusual for marketing claims to greatly exaggerate
the results found in the actual studies and do so by
focusing upon just the outcomes within the
supplement (treatment) group as opposed to how
the supplement group changed in comparison to
how a placebo group changed. Similarly, it is notuncommon for ostensibly compelling results, that
may indeed be statistically significant, to be
amplified while other relevant findings of significant
consumer interest are obscured or omitted (e.g. a
dietary supplement showing statistically significant
increases in circulating testosterone yet changes inbody composition or muscular performance were
not superior to a placebo). The only way todetermine this is to read the entire article versus
focusing an entire study’s interpretation on theprovided abstract or even the article citation, andcompare results observed in the studies to theavailable marketing claims. Reputable companies

Page 8 of 57

accurately and completely report results of studies
so that consumers can make informed decisions
about using a product.
 Were results of the study presented at a reputablescientific meeting and/or published in a peer-reviewed
scientific journal? At times, claims are based on
research that has either never been published or only
published in an obscure journal. The best research istypically presented at respected scientific meetings
and/or published in reputable peer-reviewed journals.
Three ways to determine a journal’s reputation iseither: 1) identify the publisher, 2) the “impact factor”
of the journal or 3) whether or not the journal isindexed and subsequently available for review on Pub
Med (https://www.ncbi.nlm.nih.gov/pubmed/). Many
“peer-reviewed” journals are published by companies
with ties to, or are actually owned by, companies that
do business with various nutritional products (eventhough they may be available on PubMed). Therefore,
we recommend looking up the publisher’s website
and see how many other journals they publish. If you
see only a few other journals this is a suggestion thatthe journal is not a reputable journal. Additionally,
one can also look up how many articles have been
published by the journal in the last 6–12 months andhow many of these articles are well-conducted studies.
Alternatively, one can also inquire about the impact
factor, a qualitative ranking determined by the
number of times a journal’s articles are cited. Impact
factors are determined and published by Thomson
Reuters under Journal Citation Reports® (asubscription service available at most university
libraries). Most journals list their impact factor on thejournal home page. Historically, those articles that areread and cited the most are the most impactfulscientifically.
 Have the research findings been replicated? If so,have the results only been replicated at the samelaboratory? The best way to know an ergogenic aid
works is to see that results have been replicated inseveral studies preferably by several separate, distinct
research groups. The most reliable ergogenic aids
are those in which multiple studies, conducted at
different labs, have reported similar results of safety
and efficacy. Additionally, replication of results bydifferent, unaffiliated labs with completely different
authors also removes or reduces the potentiallyconfounding element of publication bias (publicationof studies showing only positive results) andconflicts of interest. A notable number of studies on
ergogenic aids are conducted in collaboration with
one or more research scientists or co-authors thathave a real or perceived economic interest in theoutcome of the study. This could range from being aKerksick et al. Journal of the International Society of Sports Nutrition (2018) 15:38

co-inventor on a patent application that is the
subject of the ergogenic aid, being paid or receiving
royalties from the creation of a dietary supplement
formulation, providing consulting services for thecompany or having stock options or shares in acompany that owns or markets the ergogenic aid
described in the study. An increasing number ofjournals require disclosures by all authors ofscientific articles, and including such disclosuresin published articles. This is driven by the aim ofproviding greater transparency and research
integrity. It is important to emphasize that disclosureof a conflict of interest does not alone discredit or
dilute the merits of a research study. The primarythrust behind public disclosures of potential conflictsof interest is first and foremost transparency to thereader and second to prevent a later revelation ofsome form of confounding interest that has thepotential of discrediting the study in question, thefindings of the study, the authors, and even the
research center or institution where the study was
conducted.
Classifying and categorizing supplements

Dietary supplements may contain carbohydrate, protein,fat, minerals, vitamins, herbs, enzymes, metabolic intermediates (i.e., select amino acids), or various plant/foodextracts. Supplements can generally be classified asconvenience supplements (e.g., energy bars, gels, blocks,
meal replacement powders, or ready to drink supplements)
designed to provide a convenient means of meeting necessary energy or macronutrient needs while also providing
support towards attempts at managing caloric intake,weight gain, weight loss, and/or performance enhancement.
As discussed previously, evaluating the available scientific
literature is an important step in determining the efficacy ofany diet, diet program or dietary supplement. In considering this, nutritional supplements can be categorized in thefollowing manner:
I. Strong Evidence to Support Efficacy andApparently Safe: Supplements that have a soundtheoretical rationale with the majority of available
research in relevant populations using appropriate
dosing regimens demonstrating both its efficacy andsafety.
II. Limited or Mixed Evidence to Support Efficacy:
Supplements within this category are characterized
as having a sound scientific rationale for its use, but
the available research has failed to produce consistentoutcomes supporting its efficacy. Routinely, these
supplements require more research to be completed
before researchers can begin to understand theirimpact. Importantly, these supplements have no

Page 9 of 57

available evidence to suggest they lack safety or
should be viewed as harmful.
III. Little to No Evidence to Support Efficacy and/or
Safety: Supplements within this category generally
lack a sound scientific rationale and the available
research consistently shows it to lack efficacy.
Alternatively, supplements that may be harmful to
one’s health or to lack safety are also placed in thiscategory.
Several factors are evaluated when beginning to counsel
individuals who regularly complete exercise training. First,
a clear understanding of the athlete’s goals and the timewith which they have to meet those goals is important. In
addition to monitoring load and recovery, an evaluation of
the individual’s diet and training program should also becompleted. To accomplish this, one should make sure theathlete is eating an energy balanced, nutrient dense dietthat meets their estimated daily energy needs and thatthey are training intelligently. Far too many athletes orcoaches focus too heavily upon supplementation or applications of supplementation and neglect these key fundamental aspects. Following this, we suggest that theygenerally only recommend supplements in category I (i.e.,‘Strong Evidence to Support Efficacy and Apparently
Safe’). If an athlete is interested in trying supplements in
category II (i.e., ‘Limited or Mixed Evidence to Support
Efficacy’), the athlete should make sure they understandthese supplements are more experimental and they may
or may not see the type of results claimed. Obviously, theISSN does not support athletes taking supplements in
category III (i.e., ‘Little to No Evidence to Support Efficacy
and/or Safety’). We believe this approach is scientifically
substantiated and offers a balanced view as opposed tosimply dismissing the use of all dietary supplements.

General dietary guidelines for active individuals

A well-designed diet that meets energy intake needs andincorporates proper timing of nutrients is the foundation
upon which a good training program can be developed[22, 23]. Research has clearly shown that lacking sufficient calories and/or enough of the right type of macronutrients may impede an athlete’s training adaptations,while athletes who consume a balanced diet that meetsenergy needs can augment physiological training adaptations. Moreover, maintaining an energy deficient dietduring training may lead to loss of muscle mass,strength, and bone mineral density in addition to an increased susceptibility to illness and injuries, disturbancesin immune, endocrine and reproductive function, and anincreased prevalence of overreaching and/or overtraining. Incorporating good dietary practices as part of a
training program is one way to help optimize training

Kerksick et al. Journal of the International Society of Sports Nutrition (2018) 15:38

adaptations and prevent overtraining. The following isan overview of energy intake recommendations andmajor nutrient needs for active individuals.
Energy needs

The primary component to optimize training and performance through nutrition is to ensure the athlete is consuming enough calories to offset energy expenditure [22–26].
People who participate in a general fitness program (e.g.,
exercising 30–40 min per day, 3 times per week) can typically meet nutritional needs following a normal diet (e.g.,
1800–2400 kcals/day or about 25–35 kcals/kg/day for a
50–80 kg individual) because their caloric demands fromexercise are not too great (e.g., 200–400 kcals/session).
However, athletes involved in moderate levels of intense
training (e.g., 2–3 h per day of intense exercise performed
5–6 times per week) or high volume intense training (e.g.,
3–6 h per day of intense training in 1–2 workouts for 5–
6 days per week) may expend 600–1200 kcals or more perhour during exercise [24]. For this reason, their caloric
needs may approach 40–70 kcals/kg/day (2000–7000
kcals/day for a 50–100 kg athlete). For elite athletes, energy
expenditure during heavy training or competition willfurther exceed these levels [27, 28]. For example, energy
expenditure for cyclists to compete in the Tour de France
has been estimated as high as 12,000 kcals/day (150–200
kcals/kg/day for a 60–80 kg athlete) [29, 30]. Additionally,
caloric needs for large athletes (i.e., 100–150 kg) may range
between 6000 and 12,000 kcals/day depending on thevolume and intensity of different training phases [31].
Although some argue that athletes can meet caloric
needs simply by consuming a well-balanced diet, it is oftenvery difficult for larger athletes and athletes engaged inhigh volume/intense training to be able to eat enough food,on a daily basis, to meet caloric needs [2, 29, 30, 32–34].
This point was clearly highlighted in a review by Burke
who demonstrated that carbohydrate needs are largely unmet by high-level athletes [22]. Additionally it is difficult to
consume enough food and maintain gastrointestinal comfort to train or race at peak levels [35]. Maintaining anenergy deficient diet during training often leads to a number of physical (i.e., loss of fat-free mass, illness, reduced
sleep quality, incomplete recovery, hormonal fluctuations,increased resting heart rate, etc.) and psychological (i.e.,apathy towards training, heightened stress) adverse outcomes [23, 27]. Nutritional analyses of athletes’ diets haverevealed that many are susceptible to maintaining negative
energy intakes during training. It is still a question whether
there may be specific individualized occasions when negative energy balance may enhance performance in the days
prior to running performance [36]. Populations susceptible
to negative energy balance include runners, cyclists, swimmers, triathletes, gymnasts, skaters, dancers, wrestlers,
boxers, and athletes attempting to lose weight too quickly

Page 10 of 57[37]. Additionally, female athletes are at particular risk ofunder fueling due to both competitive and aesthetic
demands of their sport and their surrounding culture. Female athletes have been reported to have a high incidenceof eating disorders [38]. Low or reduced energy availability(LEA) is linked to functional hypothalamic oligomenorrhea/amenorrhea (FHA), which is frequently reported inweight sensitive sports. This makes LEA a major nutritional concern for female athletes [39]. Consequently, it isimportant for the sports nutrition specialist working withathletes to assess athletes individually to ensure that athletes are well fed according to the goals of their sport andtheir health, and consume enough calories to offset the increased energy demands of training, and maintain bodyweight. Although this sounds relatively simple, intense
training often suppresses appetite and/or alters hunger
patterns so that many athletes do not feel like eating[37, 38]. Some athletes prefer not to exercise within several hours after eating because of sensations of fullness
and/or a predisposition to cause gastrointestinal distress.
Further, travel and training schedules may limit food availability or the types of food athletes are accustomed to eating. This means that care should be taken to plan meal
times in concert with training, as well as to make sure athletes have sufficient availability of nutrient dense foods
throughout the day for snacking between meals (e.g.,
fluids, carbohydrate/protein-rich foods and supplemental
bars, etc.) [2, 33, 40]. For this reason, sports nutritionists’often recommend that athletes consume four to six meals
per day and snacks in between meals to meet energy
needs. Due to these practical concerns, the use of nutrient
dense energy foods, energy bars and high calorie carbohydrate/protein supplements provides a convenient way forathletes to supplement their diet in order to maintain energy intake during training.
Carbohydrate

Beyond optimal energy intake, consuming adequate
amounts of carbohydrate, protein, and fat is important forathletes to optimize their training and performance. In particular and as it relates to exercise performance, the needfor optimal carbohydrates before, during and after intenseand high-volume bouts of training and competition is evident [41]. Excellent reviews [42, 43] and original investigations [44–49] continue to highlight the known dependence
on carbohydrates that exists for athletes competing to win
various endurance and team sport activities. A complete
discussion of the needs of carbohydrates and strategies todeliver optimal carbohydrate and replenish lost muscle andliver glycogen extend beyond the scope of this paper, but
the reader is referred to several informative reviews on the
topic [23, 41, 50–53].
As such, individuals engaged in a general fitness programand are not necessarily training to meet any type ofKerksick et al. Journal of the International Society of Sports Nutrition (2018) 15:38

performance goal can typically meet daily carbohydrate
needs by consuming a normal diet (i.e., 45–55% CHO [3–5 g/kg/day], 15–20% PRO [0.8–1.2 g/kg/day], and 25–35%
fat [0.5–1.5 g/kg/day]). However, athletes involved in moderate and high-volume training need greater amounts ofcarbohydrate and protein (discussed later) in their diet tomeet macronutrient needs [50]. In terms of carbohydrate
needs, athletes involved in moderate amounts of intense
training (e.g., 2–3 h per day of intense exercise performed
5–6 times per week) typically need to consume a diet consisting of 5–8 g/kg/day or 250–1200 g/day for 50–150 kg
athletes of carbohydrate to maintain liver and muscle
glycogen stores [23, 24, 50]. Research has also shown that
athletes involved in high volume intense training (e.g.,
3–6 h per day of intense training in 1–2 daily workouts for
5–6 days per week) may need to consume 8–10 g/day ofcarbohydrate (i.e., 400–1500 g/day for 50–150 kg athletes)in order to maintain muscle glycogen levels [50]. Preferably, the majority of dietary carbohydrate should come fromwhole grains, vegetables, fruits, etc. while foods that empty
quickly from the stomach such as refined sugars, starches
and engineered sports nutrition products should bereserved for situations in which glycogen resynthesis needs
to occur at accelerated rates [53]. In these situations, theabsolute delivery of carbohydrate (> 8 g of carbohydrate/kg/day or at least 1.2 g of carbohydrate/kg/hour for the
first four hours into recovery) takes precedence over otherstrategies such as those that may relate to timing or concomitant ingestion of other macronutrients (e.g., protein)or non-nutrients (e.g., caffeine) or carbohydrate type (i.e.,
glycemic index) [50].
When considering the carbohydrate needs throughout
an exercise session, several key factors should be considered. Previous research has indicated athletes undergoingprolonged bouts (2–3 h) of exercise training can oxidize
carbohydrates at a rate of 1–1.1 g per minute or about 60 g
per hour [41]. Several reviews advocate the ingestion of
0.7 g of carbohydrate/kg/hr. during exercise in a 6–8% solution (i.e., 6–8 g per 100 ml of fluid) [41, 42, 50, 54]. It is
now well established that different types of carbohydrates
can be oxidized at different rates in skeletal muscle due tothe involvement of different transporter proteins that resultin carbohydrate uptake [55–59]. Interestingly, combinations of glucose and sucrose or maltodextrin and fructose
have been reported to promote greater exogenous rates ofcarbohydrate oxidation when compared to situations whensingle sources of carbohydrate are ingested [55–63]. Thesestudies generally indicate a ratio of 1–1.2 for maltodextrin
to 0.8–1.0 fructose seems to support the greatest rates ofcarbohydrate oxidation during exercise. Additional research on high molecular weight amylopectin indicates that
there may be a benefit to the lower osmolality of the starch,allowing for greater consumption (100 g/hour) and possibly greater oxidation rates and performance improvement

Page 11 of 57[64–67]. In addition to oxidation rates and carbohydrate
types, the fasting status and duration of the exercise boutalso function as key variables for athletes and coaches toconsider. When considering duration, associated reviews
have documented that bouts of moderate to intense exercise need to reach exercise durations that extend well into
90th minute of exercise before carbohydrate is shown toconsistently yield an ergogenic outcome [41, 68, 69]. Of
interest, however, not all studies indicate that shorter (60–75 min) bouts of higher intensity work may benefit fromcarbohydrate delivery. Currently the mechanisms surrounding these findings are, respectively, thought to be replacement of depleted carbohydrate stores during longer
duration of moderate intensity while benefits seen during
shorter, more intense exercise bouts are thought to operate
in a central fashion. Moreover, these reviews have also
pointed to the impact of fasting status on documentationof ergogenic outcomes [41, 68, 69]. In this respect, whenstudies require study participants to commence exercise ina fasted state, ergogenic outcomes are more consistently
reported, yet other authors have questioned the ecologicalvalidity of this approach for competing athletes [43].
As it stands, the need for optimal carbohydrates in thediet for those athletes seeking maximal physical performance is unquestioned. Daily consumption of appropriate
amounts of carbohydrate is the first and most important
step for any competing athlete. As durations extend into
2 h, the need to deliver carbohydrate goes up, particularly
when commencing exercise in a state of fasting or incomplete recovery. Once exercise ceases, several dietary strategies can be considered to maximally replace lost muscle
and liver glycogen, particularly if a limited window of recovery exists. In these situations, the first priority should
lie with achieving aggressive intakes of carbohydrate while
strategies such as ingesting protein with lower carbohydrate amounts, carbohydrate and caffeine co-ingestion or
certain forms of carbohydrate may also help to facilitate
rapid assimilation of lost glycogen.
ProteinConsiderable debate exists surrounding the amount ofprotein needed in an athlete’s diet [70–74]. Initially, it wasrecommended that athletes do not need to ingest morethan the RDA for protein (i.e., 0.8 to 1.0 g/kg/d forchildren, adolescents and adults). However, research
spanning the past 30 years has indicated that athletes
engaged in intense training may benefit from ingesting
about two times the RDA of protein in their diet (1.4–
1.8 g/kg/d) to maintain protein balance [11, 70, 71, 73,
75–80]. If an insufficient amount of protein is consumed,
an athlete will develop and maintain a negative nitrogenbalance, indicating protein catabolism and slow recovery.
Over time, this may lead to muscle wasting, injuries,
illness, and training intolerance [76, 77, 81].

Kerksick et al. Journal of the International Society of Sports Nutrition (2018) 15:38

For people involved in a general fitness program or simply interested in optimizing their health, recent researchsuggests protein needs may also be above the RDA. Phillips
and colleagues [76], Witard et al. [82], Jager et al. [11] andTipton et al. [79] report that current evidence indicates optimal protein intakes in the range of 1.2–2.0 g/kg/day
should be considered. In this respect, Morton and investigators [83] performed a meta-review and meta-regression
involving 49 studies and 1863 participants and concluded
that a daily protein intake of 1.62 g/kg/day may be an ideal
place to start, with intakes beyond that providing no further
contribution to increases in fat-free mass. In addition andin comparison to the RDA, non-exercising, older individuals (53–71 years) may also benefit from a higher daily protein intake (e.g., 1.0–1.2 g/kg/day of protein). Recent
reports suggest that older muscle may be slower to respondand less sensitive to protein ingestion, typically requiring
40 g doses to robustly stimulate muscle protein synthesis[84–86]. Studies in younger individuals, however, have indicated that in the absence of exercise, a 20 g dose canmaximize muscle protein synthesis [87, 88] and if consumed after a multiple set workout consisting of several exercises that target large muscle groups a 40 g dose might beneeded [89]. Consequently, it is recommended that athletes
involved in moderate amounts of intense training consume
1.2–2.0 g/kg/day of protein (60–300 g/day for a 50–150 kg
athlete) while athletes involved in high volume, intense
training consume 1.7–2.2 g/kg/day of protein (85–330 g/
day for a 50–150 kg athlete) [78, 90]. This protein need
would be equivalent to ingesting 3–15 three-ounce servingsof chicken or fish per day for a 50–150 kg athlete [78]. Although smaller athletes typically can ingest this amount ofprotein, on a daily basis, in their normal diet, larger athletes
often have difficulty consuming this much dietary protein.
Additionally, a number of athletic populations are
known to be susceptible to protein malnutrition (e.g.,runners, cyclists, swimmers, triathletes, gymnasts,
dancers, skaters, wrestlers, boxers, etc.) and consequently, additional counseling and education may beneeded to help these athletes meet their daily protein
needs. To this point, the periods of energy restriction
to meet weight or aesthetic demands of their sportsthat are seemingly a part of the sport’s fabric creates anarguably greater need to understand that protein intake,quality and timing as well as combination with carbohydrate is particularly important to maintain lean bodymass, training effects, and performance [25]. Overall, it
goes without saying that care should be taken to ensurethat athletes consume a sufficient amount of quality
protein in their diet to maintain nitrogen balance.
Proteins differ based on their source, amino acid profile, and the methods of processing or isolating the protein undergoes [11]. These differences influence theavailability of amino acids and peptides, which may

Page 12 of 57

possess biological activity (e.g., α-lactalbumin, ß-lactoglobulin, glycomacropeptides, immunoglobulins, lactoperoxidases, lactoferrin, etc.). Additionally, the rate ofdigestion and/or absorption and metabolic activity of theprotein also are important considerations [91]. For
example, different types of proteins (e.g., casein, whey,
and soy) are digested at different rates, which may affectwhole body catabolism and anabolism and acute stimulation of muscle protein synthesis (MPS) [91–96]. Therefore, care should be taken not only to make sure theathlete consumes enough protein in their diet but alsothat the protein is high quality. The best dietary sourcesof low fat, high quality protein are light skinless chicken,
fish, egg whites, very lean cuts of beef and skim milk(casein and whey) while protein supplements routinely
contain whey, casein, milk and egg protein. In what isstill an emerging area of research, various plant sourcesof protein have been examined for their ability to stimulate increases in muscle protein synthesis [77, 97] andpromote exercise training adaptations [98]. While aminoacid absorption from plant proteins is generally slower,
leucine from rice protein has been found to be absorbed
even faster than from whey [99], while digestive enzymes[100], probiotics [101] and HMB [102] can be used toovercome differences in protein quality. Preliminary
findings suggest that rice [98] and pea protein [103] may
be able to stimulate similar changes in fat-free mass andstrength as whey protein, although the reader should
understand that many other factors (dose provided,training status of participants, duration of training andsupplementation, etc.) will ultimately impact theseoutcomes and consequently more research is needed.
While many reasons and scenarios exist for why an athlete may choose to supplement their diet with protein powders or other forms of protein supplements, this practice is
not considered to be an absolute requirement for increased
performance and adaptations. Due to nutritional, societal,
emotional and psychological reasons, it is preferable forthe majority of daily protein consumed by athletes to occur
as part of a food or meal. However, we recognize andembrace the reality that situations commonly arise where
efficiently delivering a high-quality source of protein takes
precedence. Jager and colleagues [11] published an updated
position statement of the International Society of Sports
Nutrition that is summarized by the following points:
1) An acute exercise stimulus, particularly resistance
exercise and protein ingestion both stimulate muscle
protein synthesis (MPS) and are synergistic when
protein consumption occurs before or after resistance
exercise
2) For building and maintaining muscle mass, an overall
daily protein intake of 1.4–2.0 g/kg/d is sufficient formost exercising individuals

Kerksick et al. Journal of the International Society of Sports Nutrition (2018) 15:38

3) Higher protein intakes (2.3–3.1 g/kg fat-free mass/d) may be needed to maximize the retention of leanbody weight in resistance trained subjects during
hypocaloric periods
4) Higher protein intakes (> 3.0 g protein/kg bodyweight/day) when combined with resistance exercise
may have positive effects on body composition inresistance trained individuals (i.e., promote loss of fatmass)5) Optimal doses for athletes to maximize MPS are
mixed and are dependent upon age and recent
resistance exercise stimuli. General recommendations
are 0.25–0.55 g of a high-quality protein per kg ofbody weight, or an absolute dose of 20–40 g.
6) Acute protein doses should contain 700–3000 mg
of leucine and/or a higher relative leucine content,
in addition to a balanced array of the essential
amino acids (EAAs)
7) Protein doses should ideally be evenly distributed,
every 3–4 h, across the day8) The optimal time period during which to ingest
protein is likely a matter of individual tolerance;
however, the anabolic effect of exercise islong-lasting (at least 24 h), but likely diminisheswith increasing time post-exercise
9) Rapidly digested proteins that contain highproportions of EAAs and adequate leucine, aremost effective in stimulating MPS
10) Different types and quality of protein can affectamino acid bioavailability following protein
supplementation; complete protein sources deliver all
required EAAs
Fat

The dietary recommendations of fat intake for athletes are
similar to or slightly greater than dietary recommendations
made to non-athletes to promote health. Maintenance ofenergy balance, replenishment of intramuscular triacylglycerol stores and adequate consumption of essential fatty
acids are important for athletes, and all serve as reasonsfor an increased intake of dietary fat [104]. Depending
upon the athlete’s training status or goals, the amount of
dietary fat recommended for daily intake can change. For
example, higher-fat diets appear to maintain circulating
testosterone concentrations better than low-fat diets[105–107]. Additionally, higher fat intakes may provide
valuable translational evidence to the documented testosterone suppression which can occur during volume-type
overtraining [108]. Generally, it is recommended that athletes consume a moderate amount of fat (approximately
30% of their daily caloric intake), while proportions up to
50% of daily calories can be safely ingested by athletes during regular high-volume training [104]. In situations wherean athlete may be interested in reducing their body fat,

Page 13 of 57

dietary fat intakes ranging from 0.5 to 1 g/kg/day havebeen recommended results in situations where daily fat intake might comprise as little as 20% of total calories in thediet [2]. This recommendation stems largely from available evidence in weight loss studies involving non-athletic
individuals that people who are most successful in losing
weight and maintaining the weight loss are those who ingest reduced amounts of fat in their diet [109, 110] although this is not always the case [111]. Strategies to help
athletes manage dietary fat intake include teachingthem which foods contain various types of fat so thatthey can make better food choices and how to countfat grams [2, 33].
For years, high-fat diets have been used by athletes withthe majority of evidence showing no ergogenic benefit andconsistent gastrointestinal challenges [112]. In recent
years, significant debate has swirled regarding the impact
of increasing dietary fat. One strategy, “train low, competehigh”, refers to an acute pattern of dietary periodization
whereby an athlete first follows a high-fat, low carbohydrate diet for one to 3 weeks while training before
reintroducing carbohydrates back into the diet. While
intramuscular adaptations result that may theoretically
impact performance [113, 114], no consistent, favorable
impact on performance has been documented [112, 115].
A variant of high-fat diets, ketogenic diets, have increasedin popularity. While no exact prescription exists, nearly all
ketogenic diet prescriptions derive at least 70–80% of their
daily calories from dietary fat, prescribe a moderateamount of protein (20–25% total calories or 2.0–2.5 g/kg/day) and are largely devoid of carbohydrate (10–40 g perday). This diet prescription leads to a greater reliance on
ketones as a fuel source. Currently, limited and mixed evidence remains regarding the overall efficacy of a ketogenic
diet for athletes. In favor, Cox et al. [116] demonstrated
that ketogenic dieting can improve exercise endurance byshifting fuel oxidation while Burke and colleagues [115]failed to show an increase in performance in a cohort ofOlympic-caliber race walkers. Additionally, Jabekk and colleagues [117] reported decreases in body fat with nochange in lean mass in overweight women who resistancetrained for 10 weeks and followed a ketogenic diet. In lightof the available evidence being limited and mixed, morehuman research needs to be completed before appropriate
recommendations can be made towards the use of high fat
diets for athletic performance.
Strategic eating and refueling

In addition to the general nutritional guidelines describedabove, research has also demonstrated that timing andcomposition of meals consumed may play a role in optimizing performance, training adaptations, and preventing
overtraining [2, 25, 40]. In this regard, it takes about 4 h
for carbohydrate to be digested and assimilated into

Kerksick et al. Journal of the International Society of Sports Nutrition (2018) 15:38

muscle and liver tissues as glycogen. Consequently,
pre-exercise meals should be consumed about four to 6 h
before exercise [40]. This means that if an athlete trains in
the afternoon, breakfast can be viewed to have great
importance to top off muscle and liver glycogen levels. Research has also indicated that ingesting a light carbohydrate and protein snack 30 to 60 min prior to exercise (e.g.,
50 g of carbohydrate and 5 to 10 g of protein) serves to increase carbohydrate availability toward the end of an intense exercise bout [118, 119]. This also serves to increaseavailability of amino acids, decrease exercise-induced
catabolism of protein, and minimize muscle damage[120–122]. Additionally, athletes who are going throughperiods of energy restriction to meet weight or aesthetic
demands of sports should understand that protein intake,quality and timing as well as combination with carbohydrate is particularly important to maintain leanbody mass, training effects, and performance [25].
When exercise lasts more than 1 h and especially as
duration extends beyond 90 min, athletes should ingest glucose/electrolyte solutions (GES) to maintainblood glucose levels, prevent dehydration, and reducethe immunosuppressive effects of intense exercise [40,123–128]. Notably, this strategy becomes even more
important if the athlete is under-fueled prior to theexercise task or is fasted vs. unfasted at the start ofexercise [68, 69, 129]. Following intense exercise, athletes should consume carbohydrate and protein (e.g.,
1 g/kg of carbohydrate and 0.5 g/kg of protein)
within 30 min after exercise and consume a highcarbohydrate meal within 2 h following exercise [2, 74].
This nutritional strategy has been found to accelerate
glycogen resynthesis as well as promote a more anabolic hormonal profile that may hasten recovery[120, 130, 131], but as mentioned above only when
rapid glycogen restoration is needed or if the carbohydrate intake in the diet is adequate (< 6 g/kg/day)[53, 132]. In other words, the total carbohydrate
consumption and timing of carbohydrate consumption should be individualized to each athlete’s needs
according to the goals of the training cycle and bout[112]. Finally, for two to 3 days prior to competition, athletes should taper training by 30 to 50% and consume an
additional 200 to 300 g of carbohydrate each day in theirdiet. This eating strategy has been shown to supersaturate
carbohydrate stores prior to competition and improve endurance exercise capacity [2, 40]. Thus, the type of meal,amount of carbohydrate consumed, and timing of eating
are important factors to maximize glycogen storage and inmaintaining carbohydrate availability during training while
also potentially decreasing the incidence of overtraining.
The ISSN has adopted a position stand on nutrient timing
in 2008 [133] that has been subsequently revised [13] andcan be summarized with the following points:

Page 14 of 57

1. Intramuscular and hepatic glycogen stores are best
maximized by consumption of a high-carbohydrate
diet (8–12 g/kg/day). Strategies such as aggressive
carbohydrate feedings (~ 1.2 g/kg/hour) that favor
high-glycemic (> 70) carbohydrates, addition ofcaffeine (3–8 mg/kg) and combining a moderate
carbohydrate dose (0.8 g/kg/h) with protein (0.2–
0.4 g/kg/h) have been shown to promote rapid
restoration of glycogen stores.
2. High intensity (> 70% VO2Max) exercise bouts that
extend beyond 90 min challenge fuel supply andfluid regulation. In these situations, it is advisable toconsume carbohydrate at a rate of 30–60 g ofcarbohydrate/hour in a 6–8% carbohydrate-electrolyte
solution (6–12 fluid ounces) every 10–15 min
throughout the entire exercise bout. The importanceof this strategy is increased when poor feeding or
recovery strategies were employed prior to exercise
commencement. Consequently, when carbohydratedelivery is inadequate, adding protein may help
increase performance, mitigate muscle damage,promote euglycemia, and facilitate glycogenre-synthesis.
3. Consuming a diet that delivers adequate energy(minimum of 27–30 kcal/kg) and protein (1.6–
1.8 g/kg/day), preferably with evenly spaced (every
3–4 h) protein feedings (0.25–0.40 g/kg/dose)
during the day, should be considered for all exercisingindividuals.
4. Ingesting efficacious doses (10–12 g) of essential
amino acids (EAAs) either in free form or as aprotein bolus in 20–40 g doses (0.25–0.40 g/kg/
dose) will maximally stimulate muscle protein
synthesis (MPS).
5. Pre- and/or post-exercise nutritional interventions(carbohydrate + protein or protein alone) can be aneffective strategy to support improvements in strengthand body composition. However, the size (0.25–
0.40 g/kg/dose) and timing (0–4 h) of a pre-exercise
meal may impact the benefit derived from thepost-exercise protein feeding.
6. Post-exercise ingestion (immediately-post to 2 hpost) of high-quality protein sources stimulatesrobust increases in MPS. Similar increases in MPS
have been found when high-quality proteins areingested immediately before exercise.
Vitamins

Vitamins are essential organic compounds that serve toregulate metabolic and neurological processes, energy
synthesis, and prevent destruction of cells. Fat-soluble
vitamins include vitamins A, D, E, & K and the body stores
fat-soluble vitamins in various tissues, which can result in
toxicity if consumed in excessive amounts. Water-solubleKerksick et al. Journal of the International Society of Sports Nutrition (2018) 15:38

vitamins consist of the entire complex of B-vitamins andvitamin C. Since these vitamins are water-soluble, excessive
intake of these vitamins are eliminated in urine, with few
exceptions (e.g. vitamin B6, which can cause peripheral
nerve damage when consumed in excessive amounts).
Table 1 describes the RDA, proposed ergogenic benefit,
and summary of research findings for fat and water-soluble
vitamins. Research has demonstrated that specific vitamins
possess various health benefits (e.g., Vitamin E, niacin, folicacid, vitamin C, etc.), while few published studies have reported to find an ergogenic value of vitamins for athletes[134–138]. Alternatively, if an athlete is deficient in a vitamin, supplementation or diet modifications to improve
vitamin status can consistently improve health and performance [139]. For example, Paschalis and colleagues[140] supplemented individuals who were low in vitamin C
for 30 days and reported these individuals had significantly
lower VO2Max levels than a group of males who were highin vitamin C. Further, after 30 days of supplementation,
VO2Max significantly improved in the low vitamin C cohort as did baseline levels of oxidative stress of oxidative
stress. Importantly, one must consider that some vitamins
may help athletes tolerate training to a greater degree by
reducing oxidative damage (Vitamin E, C) and/or help tomaintain a healthy immune system during heavy training(Vitamin C). Alternatively, conflicting evidence has accumulated that ingesting high doses of Vitamins C and E
may negatively impact intracellular adaptations seen in response to exercise training [141–144], which may consequently negatively impact an athlete’s performance.
Furthermore, while optimal levels of vitamin D have been
linked to improved muscle health [145] and strength [146]in general populations, research studies conducted in athletes generally fail to report on the ergogenic impact ofvitamin D in athletes [147, 148]. However, equivocal evidence from Wyon et al. [149] suggests vitamin D supplementation in elite ballet dancers improved strength andreduced risk for injuries. The remaining vitamins reviewed
appear to have little ergogenic value for athletes who consume a normal, nutrient dense diet. Since dietary analysesof athletes commonly indicate that athletes fail to consume
enough calories and subsequently may not be consuming
adequate amounts of each vitamin, many sport dietitians
and nutritionists recommend that athletes consume alow-dose daily multivitamin and/or a vitamin enriched
post-workout carbohydrate/protein supplement during periods of heavy training [150]. Finally, athletes may desire to
consume a vitamin or mineral for various health (non-performance) related reasons including niacin to elevate highdensity lipoprotein (HDL) cholesterol levels and decreaserisk of heart disease (niacin), vitamin E for its antioxidant
potential, vitamin D for its ability to preserve musculoskeletal function, or vitamin C to promote and maintain ahealthy immune system.

Page 15 of 57

Minerals

Minerals are essential inorganic elements necessary fora host of metabolic processes. Minerals serve as structure for tissue, important components of enzymes andhormones, and regulators of metabolic and neural control. In athletic populations, some minerals have beenfound to be deficient while other minerals are reduced
secondary to training and/or prolonged exercise. Notably, acute changes in sodium, potassium and magnesium throughout a continued bout of moderate to highintensity exercise are considerable. In these situations,athletes must work to ingest foods and fluids to replacethese losses, while physiological adaptations to sweat
composition and fluid retention will also occur to promote a necessary balance. Like vitamins, when mineral
status is inadequate, exercise capacity may be reduced
and when minerals are supplemented in deficient athletes, exercise capacity has been shown to improve[151]. However, scientific reports consistently fail todocument a performance improvement due to mineral
supplementation when vitamin and mineral status isadequate [134, 152, 153]. Table 2 describes minerals
that have been purported to affect exercise capacity inathletes. Of the minerals reviewed, several appear topossess health and/or ergogenic value for athletes
under certain conditions. For example, calcium supplementation in athletes susceptible to premature osteoporosis may help maintain bone mass [151]. For years,
the importance of iron status in female athletes has
been discussed [154] and more recent efforts havehighlighted that iron supplementation in athletes prone
to iron deficiencies and/or anaemia can improve exercise capacity [155, 156]. Sodium phosphate loading canincrease maximal oxygen uptake, anaerobic threshold,and improve endurance exercise capacity by 8 to 10%[157]. Increasing dietary availability of salt (sodium
chloride) during the initial days of exercise training in
the heat helps to maintain fluid balance and prevent
dehydration. The American College of Sports Medicine(ACSM) recommendations for sodium levels (340 mg)
represent the amount of sodium in less than 1/8 teaspoon of salt and recommended guidelines for sodium
ingestion during exercise (300–600 mg per hour or
1.7–2.9 g of salt during a prolonged exercise bout)[158–161]. Finally, zinc supplementation during training can support changes in immune status in response
to exercise training. Consequently, several minerals
may enhance exercise capacity and/or training adaptations for athletes under certain conditions. However,there is little evidence that boron, chromium, magnesium, or vanadium affect exercise capacity or training
adaptations in healthy individuals eating a normal diet.
Sport nutritionists and dietitians should be aware of
the specialized situations in which different types of5 mcg/d (age < 51)

15 mg/dMales 120 mcg/dFemales 90 mcg/dMales 1.2 mg/d
Females 1.1 mg/d

Males 1.3 mg/d
Females 1.7 mg/d

Males 16 mg/d
Females 14 mg/d

1.3 mg/d (age < 51) Has been marketed as a supplement that will improve muscle mass,strength, and aerobic power in the lactic acid and oxygen systems. It also
may have a calming effect that has been linked to an improved mental
strength.

Vitamin D

Vitamin E

Vitamin K

Thiamin (B1)

Riboflavin (B2)

Niacin (B3)

Pyridoxine (B6)

No studies have shown that vitamin A supplementation improves exercise
performance [139].

Summary of research findings

Dietary availability of thiamin does not appear to affect exercise capacity
when athletes have a normal intake [713].

Vitamin K supplementation (10 mg/d) in elite female athletes has beenreported to increase calcium-binding capacity of osteocalcin and promoted
a 15–20% increase in bone formation markers and a 20–25% decrease inbone resorption markers suggesting an improved balance between boneformation and resorption [712].

Numerous studies show that vitamin E supplementation can decrease
exercise-induced oxidative stress [708–710]. However, most studies show
no effects on performance at sea level. At high altitudes, vitamin E may
improve exercise performance [711]. Additional research is necessary to
determine whether long-term supplementation may help athletes better
tolerate training.

Functions as a coenzyme in the formation of DNA and red blood cells. An
increase in red blood cells could improve oxygen delivery to the muscles
during exercise. Believed to be important to help prevent birth defects andmay help decrease homocysteine levels.

400 mcg/d

5 mg/dFolic acid (folate)

Pantothenic acid

Acts as a coenzyme for acetyl coenzyme A (acetyl CoA). This may benefit
aerobic or oxygen energy systems.

A coenzyme involved in the production of DNA and serotonin. DNA is
important in protein and red blood cell synthesis. Theoretically, it would
increase muscle mass, the oxygen-carrying capacity of blood, and decrease
anxiety.

Cyano-cobalamin (B12) 2.4 mcg/dConstituent of coenzymes involved in energy metabolism. Theorized toblunt increases in fatty acids during exercise, reduce cholesterol, enhancethermoregulation, and improve energy availability during oxidative
metabolism.

Research has reported no improvements in aerobic performance withacetyl CoA supplementation. However, one study reported a decrease inlactic acid accumulation, without an improvement in performance [722].

Studies suggest that increasing dietary availability of folic acid during
pregnancy can lower the incidence of birth defects [719]. Additionally, it
may decrease homocysteine levels (a risk factor for heart disease) [720]. In
well-nourished and folate deficient-athletes, folic acid did not improve
exercise performance [721].

In well-nourished athletes, no ergogenic effect has been reported. However,when combined with vitamins B1 and B6, cyanocobalamin has been shown
to improve performance in pistol shooting [718]. This may be due to increased levels of serotonin, a neurotransmitter in the brain, which may reduce anxiety.

In well-nourished athletes, pyridoxine failed to improve aerobic capacity, or
lactic acid accumulation [713]. However, when combined with vitamins B1
and B12, it may increase serotonin levels and improve fine motor skills that
may be necessary in sports like pistol shooting and archery [717, 718].

Studies indicate that niacin supplementation (100–500 mg/d) can help
decrease blood lipid levels and increase homocysteine levels in
hypercholesteremic patients [714, 715]. However, niacin supplementation(280 mg) during exercise has been reported to decrease exercise capacity
by blunting the mobilization of fatty acids [716].

Constituent of flavin nucleotide coenzymes involved in energy metabolism. Dietary availability of riboflavin does not appear to affect exercise capacity
Theorized to enhance energy availability during oxidative metabolism.
when athletes have a normal intake [713].

Coenzyme (thiamin pyrophosphate) in the removal of CO2 fromdecarboxylic reactions from pyruvate to acetyl CoA and in TCA cycle.
Supplementation is theorized to improve anaerobic threshold and CO2transport. Deficiencies may decrease efficiency of energy systems.

Important in blood clotting. There is also some evidence that it may affectbone metabolism in postmenopausal women.

As an antioxidant, it has been shown to help prevent the formation of free
radicals during intense exercise and prevent the destruction of red blood
cells, improving or maintaining oxygen delivery to the muscles during
exercise. Some evidence suggests that it may reduce risk to heart diseaseor decrease incidence of recurring heart attack.

Promotes bone growth and mineralization. Enhances calcium absorption.
Co-supplementation with calcium may help prevent bone loss in athletes
Supplementation with calcium may help prevent bone loss in osteoperotic susceptible to osteoporosis [707]. However, vitamin D supplementation
populations.
does not enhance exercise performance [139].

Males 900 mcg/dConstituent of rhodopsin (visual pigment) and is involved in night vision.
Females 700 mcg/d Some suggest that vitamin A supplementation may improve sport vision.

Vitamin A

Proposed ergogenic value

RDA

Nutrient

Table 1 Proposed nutritional ergogenic aids – vitamins

Kerksick et al. Journal of the International Society of Sports Nutrition (2018) 15:38
Page 16 of 57

None

Males 90 mg/d
Females 75 mg/d

Beta carotene

Vitamin C

Summary of research findings

Used in a number of different metabolic processes in the body. It isinvolved in the synthesis of epinephrine, iron absorption, and is anantioxidant. Theoretically, it could benefit exercise performance byimproving metabolism during exercise. There is also evidence thatvitamin C may enhance immunity.

In well-nourished athletes, vitamin C supplementation does not appear to
improve physical performance [138, 723]. However, there is some evidence
that vitamin C supplementation (e.g., 500 mg/d) following intense exercise
may decrease the incidence of upper respiratory tract infections[696, 724, 725].

Serves as an antioxidant. Theorized to help minimize exercise-induced lipid Research indicates that beta carotene supplementation with or without
peroxidation and muscle damage.
other antioxidants can help decrease exercise-induced peroxidation. Overtime, this may help athletes tolerate training. However, it is unclear whether
antioxidant supplementation affects exercise performance [709].

Proposed ergogenic value

Recommended Dietary Allowances (RDA) based on the 1989 Food & Nutrition Board, National Academy of Sciences-National Research Council recommendations. Updated in 2001

RDA

Nutrient

Table 1 Proposed nutritional ergogenic aids – vitamins (Continued)

Kerksick et al. Journal of the International Society of Sports Nutrition (2018) 15:38
Page 17 of 57

Phosphate has been studied for its ability to improve all three energy systems,
primarily the oxygen system or aerobic capacity.

An electrolyte that helps regulate fluid balance, nerve transmission, and acid-basebalance. Some suggest excessive increases or decreases in potassium may
predispose athletes to cramping.

1000 mg/d(ages 19–50)

Males 35 mcg/dFemales 25 mcg/d(ages 19–50)

Males 8 mg/d
Females 18 mg/d(age 19–50)

Males 420
Females 320

700 mg/d2000 mg/da

55 mcg/d

500 mg/da

None

Males 11 mg/d
Females 8 mg/d

Calcium

Chromium

Iron

Magnesium

Phosphorus(phosphate salts)

Potassium

Selenium

SodiumVanadyl sulfate(vanadium)

Zinc

Studies indicate that zinc supplementation (25 mg/d) during training minimized
exercise-induced changes in immune function [125, 698, 737, 738].

Limited research has shown that type 2 diabetics may improve their glucose
control; however, there is no proof that vanadyl sulfate has any effect on muscle
mass, strength, or power [412, 413].

During the first several days of intense training in the heat, a greater amount of
sodium is lost in sweat. Additionally, prolonged ultraendurance exercise may
decrease sodium levels leading to hyponatremia. Increasing salt availability during
heavy training in the heat has been shown to help maintain fluid balance andprevent hyponatremia [160, 736].

Although selenium may reduce lipid peroxidation during aerobic exercise,
improvements in aerobic capacity have not been demonstrated [734, 735].

Although potassium loss during intense exercise in the heat has been anecdotallyassociated with muscle cramping, the etiology of cramping is unknown [732, 733].
It is unclear whether potassium supplementation in athletes decreases theincidence of muscle cramping [160]. No ergogenic effects reported.

Recent well-controlled research studies reported that sodium phosphate
supplementation (4 g/d for 3 d) improved the oxygen energy system inendurance tasks [504–506]. There appears to be little ergogenic value ofother forms of phosphate (i.e., calcium phosphate, potassium phosphate).
More research is needed to determine the mechanism for improvement.

Most well-controlled research indicates that magnesium supplementation(500 mg/d) does not affect exercise performance in athletes unless there is a
deficiency [730, 731].

Most research shows that iron supplements do not appear to improve aerobic
performance unless the athlete is iron-depleted and/or has anemia [729].

Animal research indicates that chromium supplementation increases lean bodymass and reduces body fat. Early research on humans reported similar results[285], however, more recent well-controlled studies reported that chromium
supplementation (200 to 800 mcg/d) does not improve lean body mass or
reduce body fat [287, 291].

Calcium supplementation may be beneficial in populations susceptible toosteoporosis [726]. Additionally, calcium supplementation has been shown topromote fat metabolism and help manage body composition [727, 728]. Calcium
supplementation provides no ergogenic effect on exercise performance.

Studies which have investigated the effects of 7 wk. of boron supplementation(2.5 mg/d) during resistance training on testosterone levels, body composition,and strength have reported no ergogenic value [280, 281]. There is no evidence
at this time that boron supplementation during resistance-training promotes
muscle growth.

Summary of research findingsaRecommended Dietary Allowances (RDA) based on the 2002 Food & Nutrition Board, National Academy of Sciences-National Research Council recommendations
Estimated minimum requirement

Constituent of enzymes involved in digestion. Associated with immunity.
Theorized to reduce incidence of upper respiratory tract infections in athletes
involved in heavy training.

Vanadium may be involved in reactions in the body that produce insulin-like
effects on protein and glucose metabolism. Due to the anabolic nature of insulin,
this has brought attention to vanadium as a supplement to increase muscle mass,
enhance strength and power.

Marketed as a supplement to increase aerobic exercise performance. Working
closely with vitamin E and glutathione peroxidase (an antioxidant), selenium
may destroy destructive free radical production of lipids during aerobic exercise.

Activates enzymes involved in protein synthesis. Involved in ATP reactions. Serumlevels decrease with exercise. Some suggest that magnesium supplementation
may improve energy metabolism/ATP availability.

Iron supplements are used to increase aerobic performance in sports that use
the oxygen system. Iron is a component of hemoglobin in the red blood cell,which is a carrier of oxygen.

Chromium, commonly sold as chromium picolinate, has been marketed withclaims that the supplement will increase lean body mass and decrease bodyfat levels.

Involved in bone and tooth formation, blood clotting, and nerve transmission.
Stimulates fat metabolism. Diet should contain sufficient amounts, especially ingrowing children/adole [285] scents, female athletes, and postmenopausal women.
Vitamin D needed to assist absorption.

Boron has been marketed to athletes as a dietary supplement that may promotemuscle growth during resistance training. The rationale was primarily based on
an initial report that boron supplementation (3 mg/d) significantly increased
β-estradiol and testosterone levels in postmenopausal women consuming adiet low in boron.

None

Boron

Proposed ergogenic value

RDA

Nutrient

Table 2 Proposed nutritional ergogenic aids – minerals

Kerksick et al. Journal of the International Society of Sports Nutrition (2018) 15:38
Page 18 of 57

Kerksick et al. Journal of the International Society of Sports Nutrition (2018) 15:38

minerals may provide support to bolster an athlete’s
health or physical performance.
Water

The most important nutritional ergogenic aid for athletes is water and limiting dehydration during exercise is
one of the most effective ways to maintain exercise capacity. Before starting exercise, it is highly recommended
that individuals are adequately hydrated [162]. Exercise
performance can be significantly impaired when 2% ormore of body weight is lost through sweat (i.e., a 1.4 kg
body weight loss from a 70-kg athlete). When one considers that average sweat rates are reported to be 0.5–
2.0 L/hour during exercise and training [128, 162], performance losses due to water loss can occur after just
60–90 min of exercise. Further, weight loss of more than
4% of body weight during exercise may lead to heat illness, heat exhaustion, heat stroke, and possibly death[128]. For this reason, it is critical that athletes adopt a
mind set to prevent dehydration first by promoting optimal levels of pre-exercise hydration. Throughout the day
and without any consideration of when exercise is occurring, a key goal is for an athlete to drink enough fluids
to maintain their body weight. Next, athletes can promote optimal pre-exercise hydration by ingesting
500 mL of water or sports drinks the night before acompetition, another 500 mL upon waking and then another 400–600 mL of cool water or sports drink 20–
30 min before the onset of exercise. Once exercise commences, the athlete should strive to consume a sufficientamount of water and/or glucose-electrolyte solutions(i.e., sports drinks) during exercise to maintain hydration
status. Consequently, to maintain fluid balance and prevent dehydration, athletes need to plan on ingesting 0.5
to 2 L/hour of fluid to offset weight loss. This requires
frequent (every 5–15 min) ingestion of 12–16 fluid
ounces of cold water or a sports drink during exercise[128, 163–166]. Athletes should not depend on thirst to
prompt them to drink because people do not typically
get thirsty until they have lost a significant amount of
fluid through sweat. Additionally, athletes should weighthemselves prior to and following exercise training tomonitor changes in fluid balance and then can work to replace their lost fluid [128, 163–166]. During and after exercise, athletes should consume three cups of water for every
pound lost during exercise to promote adequate rehydration [128]. A primary goal soon after exercise should be tocompletely replace lost fluid and electrolytes during a training session or competition. Additionally, sodium intake inthe form of glucose-electrolyte solutions (vs. only drinking
water) and making food choices and modifications (added
salt to foods) should be considered during the rehydration process to further promote euhydration [167].
Athletes should train themselves to tolerate drinking

Page 19 of 57

greater amounts of water during training and makesure that they consume more fluid in hotter/humid
environments. Beyond nutrition, allowing one’s physiology the chance to acclimatize to the exercising environment for 10–14 days can help improve heat
tolerance and promote thermoregulation. Finally, inappropriate and excessive weight loss techniques (e.g.,
cutting weight in saunas, wearing rubber suits, severe
dieting, vomiting, using diuretics, etc.) are considereddangerous and should be prohibited. Sport nutritionists, dietitians, and athletic trainers can play an important role in educating athletes and coaches aboutproper hydration methods and supervising fluid intake
during training and competition.
Dietary supplements and athletes

Educating athletes and coaches about nutrition and how to
structure their diet to optimize performance and recovery
are key areas of involvement for sport dietitians and nutritionists. Currently, use of dietary supplements by athletes
and athletic populations is widespread while their overallneed and efficacy of certain ingredients remain up for
debate. Dietary supplements can play a meaningful role inhelping athletes consume the proper amount of calories,
macro- and micronutrients. Dietary supplements are notintended to replace a healthy diet. Numerous dietary ingredients have been investigated for potential benefits in an
athletic population, to enhance training, recovery and/or
performance. Supplementation with these nutrients inclinically validated amounts and at opportune times canhelp augment the normal diet to help optimize performance or support adaptations towards a training outcome.
Sport dietitians and nutritionists must be aware of thecurrent data regarding nutrition, exercise, and performanceand be honest about educating their clients about results ofvarious studies (whether pro or con). Currently, misleading
information is available to the public and this position
stand is intended to objectively rate many of the available
ingredients. Additionally, athletes, coaches and trainers
need to also heed the recommendations of scientists whenrecommendations are made according to the available literature and what will hopefully be free of bias. Throughout
the next two sections of this paper, various nutritional supplements often taken by athletes will be categorized into
three categories: Strong Evidence to Support Efficacy andApparently Safe, Limited or Mixed Evidence to Support Efficacy, Little to No Evidence to Support Efficacy and/or
Safety. Based on the available literature, the resulting classification and analysis focuses primarily on whether the proposed nutrient has been found to affect exercise and/or
training adaptations through an increase in muscle hypertrophy and later for the supplement’s ergogenic potential.
We recognize that some ingredients may exhibit little
potential to stimulate training adaptations or operate in anKerksick et al. Journal of the International Society of Sports Nutrition (2018) 15:38

ergogenic fashion, but may favorably impact muscle recovery or exhibit health benefits that may be helpful for some
populations. These outcomes are not the primary focus of
this review and consequently, will not be discussed withthe same level of detail.
Convenience supplements

Convenience supplements are commonly found in theform of meal replacement powders (MRP’s), ready to drink
supplements (RTD’s), energy bars, and energy gels. These
products are typically fortified with vitamins and minerals
and differ on the amount of carbohydrate, protein, and/or
fat they contain. Uniqueness of these products come fromthe additional nutrients they contain that are purported topromote weight gain, alter body composition, enhancerecovery, and/or improve performance. Most people view
these supplements as a nutrient dense snack and/or use
them to help control caloric intake when trying to gain
and/or lose weight. MRP’s, RTD’s, and energy bars/gelscan provide a convenient way for people to meet specificdietary needs and/or serve as good alternatives to fast food,
foods of lower nutritional quality, and during times whentravel or a busy schedule preclude the ability to consume
fresh or other forms of whole food. Use of these types of
products are particularly helpful in providing carbohydrate,
protein, and other nutrients prior to and/or following exercise to optimize nutrient intake when an athlete doesn’t
have time to sit down for a good meal or wants tominimize food volume. Consequently, meal replacements
should be used in place of a meal during unique situations
and are not intended to replace all meals. Care should also
be taken to make sure they do not contain any banned or
prohibited nutrients.
Muscle building supplements

The following section provides an analysis of the scientific
literature regarding nutritional supplements purported topromote skeletal muscle accretion in conjunction with thecompletion of a well-designed exercise-training program.
An overview of each supplement and a general interpretation of how they should be categorized is provided
throughout the text. Table 3 summarizes how every supplement discussed in this article is categorized. However,within each category all supplements are ordered alphabetically. The reader is encouraged to consider that gains orlosses in body masses may positively or negatively impact
an individual’s athletic performance. For example, increases
in body mass and lean mass are desired adaptations formany American football or rugby players and may improve
performance in these activities. In contrast, decreases inbody mass or fat mass may promote increases in performance such as cyclists and gymnasts whereby athletes suchas wrestlers, weightlifters and boxers may need to rapidly

Page 20 of 57

reduce weight while maintaining muscle mass, strengthand power.
Strong evidence to support efficacy and apparently safe

β-hydroxy β-methylbutyrate (HMB) HMB is a metabolite of the amino acid leucine. It is well-documented that
supplementing with 1.5 to 3 g/day of calcium HMB duringresistance training can increase muscle mass (+ 0.5–1 kg
greater than controls during 3–6 weeks of training) andstrength particularly among untrained subjects initiating
training [168–173] and the elderly [174]. The currently
established minimal effective dose of HMB is 1.5 g per day,with 3 g per day offering additional benefits on lean bodymass, while 6 g per day do not provide any additional gains
in lean mass beyond what was reported with a 3 g dose[169]. To optimize HMB retention, its recommend to split
the daily dose of 3 g into three equal doses of 1 g each(with breakfast, lunch or pre-exercise, bedtime) [174]. Froma safety perspective, dosages of 1.5–6 g per day have been
well tolerated [15, 169, 170]. The effects of HMB supplementation in trained athletes are less clear with selectedstudies reporting non-significant gains in muscle mass
[175–177]. In this respect, it has been suggested by Wilson
and colleagues [15] that program design (periodized resistance training models) and duration of supplementation(minimum of 6 weeks) likely operate as key factors. In
2015, Durkalec-Michalski and investigators [178] supplemented highly trained rowers (n = 16) in a randomized,
double-blind, crossover fashion with either 3 g per day ofcalcium-HMB or a placebo. Before and after each supplementation period, body composition and performance parameters were assessed. When HMB was provided, fat
mass was significantly reduced while changes in lean mass
were not significant between groups. The same researchgroup published data of 58 highly trained males athletes
who supplemented with either 3 g of calcium-HMB or placebo for 12 weeks in a randomized, double-blind, crossoverfashion [179]. In this report, fat mass was found to besignificantly reduced while fat-free mass was significantly
increased. Finally, Durkalec-Michalski and investigators[180] supplemented 42 highly-trained combat sport athletes for 12 weeks with either a placebo or 3 g ofcalcium-HMB in a randomized, double-blind, crossoverfashion. When HMB was provided, fat-free mass wasshown to increase (p = 0.049) while fat mass was significantly reduced in comparison to the changes seen whenplacebo was provided. In conclusion, a growing body of literature continues to offer support that HMB supplementation at dosages of 1.5–3 g for durations as short as three to
4 weeks in untrained populations and longer durations(12 weeks) in trained populations can lead to improvements in fat mass and fat-free mass while participating invarious forms of exercise training.

Kerksick et al. Journal of the International Society of Sports Nutrition (2018) 15:38

Page 21 of 57

Table 3 Summary of categorization of dietary supplements based on available literature
Category

Muscle building supplements

Performance enhancement

I. Strong Evidence to Support Efficacy andApparently Safe

• HMB
• Creatine monohydrate• Essential amino acids (EAA)• Protein• β-alanine• Caffeine• Carbohydrate• Creatine Monohydrate• Sodium Bicarbonate• Sodium Phosphate• Water and Sports Drinks

II. Limited or Mixed Evidence to Support
Efficacy• Adenosine-5′-Triphosphate (ATP)• Branched-chain amino acids (BCAA)• Phosphatidic acid

• L-Alanyl-L-Glutamate• Arachidonic acid
• Branched-chain amino acids (BCAA)• Citrulline• Essential amino acids (EAA)• Glycerol• HMB• Nitrates• Post-exercise carbohydrate andprotein• Quercetin• Taurine

III. Little to No Evidence to Support Efficacy
and/or Safety• Agmatine sulfate• Alpha-ketoglutarate• Arginine• Boron• Chromium• Conjugated linoleic acids (CLA)• D-Aspartic acid
• Ecdysterones• Fenugreek extract• Gamma oryzanol (Ferulic acid)• Glutamine• Growth-hormone releasing peptides andSecretogogues• Isoflavones• Ornithine-alpha-ketoglutarate• Prohomones• Sulfo-polysaccharides• Tribulus terrestris• Vanadyl sulfate• Zinc-magnesium aspartate• Arginine• Carnitine• Glutamine• Inosine• Medium-chain triglycerides (MCT)• Ribose

Creatine monohydrate In our view, the most effective
nutritional supplement available to athletes to increase highintensity exercise capacity and muscle mass during training
is creatine monohydrate. Numerous studies have indicatedthat creatine supplementation increases body mass and/or
muscle mass during training [181, 182]. Body mass increases are typically one to two kilograms greater than controls during 4–12 weeks of training [182]. The gains inmuscle mass appear to be a result of an improved ability toperform high intensity exercise enabling an athlete to train
harder and thereby promote greater training adaptations
and muscle hypertrophy [183–186]. The only clinically significant side effect occasionally reported from creatine
monohydrate supplementation has been the potential forweight gain [181, 182, 187, 188]. Although concerns havebeen raised about the safety and possible side effects ofcreatine supplementation [189, 190], multiple shorter[191–193] and long-term safety studies have reported noapparent side effects [188, 194, 195] and/or that creatine
monohydrate may lessen the incidence of injury during

training [196–199]. Consequently, supplementing the dietwith creatine monohydrate and/or creatine containing
formulations seems to be a safe and effective method toincrease muscle mass. The ISSN position stand on creatine
monohydrate [10] summarizes their findings as this:
1. Creatine monohydrate is the most effective
ergogenic nutritional supplement currently
available to athletes in terms of increasing
high-intensity exercise capacity and lean bodymass during training.
2. Creatine monohydrate supplementation is not only
safe, but has been reported to have a number oftherapeutic benefits in healthy and diseased populations
ranging from infants to the elderly. There is nocompelling scientific evidence that the short- or
long-term use of creatine monohydrate (up to 30 g/
day for 5 years) has any detrimental effects on otherwise
healthy individuals or among clinical populations who
may benefit from creatine supplementation.

Kerksick et al. Journal of the International Society of Sports Nutrition (2018) 15:38

3. If proper precautions and supervision are provided,
creatine monohydrate supplementation in children
and adolescent athletes is acceptable and may
provide a nutritional alternative with a favorable
safety profile to potentially dangerous anabolic
androgenic drugs. However, it is recommended thatcreatine supplementation only be considered for use
by younger athletes who: a) are involved in serious/
competitive supervised training; b) are consuming awell-balanced and performance enhancing diet; c)
are knowledgeable about the appropriate use ofcreatine; and d) do not exceed recommended
dosages.
4. Label advisories on creatine products that caution
against usage by those under 18 years old, while
perhaps intended to insulate their manufacturers
from legal liability, are likely unnecessary given thescience supporting creatine’s safety, including inchildren and adolescents.
5. At present, creatine monohydrate is the mostextensively studied and clinically effective form ofcreatine for use in nutritional supplements in termsof muscle uptake and ability to increase high-intensity
exercise capacity.
6. The addition of carbohydrate or carbohydrate andprotein to a creatine supplement appears to increase
muscular uptake of creatine, although the effect on
performance measures may not be greater than using
creatine monohydrate alone.
7. The quickest method of increasing muscle creatine
stores appears to be to consume ~ 0.3 g/kg/day ofcreatine monohydrate for 5–7 days followed by
3–5 g/day thereafter to maintain elevated stores.
Initially, ingesting smaller amounts of creatine
monohydrate (e.g., 3–5 g/day) will increase muscle
creatine stores over a three to 4 week period,
however, the initial performance effects of thismethod of supplementation are less supported.
8. Clinical populations have been supplemented withhigh levels of creatine monohydrate (0.3–0.8 g/kg/
day equivalent to 21–56 g/day for a 70-kg
individual) for years with no clinically significant
or serious adverse events.
9. Further research is warranted to examine thepotential medical benefits of creatine monohydrate
and precursors like guanidinoacetic acid on sport,
health and medicine.
Essential amino acids (EAA) Research examining theimpact of the essential amino acids on stimulating muscle
protein synthesis is an extremely popular area. Collectively,
this data indicates that ingesting 6–12 g of the essential
amino acids (EAA) in the absence of feeding [200] andprior to [201, 202] and/or following resistance exercise

Page 22 of 57

stimulates protein synthesis [202–208], with this response
being largely independent of the protein source or foodtype [209]. Theoretically, this may enhance increases infat-free mass, but to date limited evidence exists to demonstrate that supplementation with non-intact sources of
EAAs (e.g., free form amino acids) while resistance training
positively impacts fat-free mass accretion. Moreover, otherresearch has indicated that changes in muscle protein
synthesis may not correlate with phenotypic adaptations toexercise training [210]. An abundance of evidence is available, however, to indicate that ingestion of high-quality protein sources can heighten adaptations to resistance training[211]. While various methods of protein quality assessment
exist, most of these approaches center upon the amount of
EAAs that are found within the protein source, and innearly all situations, the highest quality protein sources arethose containing the highest amounts of EAAs. To thispoint, a number of published studies are available that state
the EAAs operate as a prerequisite to stimulate peakrates of muscle protein synthesis [212–215]. To better
understand the impact of ingesting free-form aminoacids versus an intact protein source, Katsanos et al.
[216] administered similar doses of the essential aminoacids (6.72 g) as part of an intact protein (15 g of whey
protein isolate) source or as free amino acids while
completing a resistance training program in elderly
adults. Protein accrual was greater when the amino aciddose was provided in an intact source. While the age ofthe participants in this study may have impacted outcomes [217], this study’s results do highlight the needfor more research to better understand to what extent
training adaptations are due to the EAA content or if
additional benefits are present from ingesting an intact
protein source.
While the EAAs are comprised of nine separate aminoacids, some individual EAAs have received considerable
attention for their potential role in impacting protein translation and muscle protein synthesis. In this respect, thebranched-chain amino acids have been highlighted for theirpredominant role in stimulating muscle protein synthesis[218, 219]. To this point, Karlsson and colleagues [220]demonstrated significantly higher increases in p70s6k
expression in recovery from a single bout of lower-bodyresistance exercise in seven male participants after ingesting a BCAA solution containing 100 mg/kg BCAA whencompared to ingesting a placebo. Interestingly, Moberg
and investigators [221] had trained volunteers complete astandardized bout of resistance training in conjunction
with ingestion of placebo, leucine, BCAA or EAA whilemeasuring changes in post-exercise activation of p70s6k.
They concluded that EAA ingestion led to a nine-foldgreater increase in p70s6k activation and that these results
were primarily attributable to the BCAAs. Finally, a 2017
study by Jackman et al. [222] compared the ability of a

Kerksick et al. Journal of the International Society of Sports Nutrition (2018) 15:38

5.6 g dose of BCAAs (versus a placebo) to stimulate increases in muscle protein synthesis. Myofibrillar muscle
protein synthesis rates were increased significantly (~ 20%,
p < 0.05) in comparison to a placebo. While significant, thismagnitude of change was notably less than the
post-exercise MPS responses seen when doses of whey protein that delivered similar amounts of the BCAAs wereconsumed [88, 223]. These outcomes led the authors toconclude that the full complement of EAAs was advised tomaximally stimulate increases in MPS.
Of all the interest captured by the BCAAs, leucine isaccepted to be the primary driver of acute changes in protein translation. In this respect, Dreyer et al. [224] andothers [225] have reported that providing leucine after
completion of resistance exercise can further potentiateincreases in mTOR signalling and protein translation. In
this respect, Jager et al. [11] have highlighted that an ideal
dose of leucine to stimulate increases in protein translation is likely somewhere between 1.7–3.5 g.
Protein A growing body of literature is available thatsuggests higher amounts of protein are needed by exercising individuals to optimize exercise training adaptations [11, 83, 211, 226]. Collectively, these sourcesindicate that people undergoing intense training withthe primary intention to promote accretion of fat-freemass should consume between 1.4–2.0 g of protein per
kilogram of body weight per day [83, 226]. Tang and colleagues [95] conducted a classic study that examined theability of three different sources of protein (hydrolyzed
whey isolate, micellar casein and soy isolate) to stimulate
acute changes in muscle protein synthesis both at rest
and after a single bout of resistance exercise. These authors concluded that all three protein sources significantly increased muscle protein synthesis rates both atrest and in response to resistance exercise. When this response is extrapolated over the course of several weeks,
multiple studies have reported on the ability of different
forms of protein to significantly increase fat-free mass
while resistance training [70, 227–232]. Cermak et al.
[211] performed a meta-analysis that examined the impact of protein supplementation on changes in strengthand fat-free mass. Data from 22 separate published studies that included 680 research participants were includedin the analysis. These authors concluded that protein
supplementation demonstrated a positive effect of
fat-free mass and lower-body strength in both younger
and older participants. Similarly, Morton and investigators [83] published results from a meta-analysis that also
included a meta-regression approach involving data from49 studies and 1863 participants. They concluded thatthe ability of protein to positively impact fat-free massaccretion increases up to approximately 1.62 g of protein
per kilogram of body weight per day whereby higher

Page 23 of 57

amounts beyond that do not appear to promote greater
gains in fat-free mass. Although more research is necessary
in this area, evidence clearly indicates that protein needs ofindividuals engaged in intense training are elevated andconsequently those athletes who achieve higher intakes ofprotein while training promote greater changes in fat-freemass. Beyond the impact of protein to foster greatertraining-induced adaptations such as increases instrength and muscle mass, several studies have examined the ability of different types of protein to stimulate changes in fat-free mass [229, 231, 233–235]
while several studies and reviews have critically explored the role protein may play in achieving weightloss in athletes [236, 237] as well as during periods ofcaloric restriction [238, 239]. Therefore, it is simplistic andmisleading to suggest that there is no data supporting
contentions that athletes need more protein in their dietand/or there is no potential ergogenic value of incorporating different types of protein into the diet. It is the position stand of ISSN that exercising individuals needapproximately 1.4 to 2.0 g of protein per kilogram ofbodyweight per day [11].
Limited or mixed evidence to support efficacy

Adenosine − 5′-triphosphate (ATP) ATP is the primary
intracellular energy source and in addition, has extensive
extracellular functions including the increase in skeletal
muscle calcium permeability and vasodilation. While intravenous administration of ATP is bioavailable [240], several
studies have shown that oral ATP is not systematically bioavailable [241]. However, chronic supplementation with
ATP increases the capacity to synthesize ATP within theerythrocytes without increasing resting concentrations in
the plasma, thereby minimizing exercise-induced drops in
ATP levels [242]. Oral ATP supplementation has demonstrated initial ergogenic properties, after a single dose, improving total weight lifted and total number of repetitions[243]. ATP may increase blood flow to the exercisingmuscle [244] and may reduce fatigue and increase peak
power output during later bouts of repeated bouts exercise[242]. ATP may also support greater recovery and leanmass maintenance under high volume training [245], however, this has only been reported in one previous study. In
addition, ATP supplementation in clinical populations has
been shown to improve strength, reduce pain after knee
surgery, and reduce the length of the hospital stay [246].
However, given the limited number of human studies of
ATP on increasing exercise-induced gains in muscle mass,
more chronic human training studies are warranted.
Branched chain amino acids (BCAA) BCAA supplementation has been reported to decrease exercise-induced
protein degradation and/or muscle enzyme release (anKerksick et al. Journal of the International Society of Sports Nutrition (2018) 15:38

indicator of muscle damage) possibly by promoting ananti-catabolic hormonal profile [118, 247, 248] and more
recent studies support their ability to favorably promoteresponses to damaging eccentric muscle contractions[249, 250]. Leucine, in particular, is recognized as a keystone of sorts that when provided in the correct amounts(3–6 g) activates the mTORC1 complex resulting in favorable initiation of translation [251]. To highlight this impact for leucine, varying doses of whey protein andleucine levels were provided to exercising men at rest andin response to an acute bout of lower-body resistance exercise to examine the muscle protein synthetic response.
Interestingly, when a low dose of whey protein (6.25 g)
was enriched with leucine to equal the leucine content
found in a 25-g dose of whey protein, the ability to stimulate muscle protein synthesis was retained. While the 25-gdose of whey protein did favorably sustain the increases inmuscle protein synthesis, the added leucine highlights animportant role for leucine in stimulating muscle protein
synthesis in response to resistance exercise [223]. For thesereasons, it has been speculated that the leucine content ofwhey protein and other high-quality protein sources havebeen suggested to be primary reasons for their ability tostimulate favorable adaptations to resistance training[252, 253]. Theoretically, BCAA supplementation during
intense training may help minimize protein degradationand thereby lead to greater gains in (or limit losses of)fat-free mass, but only limited evidence exists to support
this hypothesis. For example, Schena and colleagues [254]reported that BCAA supplementation (~ 10 g/d) during
21-days of trekking at altitude increased fat free mass
(1.5%) while subjects ingesting a placebo had no change inmuscle mass. Bigard and associates [255] reported thatBCAA supplementation appeared to minimize loss ofmuscle mass in subjects training at altitude for 6 weeks.
Finally, Candeloro and coworkers [256] reported that
30 days of BCAA supplementation (14 g/day) promoted asignificant increase in muscle mass (1.3%) and grip
strength (+ 8.1%) in untrained subjects. Alternatively, Spillane and colleagues [257] reported that 8 weeks of resistance training while supplementing with either 9 g of
BCAAs or placebo did not impact body composition or
muscle performance. Most recently, Jackman et al. [222]examined the ability of an acute dose of branched-chainamino acids to stimulate increases in muscle protein synthesis. While acute ingestion of BCAAs did promote a
22% greater increase in muscle protein synthesis whencompared to a placebo, the determined rates were 50%
lower than what is commonly seen when a dose of whey
protein containing similar amounts of BCAAs is ingested.
As mixed outcomes cloud the ability to make clear
determinations, studies strongly suggest a mechanisticrole for BCAAs and in particular leucine, yet translational data fails to consistently support the need forPage 24 of 57

BCAA supplementation. Alternatively, multiple studies
do support BCAAs ability to mitigate recovery fromdamaging exercise while their ability to favorably impact resistance training adaptations needs further research. This will be discussed in a later section.
Phosphatidic acid Phosphatidic acid (PA) is a diacyl-glycerophospholipid that is enriched in eukaryotic cell membranes and it can act as a signalling lipid [258].
Interestingly, PA has been repeatedly shown to activate themammalian target of rapamycin (mTOR) signalling inmuscle; an effect which ultimately leads to increases inmuscle protein synthesis. For instance, Fang et al. [259]
demonstrated that PA activates mTOR in vitro.
Hornberger et al. [260] also reported that mechanicalstretching of skeletal muscle in situ promotes an increase in intramuscular PA levels and this effect was
associated with the activation of mTOR signalling. To
date, two chronic human supplementation studies
have been performed whereby PA supplementation(750 mg/day) occurred in subjects engaged in resistance training. Hoffman et al. [261] reported that PA
supplementation increased whole-body lean bodymass (LBM) by 1.7 kg, whereas the placebo groupdemonstrated no relative change in LBM (0.1 kg; p =0.065 between groups). Joy et al. [262] performed asimilar eight-week study with more participants andsupervised training sessions, and reported that PA
supplementation significantly increased LBM by 2.4 kg,
whereas the placebo group demonstrated marginal increases in LBM (1.2 kg; p < 0.05 between groups). A third
study confirmed the beneficial effects of PA on
exercise-induced gains in lean body mass [263]. The currently established dose of PA is 750 mg per day and another study investigating lower doses, 375 and 250 mg perday, failed to show significant benefits on lean body mass[264]. Hence, preliminary human research suggests that
PA supplementation can increase anabolic signalling inskeletal muscle and enhance gains in muscle mass with resistance training. Given that PA supplementation studies
are in their infancy relative to other muscle-building supplements (e.g., whey protein, creatine, HMB, etc.), futurestudies are needed in order to determine the optimal dosage, timing, and duration of supplementation needed for
optimal muscle mass gains.
Little to no evidence to support efficacy and/or safety
Agmatine sulfate

Agmatine, the decarboxylation product of the aminoacid L-arginine, has shown different biological effects indifferent in vitro and animal models [265] indicating
potential benefits in an athletic population. Agmatine isthought to improve insulin release and glucose uptake,assist in the secretion of luteinizing hormone, influenceKerksick et al. Journal of the International Society of Sports Nutrition (2018) 15:38

the nitric oxide signalling pathway, offer protection fromoxidative stress, and is potentially involved in neurotransmission [266]. It is mostly found in fermented foods[267], with higher levels found in alcoholic beverages.
Currently, nearly all research involving agmatine is commonly from animal research models and no human studies
have been conducted to examine its impact on blood flow
or impacting resistance training adaptations such as
strength and body composition. There does not appear tobe any scientific evidence that Agmatine supports increases
in lean body mass or muscular performance.
α-ketoglutarate (α-KG)

α-ketoglutarate (α-KG) is an intermediate in the Krebs
cycle that is involved in aerobic energy metabolism andmay function to stimulate nitric oxide production. Thereis some clinical evidence that α-KG may serve as an
anticatabolic nutrient after surgery [268, 269]. However,
it is unclear whether α-KG supplementation during
training may affect training adaptations. Very little
research has been conducted on just alpha-ketoglutarate
in humans to examine exercise outcomes. For example,
Little and colleagues [270] supplemented with creatine, acombination of creatine, α-KG, taurine, BCAA andmedium-chain triglycerides, or a placebo. The combination of nutrients increased the maximal number ofbench press repetitions completed and Wingate peak
power while no changes were reported in the placebogroup. Campbell and investigators [271] supplemented
35 healthy trained men with 2 g of arginine and 2 g ofα-KG or placebo in a double-blind manner while resistance training for 8 weeks. Supplementation with arginine+ α-KG increased bench press strength and Wingate peak
power, but did not impact body composition. Finally, Willoughby and colleagues [272] examined the results ofarginine α-KG supplementation in relation to increasing
nitric oxide production (vasodilation during resistance
exercise), hemodynamics, brachial artery flow, circulatinglevels of l-arginine, and asymmetric dimethyl arginine inactive males. This study found that although plasma
L-arginine increased, there was no significant impact of
supplementation on nitric oxide production after a boutof resistance exercise. Due to the lack of research on
α-KG examining its impact on exercise training adaptations, its use cannot be recommended at this time.

Page 25 of 57

while resistance training. Tang and colleagues [274] used
an acute model to examine the ability of an oral 10-g doseof arginine to stimulate changes in muscle protein synthesis. These authors reported that arginine administration
failed to impact muscle protein synthesis or femoral arteryblood flow. Growth hormone levels did rise in response toarginine ingestion, which contrasts with the findings ofForbes et al., [275] who reported a blunting of growth hormone production after acute ingestion of arginine instrength trained males. Regardless, the Tang study [274]and others [276, 277] failed to link the increase in growth
hormone to changes in rates of muscle protein synthesis.
Notably, other studies have also failed to show a change inblood flow after arginine ingestion, one of its key purported benefits [272, 278]. Campbell and colleagues published outcomes from an 8 week resistance training study
that supplemented healthy men in a double-blind fashion
with either a placebo or 2 g of arginine and 2 g of
α-ketoglutarate. No changes in fat mass or fat-free mass
were reported in this study. Therefore, due to the limited
data of arginine supplementation on stimulating further
increases of exercise in muscle mass, its use for is not recommended at this time.
Boron

Boron is a trace mineral whose physiological role is notclearly understood. A number of proposed functions havebeen touted for boron: vitamin D metabolism, macromineral metabolism, immune support, increase testosterone
levels and promote anabolism [279]. Due to a lack ofscientific evidence surrounding boron, no official Daily
Reference Intake (DRI) is established. Several studies haveevaluated the effects of boron supplementation during
training on strength and body composition alterations.
However, these studies (conducted on male bodybuilders)
indicate that boron supplementation (2.5 mg/d) had no
significant impact on muscle mass or strength [280, 281].
Further, two investigations [282, 283] examined the impact
of boron supplementation on bone mineral density inathletic and sedentary populations. In both investigations,boron supplementation did not significantly influencebone mineral density. Therefore, due to the limited
findings on boron supplementation, its use is not recommended, and more research is warranted to determine its
physiological impact.

Arginine

Chromium

Arginine is commonly classified as a conditionally essential
amino acid and has been linked to nitric oxide production
and increases in blood flow that are purported to thenstimulate enhanced nutrient and hormone delivery andfavorably impact resistance training adaptations [273]. To
date, few studies have examined the independent impact ofarginine on the ability to enhance fat-free mass increases

Chromium is a trace mineral that is actively involved inmacronutrient metabolism. Clinical studies have suggested that chromium potentiates the effects of insulin,
particularly in diabetic populations. Due to its closeinteraction with insulin, chromium supplementation has
been theorized to impact anabolism and exercise training
adaptations. Initial research was promising with chromiumKerksick et al. Journal of the International Society of Sports Nutrition (2018) 15:38

supplementation being associated with increases in muscle
and strength, particularly in women [284–286]. Subsequentwell-controlled research studies [287] since that time haveconsistently failed to report a benefit for chromium supplementation (200–800 μg/d for 4–16 weeks) [288–294].
Most recently, chromium supplementation was investigated for its ability to impact glycogen synthesis after
high-intensity exercise and was found to exert no impact
over recovery of glycogen [295]. In summary, chromium
supplementation appears to exert very little potential for
its ability to stimulate or support improvements in fat-freemass. Therefore, due to the limited data of arginine supplementation on stimulating further increases of exercise inmuscle mass, its use for is not recommended at this time.
Conjugated linoleic acids (CLA)

Animal studies indicate that adding CLA to dietary feeddecreases body fat, increases muscle and bone mass, hasanti-cancer properties, enhances immunity, and inhibits
progression of heart disease [296–298]. Although animalstudies are impressive [299–301], human studies, at best,
suggest a modest ability, independent of exercise or dietchanges, of CLA to stimulate fat loss [302–305]. Moreover, very little research has been conducted on CLA tobetter understand if any scenario exists where its use
may be justified. Initial work by Pinkoski et al. [306] suggested that CLA supplementation may help minimize
catabolism while resistance training, but overall improvements in body composition from this study failed
to yield positive outcomes. Two studies are available that
supplemented exercising younger [307] and older individuals [308] with a combination of CLA and creatine
and reported significant improvements in strength andbody composition, but these results are thought to be
the result of creatine. Currently, it seems there is little
evidence that CLA supplementation during training canaffect lean tissue accretion and has limited efficacy [309].

Page 26 of 57

testosterone and other anabolic hormones. Later, Melvilleet al. [312] supplemented 22 men in a randomized,
double-blind fashion with either a placebo or 6 g ofD-aspartic acid and concluded that 12 weeks of supplementation exerted no impact on resting levels of free or
total testosterone and all changes observed in strengthor hypertrophy were similar to what was experienced in
the placebo group. Based on the currently available literature, D-aspartic acid is not recommended to improvemuscle health.
Ecdysterones

Ecdysterones (also known as ectysterone, 20 β-Hydroxyecdysterone, turkesterone, ponasterone, ecdysone, or
ecdystene) are naturally derived phytoecdysteroids (i.e.,
insect hormones). They are typically extracted from theherbs Leuza rhaptonticum sp., Rhaponticum carthamoides, or Cyanotis vaga. They can also be found inhigh concentrations in the herb Suma (also known as
Brazilian Ginseng or Pfaffia). Initial interest was generated for ecdysterones due to reports of research from
Russia and Czechoslovakia that indicated a potential
physiological benefit in insects and animals [313–316].
A review by Bucci on various herbals and exercise performance also mentioned suma (ecdysterone) [317].
Unfortunately, the initial work was available in obscurejournals with sub-standard study designs and presentationof results. In 2006, Wilborn and coworkers [318] completed what remains as the only study in humans to examine the impact of ecdysterones while resistance training.
Herein, a 200 mg daily dose of 20-hydroxyecdysone over
8 weeks yielded no impact on changes in fat free mass oranabolic/catabolic hormone status. Ecdysterones are notrecommended for supplementation to increase training
adaptations or performance.
Fenugreek extract

D-aspartic acid

Also known as aspartate, aspartic acid is a non-essential
amino acid. Two isomers exist within aspartic acid:
L-Aspartic acid and D-Aspartic acid. D-Aspartic acid isthought to help boost athletic performance and function asa testosterone booster. It is also used to conserve muscle
mass. While limited research is available in humans
examining D-aspartic, Willoughby and Leutholtz [310]published a study to determine the impact of D-aspartic
acid in relation to testosterone levels and performance inresistance-trained males. The results showed D-aspartic
acid did not impact testosterone levels nor did it improve
any aspect of performance. In agreement, Melville andcolleagues [311] had participants supplement with either
three or 6 g of D-aspartic acid and concluded that neither
dose of D-aspartic acid stimulated any changes in

Fenugreek (trigonella foenum-graecum) is an Ayurvedic
herb historically used to enhance masculinity and libido.
Fenugreek extract has been shown to increase testosterone levels by decreasing the activity of the aromatase enzyme metabolizing testosterone into estradiol [319, 320].
Initial research by Poole et al. [321] supplemented resistance trained men in a randomized, double-blind fashion
with a placebo or 500 mg of Fenugreek extract. After
8 weeks of supplementing and resistance training, significantly greater improvements in body fat, lower bodystrength, and upper body strength were observed.
Wankhede and colleagues [320] reported a significant
increase in repetitions performed to failure using thebench press and a reduction in body fat when 600 mg
Fenugreek extract was consumed while following a resistance training program. Initial research using Fenugreek

Kerksick et al. Journal of the International Society of Sports Nutrition (2018) 15:38

extract suggests it may help improve resistance-training
adaptations, but more research in different populations isneeded before any further recommendations can be made.
Gamma oryzanol (ferulic acid)

Gamma oryzanol is a mixture of a plant sterol and ferulic
acid theorized to increase anabolic hormonal responses,
strength and muscle mass during training [322, 323]. Although data are limited, one study reported no effect of
0.5 g/d of gamma oryzanol supplementation on strength,
muscle mass, or anabolic hormonal profiles during 9 weeks
of training [324]. Most recently, Eslami and colleagues[325] supplemented healthy male volunteers with either
gamma oryzanol or placebo for 9 weeks while resistancetraining. In this study, changes in body composition were
not realized, but a significant increase in strength was
found in the bench press and leg curl exercise. With limited
research of mixed outcomes at this point, no conclusive recommendation can be made at this time as
more research is needed to fully determine what impact, if any, gamma oryzanol supplementation may
have in exercising individuals.
Glutamine

Glutamine is the most plentiful non-essential amino acidin the body and plays several important physiological roles[74, 326, 327]. Glutamine has been reported to increase
cell volume and stimulate protein [328–330] and glycogensynthesis [331]. Despite its important role in physiologicalprocesses, there is no compelling evidence to support theuse of glutamine supplementation in terms of increasinglean body mass and a 2008 review by Gleeson concluded
that minimal evidence is available to support glutamine’s
purported role in exercise and sport training [332]. Initialresearch by Colker and associates [333] reported that subjects who supplemented their diet with glutamine (5 g)and BCAA (3 g) enriched whey protein (40 g) duringresistance training promoted about a two pound greater
gain in muscle mass and greater gains in strength thaningesting whey protein alone. In contrast, Kerksick andcolleagues [232] reported no additional impact onstrength, endurance, body composition and anaerobic
power of combining 5 g of glutamine and 3 g of BCAAs to
40 g of whey protein in healthy men and women who
resistance trained for 10 weeks. In addition, Antonio et al.
[334] reported that high-dose glutamine ingestion (0.3 g/kg) offered no impact of the number of repetitions
completed using the leg press or bench press exercises. Ina well-designed investigation, Candow and co-workers[335] studied the effects of oral glutamine supplementation combined with resistance training in young adults.
Thirty-one participants were randomly allocated to receive
either glutamine (0.9 g/kg of lean tissue mass) or a maltodextrin placebo (0.9 g/kg of lean tissue mass) during

Page 27 of 57

6 weeks of total body resistance training. The authors concluded glutamine supplementation during resistance training had no significant effect on muscle performance, bodycomposition or muscle protein degradation in young
healthy adults. While there may be other beneficial uses
for glutamine supplementation (i.e. gastrointestinal healthand peptide uptake in stressed populations [336] and, as
mentioned previously, mitigation of soreness and recovery
of lost force production [337]), there does not appear to be
any scientific evidence that it supports increases in leanbody mass or muscular performance.
Growth hormone releasing peptides (GHRP) and secretagogues

Growth hormone releasing peptides (GHRP) and othernon-peptide compounds (secretagogues) facilitate growth
hormone (GH) release [338, 339], and can impact sleep
patterns, food intake and cardiovascular functioning [340]
along with improvements in lean mass in clinical wastingstates [341]. These observations have served as the basis
for development of nutritionally-based GH stimulators(e.g., amino acids, pituitary peptides, “pituitary substances”,
Macuna pruriens, broad bean, alpha-GPC, etc.) and continue to capture interest by sporting populations for theirpotential to impact growth hormone secretion, recovery
and robustness of training [342]. Although there is clinicalevidence that pharmaceutical grade GHRP’s and some
non-peptide secretagogues can increase GH and IGF-1
levels at rest and in response to exercise, it has not been
demonstrated that such increases lead to an increase inskeletal muscle mass [343]. Finally, Chromiak and Antonio[344] reported that oral ingestion of many secretagogues
fail to consistently stimulate hormone increases in growth
hormone and fail to stimulate greater changes in muscle
mass or strength. Currently, there is no convincing scientific evidence that secretagogues support increases in leanbody mass or muscular performance.
Isoflavones

Isoflavones are naturally occurring non-steroidal
phytoestrogens that have a similar chemical structure as
ipriflavone (a synthetic flavonoid drug used in the treatment of osteoporosis) [345–347]. For this reason, soyprotein (which is an excellent source of isoflavones) andisoflavone extracts have been investigated in the possible
treatment of osteoporosis as well as their role in bodycomposition changes and changes in cardiovascular
health markers. In this respect, multiple studies havesupported the ability of isoflavone supplementation inolder women alone [348] and in combination with exercise over the course of 6–12 months to improvevarious body composition parameters [349–351].
Findings from these studies have some applications tosedentary, postmenopausal women. However, there
are currently no peer-reviewed data indicating that

Kerksick et al. Journal of the International Society of Sports Nutrition (2018) 15:38

isoflavone supplementation affects exercise, body composition, or training adaptations in physically active individuals. For example, Wilborn and colleagues [318] reported
that 8 weeks of supplementing with isoflavones with resistance training did not significantly impact strength orbody composition.
Ornithine-α-ketoglutarate (OKG)

OKG (via enteral feeding) has been shown to significantly
shorten wound healing time and improve nitrogen balance
in severe burn patients [352, 353]. A 2004 review by Cynober postulated that OKG may operate as a precursor toarginine and nitric oxide, but the overall lack of efficacy
for arginine and other precursors limits the potential of
OKG. Because of its ability to improve nitrogen balance,
OKG may provide some value for athletes engaged inintense training. A study by Chetlin and colleagues [354]reported that OKG supplementation (10 g/day) during
6 weeks of resistance training significantly increased upper
body strength. However, no significant differences wereobserved in lower body strength, training volume, gains inmuscle mass, or fasting insulin and growth hormone.
Since the previously published version of this review, noadditional human research has been published and consequently, no further recommendations can be made regarding OKG’s potential as an ergogenic aid.
Prohormones and anabolic steroids

Testosterone and growth hormone are two primary hormones in the body that serve to promote gains in muscle
mass (i.e., anabolism) and strength while decreasing muscle
breakdown (catabolism) and fat mass [355–362]. Testosterone also promotes male sex characteristics (e.g., hair, deep
voice, etc.) [356]. Low level anabolic steroids are often prescribed by physicians to prevent loss of muscle mass forpeople with various diseases and illnesses [363–374]. It is
well known that athletes have experimented with large
doses of anabolic steroids in an attempt to enhance training adaptations, increase muscle mass, and/or promote
recovery during intense training [356–358, 361, 362, 375].
Research has generally shown that use of anabolic steroids
and growth hormone during training can promote gains instrength and muscle mass [355, 360, 362, 368, 371,
376–383]. However, a number of potentially life threatening adverse effects of steroid abuse have been reported including liver and hormonal dysfunction, hyperlipidemia(high cholesterol), increased risk to cardiovascular disease,and behavioral changes (i.e., steroid rage) [378, 384–388].
Some of the adverse effects associated with the use of
these agents are irreversible, particularly in women [385].
For these reason, anabolic steroids have been banned bymost sport organizations and should be avoided unlessprescribed by a physician to treat an illness.

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Prohormones (e.g., androstenedione, 4-androstenediol,
19-nor-4-androstenedione, 19-nor-4-androstenediol, 7-keto
DHEA, and DHEA, etc.) are naturally derived precursors to
testosterone or other anabolic steroids. Their use has beensuggested to naturally boost levels of these anabolic hormones. While data is available demonstrating increases intestosterone [389, 390], virtually no evidence exists demonstrating heightened training adaptations in younger men
with normal hormone levels. In fact, most studies indicatethat they do not affect testosterone and that some may actually increase estrogen levels and reduce HDL-cholesterol[378, 389, 391–396]. On a related note, studies have examined the ability of various ingredients to increase testosterone via inhibition of aromatase and 5-alpha-reductase[397]. Rohle et al. [398] and Willoughby et al. [399]reported that significant increases in free testosterone anddihydrotesterone occurred, but soft tissue composition
either was not measured [398] or wasn’t changed as a resultof supplementation [399]. Consequently, although there
may be some potential applications for older individuals to
replace diminishing androgen levels, it appears that prohormones have no training value. Since prohormones are“steroid-like compounds”, most athletic organizations havebanned their use. Use of nutritional supplements containing prohormones will result in a positive drug test foranabolic steroids. Use of supplements (knowingly or
unknowingly) containing prohormones have been believed
to have contributed to a number of recent positive drug
tests among athletes. Consequently, care should be taken to
make sure that any supplement an athlete considers taking
does not contain prohormone precursors particularly iftheir sport bans and tests for use of such compounds.
Companies such as Informed Choice (www.informed-choice.org) and National Sanitation Foundation, NSF (aka, NSF
Certified for Sport) www.nsf.org) have developed assurance
programs to test and screen various nutrition products.
Moreover, several professional sporting organizations haveincorporated language into the collective bargaining that
requires all products provided by teams or sporting organizations must provide products that have achieved certain
3rd party approvals for safety, banned substances and/orlabel claims. It is noteworthy to mention that many prohormones are not lawful for sale in the USA since the passageof the Anabolic Steroid Control Act of 2004. The distinctive
exception to this is dehydroepiandrosterone (DHEA),
which has been the subject of numerous clinical studies inaging populations.
Sulfo-polysaccharides (myostatin inhibitors)

Myostatin or growth differentiation factor 8 (GDF-8) is atransforming growth factor known as a negative regulatorof skeletal muscle hypertrophy [400]. In humans, inhibiting
myostatin gene expression has been theorized as a way toprevent or slow down muscle wasting in various diseases,

Kerksick et al. Journal of the International Society of Sports Nutrition (2018) 15:38

speed up recovery of injured muscles, and/or promote increases in muscle mass and strength in athletes [401].
Since 2010, no additional research has been published thatexamined the impact of any nutritional ingredient or strategy to inhibit myostatin expression. In humans, myostatin
clearly plays a role in regulating skeletal muscle mass. For
example, a study by Ivey and colleagues [401] reported thatfemale athletes with a less common myostatin allele experienced greater gains in muscle mass during training andreduced atrophy during detraining. Interestingly, no suchchanges were reported for men. Willoughby and colleagues[402] supplemented untrained males with 1200 mg/day ofCytoseira Canariensis (a form of sea algae), a purported
myostatin inhibitor, and reported no changes for fat-freemass, strength and blood concentrations of myostatin.
These results were corroborated by Wilborn et al. [318]
who reported no impact of sulfo-polysaccaride supplementation on body composition or performance changes. As it
stands, there is currently no published data supporting theuse of sulfo-polysaccharides or any other ingredient touted
to act as a myostatin inhibitor for their ability to increase
strength or muscle mass.
Tribulus terrestris

Tribulus terrestris (also known as puncture weed/vine orcaltrops) is a plant extract that has been suggested tostimulate leutinizing hormone which stimulates the natural
production of testosterone [403]. Consequently, tribulus ismarketed as a supplement that can increase testosterone
and promote greater gains in strength and muscle mass
during training. In human research models, several studies
have indicated that tribulus supplementation alone[404, 405] or in combination with other segragotogues andandrogen precusors [406, 407] appears to have no effects onbody composition or strength during resistance training.
Vanadyl sulfate (vanadium)

Vanadyl sulfate is a trace mineral that has been found toaffect insulin-sensitivity (similar to chromium) and may
affect protein and glucose metabolism [403, 408]. In thisregard, reports have highlighted the potential efficacy
and support for vanadium to improve insulin sensitivity[409] and assist with the management of diabetes [410].
In relation to its potential ability to impact protein andglucose metabolism, vanadyl sulfate supplementation has
been purported to positively impact strength and muscle
mass [74, 411]. However, no studies are available that
support the ability of vanadyl sulfate supplementation to
impact strength or muscle mass in non-diabetic individuals who are currently resistance training [412, 413].
Zinc/magnesium aspartate (ZMA)

The main ingredients in ZMA formulations are zincmonomethionine aspartate, magnesium aspartate, andPage 29 of 57

vitamin B-6. ZMA supplementation is based upon the rationale that zinc and magnesium deficiency may reduce theproduction of testosterone and insulin like growth factor(IGF-1). Consequently, ZMA supplementation is advocatedfor its ability to increase testosterone and IGF-1, which isfurther suggested to promote recovery, anabolism, andstrength during training. Two studies with contrasting outcomes have examined the ability of acute ZMA administration to increase anabolic hormone concentrations. Initially,
Brilla and Conte [414] reported that a zinc-magnesium formulation increased testosterone and IGF-1 (two anabolic
hormones) leading to greater strength gains in football
players participating in spring training while Koehler et al.
[415] reported that ZMA supplementation increased
serum zinc and excretion, but failed to change free andtotal testosterone levels. Wilborn et al. [416] had resistancetrained males ingest a ZMA supplement or placebo in a
double-blind fashion and resistance train for 8 weeks andfound no change in free or total testosterone, strength or
fat-free mass (via DXA). It is noted that previous deficiencies in zinc may negatively impact endogenous productionof testosterone secondary to its role in androgen metabolism and steroid receptor interaction [417]. To this point,
Brilla and Conte [414] did report depletions of both zincand magnesium, thus increases in testosterone levels
could have been attributed to deificient nutritional statusrather than a pharmacologic effect. More research isneeded to further evaluate the role of ZMA on body composition and strength during training before definitive
conclusions can be drawn.
Performance enhancement supplements

Several nutritional supplements have been proposed toenhance exercise performance. Throughout this section,emphasis is placed upon results that directly measured
some attribute of performance. In situations where anutrient is purported to stimulate increases in fat-freemass and enhance performance (i.e., creatine), a large,
more developed section is available while a shorter, moreconcise section is available in the other category. Table 3
categorizes the proposed ergogenic nutrients into:
Strong Evidence to Support Efficacy and Apparently
Safe, Limited or Mixed Evidence to Support Efficacy,
Little to No Evidence to Support Efficacy and/or Safety.
Strong evidence to support efficacy and apparently safe

ß-alanine ß-alanine, a non-essential amino acid, has ergogenic potential based on its role in carnosine synthesis[12]. Carnosine is a dipeptide comprised of the aminoacids, histidine and ß-alanine, that naturally occur inlarge amounts in skeletal muscles. Carnosine is believed
to be one of the primary muscle-buffering substances
available in skeletal muscle. Studies have demonstrated

Kerksick et al. Journal of the International Society of Sports Nutrition (2018) 15:38

that taking four to 6 g of ß-alanine orally, in divided
doses, over a 28-day period is effective in increasing carnosine levels [418, 419], while more recent studies havedemonstrated increased carnosine and efficacy up to
12 g per day [420]. According to the ISSN position statement, evaluating the existing body of ß-alanine researchsuggests improvements in exercise performance with more
pronounced effects on activities lasting one to 4 min; improvements in neuromuscular fatigue, particularly in older
subjects, and lastly; potential benefits in tactical personnel[12]. Other studies have shown that ß-alanine supplementation can increase the number of repetitions one can do[421], increase lean body mass [422], increase knee extension torque [423], and increase training volume [421]. In
fact, one study also showed that adding ß-alanine to creatine improves performance over creatine alone [424]. While
it appears that ß-alanine supplementation can improve
performance, other studies have failed to demonstrate aperformance benefit [425, 426].
Caffeine Caffeine is a naturally derived stimulant foundin many nutritional supplements typically as guarana,bissey nut, or kola. Caffeine can also be found in coffee,
tea, soft drinks, energy drinks, and chocolate. Caffeine has
also been shown to be an effective ergogenic aid for aerobic and anaerobic exercise with a documented ability toincrease energy expenditure and promote weight loss [14].
Research investigating the effects of caffeine on time trial
performance in trained cyclists found that caffeine improved speed, peak power, and mean power [427]. Similar
results were observed in a recent study that found cyclists
who ingested a caffeine drink prior to a time trial demonstrated improvements in performance [428, 429]. Studies
indicate that ingestion of caffeine (e.g., 3–9 mg/kg taken
30–90 min before exercise) can spare carbohydrate use
during exercise and thereby improve endurance exercise
capacity [430, 431]. In addition to the apparent positive effects on endurance performance, caffeine has also beenshown to improve repeated sprint performance benefiting
the anaerobic athlete [432–434]. Research examining caffeine’s ability to increase maximal strength and repetitions
to fatigue are largely mixed in their outcomes. For example, Trexler, et al. [434] reported that caffeine can improve repeated sprint performance but failed to impact
maximal strength and repetitions to fatigue using both
upper-body and lower-body exercises. In agreement,
Astorino and colleagues [435] revealed no change inupper-body and lower-body strength after resistancetrained males ingested 6 mg/kg of caffeine. Similarly, Beckand investigators [436] provided resistance trained maleswith 201 mg caffeine (2.1–3.0 mg/kg) and reported no
impact on lower-body strength, lower-body muscular endurance or upper-body muscular endurance. Maximal
upper-body strength, however, was improved. In contrast,

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other studies have indicated that caffeine may favorably
impact muscular performance. For example, Goldstein etal. [437] reported that caffeine ingestion (6 mg/kg) significantly increased bench press strength in a group of
women but did not impact repetitions to fatigue. Studies
by Duncan and colleagues [438–441] have examined theimpact of caffeine on strength and endurance performance as well various parameters of mood state while performing maximal resistance exercise. Briefly, these authors
have reported improvements in strength and repetitions
to failure using the bench press [438, 439] and other exercises [440, 441]. In addition to potential ergogenic impact,these authors also reported that caffeine significantly improved various indicators of mood state [438, 440], lowered ratings of perceived exertion and decreased
perception of muscle pain [439, 441] when acute doses ofcaffeine (5 mg/kg) were provided before maximal resistance exercise. As illustrated, when evaluating the researchon caffeine for its ability to impact strength and muscularperformance, the findings are equivocal, and, subsequently, more research is needed to better determine whatsituations may best predict caffeine’s ability to impact
strength performance. For example, trained subjects havedemonstrated more ergogenic effects compared to untrained subjects [442, 443]. Also, people who drink caffeinated drinks regularly, however, appear to experience lessergogenic benefits from caffeine [444]. Some concern has
been expressed that ingestion of caffeine prior to exercise
may contribute to dehydration, although several studies
have not supported this concern [430, 445, 446]. Caffeine,from anhydrous and coffee sources are both equally ergogenic [434]. Caffeine doses above 9 mg/kg can result in
urinary caffeine levels that surpass the doping thresholdfor many sport organizations. In summary, consistentscientific evidence is available to indicate that caffeine
operates as an ergogenic aid in several sporting situations.
Carbohydrate One of the best ergogenic aids available
for athletes and active individuals alike, is carbohydrate.
Optimal carbohydrate in the diet on a daily basis, in thehours leading up to exercise, throughout exercise and in
the hours after exercise can ensure endogenous glycogenstores are maintained and support many types of exercise
performance [41–43, 50]. In this respect, athletes and active individuals should consume a diet high in carbohydrate(e.g., 55–65% of calories or 5–8 g/kg/day) to maintainmuscle and liver carbohydrate stores [41, 50, 54]. Research
has clearly identified carbohydrate as an ergogenic aid thatcan prolong exercise [41, 68]. For example, Below and colleagues [447] provided research that ingesting carbohydrate
throughout a time to exhaustion protocol after nearly
an hour of moderate intensity cycling can significantly
extend the time cycling is performed. Moreover,Widrick et al. [129] systematically examined all four

Kerksick et al. Journal of the International Society of Sports Nutrition (2018) 15:38

possible combinations of high and low pre-exercise
intramuscular glycogen levels with and without carbohydrate provision before a standard bout of cycling
exercise. When carbohydrate was provided, performance
was improved. In addition to traditional endurance exercise models, Williams and Hawley [42] summarized theliterature involving carbohydrate delivery and performance of team sports that are typically characterized byvariable intensities and intermittent periods of heavy exertion and concluded that carbohydrate intake can increase
performance. Pochmuller et al. [68] and Colombani et al.
[69] have critically pointed to the duration of the involved
exercise bout, the intensity of exercise involved, and thefasting status of the individuals as key factors that may impact exercise performance. Further, Burke and colleagues[23, 50], Hawley et al. [43] and Rodriguez et al. [54] haveall emphasized the importance of optimal carbohydratedelivery throughout various types of sport and recovery
scenarios to support performance. Beyond ingestion, agrowing body of literature has drawn attention to the potential impact of carbohydrate mouth rinsing as an ergogenic strategy. Initial work by Carter and colleagues [448]where they demonstrated an increase in time to exhaustion performance while cycling after rinsing (but not swallowing) the oral cavity with a carbohydrate solution versus
a no carbohydrate rinse revealed that receptors in thebrain might be linked to the mere presence of carbohydrate in the mouth, which subsequently can work to improve various types of exercise performance. While thisconcept is still emerging, some [449–452] but not all[453–455] of the studies have supported the ability ofcarbohydrate mouth rinsing to increase performance. Another carbohydrate manipulation strategy has included
utilizing high molecular weight carbohydrates solutions,in contrast to traditional low molecular weight beverages,
to theoretically accelerate glucose absorption and energy
availability. Importantly, the majority of the literature suggests that utilizing a high molecular weight solution can
impart changes in oxidized substrates, or patterns of fuelusage, but appears to have no ergogenic effect on performance in males or females [63, 456–459].
Creatine monohydrate As indicated earlier, creatine
supplementation is a well-supported strategy to increase
muscle mass and strength during training. However, creatine has also been reported to improve exercise capacity
in a variety of settings [182, 460–462]. Specifically, andas discussed by Kreider et al. [10], studies have documented improvements in: a) single and multiple sprints,b) work completed across multiple sets of maximal effort, c) anaerobic threshold, d) glycogen loading, e) work
capacity, f ) recovery, and g) greater training tolerance.
Consequently, team sports, individual activities or sportsthat consist of high intensity, intermittent exercise such

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as soccer, tennis, basketball, lacrosse, field hockey andrugby can all benefit from creatine use [182]. Moreover,a 2009 study found that in addition to high intensity
interval training creatine improved critical power [460].
Less research is available involving creatine supplementation and endurance exercise, but creatine’s ability topromote glycogen loading [463] and storage of carbohydrate [464–466], key fuels during endurance exercise,
may translate into improved endurance exercise
performance. Indeed, a 2003 study found that ingesting
20 g of creatine for 5 days improved endurance andanaerobic performance in elite rowers [467]. Since creatine has been reported to enhance interval sprint
performance, creatine supplementation during training
may improve training adaptations in endurance andanaerobic athletes, anaerobic capacity, and allow athletes
to complete greater volumes of training at or above
anaerobic threshold [468, 469]. Notably, for athletes who
struggle to maintain their body mass throughout theircompetitive season, creatine use may help athletes inthis respect. Importantly and in addition to creatine
being an effective ergogenic aid in a wide variety ofsports, studies have documented these outcomes(improvements in acute exercise capacity, work completed during multiple sets and training adaptations) inadolescents [470–474], younger adults [231, 424, 462,
475–483], and older individuals [484–490]. Regarding
creatine and athletic performance, there appears to be amisunderstanding that creatine may result in muscle
cramps and dehydration. However, based on many available studies, there is no clinical evidence that creatine
supplementation will increase susceptibility of dehydration, muscle cramps, or heat related illness [196, 491].
Sodium bicarbonate (baking soda) During high intensity exercise, acid (H+) and carbon dioxide (CO2) accumulate in the muscle and blood. The bicarbonate systemis the primary means the body rids itself of the acidity
and CO2 via their conversion to bicarbonate prior tosubsequent removal in the lungs. Bicarbonate loading(e.g., 0.3 g per kg taken 60–90 min prior to exercise or
5 g taken two times per day for 5 days) as sodium bicarbonate has been shown to be an effective way to buffer
acidity during high intensity exercise lasting one to
3 min in duration [431, 492–494]. Matson et al. [495]reported improvements in exercise capacity in events
like the 400–800 m run while Lindh and colleagues[496] reported that bicarbonate can improve 200 m freestyle swimming performance in elite male swimmers.
Similarly, studies have reported the ability of bicarbonate
to improve 3 km cycling time trials [497]. Marriott et al.
[498] published findings that sodium bicarbonate significantly improved intermittent running performance by
23% and reduced perceived exertion in male team-sportKerksick et al. Journal of the International Society of Sports Nutrition (2018) 15:38

athletes. Interestingly, Percival and investigators [499]reported that sodium bicarbonate supplementation
resulted in significantly higher levels of PGC-1-α, a key
protein known to drive mitochondrial adaptations.
Finally, a meta-analysis by Peart and investigators [500]involving sodium bicarbonate reported the overall treatment effect to be moderate at improving performancewith nearly all measured ergogenic outcomes being influenced by the training status of the participants.
In addition, other studies have examined the potential
additive benefit of ingesting sodium bicarbonate with either
caffeine or beta-alanine. In this respect, Kilding et al. [497]reported significant independent effects of caffeine andbicarbonate on three-kilometer cycling time trial performance, but no additive benefit. Alternatively, Tobias andassociates [501] also reported a significant improvement inupper-body power production in trained martial arts
athletes after ingesting either beta-alanine or sodium bicarbonate, but noted a distinct synergistic improvement inupper-body power and performance when beta-alanineand sodium bicarbonate were ingested together. In contrast, Danaher et al. [502] had eight healthy males supplement with either beta-alanine, sodium bicarbonate or their
combination for 6 weeks in a crossover fashion before
completing a repeated sprint ability test while cycling.
While buffering capacity was increased, performance wasonly improved when beta-alanine was provided. Due to themixed outcomes and relative lack of available studies, more
research is recommended examining the synergistic impact
of sodium bicarbonate and other ingredients. It is important to highlight that a common complaint surrounding theingestion of sodium bicarbonate is gastrointestinal distress,
thus athletes should experiment with its use prior toperformance to evaluate tolerance.
Sodium phosphate Phosphate is best known as an
essential mineral found in many common food sources(e.g., red meat, fish, dairy, cereal, etc.) with key functions
in bone, cell membranes, RNA/DNA structure and as
backbones of phosphocreatine and various nucleotides.
In addition, phosphate has been suggested to operate inan ergogenic fashion due to its potential to improveoxygen transport through modulation of 2,3-diphosphoglycerate (DPG) and other lactic-acid-buffering components. Sodium phosphate (NaPO4) supplementation has
been reported in multiple studies to improve aerobic
capacity by 5–12% [503–505], anaerobic threshold by 5–
10% [504–507], mean power output [503, 508] and intermittent running performance [509–511]. Collectively
these studies have employed a dosing regimen that required 1 g of NaPO4 to be taken four times daily forthree to 6 days. Not all studies, however [512–514], havereported ergogenic outcomes while factors that impact
phosphate absorption, training status and gender posed

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as potential reasons why supplementation has not universally impacted performance. Brewer and colleagues[513] reported modest (non-significant) effects of NaPO4
supplementation on repeated supplementation regimens
in trained cyclists completing a time trial. Furthermore,West and investigators [514] used a mixed gender cohort and concluded no change in VO2Max resulted after
supplementation. Buck et al. [515] were the first to solely
examine the impact of NaPO4 in female athletes when
they had 13 trained female cyclists complete a 500-kJ
time trial after supplementing with either 25, 50, or
75 mg/kg of NaPO4 in a randomized, double-blind
manner. No significant impact of supplementation
was seen at any dosage leading the authors to conclude that females may not respond in the same manner as men. However, the same authors on two
occasions [510, 511] examined the impact of NaPO4in female team sport athletes completing repeatedbouts of sprint running and found that NaPO4 significantly improved best and total sprint times whencompared to a placebo. Consequently, the impact ofgender on the ergogenic potential of NaPO4 remains
unclear with consistent benefits in females when repeated sprints are performed but no such benefits
during time-trial work.

Water and sports drinks Adopting strategies to limit
the loss of body mass due to sweating is critical to maintain exercise performance (particularly in hot/humid environments). People engaged in intense exercise or work in
the heat are commonly recommended to regularly ingest
water or sports drinks (e.g., 12–16 fluid ounces every 10–
15 min) with the overarching goal being to minimize theloss of body mass commonly seen as a result of exercisingin a hot and humid environment [516]. Below and colleagues [447] demonstrated the independent ability ofboth fluid (no carbohydrate) and carbohydrate ingestion
to significantly increase cycling performance. Moreover,when the two treatments were combined a synergistic
impact on performance was observed. Studies showthat ingestion of sports drinks during exercise in hot/humid environments can help prevent dehydrationand improve endurance exercise capacity [517–519].
Of note and like carbohydrate, it appears that exercise
factors such as the duration and intensity of the exercise bout operate as strong predictors of cycling
time-trial performance [520, 521]. Consequently, frequent ingestion of water and/or sports drinks during
exercise is one of the easiest and most effective ergogenic aids due to its ability to support thermoregulation and reduce cardiovascular strain during
prolonged bouts of exercise, particularly when completed in hot and humid conditions [162, 516].

Kerksick et al. Journal of the International Society of Sports Nutrition (2018) 15:38

Limited or mixed evidence to support efficacy

L-alanyl-L-glutamine Operating under the same theoretical framework as glutamine, interest in supplementing with L-alanyl-L-glutamine has increased in recent
years. The ingredient has two parts: L-alanine andL-glutamine, both of which are amino acids that are
mainstays in the transamination processes involving
amino acids. Rogero and colleagues [522] supplemented
rats with L-alanyl-L-glutamine for the final 21 days of asix-week exercise training program. Supplementation did
not impact time to exhaustion performance, but higher
levels of glutamine were found when compared to acontrol group. Cruzat and Tirapequi [523] also reported
increases in plasma and intramuscular glutamine alongwith an improved antioxidative profile in blood, muscle
and liver tissue samples of laboratory rats. These results
were extended in 2010 to also report an attenuation of
inflammation and plasma creatine kinase levels in laboratory rats after exercise training [523].
Since 2010, five peer-reviewed studies have been published using human subjects. Hoffman and colleagues[524] reported, in a group of ten physically active males,that L-alanyl-L-glutamine increased time to exhaustion
on a cycle ergometer when exposed to mild dehydrationstress. Two years later, the same research group reported
that rehydration with L-alanyl-L-glutamine after 2.3%
dehydration in a basketball scrimmage led to an
improvement in basketball skill performance and visual
reaction time when compared to water [525]. A 2016
study indicated that L-alanyl-L-glutamine maintained
reaction time in an upper and lower-body activities afteran exhaustive bout of treadmill running [526]. Finally, a2015 paper determined that L-alanyl-L-glutamine significantly improved treadmill running performance whencompared to no hydration [527]. Collectively thisresearch indicates that L-alanyl-L-glutamine at dosages
ranging 300–1000 mg per 500 mL of fluid can favorably
influence hydration status and performance when compared to no fluid ingestion or water only ingestion.
Arachidonic acid Arachidonic acid (ARA) is a longchain polyunsaturated fatty acid (20:4, n-6) that resides
within the phospholipid bi-layer of cell membranes at concentrations that are dependent upon dietary intake [528].
ARA is not found in high amounts in the typical American
diet [529]. However, as little as 1.5 g per day of supplementation over a 50-day period has been shown to increasetissue cell membrane stores of ARA [530]. In skeletal
muscle, there is evidence that ARA drives some of theinflammatory response to strength training via enhanced prostaglandin signalling [531]. Specifically, exercise liberates ARA from the muscle cell membrane via
phospholipase A2 activation. Resultant free intracellular

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ARA is subsequently converted into certain prostaglandins (i.e., PGE2 or PGF2α) via cyclooxygenase (COX)
enzymes [532], and these prostaglandins can signal associated receptors in an autocrine and paracrine manner to up-regulate signalling associated with increases
in muscle protein synthesis. Roberts and colleagues[533] were the first group to examine the impact of ARA
supplementation on changes in strength and body composition. Over an eight-week period, resistance-trained,
college-aged males were supplemented in a double-blindfashion with either a placebo or ARA at a dosage of 1 g per
day in conjunction with 90 g/day of whey protein. A significant increase in anaerobic peak power was found in the
ARA group, but no other changes in strength or bodycomposition were found. The second study by DeSouza etal. [534] investigated the effects of ARA supplementation(0.6 g/d vs. placebo) in strength-trained college-aged malesfor 8 weeks with concomitant resistance training and without protein supplementation. These authors reported thatlean body mass (2.9%, p < 0.05), upper-body strength (8.7%,
p < 0.05), and anaerobic peak power (12.7%, p < 0.05) significantly increased only in the ARA group. Mitchell andcolleagues [535] have also published data in 19
resistance-trained men who supplemented, in a doubleblind, placebo-controlled fashion, with 1.5 g per day of ARA
for 4 weeks and found that ARA supplementation did not
impact acute changes in muscle protein synthesis and othermechanistic links to protein translation. The authors concluded that ARA supplementation did not support a mechanistic link between ARA supplementation and short-term
anabolism, but may increase translation capacity. Given thelimited human data and inconsistent nature (two positive
outcomes, one negative outcome) of the findings regarding
the efficacy of ARA, it is too early to recommend ARA at
this time. In this respect, more chronic human studies testing different doses of ARA supplementation are needed to
fully examine its safety and potential efficacy as a performance enhancing or muscle building aid. From a safety perspective and due to ARA being a known pro-inflammatory
fatty acid, use of ARA may be contraindicated in populations that have compromised inflammatory health (i.e.,
inflammatory bowel syndrome, Chron’s disease, etc.).
Branched chain amino acids (BCAA) Ingestion of
BCAA (e.g., 6–10 g per hour) with sports drinks during
prolonged exercise has long been suggested to improve
psychological perception of fatigue (i.e., central fatigue).
Accordingly, Mikulski and investigators [536] used 11
endurance trained men to examine the impact of ingesting 16 g of BCAAs and 12 g of ornithine aspartate overa 90-min cycling exercise bout and found that the aminoacid combination significantly improved reaction time,
but no ergogenic impact was seen when BCAAs wereingested independently. Although a strong rationale andKerksick et al. Journal of the International Society of Sports Nutrition (2018) 15:38

data exist to support an ergogenic outcome, mixed outcomes currently prevail as other studies have failed toreport an ergogenic impact of BCAAs [247, 537]. Consequently, more research is needed to fully determine theergogenic impact, if any, of BCAAs. An important point
to highlight surrounding BCAAs is the growing body ofliterature supporting their ability to mitigate outcomessurrounding muscle damage. In this respect, multiple
studies have investigated and offered support for BCAA’s
ability to promote recovery, mitigate soreness and attenuate losses in force production [249, 250, 537, 538].
Citrulline Citrulline (2-Amino-5-(carbamoylamino)pentanoic acid or L-Carnitine) is endogenously produced
from ornithine and carbamoyl phosphate in the urea cycle.
In the body, citrulline is efficiently recycled into arginine
for subsequent nitric oxide production through thecitrulline-nitric oxide cycle [539]. Unlike arginine, citrulline catabolism is limited in the intestines [540] as well as
its extraction from hepatic tissue [541] resulting in the
majority of citrulline passing into systemic circulation
before conversion to arginine [542]. Due to this and its
non-competitive uptake for cell transport [542], oral
citrulline supplementation has been shown to be more
effective in increasing arginine [543, 544] and activation of
nitric oxide synthase (NOS) [544] as well as various
biomarkers of nitric oxide [545]. Multiple studies have
employed aerobic exercise models to examine citrulline’s
impact on performance. Suzuki et al. [546] showed that
2.4 g/day of L-citrulline for 7 days increased plasma nitricoxide metabolites, plasma arginine and 4-km time trial
performance. Using a finger flexor exercise model and P31
nuclear magnetic resonance spectroscopy, Bailey and colleagues [547] reported that 7 days of citrulline (6 g/day)significantly increased plasma arginine and nitrite levels
and significantly improved VO2 kinetics and exercise performance. However, not all studies reported an ergogenic
effect whereby Cunniffe et al. [548] reported no impact of
12 g of citrulline malate on the performance of a single
bout of high-intensity cycling. In addition to aerobic exercise research, three studies examined the impact of an 8-g
citrulline dose while resistance training on various performance outcomes [549–551]. One study [550] evaluatedthe effects on the number of repetitions performed forchin-ups, reverse chin-ups, and push-ups to failure intrained males. A second study [551] evaluated the effect of
citrulline supplementation on the number of repetitions
performed for five sequential sets (60% 1RM) to failure on
the leg press, hack squat, and leg extension exercises intrained males. The third study [549] evaluated the effectsof citrulline supplementation on the number of repetitions
performed during six sets each of bench press and legpress exercises to failure at 80% 1RM in trained females.
In all three studies, citrulline malate was shown toPage 34 of 57

significantly increase performance during upper- andlower-body multiple-bout resistance exercise performance.
Alternatively, Cultrufello and colleagues [552] reported
that a 6 g dose of L-citrulline failed to impact both aerobic
and anaerobic indicators of exercise performance. The roleof malate in combination with citrulline is largely undetermined. Since malate is an important tricarboxylic acidcycle intermediate, this could possibly account for improvements in muscle function [553]. Therefore, it is presently unclear whether these benefits can be solely
attributed to citrulline, as well as what role citrulline may
play in aerobic and anaerobic performance.
Essential amino acids (EAA) Research exploring theimpact of essential amino acids with various forms of exercise has exploded. To date, it is well accepted that ingestionof at least 2 g of the essential amino acid, leucine, isrequired to stimulate cellular mechanisms controllingmuscle hypertrophy [225, 554] and that ingestion of
6–12 g of a complete essential amino acid mixture areneeded to maximize muscle protein synthesis [201–208,555]. However, their impact on performance remains
largely unexplored. While sound theoretical rationale exists
and multiple acute study designs provide supportive evidence, it is currently unclear whether following this strategy would lead to greater training adaptations and/or
whether EAA supplementation would be better than simply ingesting carbohydrate and a quality protein following
exercise. Moreover, very little research is available that has
examined the ability of EAAs to impact exercise performance. For these reasons, many authors and review articles
have encouraged the prioritization of intact protein sources
over ingestion of free form amino acids [11, 13, 54, 222] topromote accretion of fat-free mass, but, as mentioned, theimpact of this recommendation on performance changes
remains undetermined.
Glycerol Ingesting glycerol with water has been reported
to increase fluid retention, and maintain hydration status[556–558]. Theoretically, this should help athletes prevent
dehydration and improve thermoregulatory and cardiovascular changes. Although studies indicate that glycerol
can significantly enhance body fluid, results are mixed onwhether it can improve exercise capacity [166, 559–564].
Regarding endurance performance Coutts and investigators [565] had ten trained endurance athletes complete an
Olympic distance triathlon under both placebo and glycerol hyperhydration (1.2 g/kg) + 25 mL/kg fluid solution)
2 h before completion of each triathlon and reported thatcompletion time was significantly improved with glycerol
hyperhydration over placebo. These findings were corroborated by Goulet et al. [566] when they had six
endurance-trained subjects hyperhydrate with glycerol orwater 2 h before a prolonged (2 h) bout of cycling at 65%

Kerksick et al. Journal of the International Society of Sports Nutrition (2018) 15:38

VO2max in hot conditions (26-27 °C) followed two-minuteintervals at 80% VO2max and concluded that glycerol
hyperhydration significantly improved performance. In contrast, Marino et al. [567] reported that a similar glycerol
hyperhydration protocol did not improve the total distancecovered when moderately trained cyclists completed avariable-intensity cycling protocol. Additionally, Goulet etal. [568] combined a hyperhydration strategy (1.2 g/kg glycerol + 26 mL/kg water) 2 h before commencing a
two-hour cycling bout at 66% VO2max and 25 °C with consuming (500 mL/hour) a sports drink and reported that glycerol hyperhydration failed to impact cardiovascular or
thermoregulatory functions as well as endurance performance. McKenna and investigators [569] were one of the
only research groups to examine glycerol’s potential to impact anaerobic power after glycerol hyperhydration. After
following a double-blind hyperhydration protocol, male collegiate wrestlers lost 3% of their body mass from fluid andcompleted an anaerobic test where no impact on performance was found. Variable outcomes surrounding glycerol
continue to undermine its potential and the ability to offera recommendation for its use. Consequently, as pointed
out by Goulet et al. [556], it is concluded that more research needs to be completed to work through the nuancesurrounding glycerol’s potential efficacy, a key point previously summarized by Nelson et al. [570].
β-hydroxy β-methylbutyrate (HMB) For several years,
beta-hydroxy-beta-methyl-butyrate (HMB) has received
interest for its ability to enhance training adaptations andperformance while also delaying or preventing muscle
damage [15, 168, 571]. Initial work by Nissen andcolleagues [171] showed significant increases in lean bodymass and strength with doses 1.5 and 3 g/day in untrained
males, with the 3 g dose showing additional benefits overthe lower dose. Gallagher and colleagues [169] indicatedthat a dose of 38 mg/kg/day (approximately 3 g/day)promoted improvements in fat-free mass, peak isometricforce and isokinetic torque production, while no changes
in maximal strength were seen. In agreement, Thomson
and researchers [572] had 22 resistance trained men
supplement, in a double-blind fashion, with either HMB orplacebo for 9 weeks and concluded that HMB was
responsible for a significant increase in lower-bodystrength. Not all studies, however, have provided support.
For example, Kreider et al. [175] used a dose-response,
placebo-controlled approach and concluded that three or
6 g of calcium-HMB did not impact body composition orstrength adaptations in individuals experienced with resistance exercise after 4 weeks of supplementation and resistance training. Similarly, Hoffman and colleagues [573]reported that HMB supplementation failed to improveanaerobic power production in collegiate football players, aPage 35 of 57

conclusion which aligns with other previous studies [172,574]. Differences in training regimens (intensities),
randomization, and supervision varied in the initial studies
and may have contributed to the mixed results. HMB
appears to have the greatest effects on performance whentraining intensity is maximized.
While many of the previous studies have examined, with
mixed results, the ergogenic potential of calcium-HMB
supplementation in active, recreationally active individuals, Durkalec-Michalski and colleagues completed three
investigations [178–180] that all sought to determine theimpact of calcium-HMB supplementation in different
athlete types. For instance, HMB supplementation (3 g/day) in elite rowers over a 12-week period significantly
improved aerobic (VO2max, time to reach ventilatory
threshold) performance markers and decreased fat mass
when compared to changes seen with placebo [178]. Later,
Durkalec-Michalski and Jeszka [179] required 58 highly
trained males to supplement with calcium-HMB (3 g/day)for 12 weeks. In this study, fat-free mass increased and fat
mass decreased along with multiple markers of aerobic
capacity when HMB was provided in comparison to aplacebo. Most recently, HMB supplementation over
12 weeks in highly-trained combat sport athletes significantly increased (in comparison to placebo) several indicators of aerobic and anaerobic exercise performance [180].
The recent studies by Durkalec-Michalski and colleagues
confirmed earlier works by Vukovich [575] and Lamboley[576] that HMB does have a positive effect on increasing
aerobic capacity.
HMB is available as calcium-HMB and as free acid. In
comparison to calcium HMB, HMB-free acid shows
greater and faster absorption (approx. 30 min vs. 2–3 h)[577]. Much of the initial research used calcium-HMB
with largely mixed outcomes while studies using the freeacid form are more limited. Studies by Wilson and colleagues using the free acid form have indicated robustchanges in strength, vertical jump power and skeletal
muscle hypertrophy while heavy resistance training
alone [578] and in combination with supplemental ATP[579], but others have critically questioned theseoutcomes [580]. A recent systematic review by Silva andinvestigators [581] concluded that the free acid form of
HMB may improve muscle and strength and attenuate
muscle damage when combined with heavy resistancetraining but stated that more research is needed before
definitive conclusions can be determined.
Nitrates Nitrate supplementation has received muchattention due to their effects on vasodilation, blood pressure, improved work efficiency, modulation of force production, and reduced phosphocreatine degradation[582–584] all of which can potentially improve sports performance. Nitrate supplementation is most commonlyKerksick et al. Journal of the International Society of Sports Nutrition (2018) 15:38

consumed two to 3 h prior to exercise as beetroot juice or
sodium nitrate [585] and is prescribed in both absoluteand relative amounts ranging from 300 to 600 mg [585]or 0.1 mmol per kilogram of body mass per day, respectively [583, 586]. These dosing amounts appear to be welltolerated when consumed as both supplemental [587] andsupplemental sources [588] without significant alterationsin hemodynamics or clinical boundaries of hepatorenal
and muscle enzyme status [478, 589]. Supplementing
highly trained cyclists with sodium nitrate (10 mg per kilogram of body mass) significantly reduced VO2peak without
influencing time to exhaustion or maximal power outputs[590]. Additionally, 600 mg of nitrate supplementation(given 2 h prior) non-significantly improved the performance of a 500-m time trial performance in elite-level kayak
athletes by 2 s [591]. Of practical significance, it should be
noted that first place and last place in the 2008 Beijing
Olympics, was separated by 1.47 s in the 500-m men’scanoe/kayak flatwater race. Amateur cyclists at simulated
altitude (~ 2500 m) observed improved 16.1 km time trial
performance with a concomitant decrease in oxygen consumption after beetroot juice (310 mg nitrate) supplementation [592]. Not all findings, however, have reported
performance benefits with nitrate supplementation. Nitrate
supplementation (~ 385 mg nitrate) 2.5 h before a 50-miletime trial in well-trained cyclists failed to improve performance [593], which was also reported by MacLeod et al.
[594] after examining nitrate supplementation (~ 400 mg
nitrate) on 10-km time trial performance in normoxia or
simulated altitude (~ 2500 m). In well-trained runners, nitrate supplementation (~ 430 mg nitrate) did not improve
performance during an incremental exercise test to exhaustion (simulated altitude 4000 m) or a 10-km time trial(simulated altitude, 2500 m) [595] and Nyakayiru et al.
[596] reported no impact of nitrate supplementation onchanges in VO2 and time trial performance in highly
trained cyclists. Other studies have also reported an additive or synergistic effects of high-intensity intermittent exercise, endurance exercise, or resistance training when
nitrate supplementation is combined with sodium phosphate [511], caffeine [597], or creatine [478], respectively. It
is important to mention that dietary nitrates have a healthbenefit in some, but not all populations [598]. Daily consumption of beetroot juice (~ 320–640 mg nitrate/d) significantly decreased resting systolic blood pressure in older
adults by approximately 6 mmHg [599, 600]. Nitrate
supplementation (560 mg – 700 mg nitrate) significantly increased blood flow to working muscle andexercise time in older adults with peripheral arterydisease [601] as well as significantly improved endothelial function via increased flow-mediated dilation
and blood flow velocity in older adults with risk factors of cardiovascular disease [602]. Collectively, theseresults indicate that nitrate supplementation may improve

Page 36 of 57

aerobic exercise performance and cardiovascular health insome populations.
Post-exercise carbohydrate and protein Ingesting
carbohydrate with protein following exercise has been a
popular strategy to heighten adaptations seen as part ofa resistance training program. The rationale behind thisstrategy centers upon providing an energy source tostimulate MPS via key signal transduction pathways.
Additionally, carbohydrate intake will impact insulin status which could promote MPS, limit protein breakdown
or both [603–605]. Furthermore, combining carbohydrate with protein can heighten glycogen resynthesis
rates, particularly when carbohydrate intake is not optimal [120] and can improve muscle damage responses
after exhaustive exercise [606]. A key point for readers
to consider when interpreting findings from this literature is the amount of protein, essential amino acids or
leucine being delivered by the protein source [11]. In thelast few years many studies have agreed that post workout supplementation is vital to recovery and training adaptations [133, 230, 232, 607, 608]. However, the needfor adding carbohydrate to protein to maximize hypertrophic adaptations continues to be questioned. For example, Staples and investigators [605] used an acutestudy design involving stable isotope methodology to investigate the impact of adding 50 g of carbohydrate to 25 gof whey protein ingestion after a single bout of lower bodyresistance exercise. The authors concluded that the combination of carbohydrate and protein was no more effectiveat stimulating muscle protein synthesis or blunting rates ofmuscle protein breakdown than protein alone. Furthermore, Hulmi and colleagues [609] had participants resistance train for 12 weeks and supplement with equivalentdoses of whey protein, carbohydrate or whey protein +carbohydrate while having strength and body compositionassessed. Overall, changes in strength were similar in allgroups while changes in fat-free mass were greater in theprotein group when compared to the carbohydrate group.
Fat mass was found to significantly decrease in both groups
that contained protein in comparison to carbohydrate, but
no differences between the two protein-containing groups
were noted. In conclusion, these findings underscore theimportance of ingesting adequate protein to stimulate resistance training adaptations. Whether or not the additionof carbohydrate can heighten these changes at the current
time seems unlikely. This outcome, however, should not
distract the reader from appreciating the fact that optimalcarbohydrate delivery will absolutely support glycogenrecovery, aid in mitigating soreness and inflammation andfuel other recovery demands.
Quercetin Quercetin is a flavonoid commonly found in
fruits, vegetables and flowers, and is known for having

Kerksick et al. Journal of the International Society of Sports Nutrition (2018) 15:38

some health benefits with therapeutic use. In addition,
quercetin has been purported in both animal and humanmodels to improve endurance performance. In thisrespect, Cureton and colleagues [610] supplemented 30
recreationally active, but not highly trained men in a
double-blind fashion to ingest either quercetin (1 g/day)or placebo. No changes in total work performed, substrateutilization, or perception of effort were found after supplementation. Similarly, Bigelman and investigators [611]supplemented ROTC cadets with either 1 g of quercetin
or a placebo and concluded that VO2max was unchanged
as a result. These results correspond with the outcomes ofother studies that failed to document ergogenic potential
for quercetin [612, 613]. In contrast, Nieman et al. [614]supplemented untrained adult males with 1 g of quercetin
in a double-blind fashion for 2 weeks and reported thattreadmill performance and markers of mitochondrial biogenesis were improved. Similarly, Patrizio et al. [615] useda resistance exercise model and reported quercetin may
improve neuromuscular performance while Davis et al.
[616] had 12 study participants supplement with either
quercetin and placebo and found that quercetin may improve VO2max and endurance capacity. A meta-analysis
was completed by Pelletier and researchers [617] tosummarize the potential impact of quercetin supplementation on endurance performance. This analysis involved
seven published studies representing 288 research participants. Only in untrained participants was quercetin foundto significantly increase endurance performance. A 2011
meta-analysis by Kressler et al. [618] drew a similar conclusion whereby they indicated quercetin does have benefit, but the size of this effect is trivial and small.
Consequently, more research needs to be completed tobetter identify what situations may exist that support
quercetin’s ability to impact exercise performance.
Taurine Taurine is an amino acid found in high abundance in human skeletal muscle [619, 620] derived fromcysteine metabolism that plays a role in a wide variety ofphysiological functions [621–623]. Studies have indicated that training status (higher in trained vs. untrained
muscle, reviewed in [624]) and fiber type (higher in typeI vs. type II, reviewed in [619]) impact the amount oftaurine found in muscle. It has been reported in some
[625, 626] but not all studies [627, 628] that taurine may
improve exercise performance and mitigate recovery
from damaging and stressful exercise [629]. In recent
years, many studies have examined the impact of taurine
ingestion on various types of exercise performance. In
accordance with previous work, ergogenic outcomes related to taurine administration continue to be mixed.
Milioni and investigators [628] failed to show an improvement in performance with a 6 g dose of taurine while
completing high-intensity treadmill running. Similarly,

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Balshaw et al. [625] indicated that taurine failed to positively impact 3-km running performance in trained runners. In contrast, a 2017 study by Warnock et al. [630]reported that a 50 mg/kg dose of taurine outperformed
caffeine, placebo and caffeine + taurine on performancechanges after repeated Wingate anaerobic capacity tests.
Finally, a 2018 meta-analysis by Waldron et al. [631] reported that single daily dosages ranging from one to 6 g
for up to 2 weeks can significantly improve endurance exercise performance in a range of study participants. Twostudies [632, 633] have been completed that examined
taurine’s ability to mitigate decrements associated withmuscle damage and resistance exercise performance. Notably, oral ingestion at a dosage of 50 mg/kg for 14 days
prior to damage and for 7 days after damage significantly
increased strength, and decreased soreness and markers ofmuscle damage [633]. Finally, studies have also supported
the ability of taurine to function in an anti-oxidative role,
which may promote an improved cellular environment totolerate exercise stress [634, 635]. While more researchcontinues to be published involving taurine, the consensus
of these outcomes continue to be mixed regarding taurine’s potential to enhance physical performance.
Little to no evidence to support efficacy and/or safety

Arginine Arginine is known as a conditionally essential
amino acid which has been linked with the ability to increase exercise performance, increase growth hormone production, support immune function, increase
training tolerance and promote accretion of fat-freemass [273, 636]. Several studies have sought to examine the ergogenic potential of arginine using both endurance and resistance exercise models with largely
mixed results. For example, Greer and investigators [637]examined the ability of arginine + alpha-ketoglutarate andreported that the combination did not significantly impact
muscle endurance and significantly reduced the numberof chin-ups completed. Similar outcomes were found by
Aguiar et al. [638] in older women whereby arginine supplementation failed to impact muscle performance.
Sunderland et al. [639] supplemented 18 endurancetrained cyclists for 28 days with either arginine (12 g/day)or corn starch and concluded that arginine did not impact
VO2Max or ventilatory threshold. In accordance, several
other studies have failed to positively report on the abilityof arginine to operate as an ergogenic aid [278, 640–644].
Alternatively, a few studies have provided evidence of ergogenic potential for arginine. For example, Campbell andresearchers [271] supplemented 35 resistance-trained
males in a double-blind fashion with arginine (2 g) +alpha-ketoglutarate (2 g) or a placebo and concluded
that maximal upper-body strength and wingate peak
power were significantly increased after supplementation.

Kerksick et al. Journal of the International Society of Sports Nutrition (2018) 15:38

Similarly, Bailey and colleagues [645] concluded that acutearginine supplementation reduced the oxygen cost ofmoderate-intensity exercise and increased tolerance tohigh-intensity training. Moreover, Pahlavani et al.
[646] supplemented male athletes with arginine in a
double-blind fashion and concluded that arginine supplementation significantly increased sport performance. As it stands, most of the published literaturethat has examined the ability of arginine to operate inan ergogenic fashion has failed to report positive outcomes. While more research is certainly indicated,consumers should exercise caution when using arginine toenhance exercise performance.
Carnitine Carnitine is produced endogenously by theliver and kidneys and plays a pivotal role in lipid metabolism. Consequently, many are led to believe that carnitine
ingestion will increase the concentration of endogenous
carnitine, thereby increasing lipid metabolism anddecrease adipose reserves. To date, the majority of the data
continues to suggest that carnitine supplementation does
not markedly affect muscle carnitine content [647–649],
fat metabolism [648, 650, 651], exercise performance[648, 649, 652, 653], or weight loss in overweight[650, 654], obese [651, 655, 656] or trained subjects[657]. For example, Burrus and investigators [658] had ten
cyclists ingest combinations of carbohydrate and carnitine
while completing a 40-min ride at 65% VO2peak before
completing an exhaustion ride at 85% VO2Peak. No differences in power outputs or times to exhaustion were foundwith cycling at 85% VO2Peak. Of note, studies have suggested that co-ingesting carnitine with carbohydrate canlead to significant increases in intramuscular carnitine[659, 660]. Later, Wall and colleagues [661] reported that
endurance exercise performance was improved andimprovements in fuel selection appeared to occur.
While interesting, more research is needed regarding
changes in performance before further recommendations can be made.
Glutamine As outlined above, a strong theoreticalframework exists for glutamine’s ability to help an individual tolerate stress, particularly when relying on animalstudies. A close examination into the available humanresearch on glutamine makes it more challenging tocharacterize glutamine’s potential. Theoretically, glutamine supplementation during training should enhance gains
in strength and muscle mass, but evidence in this respect
has not been consistent. Glutamine supplementation has
been shown to improve glycogen stores which could go
on to impact certain types of exercise performance [331]and two recent studies suggest that glutamine provision
may help support recovery from damaging resistance
exercise. In this respect, Street and colleagues [662]Page 38 of 57

concluded that adding glutamine (0.3 g/kg) to a carbohydrate drink significantly improved muscle soreness andforce production, but did not impact changes in creatine
kinase, when compared to carbohydrate only ingestion. A
similar outcome was found by Legault and colleagues[337] who reported that glutamine supplementation significantly lowered perceived soreness levels and led to improved recovery of force production after a damaging
bout of eccentric muscle contractions. From an ergogenic
perspective, limited research is available, but Antonio etal. [334] reported that 0.3 g/kg glutamine ingestion did
not impact the number of repetitions completed with theleg press or bench press exercises. Consequently, minimal
research is available to support glutamine’s ability to operate as an ergogenic aid.
Inosine Inosine is a building block for DNA and RNA
that is found in muscle. Inosine possesses important roles
that may enhance training and/or exercise performance[663]. Although there is some theoretical rationale, available studies indicate that inosine supplementation has noapparent effect on aerobic or anaerobic exercise performance [664–666].
Medium chain triglycerides Medium chain triglycerides(MCT’s) are shorter chain fatty acids known to readily
enter the mitochondria and be converted to energy
through beta-oxidation [667]. Studies are mixed as towhether MCT’s are ergogenic and can serve as an effective
source of fat during exercise [667–671]. A 2001 study
found that 60 g/day of MCT oil for 2 weeks did improve
running performance [672]. Additionally, Van Zyl andcolleagues [671] reported that while MCTs negatively
influenced cycling time trial performance when ingested
alone in comparison to carbohydrate ingestion, performance was improved when MCTs were combined withcarbohydrate. Using a similar exercise model, Goedecke etal. [668] also reported that MCT administration throughout a two-hour moderate intensity cycle ride resulted in asimilar performance in completing a 40-km time trial bytrained cyclists. A similar outcome was also reported by
Vistisen et al. [673]. Beyond equivocal findings, Goedecke
et al. [674] and Jeukendrup et al. [667] both reported ergolytic outcomes of MCT administration on sprint performance in trained cyclists and cycling time trial performance,
respectively, while the incidence of gastrointestinal complaints increased in both studies. These findings have been
confirmed by others that MCT oils are not sufficient to
induce positive training adaptations and may cause gastric
distress [675, 676]. Consequently, it does not appear likelythat MCT favorably impacts acute exercise performanceand no evidence exists that training adaptations may bepositively impacted either, while multiple studies have

Kerksick et al. Journal of the International Society of Sports Nutrition (2018) 15:38

reported that MCT ingestion may cause gastrointestinal
upset and decrease exercise performance.
Ribose Ribose is a 5-carbon carbohydrate that is involvedin the synthesis of adenosine triphosphate (ATP) andother adenine nucleotides. Clinical studies have shownthat ribose supplementation can increase exercise capacity
in heart patients [677–681] leading to the development oftheories that it can operate as ergogenic aid for athletes.
Of the available research, most fail to show an ergogenic
value for ribose supplementation on exercise capacity inhealthy untrained or trained populations [682–684]. A
2006 study [685] investigated the effects of supplementing
with either ribose or dextrose over 8 weeks on rowing performance and concluded that ribose was outperformed by
the dextrose control [685]. Kreider and associates [684]and Kerksick and colleagues [686] investigated ribose supplementation on measures of anaerobic capacity in trained
cyclists and concluded ribose had no positive impact on
performance. In 2017, Seifert and investigators [687] had
26 healthy subjects supplement with either 10 g of ribose
or 10 g of dextrose for 5 days while completing a single
bout of interval exercise and a two-minute power output
test. When splitting the participants into high vs. low oxygen uptake levels, the people with low peak VO2 experienced significant increases in mean and peak power
output along with reductions in ratings of perceived exertion and creatine kinase. No such changes were reported
in individuals with high peak VO2. As it stands, clinicalfindings provide support while studies in healthy, trained
populations generally fail to report a positive outcome forribose supplementation. Healthy individuals with lower
fitness levels may afford some benefit.
Supplements to promote general healthIn addition to the supplements previously described, several nutrients have been suggested to help athletes stayhealthy during intense training. For example, the American Medical Association has recommended that all
Americans ingest a daily low-dose multivitamin in orderto ensure that people get a sufficient level of vitamins
and minerals in their diet [688, 689]. Although daily
vitamin and mineral supplementation has not beenfound to improve exercise capacity in athletes, it may
make sense to take a daily vitamin supplement for healthreasons. Vitamin D is often recommended to athletes,
especially those participating in indoor sports or incloudy geographies [690]. Although direct evidence linking vitamin D with performance is equivocal, it is clearthat vitamin D has a role in regulating immune function,
cardiovascular health, and growth and repair. Dosing
should be dependent upon baseline levels, which can bemeasured by any physician [691]. Glucosamine and chondroitin have been reported to slow cartilage degeneration

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and reduce the degree of joint pain in active individuals
which may help athletes postpone and/or prevent joint
problems [692, 693]. Meanwhile, other ingredients including undenatured type II collagen (UC-II) may be helpful
as well although more research is needed involving athletic applications [694, 695]. Supplemental vitamin C, glutamine, echinacea, quercetin, and zinc have been reported
to enhance immune function [125, 696–699]. However,consuming carbohydrate during prolonged strenuous exercise attenuates rises in stress hormones and appears tolimit the degree of exercise-induced immune depression[699]. Similarly, although additional research is necessary,
vitamin E, vitamin C, selenium, alpha-lipoic acid andother antioxidants may help restore overwhelmed antioxidant defenses exhibited by athletes [700]. One counteringargument against higher doses is the potential for these tointerfere with adaptive responses to training [699]. Finally,
the omega-3 fatty acids docosahexaenoic acid (DHA) andeicosapantaenoic acid (EPA), in supplemental form, arenow endorsed by the American Heart Association forheart health in certain individuals stemming from initialscientific statements made in 2002 [701]. This supportive supplement position stems from: 1) an inability to consume cardio-protective amounts by dietalone; and, 2) the mercury contamination sometimes
present in whole-food sources of DHA and EPA
found in fatty fish. For general health, dosing recommendations range from 3000 mg-5000 mg daily ofdeep, cold water fish [702]. Consequently, prudent
use of these types of nutrients at various times during
training may help athletes stay healthy and/or tolerate
training to a greater degree.
High intensity exercise can compromise an athlete’s
immune health. Infection risk and exercise workload follow
a J-Shape curve with moderate intensity exercise reducing
the infection risk, and high intensity exercise actually increasing the risk of infection [703]. Immune suppression inathletes further worsens by the psychological stress, foreign
travel, disturbed sleep, environmental extremes, exposure
to large crowds or an increase exposure to pathogens due
to elevated breathing during exercise or competition.
Athletes have several nutritional options to reduce the risk
and symptoms of upper respiratory tract infections, including probiotics and baker’s yeast beta-glucan. Beta-glucan isa natural gluco polysaccharide derived from the cell wallsof highly purified yeast (Saccharomyces cerevisiae) and has
been shown to significantly decrease upper-respiratory
tract infection symptoms in men and women participatingin the Carlsbad marathon [704]. Probiotics, often referred
to as “friendly” or “good” bacteria, are live microorganisms
which when administered in adequate amounts confer ahealth benefit on the host. An estimated 70% of our immune system is located in your digestive system indicating
the importance of a balanced gut microflora on immune

Kerksick et al. Journal of the International Society of Sports Nutrition (2018) 15:38

health. Probiotics have been shown to reduce the number,
duration and severity of upper-respiratory tract infections
and gastrointestinal distress in the general population andin athletes, certain strains of probiotics have been shown tosignificantly reduce the number of upper-respiratory tract
infection episodes a well as their severity [705]. Healthbenefits of probiotics are strain specific and dose
dependent, and some strains have failed to show beneficial effects in athletes [706]. Also, consuming carbohydrate during prolonged strenuous exercise attenuatesrises in stress hormones and appears to limit the degreeof exercise-induced immune depression [699].

Conclusion
Several factors operate as cornerstones to enhance athletic
performance and optimize training adaptations including
the consumption of a balanced, nutrient and energy dense
diet, prudent training, and obtaining adequate rest. Use ofa limited number of nutritional supplements that research
has supported to improve energy availability (e.g., sports
drinks, carbohydrate, creatine, caffeine, β-alanine, etc.)
and/or promote recovery (carbohydrate, protein, essential
amino acids, etc.) can provide additional benefit in certain
instances. Dietitians and sport nutritionists should stay up
to date on current research regarding the role of nutrition
on exercise so they can provide honest and accurate information to their students, clients, and/or athletes about therole of nutrition and dietary supplements on performanceand training. Furthermore, these professionals should
actively participate in exercise nutrition research, write
unbiased scholarly reviews for journals and lay publications, and help disseminate the latest research findings to
the public. Through these actions, consumers and otherprofessionals can make informed decisions about
appropriate methods of exercise, dieting, and/or whether
various nutritional supplements can affect health, performance, and/or training. In all situations, individuals are
expected and ethically obligated to disclose any commercial or financial conflicts of interest during such promulgations. Finally, companies selling nutritional supplements
or promoting exercise, diet or supplementation protocols
should develop scientifically based products, conduct research on their products, and honestly market the resultsof studies so consumers can make informed decisions.
Abbreviations
1RM: One-repetition maximum; ACSM: American College of Sports Medicine;
AER: Adverse Event Reporting; AMA: American Medical Association;
ARA: Arachidonic acid; ATP: Adenosine – 5′ – Triphosphate; BCAA: Branchedchain amino acids; cGMP: Good Manufacturing Practices; CHO: Carbohydrate;
CLA: Conjugated linoleic acid; CO2: Carbon dioxide; COX: Cyclooxygenase;
DHA: Docosahexaenoic acid; DHEA: Dehydroepiandrosterone;
DMAA: Dimethylamylamine; DNA: Deoxyribonucleic acid; DPG: Diphosphoglycerate;
DRI: Daily Reference Intake; DSHEA: Dietary Supplement Health Education Act;DXA: Dual-energy x-ray absorptiometry; EAA: Essential amino acids;
EPA: Eicosapantaenoic acid; FDA: Food and Drug Administration; FDCA: Food,
Drug, and Cosmetic Act; FHA: Functional hypothalamic oligomenorrhea/

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amenorrhea; FTC: Federal Trade Commission; g: Grams; g/hour: Grams per hour;g/kg: Grams of a certain nutrient per kilogram (usually kilograms of body mass);
g/kg/day: Grams of a certain nutrient per kilogram per day (usually per kilogramof body mass); GDF-8: Growth differentiation factor-8; GES: Glucose-electrolyte
solutions; GH: Growth hormone; GHRP: Growth hormone releasing peptides;
GPC: Glycerophosphocholine; GRAS: Generally Recognized as Safe; HDL: Highdensity lipoprotein; HMB: β-hydroxy- β-methylbutyrate; IGF-1: Insulin-line
growth factor 1; ISSN: International Society of Sports Nutrition; JISSN: Journal of
the International Society of Sports Nutrition; Kcals: Kilocalories; Kcals/
day: Kilocalories per day; Kcals/kg/day: Kilocalories per kilogram per day (usually
per kilogram of body mass); kg: Kilogram(s); L/hour: Liters per hour; LBM: Leanbody mass; LEA: Low energy availability; MCT: Medium-chain triglycerides;
Mg: Milligrams; mL: Millilitres; MLB: Major League Baseball; mmol: Millimoles;
MPS: Muscle protein synthesis; MRP: Meal replacement powders;mTOR: Mammalian target of rapamycin; NaPO4: Sodium phosphate;
NCAA: National Collegiate Athletic Association; NDI: New Dietary
Ingredient; NFL: National Football League; NHL: National Hockey League;
NHP: Natural Health Product; NLEA: Nutrition Labeling and Education
Act; NOS: Nitric oxide synthase; NSF: National Sanitation Foundation;
OKG: Ornithine alpha-ketoglutarate; PA: Phosphatidic acid; PDR: Physician’s Desk
Reference; PGC-1-α: Peroxisome proliferator-activated receptor gamma
coactivator 1-alpha; PRO: Protein; RDA: Recommended daily allowance;
RNA: Ribonucleic acid; ROTC: Reserve Officers’ Training Corps; RTD: Readyto drink; U.S.: United States; UC-II: Undenatured type II collagen; VO2Max: Maximal
volume of oxygen consumption; ZMA: Zinc magnesium aspartate; α-KG: Alphaketoglutarate; μg/d: Micrograms per day
Acknowledgements
Preparation of these documents require the help of many individuals. For
starters, the authors would like to acknowledge all of the authors from the2010 publication: Lem Taylor, Bill Campbell, Anthony Almada, Conrad Earnest,
Doug Kalman, Brian Leutholtz, Hector Lopez, Ron Mendel, Marie Spano, Darryn
Willoughby, Tim Ziegenfuss and Joey Antonio. In particular, the authors areindebted to the assistance provided by Jonathan Manfre, Esq who assisted withcritical edits to many parts related to regulation and to Darryn Willoughby whooffered valuable additions to sections of manuscript. The authors would like tothank all the research participants, graduate students, and researchers that
contributed to the body of research cited in this comprehensive review. Finally,
we would like to thank the late Mel Williams who inspired many of the authors
to pursue research evaluating the role of nutrition on exercise andperformance. Any discussion provided for any given supplement is notintended to be nor should it be construed as any form of endorsementby any of the authors, the ISSN or the respective universities, corporations or
entities that each author is affiliated. Individuals interested in trying some ofthese nutritional recommendations should do so only after consulting with
their personal physician.
Authors’ contributions
RBK and CMK contributed most of the content and served as senior editorson the paper; CDW and MDR provided substantial support in revising anddrafting several sections. RC, SMK, MBC, JND, EG, MG, RJ, LML, ASR, and RW
all contributed to the development of selected parts of the manuscript. All
authors reviewed and approved the final draft of this manuscript. RBK is thecorresponding author.
Ethics approval and consent to participate
This paper was reviewed by the International Society of Sports Nutrition ResearchCommittee and represents the official position of the Society.
Consent for publication
Not applicable.
Competing interests
Authors of this paper have not received any financial remuneration for
preparing or reviewing this paper. All authors report the following competinginterests: CMK consults with and receives external funding from companies
who sell supplemental protein, has received remuneration from companies fordelivering scientific presentations at conferences and writes online, print andother media on topics related to exercise, nutrition and protein for relatedcompanies. Has served as an expert witness and provided testimonies related
to exercise, supplementation and nutrition. CDW has received external funding

Kerksick et al. Journal of the International Society of Sports Nutrition (2018) 15:38

from supplement companies to do research, served on multiple advisoryboards for supplement companies, and has served as a consultant, advisor, andspokesperson for various nutrition companies. MDR has received academic andindustry funding related to dietary supplements, served as a non-paid consultant for industry and received honoraria for speaking about topics discussed inthis paper. He currently has no patents, stock or ownership in any companies
doing business on topics discussed in this paper. RC is the attorney for numerous companies in the dietary supplement industry and has received payment
for consultancy and the writing of lay articles discussing nutritional supplements. SMK has served as a paid consultant for industry; has received
honoraria for speaking at conferences and writing lay articles about topics discussed in this paper; receives royalties from the sale of several exercise and nutrition related books; and, receives commission and has stock in companies thatsell products produced from several ingredients discussed in this paper.
JND has no conflicts of interest to report. MBC has received academic andindustry funding related to dietary supplements, served as a consultant forindustry and received honoraria for speaking about topics discussed in thispaper. EG has no conflicts of interest to report. MG has received externalfunding and nutritional product from companies who sell protein supplements
and has received remuneration from companies for presenting scientific based
nutritional supplement and exercise research at professional conferences. RJ has
received grants to evaluate the efficacy and safety of dietary and foodingredients, serves on scientific advisory boards, and has served as anexpert witness, legal and scientific consultant. LML has received academic andindustry funding related to dietary supplements and honoraria from speaking
engagements on the topic and has received payment for consultancy and thewriting of lay articles discussing nutritional supplements. ASR has received
grants to evaluate the efficacy of dietary supplements, serves as a scientificadvisor for sports nutrition companies, and received remuneration fromcompanies for presenting evidenced-based nutritional supplement andexercise research at professional conferences. RW has received industry
funds for consultancy and employment related to dietary supplement
development and marketing and currently works as the Chief Science
Officer for Dymatize Nutrition. RBK has received externally-funded grants
from industry to conduct research on dietary supplements and has served as ascientific and legal consultant.

Publisher’s NoteSpringer Nature remains neutral with regard to jurisdictional claims inpublished maps and institutional affiliations.
Author details
1
Exercise and Performance Nutrition Laboratory, School of Health Sciences,
Lindenwood University, St. Charles, MO, USA. 2Exercise & Sport Science
Department, University of Mary-Hardin Baylor, Belton, TX, USA. 3School ofKinesiology, Auburn University, Auburn, AL, USA. 4Department of Exercise
and Sport Science, University of North Carolina, Chapel Hill, NC, USA. 5High
Performance Nutrition LLC, Mercer Island, WA, USA. 6Increnovo, LLC,
Milwaukee, WI, USA. 7Collins Gann McCloskey and Barry PLLC, Mineola, NY,
USA. 8Department of Health and Medical Sciences, Swinburne University ofTechnology, Hawthorn, Victoria, Australia. 9University of Texas Medical
Branch, Galveston, TX, USA. 10Exercise & Sports Nutrition Lab, Human ClinicalResearch Facility, Texas A&M University, College Station, TX, USA.
11
Department of Human Performance & Sport Business, University of Mount
Union, Alliance, OH, USA. 12Dymatize Nutrition, LLC, Dallas, TX, USA.
13
Department of Health and Human Performance, Nova Southeastern
University, Davie, FL, USA.

4.
5.

6.

7.
8.
9.
10.

11.

12.

13.

14.

15.

16.

17.

18.

19.

20.

Received: 1 June 2018 Accepted: 17 July 2018

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