Highly Concentrated Caffeine in Dietary 
Supplements: Guidance for Industry 
Additional copies are available from: 
Office of Dietary Supplement Programs 
Center for Food Safety and Applied Nutrition 
Food and Drug Administration 
5001 Campus Drive 
College Park, MD  20740 
Tel: 240-402-2375 
https://www.fda.gov/FoodGuidances 
You may submit electronic or written comments regarding this guidance at any time.  
Submit electronic comments to https://www/regulations.gov.  Submit written comments 
on the guidance to the Dockets Management Staff (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852.  All comments 
should be identified with the docket number [FDA-2018-D-1189] listed in the notice of 
availability that publishes in the Federal Register.   
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Food Safety and Applied Nutrition  
April 2018  Contains Nonbinding Recommendations 
Table of Contents 
I. Introduction ..........................................................................................................1   
II. Background .........................................................................................................2   
III. Product Types ....................................................................................................2   
A. Powdered Dietary Supplements Containing Highly Concentrated
Caffeine ............................................................................................................2   
B. Liquid Dietary Supplements Containing Highly Concentrated Caffeine .. 5
IV. Guidance on Producing Safer Dietary Supplements Containing Caffeine .. 6
V. References ............................................................................................................7    Contains Nonbinding Recommendations 
Highly Concentrated Caffeine in 
Dietary Supplements: Guidance for 
1
Industry  
This guidance represents the current thinking of the Food and Drug Administration (FDA or we) 
on this topic.  It does not establish any rights for any person and is not binding on FDA or the 
public.  You can use an alternative approach if it satisfies the requirements of the applicable 
statutes and regulations.  To discuss an alternative approach, contact the FDA staff responsible 
for this guidance as listed on the title page.  
I. Introduction
Products consisting of or containing only pure or highly concentrated caffeine have been linked 
to at least two deaths in the United States in the last few years, and continue to present a 
significant public health threat.  Many products that consist of only or primarily pure or highly 
concentrated caffeine are sold as dietary supplements.  FDA considers some such products to be 
adulterated under section 402(f)(1)(A) of the Federal Food, Drug, and Cosmetic Act (FD&C 
Act) [21 U.S.C.  342(f)(1)(A)], because they are dietary supplements that present a significant 
or unreasonable risk of illness or injury under the conditions of use recommended or suggested 
in the labeling or, if no conditions for use are suggested or recommended, under ordinary 
conditions of use.   
This document is intended to provide guidance to firms that manufacture, market, or distribute 
dietary supplement products that contain pure or highly concentrated caffeine, or are considering 
doing so.  This guidance should help such parties determine whether their products are or would 
be adulterated under section 402(f)(1)(A) of the FD&C Act.  
FDAs guidance documents, including this guidance, do not establish legally enforceable 
responsibilities.  Instead, guidances describe our current thinking on a topic and should be 
viewed only as recommendations, unless specific regulatory or statutory requirements are cited. 
1 This guidance has been prepared by the Office of Dietary Supplement Programs in the Center for Food Safety and 
Applied Nutrition (CFSAN) at the Food and Drug Administration. 
1  Contains Nonbinding Recommendations 
 
The use of the word should in FDA guidances means that something is suggested or 
recommended, but not required. 
II.  Background 
Caffeine (1, 3, 7-trimethylxanthine) is a naturally-occurring member of the methylxanthine class 
of compounds (Ref 1).  Even though it is not an essential nutrient, caffeine is one of the most 
commonly consumed stimulants world-wide due to its abundant presence in food products, as 
well as over-the-counter and prescription drugs.  While caffeine content varies in different 
products, a typical eight-ounce cup of ground coffee contains approximately 95 milligrams (mg) 
of caffeine.   
 
Caffeine is rapidly absorbed into the bloodstream after ingestion, reaching peak serum 
concentration in less than two hours (Ref 4, 7, 8, 9, 10, 11).  Its metabolism is slowed after 
consumption of more than 500 mg, leading to symptoms being experienced for an extended 
period of time (Ref 8, 12, 13).  In short, this means that when an individual consumes a high 
dose of caffeine, he or she will experience the effects quickly and for a longer period of time.  
Toxic effects (including tachycardia, ventricular arrhythmia, and seizures) are observed at 
approximately 1200 mg, or 1.2 grams (0.15 tablespoons of caffeine) (Ref 2, 3, 4, 5, 6).  A life-
threatening dose of caffeine is typically estimated at between 10,000 and 14,000 mg, or 10 and 
14 grams (g) (1.2  1.7 tablespoons of caffeine), although smaller doses can be life-threatening in 
certain individuals (such as children or other sensitive populations) (Ref 5, 14, 15, 16, 17).  
  
In recent years, dietary supplement products containing pure or highly concentrated caffeine in 
powder or liquid forms have been increasingly marketed to consumers, often through online 
retailers.  These products are often marketed in bulk packaging with up to thousands of servings 
per container, requiring the consumer to measure out a safe serving (often estimated at 1/16 of a 
teaspoon or less for powdered products) from what can be a toxic or even lethal amount of bulk 
product.  For example, just one teaspoon of a powdered pure caffeine product can contain 
approximately 3200 mg (or 3.2 g) of caffeine, or the equivalent of 28 cups of coffee  in other 
words, two and a half times a toxic dose.  And a half cup of a representative liquid concentrated 
caffeine product contains approximately 2,000 mg of caffeine, which is the equivalent to more 
than twenty typical cups of coffee and is well more than a toxic dose.  Many of these products 
can present a significant or unreasonable risk of illness or injury.   
 
III.  Product Types 
A.  Powdered Dietary Supplements Containing Highly Concentrated Caffeine  
One product type that has appeared on the market in recent years is powdered caffeine-
containing products labeled as dietary supplements.  FDA has issued warning letters to 
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  Contains Nonbinding Recommendations 
 
manufacturers of some of these products based on our finding that the products are 
adulterated.2,3,4,5,6  
 
Pure or highly concentrated powdered caffeine is often sold in packages containing enough 
powder for thousands of recommended servings.  Large or bulk packages like these contain 
hundreds of potentially lethal doses. 
 
The package labeling for these products often includes directions suggesting that a consumer 
consume 50 to 200 mg of caffeine multiple times daily.  To obtain quantities such as these from 
a bulk container, a consumer must be able to accurately and precisely measure out a 
recommended serving in the range of 1/64 of a teaspoon (50 mg of powder) to 1/16 of a teaspoon 
(200 mg of powder).  While we do not rule out the possibility that a powdered caffeine product 
sold in bulk could be permissible under the FD&C Act (for example, if it were sufficiently 
diluted), in general we consider these types of products  i.e., products containing amounts of 
pure or highly concentrated powdered caffeine that could be toxic or even lethal several times 
over, sold in bulk such that the consumer is required to separate out a safe serving from a 
potentially lethal amount  to meet the standard for adulteration under section 402(f)(1)(A) of the 
FD&C Act.  Under section 301(a) of the FD&C Act [21 U.S.C.  331(a)], adulterated products 
may not be introduced or delivered for introduction into interstate commerce. 
 
Some of the pure or highly concentrated powdered caffeine products bear warning statements on 
their package labeling and/or websites.  However, FDA considers many of these products to be 
sufficiently dangerous such that a warning cannot remedy the adulteration.  Bulk powdered 
caffeine products are sold to consumers in packages as large as 10 kilograms, which contains the 
equivalent to more than 10,000 recommended servings of the product.  A bulk product of that 
size contains hundreds of potentially lethal doses.  For a number of reasons, no warning 
statement on the labeling of these products is adequate to prevent the products from being 
adulterated under section 402(f)(1)(A) of the FD&C Act.   
 
Through surveillance we have observed discussions and comments on caffeine product websites 
and other fora indicating that these products are frequently shared by or dispensed to multiple 
users, increasing the risk of the product being separated from the warning statement.  In many 
cases there is enough product in the package to last for years beyond the labeled expiration date, 
unless the product is shared among multiple consumers.  
 
                                                           
 
4 https://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2015/ucm460201.htm  
5 https://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2015/ucm460204.htm 
6 https://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2015/ucm460208.htm  
7 https://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2015/ucm460200.htm  
8 https://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2015/ucm460203.htm  
 
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Additionally, some consumers who are familiar with caffeine and have not encountered safety 
problems when consuming it in other ways (e.g., in coffee or soft drinks), might incorrectly 
assume they are personally able to disregard a warning statement and safely consume the product 
without careful attention to the precise serving and measurement recommendations.  The volume 
of the product available and the labeled expiration date (which, taken together, could imply that a 
single consumer can finish the product before it expires) might further promote the 
misconception that the warning can be disregarded. 
 
The serving size measurement can also limit the effectiveness of any warning statement.  Some 
products specify that a serving is a non-standard measure, such as 1/16 of a teaspoon (the 
smallest standard kitchen measuring spoon is usually 1/4 teaspoon) or 200 mg (most household 
scales measure in kilograms and grams, not milligrams).  Because consumers are unlikely to 
have the correct tools to accurately measure these amounts, even a consumer who reads the 
warning statement and attempts to measure a safe serving might inadvertently consume an 
unsafe amount.  A simple mistake, such as measuring a serving in grams rather than milligrams, 
could result in a toxic dose being consumed. 
 
Some pure or highly concentrated powdered caffeine products are packaged with tiny measuring 
scoops that purport to measure a single serving.  However, FDA still considers many of these 
products to be adulterated.  As discussed above, we are aware that these products are frequently 
shared among multiple users.  If the product is physically divided up to be shared by multiple 
people living separately, some consumers will not have the benefit of the measuring scoop. 
 
Furthermore, reasonably foreseeable measurement errors, such as packing the powder too tightly 
or use of a heaping scoop instead of a level scoop, can increase the amount of caffeine in a 
single dose by more than 200%, resulting in the ingestion of a toxic quantity of caffeine.  These 
scoops can also easily be lost, in which case consumers might substitute common household 
measuring tools or even just regular spoons without realizing the possible impact.    
 
For these reasons, in general we consider products containing potentially lethal amounts of pure 
or highly concentrated powdered caffeine, sold in bulk such that the consumer is required to 
separate out a safe serving from a potentially lethal amount, to meet the standard for adulteration 
under section 402(f)(1)(A) of the FD&C Act.  Even if the product label specifies a serving size 
that could be considered safe for many healthy adult consumers, a scoop is provided that can 
approximate that serving size, and a warning statement urges the consumer not to exceed the 
serving size, this type of product can still present a significant or unreasonable risk of illness or 
injury under the conditions of use recommended or suggested in the labeling.  An inherent 
feature of the conditions of use for such products is that the consumer must separate out a very 
small, precise serving from a potentially lethal amount of product  a task that poses a significant 
or unreasonable risk of illness or injury. 
 
 
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B.  Liquid Dietary Supplements Containing Highly Concentrated Caffeine  
We have also begun to see liquid products containing highly concentrated caffeine that are 
labeled as dietary supplements.  These products are often sold in containers holding enough 
liquid for hundreds of recommended servings.  As with the powdered bulk caffeine products, 
large or bulk containers of liquid like these contain multiple toxic or potentially lethal doses.  
While we do not rule out the possibility that a liquid dietary supplement product containing 
highly concentrated caffeine, sold in bulk, could be permissible under the FD&C Act (for 
example, if its concentration were sufficiently low), in general, we consider the types of products 
described here  i.e., products containing amounts of highly concentrated liquid caffeine that 
could be toxic or even lethal several times over, sold in bulk such that the consumer is required 
to separate out a safe serving from a potentially lethal amount  to meet the standard for 
adulteration under section 402(f)(1)(A) of the FD&C Act.  Under section 301(a) of the FD&C 
Act, adulterated products may not be introduced or delivered for introduction into interstate 
commerce. 
 
The package labeling for these highly concentrated liquid caffeine products often includes 
directions suggesting that a consumer consume one teaspoon, which is equivalent to 
approximately 80 mg of caffeine.  These products are often sold to consumers in packages as 
large as a gallon, which contains the equivalent of more than 750 recommended servings of the 
product.  A product of that size contains multiple potentially lethal doses.  
 
These products are typically meant to be diluted before being consumed, and not consumed as 
is.  An amount of highly concentrated liquid caffeine that would be safe for a given individual 
to consume in a properly diluted solution could nonetheless be unsafe for the same individual if 
the highly concentrated liquid were consumed directly.  In the reasonably foreseeable scenario 
where a consumer makes an error diluting the product, or does not dilute it at all, that consumer 
could ingest a toxic quantity of caffeine.  For example, a consumer who pours a representative 
liquid product from its bulk container into an empty container from a commonly-available single 
serving energy shot, would consume approximately five times the amount of caffeine 
contained in the original product  a potentially toxic amount. 
 
Some highly concentrated liquid caffeine products bear warning statements on their package 
labeling and/or websites.  However, FDA considers many of these products to be sufficiently 
dangerous such that a warning cannot remedy the adulteration.  The high concentration of these 
products is such that reasonably foreseeable measurement errors, such as using a tablespoon 
instead of a teaspoon, could result in consumption of a toxic amount.  Moreover, because many 
consumers are familiar with caffeine and have not encountered safety problems when consuming 
it in other ways, often as a beverage (e.g., in coffee or soft drinks), consumers might incorrectly 
assume that they are personally able to disregard a warning statement and safely consume the 
product without diluting it properly, or without careful attention to the precise measurement and 
serving recommendations. 
 
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Additionally, similar to their powdered counterparts, highly concentrated liquid caffeine products 
are often sold in containers so large that they contain enough recommended serving sizes to last 
beyond the labeled expiration date, which suggests that the products are meant to be consumed 
by multiple users.  It is reasonable to infer that liquid dietary supplements containing highly 
concentrated caffeine are being shared by or dispensed to multiple users, thereby increasing the 
risk of the product being separated from the warning statement and the directions for use.   
 
Some highly concentrated liquid caffeine products are packaged with measuring devices that 
purport to measure a single serving.  However, FDA still considers many of these products to be 
adulterated.  These measuring devices are typically not accurate enough to prevent measurement 
errors, such as accidentally overpouring the liquid caffeine product, that can increase the amount 
of caffeine in a single dose, resulting in the ingestion of a toxic quantity of caffeine.  Also, as 
discussed above, consumers who frequently consume caffeine in other contexts (e.g., in coffee or 
soft drinks) might incorrectly assume that they are personally able to exceed the serving size 
recommendation, without understanding the extent to which even a small dose of these highly 
concentrated products can be toxic or even lethal.  
 
Furthermore, these products are often sold as clear liquids that could be relatively easily 
confused with commonly-available safe, clear liquids (e.g., water or white vinegar).  A consumer 
could mistakenly confuse one of these products with water and quickly ingest enough highly 
concentrated liquid caffeine to cause toxic or even lethal consequences.  Some highly 
concentrated liquid caffeine products are sweetened with a flavoring agent, which could increase 
the likelihood that a consumer would quickly ingest a toxic or even lethal amount. 
 
For these reasons, in general we consider products containing potentially lethal amounts of 
highly concentrated, liquid caffeine, sold in bulk such that the consumer is required to separate 
out a safe serving from a potentially lethal amount, to meet the standard for adulteration under 
section 402(f)(1)(A) of the FD&C Act.  Even if the product label specifies a serving size that 
could be considered safe for many healthy adult consumers, a measuring device is provided that 
can approximate that serving size, and a warning statement urges the consumer not to exceed that 
serving size, this type of product can still present a significant or unreasonable risk of illness or 
injury under the conditions of use recommended or suggested in the labeling.  An inherent 
feature of the conditions of use for such products is that the consumer must separate out a small, 
precise serving from a potentially lethal amount of product  a task that poses a significant or 
unreasonable risk of illness or injury. 
 
IV.  Guidance on Producing Safer Dietary Supplements Containing 
Caffeine  
When formulated and marketed appropriately, caffeine can be an ingredient in a dietary 
supplement that does not present a significant or unreasonable risk of illness or injury.  
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Assuming that the product otherwise complies with all applicable legal requirements, we do not 
expect to consider the following types of dietary supplements to be adulterated: 
A.  Dietary supplements sold in solid dosage forms, such as tablets or capsules that do 
not provide an excessive amount of caffeine per item.  Products in these forms 
eliminate the need for a consumer to accurately measure the appropriate serving.  
B.  Dietary supplements containing powdered or liquid caffeine (either diluted or 
undiluted) that are sold in premeasured packets or containers, with each 
premeasured unit containing an amount of caffeine that is not excessive.  Products 
that are sold in pre-measured quantities eliminate the need for a consumer to 
measure the appropriate amount. 
C.  Bulk powdered or liquid caffeine dietary supplement products that have been 
significantly diluted to low enough concentrations of caffeine, such that a 
reasonably foreseeable measurement error, misreading of the directions, or 
misunderstanding about the nature of the product would not normally be expected 
to lead to toxic or life-threatening symptoms.  
All dietary supplements are required to comply with the adulteration provisions of the FD&C 
Act, and we intend to carefully review any dietary supplement products that contain potentially 
dangerous amounts of caffeine in any form. 
V.  References 
Ref. 1. Artin B, Singh M, Richeh C, Jawad E, Arora R, Khosla S. 2010. Caffeine-related atrial 
fibrillation Am J Ther 17: e169-171. 
Ref. 2.  Bonsignore A, Sblano S, Pozzi F, Ventura F, Dell'Erba A, Palmiere C. 2014. A case of 
suicide by ingestion of caffeine. Forensic Sci Med Pathol 10 :448-451. 
Ref. 3.  Holmgren P, Norden-Pettersson L, Ahlner J. 2004. Caffeine fatalities--four case 
reports. Forensic Sci Int 13971-73. 
Ref. 4.  Jabbar SBH, M.G. 2013. Fatal caffeine overdose: A case report and review of literature. 
American Journal of Forensic Medicine and Pathology 34: 321-324. 
Ref. 5.  Bannerjee PA, Z.; Levine, B.; Fowler, D.R. 2014.Fatal caffeine intoxication: A series 
of eight cases from 1999 to 2009. Journal of Forensic Sciences 59: 865-868. 
Ref. 6.  Riesselmann BR, F.; Roscher, S.; Schneider, V. 1999. Fatal caffeine intoxication. 
Forensic Science International 103: S49-S52. 
Ref. 7.  Nawrot P, Jordan S, Eastwood J, Rotstein J, Hugenholtz A, Feeley M. 2003. Effects of 
caffeine on human health. Food Addit Contam 20: 1-30. 
Ref. 8.  Kaplan GB, Greenblatt DJ, Ehrenberg BL, Goddard JE, Cotreau MM, Harmatz JS, 
Shader RI. 1997. Dose-dependent pharmacokinetics and psychomotor effects of 
caffeine in humans. J Clin Pharmacol 37: 693-703. 
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Ref. 9.  Fredholm BB, Battig K, Holmen J, Nehlig A, Zvartau EE. 1999. Actions of caffeine in 
the brain with special reference to factors that contribute to its widespread use. 
Pharmacol Rev 51: 83-133. 
Ref. 10.  Mandel HG. 2002. Update on caffeine consumption, disposition and action. Food and 
Chemical Toxicology 40: 1231-1234. 
Ref. 11.  Zulli AS, R.M.; Kubatka, P.; Novak, J.; Uehara, Y.; Loftus, H.; Qaradakhi, T.; 
Pohanka, M.; Kobyliak, N.; Zagatina, A.; Klimas, J.; Hayes, A.; La Rocca, G.; Soucek, 
M.; Kruzliak, P. 2016. Caffeine and cardiovascular diseases: Critical review of current 
research. European Journal of Nutrition 55: 1331-1343. 
Ref. 12.  Dalvi RR. 1986. Acute and chronic toxicity of caffeine: A review. Vet Hum Toxicol 
28: 144-150. 
Ref. 13.  Magkos FK, S.A. 2006. Caffeine use in sports, pharmacokinetis in man, and cellular 
mechanisms of action. Critical Reviews in Food Science and Nutrition 45:535-562. 
Ref. 14.  Shum S, Seale C, Hathaway D, Chucovich V, Beard D. 1997. Acute caffeine ingestion 
fatalities: management issues. Vet Hum Toxicol 39: 228-230. 
Ref. 15.  Thelander G, Jonsson AK, Personne M, Forsberg GS, Lundqvist KM, Ahlner J. 2010. 
Caffeine fatalities--do sales restrictions prevent intentional intoxications? Clin Toxicol 
(Phila),48: 354-358. 
Ref. 16.  Laskowski LK, Henesch JA, Nelson LS, Hoffman RS, Smith SW. 2015. Start me up! 
Recurrent ventricular tachydysrhythmias following intentional concentrated caffeine 
ingestion. Clin Toxicol (Phila) 53: 830-833. 
Ref. 17.  Ammar R, Song JC, Kluger J, White CM. 2001. Evaluation of electrocardiographic and 
hemodynamic effects of caffeine with acute dosing in healthy volunteers. 
Pharmacotherapy 21: 437-442. 
 
 
  
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