Juice Plus
Juice Plus+ is a branded line of dietary supplements containing concentrated fruit and vegetable juice extracts fortified with added vitamins and nutrients. Introduced in 1993 and sold via direct or multi-level marketing, the supplements are advertised as "the next best thing to fruits and vegetables," a claim which has stirred considerable controversy.
Marketing claims made about Juice Plus products suggest that they can provide benefits such as reducing oxidative stress and promoting cardiovascular health. Critics have argued that there is no scientific proof that Juice Plus offers significant health benefits, and that deceptive claims are used in the product's marketing information. Studies which have set out to test the effects of Juice Plus have generated conflicting and controversial results.

# Product overview
Juice Plus is manufactured by Natural Alternatives International in San Marcos, CA and distributed by National Safety Associates (NSA; Collierville, TN) via direct or multi-level marketing. NSA was founded in 1970 and before introducing Juice Plus in 1993, was known for other multilevel-marketed products such as water filters, air filters, and fire-protection equipment. Naturopath Humbart "Smokey" Santillo is credited with having developed the Juice Plus concept and nutritional philosophy and for creating what has been described as the original formula for the product. According to Santillo, he has also worked with NSA to develop other Juice Plus products.
The primary products in the Juice Plus line are Orchard Blend (a fruit juice powder-based vitamin supplement) and Garden Blend (vegetable juice powder-based) capsules, which are sold together in 4-month supplies at a cost, in 2007, of approximately $160 USD. Other Juice Plus supplement products include gummie candies, chewable tablets, wafers, meal replacement powders, and a vitamin formulation for dogs and cats.
Nutrients used in the manufacture of Juice Plus are purchased from third-party suppliers, including the Henkel Corporation (now doing business as  Cognis Corporation) and Schweizerhall Pharma, and added as fortifiers to the product's plant powders. According to the manufacturer, the additives are used to restore the levels of micronutrients lost during processing and to ensure uniformity. Juice Plus Gummies, a candy-like supplement for children, were shown to consist of 85% corn syrup and 10% beef gelatin, plus added nutrients.
Juice Plus products are marketed by individual distributors who receive sales commissions ranging from 6% (for enrolling five customers in 30 days) to 14% (for enrolling twenty customers in 30 days). Detailed sales figures for Juice Plus are not publicly available but NSA representatives claimed that Juice Plus achieved monthly sales of $6 million USD in 1993 and that it was the companys most successful new product.

# Product research
National Safety Associates refers to Juice Plus as the next best thing to eating fruits and vegetables and describes the products as containing the nutritional essence of 17 different fruits, vegetables, and grains. NSA also claims that Juice Plus delivers key phytonutrients that are absorbed by the body, reduces oxidative stress, promotes cardiovascular wellness, supports a healthy immune system, and helps protect DNA. However, multiple studies of varying standards have produced conflicting results as to the truth of these claims.
Of the published peer-reviewed studies on Juice Plus products, seven were funded and/or authored by the manufacturer, NAI; four were funded by the main distributor, NSA; two were funded by individual Juice Plus distributors; and one was conducted independently. The products examined in most of the studies were Garden Blend and Orchard Blend; three studies were performed on Vineyard Blend (a berry juice powder-based version) taken with Garden and Orchard Blend, and one study was on Juice Plus Gummies.

## Nutrient absorption
Though Juice Plus contains some nutrients, concerns have been raised that these nutrients may not be bioavailable, meaning not effectively absorbed by the human body, and that some of the nutrients claimed to be in the products may not be present in significant amounts. Studies on nutrient absorption showed that subjects taking Juice Plus had elevated blood levels of folate and -carotene but the effects on blood levels of vitamin E and vitamin C were inconsistent. Some studies have shown significant increases in vitamin E and C levels, while  other studies have shown much weaker effects on vitamin E and C levels, and that the levels of the two vitamins are not significantly increased. Studies have also found that Juice Plus does not raise the blood levels of other key phytonutrients from fresh fruits and vegetables, such as lycopene, lutein, zeaxanthin, and -cryptoxanthin.

## Antioxidant activity
NSA claims that Juice Plus is an effective antioxidant, and quotes a study that showed a 75% reduction in lipid peroxidation (an oxidative stress marker) in subjects that took Juice Plus for 7 to 28 days. Other studies have also reported reductions in lipid peroxidation and DNA oxidation. These three studies were not blinded or placebo-controlled, included few participants (in one case no more than 15), and did not include monitoring or control of the participants' food intake. One of the studies was criticized as a particularly poor study by Rosemary Stanton in the Australian journal, The Skeptic. Three other studies which were conducted under more rigorous conditions, meaning randomized, double-blind, placebo-controlled studies, longer in duration and with more subjects, found no significant reductions in lipid peroxidation, DNA oxidation,  or other markers of oxidative stress.
One study, which used an in vitro test of antioxidant activity, found that 1 g of Juice Plus Garden Blend/Orchard Blend powder had the corresponding antioxidant capacity to approximately 10 g (fresh weight) of fruit or vegetable, amounting to 30 g (roughly one-third of a serving) per 4 capsules.
One placebo-controlled study conducted in 2002 found that Juice Plus Gummie candies did not significantly improve the antioxidant status of children, as indicated by negative results from 6 different antioxidant tests. The authors explained this by saying it was possible that the supplement did not contain enough of the proper antioxidants to make a significant difference or that the antioxidants extracted in the fruit/vegetable extract were not bioavailable.

## Cardiovascular effects
Several studies have examined the effects of Juice Plus capsules on biochemical parameters associated with cardiovascular function, again with conflicting results. One study, which was not double blinded or placebo controlled, found a 37% decrease in homocysteine levels. Other more rigorous studies, including two that were randomized, double-blind, placebo-controlled trials, found that homocysteine levels were not reduced or were reduced only marginally (7%). Two randomized, double-blind placebo controlled studies have examined the effect of Juice Plus on serum cholesterol and LDL levels. One study found that Juice Plus had no significant effects; the other found slight decreases in cholesterol (6%) and LDL (9%) in subjects that took Orchard/Garden Blend, but no reductions among subjects who took Juice Plus Vineyard blend in addition.
One study found that Juice Plus had no effect on blood pressure in healthy subjects. This study also reported that a combined regimen of Juice Plus Orchard Blend and Garden Blend significantly decreased the impairment of brachial artery vasoactivity caused by a high-fat meal; however, the addition of Vineyard Blend to this regimen had no additional effect on brachial artery vasoactivity and led to an increase in total lipoprotein and LDL.

## Immune effects
A non-randomized, non-blinded, non-controlled study in elderly cigarette smokers and non-smokers examined the effects of Juice Plus Orchard Blend and Garden Blend on 8 immunologic parameters, including stimulated T-cell cytokine production (IL-2, IL-6, TNF- and IFN-) and the activity of various immune cells (peripheral blood monocytes, natural killer  cells, T-helper cells, and cytotoxic T cells). Juice Plus significantly increased peripheral blood monocyte proliferation and NK cell cytotoxicity in non-smokers but not in smokers, and increased in vitro IL-2 production by stimulated monocytes in both smokers and non-smokers. None of the other 5 immune parameters were affected in either smokers or non-smokers. Memorial Sloan-Kettering Cancer Center noted several faults with this study including that it lacked placebo controls and was not blinded, that the results do not necessarily correlate with an overall increase in immunity, and that it would have been more informative had clinical parameters been measured, such as whether fewer patients became sick.
A double-blind, randomized, placebo-controlled study examined the effect of Juice Plus Orchard Blend and Garden Blend on T cell counts, lymphocyte cytokine production, Epstein-Barr virus (EBV) antibody titers, and the incidence of illness in healthy subjects. The percentage of circulating -CD3+ T cells and -CD3+ T cells did not change significantly in subjects who took Juice Plus; however, at the end of the supplementation period, subjects taking the supplement had a higher percentage of -CD3+ T cells (7.2%) as compared with placebo (5.4%). IFN- produced by stimulated lymphocytes in vitro was reduced in the Juice Plus (68%) and placebo groups (41%), but the reduction was statistically significant only in the Juice Plus group. The levels of other cytokines (IL-4, IL-6, TGF-) were unchanged and Juice Plus had no significant effect on the incidence and symptoms of illness or on EBV antibody titers.

## Adverse effects
Adverse effects of Juice Plus have been mentioned in three studies, none of which were randomized, blinded, or placebo-controlled. No monitoring of adverse effects was reported in other published Juice Plus studies. Memorial Sloan-Kettering Cancer Center noted that in one study, some subjects who took Orchard Blend and Garden Blend developed a hive-like rash. Another study  in 2000 reported adverse effects (upper-respiratory tract, urinary, and musculoskeletal) in roughly a third of the participants who took the products for 7 days. However, these events resolved spontaneously and were deemed by the researchers to be unrelated to treatment. In a third study from 2007, some subjects withdrew due to gastrointestinal distress possibly caused by the Juice Plus regimen (a combination of Orchard Blend, Garden Blend, and Vineyard Blend).

# Juice Plus Children's Research Foundation
The Juice Plus Children's Research Foundation, founded in 1997, is a non-profit organization whose stated goal is to initiate and/or support programs that advance the principle that improved nutrition leads to healthier lifestyle and overall better health in children. The foundation is chaired by executives of National Safety Associates and operates from the company's head office in Collierville, Tennessee.
As of 2007, no research had been published by the Foundation, but it does conduct an ongoing survey which seems to link Juice Plus consumption to a general improvement in diet and lifestyle habits.  Critics, including the University of California Berkeley Wellness Letter and Dr. Stephen Barrett of MLMWatch, question the survey's scientific value, and state that the Foundation is being used mainly as a marketing gimmick to get families to buy Juice Plus products.

# Criticism
According to Consumer Reports, in 2005, National Safety Associates used advertising featuring Dr. William Sears, which implied that Juice Plus Gummies are low in sugar and a nutritional alternative to fruits and vegetables.  This claim resulted in consumer complaints to the Better Business Bureau's National Advertising Division (NAD).  The BBB issued a complaint that NSA's claims were misleading, and as a result, NSA promised to modify its ads and stop calling Gummies the next best thing to fruits and vegetables. However, as of 2007, the Juice Plus homepage still advertises that the products are the next best thing to fruits and vegetables, though not specifically in reference to the Gummies.
University of California Berkeley Wellness Letter and MLMWatch also commented on the unreliability of Juice Plus testimonials provided by former professional athlete O.J. Simpson, who was tried and acquitted for the June 12, 1994 murder of his ex-wife Nicole Brown Simpson and her friend, Ronald Goldman. Simpson signed a multi-year six-figure contract with NSA in January 1994 and became an official celebrity endorser of Juice Plus. In March 1994, shortly before the murders took place, Simpson was videotaped telling 4,000 Juice Plus distributors at a sales meeting that the product had cured his arthritis, improved his golf game, and freed him from using anti-arthritic drugs. However, during his  criminal trial in 1995 and  civil trial in 1997 (and in his 2007 book If I Did It) Simpson claimed that he was too incapacitated by arthritis to have committed the murders and that he had continued to take a variety of potent anti-inflammatory drugs, including sulfasalazine and Motrin. After controversy surrounding Simpson erupted, NSA cancelled his endorsement contract and stopped using the Simpson videotape to promote Juice Plus.
Concerns have also been raised about the accuracy of product labeling. Three studies which included chemical analyses of Juice Plus have indicated nutrient amounts that differ from the amounts listed on the product labels.
Doubts have been raised about the benefits of Juice Plus by the Memorial Sloan-Kettering Cancer Center, the University of California Berkeley and other sources. Specific criticisms include: the products marketing being unsupported by research data, the product contains too little fruit and vegetable powder to offer significant clinical benefits, concerns that the effects can be attributed to the inclusion of added exogenous vitamins and micronutrients, and complaints that the products are excessively priced relative to their potential benefits. In a January 2007 article in the St. Louis Post Dispatch, dietitian Renee Schwendinger said, "the average person should eat actual fruits and vegetables, not take a supplement such as Juice Plus," and that barring that, "a single multivitamin will give you all the nutrition you need if your diet is lacking, and it's less expensive." Nutritionist Rosemary Stanton echoed similar sentiments, stating Juice Plus...contains added vitamins, and as such may have some value, although regular vitamins cost only a fraction of the Juice Plus product" and that "there is no evidence the supplement has enough fruits and vegetables to provide an alternative to the real thing. Registered dietician Kathleen Goodwin noted that while there have been some clinical research studies about the effectiveness of Juice Plus, the evidence overall is inconclusive, the research flawed, and the funding provided by the manufacturer of the supplements themselves...Juice Plus supplements simply do not compare to the thousands of naturally occurring nutrients and phytochemicals we derive from the real thing. The University of California Berkeley Wellness Letter claimed no matter how compressed these capsules are, or what they contain, its impossible to deliver the nutrients of five to ten servings of fruits and vegetables in several capsules weighing 800 to 850 milligrams (about one-thirtieth of an ounce) each. It would take two dozen 800-milligram capsules just to provide all the nutrients in six ounces of carrot juice and concluded you dont need Juice Plus. Registered dietician Fudeko T. Maruyama and nutritional education specialist Mary P. Clarke of Kansas State University commented that the promotional literature for Juice Plus, billed as a whole food concentrate, is a carefully worded blend of incorrect information, misleading health claims, and nonscientific jargon and concluded that Juice Plus probably won't harm you, but can hurt your pocketbook." Memorial Sloan-Kettering Cancer Clinic referred to Juice Plus as a pricey supplement that is distributed through a multi-tiered marketing scheme with exaggerated value and cost." 
In a critique of Juice Plus, Stephen Barrett of MLMWatch remarked upon the previous association between two authors of a 1996 Juice Plus research study  and United Sciences of America, Inc. (USAI), a multilevel marketing company that sold vitamin supplements with illegal claims that they could prevent many diseases. In 1986, lead author John A. Wise, who later co-authored several other Juice Plus research studies, was USAI's Executive Vice-President of Research and Development; and second author Robert J. Morin was a scientific advisor who helped design the products. State and federal enforcement actions drove USAI out of business in 1987. Wise became a consultant to Natural Alternatives International (NAI) in 1987 and a company executive (Vice-President of Research and Development) in 1992. Barrett noted that Wise was also an NAI shareholder and that production of Juice Plus for National Safety Associates (NSA) was responsible for 16% of NAIs sales in 1999. In 2006, NSA accounted for 38% of NAIs sales. Wise was appointed Chief Scientific Officer of NAI in 2002 and resigned from the companys executive board on June 30, 2007. Wise then entered into a consultancy agreement with NAI stipulating a fee of $10,000 USD per month, and as of August, 2007, was listed as an NAI insider, with direct ownership of 59,600 shares of NAI stock and short-term vested options to purchase an additional 130,000 shares.