The Dubious Promotion of Herbalife’s Niteworks

Stephen Barrett, M.D.
June 15, 2014

Herbalife would like you believe that taking Niteworks™ will benefit your heart. The product was formulated by Louis J. Ignarro, PhD., professor of molecular and medical pharmacology at the UCLA School of Medicine, who shared the 1998 Nobel Prize in Medicine for his research concerning nitric oxide as a signaling molecule in the cardiovascular system [1,2]. This article tells why I believe that Niteworks is being promoted with improper claims and Ignarro’s conduct has been highly questionable.

Ingredients and Claims

Niteworks, which has been marketed since 2003, is a powdered mixture, each dose of which contains 500 mg of vitamin C, 200 international units of vitamin E, 400 micrograms of folic acid, 50 mg of lemon balm extract, 10 mg of alpha lipoic acid, 300 mg of l-taurine, and 5.2 grams of a proprietary blend of l-arginine and l-citrulline [3]. The list price is $89.95 for a 30-day supply. The label, shown below, carries Ignarro’s signature and endorsement states that the product is a dietary supplement.

Herbalife’s Web site says that Niteworks “supports energy, vascular and circulatory health”; “promotes a healthy cardiovascular system; “enhances blood flow to support function of the heart, brain and other organs”; and helps you wake up feeling rejuvenated.” [4] An Herbalife fact sheet states:

Discoveries relating to Nitric Oxide led to Dr. Louis Ignarro and two other scientists winning the Nobel Prize in Physiology or Medicine in 1998. Herbalife teamed with Dr. Ignarro to develop Niteworks™, a lemon-flavored powder mix. Niteworks™ is formulated to help you create more life-supporting Nitric Oxide during the night, when Nitric-Oxide levels are naturally at their lowest. . . .

Through vascular nutrition, you can increase the production of Nitric Oxide, which “exercises” or expands your vessels, increasing their youthful elasticity. In addition, Nitric Oxide is an important biological messenger that causes a cascade of benefits at the cellular level, which can improve circulatory, immune and nervous-system function. Nitric Oxide influences the functioning of virtually every organ in the body, including the lungs, liver, kidneys, stomach, brain and, of course, the heart [3].

In 2010, I noticed that Herbalife’s “Product Details” listed “Keep blood vessels toned, flexible and youthful for improved circulation” as a key benefit. However, there is little scientific support for this claim. Some studies of arginine supplementation have found possible benefit, some have found none, and some have found possible harm. As far as I know, the full Niteworks formula has not been tested in a clinical trial that looked for a protective effect against cardiovascular disease.

Ignaro’s Promotion

In June 2003, Ignarro was featured at Herbalife’s Extravaganza in Las Vegas, where he talked to thousands of enthusiastic Herbalife distributors for more than an hour. As part of Ignarro’s introduction, Herbalife’s CEO MIchael O. Johnson played a video in which Ignarro said: “We’ve done a lot of work to show that one does not have to take prescription drugs to be effective in treating cardiovascular disease. One can just engage in natural sorts of things—dietary supplements . . . exercise, diets that are low in fat, and so on. All of these things increase or enhance nitric acid production in the body; and the more nitric oxide that is produced, the more protection you have against cardiovascular disease.” [5] The video ended with a plea from Ignarro “take this message to tens of millions of people out there.”

Ignarro’s walk to the stage was accompanied by loud music, rhythmic clapping, and audience cheering that resembled what happens when boxers and wrestlers are introduced at championship events. Before and after speaking, Ignarro spent several minutes giving autographs to distributors who pressed toward him with papers held high. His talk covered his research; the physiological characteristics of nitric oxide; his Nobel award; his beliefs about Niteworks; and what taking the product has done for him, his wife, and his friends. During parts of his talk, he seemed euphoric. The audience lapped it all up; many portions of his talk were met with applause and enthusiastic shouts.

The “scientific” part of Ignarro’s talk was centered around a slide show titled “No More Heart Disease: The Nitric Oxide Story.” After promising to provide “easy steps you can take to prevent cardiovascular disease,” and “what we can do to reverse this process,” he stated that Herbalife’s “Cellular Nutrition Program nourishes all the cells in the body” and that nitric oxide can do the same. He went on to describe how nitric oxide allows cells to “communicate” with each other and can help prevent a wide variety of diseases. He claimed that among other things, it can help lower blood pressure, improve blood flow, inhibit clotting (to prevent strokes and heart attacks); prevents against early stages of atherosclerosis; prevent vascular complications of diabetes; protect against ulcers and Alzheimer’s disease; and affect erectile function.

Ignarro further claimed that “cardiovascular disease is associated with localized nitric oxide deficiency,” and that production can be increased by a low-fat diet, mild-to-moderate exercise, smoking cessation, and better “cellular nutrition.” Niteworks, he said, contains the amino acid arginine, which the body converts to nitric oxide; citrulline, which the body “recycles” to arginine; and the antioxidant vitamins A and C, which protect against the destruction (oxidation) of nitric oxide. Although arginine is found in common foods (such as meat, poultry, fish, nuts, cereals, milk and certain vegetables), Ignarro told the audience:

You probably don’t get sufficient amounts of arginine from your diet. . . . To really get the increased production of nitric oxide that I’d like to see . . . you’d probably have to eat the whole leg of a cow every day or as a barrel of fish. . . . So you should supplement your diet with arginine . . . and the same thing goes for citrulline, which is another amino acid. It’s found together with arginine but is present in much smaller amounts. That’s why it’s particularly important to supplement with citrulline. And, of course, our Niteworks product contains both arginine and citrulline.

After finishing his “chemistry lesson,” Ignarro focused on the personal experience of himself, his wife and his friends. Among other things, he bragged that after taking Niteworks, he and his wife greatly improved their treadmill performance and that he slept better and generally felt better. He also said that friends had lowered their blood pressure and become less depressed, that “everyone” he knows who took the product had reported substantial benefits; and that he really believes that “soon there will be no more heart disease.” (This statement was followed by a standing ovation from the audience.) The fact that mouse studies and haphazardly collected anecdotes do not provide an adequate basis for Ignarro’s conclusions was not mentioned to the audience.

A few months after the Extravaganza, the Washington Post published an article in which Ignarro told the reporter that the ingredients in Niteworks generate nitric oxide slowly over a prolonged period so that it can be provided when the body needs it. However, he said that this had been shown so far only in animal studies and test-tube studies with human cells. Ferid Murad, M.D., Ph.D., who directs the Institute of Molecular Medicine at the University of Texas Medical School at Houston and shared the Nobel Prize with Ignarro, said that Niteworks’ blend of ingredients makes sense, except for l-citrulline, which he said acts only marginally in recycling l-arginine and is probably in the product for patenting reasons. Murad also said that Niteworks’ $90-per-month price was obscene because the vitamins C and E are available for pennies a day and arginine is obtainable for about a dollar a day [6].

Questionable Conduct

In May 2004, the Proceedings of the National Academy of Sciences published an article by Ignarro and 11 co-authors about a study in which mice with high cholesterol levels who exercised and were given arginine, vitamin C, and vitamin E were compared to sedentary mice and to mice who exercised but did not get the supplements. The researchers found that the supplemented mice developed fewer problems with their coronary arteries [7]. Scientific journals require authors to disclose any financial interest they have in the subject matter they write about. However, the article did not disclose Ignarro’s tie to Herbalife or his financial interest in a product related to the study. In fact, the lack of disclosure and extent of the connection did not come to light until David Evans, an investigative reporter for Bloomberg News, learned how much amount of money was involved as reported in documents submitted to the Securities and Exchange Commission as part of Herbalife’s application to become a publicly-held company. After further investigation, Evans reported:

  • In January 2003, Ignarro and David Brubaker formed a consulting company called Healthwell Ventures LLC to receive royalties for the sale of Niteworks. Brubaker told Evans that Herbalife pays Healthwell 1% of Niteworks sales revenue. Since June 2003, Healthwell has received $1 million, some of which represented an advance payment.
  • When the mouse study was published, UCLA issued a press release in which Ignarro claimed that “what’s good for mice is good for humans” and that the study “shows that supplements work well even in the absence of exercise.” The release didn’t name Herbalife and didn’t disclose Ignarro’s financial interest in Niteworks.
  • Pharmacologist Robert Furchgott, Ph.D., who also shared the 1998 Nobel Prize with Ignarro said that Ignarro’s claims of effectiveness are improperly founded. “They jumped the gun,” he said.” I haven’t seen any properly controlled studies. It just seems to me a mouse model isn’t transferable to humans.” He also said, “I think with the sort of money they’re raking in, they could have done some human studies.”
  • Former New England Journal of Medicine editor Marcia Angell, M.D., agreed that Ignarro needs more than mouse studies to support his claims. “There’s a way to find out if it works in humans,” by conducting clinical trials on people, she said. “You can’t assume it will work for people.” [8]

Brubaker, who was also an Herbalife distributor, sells Niteworks and other products from his HealthWellLife Web site from 2004 through 2007. Shortly before Evans’s exposé was published, I downloaded a video that contained Ignarro’s Las Vegas presentation followed by an invitation to order Niteworks via Brubaker’s toll-free number. Ignarro’s presentation, combined with the introduction shown at the Extravaganza, has also been promoted through the Herbalife Broadcast Network (HBN), which Herbalife International uses to communicate with its distributors.

Ignarro notified the journal editor that he thought that disclosing his financial connection to Herbalife was unnecessary because (a) the study was conceived before he teamed up with Herbalife and (b) he had only played a minor role as a reviewer of the article [9]. However, I believe that (a) the connection was established before the article went to press and (b) if Ignarro did enough to get his name on the article, he did enough to require a disclosure. Moreover, the news release associated with the article should have made the disclosure.

In 2012, a Pershing Square Capital Management report noted that since 2004, Herbalife had paid Ignarro and his affiliated consulting firm more than $15 million since 2004 [10]. In 2013, the Los Angeles Times noted Herbalife’s support of UCLA medical school’s Center for Human Nutrition [11].


Ferid Murad, Ph.D., the third scientist who shared the 1998 Nobel award, has cast his lot with another manufacturer. In December 2004, Leiner Health Products announced that it had created Cardio Discovery™, which it said was “based on 28 years of research by Nobel Prize winner Dr. Ferid Murad.” A company press release stated: “Cardio Discovery helps support the cardiovascular system by increasing production of nitric oxide. Naturally produced in the body, nitric oxide helps to maintain the flexibility of veins and arteries so that blood flows freely. Cardio Discovery contains the amino acids l-arginine and l-glutamine. l-arginine is one of the body’s key nutrient sources for nitric oxide production, which is necessary for the maintenance of a healthy cardiovascular system.” [12] The list price was $32/month, but some distributors were discounting it. Now called Cardio Support, the product retails for $39.95.

Applicable Laws

Under federal law, products (except for devices) intended for the cure, mitigation, treatment, or prevention of disease are drugs, and all drugs must be labeled with adequate directions for use. Labeling includes any written, printed, or graphic material that accompanies a product; and intended use is determined by the facts at hand. Drugs not generally recognized as safe and effective by experts are considered “new” drugs that cannot be marketed in interstate commerce without FDA approval. It is a federal crime to market a new drug that lacks approval or does not bear adequate directions. The 1994 Dietary Supplement Health and Education Act (DSHEA) permits dietary supplements to be marketed with “structure/function” claims that are truthful and supported by scientific evidence [13,14]. It appears to me that Niteworks is intended for the prevention of disease but is not generally recognized by experts as safe and effective for this purpose. I also believe that many of the claims made by Herbalife and Ignarro go beyond what DSHEA permits for a dietary supplements. Thus, for example, the claim that Niteworks can lead to “no more heart disease” appears to be illegal as well as preposterous.

In 1985, the California Attorney General sued Herbalife International and its founder/president Mark Hughes for making false claims about several products. The case was settled in 1986 with a consent agreement under which the defendants paid $850,000 in penalties and were permanently barred from making unsubstantiated health claims for any product [15].

In 2003, the Federal Trade Commission took action against the marketers of another arginine-containing product (HeartBar) that was claimed to protect its users against cardiovascular disease [16]. The consent agreement [17] prohibits unsubstantiated representations that any such product:

  • Substantially decreases leg pain for people with cardiovascular disease;
  • Reverses damage or disease to the heart caused by high cholesterol, smoking, diabetes, estrogen deficiency, or any other medical condition or health risk;
  • Prevents age-related vascular problems, including “hardening of the arteries” and plaque formation, or reduces the risk of developing cardiovascular disease;
  • Reduces or eliminates the need for surgery, such as a coronary bypass or angioplasty, or for medications, such as nitroglycerin, in patients with cardiovascular disease; or
  • Improves endurance, circulation, and energy for the general population.
Arginine Research

As far as I know, Niteworks has never been studied studied in humans to determine whether it can help people with cardiovascular disease. But three studies suggest that one of its key ingredients—arginine—might do more harm than good for people with impaired artery function:

  • One study found that giving 9 grams of arginine per day for 4 days to 28 patients with coronary artery disease did not improve the function of the inner lining (endothelium) of their arteries [18].
  • Another study found that subjects with peripheral artery disease who took arginine supplements for 6 months did worse than that imilar people who received a placebo [19].
  • The third study found that 9 grams of arginine given every day for 6 months did not improve arterial functioning among 153 people who had suffered a heart attack. But during or shortly after the trial, death occurred in six of the arginine-takers but none of the placebo-takers [20].

The Herbalife Science Web site mentions a clinical trial in which 16 healthy elderly men who exercised regularly were given either Niteworks or a placebo for three weeks. The study was supported by an NIH grant and done at UCLA’s Center for Human Nutrition. The researchers reported that the men who received Niteworks were able to do strenuous exercise a bit longer before they got tired [21]. Whether this finding has any practical significance remains to be seen.

The Bottom Line

Niteworks is promoted as a powerful preventive against cardiovascular disease even though, as far as I know, the product has never been studied for this purpose in humans. Nobel Prize winner Louis Ignarro, Ph.D, who has a substantial financial interest in the matter, is using his prestige to facilitate the sales process. Although research into nitric oxide may lead to some practical use of arginine supplementation, it seems unlikely to result in “no more heart disease.” Meanwhile, I believe it is foolish to spend $90 a month for a product that is overpriced, has no proven value, and might even be harmful.

  1. Louis J. Ignarro. The Nobel Prize Internet Archive Web site, accessed Dec 10, 2004.
  2. Niteworks™. Herbalife Web site, accessed Dec 9, 2004.
  3. Niteworks fact sheet. Undated (probably 2003). Downloaded from a distributor Web site, Dec 9, 2004.
  4. Jahangir E and others. The effect of L-arginine and creatine on vascular function and homocysteine metabolism. Vascular Medicine 14:239-247, 2009.
  5. 2003 Extravaganza Las Vegas – Nitrous Oxide. Herbalife Broadcase Network video, 2003. Accessed online, Dec 12, 2004.
  6. Wanjek C. Nitric oxide now—ask me how: Some find Nobel laureate ‘s alliance with supplement maker hard to swallow. Washington Post, Oct 7, 2003.
  7. Napoli C and others. Long-term combined beneficial effects of physical training and metabolic treatment on atherosclerosis in hypercholesterolemic mice. Proceedings of the National Academy of Sciences 101:8797-8802, 2004.
  8. Evans D. Nobel Prize winner didn’t disclose his Herbalife contract. Bloomberg News, Dec 8, 2004.
  9. Ignarro LJ. Letter to Nicholas Cozzarelli, Ph.D. Dec 12. 2004.
  10. Who wants to be a millionaire? Pershing Square Capital Management, LP., Dec 20, 2012, p 48.
  11. Hitzik M. Herbalife cozies up with UCLA. Los Angeles Times, Feb 22, 2013.
  12. Nobel Prize research leads to development of innovative nutritional supplement for cardiovascular health: Developed by Nobel Prize Winner Dr. Ferid Murad, Cardio Discovery™ boosts the body’s production of nitric oxide, supporting artery flexibility and functioning. Leiner Health Products news release, Dec 6, 2004.
  13. FDA finalizes claims for claims on dietary supplements. FDA Talk Paper T00-1. Jan 5, 2000.
  14. Regulations on statements made for dietary supplements concerning the effect of the product on the structure or function of the body; final rule. Federal Register 65:999-1050, 2000.
  15. Final judgment and permanent injunction. People of the State of California and the Director of the Department of Health Services vs. Herbalife International, Inc., and Mark Hughes et al. Superior Court of the State of California County of Santa Cruz. Case No. 92767, Oct 14, 1986.
  16. FTC alleges Maryland companies lack support for claims that heartbar is effective against cardiovascular diseases. FTC news release, June 12, 2003.
  17. Agreement containing consent order. In the matter of Unither Pharma, Inc., and United Therapeutics Corporation, FTC File No. 022 3036.
  18. Schulman SP. L-arginine therapy in acute myocardial infarction: the Vascular Interaction With Age in Myocardial Infarction (VINTAGE MI) randomized clinical trial. JAMA 295:58-65, 2006.
  19. Wilson AM and others. L-arginine supplementation in peripheral arterial disease: no benefit and possible harm. Circulation 116:188-196, 2007.
  20. Jahanjir E and others. The effect of L-arginine and creatine on vascular function and homocysteine metabolism. Vascular Medicine 14:239-248, 2009.
  21. Chen S and others. Arginine and antioxidant supplement on performance in elderly male cyclists: a randomized controlled trial. Journal of the International Society of Sports Nutrition 7:13, 2010.

This article was revised on June 15, 2014.