In the comment thread of my recent post about Herbalife, the multilevel supplement marketing company, I brought up the company’s association with Dr Louis Ignarro who shared the 1998 Nobel Prize in Physiology or Medicine for the discovery of nitric oxide as a signaling molecule in the cardiovascular system.

My medblogging colleague, Orac, reminded me of a post he put up last October about his personal experience hearing Dr Ignarro talk at the American Association for Academic Surgery meeting:

You see, what happened is that Dr. Ignarro started delving into what sounded to me like woo about diet and heart disease, discussing evidence that he had developed that arginine supplementation increases nitric oxide levels and protects against heart disease. It was somewhat interesting, and he might have been on to something. However, he was clearly vastly overselling it, indeed outright advocating that everyone should be taking arginine supplementation because it would greatly reduce the risk of developing heart disease through its generation of nitric oxide. I might not have thought about it much again, but then he did something that I’ve never seen a scientific speaker do before at an invited scientific talk at a conference. He started discussing (almost hawking) a diet book he had written called No More Heart Disease: How Nitric Oxide Can Prevent—Even Reverse—Heart Disease And Stroke. In a single–if you’ll excuse the term–stroke during the last 15 minutes of his talk, Ignarro turned what should have been an inspiring talk given to a bunch of young surgeon-scientists to fire them up to want to be great researchers and push the boundaries of surgical science into little more than an infomercial for his book and a forum to pontificate about his outside the mainstream ideas regarding nutrition. Even if his work on arginine pans out, when he gave his talk it was clearly not ready for prime-time, and it’s not as though alties pushing various nutritional “treatments” haven’t been pushing arginine supplementation for a long time now. Ignarro gave them a seemingly scientific basis for these claims. He might turn out to be right, but even if he is, he had no business making the claims that he did based on the evidence that he had.

The reference is to this work begins with a paper in the Proceedings of the National Academy of Sciences indicating that high doses of L-arginine and vitamin E together with low doses of vitamin C in the diet reduce the appearance of atherosclerosis in mice fed a high-cholesterol diet and forced to exercise to increase systemic oxidative stress. While Ignarro was criticized by the press for not making known his association with Herbalife for that paper, a subsequent paper using some of the same supplements in rabbits did note, “L.J.I. wishes to disclose that he helped develop and has a financial interest in a commercially available dietary supplement that contains some of the amino acids and antioxidants studied in this report.” Subsequent papers building on this work also carry similar disclaimer/conflict of interest statements.

Frankly, I’d be very interested to know whether reasonably achievable concentrations of nitric oxide precursors (L-arginine and L-citrulline) and antioxidants actually do decrease the risk of stroke or even atherosclerotic lesions in humans, especially in folks who exercise and/or eat high-cholesterol foods. At least one trial has examined high-dose (8.3 grams/day) L-arginine supplementation together with diet and exercise in obese, insulin-resistant diabetics and found improvements in surrogate markers of endothelial cell function, glucose metabolism, and insulin senstivity.

Herbalife is not a small player in this business; their website notes 2006 annual sales were US$3 billion. You’d think that a company like this would support a decent-sized human clinical trial to answer the questions raised by Ignarro’s animal studies. Of course, a negative outcome would hurt future sales and I would be naive to think they would want to put their current market share at risk. But the goal of any scientist is to see their work translate ultimately into benefit for human populations.

Perhaps Dr Ignarro could use his influence at Herbalife to go for the jugular, as it were, and actually test the supplement combo in a relevant human population. I would.

Note added in proof: A reader (Joe) has pointed out that L-citrulline is not an NO donor but rather a byproduct of L-arginine. I stand corrected. However, L-citrulline gets recycled back to L-arginine in many systems so it might be considered an indirect NO precursor.