Protandim: Another Kind of Antioxidant

Four years ago I received an e-mail inquiry about Protandim. I had never heard of it; but I looked it up and wrote a quick, informal, somewhat snarky answer that got posted on the Internet. It got a lot of attention. Googling for Protandim now brings up my critique right after the Protandim website itself: that can’t be good for sales. Over the years, several e-mails and blog comments have informed me that I was wrong (usually offering testimonials or calling me closed-minded), and recently I’ve been getting inquiries asking if I’ve changed my mind now that a clinical study has been published. I haven’t.

Instead of providing antioxidants directly, Protandim is supposed to stimulate the body to produce its own antioxidants. The website tells us it is “the only supplement clinically proven to reduce oxidative stress by 40%, slowing down the rate of cell aging to the level of a 20 year old.” It provides “thousands of times more antioxidant power than any food or conventional antioxidant supplement.” It signals the body’s genes to produce the enzymes SOD (superoxide dismutase) and CAT (catalase) that act as catalysts to neutralize free radicals and are not “used up” like ingested antioxidants are. It “creates a cascade of your body’s natural catalytic antioxidants that are able to destroy millions of free radicals per second.” It raises the level of glutathione by 300%. Glutathione is good, apparently.

What is Protandim? It’s a combination of Milk thistle, Bacopa extract, Ashwagandha, Green tea extract, and Turmeric extract. I looked these up in the Natural Medicines Comprehensive Database. None of them is known to have any significant clinical benefit from antioxidant effects. Some of them are listed as “not enough information” to know if they are safe. One has estrogenic properties and more than one has known side effects and potential interactions with other drugs. The only one that even sounds remotely like it might have some pertinent data behind it is green tea. Green tea contains antioxidant catechins that are “thought to possibly have a protective effect against atherosclerosis and heart disease” and contains flavonoids that “might reduce lipoprotein oxidation; however benefits have not yet been described in humans.”

A Pubmed search for “Protandim” yielded only 3 studies: One in mice, one in cell cultures and one in humans.

1. The mouse study. Protandim reduced the development of skin cancers in a mouse model.
2. The cell culture study. Cells in cell culture produced more glutathione in the presence of Protandim. There was a synergistic effect of components in the induction of heme oxygenase-1.
3. The human study. The only clinical study so far.

After 30 days of supplementation, TBARS declined by an average of 40% (p = 0.0001) and the age-dependent increase was eliminated. By 120 days, erythrocyte SOD increased by 30% (p < 0.01) and catalase by 54% (p < 0.002). We conclude that modest induction of the catalytic antioxidants SOD and catalase may be a much more effective approach than supplementation with antioxidants (such as vitamins C and E) that can, at best, stoichiometrically scavenge a very small fraction of total oxidant production.

The concept is intriguing, and it may have promise, but the current evidence is not sufficient to make clinical recommendations. There is only one study to date in humans, and it only measured markers in the blood. TBARS (thiobarbituric acid reactive substances) is a measurement that has not demonstrated clinical usefulness. I could only find one study suggesting that TBARS levels might be helpful in predicting outcome in patients who already have cardiovascular disease. This review article critiques TBARS and other measures of antioxidant activity and suggests that measuring isoprostanes might be more meaningful.

It’s all very well to show that a remedy changes blood test results or even a known marker for disease; but what we really need to know is whether it improves health, prevents cancer, prolongs life…We need POEMS: Patient Oriented Evidence that Matters. Avandia improves hemoglobin A1C levels in diabetics but increases mortality. Mortality matters a lot; Hgb A1C levels don’t matter so much. “The operation was a success but the patient died” is not good enough.

I went to Wikipedia not as a reliable source but because it often has links to more information from primary sources. For what it’s worth, the Wiki article on Protandim concurs with my assessment, stating “There is no acceptable evidence that it improves health.” Wiki links to a very useful “Protandim Watch” website that has gathered a lot of information in one place, including information about the company and its multilevel marketing. It is skeptical and recommends caution. Wikipedia also questions Protandim’s claim of life extension, listing several studies on animals suggesting that increasing production of those catalytic enzymes might not increase life span and possibly might shorten it.

From the Protandim Watch website I learned that a second patent was awarded to Protandim in 2008. In the patent application, they claimed that

The compositions of the present invention are useful to prevent or treat the following disorders and diseases: memory loss; Parkinson’s disease; aging; toxin-induced hepatotoxicity, inflammation; liver cirrhosis; chronic hepatitis; and diabetes due to cirrhosis; indigestion; fatigue; stress; cough; infertility; tissue inflammation; cancer; anxiety disorders; panic attacks; rheumatism; pain; manic depression; alcoholic paranoia; schizophrenia; fever; insomnia; infertility; aging; skin inflammations and disorders; alcoholism; anemia; carbuncles; convalescence; emaciation; HIV; AIDS; immune system problems; lumbago; multiple sclerosis; muscle energy loss; paralysis; swollen glands; ulcers; breathing difficulties; inflammation; psoriasis; cancer (e.g.; prostate cancer, lung cancer and breast cancer); pain; cardiovascular disease (e.g.; arteriosclerosis and atherosclerosis); ischemia/reperfusion injury; anxiety; attention deficit disorder; leprosy; arthritis (e.g., psoriatic arthritis; ankylosing spondylitis; and rheumatoid arthritis); hemorrhoids; tuberculosis; high blood pressure; congestive heart failure; venous insufficiency (pooling of blood in the veins; usually in the legs); sore throat; hepatitis; syphilis; stomach ulcers; epilepsy; diarrhea; asthma; burns; piles; sunburn; wrinkles; headache; insect bites; cuts; ulcers; sores; herpes; jaundice; bursitis; canker sores; sore gums; poison ivy; gastritis; high cholesterol; heart disease; bacterial infection; viral infection; acne; aging; immune disorders; dental caries; periodontitis; halitosis; dandruff; cardiovascular disease (e.g., hypertension; thrombosis; arteriosclerosis); migraine headaches; diabetes; elevated blood glucose; diseases of the alimentary canal and respiratory system; age-related physical and mental deterioration (e.g., Alzheimer’s Disease and age-related dementia); cardiovascular disease; cerebral vascular insufficiency and impaired cerebral performance; congestive symptoms of premenstrual syndrome; allergies; age-related vision loss; depression; Raynaud’s disease; peripheral vascular disease; intermittent claudication; vertigo; equilibrium disorder; prevention of altitude sickness; tinnitus (ringing in the ear); liver fibrosis; macular degeneration; asthma; graft rejection; and immune disorders that induce toxic shock; bronchpulmonary disease as cystic fibrosis; chronic bronchitis; gastritis; heart attack; angina pectoris; chronic obstructive pulmonary disease; kidney damage during coronary angiography; Unverricht-Lundborg disease; pseudoporphyria; pneumonia; and paracetamol hepatotoxicity.

Did they leave anything out?

Clearly, these claims can’t be substantiated, and they can’t legally list them on their website. LifeVantage Corporation’s website still states that it

does not market and sell Protandim® for the purposes of preventing, treating, curing, or mitigating any disease, including MS.

I guess we can assume they only market and sell it for the purposes of making money.

The second study listed above really intrigues me. They tested the individual components and apparently established that there was a marked synergism when the ingredients were combined. If this is true, it is unusual and deserves further investigation. In general, mixing natural medicines has produced additive but not synergistic effects, despite the claims of naturopaths that synergistic effects are common and are a basic principle of herbal medicine.

Some 20 studies in humans are said to be in progress. I’ll watch developments with great interest. Meanwhile, I can’t recommend taking Protandim. There has been a lot of hype about antioxidants. Most of the research indicates that eating fruits and vegetables is beneficial, but taking antioxidant supplements is either useless or counterproductive.

If you did want to raise your antioxidant levels, how could you rationally choose from all the products on the market? For instance, how about Seanol? – they say it has some of “the most powerful antioxidants on earth” and is responsible for the longevity of Okinawans.

I’m not buying.

This article was originally published in the Science-Based Medicine Blog.

Dr. Hall is a contributing editor to both Skeptic magazine and the Skeptical Inquirer. She is a weekly contributor to the Science-Based Medicine Blog and is one of its editors. She has also contributed to Quackwatch and to a number of other respected journals and publications. She is the author of Women Aren’t Supposed to Fly: The Memoirs of a Female Flight Surgeon and co-author of the textbook, Consumer Health: A Guide to Intelligent Decisions.

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