Protandim: A “Science-backed” Miracle Supplement?

Recently, my neighbor approached me about a “very exciting and lucrative business opportunity.” Those are the magical words to pique my curiosity, but I’m also a skeptic by default, so I can’t say I was immediately on board.  She encouraged me to watch this Primetime live video, excitedly told me research about it had been published in Circulation and invited me to a meeting to learn more. I won’t keep you in suspense any longer about this business opportunity- it was to become an independent distributor for a dietary supplement called Protandim, by LifeVantage Corporation.  LifeVantage says Protandim is beneficial for reducing oxidative stress, preventing and treating chronic disease and aging.  It tries to differentiate itself from the dietary supplement pack by emphasizing the science behind its products. This alone might be enough to convince the typical consumer, but not this curious pharmacist. In fact, after attending the meeting and doing more research I find Protandim to be an egregious example of deceptive marketing, the misuse of science and society’s yearning to stay young forever.

A Little About Aging

Aging is not a disease; it’s a normal biochemical process.   It’s defined as the time-related deterioration of the physiological functions necessary for survival and reproduction.  Aging is not to be confused with diseases of aging like heart disease, cancer and Alzheimer’s disease.  Death is the inevitable consequence of aging, and arguably the one thing humans fear the most.  Luckily death comes later in life for us than it did for our ancestors.  Thanks to improved hygiene and medical advancements, global life expectancy has increased from 48 years in the 1950’s to 71 years today.  Unfortunately, the human lifespan- the maximum number of years a human can live- remains unchanged at 120 years.  Modern science has been attempting to unravel the mystery of the aging process to increase human lifespan, but it hasn’t been successful yet.  Don’t allow the plethora of “anti-aging” pills on the market fool you; use of the term is a misnomer and deceptive marketing.

The Free Radical Theory of Aging

Hundreds of theories of aging have been proposed: immunological, telomere, mitochondrial and inflammation theories among the more notable.  The most well-known and researched of them all is the free radical theory.  It’s important to note that while in the past researchers searched for a single cause of aging, because it is complex and multi-factorial, the scientific world now accepts that aging is most likely explained by a combination of theories.  Although heavily debated, the free radical theory remains among the most widely accepted.

Developed in the 1950’s by Dr. Denham Harman, the theory states that aging and age-related disease occurs as a result of the accumulation of damage caused by reactive oxygen species (ROS), or free radicals, at the cellular and tissue level.  Free radicals like superoxide (O2) are chemically unstable molecules that react with DNA, protein, fat and even the lining of arteries to become stable, wreaking havoc on our bodies in the process.  To make matters worse (gasp), free radical formation is unavoidable because normal cellular metabolism and energy production produce free radicals.  Fortunately, our bodies have a defense mechanism: endogenous antioxidant enzymes.  The enzymes superoxide dismutase (SOD) and catalase (CAT) work by graciously donating an electron to free radicals to stabilize them before they can do too much damage.  Sometimes the body’s antioxidant system can’t keep up with demand, and levels of free radicals exceed antioxidant levels.  This results in oxidative stress, and it tends to increase with age.  Dr. Joe McCord is credited with discovering superoxide dismutase (SOD) in the 1960’s, and he spent his career researching oxidative stress and the potential role of SOD in aging and chronic disease prevention.

Antioxidants and Chronic Disease

Studies have shown a correlation between low blood levels of antioxidants and a higher incidence of chronic diseases.  In fact, the entire antioxidant supplement industry is built on this research.  The theory is that by increasing our antioxidant levels we can prevent chronic disease.  One way to do this is by taking oral supplements like Vitamin C and E which themselves act as antioxidants to scavenge and neutralize free radicals.  Although early research on these exogenous antioxidants showed promise for preventing chronic disease, in several larger trials subjects receiving antioxidants tended to have higher rates of chronic disease and death.  It’s another reminder that correlation is not the same thing as causation (as in the 1950’s when researchers proposed that ice cream caused polio).  The lack of evidence hasn’t stopped the $120 billion dietary supplement industry that is expected to grow to $270 billion by 2024.  There is another way to increase antioxidant levels, however.  Research has shown that certain botanicals can trigger the production of endogenous antioxidants like SOD.  LifeVantage says its cutting-edge research in this area has helped them develop products to combat aging and chronic disease.  Enter Protandim stage left

A Closer Look at Protandim

The Product

Protandim is formulated based on previous research on botanicals that increase endogenous SOD and CAT levels in mammals.  It is a proprietary blend of five ingredients: Bacopa monnieri 150 mg (spelled monierra in most Protandim studies and the patent)Silybum marianum 225 mg (milk thistle), Withania somnifera 150 mg (Ashwagandha), Camellia sinensis 75 mg (green tea) and Curcuma longa 75 mg (turmeric)- totaling 675 mg per capsule.  Individually, each of these has been shown to increase endogenous antioxidants levels in rodents.  The theory is by combining them in one capsule they will have an additive effect, which a study in mice showed some evidence for.  One bottle of Protandim (30 capsules) costs between $40 and $50, or $500 to $600 per year.  Although the price is in line with similar products, it looks like the additive effect doesn’t come cheap.

Mechanism of Action

Protandim apparently works by activating Nrf2, a transcription protein within cells that when activated triggers the production of endogenous antioxidants.  This is not to be confused with the Protandim Nrf1 product, which stimulates the production of proteins needed to increase cellular energy production.  But wait; if you were paying attention earlier you might remember that cellular energy production produces free radicals.   So taking Protandim Nrf1 results in more energy (and more free radicals), and Protandim Nrf2 counteracts it.  A genius marketing ploy and a perfect segue into the LifeVantage story and business model.

The LifeVantage Corporation


LifeVantage Corporation (Nasdaq: LFVN) was founded in 2003.  According to their website, they are a science-based nutraceutical company dedicated to helping people reach their health and wellness goals by developing products intended to deliver significant health benefits to consumers.  Their focus is Nutrigenomics- the new science of how food and food constituents affect the genome used to develop “biohacking” products that optimize mind and body performance.  Although Dr. Joe McCord, former LifeVantage Chief Science Officer, is credited with inventing the Protandim formula, a closer look at the patent reveals Paul Myhill and William J. Driscoll, former LifeVantage executives, as the actual inventors.  Both have backgrounds in business and marketing; neither has a science degree.  The company admitted hiding this and bringing Dr. McCord on board to provide more scientific credibility.  Apparently it’s hard to pass off a supplement developed by an ex-oil executive as “rooted in science.”

The Business Model

Protandim was initially sold direct to consumer in retail, but after the buzz from the Primetime segment wore off sales tanked, and LifeVantage knew they needed a different strategy- multi-level marketing.  If you head to GNC to purchase Protandim you’re out of luck; it can only be purchased from their distributor network.  Distributors make money selling product, but they can also recruit new distributors and receive a percentage of the sales from those “downline distributors.”  The more they sell, the higher their rank.  It’s a tall order to make it to the top of the distributor ranking ladder at LifeVantage; apparently, 60% never make it past the second rung, averaging only $79 per month in revenue.  Notice this is reported as an average, so the reality could be even worse.  This is a legitimate business model per se, but multi-level marketing can be hard to differentiate from an illegal pyramid scheme.  Pyramid schemes often rely more on recruitment and sales to members than sales to consumers for revenue.  LifeVantage does have an A- rating with the Better Business Bureau, which is a good sign.  I can’t say for certain which business model LifeVantage follows, but I tend to trust my intuition.  In that distributor meeting something definitely smelled fishy and I don’t think it was the smoked salmon appetizer being served.

Marketing Strategy

Thanks to the Dietary Supplement Health and Education Act (DSHEA) of 1994, supplement manufacturers have specific mandates to follow when making structure/function claims because their products are not FDA-approved.  Manufacturers cannot make implicit or explicit claims that supplements prevent, treat, mitigate, cure or diagnose a disease.  If such claims are made they must be supported by sufficient evidence.  This evidence, again according to the FDA, should be from randomized, placebo-controlled, double-blinded clinical studies in humans.  According to LifeVantage’s investor presentation, patent (see page 26) and distributor meeting, Protandim can prevent or cure about a hundred diseases and is an anti-aging product.  Surely LifeVantage has robust data to support all of these bold claims.  Let’s dive in.

The Science

LifeVantage and its distributors talk endlessly about the science behind Protandim, stating it has “peer-reviewed research that is published in major scientific journals.”  Unfortunately, this statement will not suffice because journals also publish peer-reviewed research about treatments and procedures that do not work.  After combing through the Protandim studies, I agree that much research has been done and published to support the theory behind why Protandim should work.  There is some bias present, as most of the research was done at the University of Colorado at Dr. Joe McCord’s lab, who purportedly receives a commission for each bottle sold.  Ultimately, however, the scientific evidence is not only about the amount of research and where it is published- it’s also about the type of study, the quality, and the results. 

Preclinical Research

Most of the research done on Protandim is preclinical research in rodents or cells in vitro.  It has been studied extensively in mice for potential use in cancer, cardiovascular disease, liver disease, osteoarthritis and muscular dystrophy to name a few.  According to the FDA, “preclinical studies provide detailed information on dosing and toxicity levels. After preclinical testing, researchers review their findings and decide whether the drug should be tested in people.”  The purpose of preclinical research is to test the feasibility and safety of a drug before it is tested for effectiveness in humans; it should not be used on its own to support definitive prevention or treatment claims.  Protandim’s preclinical research indicates it may have the potential for use in chronic disease prevention or treatment in the future, but it cannot be said to cure cancer or heart disease.  This leaves just a handful of human studies, only one of which has positive results.

Studies in Humans

A study from 2006, also at the University of Colorado, researched whether Protandim could reduce oxidative stress in healthy adults by measuring thiobarbituric acid-reactive substances (TBARS), SOD and CAT levels at 30 and 120 days.  TBARS is a common but somewhat controversial way to measure oxidative stress.  At 30 days, subjects receiving 675 mg Protandim daily experienced a 40% reduction in TBAR levels from baseline.  At 120 days subjects experienced a 30% increase in SOD and a 54% increase in CAT antioxidant enzyme levels.  Although results were positive, this was a small, open-label, non-randomized study in 29 healthy adults with no placebo group.  Also, TBARS, SOD and CAT are surrogate markers, not hard endpoints like a chronic disease and death.  Until a human interventional study can show a reduction in oxidative stress translates to improvement in hard endpoints, the health claims of Protandim are still theoretical, scientifically speaking.

Little reference is ever made to a study published in 2016 on whether Protandim could affect athletic performance and antioxidant blood levels in runners.  In this randomized, placebo-controlled, double-blind study of 40 runners taking Protandim 675 mg once daily for 90 days, there was no significant difference in running time, TBARS, or SOD levels compared to placebo.  A post-hoc analysis showed SOD levels increased almost two-fold in subjects > 35 years old.  Interestingly, both the Protandim and placebo groups experienced a similar drop in TBAR levels.  The authors also mention previous research showing that endurance training on a regular basis can increase SOD levels up to 45% in blood- more than Protandim did in the previous study.  Based on these together, one could suggest that Protandim may be no more effective than regular endurance training in reducing oxidative stress.  To date, Protandim has not shown any positive results in randomized, blinded, placebo-controlled studies in humans.

The Mouse Longevity Study

For those of you dying to ask if I’ve read the study in which Protandim-treated male mice had longer lifespans: I’ll bite.  In this study performed by the National Institute on Aging Interventions Testing Program (ITP), the survival of mice fed Protandim chow was compared to mice fed normal chow.  Male mice fed Protandim chow showed a 7% increase in median survival (p < 0.012).  At the distributor meeting, this study was cited as scientific evidence of Protandim’s anti-aging benefits in humans- and I almost fell out of my chair.

There are a few problems with the above conclusion.  First, we have to remember the study was in mice, not humans.  Until Protandim increases lifespan in a human clinical trial, anti-aging claims should not be made.  This has yet to be studied.  There is also an important distinction between median and maximal lifespan.  If a treatment alters an underlying disease of aging but does not affect the aging mechanism, it will only increase median lifespan.  If a treatment has unlocked the aging mechanism and slows, reverses or prevents the aging process, it will increase maximal lifespan.  The authors state Protandim increased median, but not maximal lifespan.  This means Protandim affected an underlying age-related disease, but it did not affect aging.  Ironically, the study used to prove Protandim is anti-aging is evidence that it is not.  In this same study, metformin did increase maximal lifespan, and is being studied further for its potential as the first-ever anti-aging pill.

In case you are wondering about the article in Circulation, it studied the association between pulmonary artery hypertension and heart failure, and the cardioprotective abilities of Protandim in rats.  The research is interesting and yielded positive results, but again, it is early research in rats.  This is not yet proof that Protandim cures heart disease.  Plus, the rats received their Protandim intraperitoneally.  Need I say more.

The Bottom Line

At the distributor meeting, I did hear stories about Protandim helping people feel better.  Although these stories are anecdotal, I don’t want to take anything away from them.  If you are having success with Protandim and no side effects, by all means, continue taking it.  But if you are only considering it, I don’t see a reason to recommend it over other antioxidant products on the market, or a balanced diet and exercise.  At best, preliminary research indicates that Protandim can reduce oxidative stress and increase endogenous antioxidants in healthy adults for up to four months, but more research is needed to see how this translates to aging and chronic disease prevention and treatment.  LifeVantage makes very bold statements about the science supporting the effectiveness of Protandim, but there is a difference between a testimonial, published data and scientific evidence.  The FDA agrees and sent LifeVantage a warning letter this year asking them to remove all prevention and treatment claims from their website and products.  Last I heard it has yet to respond.  With such a negative stigma placed on aging in our society, there will always be thousands of products claiming to be magical anti-aging cures.  Every time I see my neighbor driving her 1990’s Minivan, proudly displaying her Nrf2 sticker on the back windshield, I’m reminded that Protandim hasn’t proven itself to be one of them.  Needless to say, I never became a LifeVantage distributor.