Brief Update: Protandim

I’ve already devoted more time to Protandim than it deserves. I’ve written about it twice on SBM: here  and here . But I can’t resist covering a new Protandim study that not only serves as a bad example but that made me laugh.

Protandim is a mixture of 5 herbal supplements intended to upregulate the body’s own production of antioxidants. Its patent application claimed that it was useful to treat or prevent an astounding 126 diseases and medical conditions, from tinnitus to aging, from hemorrhoids to cancer.  At the time of my last article, only one human study had been done. It found increases in blood test markers and interpreted them as a surrogate for increased antioxidant activity in the body, but did not even attempt to assess whether those increases corresponded to any measurable clinical benefit, for cancer or for anything else. I begged Protandim supporters not to ask me about it again until there were human clinical studies with meaningful outcomes. 

Now there is finally a second human study, although still not one that qualifies as a clinical trial.  Curiously, it is not listed on the company’s website. I wonder why? Perhaps because it showed Protandim didn’t work. Oops. 


Most customers seem to be taking Protandim because of its alleged ability to prolong life, improve diabetes, prevent cancer, make them feel better, etc.  Instead of studying any of those things, the researchers chose to study alveolar epithelial permeability.

In the introductory section of their paper, they explain that alcohol use disorders (AUDs) have been linked to the development of acute lung injury. They admit that the underlying factors are elusive and probably multifactorial. One potential contributor is the patients’ propensity for severe pulmonary infections mediated through abnormal pulmonary innate immunity. Additionally, they say that prior research had “suggested” an association between AUDs and abnormal alveolar epithelial permeability which “might” be mediated through pulmonary oxidative stress. So they did a double blind study, not to test whether Protandim would improve lung disease or reduce the rate of infections in alcoholics, but to see if Protandim would reduce markers of oxidative stress and normalize abnormal alveolar epithelial permeability. 

To recap their chain of reasoning: alcoholics might develop lung disease, that lung disease might be correlated with abnormal epithelial permeability, protein levels measured by bronchoalveolar lavage (BAL) might be a valid measure of permeability, permeability might be affected by underlying oxidative stress, and Protandim might reduce oxidative stress by stimulating the body to produce its own antioxidants. Do they perhaps think that lots of “mights” add up to a “mighty” argument?

Why would they want to study this particular mixture of 5 herbs? The second listed author, Joe McCord, has a vested interest: he is an officer of the LifeVantage company, the manufacturer of Protandim. They explain that Protandim is “a nutraceutical with a lengthy history of use in homeopathic, Ayurvedic, and traditional Chinese medicine.”  An interesting statement, since Protandim was invented only a few years ago by a person with no medical background and it was patented in 2007. Doubly interesting since it belies the common myth that natural medicines are not profitable because they can’t be patented.

How many Protandim customers are alcoholics taking it for lung injury due to alcohol abuse? I would guess not many. Why on earth would they pick an esoteric detail like this to study and why would they look at Protandim’s influence on lab tests instead of looking for a useful clinical benefit?

Bronchoalveolar Lavage (BAL)

They randomized 30 alcoholics and gave 16 of them placebo and 14 of them a double dose of Protandim. There are some methodological problems: randomization was imperfect, with unequal numbers and some significant differences between the groups; some possible confounders were not eliminated (for instance, some of the subjects got intermittent benzodiazepines for alcohol withdrawal symptoms); and some of the blood tests were only done on smaller subsamples of the group. A separate small control group of 11 normal subjects also got a single BAL and their BAL protein levels were not significantly different from the AUD subjects, which sheds doubt on the whole rationale for the study by failing to confirm that alveolar permeability correlates with AUD. They did BAL twice on the AUD subjects, before and after a week’s treatment with Protandim or placebo. The utility of BAL is limited, since there is a large range of normal values for the substances measured and a number of confounding factors. Of more concern, this procedure is invasive, unpleasant, and far from benign. It requires the use of drugs for topical anesthesia and conscious sedation and can result in serious complications. It involves passing a bronchoscope deep into the lungs, wedging it into a lung segment, squirting in a small amount of saline, and then sucking out the liquid for analysis. In other words, putting water into the airways: sort of a partial drowning. With known risks and no possible benefit to patients, why did the Institutional Review Board approve it? I hope their consent forms were adequate, and I hope they paid their subjects well.


They assessed alveolar epithelial permeability by measuring the total protein in bronchoalveolar washings. Total protein levels did not change in either experimental group. They also found no change in oxidative stress indices, epithelial growth factor, fibroblast growth factor, interleukin-1β, interleukin-10, liver function tests, or other blood chemistry tests. The one finding that was statistically significant was a significant decrease in plasma thiobarbituric acid reactive substances (TBARS), a marker of lipid peroxidation — but that was only in the placebo group!

In short, Protandim was significantly (p<0.01) worse than placebo. No wonder they’re not bragging about this study!


I really don’t get it. Why did they do this study? Why did they use twice the recommended dose? What was the IRB thinking? Why didn’t they study something with a useful clinical endpoint? As an e-mail correspondent said, “They make claims about diabetics being able to go off of insulin or reduce insulin…why not do a trial on that?”  That’s an excellent point: a diabetes trial would not involve invasive procedures and would be far easier to carry out and far more meaningful. When advocates do esoteric, convoluted laboratory studies instead of straightforward simple clinical trials, it raises the suspicion that they believe at some level that such clinical trials wouldn’t help their case.

No, on second thought, I think I do get it: they want to prove, by any means possible, no matter how circuitous or far-fetched, that Protandim does something, anything, antioxidantish (not a word? Well it is now!). Then they can dredge the literature for every condition where a possible correlation with oxidative stress has been mentioned. Then they can try to convince customers they should take Protandim for all those conditions.

Big Pharma gets a lot of criticism, but aren’t Big Supplement and Big Multi-Level Marketing every bit as guilty of self-interest, distortions, and profit motives? At least Big Pharma can’t make its big bucks without first demonstrating effectiveness and safety to the FDA with clinical trials.

Does Protandim provide any real benefit to its customers? I don’t know, and they can’t hope to know unless they do proper clinical studies.

Posted in: Herbs & Supplements

Leave a Comment (14) ↓

14 thoughts on “Brief Update: Protandim

  1. windriven says:

    “In other words, putting water into the airways: sort of a partial drowning. ”

    Hmmm, waterboarding for woo.

  2. I think you’ve nailed an important point there regarding the motive for such a peculiar trial: it’s a fishing expedition for any biological effect whatsoever in a human subject, anything that can be spun as “antioxidantish” (thanks for that laugh!). That’s all Protandim believers will see, their confirmation bias dialed up to 11.

  3. gippgig says:

    The idea of inducing the antioxidant response makes sense but using Protandim doesn’t. A much better way to do this is with glucoraphanin(precursor)/sulforaphane(active compound) (see Food: The omnivore’s labyrinth, Nature 471 S22; by the way, what do you think of Nature’s section on cancer prevention that this article appears in?). Broccoli sprouts (available in grocery stores) are an excellent source and it’s sold as a supplement (very cheap).

  4. annappaa says:

    Big Pharma gets a lot of criticism, but aren’t Big Supplement and Big Multi-Level Marketing every bit as guilty of self-interest, distortions, and profit motives? At least Big Pharma can’t make its big bucks without first demonstrating effectiveness and safety to the FDA with clinical trials.

    YES, thank you. Now to get that onto a bumper sticker …

  5. Harriet Hall says:

    I just heard through the grapevine that Dr. McCord is putting this spin on the results for his followers: They will have to do it over because “it wasn’t significant enough….. only 82 or 87% significant and it MUST be 95% in order to be deemed significant.” Ha!

  6. Lazy Man and Money says:

    Thank you Ms. Hall for continue to cover Protandim.

    I realize that the science behind it doesn’t merit as much coverage as you’ve given it.

    However, LifeVantage’s marketing is very persuasive for those who lack critical thinking skills. It seems like the quote attributed to P.T. Barnum of a sucker being born every minute applies here.

    I don’t know if you’ve looked into the multi-level marketing phenomenon, but it relies largely on misleading consumers and cult tactics (see: Protandim is simply one example of quite a few products that follow the same business model.

    I appreciate you showing how these companies scam consumers. Please continue to spread the word and use any connections you have with the FDA and FTC to put an end to this. On my website, I have a few examples of how the company breaks their laws.

  7. ConspicuousCarl says:

    I suppose their intent is to keep doing weird little tests with high doses hoping that anything at all will happen so they can start making a stack of paper. This round was a stroke of bad luck, with their product randomly looking like a negative influence, but maybe the next one will look good when they look for changes in white blood cell counts or whatever else they come up with.

  8. Robermax says:

    I’m a science based bronchocopist. I think the risk/benefit ratio of bronchoscopy should be carefully considered for that as well as any other medical intervention but that crack about “partial drowning” was NO FAIR. :-(

    (the rest of the article was well done and I enjoyed it,though)

  9. MysticGypsy says:

    Dr. Hall,
    I appreciate your attempt to keep us all informed about Protandim. I support and endorse evidence-based medicine. I’ve been an RN for 25 years in all areas of Pediatrics and have a broad range of skills and experience. I also appreciate natural medicine with a more Integrative science-based approach. I hope for a happier marriage between natural healing techniques/time tested Traditional practices and the allopathic style of Western medicine today (which also has gaps in my opinion) in day-to-day practice.
    I was recently diagnosed with MS. I was quickly worstening. I started Copaxone in November with the explanation that I wouldn’t see any clinical improvent for about 3 months. I’d been hearing about many Protandim success stories and researched the data, which in my opinion at that time was not able to scientifically support the claims I was hearing due to the lack of human trials. I was familiar with all of Protandim’s ingredients and have used them separately so didn’t feel threatened by that area and the research I did see was quite hopeful. I started taking Protandim in November (at the same time as Copaxone since there was a theraputic delay) one a day but increasing after a week to 2/day. Honestly, I was pretty skeptical initially but that changed quickly. After 24 hours, my urinary urgency stopped, I slept thru the night (ashwaganda?) and the general anxiety I’d been living with disappeared. Pretty cool for the first day. After the first week, my energy/fatigue started showing a noticable improvement, my tinnitus started decreasing. My double vision was improved (an inflammation/fatigue symptom for me.) I was able to go down on my CPAP flow by 2 (from 14 to 12). I’d had to start on CPAP in Oct ’11 due to REM hypopneas/apneas. I’d been living with the feeling of a ‘tight hug’ around my ribs for weeks. The hot sensations in my rib area were decreasing in intensity and duration after the first week on Protandim. All this coincidental?? Maybe so…maybe no. 10 weeks later after starting the Copaxone injections, I noticed a subtle increase in general well-being, from eyes to balance and I believe that was the Copaxone starting to kick in.

    My opinion as of today: Protandim and Copaxone were the only changes I made in meds/supplements during that 10 week time period. Copaxone wasn’t supposed to be noticable for weeks but I had symptom changes immediately for the better after 24 hours of starting Protandim. Placebo affect? Don’t think so. Especially since I was feeling quite skeptical and hopeless at the time. In my anecdotal experience, Protandim and Copaxone have a cooperative/synergistic effect and I wouldn’t want to be without either of them! I have continued to improve/stablize since then. Nothing has continued to worsen. As of two weeks ago, I can now balance on my L leg in yoga! Yea! (it’s been 8 months since I could say that!)

    My MS doc participated in the BG-12 human trials last year. He says it’s showing a ‘neuro-protective quality and a potent anti-inflammatory effect.’ BG-12 is in it’s 3rd phase of FDA trials and is using the same nrf2 activating science as Protandim so I’m anxiously awaiting those studies to be released. I haven’t tried going off Protandim for 3 weeks. Don’t dare to! When I’ve missed 2-3 doses (which I have done), my fatigue, eye control and tinnitus worsten, that quickly. Interesting…

    Please continue to update Protandim research. I appreciate your critical eye. I do think nrf2 research is cutting edge and hope it turns out to be as efficable in humans as it has in the lab…

  10. Chris says:

    It is spammy Franky!

  11. Joyster says:


    There is a Doctor I know who has 6 patients who were Alzheimer’s patients in a vegetative state who woke up after being given Protandim. It seems to me that the “placebo” effect is irrelevant when administered to people who are in a vegetative state. Further, it is unnecessary to do such studies to determine harmful side effects when the ingredients in Protandim have been used for centuries without harmful side effects. Protandim is not “new” in the same way that synthetic drugs are “new.”

    While it may be necessary by law to require double bind studies for new synthetic drugs, it is not necessary to do so for herbal supplements that have been used for centuries. My research indicates that it takes around ten years and between $500 and $700 million to do the type of testing required for pharmaceuticals. Protandim has not been sold (in its compound form) that long, and a small company like Lifevantage could not afford the cost of such testing.

    If you were open-minded, you would encourage the use of products like this as an alternative to pharmaceuticals that have known harmful side-effects. The Pharisees claimed that Jesus healed people by the power of Satan. He correctly called them blind guides of the blind. Perhaps that is where the term “double blind” originated.

    1. Harriet Hall says:


      “6 patients who were Alzheimer’s patients in a vegetative state who woke up after being given Protandim.”

      If this anecdote is true, why hasn’t the doctor published a case series? What is the doctor’s name? Can we contact him for more information? Does he sell Protandim?If a patient in a vegetative state wakes up after being given Protandim, that doesn’t mean that he woke up BECAUSE of the Protandim. He might have awakened because of some other factor, or spontaneously without any treatment. Even if true, your anecdote wouldn’t prove anything.

      “it is unnecessary to do such studies to determine harmful side effects when the ingredients in Protandim have been used for centuries without harmful side effects.”

      It is ALWAYS necessary to test. Records were not kept for all those centuries, there was no systematic surveillance, and rare side effects would not have been detected. Furthermore, when several ingredients are mixed, the mixture might have effects not seen with the individual ingredients. All medical claims must be tested: that’s “medicine’s beautiful idea” – see

      “If you were open-minded, you would encourage the use of products like this as an alternative to pharmaceuticals that have known harmful side-effects.”

      I agree that the ingredients in Protandim are probably safer than many pharmaceuticals. But there’s no point in a “safe” treatment that doesn’t work. And without testing, there’s no way to judge which of the many products on offer might work. If you just want to take a chance and try things at random, or based on your personal speculations, that’s OK by me. But it isn’t OK to represent that a product will prolong life, improve health, or wake patients from vegetative states without any evidence.

Comments are closed.