I’m fed up! In August 2009 I wrote about Protandim, pointing out that it’s not supported by good evidence. I thought I had made myself clear; but apparently I had only made myself a target. True believers have deluged the Internet with attacks on my article, calling it mere “opinion,” ignoring its main points, and denigrating me personally. I have ignored the Internet attacks, but I’m beginning to feel personally harassed: I have lost count of the e-mails I have received from Protandim enthusiasts trying to convince me that it works and that I should change my mind. I’ve spent hours trying to explain my reasoning in e-mails, and it’s becoming a repetitive chore, so I am writing this so that next time I get an e-mail inquiry I can simply forward this link.

What Is In It?

Protandim is a mixture of milk thistle, bacopa extract, ashwagandha, green tea extract, and turmeric extract (all of which, incidentally, can be purchased individually at much lower cost).

What Do They Claim It Does?

As described on Wikipedia:

The manufacturers of Protandim claim the product can indirectly increase antioxidant activity by up-regulating endogenous antioxidant factors such as the enzymes superoxide dismutase (SOD) and catalase, as well as the tripeptide glutathione, and by activation of theNrf2 pathway.

Nrf2 is a transcription factor that upregulates the expression of various genes that may regulate oxidative stress. Drugs to target that pathway might have benefits for diseases that are caused or exacerbated by oxidative stress. Such drugs are investigational at this point, but the makers of Protandim have skipped the investigational stage and are marketing a product that they think is effective for almost every ailment known to man and that they are promoting as an anti-aging supplement.

In the application for their second patent, awarded in 2008, they wrote:

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.

Wow! Yet the website says it “does not market and sell Protandim® for the purposes of preventing, treating, curing, or mitigating any disease, including MS.”

So what purposes are we to think they do market and sell it for? Since oxidation is thought to be somehow involved in all the listed conditions, they are speculating that Protandim should prevent or treat those diseases by increasing the body’s production of antioxidants. They are promoting it for “anti-aging” because they are speculating that it will prevent or treat age-related diseases. They have no credible evidence to support their speculations.

An Update of Their Evidence

My original article only mentioned the 3 studies available at that time. As of this writing (October 2011), a query to PubMed brings up 8 published, peer-reviewed studies:

  1. A human study showing changes in TBARS, SOD, and catalase.(2006)
  2. A cell culture study showing increases in glutathione. (2009)
  3. A mouse study showing an effect on skin tumor carcinogenesis. (2009)
  4. A study in a mechanical animal model showing that chronic pulmonary artery pressure elevation is insufficient to explain right heart failure. (2009)
  5. Another mouse study showing that Protandim suppressed experimental carcinogenesis and suggesting that suppression of p53 and induction of MnSOD may play an important role.  (2010)
  6. A study of muscular dystrophy mice showing that Protandim decreased plasma osteopontin and improved markers of oxidative stress. (2010)
  7. An ex vivo (tissue culture) study of human saphenous veins, showing that Protandim attenuated intimal hyperplasia. (2011)
  8. An evaluation of the role of manganese superoxide dismutase in decreasing tumor incidence in a two-stage skin carcinogenesis model in mice. (2011)

Note that there have been no human clinical studies since the one in 2006. The newer studies are just more animal and laboratory studies, so they do nothing to change my previous conclusion.  If I were a mouse being artificially induced to develop skin cancer in a lab study, I might seriously consider taking Protandim.  But so far, the only study in humans measured increased antioxidant levels by a blood test but did not even attempt to assess whether those increases corresponded to any measurable clinical benefit, for cancer or for anything else.

My Assessment of the Evidence

This sounds like a promising area of investigation, but many treatments look promising in animal and in vitro (test tube) studies in the lab and then fail to translate to any useful clinical applications in humans. Much has been said about the benefits of antioxidants, but giving antioxidants as supplements has generally resulted in no benefits and even sometimes in harm. Protandim is trying another approach: getting the body to produce more of its own antioxidants. Even if it does that, it still remains to be seen whether those higher levels will correspond to any meaningful clinical benefits. And the tests they are using for antioxidant levels may not mean what they would like to think they mean. Sometimes the same substance can show either anti-oxidant or pro-oxidant effects depending on which test is used. And adverse consequences haven’t been ruled out. Free radicals play important roles in human health: they are essential for killing bacteria, cell signaling, and other functions. Raising antioxidant levels might interfere with some of these essential functions. Human biochemistry is complex, and changing one factor often has unexpected effects elsewhere in the web.


We simply don’t know enough at this point to recommend Protandim for treatment or prevention of any disease, for anti-aging, for making people feel healthier or more energetic, or for anything else. We need good human studies showing that people who take Protandim have better clinical outcomes than people who don’t. For instance, fewer heart attacks or fewer cancers…not just higher levels on a TBARS test. What we need is POEMS: patient-oriented evidence that matters.

I Get Mail

I heard from doctors working with the company, from company employees, from distributors, from customers, from relatives of customers, and even from people who were none of the above. Most of my correspondents completely failed to understand what I meant by human studies with meaningful clinical outcomes. Some of them thought I was not aware of the published evidence. Some of them wanted to insult me and the whole medical profession. Some offered testimonials. One wanted to revise the Hippocratic Oath. Others wanted to inform me that Protandim had been awarded patents and that its shares were doing well on the stock market. Some were more coherent than others. Here’s a sampling (errors in the original):

  • My wife has stage 4 metastatic breast cancer, a friend was telling about a natural supplement called Protandim. I was thinking about buying it after he showed me a study from LSU that says is maybe helpful in fighting cancer. I just ran across your blog and you say it is a scam. I am wondering if you are familiar with the LSU study
  • Did LSU not just present evidence that TBAR reduction with Protandim led to a meaningful clinical outcome?.. Regarding glutathione’s potential efficacy: go to youtube and search Dr. David perlmutter. Check out the before and after videos of Parkinson’s patients being injected with glutathione… Protandim is unique in having extensive scientific validation published in our most well respected, peer reviewed journals..
  • How do you feel about Protandim now that it has a clinical study?
  • I was impressed that Dr Perlmutter and Dr Colker both endorse protandim. What about the recent peer reviews on Cancer and Heart disease as well as the one on Glutathione?
  • Purpose of the email is to entice, I hope, you into taking a closer look at Protandim… Publishing a negative opinion will impact these people and if you are wrong and Dr. McCord is correct, there are a number of people who will not benefit from what is considered by a growing number of scientists to be cutting edge science in ageing and disease prevention.  My opinion is that you would benefit from getting up to speed in this arena.
  • You quackbusted on a Protandim back in 2005.  I’m wondering if you still feel the same about Protandim and Dr Joe McCord now that it’s 5 years later???  I was just made aware of protandim and wanted to know more because everything I am seeing is pointing me in the direction of yes you should be taking the stuff!!
  • Obviously there are 2 sides to what is going on here and I’m quite disturbed with the medical community and the belief that it’s their way or the highway and that the human body isn’t capable of fixing itself as Gerson explains it!!  I have been on the Protandim for 3 weeks tomorrow just 1 supplement a day and I feel a difference in my knees and ankles with a little more kick when going up the stairs…I’m actually bouncing a lot better than I was 3 weeks ago…I’m still on a 12,000 ORAC Unit intake so nothing has changed except the protandim supplements…it appears I’m experiencing the same thing I am seeing/hearing from the others!!
  • you stille hold that opinion after the new studies ?How can you explain the fact that many universities fundind their own research ?Is dr Pearlmuter that endors protandim will risk his reputation if it is not the real deal
  • Protandim was up 10% yesterday on volume of 177,000.  Another step in the right direction.
  • (paraphrased) My friend’s lipid peroxidase levels rose; here’s his lab report to prove it.
  • proven by peer reviewed, published scientific research to reduce oxidative stress by an average of 40%, slowing down the cellular aging process to that of a 20 year-old!
  • I accept your views and beliefs for they are yours, and who am I to disagree?  I do have a couple points to voice which may offer some advice on confirming whether a product is legitimate or fake….I notice that you mentioned because something is not FDA approved that it must therefore be quackery.  Again, this is your belief, so ok…. Herbs have been used in medicines around the world, successfully, and for thousands of years…prior to Western medicine.  The FDA and many doctors here in the ‘West’ are unsure of these remedies and this causes fear.  Ego, a human trait, can also get in the way.  It’s just our nature.” (this was from someone who has yet to try the product but plans to do so soon)
  • that’s the problem with modern medicine.  they are challenged by something, so incredibly, that they would rather eliminate it than find perhaps a new direction for health and medicine.   Ego?  Fear?
  • btw, you know an underlying problem in medicine today?  the hippocratic oath.   “First, do no harm.”    The reason this needs to be improved is because that oath has the words:  ‘no’ and ‘harm’ in it.   Modern psychology today will confirm that our brains really only focus on the key words, rather than a ‘no’ or ‘dont’ that precedes a statement.
  • Harriet, have you ever challenged any modern medicine, Lipitor as an example? Or any so called modern medicine?
  • I am not against allopathic medicine, however, I feel that our bodies work better with organic natural medicine.
  •  while I share some of your concerns, I feel that the house is burning and something must be done for our poorly aging population.
  • Just wanted to make you aware that Protandim received its 4th patent.”Compositions for alleviating inflammation and oxidative stress in a mammal
  • I have tons of them [clinical studies] , I have MD ‘s by the tons getting involved . I have clients getting of MEDs , cholesterol , Bp’s. Insulin cut in half , sleep apnea gone, chronic fatigue gone. Should I listen to results and MD’s and Using Godly wisdom or your bashing and other people see a nutritionist’s opinion as important. Thanks any way ms. Hall”
  • “It more than establish’s things when people’s lives have been changed. I didn’t see your name on the winners of the Elliot Cresant award hince , Joe McCord . Last time I checked all my clients were humans . All of them have been on for 4 months or more so there is no placebo affect. Oh and I trust the holy spirit more than all the above things. Thanks
  •  I have read some of your older write-ups about Protandim… it seems many are dated 2005.  Surely by now you have changed your mind about Protandim. The proof it works is now everywhere. I have seen many benefits myself and my wife has finally got her sugar levels under control by doing nothing other than take Protandim.  I do not sell this nor own stock in the company but I try to get as many people on this as I can… because it works. Are you on board or are you still against Protandim?

One Skeptical Message

I did get one message (only one) that was skeptical about Protandim. It pointed out further problems with the research:

Both Protandim and Mona Vie site numerous peer reviewed, published studies that support their claims. Upon basic investigation you will see that all the peer review studies are lead by the same shareholder / researcher (One for Mona Vie and One for Protandim). Shouldn’t this obvious conflict be a red flag for the peers that are reviewing? In addition for Protandim products most of the papers were published in one journal of which that lead researcher is also an editor. The only other journal they were published in is Plos One which appears to be an open access online journal with a very high publish rate per submission (I read 98%).

A message to Protandim supporters

I am not “against” Protandim. I would be very pleased if it turns out to improve people’s health. I await clinical research with great interest. I would not take it myself or recommend it at this time because I have seen too many initially promising treatments turn out not to work or even to cause harm.  I understand why some people are enthusiastic about Protandim and want to take it now rather than wait for better evidence, and I have no objection to their taking it. I am not “quackbusting;” I am only asking for the same kind of evidence that the scientific community requires before it accepts any new treatment. Please try to understand what I mean by clinical studies with meaningful outcomes and contact me again when such studies are available… and not before.



Posted by Harriet Hall

Harriet Hall, MD also known as The SkepDoc, is a retired family physician who writes about pseudoscience and questionable medical practices. She received her BA and MD from the University of Washington, did her internship in the Air Force (the second female ever to do so),  and was the first female graduate of the Air Force family practice residency at Eglin Air Force Base. During a long career as an Air Force physician, she held various positions from flight surgeon to DBMS (Director of Base Medical Services) and did everything from delivering babies to taking the controls of a B-52. She retired with the rank of Colonel.  In 2008 she published her memoirs, Women Aren't Supposed to Fly.