SUPPLEMENT FINAL

I have written critiques of several dietary supplements sold through multilevel marketing (MLM) schemes, and they keep coming back to haunt me. I get testimonials from users who believe they have been cured of every ailment under the sun; and every time another study is done, I get e-mails from distributors who apparently think the new “evidence” will change my mind. Recently I received three more emails about ASEA, one about Protandim, and three about dōTERRA essential oils, asking me to reconsider. I thought this would be a good opportunity to explain why I have not changed my mind and to explain once again what constitutes evidence in science-based medicine.

ASEA

Recently an email from “The ASEA Team” asked us to delete the article I wrote about ASEA in 2012, based on their opinion that it “was not constructive” and “was not based on decent and verifiable facts.” They did not mention two other followup articles I wrote here and here. And they did not directly try to refute most of the points I made in my critique; I think they failed to understand what I was saying. They provided six attachments with studies they said were “made to prove the effectiveness of ASEA” but those studies didn’t prove any such thing.

Last week Steven Novella answered them very effectively, calling ASEA snake oil and pointing out the deceptive marketing practices of the company, the pseudoscientific nature of their claims, and the worthlessness of the studies they cite.

The claims

The ASEA website currently makes these claims:

As we age, and as stress and environmental toxins inundate our lives and weaken our defenses, normal cellular function declines, and with it, the body’s ability to produce and maintain a proper balance of redox signaling molecules. ASEA has developed the only technology that can create and stabilize active redox signaling molecules in a consumable form. No matter what your health concern may be, ASEA Redox Supplement can bring your cellular communication to optimal levels, improving the health of every system of your body.

Questions

This brings up several questions:

  • How exactly does normal cellular function decline? How would improved cellular communication reverse the decline?
  • What is a proper balance of redox signaling molecules? How do they know? How is it measured?
  • What active redox molecules are in the product? (They won’t tell us. The label just lists salt and water. In my opinion, if there are redox molecules in ASEA, listing only salt and water constitutes false labeling.)
  • What evidence do they have that the product improves health?

What redox molecules?

All they have is a statement from a lab, BioAgilytix, that indirectly measures “biomarkers” of redox levels in ASEA using a fluorescent indicator as a probe for unspecified highly reactive oxygen species. I don’t know what that means. There is no direct evidence that redox molecules are present. No other lab has analyzed the product.

Safety

Their claim that the product is safe is based on a brief description of two unpublished studies. In the first study, 106 overweight women took ASEA or placebo for 12 weeks; they reported no adverse effects, (None?! In most studies, even the placebo group typically reports some symptoms.) and there were no changes in liver or kidney function tests or complete blood counts. In the second study, an in vitro study of cultured eukaryotic cells, the cells “did not register a significant toxic response as measured by a visual assessment of green dye that indicated “nuclear translocation.” Based only on this flimsy subjective and in vitro evidence, they claimed “ASEA Redox Supplement, orally administered, does not manifest a toxic response or inflammation to exposed tissue.” Such thin gruel does not constitute convincing evidence that the safety of the product has been established.

Studies

Before I accept that a treatment works, I want to see human studies published in peer reviewed journals. There are none on their website, but I was able to locate two articles in the FASEB Journal here and here.

It quickly became obvious why these are not featured on the company website: they are not full articles, but abstracts from a meeting that were published in a supplement to the journal. One is a human study, the other is in mice (the poor mice were gavaged with ASEA and then run to exhaustion). One of my correspondents claimed that these are peer-reviewed studies, but peer review is not possible when all that is available is an abstract.

As far as I could determine, there have been three studies in humans. One, a small study of 17 cyclists, has been deleted from the web. It was not placebo-controlled. There is an abstract of a similar study of 20 cyclists that did use a placebo control and was double-blinded. It was essentially negative: ASEA did not improve time trial performance. They found that it caused a significant shift (good or bad?) in 43 metabolites, but had no apparent influence on traditional biomarkers of inflammation, oxidative stress, or immunity.

The third, most recent human study is the one my true believer correspondents are currently crowing about. They refer to it as a “genetic” study. One of them snarkily commented “It’s called science, u should look into it sometime.” I did look into it, and I was not impressed. The title is “Initial Gene Study Showed ASEA REDOX Affected Important Signaling Pathway Genes.” The company paid Tauret Labs to do the study. It has not been published in a peer-reviewed journal. It was an 8-week double-blind randomized placebo controlled study with 60 participants that measured changes in expression of 5 genes and found statistically significant changes of 20-31% with ASEA. They claim that “These genes are key in the health of the individual and play a vital role in five human health areas and dozens of pathways.” Maybe, but they have not demonstrated that human health benefits in any way from these changes in gene expression. Their summary of results states “Effects are non-specific to race, sex or age, and were observed in all populations tested.” This conclusion is not supported by their data. The only population tested was 60 individuals, 41% male, 92% Caucasian, average age 35 with age distribution not reported.

Conclusion

The evidence for their claims is indirect and inadequate. Half of all research studies turn out to be wrong. Changes in blood tests might be spurious; they have not been independently replicated. Changes may be statistically significant but not clinically significant. If they want us to believe ASEA causes objective, meaningful improvements in human health, they’ll have to do better. They’ll have to test directly for meaningful clinical outcomes. And if they want us to believe ASEA contains all those redox signaling molecules, they’ll have to prove it with a direct analysis by an independent lab and name those molecules.

As Steven Novella put it,

Asea, however, is still a fantastical and unbelievable claim supported by nothing but hype, sales copy, and empty promises. It is salt water. The hand-waving nonsense about redox reactions is incoherent technobabble – the very essence of pseudoscience. What would be convincing is published, peer-reviewed, independent, rigorous scientific studies with clear results. These don’t exist. No amount of distraction will change that fact.

Protandim

I have written about Protandim four times, here, here, here, and here.

What is it?

It is a mixture of five dietary supplements (Milk thistle, Bacopa extract, Ashwagandha, green tea extract, and turmeric extract) that allegedly stimulates the body to produce its own antioxidants. They claim 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 [and they measured this how?].”

An email from a reader

You really need to up date your studies on this product! There are thousands of people with improved health because of PROTANDIM. For example, my son in law with high blood pressure was able to cut his BP medication in half after only two months on it and after three months, he is off meds completely with normal blood pressure; my daughter suffered for a year with a horrible rash under her arm that looked like tree bark. After several visits to her doctor where he prescribed cortisone and antibiotics nothing worked. She finally went to a dermatologist who was shocked to see that she had Granular Parakeratosis a rare skin disease. My daughters case was only the second time she has seen it, and at a follow up visit was told that there is no cure, only palliative care. Three days later the crud came off in her washcloth in the shower, and she had been on PROTANDIM for about two months. See photos. On the after picture you can see a round sore which is from the biopsy. In addition, my husband who has cOPD and had bypass surgery last year, and myself have great, new energy. In addition, my nerve damaged feet and numbness in my right foot have improved by at least 80 per cent after only 5 weeks! For the first time in 15 years or so, I can now feel my right big toe and it is no longer cold, like a piece of granite, and our bad backs have greatly improved. I could go on and on and I don’t need someone like you to tell me and thousands of others that it does not work! We are walking human studies for this amazing product! Check out the human studies for liver disease! I am proof it works so you should take another look: in fact go to You Tube PROTANDIM testimonials and see for yourself what this product does when it reduces oxidative stress!

My most recent article was in May 2017, and I’m not aware of any new studies requiring me to “update my studies” in the last six months. The evidence on the website is mainly about Nrf2 protein messengers in general, and studies of Protandim in cell culture (in vitro) and in mice. One 2006 human study found changes in lab tests such as TBARS but did not even attempt to look for any clinically meaningful improvement in health outcomes. A second human study in 2016 was negative: It concluded “Protandim® did not (1) alter 5-km running time, (2) lower TBARS at rest (3) raise antioxidant enzyme concentrations compared to placebo (with exception of SOD in those ≥ 35 years old) or, (4) affect quality of life compared to placebo.” And another study of patients with alcohol use disorders was also negative. Not only negative but laughable.

Conclusion

Increasing levels of antioxidants could be beneficial or harmful. The only way to know if Protandim improves human health is to do properly designed, placebo-controlled human studies looking for meaningful clinical outcomes.

dōTERRA essential oils

I have written about dōTERRA twice before: here and here.

An email asked me to “Check with Johns Hopkins and the research published about dōTERRA oils. Dr. Nicole Parrish claims that dōTERRA oils have killed three super bugs that synthetics cannot. It is published and the medical world is learning more about essential oils in September.” I asked her for links to that research; she never responded.

Another email chastised me for having a “complete scientific mindset.” (I thought that was a good thing!) She said, “It really is worth looking further into to help people stay healthy.” She provided all kinds of testimonials: her dentist and her real estate agent use it, her son and stepson carry the beadlets with them during allergy season, and when her husband got cancer, they used essential oils for diabetes, neuropathy, infections, and asthma. She also chastised me for not mentioning what the Bible says about oils and plants! She believes “science is here to prove God’s existence and the Bible can be used for medicinal research.” I didn’t try to answer her.

An in vitro study was done on dog kidney cells infected with influenza virus. Based on their results, they speculated that essential oils might be useful in treating humans with influenza (or might not). In my article critiquing that study, I provided some guidelines on how to read research studies that claim to support a product.

A third email said I needed to visit the website again and review the 17 studies published in peer-reviewed journals. I found an in vitro study of frankincense and an in vitro study of Deep Blue, a mixture of essential oils. There was also an extensive bibliography which included a lot of irrelevant articles along with in vitro and animal studies. There were a lot of scattershot preliminary studies on individual oils, but these were seldom if ever followed by replications or confirmations. My own PubMed search found a few studies supporting the use of an essential-oil-containing mouthrinse, reports of adverse effects of essential oils, some negative studies, and a couple of Cochrane reviews that pointed out the poor methodology of the few studies they found. A 2012 systematic review of aromatherapy concluded “the evidence is not sufficiently convincing that aromatherapy is an effective therapy for any condition.”

My correspondent said, “In my opinion, there are too many confirmed reports of improved health & well-being (when using essential oils) to chalk it all up to “hysteria” or “ignorance” or even chance.” Her opinion is misguided. The plural of anecdote is not data. Confirmed reports of improved health and well-being, no matter how numerous, are meaningless without a control group. Reports of failures are not systematically collected. Patients may improve for reasons other than the oils: suggestion, placebo effect, social factors, the natural course of the disease, regression to the mean, etc.

Essential oils can be very pleasant to use, and I have no problem with using them as “comfort” measures. And the company website is careful not to make any egregious disease-prevention or -treatment claims. But at their in-home presentations, the distributors feel free to claim that the oils can cure anything and everything, including cancer. These claims are not backed by any science but are illustrated by persuasive anecdotes, touching and heartwarming stories, testimonials from users that the attendees may know personally. Attendees are easily influenced to believe and to buy.

The published evidence for each of dōTERRA’s many products is sparse to nonexistent. There are clinical studies to support a few of the recommended uses, but they are generally poorly designed, uncontrolled, unreplicated, and unconvincing. Research is difficult, because patients can’t be blinded to the odors, and mental associations and relaxation could account for most of the observed effects. I remain skeptical of the claims for objective benefits in treating diseases.

Conclusion: No reason to change my mind

Testimonials are notoriously unreliable. These products are not supported by acceptable scientific evidence. I’m not saying they don’t work. No one knows whether they work or not, because they have not been properly tested. I am simply asking for a single standard of evidence, the kind of evidence required to achieve a scientific consensus that any treatment is effective and safe. If they want us to buy their products, they should test them against placebo controls in human studies looking for objective, meaningful improvements in health; and they should get those studies published in reputable peer reviewed journals. In the pharmaceutical industry, only a small percentage of promising candidates survive testing. Considering the huge number of dietary supplement products like these on the market, the chance that any one of them will prove to be truly effective is vanishingly small.

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.