So, what if the solution came along?

Posted on August 1, 2011. Filed under: medical ethics, Medical marketing, Protandim, Self-deception |

Nothing here since January, 2009! Why? I’m reminded of the parents who had a child who never spoke. They took him to pediatricians, speech therapists, witch doctors: everyone they thought could help. Not a syllable came forth. They accepted that he was mute, and got on with it. One day at breakfast, when the child was six years old, he said, “This toast is burnt.” The parents almost collapsed, and with tears in her eyes, the mom said, “Johnny, you can talk!” The child responded, “Of course I can talk; I’m six years old.” Bewildered, his mom asked, “So, why haven’t you ever said anything before?” Without hesitation, the boy replied, “Up ’til now, everything’s been OK.”

So, here’s the deal. I wrote a number of posts in 2008 and 2009 about the medical profession and medical marketing.The blog generated about 10,000 hits, but not much discussion. At the time, I didn’t have anything else to say that I felt was important or revelatory. Now I do. If you have ever read my posts, you know that I am searching, and that I am a student of bias. I rejoice in learning how things work: not how they seem to work, nor how we would like for them to work, nor what the majority thinks about how things work, but how the evidence describes how things work.

Enter Nrf2. Nrf2 is an abbreviation for Nuclear factor (erythroid-derived 2)-like 2, also known as NFE2L2. Your doctor knows this, right? Wrong! When we matriculate into medical school, our teachers typically are not medical doctors, but PhD’s, who have extensive, up-to-the-minute knowledge of their niche. Among the first things they teach us are these two:

  • a vocabulary that is the equivalent of a foreign language, and like any foreign language, it is mastered when the words themselves cause concepts to appear in the brain without translation.
  • basic medical sciences.

Your doctor (and I) have mastered the vocablulary.We can read the peer-reviewed articles, and we have at least the potential to understand what they say. But the basic sciences? There are few practicing physicians who could pass a current freshman medical school test on any of the basic sciences, and the  information is changing at an almost exponential rate. Nrf2 is one of those things that basic scientists, in this case, biochemists, know about that your doctor does not.

Here’s the story. Did you know that oxygen is the source of our ultimate demise? We have to have it to survive, and to create the energy we use daily. But, in producing that energy, one of the products is a nefarious substance called “reactive oxygen species” (ROS). ROS will kill any oxygen-dependent organism. So, it is not surprising that all aerobes have evolved a method for dealing with these destructive ROS “free radicals”. The 25,000 or so genes in the human genome include 4-6 thousand genes that have evolved specifically to deal with ROS. That’s about a quarter of all the instructions that make us who and what we are. How do they do this? By up-regulation of protective enzymes that neutralize ROS, and by down-regulation of associated inflammatory and fibrotic processes stimulated by ROS. This is important. For me, it is revelatory. For your doctor? Maybe not so much.

It was a biochemist who first discovered the protective enzyme, SOD (superoxide dismutase). His name is Joe McCord. Your doctor has his own Wikipedia page, right? As Dr. McCord puts it, the discovery of SOD was the beginning of the solution, but no one knew the problem it solved. And what is the problem? Aging and degeneration itself! What is aging? Surprisingly, to a biochemist/medical school professor like Joe McCord, aging is defined as a ratio. The numerator is the level of protective antioxidant enzymes one’s genes produce, and the denominator is the amount of oxygen one consumes. Up until about the age of 18 -20 years, that ratio in genetically “normal” folks is such that very little degeneration occurs. You’ll starve if you are a doctor specializing in teen-age heart attacks, strokes, hypertension, osteoarthritis, type 2 diabetes, Alzheimer’s, Parkinson’s Disease, coronary bypasses and stents (continue the list to include almost everything non-infectious that eventually gets us), but you’ll be overworked with the same disorders if your field is geriatrics. Why? The ratio of protective enzymes to destructive ROS declines as we age, and oxygen gradually destroys us all.

What if we could stimulate our genes to rev up the protective enzyme levels to what they were when we were young? It would make front-page headlines! Fox News and PBS would find common ground featuring it! Your doctor would be calling YOU to make sure you were aware of this wellness breakthrough! NOT!!

Nrf2 was described and isolated in 1994. It’s role as the key activator for all the “survival genes” has been known to biochemists for over 10 years. There are 2088 peer-reviewed articles about it (as of today) listed on the National Institutes of Health website, pubmed.gov. Researchers in both independent university roles and as employees of pharmaceutical companies have been frantically searching for methods to activate Nrf2 safely, both to prevent and to treat the ravages of human physical degeneration. It could play a major role in reducing our runaway healthcare costs. EVERYONE’S TALKING ABOUT IT.

Well, maybe not. In fact, among all my physician friends to whom I have mentioned Nrf2, only one has ever heard of it. Furthermore, that one physician is the only one of my doctor friends who seems remotely interested in the concept. What’s going on here?! Artificial-intelligence researcher Eliezer Yudkowsky has observed: You know better than to think that a random doctor will have extraordinary clarity of mind and the power to find truth within confusion. Our medical education system stops teaching science and the scientific method after the early years of medical school; from then on, we learn and memorize prescribed solutions for various problematic scenarios.The system eschews independent thought and investigation. In fact, we are held legally liable for employing methods that deviate from the accepted norms. Those norms come down to practicing physicians through established channels, as I’ve previously mentioned here, herehere, and here. Currently, none of the established channels involves Nrf2 nor its activation, and few doctors make the effort to search for the truth within the confusion.

Enter what I will call a form of “intellectual attribution bias”. According to Michael Shermer in his book, Why People Believe Weird Things, because of this cognitive bias, smart people are about nine times more likely to attribute their own position on a given subject to rational reasons than they are other people’s position, which they will attribute to emotional reasons. Although major pharmaceutical companies are trying to develop synthetic Nrf2 activators as prescription drugs, the only currently available clinically effective Nrf2 activator is a compound of natural phytonutrients called Protandim. It is classified by the FDA not as a drug, but as a dietary supplement, and it is available not by prescription or in pharmacies, but only through network marketing.

In spite of peer-reviewed studies listed on pubmed.gov documenting the compound’s ability to raise Nrf2 activation to unprecedented levels, and subsequently lower oxidative stress to unprecedented levels, practicing physicians are not likely to give it any credence because it doesn’t fit in the mold of their established channels of information. Their position seems to be: “I am an expert, and I haven’t heard of Nrf2 activation. Now you’re telling me that a network marketed supplement could be the most important advancement yet in my own specialty, and I don’t know about it? It’s bulls**t.”

UPDATE: Biogen’s synthetic Nrf2-activator drug Tecfidera was approved in the Spring of 2013 for the treatment of Multiple Sclerosis. Available by prescription only at a cost of about $50,000 annually. Biogen’s research shows that Tecfidera has about 50% of the Nrf2 activation of the natural-ingredient compound, Protandim, which costs $40/month, without Tecfidera’s side-effects.

Here’s an exercise your doctor hasn’t done: go to pubmed.gov, and in the search box enter “Nrf2” followed by the name of any disorder that interests you, e.g., “Nrf2 diabetes”. As one enters disorder after disorder, and sees the scientifically documented correlation with levels of Nrf2 activity, one comes to realize that we have evolved to deal with oxygen consumption in a healthy way until we reach the years of reproduction, and then our Nrf2 activity drops off and we begin to die. We can begin to control that now by controlling Nrf2 activation. Doctors treat symptoms and the results of disease. Nrf2 activation removes the cause. The solution, or the beginning of it, has come along: Nrf2 activation. Your doctor doesn’t know about it. Tell him/her. He’ll tell you it’s bulls**t.

If you want to know more, click on “contact retired urologist” at the top of the page and send me a message. Or educate yourself at ABCliveit.

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18 Responses to “So, what if the solution came along?”

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Bullshit indeed. I guess one method of avoiding bullshit is to put the cart before the ox, which seems to be what you are doing by promoting Protandim. I’m not a doctor, nor even a retired doctor, but I am nerdy enough to get the gist and value of a scientific paper, and I can see those relating to Protandim are far cry from “documenting the compound’s amazing effectiveness”.

What have I missed? Based on those studies, what are your rational (as apposed to emotional or financial) reasons for having such high hopes for Protandim? Please point out the most salient evidence and I’ll try to keep an open mind. So far you seem to have ridden that ox cart down the “correlation = causation” road, then took a sharp turn down a blind alley called Protandim.

Hi Craig. I’m guessing that you have not read the nine peer-reviewed studies on Protandim.The most recent (here’s a link to the abstract) shows that Protandim is the most potent clinical Nrf2 activator known. Abbott and Biogen have collectively spent over a billion dollars developing and trying to get FDA approval for their synthetic Nrf2 activators, bardoxolone and BG-12, respectively; it’s a big deal. The former has half the Nrf2 activation of Protandim, and the latter has one-third. If you were to look into it seriously, and if you’re the open-minded nerd you claim, I think you’ll see that Nrf2 activation is certainly a candidate for being one of the most important medical advances of our time (I happen to think THE most).

That same most recent publication also shows that in degenerative disorders in which gene dysregulation has been identified as a correlative factor, Protandim (and Nrf2 activation) “tunes” each of the associated gene groups back to its benign level of activity. The three disorders studied are atherosclerosis, Alzheimer’s, and colon carcinoma. This is, indeed, “documentation of the compound’s amazing effectiveness”. Studies on 200 more gene-regulated disorders are in process.

Since the abstract does not give all the information I have discussed, and since the full article is available only for purchase, please notify me if you would like to have the full version, and I will email it to you.

Laughable. Just because Joe McCord and his flunkies say that Protandim is the most potent activator of Nrf2, does not make it so. Nor is there any therapy approved for medical use based on Nrf2 activation as a mechanism of action. You also made the the mistake of throwing in the word “clinical” when referring to the effects of Protandim on Nrf-2. “Clinical” means tested in humans. So far only one clinical study has been conducted on Protandim. It was a very poor, biased and flawed study in a small cohort of healthy people, and it did not report anything at all about Nrf2. In other words, there is no clinical data regarding the effect of Protandim on Nrf2.

As for your statement “Nrf2 activation is certainly a candidate for being one of the most important medical advances of our time (I happen to think THE most)” — putting it nicely, that’s onerous hyperbole.

The same applies to your other statement: “disorders studied are atherosclerosis, Alzheimer’s, and colon carcinoma. This is, indeed, ‘documentation of the compound’s amazing effectiveness’.” They didn’t study any diseases at all in the article to which you are referring. They did a simple gene chip study and then made claims (which they didn’t back up with citations) that those genes have been implicated in certain diseases. That’s a far cry from the way you tried to spin it. It’s certainly not documentation of “amazing effectiveness”.

Lastly, you claimed that “studies on 200 more gene-regulated disorders are in process”, but you didn’t provide any evidence at all to back it up. Where is the evidence that such studies a study is taking place, and even if it is, so what? A planned study is not evidence of effectiveness; it is at best just a fishing expedition, and one that is at least as likely to show negative results as positive results (or at least it would be if it were a fair and impartial trial).

My suggestion to EB142: don’t take Protandim. Wait for whatever evidence it is that you require before you accept anything about Nrf2 activation. We should all use due diligence.

Thanks for the offer, please do send the report.

The closing sentence of the abstract states: “Pathway analysis of results shows significant modulation by Protandim of pathways involving not only antioxidant enzymes, but of those related to colon cancer, cardiovascular disease, and Alzheimer disease.”

Again, I have no medical training, but my interpretation is that this in no way means that Protandim can be considered either as a cure for or preventative of colon cancer, cardiovascular disease, and Alzheimer disease. Am I right?

Why would big pharma have such a hard time isolating what Protandim gets from a mix if rather common food ingredients? And why can’t Protandim’s makers get some meaningful human studies done? Sorry for so many questions, but your strong advocacy seems to warrant more than the current evidence shows. Seems more like a case of, interesting prospects, let’s see what comes out of it.

@ Craig: I sent the full publication via email. Protandim cannot be considered a cure, treatment, or prevention of anything until human studies are published by independent researchers and published in peer-reviewed journals. The company itself is forbidden by the FDA from making any such claims because the FDA has classified Protandim as a “dietary supplement”. Consequently, the maker (LifeVantage, publicly traded LFVN) has chosen to await the publication of studies not funded by the company. You can see the results so far by searching “Protandim” on pubmed.gov. At this point, it is a “connect the dots” issue. Protandim has been shown to be a potent Nrf2 activator, and Nrf2 activation has been shown to have profound effects on degenerative disorders. Protandim has been shown to reduce the markers of oxidative stress by more than anything else known, and oxidative stress has been shown to be associated with almost every degenerative disorder. As to the paucity of human studies on Protandim itself, they are underway, but publicly traded companies cannot discuss those preliminary findings until they are published, as regulated by the SEC.

Big pharma has no trouble isolating Protandim’s ingredients, but the specific combinations are patented (4 patents). In addition,big pharma is not interested in phytonutrient products because of poor patentability and the fact that they are never classified as drugs, consequently no claims can be made.

I agree with your assessment: I am an early adopter when it comes to Nrf2 activation. The 2000+ publications on pubmed.gov, plus the 90,000+ publications on oxidative stress won me over. Unlike drugs, the fact that there is no downside to taking Protandim makes the decision an easy one for me.

I tend to lean to the view expressed in this article:

http://www.skeptic.com/eskeptic/11-10-26/#feature

I am dubious about claims for a magic bullet, especially when the sales precede the science. And I’m more dubious about the concept expressed in your statement, “there is no downside to taking Protandim “. So it may alter your body enough to “stimulate our genes to rev up the protective enzyme levels to what they were when we were young?”, yet have no possible counter-reaction? And I just saw a video in which Kirby Zenger said that Protandim works against cancer and many other diseases — yet all without side effects? How would you know how much to take, the optimal balance to achieve? Even too much of certain nutrients, like vitamin A, can be detrimental to one’s health, so can you confidently say what you did about no downside? Again, the evidence isn’t there yet, one way or the other.

All in all, it just sounds too good to be true. I’ll sit it out until there is much more meaningful research done. And I’m sure that the company making Protandim is not in a hurry to get real clinical trials because they already have a product on the market and “the possibility of” and “it’s just around the corner” seems to be working for them.

Please comment on Harriet Hall’s article, because I suspect she’s not an expert on the topic.

1. I am a dues-paying member of the Skeptic Society. Harriett Hall is no longer effective as a medical spokesman for the group. She pontificates, rather than researches, not just on this topic, but generally. Quite typical of medical doctors, actually, IMO. She gives no evidence of her understanding of the Nrf2 pathway, nor of the difference between the effects of exogenous antioxidant substances such as fruits and vegetables, and those substances that activate the Nrf2 transcription protein to induce endogenous antioxidant enzymes. Perhaps you and Dr. Hall fall into the same category, since there are 1124 peer-reviewed (not blogger reviewed) publications on Nrf2 activation listed on pubmed.gov, the NIH site. Abbott and Biogen, and others in the early stages, are betting not with their mouths, but with their dollars, on the efficacy of Nrf2 activation. And they have published human trials. Nrf2 is not a figment of some blogger’s imagination.

It’s not my purpose to convince you, not to answer your objections to my opinions. If you need guidance to peer-reviewed sources of information, that’s another matter. I would never accept your opinion, nor Harriett Hall’s, nor “EB142″‘s on any of this, just as you should not accept mine. If I have stimulated your curiosity, do your homework among the scientific literature, not among the blogs and YouTube and commercial sites, as I have for the past 8 months. Find out who Joe McCord, PhD, is and what his biochemistry colleagues worldwide think of his integrity and expertise. Then get back to me.

BTW, please send me a link showing Kirby Zenger saying that Protandim works against cancer. That’s reportable to the FDA as a violation.

http://lvasap.com/lifevantage-inside-story/

I appreciate your take on this and I’ll take your advice on who to trust. I’ll be on vacation for 5 weeks, when I get back I’ll look at the article you sent and will try to get back to you.

Thanks.

Hi Craig,
I looked at the YouTube you linked regarding LifeVantage CFO Kirby Zenger saying “Protandim works against cancer and many other diseases”. What he said was that the peer-reviewed published studies from LSU and other centers said that. Big difference. No manufacturer of a dietary supplement can make claims regarding the diagnosis, treatment, prevention or cure of any disease. However, the FDA fully allows the reference to peer-reviewed studies and their published findings. That’s the main reason the news about Protandim is so slow getting out. It requires waiting for independent researchers to make the findings and publish the story.

“The most beautiful thing you guys have right here is LSU confirmed EVERYTHING. And it confirmed that Protandim works against the what? [someone says, ‘cancer’]. The BIG C! Who gets that anywhere in the world, including Pharma companies?”

So it’s a game of semantics and intentions? As a typical listener, I’d say his meaning is “Protandim works against cancer and many other diseases. And better than anything pharma is offering.” Though if I think about it, I have to ask, “confirmed what?” Someone’s prior claim? Who made the claim and what was it?

He is playing somewhat safe, like a savvy politician making promises that he can later talk himself out of. His first implication — “independent studies”. Second implication — “works” against cancer; i.e., prevents and/or cures. Third implication — “in humans”. Think about it, he’s in a position of authority and he’s telling distributors “Protandim works against the big C!”

So, as an example: http://www.plosone.org/article/info:doi/10.1371/journal.pone.0005284

It’s not independent (McCord is heavily involved in the company and the study), it’s a small lab experiment and it’s on mice. Why the massively overblown rhetoric? Again, it’s because they’re doing this backward – product first, proof second. If this was a cross country trip, we’re still in the driveway, packing the car, and we’re not sure there’s actually any gas in the tank.

Yes, it’s a word game. When you can make no claims, and the findings are in medical science journals, and only a tiny fraction of the population reads those journals, it’s difficult to get the message out.

It’s not independent (McCord is heavily involved in the company and the study), it’s a small lab experiment and it’s on mice. Why the massively overblown rhetoric?

The Nrf2 system is present not only in all mammals, but in all aerobes. Anti-neoplastic activity in mice is very significant, and the basis for current human studies in progress.

As to McCord’s role in all the studies, I asked him the same question.Here is the reply he sent to me:

Why is Dr. McCord’s name on all of the studies?

LifeVantage funded the first two studies on Protandim, although the
studies were performed in an academic institution, the University
of Colorado, by academic investigators. The next five studies
have all been performed by various academic institutions, and all
FUNDED INDEPENDENTLY by the American Heart Association, the
National Institutes of Health, etc. For the last decade or so, academic
institutions have had strict committee oversight to guarantee
appropriate authorship. You cannot add someone’s name if they
made no contribution to the work, nor can you omit a person’s name
if they contributed significantly to the idea or the execution of the
project. I am the expert on Protandim, and have advised every
project so far with regard to dosing, experimental design, and have
assisted in writing the manuscripts. That’s why my name is on
the papers. I have been the principal investigator on only the first
publication.
I picked a statin drug at random, atorvastatin, developed by Parke-
Davis Pharmaceuticals. I looked at the first 20 research papers
published on the drug. Eighteen of the twenty were authored solely
by Parke-Davis employees, funded solely by Parke-Davis, and
performed at Parke-Davis facilities, not at academic institutions by
independently funded academic investigators.
Joe M. McCord,
Ph.D.
Professor of Medicine
Division of Pulmonary Sciences
and Critical Care Medicine

What a fantastic article! Thank you for explaining it eloquently. I’ve spent the past several hours searching pubmed and found it very interesting indeed. I think you’re right in calling a connect the dots process. It will be interesting to keep watch on the future research. I read an article in last April’s Vanity Fair magazine regarding the process for approving prescription drugs, yet people seem to have no problem popping a pill if it is recommended by a doctor. I think we should be very afraid of this practice, and I am excited to see a supplement like Protandim come along which could change everything in how we view “health care”.

Personally, I haven’t seen any reason to NOT take the supplement. Thanks for sharing.

Hi,

I’m back from vacation and finally read the article, “Oxidative stress in health and disease: The therapeutic potential of Nrf2 activation”. It was boring 🙂

There are lots of “mays”, “mights”, and “coulds” in the conclusion. It seems to be more of the same — very preliminary research using cells in petri dishes. I know these humble beginnings are necessary, but it’s such a far cry from the claims made by Kirby Zenger and the sales force he’s unleashed.

Are you still enthused, or have you tempered your outlook?

And Donny Osmond with Dr. Dan Royal?

I’m not trying to convince anyone of anything. I’m just informing. Get in touch with me in 2 years.

Sir, you might want to check out page 13 I believe of the patent, dated July 10, 2007, the paragraph starts, The composistions of the present invention are useful to prevent or treat the following disorders and diseases, the list is long starting with memory loss, Parkinsons, HIV, AIDS, the list goes on and on. They do make the claim.

The patent # is 7,241, 461

Thanks for your comment. I’m a doctor, not a patent lawyer, but I’ve inquired about these claims with patent attorneys. I have been informed that patent applications, and approvals, are permitted to contain all sorts of claims that have not yet been proven, but which fall within the reasonable scope of the product. Apparently the laws for patents are completely separate and different from the laws governing marketing of nutritional supplements. Consequently, no claims regarding the diagnosis, treatment, prevention, or cure of any DISEASE is allowed in the MARKETING of nutritional supplements. However, claims in the patents (which in Protandim’s case involve 5 USA and 2 overseas) may include anything that is reasonably concluded from the preliminary evidence. These issues infrequently occur with most nutritional supplements, which have no patents, nor any basis for such.


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    The director of the Sexual Medicine Center leaves penile implants behind, and launches a quest for knowledge about Artificial Intelligence, extended life, and the issues inside the health-care industry.

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