Why Do Scientists Disdain Supplements?

Posted on November 16, 2013 by Scott Jackisch

I’ve been taking supplements for a long time now. Gretchen, my partner of many years, gave me a niacin flush back when we were in our 20s. I can’t say that I recommend it. Imagine taking enough niacin to turn bright red all over and feel as though your entire body was being pricked by needles for a couple of hours. Also, I just learned that the fact that I flushed at all is evidence that I probably wasn’t schizophrenic in the first place, which may come as a surprise to my friends from that time. I was even fed Flintstone’s chewable vitamins as a child, so I feel as though I grew up in a culture of supplementation. Why do I take them? To be healthier? More productive? To live longer? Take your pick.

So when I read Fantastic Voyage by Ray Kurzweil, it was right up my alley. I happily went out and bought the top twenty supplements that Ray & Terry were suggesting right away. My friend John warned me about this. He had initially tried the same strategy, but stopped in favor of eating whole foods. We haven’t learned enough about biology yet to know what will be effective, he said. But John had the discipline to sit and eat an entire tub of organic lettuce while chatting at my Futurist Meetup, and I doubted that I had his same level of resolve. So I reduced my confidence in supplements, but I figured they might help offset my shoddy diet.

As the years go by, more and more studies about supplements have shown a lack of efficacy or even detrimental effects. Of course I was quick to defend my beliefs and look for flaws in the studies, blissfully ignoring my own confirmation bias. Sure, the science is flawed in some cases. Maybe big pharma actually works to game the results since naturally occurring substances that can’t be patented could pose competition to its products if proven effective. But as irrational as I may be in defense of my pet concepts, my confidence in supplements erodes further and further over time.

But as irrational as I may be in defense of my pet concepts, my confidence in supplements erodes further and further over time.

In this Bay Area futurist scene, it isn’t hard to find plenty of folks looking for hacks to optimize their personal performance. Rationalists seem particularly fond of nootropics, etc. So my faith in supplements was bolstered somewhat by various things I learned. I might say, oh sure, maybe even mixed tocopherol vitamin E isn’t very effective, but surely this acetyl-glutathione will do the trick. You just need to find the right pill to pop.

As I got involved in Quantified Self, where everyone does self experimentation, I realized how utterly foolish I was being by not monitoring my biomarkers more frequently. Ray Kurzweil might choke down 200 pills a day, but he’s constantly getting blood work done and poring over the results. So my approach of performing a single liver test once a year wasn’t looking too responsible, especially when other QS’ers were monitoring their blood sugar in real time for kicks.

I also had jarring experiences trying to talk about supplementation with actual scientists. Several smart biologists mocked my supplement regimen. Recently, I was at a party and asked Joe Betts-LaCroix and some other science people if anyone followed the paleo diet or did supplements, and I was a bit surprised to find general disdain. Should we return to a paleo era life expectancy? Perhaps we should forego vaccines and sanitation as well? Joe referred me to his brief blog post on this topic, the gist of which being that although there are billions of people with a broad range of diets, no one population is extraordinarily long lived. Thus, we can assume that diet doesn’t contribute much to longevity.

Although there are billions of people with a broad range of diets, no one population is extraordinarily long lived. Thus, we can assume that diet doesn’t contribute much to longevity.

Now some might argue that this speaks to longevity, but not to performance. Maybe it can be shown that diet and supplements can improve performance. At one time I would have been more open to that idea, but I am starting to grow skeptical. Joe’s point is that folks should stop wasting large amounts of effort for small or nonexistent personal gains and should focus instead on the basic research needed to unlock the deep complexity in the foundations of our biology. Of course, not all of us are cut out to do that research.

Dan Millman actually touched on this point at Ted X Berkeley this year. Millman ponders the question of whether it is better to focus energy on improving the world or on improving ourselves. He concluded that self improvement gives us the leverage to change the world more effectively. I am no great fan of Millman’s productized philosophy. He’s like some of these other “gurus” who package up ideas as products and sell them in a way that seems as though they have never heard punk rock or read post-modernism. But I think I can agree with that point – self improvement lends leverage to our endeavors. The question then becomes a cost/benefit analysis. At what point does self improvement offer diminishing returns?

Joe is an interesting person to listen to in this regard. No one can accuse him of not working on himself. He was a big QS’er from the beginning and did calorie restriction for years. He does HIIT, and he even broke out and tried living a 28 hour day. He has also been working fervently to improve the world for years, from his work at the ill fated Halcyon Molecular to his current Health Extension Salon project to combat aging. Yet, here he is admonishing folks to stop piddling around with diet and supplements and get to work on the real problems of this world.

Then there is this other fellow I happen to know named Walter Funk. A friend shared an article about a TA-65 alternative supplement that can supposedly increase your telomeres and roll back aging. This seemed at first to be utter quackery, yet there in the references, low and behold, was a paper by the venerable Dr. Walter Funk. So I said, Walter, tell me, what is this nonsense? He said that the basis of TA-65 is astragalus and that it modestly but reproducibly increases telomerase activity (i.e. protects telemeres which keep your DNA from unraveling, sort of like the plastic on the tips of shoelaces). He pointed out that astragalus is just an herb and regulation of herbs is becoming lax, but that other organic compounds that are purported to increase telomere activity would require clinical trials for FDA approval.

Then I found this article which seemed to suggest that telomerase might contribute to the immortality of tumor cells. But Dr. Funk assured me that reasonable animal data suggested that telomerase might actually prevent cancer. The telomerase activation associated with tumors occurred at a later stage after a bunch of other damage had occurred. So I said, well, that sounds OK then. Do you take TA-65, Walter? But I got a sardonic reply about him relying on good women and the kindness of strangers. He also offered to forward me a summary of all the NIH supplement studies that showed no benefit or some detriment.

Furthermore, when Cynthia Kenyon spoke at the Health Extension Salon in July 2013, she mentioned a study which showed that antioxidants prevent the increase of insulin sensitivity following physical exercise. In other words, exercise causes stress which normally triggers your body to repair the damage, however, antioxidants seem to prevent your body from recognizing the damage that has occurred. So antioxidants fix some of the damage, but prevent your body from providing a more robust response. This goes hand in hand with recent research, which calls into question the long held belief that aging is caused by oxidative stress (or free radical damage). There’s something else going on here.

Recent research calls into question the long held belief that aging is caused by oxidative stress (or free radical damage).

Part of me wonders if there is something in the personalities of scientists that makes them disdain diet and supplementation. Gretchen suggested that they may all be absent minded professors forgetting that their brains are attached to bodies that need nutrients. The performance hackers seem like a more charismatic and risk tolerant crowd, almost thrill seeking, though I must say they seem to have fewer papers to their credit. At the end of the day, I suspect that scientists disdain diets and supplements because they hold assertions of efficacy to higher standards than many of us do. I strongly suggest that my fellow supplementers listen more closely to what the science is trying to tell us. I will attempt to do the same, although it sure isn’t easy to give up your imagined silver bullet.

Additional references:
Walter sent me these additional references for those of you who are still clinging to your vitamin bottles. (I probably need to read these myself in order to let go.)

Here’s the big flop of one of the most touted supplements, omega-3 for heart disease has absolutely no effect on normal individuals.
http://www.medpagetoday.com/Cardiology/Prevention/38969

No one, especially males, should take vitamin E (tocopherol).
http://www.cancer.gov/newscenter/newsfromnci/2011/SELECTupdateJAMAOct2011

Antioxidants have been shown to not help with cancer.
http://www.cancer.gov/cancertopics/factsheet/prevention/antioxidants

An attack on the low carb crowd from a microbiome investigator.
http://humanfoodproject.com/sorry-low-carbers-your-microbiome-is-just-not-that-into-you

Health Extension Salon #14: Greg Fahy Regrew His Thymus

Posted on November 12, 2013 by Scott Jackisch

Greg Fahy and Joe Betts-LaCroix at Health Extension Salon #14. Photo courtesy of Traci Parker.

Health Extension Salon yet again lit up my life with wonderment at Hacker Dojo in Mountain View. As usual, there was a great crowd of lively and brilliant attendees. I got to chat with some old acquaintances and some new folks as well. I met techno optimist Kevin Russell, whose website Serious Wonder is worth consideration. Being the hip traveller that he is, he just got back from the Singularity University’s FutureMed conference down in San Diego. He promised that he would be writing it up soon. When pressed for a highlight, he mentioned something about laser surgery at the nucleus level, which sounds fascinating. So I will be looking forward to his write-up. He also pointed out that Craig Ventner has a new book on synthetic life called Life at the Speed of Light. Russell mentioned the CRISPR technique that allows for precise gene editing, which is back in the news these days. George Church was excited about CRISPR back in January at Foresight this year. So it looks like CRISPR may not be another one of these flash in the pan science blurbs that go nowhere. Let’s keep an eye on it.

Health Extension Salon founder Joe Betts-Lacroix always gives an introductory talk during which he highlights the goal of the Health Extension Salon, “to accelerate efforts toward therapies to prevent age-related diseases.” He makes a strong case that aging research needs more funding given the huge cost of age-related diseases. Joe mentioned a recent geroscience summit at the NIH to further this cause. The NIH is a vast source of research funding, but aging research only represents a tiny fraction of that pie. This summit gave the geroscience community within the NIH a chance to share some of their findings with their peers at the NIH who work in other fields. The goal was to raise interest and possibly funding for basic research into the biology of aging.

Joe also mentioned Google’s new health extension company, Calico, headed by Art Levinson of Genentech and Apple. I guess Joe was impressed when he saw Levinson at this aging research conference scribbling madly away, taking notes. Not many CEO’s do this sort of thing, so it may bode well for Calico. I had previously heard that Levinson has a vast network of connections, and now it seems that he is immersing himself in the field to learn what directions to explore firsthand. Very promising indeed.

The next Health Extension Salon will be a fundraiser held at Mithril Capital. Check healthextension.co for details. Mithril is Thiel’s vehicle for investing in middle range companies that fall between the initial startup phase and the pre-IPO. Nonetheless, it wouldn’t be a bad idea for bright young founders in need of funding to show up and rub elbows with the well heeled hosts. Just saying.

Joe introduced Greg Fahy by playing a clip from a recent episode of Nova that features Fahy’s work in the cryopreservation of organs. Apparently Fahy was able to find an antifreeze (M22) that is nontoxic to mammals and allowed him to freeze and rethaw a functional rabbit kidney. This research could lead to organ banks in which human organs could be safely stored long-term. It seems that Alcor switched to M22 in 2005 for freezing heads, but I am not sure if they still use it. But that was just a glimpse into the polymathic Fahy’s varied work.

When Fahy took the mic, he outlined the goal of his new company, Intervene Immune, to combat immunosenescence (the crapping out of your immune system over time) by rejuvenating the thymus. The thymus is this organ behind your breastbone that is sort of a university for white blood cells. Apparently it degrades severely as you age until it basically dries up by the time you are 65. (Am I the only one who didn’t even know this about the thymus?) The immune system incompetence that results from the aged thymus shriveling up results in a lot of flu deaths. Fahy said that some think this thymus degradation is an adaptive trait since the thymus must discard most of the T-cells it educates and thus is highly energy intensive. Though he seemed to agree with Cynthia Kenyon that aging may be a programmed process.

Fahy was inspired by the work of Dr. Laura Napolitano, who showed that human growth hormone could reverse this thymic involution (shrinking of thymus with age) in AIDS patients. Now given that AIDS kills T-cells, but a regenerated thymus makes more and better T-cells, that’s a really good thing. Go Dr. Napolitano, go! Though we westerners have pills to fight AIDS pretty effectively, it’s still a huge problem in the global south, and this thymus regeneration approach might be a better solution there.

So Fahy decided to regrow his own thymus using growth hormone and DHEA. Yep. He just performed an N=1 experiment by himself, on himself. It was very difficult and expensive though. First of all, HGH (human growth hormone) blocks insulin function. So that’s a problem. Fahy figured out that DHEA counteracts this effect. He speculated that the high HGH levels in young people didn’t impact their insulin function due to high levels of DHEA. DHEA has a plethora of other beneficial side effects, so that was a win win situation. Another problem is that HGH works by stimulating IGF-1, but IGF-1 can cause cancer at high levels. So the HGH dosage must be carefully controlled to keep IGF-1 levels in range. But he figured it all out and he estimates that he was able to basically roll back the clock 25 years in terms of this thymus function. He physically regrew the organ as evidenced by MRI scans. He also showed that his level of good “naive” T-cells increased. That’s a good thing. Look it up.

Now Fahy is a super scientist who vitrifies rabbit organs by day and unlocks thymic magic by night, so definitely don’t try this at home. Sign up for his human trial instead. Intervene Immune is kicking off a Thymus Regeneration, Immunorestoration, and Insulin Mitigation Trial (TRIIM). This study is for men only, between 50-65 years old, in good health, with low cancer risk, who have not used HGH before. Contact Fahy [at] interveneimmune.com for information on how to join. If I was a little bit older, I would definitely check it out. Fahy has worked out a very rigorous protocol in which he improves upon previous protocols by Napolitano, et al. He also looks amazingly good for his age, and I have to wonder if that thymus rejuvenation hasn’t helped preserve his appearance as well.

But as amazing and exciting as the real prospect of immunorestoration is, that’s not all Fahy has in store. Killer T-Cells attack invaders. The thymus trains these T-cells to differentiate between invaders and native tissues. In autoimmune disorders such as Type-1 diabetes, this process goes astray. I guess animal studies have succeeded in taking small sections of the affected tissue, putting them into the thymus, and retraining the T-cells not to attack that tissue. (Still looking for references.) Fahy said that the same thing has been done with organ transplants in animals. So you could transplant organs without needing to knockout the immune system. Just trick the thymus into treating the transplanted organ tissue as native. This is really mind-blowing stuff. Thymic magic.

I have to extend my thanks and admiration to Joe and the Health Extension Salon team for putting on yet another inspiring and mind-expanding event. It’s really exciting to see the amazing talent being applied to these tough problems of aging. Even my persistent pessimism is disarmed by the audacity and vision of people like Greg Fahy. Aging really is a problem that can be conquered. Human suffering can be vastly reduced. Get on board people! Let’s make it happen.

Health Extension Salon #13

Posted on October 26, 2013 by Scott Jackisch

The only events I can seem to attend these days are Health Extension Salons. But I also attended the 2013 Quantified Self Conference in San Francisco, so I was exposed to plenty of new ideas there as well, which I will be sharing soon. Health Extension Salon #13 was held at Runway SF, which is a cross between a co-working space and an incubator. At the beginning of the talks, the operations person from Runway said that their uniquely high percentage of shared public space supercharged the startups based there as the teams intermingled and ideas were cross-pollinated. Apparently they have have a good number of successful exits, which for an incubator must mean getting funding or something. It’s an amazing space, but they are still pretty stealthy. They don’t even have a website that I could locate.

For those who don’t know:

The Health Extension community is committed to collaborative action to extend healthy and happy human life spans to 123 years and beyond. Our members are scientists, entrepreneurs, and social influencers dedicated to fixing the degenerative cellular processes that cause deadly human diseases.

Health Extension was founded and is executively directed by scientist/entrepreneur Joe Betts-LaCroix. Joe gave his standard presentation pointing out how absurdly underfunded aging related research is. Basic research into the biochemical processes behind aging represent a tiny fraction of healthcare spending, while aging related diseases account for the vast majority of healthcare costs. So obviously there is a disconnect somewhere.

The field of aging research it clearly underfunded, so Google’s new Calico project seems very encouraging. Aubrey De Grey is certainly in favor of it. Google clearly has cash to throw at the problem, but some folks question whether they can find the right talent. However, accomplished biotech scientists have assured me that Calico’s CEO Arthur Levinson has an extraordinary contact list and can get the talent he wants. So the hunt is on in earnest with the data wizards over at Google on the case.

Joe highlighted some very interesting findings by researchers at the University of Pittsburgh School of Medicine. They looked at lymph nodes and reconsidered why cancers often begin their deadly migration of metastasis there. Lymph nodes provide direct access to nutrients, growth factors, and signaling proteins that aid in cell recruitment. Then they turned this idea on its head and asked – “Hey, why don’t we see if we can grow little mini-organs there in the lymph nodes?” And so they did. They injected mouse lymph nodes with liver cells, and the little masses of liver cells that grew in the lymph nodes were functional enough to save the mouse from liver failure. Then they performed the same trick with thymus cells and pancreatic cells. So yeah, that sort of blew my mind.

When you stop to think about it, you can imagine ways to make all organs fault tolerant by overloading lymph nodes with little micro-organs distributed throughout the body. This almost reminds me of highly-available computer clusters. Of course, evolution probably arrived at a centralized liver for a reason. It may be that a single large mass of liver tissue can more quickly transfer bigger doses of important factors like glycogen to other vital organs. Messing with any complex system like this will surely lead to a bunch of broken functions. But if I were faced with the choice of that or liver failure, I might take the chance. There aren’t enough donor livers to go around.

Next, Joe went on to relate that HE’s Aging Variant Database Project was rejected by the Nucleic Acid Research journal. Apparently an editor fell victim to the halo effect bias. They decided that the database must be tainted because it was hosted on a site that also hosted links to life extension topics and the mere mention of life extension is disreputable. This database is a meta-analysis of existing studies meant to identify genetic variants related to aging. This certainly isn’t quackery or pseudo-science and most of the reviewers realized that. But Nucleic Acid Research is a prestigious journal. And prestige is something that must be jealously guarded. So the Health Extension researchers will be submitting the Aging Variant Database to another journal, possibly the modern, open-source PLOS One.

One thing I like about Health Extension is all the interesting people you can meet during the social periods. I bumped into biotech entrepreneur and fellow Oaklander Ryan Bethencourt, who co-founded Sudo Room, Counter Culture Labs, and BerkeleyBiolabs. He told me a bit about this “hackubator” Berkley Biolabs is setting up, which is biotech space for scientists with promising ideas to work out proofs of concept. I guess there is this new crowdfunding site, Wefunder.com, that will be involved somehow. He then introduced me to Andre Watson, who won my admiration first by having seen every Star Trek episode, and secondly by telling me a bit about his work on nanotechnology for genome editing. At Foresight this year, I had heard George Church mention the CRISPR gene editing technique that is a biomimicry of a bacterial proto-immune system. So accurate human gene editing therapies might be coming down the pipe at some point.

As much I do love Star Trek (Picard not Kirk), I have this dark side that is contrary to the Gene Roddenberry optimism of Star Trek. I am picturing governments editing the genes of their citizenry to make them more pliable. Imagine the marketing potential there! I asked Andre if he thought gene editing would be used for good or evil, and he sensibly replied “both.” Which is, of course, the fate of all technology. But a world where genes can be altered at will or against your will is very strange to imagine. Will genetic traits be taken up and discarded like fashion statements? Will we accidentally break all manner of delicately balanced genetic network interactions and wreak untold havoc? It’s hard to say.

I then went on to talk to another scientist that I admire, JR, to hear what he was up to. I had been wondering why SENS didn’t seem to be pursuing a strategy to activate protective pathways that prevent aging, similar to what Cynthia Kenyon found in her long-lived nematode mutants. JR pointed out that since calorie restriction doesn’t even seem to increase longevity in mice, let alone primates, it would be difficult to exploit those pathways that Kenyon discovered. He framed the question thus: would it be easier to tweak metabolism to prevent damage or to repair damage once it occurred? He considered the latter to be simpler. And this seems consistent with the SENS approach. Repair damage as it occurs. And that is perfectly reasonable, but I find myself a bit disappointed. Kenyon seemed to point toward hidden capabilities just waiting to be unlocked. Like a biological equivalent of the software Easter egg. But practical people are pointing to something more like automobile maintenance. Not that I would turn down longevity via that method. I just want to believe I can fly.

Err, yeah. So then JR clued me into the immense potential of bone marrow transplants. These have been found to “cure” AIDS. It’s not clear how this applies to his own work, but he does like to work with blood because it’s easier to manipulate than organs or solid tissues. See, this is why I like JR so much. His approach appeals to my pragmatic side. I look forward to seeing what practical human rejuvenation techniques he will develop.

Again, this is why I love Health Extension Salons. I have already been inundated with exciting ideas and the main speaker hasn’t even presented yet. The main speaker was Sean Mooney, Director of Bioinformatics at the Buck Institute for Research on Aging. He started out by encouraging biotech startups to consider government SBIR and STTR grants to access non-dilutive capital. He, like many academics, sits on various “study sections” that review these grants and said that he often doesn’t see enough projects worth funding. I had never heard of these study sections, but I guess the recent government shutdown really threw a wrench into the works and some think that this threatens the US position as the worldwide leader in scientific research. Of course my libertarian friends would have something to say in rebuttal, I’m sure.

Mooney then asked the room how many people had their entire genome sequenced. I initially raised my hand, foolishly thinking that my paltry 23andMe SNPs qualified. But Mooney repeated the phrase “entire genome.” And only one person raised their hand. Apparently they had participated in a study through Personalis. Mooney was impressed and said that he had asked that question at many conferences but rarely had anyone raise their hand. He predicted that the entire genome sequencing would become very common as soon as the price plummets. And the price is plummeting exponentially in a way that would warm Ray Kurtzweil’s heart.

Mooney talked a bit about his work in translational research, which aims to bridge the gap between basic and applied research to move findings from research labs into medical clinics and move empirical data from the clinics back into the research labs. This is a fascinating topic that certainly warrants further examination, but then Mooney went on to an even more interesting topic. He brought up the CAGI challenge, which invited researchers to predict clinical medical outcomes based on genomic data using George Church’s Personal Genomes Project. Currently, 23andMe gives you some estimates of that sort of thing for many diseases, but apparently their stuff doesn’t cut the mustard in the clinical world. So this was a pretty tough challenge and actually none of the teams were able to accurately match more than a small minority of the genomes to medical outcomes. I found this surprising. I would have expected better results. It’s not clear if this poor showing was the result of insufficient data, or if nurture really does trump nature in medical outcomes. I understand that throwing methylation information into the mix would help improve the predictive power. One biologist I related these finding to quipped that he wasn’t surprised by the results since DNA can’t tell you whether a person is alive or dead.

So what does this mean? It seems to mean that scientists don’t yet have good models to predict what the real effect of genes are on phenotypes. Yeah, so what good is this genetic data then? Best take those 23andMe predictions with a grain of salt. Mooney was quick to point out that he obviously wasn’t bearish on genomics being a bioinformatics person. While genetic data might not be ready for clinical prime time, he had little doubt that doctors will be using genetic data in the near future.

One challenge to reaching this goal is that gene expression differs from tissue to tissue. It was speculated during discussion after the talk that these differences in gene expression could pose unforeseen risks to Induced Pluripotent Stem Cell treatments. Consider a cheek cell which expressed a mutation that increased the chance of liver disease. This would be harmless since the cheek cell isn’t in the liver, but if that cell were scraped and converted into a stem cell to regrow liver tissue… well, that would be a problem. At first, I naively thought that IPS stem cells would be better for medicine since the immune system wouldn’t need to be suppressed to avoid rejection. But several scientists I spoke with pointed out that the complexity of modifying IPS posed more risks than naturally pluripotent embryonic stem cells, though having your own cord blood would be optimal. Anyone have parents forward thinking enough to bank that stuff? No? Too bad.

Health Extension continues to provide an amazing forum to learn about real science from serious scientists who are pushing the field of aging research forward. The more I learn about this stuff, the more daunting the problems seem sometimes. But there are other ideas that seem so much closer to implementation, such as Justin Rebo’s blood scrubber, or even the idea of blood infusions from young to old to provide regeneration. Health Extension is a real thing that can happen if the right resources are focused upon it, and that’s an exciting future to consider.