The last year left enormous personal progress.  It’s been a difficult year in terms of time, but scientifically rewarding. There are many reasons people launch blogs. Some need attention. Others need authority. Then there are others that are bored.  Probably the most common are those that just want to make a contribution in an area that find passionate.  Health, fitness, and cooking are among the top blogs and there are many, often conflicting, opinions on the subject.  While people might “agree to disagree,” there are many opinions that are just wrong.

This blog really started, because Tim Ferriss insisted I put “something” up before our 4 Hour Body Nightline segment aired in late 2010.  I had no idea what direction my research would take at that point and certainly no idea how this blog would unfold. But make no mistake, I’ve had wrong ideas about the world

I’ve unintentionally held these wrong ideas throughout my science career.  Sometime it’s due to lack of data, the inability to see the picture clearly, which causes one to make a (wrong) educated best-guess.  Many times it’s simply a key element of information that is missing or present that skews opinion one side or the other of “correct.” More often than I care to admit, it’s because I blindly accepted something I read (ironically, just like you and this blog) and either didn’t care to verify what was said or I simply didn’t have the requisite background to see through the “trickery.”  Sometimes we are fooled, not merely by another author’s ignorance, but intentionally.

That’s not the spirit of science. The goal is to learn and of course we only learn when we are wrong about an idea. Simply repeating what we know isn’t learning – our view about the world must change to learn and hence those that haven’t given this any careful consideration might say, “these scientists, they are always conflicting, this week one thing, next week something else.”

Exactly. That is THE point. When our ideas conflict with what is observed in the universe, it’s not the universe that needs to be fixed.

The Emotion of Science

Recently a major milestone occurred with the collection of evidence that supports cosmic inflation theory.  A moment that’s repeated throughout time – a scientist’s ideas verified – was captured in this incredible video as Assistant Professor Chao-Lin Kuo surprises Dr. Linde at his home:

Did you get that?

“I always live with this feeling, what if I’m tricked? What if I believe into this just because it is beautiful…”

If you aren’t in science, this video portrays an emotion you might not be aware exists. Not to imply scientists are objective robots or blind to emotional trickery, but that what must be overcome is the human urge to find that beauty or pattern.  Before we push send, publish, or make the call, all good scientists have that queasy feeling and few put it into such eloquent and simple words as Dr Linde has here. That’s a different kind of beauty and it happened quite automatically in this extemporaneous interview.

Trying to chip away and find a nugget a truth in a noisy world is what drives many and while information is more plentiful than ever, blogs have unintentionally added  even more noise and created extra layers of difficulty. Who do we believe?

What if I’m Tricked

Two weeks ago one of several journal articles I’ve been working on was accepted. It’s finished peer review and I will update when it it publishes. Later in this blog you can help by donating to the Open Access Fee for the journal.   When I began my journey 5 years ago, I wasn’t doing a science project or an N = 1 trial. The goal wasn’t why I lose weight it was to simply lose it.  Soon thereafter, I was confronted with health issues that didn’t go away with the weight loss as surmised and that started me on yet another, parallel journey.

When Tim Ferriss asked if he could tell my story, I consented having no idea the magnitude of that agreement.  I had data only because that’s what I do by habit, not because I was trying to “prove” something.  As soon as one makes a claim that is unconventional, the “truth” police come out and one finds their ideas attacked. Much of it was nonsense that didn’t really deserve the rebuttal, but there was some honest criticism that was certainly welcome.

It necessitated digging in even further to demonstrate an idea I thought to be a simplistic and self-evident truth. Is it “out there” to suggest that it take more energy to maintain constant body temperature in a cooler environment?  I think most people reacted to this innate phobia of cold and it didn’t help that some wanted to summarize it as the “ice cube diet.” Either way, I needed good data – what if I’m tricked? In looking at the overall thermodynamics, mild cold stress was certainly important, but the thermodynamics of food was absolutely key.

There are a lot of smart people being “tricked.”  Thermodynamics is relatively sound and accountable – if one establishes the boundary conditions. My confidence was not born out of hubris, but because I had some of the greatest minds on my team. Richard Feynman said it best,

“There is a fact, or if you wish, a law, governing natural phenomena that are known to date. There is no known exception to this law; it is exact, so far we know The law is called conservation of energy; it states that there is a certain quantity, which we call energy, that does not change in manifold changes which nature undergoes. That is a most abstract idea, because it is a mathematical principle; it says that there is a numerical quantity, which does not change when something happens. It is not a description of a mechanism, or anything concrete; it is just a strange fact that we can calculate some number, and when we finish watching nature go through her tricks and calculate the number again, it is the same.”

Our problem is understanding “nature and her tricks.” When our ideas don’t conform to the universe, it’s our ideas that need reformed. Some might make the absurd claim that obesity is proof that the conservation of energy is wrong. I’m betting the error happens when we “calculate some number.”

Fast forward to the review article that is about to publish. In it, we make an argument for a metabolic winter hypothesis. My collaborators are two esteemed researchers.  I am not saying this for an empty “appeal to authority argument” (attack logic flaws when one doesn’t have their own data is the vogue approach taken on many blogs these days), but out of genuine respect for both of them.

Dr. Andrew Bremer was at Vanderbilt Children’s Hospital serving as a pediatric endocrinologist and professor of medicine at Vanderbilt Medical School when we met.  Last November, he was tapped by the National Institutes of Health to become the Director for Type 2 Diabetes Prevention and Treatment Research and Digestive and Kidney Diseases Medical Officer.  Many of you know his work already if not by name, as he’s a co-author and first author on many of the fructose/endocrinology  articles by Robert Lustig.  He’s a PhD/MD and his publication record is phenomenal.

When I began describing some alternate explanations for the etiology of metabolic syndrome and obesity, he listened and ultimately it changed his perspective. He too, is not beyond being “tricked.”  He’s also an incredible mentor and researcher and I’ve learned so much from him in the process.  He was able to put aside things he was taught in medical and graduate school to explore new ideas. We now have a lifetime of future work to do after securing funding. When we originally met during one of my children’s office visits, I had no idea who he was and he asked me if I’d mind reading a paper he’d recently published.  Later that evening I was shocked to read it and a week later got the nerve to ask him about potential collaboration on my project.

My second co-author, Dr. David Sinclair, is at Department of Genetics Harvard Medical School and Department of Pharmacology School of Medical Sciences, The University of New South Wales, Australia.  He’s one of the world authorities on longevity, in fact voted Time Magazine’s Top 100 Most Influential People a few weeks ago.  He’s probably one of the people most responsible for the last few years of my exhaustive research. He is also an incredibly well-published author and most recently his paper in Dec 2013 Cell on NAD/HIF-1α has taken another critical step towards untangling the web of aging.

Like Andrew Bremer, I had no idea who David Sinclair was when standing in line the first day of TEDMED 2009.  He overheard me talking to another person in line and joined in the conversation.  He was very certain that mild cold stress had more application than just weight loss and really encouraged me to think very differently about the problem. Later, when he got up on the TEDMED stage  for his talk, I was shocked by just how much of an authority on the subject he was.  The entire TEDMED experience granted me the opportunity to brainstorm with top scientists – people I certainly would have never had access to without this event.

We continued our conversations and even picked them up the years following and he kept encouraging me to push.  There was, and still is, so much I don’t know about longevity, but he’s on top of it and it is a huge advantage to have someone like this on a collaborative team.

Together, we were able to create a fantastic multi-disciplinary team to tackle this first review and others are in preparation. Unfortunately I was drinking from a firehose and it took many hours to digest the several thousand papers, couple hundred textbooks, and do my own self experiments in the lab. These guys are way ahead of me and still are on so many facets of our research.   The blog wasn’t the top priority. I apologize for the absence, but it’s important to have an influence on the other publication machine that pushes all ideas forward as well.

Confidence in Nonsense

So this brings up the question we need to all ask ourselves about the things we repeat every day.

How do I know?

I ask myself this question all the time. Who did it come from and how do they know? Science investigation and curiosity has permeated my entire adult life and I think that begins with the natural curiosity of all children. I guess I just didn’t grow up. I’ve had the privilege to work with some of the most innovative, bright minds in the world. It’s help me to develop an arsenal of tools and disruptively innovate in many different industries. Attending various scientific gatherings allows me to work with others that disrupt and that moves everything forward. It also keeps me honest, people are quick to point out when I’m being tricked.

One of my mentors in creativity, Aerospace Maverick Burt Rutan, says, “you have to have confidence in nonsense If you want to innovate.” Rutan is arguably one of the most innovative aeronautical engineers of the past 50 years. Rutan adds, “an innovation is by definition something that half of the people think is impossible, and half say, well, maybe it can be done.”

Rutan knows innovation—he was the first to fly around the world nonstop without refueling. He was first to launch a privately funded spaceship, winning the $10 million Ansari X Prize. He joined forces with billionaire entrepreneur Richard Branson to build the first private suborbital spaceship for Virgin Galactic’s launch into space tourism. His very success in all these projects was a result of breaking all the rules and letting his goals define his approach. How else does one come up with an airplane design as unconventional as the Boomerang.

Aviation has certainly advanced over the years. Let’s focus our attention on the year 1894. Two significant, separate innovative events occurred – 120 years ago.  Karl Benz introduced the Velo, becoming the first production automobile and that very same year Wilbur Olin Atwater published the USDA’s first Bulletin on the Nutritive Value of Food.

What has happened in the intervening Century in Food Science versus Transportation? On the transpiration front we blew past trains, automobiles, airplanes, sound barrier and spaceships! Space is on the verge of privatization – companies I co-founded in the 90s have flow over 10,000 people in weightlessness (gozerog.com) and 7 people to Space Station (Space Adventures); one flew twice! Humankind has walked on the moon and sent probes to other planets and even out of our solar system! We’ve made huge progress on the shoulders of visionary, disruptive innovators. Today, the entire U.S. access to space rests on the work of PayPal founder, Elon Musk, and his company Space-X.

Now consider how much progress have we made in nutritional health as it relates to food science since the 1894 with introduction first USDA nutritional guidelines? Not very much. Our nutritionally driven chronic diseases have become MUCH worse.  Having now researched metabolism and nutrition reaching all the way back to Hippocrates (460-377 BC), I can certainly say that any one of the 19th century great nutrition researchers, Atwater, Rubner, von Voit, etc… would readily recognize and not be too terribly surprised by a modern day diet book. We are still obsessed with juggling mythical ratio of “proteins, carbohydrates, and fats” something I would argue is a somewhat irrelevant and certainly a dated way to look at food. We simply heap lots of multi-syllable organic chemistry, endocrinology, and molecular biology words onto these antiquated and overly simplistic organization of foods. It’s like strapping explosives onto a Velo with the idea that will take us to Mars.

What do you think Mr. Benz reaction would be sitting in a Mercedes SLS AMG GT as compared to a Benz Velo?  I’m certain that Lavoisier would be impressed with the simplicity of running a calorimetry experiment in my lab – vous appuyez sur le bouton?  Mais, c’est incroyable! But the data we collected would not differ significantly from what he knew to be true as I describe in Muscling Your Metabolism (part 1). How do I know? because I repeated it and generated numbers that were very close.

I am not suggesting we’ve made no progress in molecular biology, genetics, or physiology, but our ability to treat chronic disease through nutrition or public information about food is an utter failure.  The average walking around advice for diet and exercise is broken and most diet books are written by people that couldn’t possibly have measured many metabolisms.   Most importantly our relationship with food is broken. Nutritionism is broken.  Worse yet are the industry authorities and blogs that repeat unsubstantiated “facts” over and over again – insanity through inundation. I was guilty of the same thing not too long ago, but for the last 4 years, I haven’t taken anything at face value.

A Good Skeptic

In areas of food and metabolism we are inundated by an inordinate amount of untested hypotheses and anecdotal evidence. To be sure, the diet and fitness industry is loaded with R&D (rip off and duplicate), but where are the people with what Rutan calls “confidence in nonsense?” Does anyone else notice the sheer-volume of myths and urban legend that permeate every level of our daily discussion of food and nutrition?

I am not alone in this opinion.

In the January 31, 2013 issue of The New England Journal of Medicine article, Myths, Presumptions, and Facts about Obesity, the authors had this to say:

“Why do we think or claim we know things that we actually do not know? Numerous cognitive biases lead to an unintentional retention of erroneous beliefs. When media coverage about obesity is extensive, many people appear to believe some myths (e.g., rapid weight loss facilitates weight regain) simply because of repeated exposure to the claims.

Cognitive dissonance may prevent us from abandoning ideas that are important to us, despite contradictory evidence (e.g., the idea that breast-feeding prevents obesity in children). Similarly, confirmation bias may prevent us from seeking data that might refute propositions we have already intuitively accepted as true because they seem obvious (e.g., the value of realistic weight loss goals). Moreover, we may be swayed by persuasive yet fallacious arguments (Whately provides a classic catalogue) unless we are prepared to identify them as spurious.”

This pretty much sums up my existence and excitement over the last 5 years. It is amazing to be able to walk out of my kitchen and into a lab to test dogma, spend days reading historic old textbooks, and visit locations where past and present ideas about our bodies and nutrition were born.

I decided not to take anyone’s opinion for granted and invested in my own laboratory. I have what you might call a scientist’s mid life crisis indirect calorimeter instead of a sports car. It’s allowed me to carryout experiments in an attempt to separate fact from fiction. We all need to be a little more skeptical, but at the end of the day the truth is in what is demonstrable and repeatable.

Much like the words protein, carbohydrate and fat, metabolism is another word that’s bandied around and in some sense has become meaningless. Do we all have slow metabolism? Does muscle burn more than fat and by how much? What happens to our metabolism if we skip meals? I have tried to answer some of these questions in previous posts and more informations is coming.  It’s my hope to help people see through the inundated insanity.

An Incredible Opportunity

I think many people overlook one of the best points in The 4 Hour Body. You can dismiss the individual ideas, or even dismiss the author, but there is one part about the book that rarely get’s highlighted and can’t be dismissed, the Appendix. So many love to read “freeze your ass off” sensationalism into the chapter on my work or imagine themselves as the modern day version of Woody Allen’s Ograsmatron, but I say dig in on pages 484-510 if you want to see what motivates me on a daily basis. That is the meat  of the book (cruciferous vegetables didn’t have the same ring) and that is why I agreed to allow my work to be featured. Tim does understand the world of self-experimentation.

It doesn’t matter if he is right or wrong about any of the chapters as long as he’s pushing the envelope, measuring, and aggregating data. I think his “confidence in nonsense” is a good contrast to a century of metabolic stagnation. If you want to see a glimpse at just how powerful this idea self experimentation can be, watch this TEDMED presentation by Jamie Heywood:

We are sitting on an unprecedented opportunity – the aggregation of N of 1 data that eclipses the expensive and slow clinical trials that now dominate science. These are necessary and will still go on, but I can’t imagine there’s much “confidence in nonsense” taking place in most funded proposals today. Conservative claims and reach has become the mainstay of academia.  Science isn’t halted and we still have plenty of risk takers, but the preponderance of funding is placed on incremental progress.  You have the opportunity to collect data – technology has never been more accessible. We have the opportunity to ferret out what’s right and wrong, and avoid focus on who.

Let’s all be more skeptical and open minded. They aren’t mutually exclusive efforts.

Copies of  Our Paper

One final request.  The open access fee for the journal, allowing anyone to download it without charge, is $3200.  I know many of you contribute monthly to the blog and I very much appreciate it. I am asking that you make a one time donation to help me defer that cost of 0pen access publication. Most don’t donate, so this is one of those few times I’ll ask you to think bigger.

If the fancy button doesn’t work, try this old-fashion hyperlink.

I will make sure to update everyone when it is available for download and if I can raise the Open Access fees, everyone will be able to access it.  This is just the foundation and I have conducted a lot of experiments in my lab that aren’t directly publishable, but give us a good idea of what to look at in future clinical trials and proposals.

After this series of review articles has made it through the peer review process, I’ll likely publish the book I’ve been researching for a couple of years. The notes and references are all in place as is the table of context and many chapters.   In the summer I will be announcing a crowd-sourced fund for another set of self-experiments I intend to do in late August and will need to raise money to cover the extensive cost of lab work and extended travel time  in the NYC/Boston area near my science collaborators.  This is all directly related to surprising things I learned last summer in my own lab.  I’m sorry again about the delay in sharing results, but so many things get duplicated (unattributed) these days that I really need to get the publications in first and that process is unfortunately slow.

I hope everyone understands.

I have the outline for another summary blog that goes over the many related publications that have come out in the last couple of months that support The Metabolic Winter Hypothesis and will put it up when the paper is released.

As always, thanks for your support, ideas, questions and participation.

Ray