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Caloric restriction: here are the results of future studies

Caloric Restriction (CR) is all the rage these days; even the National Institutes of Health has a study on whether drastically reducing caloric intake will make humans live longer.  Supporters of the premise of CR cite multiple animal studies (rodents, of course; fish; dogs; and primates) which in each case the CR subgroup of animals either actually lived longer or showed markers (e.g., blood pressure, serum lipids, lower body temperature, etc.) that predicted they would live longer.  Wow, with all those different animal species living longer, isn’t it a given that humans would benefit similarly to CR?  Well, no.  Let me tell you why I’m not only convinced that CR will not show an actual increased lifespan in humans, but why CR will probably turn out to be injurious. Update, March 2016-it is injurious: https://www.sciencedaily.com/releases/2016/03/160314101759.htm

 

In the pharmaceutical industry, new drug discovery candidates are screened through a host of animals before they are put into humans, under the “better to kill a goldfish than a person” philosophy.  If the candidate drug behaves itself in various animal models, it gets to be in a “first in man” study.  These Phase I studies are again to check the safety of the drug, not to determine its efficacy-although efficacy results are certainly noted.  What is often not appreciated is how unique  a candidate drug is: hundreds of thousands, if not millions of compounds were screened and our Drug of Interest was the winner.  Pharmaceutical companies screen tens of thousands of compounds daily to find viable drug candidates.  What does the drug screening process have to do with CR?-it shows how unlikely a given approach to solving a human condition with a drug really is.  Let’s think of CR as one of the millions of approaches to increasing human lifespan in a parallel manner that drug  candidates are screened for much the same end result, that is, better health or longer life.  So of all the interventions we could imagine-and there would be millions of them, what are the chances that CR is the Fountain of Youth?  Hey, but wait-don’t forget those studies where rats lived oodles longer when they starved the little rascals, doesn’t that count for something?-aren’t we all just one Big Animal Family and run biochemically pretty much the same?  No.

For every drug that makes it into man, there are a huge number of drugs that are safe in animals and even show efficacy-sometimes amazing efficacy, but these same drugs don’t work at all in humans.  Having seen this phenomenon on so many times, I once asked a pharmacologist why the Exciting Drug of the Month had just gone bust in humans after having really exciting results in several other animal species.  During the study we were discussing, a  drug was posed to be an anti-cancer drug and it had remarkable credentials.  Human cancer tumors were grown in a number of rats and then the drug was dosed to the rats.  The standard of a really good response is if the human tumor, residing in a rat, shrunk in size.  With this particular drug, something amazing happened: the human tumors didn’t just shrink, they disappeared: the rats were cancer-free:  unheard of results.  A cure for cancerous tumors, here we come.  Sorry.  The drug was introduced into patients with cancer and it did nothing but attempt to destroy their stomach lining sans anti-cancer effect.  So back to my friend the pharmacologist for an answer as to why the drug had worked so marvelously in several animal models but not only didn’t work in humans, but did significant harm.  The pharmacologist said (and you might want to write this down, it’s biochemically sophisticated), “rabbits aren’t people”.

Even when drugs show efficacy, they very often show toxicity as well, much to the disgruntlement of the company’s CEO and shareholders.  Probably last month the CEO told the stockholders the now-defunct drug was going to gross several billion a year when it hit the market.  That happens all the time, too; CEO’s don’t like to say, “we have an empty pipeline (industry-speak for how many promising drugs are on their way to market)”.  As an aside to my current aside, you might be entertained by watching for when a pharmaceutical executive uses a new term for a familiar concept and see how all the other pharmaceutical company executives will start parroting it almost immediately.  But I digress.

In summary, the vast majority of drugs never get to be in a Phase I (human) study to see if they are at least not-too-toxic.  The vast majority of drugs that make it past Phase I eventually show some toxicity that precludes them from being a product.  Even those drugs that make it to market only exhibit 50% of their side effects after seven years of thousands of people using them.  Some drugs are taken off the market or given the dreaded “black box” warning by the FDA which means, “take this drug if you want, but some Really Bad Things might happen”.

An important, but ignored aspect of CR is that to some degree, the results are already in-studies which correlate BMI with lifetime predominately show a "U-shaped curve"- individuals who  have a very high or a very low BMI (as CR individuals will have) have shorter lifetimes.  The explanation  to this observation has been  that the very low BMI individuals may have low BMI's precisely because they are chronically ill and would therefore be expected to have shorter lifetimes.  This objection must include with it  a postulation of an absolute scientific ignorance on the part of the researchers involved: certainly if low BMI, in the absence of disease, extended life, there would be a subset within the low BMI population that would have clearly longer lifespans-an exciting result that no competent researcher could ignore.

I think parallel reasoning of drug development and  studies on CR is very sound.  Like 99.99+% of drug candidates, we’ll probably find out CR doesn’t work-and worse, my guess is we’ll find out some things about nutrition and biochemistry that we didn’t know before, but we will know-and the result will be that overall, CR is not only not beneficial, it’s harmful. 

The results of the NIH study will be interesting, but they will no doubt draw conclusions from “markers” of good health  (insulin resistance, blood pressure, serum lipids, which may well be much better in the CR group)-but no one knows if  those results truly  translate into a longer life, nor will that be known until all of the study participants go to Their Reward.  My guess is that long before then, the problems associated with CR will be common knowledge.

As a passing philosophic aside, we humans have a great deal of trouble letting go of beliefs that we really want to believe and that make some common sense. Example: we like to believe that when faced with a serious health condition, optimistic patients fare better-unfortunately, that isn't true, despite its emotional and common sense appeal. CR fits both acceptance criteria: we want to believe there is a way that we have control over how long we live, and from a common sense point of view, if obese individuals get sick more often, and on the average, die sooner (which they do), then maybe the old phrase "you can never be too rich or too thin" is valid.

Note: after I wrote this article, I found really  interesting Web site on caloric restriction that presents an extensive list of articles (as opposed to my purely experience-based predictions)-it can be found at http://qualitycounts.com/fpcalorie.html . I suggest the interested reader check the site out-it contains dozens of references with summary sentences for each.  See also http://www.sciencedaily.com/releases/2009/01/090123101224.htm.

 

 

 

 

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