My 12/15/12 column, “Calorie Restriction and Longevity” (#79 here), dealt with one aspect of the first part of a scientific paper, “The Neuroprotective Properties of Calorie Restriction, The Ketogenic Diet, and Ketone Bodies.” This NIH Public Access article published in 2008 is, frankly, very technical, so to make the subject a little more “accessible” (for us both), I also included in the column several Gary Taubes quotes from “Good Calories – Bad Calories.” Taubes is an award-winning science writer, but that book is also pretty dense. I call it a “tough slog”, but I underlined about one-third of the 560 page text. It’s a very compelling read, and I strongly recommend it to all open-minded and serious health readers.
In #79 I took the subject of Calorie Restriction only far enough to establish some of the health and longevity benefits. Unfortunately, they were limited to yeast, worms, fruit flies and mice. And I did not address the “potential pitfalls and health concerns” of calorie restriction in humans. Taubes, by the way, calls conventional calorie restricted diets in humans “semi-starvation” diets, because they are! But I am not advocating Calorie Restriction (CR) per se. That will be clear next week when I lay out what I think is perhaps a new dietary paradigm. But first, the pitfalls and concerns.
“CR has many consequences, the majority of which are unknown at this time,” wrote Barbara Hansen in The Journal of Nutrition. This now dated 2001 Introduction to “Calorie Restriction: Effects on Body Composition, Insulin Signaling and Aging,” can be seen here. The data she presents, from a 1995 paper by Bodkin, is also dated, but prescient: “Neither the mechanisms by which life extension takes place (in rodents) nor the mechanisms by which the complex features associated with insulin resistance and Metabolic Syndrome are prevented by CR, are understood. Clearly advancements in this area will lead to better understanding of this powerful nutritional tool.” Indeed, as we have seen, they did.
Quoting Hansen and Bodkin from 1993: “CR produces altered pathways of nutrient disposal, including reduced plasma glucose, insulin and leptin levels” (emphasis mine); and Hansen et.al. (1996): “CR carried out for 10 to 15 years in adult rhesus monkeys has been shown to result in sustained alteration in glycogen metabolism, despite apparent retention of normal insulin-stimulated glucose uptake, normal glucose tolerance and normal fasting glucose and insulin levels.”
Hansen cites another research paper (Ortmeyer, 2000) to demonstrate the effect of CR on insulin action by the “rate-limiting enzyme of glycogen storage, glycogen synthase.” Ortmeyer reported, “CR appeared to unveil a predisposition in approximately one half of the CR monkeys toward metabolic abnormalities in response to insulin” (again, my emphasis). Continuing, “Although glycogen content remained normal in all CR monkeys, we suspect that the induction of abnormal insulin action on glycogen synthase by long-term CR may represent a pointer toward the underlying defect that, under ad libitum conditions, would lead to obesity, insulin resistance, and eventually Type 2 diabetes in approximately one half of aging rhesus monkeys.” This is all very important, if, of course, it translates from non-human primates to humans.
A cautionary note, though: A 2006 ncbi.nih abstract in PubMed here, “Calorie Restriction in Humans: Potential Pitfalls and Health Concerns,” makes two very good points that illustrate the proper skepticism of the scientific mind. 1) “In humans, several studies investigating short-term calorie restriction or ‘weight-loss’ programs suggest beneficial outcomes on parameters of cardiovascular disease.” “However, few studies are currently investigating the quality of life and potential pitfalls of long-term calorie restriction in humans. It is likely that some of the physiological and psychological effects of calorie restriction that occur in animals may impact the human life very differently.” And 2) “For certain, calorie restriction has a plethora of health benefits in mammals, such as a reduction in age-related diseases such as cancer. However, despite the ‘magic’ of CR, this intervention in humans may present itself with a number of health concerns, which may not be applicable to or impact the life of experimental animals, but may do so in humans.” Now this may sound like the perfunctory disclaimer one sees in all ‘objective’ research papers, but it is worth keeping in mind.
The closing paragraph of Hansen’s piece above reveals what she regards as a “missed opportunity.” For me, it reveals the myopic vision of an out-of touch research biologist unable to see a clinical approach informed by nutrition: “The power of CR to mitigate, delay or prevent this clinical development of disease, despite the presence of underlying defects in insulin action, points to the critical need for effective CR mimetic approaches to slow or halt the consequences of the underlying genetic predisposition toward obesity and Type 2 diabetes in humans (and in non-human primates).”
That’s a touching sentiment toward her aging rhesus monkey colony, but it calls for a pharmacological approach to address the genetic predisposition to a metabolic disorder of fat regulation affecting perhaps half of humankind, at least in the context of the Western Diet. A pill to pop! How absurd this is, especially when the solution is staring us all right in the face. It couldn’t be clearer or more apparent to me. If you haven’t figured it out yet, you’ll have to wait ‘til next week for me to spell it out for you.© Dan Brown 12/29/12