Monday, May 6, 2019

Retrospective #80: Calorie Restriction in Humans

Retrospective #79R, “Calorie Restriction and Longevity,” (scroll down to read it), was a rather geeky treatment that dealt with “The Neuroprotective Properties of Calorie Restriction.” 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 compelling read, and I strongly recommend it to all open-minded and serious readers interested in their metabolic health.
In #79R 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. So, in fairness, a little on the pitfalls and concerns.
“CR has many consequences, the majority of which are unknown at this time,” wrote Barbara Hansen in her Journal of Nutrition article, “Calorie Restriction: Effects on Body Composition, Insulin Signaling and Aging” (1995). In it she quotes Bodkin, “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.”
Quoting Hansen and Bodkin (1993): “CR produces altered pathways of nutrient disposal, including reduced plasma glucose, insulin and leptin levels”; and Hansen (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.” “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 it translates from non-human primates to humans.
Two cautions: “Calorie Restriction in Humans: Potential Pitfalls and Health Concerns,” makes two very good points: 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.” 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.”
Hansen’s 2001 piece above reveals what she regards as a “missed opportunity”: “The power of CR to mitigate, delay or prevent the 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 like a typical laboratory scientist, she calls for a pharmacological approach to address the genetic predisposition to a metabolic disorder of fat regulation affecting perhaps half of humankind who’ve adopted the “Standard American Diet.” A pill to pop! How absurd is this, especially when the solution is staring us all right in the face. Taubes, by the way, calls conventional calorie restricted diets in humans “semi-starvation” diets, which they are! But I am not advocating Calorie Restriction (CR) per se.  That will be clear in Retrospective #81, tomorrow, when I lay out my idea of A NEW DIETARY PARADIGM.

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