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