Tuesday, November 5, 2013

Diet Dogma Rears Ugly Head Again: Become a Fat Burner, Eat Your Own Crap, and Live Longer

Holding my dog up against my chest moments before he had peacefully taken his last few breaths, I thought about how cold his hands and feet were; how slow his heart beat and breathing were; and just how much he had shrunk and atrophied.  Of course, these are all the consequences of aging, a topic that I try to avoid thinking about because thinking about aging leads to thinking about your own mortality, or the mortality of those close to you. 

A great amount of money is spent on things that could possibly delay the aging and the advent of the diseases associated with it, including hormone replacement therapy.  But this demented idea to meaningfully delay aging has spawned some dreadful ideas that have little basis in science. 

One such idea, actually a few related ideas that I’ll roll into one idea here, is to limit the amount of glucose our cells burn over the course of a lifetime, so as to turn on a primitive stress response mechanism called autophagy, a process whereby cells degrade and recycle their dysfunctional components in nutrient depleted conditions.  Unfortunately, this entails burning more fatty acids for fuel (or being “fat adapted” in horribly egregious articles filled with wishful thinking like this one) and turning down thyroid functioning, or the rate at which we live -- adaptations that are directly at odds with reaching our full potential as humans.

The physiological adaptations I am most interested in are the increased secretion of ACTH, insulin, and beta-endorphins (anandamides and 2-araichdonylglycerol [derived from arachidonic acid]) and decreased secretion and tissue responsiveness to the thyroid hormones – all of which are disease-promoting in excess, while incidentally predisposing to weight gain.  ACTH is a subject that deserves its own post.  The same goes for the beta-endorphins.  The discussion herein will center on the thyroid hormone.

Maintaining tissue responsiveness to hormones is, I believe, a key factor in slowing down the aging process.  Consider Progeria, a syndrome famous for producing an apparent accelerated aging in children.  Progeria is characterized by a massive reduction in the responsiveness of cells to all hormones – a defect thought to drive the degenerative conditions that appear in children with the condition.

A cell’s responsiveness to hormones is most sensitive when the stress hormones, free amino acids, and free fatty acids in the blood are low. For example, a deficiency of growth hormone, a stress hormone secreted by the pituitary gland, leads to an inflated sensitivity to the hormone insulin in adulthood.1

Next, consider for a moment people who diet often.  Despite having normal lab tests these people will experience all the signs and symptoms of hypothyroidism.  This paradox indicates a reduced sensitivity of tissues to the thyroid hormones, brought about by the stress of under-eating.  In point of fact, the uptake of thyroid hormones into the central nervous system is impaired by high levels of the stress hormones, free amino acids, and free fatty acids.2 In the central nervous system, the thyroid hormones, in conjunction with the sex hormones, are not only essential for brain development, but also for brain growth, repair, and maintenance in adulthood.3

A low carbohydrate diet, another self-imposed stressor, not only impairs the ability of cells to uptake thyroid hormone, but also hampers the conversion of T4 (pro-hormone) to T3 (active hormone) in the body or directs the conversion of T4 to reverse T3 (inactive hormone), rather than T3.  These conversion problems could alternatively explain the pattern of having normal lab tests and hypothyroid signs and symptoms.4 In the pituitary gland, for example, anything that inhibits the production of T3 from T4 disinhibits the release of TSH, resulting in the following pattern: TSH, T4, and T3.5

The thyroid hormones are the principle regulators of all the things concerned with metabolism, including the process of tissue repair and renewal.  Because the thyroid hormone both facilitates the release of glucose from the liver and stimulates the uptake and oxidation of glucose in the tissues outside the liver (thereby working antagonistically and synergistically with insulin, respectively) there’s really no surprise here.6 In fact, even topically applied active thyroid hormone accelerates wound healing and repair following injury.7

But in so turning up the metabolism by way of the thyroid and supplying nutrient replete conditions to cells, are we not incidentally shutting off the mysterious and magical powers of autophagy?

Another feature of Progeria, which animal models of Progeria and the like have unexpectedly found, is an increase in autophagy – an effect touted as highly desirable among Paleo, low-carbohydrate, and caloric restriction advocates.  The molecular mechanisms are not well understood, but it does help to explain, to me at least, why chronic dieters look so haggard and the opposite of healthy, vibrant, and attractive; sometimes, as if death has warmed over.  Simply put, autophagy is an adaptive response to metabolic stress that when chronically activated drives premature aging by inducing catabolic processes that outpace the renewal ability of cells.8 An increased oxidization of fat in preference to glucose is a key feature underlying this downward metabolic shift, as well as an impairment of mitochondrial respiration and a decline in ATP levels. 

As an aside, the fact that Internet diet gurus had made a claim – which probably led to undue misery – about their diets based on a study in a roundworm should piss you off.

The positive association between resting metabolic rate and maximum lifespan may suggest two things.  The first is that without having to call upon the mysterious and magical powers of autophagy, a high resting metabolic rate accelerates cell protection and repair mechanisms by way of enhanced protein synthesis.  The second is that the thyroid hormones are efficiently acting on their target tissues on which they activate the uncoupling proteins, thereby diffusing the reductive stress imposed on cells (by for instance a sluggish metabolism) to discourage the formation of reactive oxygen species and oxidative stress.

Patented, synthetic thyroid hormone products are on their way to the market pending approval by the FDA and, from the outside looking in, they seem to be highly effective for all the conditions for which a deficiency of thyroid hormone directly cause, from easy fat gain to heart disease.  They also would eradicate the uncertainties associated with glandular products and the cardiovascular side effects associated with the synthetic products because thyroid hormones, to be effective, only really require identical big and bulky groups attached to each of their two tyrosine amino acid residues to restrict movement around the bond which holds these two tyrosine amino acid residues together via an ether linkage. (I wanted to blog about this in the past but I was 99.97% sure it would interest no one.) 

Whether we like it or not, autophagy will occur in all of our cells.  It is a primitive form of protection that allows cells to dispose of misfolded proteins, misassembled protein complexes, damaged mitochondria, and so forth.  There is absolutely no need or reason to force it to occur artificially with special diets – especially so if you’re already healthy.  Undue misery is sure to follow from this self-imposed deprivation.  Interestingly, all the conditions that bring about autophagy are at odds with the conditions that maximize our potential as organisms, and this entails the thyroid hormone and oxidation of glucose for fuel.  I think it’s time for us to toss the idea of diet-induced autophagy into the pile with the other worthless dogmas that have done little more than leave the landscape of diet and nutrition understanding in disarray. 


1.       Bartke, A., Sun, L. Y. & Longo, V. Somatotropic signaling: trade-offs between growth, reproductive development, and longevity. Physiol. Rev. 93, 571–98 (2013).
2.       Hennemann, G. et al. Plasma membrane transport of thyroid hormones and its role in thyroid hormone metabolism and bioavailability. Endocr. Rev. 22, 451–76 (2001).
3.       Correia, H. R., Balseiro, S. C. & de Areia, M. L. Are genes of human intelligence related to the metabolism of thyroid and steroids hormones? - endocrine changes may explain human evolution and higher intelligence. Med. Hypotheses 65, 1016–23 (2005).
4.       Araujo, R. L. et al. High-fat diet increases thyrotropin and oxygen consumption without altering circulating 3,5,3’-triiodothyronine (T3) and thyroxine in rats: the role of iodothyronine deiodinases, reverse T3 production, and whole-body fat oxidation. Endocrinology 151, 3460–9 (2010).
5.       Larsen, P. R., Dick, T. E., Markovitz, B. P., Kaplan, M. M. & Gard, T. G. Inhibition of intrapituitary thyroxine to 3.5.3’-triiodothyronine conversion prevents the acute suppression of thyrotropin release by thyroxine in hypothyroid rats. J. Clin. Invest. 64, 117–28 (1979).
6.       Brenta, G. Why can insulin resistance be a natural consequence of thyroid dysfunction? J. Thyroid Res. 2011, 152850 (2011).
7.       Safer, J. D., Crawford, T. M. & Holick, M. F. Topical thyroid hormone accelerates wound healing in mice. Endocrinology 146, 4425–30 (2005).
8.       MariƱo, G. et al. Premature aging in mice activates a systemic metabolic response involving autophagy induction. Hum. Mol. Genet. 17, 2196–211 (2008).