More than a decade ago, we launched the first study of long-term serious calorie-restricted humans. That research was picked up by Washington University in Saint Louis School of Medicine, and human calorie restriction research was off and running.
Building on animal studies, clinical responses to human calorie restriction were established:
Calorie restriction lowers fasting glucose levels– Average glucose levels of the human CR cohort at Washington University were 81 mg/dL.1 This makes sense: With less available energy from calories eaten, cells
burn voraciously the blood glucose they can find. This causes glucose levels to fall – provided that healthful, low-GI carbohydrates are partof the diet.
Calorie restriction lowers triglycerides – With less available energy, the body burns fat for fuel, so triglycerides fall. The average triglyceride level for the Washington University CR cohort was 49 mg/dL 2
Calorie restriction lowers IGF-I, Insulin-like Growth Factor, a hormone that’s a major growth-driver. Ah, but this one is tricky: If protein levels are high, IGF-I stays high, whether calories are lower or not.3 So if you want to turn down anabolic activity, a fundamental tenet of calorie restriction’s effects, dietary protein intake should be moderate – around the RDA. Anyone who doubts that calorie restriction lowers glucose, triglycerides. and IGF-I can easily test them at a local laboratory. They are lab tests that most doctors use routinely to assess health.
It should go without saying that to conduct objective research oncalorie-restricted humans, the subjects must neither be ill nor be on medication to control an illness.
Does it not seem surprising then that the results of the recently reported NIA study, did not meet any of these criteria?
Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study. (Nature. 2012 Aug 29. doi: 10.1038/nature11432. PMID: 22932268),
These monkeys ate a high protein diet – likely to raise IGF-I, and their triglyceride and glucose levels were also high – uncharacteristic of calorie-restricted animals in research studies. Further, the cohort included animals previously used at a military research facility. Many of these animals died of illness unrelated to the present study.
For some, the study and the resulting headlines rewrote calorie restriction physiology in one fell swoop. For us, the results give the same message that we get when working with new LivingTheCRWay.com members who have not yet achieved the results they strive for: It is time to take a careful look at dietary intake to see what prevents the member from achieving basic effects of following a CR diet. Unless someone is ill, these dietary adjustments always produce lower glucose, triglycerides and IGF-I.
Then there is the imprisonment issue. The monkeys in the NIA experiment were kept in small cages for their entire lives. This would have a profound effect that extends to the monkey’s genetic physiology. Rhesus monkeys maintain social systems that affect their physiology. Consider these research results:
Social environment is associated with gene regulatory variation in the rhesus macaque immune system.
Tung J, Barreiro LB, Johnson ZP, Hansen KD, Michopoulos V, Toufexis D, Michelini K, Wilson ME, Gilad Y.
Proceedings of the National Academy of Sciences of the U.S.A 2012 Apr 24;109(17):6490-5. Epub 2012 Apr 9.
Abstract
Variation in the social environment is a fundamental component of many vertebrate societies. In humans and other primates, adverse social environments often translate into lasting physiological costs.
The biological mechanisms associated with these effects are therefore of great interest, both for understanding the evolutionary impacts of social behavior and in the context of human health. However, large gaps remain in our understanding of the mechanisms that mediate these effects at the molecular level. Here we addressed these questions by leveraging the power of an experimental system that consisted of 10 social groups of female macaques, in which each individual’s social status (i.e., dominance rank) could be experimentally controlled.
Using this paradigm, we show that dominance rank results in a widespread, yet plastic, imprint on gene regulation, such that peripheral blood mononuclear cell gene expression data alone predict social status with 80% accuracy. We investigated the mechanistic basis of these effects using cell type-specific gene expression profiling and glucocorticoid resistance assays, which together contributed to rank effects on gene expression levels for 694 (70%) of the 987 rank-related genes. We also explored the possible contribution of DNA methylation levels to these effects, and identified global associations between dominance rank and methylation profiles that suggest epigenetic flexibility in response to status-related behavioral cues. Together, these results illuminate the importance of the molecular response to social conditions, particularly in the immune system, and demonstrate a key role for gene regulation in linking the social environment to individual physiology.
The NIA study was started in 1987, long before human CR research began. Its value now is questionable, given its many incongruities and the cruel imprisonment of the animals. We suggest that it best be abandoned in favor of serious human CR research that holds promise for preventing disease and increasing healthy lifespan.
References
1 Long-term calorie restriction is highly effective in reducing the risk for atherosclerosis in humans.
Proceedings of the National Academy of Sciences of the USA. 2004 Apr 27;101(17):6659-63.
Fontana L, Meyer TE, Klein S, Holloszy JO.
PMID: 15096581
2 Caloric restriction in humans.
Experimental Gerontology. 2007 Aug;42(8):709-12.
Holloszy JO, Fontana L.
PMID: 17482403
3 Long-term effects of calorie or protein restriction on serum IGF-1 and IGFBP-3 concentration in humans.
Aging Cell. 2008 Oct;7(5):681-7.
Fontana L, Weiss EP, Villareal DT, Klein S, Holloszy JO.
PMID: 18843793
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