Is calorie restriction the path to victory against fat?

August 18, 2016

Steven Lamm, MD and Darren Sultan, BA look at this and several other misconceptions.

Men’s Health Mythbuster is a new section on that explores common statements and beliefs about men’s health and evaluates whether these statements are false. To leave feedback or suggest future myths, send an email to or post a comment below.

Steven Lamm, MDDr. Lamm

The calorie restriction diet myth suggests you will win the war against fat.

We are skeptical about this suggestion unless one’s homeostatic mechanisms are deactivated.

Recent revelations into the neurohormonal pathways involved in obesity have led to novel therapies in weight loss as well as a systematic rethinking of previously touted approaches for obesity. The idea that calorie restriction leads to weight loss is probably as old as the adage, “You are what you eat.” The trouble with this assumption is that it neglects the role of the hypothalamus in maintaining energy homeostasis.

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In 1953, Kennedy observed that rats adjust their food intake as a way of maintaining near-constant fat stores. He discovered that damage to the hypothalamus results in hyperphagia and obesity, but more importantly, feeding hyperphagic rats unpalatable food resulted in a transient weight loss through calorie restriction that is immediately reversed by resumption of the previous diet (Proc R Soc Lond B Biol Sci 1953; 140:578-96). What remained to be determined at that time was the connection between the hypothalamus and metabolism, which some had postulated to be the result of thermoregulation (Physiol Rev 1946; 26:541-59).

Nearly four decades later, researchers working on the ob gene in mice discovered the first adipokine, subsequently termed leptin. The difficulty with transitioning these findings to the clinical realm was that humans rarely if ever carried leptin or leptin receptor mutations. In fact, obese individuals were found to have increased ob gene expression compared to lean individuals, suggesting that leptin resistance was at play (J Clin Invest 1995; 95:2986-8).

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During starvation, leptin levels fall dramatically and out of proportion to the decreased fat stores. Additionally, upregulation of neuropeptide Y and other corticotropin secretagogues stimulate the hypothalamic-pituitary-adrenal axis to create a stress response that feeds back to inhibit release of corticotropin-releasing hormone, which has anorexic properties (N Engl J Med 1997; 336:1802-11).

With regard to clinical practice, behavior modification is often an expedient approach to weight loss that physicians pitch to patients. However, while calorie restriction is effective in the short term, studies on calorie restriction are rarely, if ever, carried out beyond 2 years (Nutr Clin Pract 2011; 26:512-25). New guidelines suggest that physicians should focus on weight reduction as an independent treatment goal in patients and also as part of selecting therapies for comorbidities such as hypertension, hyperlipidemia, and diabetes (J Clin Endocrinol Metab 2015; 100:342–62).

Myth debunked? It is important for clinicians to recognize that negative energy balance is quickly opposed by aggressive homeostatic mechanisms. Meaningful weight loss is achieved instead through neurohormonal modifications. This understanding has led to a number of new pharmacologic therapies that have shown a clear benefit for patients with a body mass index of 30 kg/m2 or those with a BMI of 27 kg/m2 and other comorbid conditions.

Next: Do protein supplements actually increase muscle mass?


The more protein you eat, the more muscular you become.

Many if not most people are aware that protein intake alone cannot increase muscle mass. The question that is often asked by athletes is whether there is utility to protein supplements to facilitate muscle anabolism achieved through resistance exercise.

This question is complicated by a lot of mixed information in the media on the pros and cons of various formulations. Several years ago, various organizations, including the American College of Sports Medicine, put out a paper regarding the evidence for a variety of health supplements. Their conclusion was that it is of course important to maintain adequate fluid, electrolyte, nutrient, and glucose balance during exercise to prevent adverse side effects of dehydration or malnutrition.

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As for ergogenic compounds, there is limited evidence due to the lack of regulation regarding their safety and efficacy (Med Sci Sports Exerc 2009; 41:709-31). Also, there is insufficient data to provide any recommendations regarding preferable sources of protein such as whey, soy, or meat.

In the laboratory, research shows that certain supplements are associated with favorable cellular signaling. In one study, branched-chain amino acid supplementation given to subjects before and after quadriceps training led to increased mTOR and ribosomal protein S6 phosphorylation, which in turn led to increased mRNA translation in skeletal muscle. Additionally, they found that effects were seen primarily in the recovery phase after exercise (J Nutr 2006; 136:269S-73S).

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A subsequent meta-analysis looking at the effect of the timing of supplement ingestion on muscle hypertrophy found that there was no significant difference for groups who consumed supplements either directly before or hours after resistance exercise (J Int Soc Sports Nutr 2013; 10:53). The caveat to this study came in a subsequent meta-analysis that showed that in untrained athletes, there was no advantage to protein supplementation in the first few weeks of training. A benefit in muscle hypertrophy and strength was seen only when the frequency, duration, and volume of exercise were later increased in these individuals (Sports Med 2015; 45:111–31).

Myth debunked? The use of protein powders and other related supplements may be appropriate for certain athletes who routinely engage in resistance training. However, it is important to note that only essential amino acids have a clear benefit for muscle building. Recommended dietary protein intake is 0.8 g/kg/day for an average adult, but for athletes who routinely engage in resistance training, recommended intake may be double this. As for carbohydrate mixtures, there is limited evidence for any benefit.

Next: Is muscle mass loss inevitable with age?


Muscle mass loss is inevitable with age.

While the term sarcopenia is less than 20 years old, research into the loss of muscle mass in the elderly is decades older. In coining the term, Rosenberg considered this question of the inevitability of functional decline in the elderly (J Nutr 1997; 127:990S-1S).

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Aging is of course apparent at the cellular level in terms of telomere shortening, oxidative stress, and sporadic genetic mutations. The role of aging on the macroscopic level is defined in part by these cellular changes but also by other large-scale factors. The observation that sarcopenia is found in a significant number of chronically ill nonelderly patients is consistent with the hypothesis that atrophy through nonuse is the primary driver of the sharp decline in muscle mass (Nutr Clin Pract 2016; 31:40-8).

In the elderly, it may be hard to determine whether sarcopenia leads to decreased physical activity or whether the converse is true. Regardless, increased physical activity may have a role in preventing a decline in muscle mass in elderly men. The benefit of exercise in maintaining high lean mass and grip strength in old age was seen only in the cohort of men who exercised in early and late adulthood. As for those who exercised in old age only, there was no significant difference in lean mass as compared to controls. In women, no statistical benefit was seen for any of the cohorts, though the study may have had insufficient power due its limited population size (J Gerontol A Biol Sci Med Sci 2016; 71:515-20).

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There are a number of modifiable risk factors, such as nutritional status, that can be addressed. However, sarcopenia is also the result of decreased nerve innervation, increased levels of catabolic hormones with concurrent decreases in growth hormone and testosterone, altered gene expression, and apoptosis (J Gerontol A Biol Sci Med Sci 2003; 58:M911-16).

Myth debunked? The evidence is somewhat pessimistic. The imbalance between skeletal muscle protein synthesis and breakdown in the elderly is overall difficult to counteract. Perhaps there are still strategies to be gleaned from the treatment of osteopenia. Additionally, continuous weight-bearing exercise may be the most effective strategy at this point for staving off frailty.

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Section Editor Steven A. Kaplan, MDDr. Kaplan

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