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    Is calorie restriction the path to victory against fat?

    Men’s Health Mythbuster is a new section on UrologyTimes.com 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 [email protected] or post a comment below.


    Steven Lamm, MDSteven Lamm, MD

    Dr. Lamm is clinical professor of medicine and medical director of the Preston Robert Tisch Center for Men’s Health and Mr. Sultan is an MD candidate at New York University School of Medicine, New York.

    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?

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