A4M Appetite and Anti-Aging

Stephen Holt, MD

Excessive dietary intake of calories is causally associated with obesity, the metabolic syndrome X, type II diabetes mellitus and their related diseases (1). These common conditions have been redefined as diseases of premature aging because they cause much disability and death. New guidelines for the US, Food Pyramid Guide (January 2005) stress the need for reduced calorie intake for health, without acknowledgment of the benefit of nutrient dense foods. Excess calorie intake is driven by appetite regulation and the pivotal step in weight control is a calorie-reduced diet, complemented by healthy lifestyle and exercise. Socio-behavioral and psychological factors regulate both appetite and individual responses to safety signals (2). The waning interest in drugs, dietary supplements and fad diets for weight control highlights the lack of effectiveness of focused approaches to weight control.

Weight loss is now a major public health concern, as obesity emerges as one of the most important causes of premature death and disability, with clear import for anti-aging initiatives. By interference, appetite suppression is a logical anti-aging tactic for the nation, but appetite suppression with stimulant drugs or supplements may often be unhealthy. Increasing knowledge about central nervous system (CNS) and peripheral controls of appetite, hunger and satiety has led to intensive research into compounds that can regulate appetite (2). The greatest promise of pharmacological control of appetite has emerged from natural compounds that regulate CNS functions. Several plant-derived compounds are involved in CNS signaling. For example, Cannabis sativa contains cannabinoids which are both powerful exogenous messages to control appetite or other body functions; and the human CNS elaborates its own endocannabinoids as messenger molecules (3). The same is true for opioids, botanically-derived and similar in structure to opioids found in poppies (3). Endogenous opioids regulate appetite and other somatic functions (3). This concept of “plants talking to the brain” is novel and it forms the basis of new research pathways for the development of anti-obesity drugs and supplements (3-5). This pharmacological approach is further highlighted by the recent discovery of the ability of sterol glycosides, found in succulent plants (e.g. Hoodia gordonii), to act directly on the hypothalamus to increase neuronal ATP and promote “deceptive” satiety signals (4,5). Appetite regulation has not been the focus of anti-aging medicine, but it is now at the forefront of attempts to promote longevity, largely through its role in the control of the obesity pandemic.


  • Holt S, Wright JV, Taylor TV, Nutritional Factors for Syndrome X, Wellness Publishing, NJ, 2004.
  • Kalra SP Dube MG, Pu S et al Interacting appetite regulating pathways in the hypothalamic regulation of weight Endocrine Rev, 20, 68-100, 1999.
  • Nicoll RA, Algar BE, The Brains own Marijuana, Scientific American, 70-75, Dec. 2004
  • MacLean D, Lu-Guang L, Increased ATP content/production in the hypothalamus may be a signal for energy-sensing of satiety: studies of the anorectic mechanism of plant steroidal glycoside. Brain Research, 1020, 1-11, 2004.
  • Holt S, The Supreme Properties of Hoodia Gordonii, Wellness Publishing Inc., NJ 2005

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