Effects of an Oral Ghrelin Mimetic on Body Composition and Clinical Outcomes in Healthy Older Adults

What is the problem and what is known about it so far? People who are fortunate enough to avoid serious illness usually decline as they reach advanced age. One wordfrailtysums up this decline. One of the characteristic features of frailty is loss of soft tissue, both fat and muscle. Loss of muscle leads to loss of mobility and balance and, ultimately, loss of independence. The cause of frailty is not yet known, but many factors are probably at work. Among the possible causes is reduced levels of growth hormone in the body. Growth hormone is a protein hormone, secreted by the pituitary gland throughout the day, that stimulates increased muscle mass, decreases fat mass, and affects bone and cartilage. Growth hormone levels are highest during puberty and decline gradually over a lifetime. Giving growth hormone to healthy older adults as an injection increases muscle and decreases fat but does not seem to affect strength; doing so also does not mimic normal growth hormone release patterns. Why did the researchers do this particular study? These investigators tested an experimental oral drug (MK-677) that stimulates normal release of growth hormone to see its effects on fat and muscle, various other body systems, and function. Who was studied? 65 healthy men and women ranging from 60 to 81 years of age. How was the study done? The authors assigned the participants to receive MK-677 or a placebo for 1 year. After 1 year, the volunteers who received placebo started taking MK-677. Those who received MK-677 during the first year were randomly assigned to continue receiving it or to receive placebo instead. What did the researchers find? The new drug increased growth hormone levels to those of healthy young adults. Moreover, the pituitary gland released growth hormone in the normal pulsatile pattern throughout the day. Compared with placebo, MK-677 had several effects. Body weight increased, as did fat-free mass (most of which is muscle), water inside cells, and fat on the arms and legs. Also, the body's sensitivity to insulin decreased, and blood sugar increased. Neither MK-677 nor placebo had an effect on thigh muscle area, muscle strength, or function. The effects of MK-677 were sustained in those who received it for 24 months and went away when people stopped receiving the drug in the second year. Participants who were switched from placebo to MK-677 during the second year had the same effects as those who started the drug in the first year. What are the limitations of the study? The number of participants in the study was too small to evaluate the safety of MK-677 or to be sure of some results. The study did not last long enough to evaluate the long-term effects of increasing growth hormone secretion. What are the implications of the study? This study is an early step in the process of seeing whether stimulating growth hormone secretion helps to overcome the effects of aging on muscle. Much more research is needed to see whether older people will benefit from stimulating their body's ability to secrete growth hormone.