GROWTH HORMONE REVIVED?

The use of human growth hormone as an "elixir of youth" still has a substantial body of followers despite its sometimes severe side-effects and dubious benefits. So is there a way getting a better deal out of it? The study below has a brief look at that. It looks at stimulating the body to produce more of its own growth hormone. The results after two years seem good -- a more youthful body and only minor side-effects. As the authors note, however, longer-term side-effects are the big question. Also note that it did not reduce fat overall

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

Background: Growth hormone secretion and muscle mass decline from midpuberty throughout life, culminating in sarcopenia, frailty, decreased function, and loss of independence. The decline of growth hormone in the development of sarcopenia is one of many factors, and its etiologic role needs to be demonstrated.

Objective: To determine whether MK-677, an oral ghrelin mimetic, increases growth hormone secretion into the young-adult range without serious adverse effects, prevents the decline of fat-free mass, and decreases abdominal visceral fat in healthy older adults.

Design: 2-year, double-blind, randomized, placebo-controlled, modified-crossover clinical trial.

Setting: General clinical research center study performed at a university hospital.

Participants: 65 healthy adults (men, women receiving hormone replacement therapy, and women not receiving hormone replacement therapy) ranging from 60 to 81 years of age.

Intervention: Oral administration of MK-677, 25 mg, or placebo once daily.

Measurements: Growth hormone and insulin-like growth factor I levels. Fat-free mass and abdominal visceral fat were the primary end points after 1 year of treatment. Other end points were body weight, fat mass, insulin sensitivity, lipid and cortisol levels, bone mineral density, limb lean and fat mass, isokinetic strength, function, and quality of life. All end points were assessed at baseline and every 6 months.

Results: Daily administration of MK-677 significantly increased growth hormone and insulin-like growth factor I levels to those of healthy young adults without serious adverse effects. Mean fat-free mass decreased in the placebo group but increased in the MK-677 group (change, -0.5 kg [95% CI, -1.1 to 0.2 kg] vs. 1.1 kg [CI, 0.7 to 1.5 kg], respectively; P < 0.001), as did body cell mass, as reflected by intracellular water (change, -1.0 kg [CI, -2.1 to 0.2 kg] vs. 0.8 kg [CI, -0.1 to 1.6 kg], respectively; P = 0.021). No significant differences were observed in abdominal visceral fat or total fat mass; however, the average increase in limb fat was greater in the MK-677 group than the placebo group (1.1 kg vs. 0.24 kg; P = 0.001). Body weight increased 0.8 kg (CI, -0.3 to 1.8 kg) in the placebo group and 2.7 kg (CI, 2.0 to 3.5 kg) in the MK-677 group (P = 0.003). Fasting blood glucose level increased an average of 0.3 mmol/L (5 mg/dL) in the MK-677 group (P = 0.015), and insulin sensitivity decreased.

The most frequent side effects were an increase in appetite that subsided in a few months and transient, mild lower-extremity edema and muscle pain. Low-density lipoprotein cholesterol levels decreased in the MK-677 group relative to baseline values (change, -0.14 mmol/L [CI, -0.27 to -0.01 mmol/L]; -5.4 mg/dL [CI, -10.4 to -0.4 mg/dL]; P = 0.026); no differences between groups were observed in total or high-density lipoprotein cholesterol levels. Cortisol levels increased 47 nmol/L (CI, 28 to 71 nmol/L (1.7 æg/dL [CI, 1.0 to 2.6 æg/dL]) in MK-677 recipients (P = 0.020). Changes in bone mineral density consistent with increased bone remodeling occurred in MK-677 recipients. Increased fat-free mass did not result in changes in strength or function. Two-year exploratory analyses confirmed the 1-year results.

Limitation: Study power (duration and participant number) was insufficient to evaluate functional end points in healthy elderly persons.

Conclusion: Over 12 months, the ghrelin mimetic MK-677 enhanced pulsatile growth hormone secretion, significantly increased fat-free mass, and was generally well tolerated. Long-term functional and, ultimately, pharmacoeconomic, studies in elderly persons are indicated.

Annals of Internal Medicine, 4 November 2008 | Volume 149 Issue 9 | Pages 601-611





Forgotten but not gone: leprosy lives on in America

Long seen as a disease of biblical times, leprosy still appears and may be spreading in the United States, researchers say. But it's often misdiagnosed, they warn, with disastrous results.

Also known as Hansen's disease, leprosy is a slow, chronic illness that often leads to disability and disfigurement by attacking the peripheral nervous system and by degrading motor skills. Scientists don't clearly understand how it's transmitted. "We believe there are more cases of leprosy not identified due to the lack of awareness about the disease among physicians in the U.S.," said James Krahenbuhl, director of the Health Resources Service Administration's National Hansen's Disease Program in Baton Rouge, La. This leads to "misdiagnosis and wrong treatments," he added. About 150 leprosy cases are diagnosed yearly; 3,000 people in the United States are being treated, he said.

Leprosy, whose patients have historically been quarantined in isolated "leper colonies" throughout many countries and time periods, is caused by a rodshaped bacterium, Mycobacterium leprae. Infection and symptoms can take three to 10 years to set in, making it hard for researchers to pinpoint where or how people catch the illness, according to the Hansen's Disease program.

Patients gradually lose feeling in their fingers and toes, leaving them open to repeated burns and cuts which get infected. The repeated damage leads to bone absorption and motor nerve deterioration causing fingers to shorten and curve, resulting in a clawlike appearance. Leprosy is fully treatable with medicine in early stages. But nerve damage that occurs in later stages can't be reversed.

Because many U.S. leprosy patients are poor immigrants who turn to free clinics or emergency rooms, many of the doctors involved aren't familiar with the disease, according to the program. They often mistake the skin lesions for a fungus or ringworm and prescribe a topical cream. Because leprosy progresses slowly, it can take months or longer before it becomes clear the treatment is failing -- giving the disease a sizeable head start.

Leprosy prevails most in the tropics and poor countries. Due to changes in immigrant relocation, leprosy is now being diagnosed throughout the United States, Krahenbuhl said. The program sees about 30 cases each year among residents in southern Louisiana and the Gulf Coast of Texas who were born in the U.S. and who have never visited an endemic country.

"As we see leprosy move toward internal regions of the States, it becomes more urgent to reach those physicians to let them know about the symptoms of this disease," said Krahenbuhl. To raise awareness among physicians, he plans to lead a symposium on the topic at the American Society of Tropical Medicine and Hygiene meeting Dec. 7 to 11 in New Orleans.

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