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Life Extension Magazine March 2009

Growth Hormone

The effects of growth hormone and sex steroid on lean body mass, fat mass, muscle strength, cardiovascular endurance and adverse events in healthy elderly women and men.

Decreases in growth hormone (GH) and insulin-like growth factor I occur with age, in addition to oestrogen deficiency in women and a reduction in the levels of testosterone in men. These age-related hormonal changes may contribute to reductions in lean body mass, muscle strength and cardiac endurance, which can be partially reversed in elderly people with GH treatment, and testosterone supplements and oestrogen/progestin hormone replacement therapy in men and women, respectively. These treatments are, however, thought to have potentially serious adverse effects. We conducted a study to evaluate the separate and interactive effects of GH and sex steroids on body composition, muscle strength and cardiac endurance as well as the rate of adverse events in healthy elderly people. The results of the study showed that although there were beneficial effects with GH and sex steroid treatment, a high percentage of adverse effects occurred after 26 weeks of treatment, demonstrating a need for more research on the safety of hormonal therapy in the elderly population.

Horm Res. 2003;60(Suppl 1):121-4

Use of growth hormone for prevention or treatment of effects of aging.

Decreases in growth hormone (GH) and insulin-like growth factor-I, estrogen deficiency in women, diminished testosterone in men, and loss of lean body mass, increased fat, and other changes consistent with hormone deficiencies occur during aging. Treatment of nonelderly GH-deficient adults with recombinant human GH (rhGH) improves body composition, muscle strength, physical function, and bone density, and reduces blood cholesterol and cardiovascular disease risk, but is often accompanied by carpal tunnel syndrome, peripheral edema, joint pain and swelling, gynecomastia, glucose intolerance, and possibly increased cancer risk. Reports that rhGH augments lean body mass and reduces body fat in aged individuals increased use of rhGH to delay aging effects. However, clinically significant functional benefits, prolongation of youth, and life extension have not been demonstrated. Moreover, marketing of rhGH and other hormone supplements largely ignores adverse effects. Until more research has better defined the risk/benefit relationships, treatment of elderly individuals with rhGH should be confined to controlled research studies.

J Gerontol A Biol Sci Med Sci. 2004 Jul;59(7):652-8

Evaluation and treatment of adult growth hormone deficiency: an Endocrine Society Clinical Practice Guideline.

OBJECTIVE: The objective is to provide guidelines for the evaluation and treatment of adults with GH deficiency (GHD). PARTICIPANTS: The chair of the Task Force was selected by the Clinical Guidelines Subcommittee of The Endocrine Society (TES). The chair selected five other endocrinologists and a medical writer, who were approved by the Council. One closed meeting of the group was held. There was no corporate funding, and members of the group received no remuneration. EVIDENCE: Only fully published, peer-reviewed literature was reviewed. The Grades of Evidence used are outlined in the Appendix. CONSENSUS PROCESS: Consensus was achieved through one group meeting and e-mailing of drafts that were written by the group with grammatical/style help from the medical writer. Drafts were reviewed successively by the Clinical Guidelines Subcommittee, the Clinical Affairs Committee, and TES Council, and a version was placed on the TES web site for comments. At each level, the writing group incorporated needed changes. CONCLUSIONS: GHD can persist from childhood or be newly acquired. Confirmation through stimulation testing is usually required unless there is a proven genetic/structural lesion persistent from childhood. GH therapy offers benefits in body composition, exercise capacity, skeletal integrity, and quality of life measures and is most likely to benefit those patients who have more severe GHD. The risks of GH treatment are low. GH dosing regimens should be individualized. The final decision to treat adults with GHD requires thoughtful clinical judgment with a careful evaluation of the benefits and risks specific to the individual.

J Clin Endocrinol Metab. 2006 May;91(5):1621-34

Aging and the growth hormone/insulin like growth factor-I axis.

Growth hormone release and IGF-I synthesis decrease with increasing age. The regulation of the GH/IGF-I system is dependent on the integrity of the hypothalamus, pituitary and liver. During aging there are several changes which contribute to the decline in GH/IGF-I including changes in signal to the somatotrophs from growth hormone releasing hormone, somatostatin and other factors such as body composition, exercise, diet and sleep. All of these factors are discussed in detail within this review. The phenotypic similarities between aging and adult growth hormone deficiency syndrome combined with this decrease in GH/IGF-I with aging have prompted the question whether aging is a GH deficient state. The advent of recombinant growth hormone has led to a number of studies treating elderly patients with GH alone or in combination with sex steroids or exercise. The results of these studies would not back up the use of GH in elderly non-hypopituitary patients as they did not show efficacy, showed high rates of adverse events and there is also some evidence associating GH/IGF-I and risk of neoplasia. If GH therapy is to be used in this cohort of patients further long term efficacy and safety studies are required.

Pituitary. 2007;10(2):189-203

Systematic review: the safety and efficacy of growth hormone in the healthy elderly.

BACKGROUND: Human growth hormone (GH) is widely used as an antiaging therapy, although its use for this purpose has not been approved by the U.S. Food and Drug Administration and its distribution as an antiaging agent is illegal in the United States. PURPOSE: To evaluate the safety and efficacy of GH therapy in the healthy elderly. DATA SOURCES: The authors searched MEDLINE and EMBASE databases for English-language studies published through 21 November 2005 by using such terms as growth hormone and aging. STUDY SELECTION: The authors included randomized, controlled trials that compared GH therapy with no GH therapy or GH and lifestyle interventions (exercise with or without diet) with lifestyle interventions alone. Included trials provided GH for 2 weeks or more to community-dwelling participants with a mean age of 50 years or more and a body mass index of 35 kg/m2 or less. The authors excluded studies that evaluated GH as treatment for a specific illness. DATA EXTRACTION: Two authors independently reviewed articles and abstracted data. DATA SYNTHESIS: 31 articles describing 18 unique study populations met the inclusion criteria. A total of 220 participants who received GH (107 person-years) completed their respective studies. Study participants were elderly (mean age, 69 years [SD, 6]) and overweight (mean body mass index, 28 kg/m2 [SD, 2]). Initial daily GH dose (mean, 14 microg per kg of body weight [SD, 7]) and treatment duration (mean, 27 weeks [SD, 16]) varied. In participants treated with GH compared with those not treated with GH, overall fat mass decreased (change in fat mass, -2.1 kg [95% CI, -2.8 to -1.35] and overall lean body mass increased (change in lean body mass, 2.1 kg [CI, 1.3 to 2.9]) (P < 0.001), and their weight did not change significantly (change in weight, 0.1 kg [CI, -0.7 to 0.8]; P = 0.87). Total cholesterol levels decreased (change in cholesterol, -0.29 mmol/L [-11.21 mg/dL]; P = 0.006), although not significantly after adjustment for body composition changes. Other outcomes, including bone density and other serum lipid levels, did not change. Persons treated with GH were significantly more likely to experience soft tissue edema, arthralgias, carpal tunnel syndrome, and gynecomastia and were somewhat more likely to experience the onset of diabetes mellitus and impaired fasting glucose. LIMITATIONS: Some important outcomes were infrequently or heterogeneously measured and could not be synthesized. Most included studies had small sample sizes. CONCLUSIONS: The literature published on randomized, controlled trials evaluating GH therapy in the healthy elderly is limited but suggests that it is associated with small changes in body composition and increased rates of adverse events. On the basis of this evidence, GH cannot be recommended as an antiaging therapy.

Ann Intern Med. 2007 Jan 16;146(2):104-15

Growth hormone treatment in human ageing: benefits and risks.

This paper will focus on the rationale of using Growth Hormone (GH) as an anti-ageing therapy in the healthy elderly with age-related decline in the activity of the GH/IGF-I axis, the so called “somatopause”. Although the age-related decline in the activity of the GH/IGF-I axis is considered to contribute to age-related changes similar to those observed in Growth Hormone Deficient (GHD) adults, GH/IGF-I deficiency or resistance is also known to result in prolonged life expectancy, at least in animals. These data raise the question whether or not GH deficiency constitutes a beneficial adaptation to ageing and therefore requires no therapy. Moreover, although GH therapy has been shown to exert positive effects in GHD patients, its safety, efficacy and role in healthy elderly individuals is highly controversial. This review provides a comprehensive account of the implications of GH therapy in the ageing subject.

Hormones (Athens). 2008 Apr-Jun;7(2):133-9

Growth hormone status in morbidly obese subjects and correlation with body composition.

Morbidly obese subjects are characterized by multiple endocrine abnormalities and these are paralleled by unfavorable changes in body composition. In obese individuals, either 24-h spontaneous or stimulated GH secretion is impaired without an organic pituitary disease and the severity of the secretory defect is proportional to the degree of obesity. The GHRH+arginine (GHRH+ARG) test is likely to be the overall test of choice in clinical practice to differentiate GH deficiency (GHD) patients. Similarly to other provocative tests, GHRH+ARG is influenced by obesity per se. Therefore, a new cut-off limit of peak GH response of 4.2 microg/l in obese subjects has been recently assumed. The aim of the present study was to investigate the reciprocal influence between decreased GH secretion and body composition in a group of 110 morbidly obese subjects, using the new cut-off limit of peak GH response to GHRH+ARG test for these subjects. In our study, GHD was identified in 27.3% of the obese subjects, without gender difference. In GDH obese subjects body mass index (BMI), waist circumference, waist-to-hip ratio (WHR), fat mass (FM), and resistance (R) were higher while reactance (Xc), phase angle, body cell mass (BCM), IGF-I, or IGF-I z-scores were lower than in normal responders (p<0.001). In all obese subjects, GH peak levels showed a negative correlation with age, BMI, waist circumference and FM, and a positive correlation with IGF-I. In the stepwise multiple linear regression, waist circumference and FM were the major determinants of GH peak levels and IGF-I. In conclusion, using the new cut-off limit of peak GH response to GHRH+ARG test for obese subjects, about 1/3 morbidly obese subjects were GHD. GHD subjects showed a significantly different body composition compared with normal responders, and the secretory defect was correlated to different anthropometric variables with waist circumference and FM as the major determinants.

J Endocrinol Invest. 2006 Jun;29(6):536-43

Adult-onset growth hormone deficiency: causes, complications and treatment options.

PURPOSE OF REVIEW: Desc-ription of the progresses related to the complications and treatment of adult-onset growth hormone deficiency. RECENT FINDINGS: Growth hormone deficiency in adults has gained attention as a clinical syndrome associated with increased morbidity and possibly mortality. Many studies have been conducted on the consequences of growth hormone deficiency and of its replacement, supporting its use in appropriate patients. Early studies were characterized by a high incidence of side effects due to a lack of pilot data to guide appropriate dosing. Given the wide variability in individual responsiveness to growth hormone therapy based on age, sex, and body composition, recent work has been dedicated to understanding which patients derive benefit from therapy, minimizing side effects, and ensuring cost-effectiveness. SUMMARY: Long-term prospective trials have shown that growth hormone replacement therapy results in improvements in body composition, dyslipidemia, bone mineral density, and quality of life. The effects on endpoints such as cardiovascular morbidity and mortality and fractures are, however, not fully proven. Randomized trials that compare homogenous groups of growth hormone deficiency patients are still needed. Given the high cost of treatment, dynamic testing for growth hormone deficiency should only be performed in patients in whom there is high clinical suspicion, and therapy should be limited to those with biochemically proven growth hormone deficiency.

Curr Opin Endocrinol Diabetes Obes. 2008 Aug;15(4):352-8

Growth hormone decreases visceral fat and improves cardiovascular risk markers in women with hypopituitarism: a randomized, placebo-controlled study.

CONTEXT: Data regarding gender-specific efficacy of GH on critical endpoints are lacking. There are no randomized, placebo-controlled studies of physiological GH therapy solely in women. OBJECTIVE: Our objective was to determine the effects of physiological GH replacement on cardiovascular risk markers and body composition in women with GH deficiency (GHD). DESIGN: This was a 6-month, randomized, placebo-controlled, double-blind study. SETTING: The study was conducted at the General Clinical Research Center. STUDY PARTICIPANTS: 43 women with GHD due to hypopituitarism were included in the study. INTERVENTION: Study participants were randomized to receive GH (goal mid-normal serum IGF-1) or placebo. MAIN OUTCOME MEASURES: Cardiovascular risk markers, including high-sensitivity C-reactive protein, tissue plasminogen activator, and body composition, including visceral adipose tissue by cross-sectional computed tomography, were measured. RESULTS: Mean daily GH dose was 0.67 mg. The mean IGF-1 sd score increased from -2.5 +/- 0.3 to -1.4 +/- 0.9 (GH) (P < 0.0001 vs. placebo). High-sensitivity C-reactive protein decreased by 38.2 +/- 9.6% (GH) vs.18.2 +/- 6.0% (placebo) (P = 0.03). Tissue plasminogen activator and total cholesterol decreased, and high-density lipoprotein increased. Homeostasis model assessment-insulin resistance and other markers were unchanged. Body fat decreased [-5.1 +/- 2.0 (GH) vs. 1.9 +/- 1.0% (placebo); P = 0.002] as did visceral adipose tissue [-9.0 +/- 5.9 (GH) vs. 4.3 +/- 2.7% (placebo); P = 0.03]. Change in IGF-1 level was inversely associated with percent change in visceral adipose tissue (r = -0.61; P = 0.002), total body fat (r = -0.69; P < 0.0001), and high-sensitivity C-reactive protein (r = -0.51; P = 0.003). CONCLUSIONS: Low-dose GH replacement in women with GHD decreased total and visceral adipose tissue and improved cardiovascular markers, with a relatively modest increase in IGF-1 levels and without worsening insulin resistance.

J Clin Endocrinol Metab. 2008 Jun;93(6):2063-71

Recombinant human GH replacement increases CD34+ cells and improves endothelial function in adults with GH deficiency.

OBJECTIVE: Adult patients with GH deficiency (GHD) are at increased risk for cardiovascular morbidity and mortality. Endothelial function, vascular stiffness, and loss of circulating CD34+ cells are considered biomarkers for cardiovascular disease. The aim of this study was to assess vascular structure and function in relation to circulating CD34+ cells in adults with GHD before and during 1 year of recombinant human GH (rhGH) replacement. DESIGN: One-year intervention with rhGH. PATIENTS AND METHODS: Vascular function (flow-mediated dilatation (FMD)) and structure (pulse wave velocity (PWV) and analysis) were assessed in 14 adult patients (nine men) with GHD (mean age 57 years, range 27-71 years). In addition, the number of CD34+ cells was evaluated using flow cytometric analysis. Study parameters were analyzed at baseline, and after 6 months and 1 year of rhGH replacement. RESULTS: rhGH replacement increased IGF-I levels from 10.4+/-4.5 mmol/l at baseline to 18.4+/-10.1 mmol/l, and 20.5+/-8.0 mmol/l, at 6 months, and 1 year respectively (P=0.001). FMD increased from 3.5+/-1.8% to 6.0+/-2.5% and 5.1+/-2.5% during 1 year of rhGH replacement (P=0.008). There was no beneficial effect on PWV, central pulse pressure, central systolic pressure, and augmentation index. The number of CD34+ cells increased from 794.9+/-798.8 to 1270.7+/-580.1 cells/ml and to 1356.9+/-759.0 cells/ml (P=0.010). CONCLUSION: One year of rhGH replacement in adults with GHD improves endothelial function and increases the number of circulating CD34+ cells.

Eur J Endocrinol. 2008 Aug;159(2):105-11

Bone density and turnover in young adult patients with growth hormone deficiency after 2-year growth hormone replacement according with gender.

GH deficiency (GHD) in adults is accompanied by reduced bone mass that may revert only after 2 yr of GH replacement. However, it is unclear whether the gender may modify bone responsiveness to GH replacement in adults. In this study we have evaluated whether bone mineral density (BMD) and turnover improve after GH replacement according to patients’ gender. BMD at lumbar spine (LS) and femoral neck (FN), serum osteocalcin (OC), and urinary cross-linked N-telopeptides of type I collagen (Ntx) were assessed in 64 hypopituitaric patients (35 men, 30-50 yr) before and 2 yr after the beginning of GH replacement. Values of IGF-I and BMD at LS and at FN were expressed as Zscores. At study entry, IGF-I and BMD resulted similar among men and women with GHD. During GH replacement, IGF-I levels increased in both men and women without any difference in the percentage of IGF-I increase between the genders (p=0.47). In women receiving estrogen replacement, however, the percentage of IGF-I increase (p<0.05), and the Z IGF-I score (p<0.001) were significant lower than estrogen untreated women, although IGF-I levels were similar in the 2 groups (p=0.53). The GH dose adjusted for body weight required to restore normal age- and sex- matched IGF-I levels was lower in men than in women (p<0.001), and was higher in women receiving than in those not receiving estrogen replacement (p<0.05). In contrast, hypogonadal men treated with testosterone and eugonadal men received a similar GH dose (p=0.97). Also OC, Ntx levels, lumbar and femoral BMD improved (p<0.001) in all patients. Nevertheless, a greater increase in lumbar BMD increase was observed in men than in women (8.0+/-2.1 vs 2.6+/-0.4%; p<0.05). No significant difference was revealed in bone parameters in women treated or untreated with estrogen replacement and in men treated or not with testosterone replacement for concomitant hypogonadism. At the multiple correlation analysis, gender was a stronger predictor for the required GH dose than the age (p<0.001 and p=0.02, respectively). In conclusion, a 2-yr GH replacement normalizes IGF-I levels, increases bone mass and improves bone turnover both in men and in women with GHD without any difference between the 2 groups, provided that the dose of GH was modulated on the basis of IGF-I levels. Women receiving oral estrogens should receive a GH dose approximately doubled, as compared to men and women not receiving oral estrogens, to achieve similar effects on bone density and turnover. In particular, GH replacement dose, to be successful on bone mass and turnover, depends on gender in hypopituitary patients aged below 50 yr.

J Endocrinol Invest. 2008 Feb;31(2):94-102

Growth hormone treatment of adults with Prader-Willi syndrome and growth hormone deficiency improves lean body mass, fractional body fat, and serum triiodothyronine without glucose impairment: results from the United States multicenter trial.

CONTEXT: GH replacement in Prader-Willi syndrome (PWS) children has well-defined benefits and risks and is used extensively worldwide. Its use in PWS adults has been limited by documentation of benefits and risks, as determined by larger multisite studies. OBJECTIVES: Our objective was to evaluate the effectiveness and safety of GH in GH-deficient genotype-positive PWS adults. DESIGN: We conducted a 12-month open-label multicenter trial with 6-month dose-optimization and 6-month stable treatment periods. Setting: The study was conducted at outpatient treatment facilities at four U.S. academic medical centers. PATIENTS: Lean and obese PWS adults with diverse cognitive skills, behavioral traits, and living arrangements were recruited from clinical populations. INTERVENTION: Human recombinant GH (Genotropin) was initiated at 0.2 mg/d with monthly 0.2-mg increments to a maximum 1.0 mg/d, as tolerated. MAIN OUTCOMES MEASURES: Lean body mass and percent fat were measured by dual-energy x-ray absorptiometry. RESULTS: Lean body mass increased from 42.65 +/- 2.25 (se) to 45.47 +/- 2.31 kg (P < or = 0.0001), and percent fat decreased from 42.84 +/- 1.12 to 39.95 +/- 1.34% (P = 0.025) at a median final dose of 0.6 mg/d in 30 study subjects who completed 6-12 months of GH. Mean fasting glucose of 85.3 +/- 3.4 mg/dl, hemoglobin A1c of 5.5 +/- 0.2%, fasting insulin of 5.3 +/- 0.6 microU/ml, area under the curve for insulin of 60.4 +/- 7.5 microU/ml, and homeostasis model assessment of insulin resistance of 1.1 +/- 0.2 were normal at baseline in 38 study initiators, including five diabetics, and remained in normal range. Total T(3) increased 26.7% from 127.0 +/- 7.8 to 150.5 +/- 7.8 ng/dl (P = 0.021) with normalization in all subjects, including six (20%) with baseline T(3) values at least 2 sd below the mean. Mildly progressive ankle edema was the most serious treatment-emergent adverse event (five patients). CONCLUSIONS: This multicenter study demonstrates that GH improves body composition, normalizes T(3), and is well tolerated without glucose impairment in PWS genotype adults.

J Clin Endocrinol Metab. 2008 Apr;93(4):1238-45

GH replacement reduces increased lipid peroxidation in GH-deficient adults.

BACKGROUND: GH replacement improves numerous metabolic abnormalities in GH-deficient patients; increased lipid peroxidation (LPO) has been observed in GH-deficient patients; however, it is unknown if LPO is influenced by GH replacement. AIM AND METHODS: To evaluate the extent to which GH replacement might reverse the increased LPO in GH-deficient adults and to analyse if this phenomenon might be involved in the improvement of metabolic disturbances due to GH treatment. Serum concentrations of malondialdehyde + 4-hydroxyalkenals (MDA + 4-HDA), as an index of LPO, were measured at baseline, and after 12 and 24 months of GH replacement in 40 adult patients with severe GH deficiency (both in adult- and childhood-onset) and in 40 healthy volunteers, matched for sex, age and body mass index (BMI). Correlations were evaluated between LPO and lipids, IGF-I, metalloproteinase-2 and -9 (MMP-2, -9), vascular endothelial growth factor (VEGF), BMI and GH dose. RESULTS: LPO values in GH-deficient patients were several-fold higher than in controls [55.36 +/- 2.27 vs. 4.19 +/- 0.42 nmol/mg protein (mean +/- SEM), P < 0.0001] and decreased significantly over time with GH replacement to 38.61 +/- 2.15 nmol/mg protein (i.e. by approximately 30%), though still remaining markedly elevated compared with controls (P < 0.0001). The proatherogenic lipid profile parameters correlated positively with LPO in the childhood-onset subgroup before GH replacement. GH replacement restored the positive correlation between LPO and age in male patients (r = 0.57, P = 0.013; r = 0.8, P < 0.001, at 12 and 24 months of GH replacement, respectively). CONCLUSIONS: GH replacement partially reverses the grossly abnormal LPO in GH-deficient adults. It is highly probable, therefore, that oxidative mechanisms are involved in the overall improvement of metabolic changes due to GH replacement.

Clin Endocrinol (Oxf). 2008 Jun;68(6):957-64

Systematic review: the effects of growth hormone on athletic performance.

BACKGROUND: Human growth hormone is reportedly used to enhance athletic performance, although its safety and efficacy for this purpose are poorly understood. PURPOSE: To evaluate evidence about the effects of growth hormone on athletic performance in physically fit, young individuals. DATA SOURCES: MEDLINE, EMBASE, SPORTDiscus, and Cochrane Collaboration databases were searched for English-language studies published between January 1966 and October 2007. STUDY SELECTION: Randomized, controlled trials that compared growth hormone treatment with no growth hormone treatment in community-dwelling healthy participants between 13 and 45 years of age. DATA EXTRACTION: 2 authors independently reviewed articles and abstracted data. DATA SYNTHESIS: 44 articles describing 27 study samples met inclusion criteria; 303 participants received growth hormone, representing 13.3 person-years of treatment. Participants were young (mean age, 27 years [SD, 3]), lean (mean body mass index, 24 kg/m2 [SD, 2]), and physically fit (mean maximum oxygen uptake, 51 mL/kg of body weight per minute [SD, 8]). Growth hormone dosage (mean, 36 microg/kg per day [SD, 21]) and treatment duration (mean, 20 days [SD, 18] for studies giving growth hormone for >1 day) varied. Lean body mass increased in growth hormone recipients compared with participants who did not receive growth hormone (increase, 2.1 kg [95% CI, 1.3 to 2.9 kg]), but strength and exercise capacity did not seem to improve. Lactate levels during exercise were statistically significantly higher in 2 of 3 studies that evaluated this outcome. Growth hormone-treated participants more frequently experienced soft tissue edema and fatigue than did those not treated with growth hormone. LIMITATIONS: Few studies evaluated athletic performance. Growth hormone protocols in the studies may not reflect real-world doses and regimens. CONCLUSION: Claims that growth hormone enhances physical performance are not supported by the scientific literature. Although the limited available evidence suggests that growth hormone increases lean body mass, it may not improve strength; in addition, it may worsen exercise capacity and increase adverse events. More research is needed to conclusively determine the effects of growth hormone on athletic performance.

Ann Intern Med. 2008 May 20;148(10):747-58

Use of amino acids as growth hormone-releasing agents by athletes.

Specific amino acids, such as arginine, lysine and ornithine, can stimulate growth hormone (GH) release when infused intravenously or administered orally. Many individuals consume amino acids before strength training workouts, believing this practice accentuates the exercise-induced GH release, thereby promoting greater gains in muscle mass and strength. The GH response to amino acid administration has a high degree of interindividual variability and may be altered by training status, sex, age, and diet. Although parenteral administration consistently leads to increased circulating GH concentration, oral doses that are great enough to induce significant GH release are likely to cause stomach discomfort and diarrhea. During exercise, intensity is a major determinant of GH release. Although one study showed that arginine infusion can heighten the GH response to exercise, no studies found that pre-exercise oral amino acid supplementation augments GH release. Further, no appropriately conducted scientific studies found that oral supplementation with amino acids, which are capable of inducing GH release, before strength training increases muscle mass and strength to a greater extent than strength training alone. The use of specific amino acids to stimulate GH release by athletes is not recommended.

Nutrition. 2002 Jul-Aug;18(7-8):657-61

Growth hormone administration and exercise effects on muscle fiber type and diameter in moderately frail older people.

OBJECTIVE: Reduced muscle mass and strength are characteristic findings of growth hormone deficiency (GHD) and aging. We evaluated measures of muscle strength, muscle fiber type, and cross sectional area in response to treatment with recombinant human growth hormone (rhGH) with or without a structured resistance exercise program in frail older subjects. DESIGN: Placebo-controlled, randomized, double blind trial. SETTING: Outpatient clinical research center at an urban university-affiliated teaching hospital. PARTICIPANTS: Thirty-one consenting older subjects (mean age 71.3 +/- 4.5 years) recruited as a subset of a larger project evaluating rhGH and exercise in older people, who underwent 62 quadricep-muscle biopsies. INTERVENTION: Random assignment to a 6-month course of one of four protocols: rhGH administered subcutaneously daily at bedtime, rhGH and a structured resistance exercise program, structured resistance exercise with placebo injections, or placebo injections only. MEASUREMENTS: Muscle biopsy specimens were obtained from the vastus lateralis muscle. Isokinetic dynamometry strength tests were used to monitor individual progress and to adjust the weights used in the exercise program. Serum insulin-like growth factor-I (IGF-I) was measured and body composition was measured using a Hologic QDR 1000W dual X-ray densitometer. RESULTS: The administration of rhGH resulted in significant increase in circulating IGF-I levels in the individuals receiving rhGH treatment. Muscle strength increased significantly in both the rhGH/exercise (+55.6%, P =.0004) as well as the exercise alone (+47.8%, P =.0005) groups. There was a significant increase in the proportion of type 2 fibers between baseline and six months in the combined rhGH treated subjects versus those not receiving rhGH (P =.027). CONCLUSIONS: Our results are encouraging in that they suggest an effect of growth hormone on a specific aging-correlated deficit. IGF-I was increased by administrating rhGH and muscle strength was increased by exercise. The administration of rhGH to frail older individuals in this study resulted in significant changes in the proportions of fiber types. Whether changes in fiber cross-sectional area or absolute number occur with long-term growth hormone administration requires further study.

J Am Geriatr Soc. 2001 Jul;49(7):852-8

GH administration changes myosin heavy chain isoforms in skeletal muscle but does not augment muscle strength or hypertrophy, either alone or combined with resistance exercise training in healthy elderly men.

GH administration, either alone or combined with resistance exercise training (RT), has attracted interest as a means of increasing muscle mass and strength in the elderly. In the present study, 31 healthy, elderly men [age, 74 +/- 1 yr (mean +/- SEM)] were assigned to either RT [3 sessions/wk, 3-5 sets of 8-12 repetition maximum (RM)/session] + placebo (n = 8), RT + GH (n = 8), GH (n = 8), or placebo (n = 7) in a randomized, placebo-controlled, double-blinded (RT + placebo and RT + GH) or single-blinded (GH or placebo) design. Measurements of: 1) isokinetic quadriceps muscle strength; 2) quadriceps muscle power; 3) quadriceps muscle fiber type, size, and myosin heavy chain (MHC) composition; 4) quadriceps cross-sectional area (CSA) [nuclear magnetic resonance imaging (NMRI)]; 5) body composition (dual-energy x-ray absorptiometry scanning); and 6) GH-related serum markers were performed at baseline and after 12 wk. The final GH dose was 1.77 +/- 0.18 IU x d(-1) (approximately 7.2 +/- 0.8 microg x kg(-1) x d(-1)). GH alone had no effect on isokinetic quadriceps muscle strength, power, CSA, or fiber size. However, a substantial increase in MHC 2X isoform was observed with GH administration alone, and this may be regarded as a change into a more youthful MHC composition, possibly induced by the rejuvenating of systemic IGF-I levels. RT + placebo caused substantial increases in quadriceps isokinetic strength, power, and CSA; but these RT induced improvements were not further augmented by additional GH administration. In the RT + GH group, there was a significant decrease in MHC 1 and 2X isoforms, whereas MHC 2A increased. RT, therefore, seems to overrule the changes in MHC composition induced by GH administration alone. Changes in body composition confirmed previous reports of decreased fat mass, increased fat-free mass, and unchanged bone mineral content with GH administration. A high incidence of side effects was reported. Our results do not support a role for GH as a means of increasing muscle strength or mass, either alone or combined with RT, in healthy elderly men; although GH administration alone may induce changes in MHC composition.

J Clin Endocrinol Metab. 2002 Feb;87(2):513-23

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