Life Extension Magazine March 2009
Enhancing Growth Hormone Naturally
During our youth, abundant levels of growth hormone (GH) promote an energetic physiology essential for healthy metabolism and an optimal ratio of lean muscle tissue to body fat.
By the time we reach middle age, however, levels of essential hormones such as testosterone and DHEA decline, while age-associated decreases in muscle mass and increases in body fat become noticeable.
Furthermore, research shows that in aging men, the amplitude of pulsatile GH release (the magnitude of the GH pulse) declines by 50% every seven years after 18-25 years of age.1
Exogenous subcutaneous injection of human recombinant growth hormone is expensive and still controversial. Fortunately, studies have shown that there are strategies that may naturally boost the endogenous production of growth hormone and thus provide a viable alternative to expensive injections. In particular, exciting research suggests that the growth hormone-blocker somatostatin can itself be inhibited with a nutrient called CDP-choline, thus slowing the rate at which growth hormone declines.
Naturally supporting the body’s own endogenous growth hormone production using targeted lifestyle and nutritional strategies may provide a safe method of harnessing the vigor and vitality associated with youthful growth hormone levels.
Growth Hormone Basics
Growth hormone (GH), also known as somatotropin, is a peptide hormone produced by the anterior lobe of the pituitary gland. Growth hormone secretion occurs in a pulsatile fashion following a circadian (daily) rhythm, which is controlled by a central area of the brain known as the hypothalamus. The hypothalamus regulates serum GH levels through the release of two functionally opposing hormones: growth hormone-releasing hormone stimulates GH release, while somatotropin release-inhibiting hormone reduces it.
Endogenous (made within the body) GH exerts its actions by binding directly to specific receptors on target tissues including muscle, connective tissue (tendons, ligaments, bone, and fat), as well as every major organ. Growth hormone also works indirectly by stimulating liver cells to produce and secrete polypeptide molecules known as somatomedins, the best studied of which is insulin-like growth factor-1 (IGF-1). Like GH, IGF-1 boasts receptors throughout the body and serves many functions. Together, GH and IGF-1 play influential roles in virtually every system—from muscle, bone, and connective tissue growth and repair, to the selective regulation of various aspects of metabolism, as well as helping maintain normal brain function and cardiac health.
However, GH secretion falls precipitously with advancing age. Furthermore, research shows that in aging men, the amplitude of pulsatile GH release (the magnitude of the GH pulse) declines by 50% every seven years after 18-25 years of age.1
This decline is also mirrored by diminishing IGF-1 levels. The decrease in the secretory activity of the GH/IGF-1 axis, commonly referred to as somatopause, correlates with a number of undesirable symptoms generally associated with aging. Most notably, diminishing GH/IGF-1 has been shown to reflect disordered sleeping patterns, bone frailty, increases in central adiposity (fat accumulation around the middle of the body including the abdomen), as well as decreases in cognition and muscle mass, strength, and conditioning.2-9
Is Synthetic GH Replacement Therapy Beneficial?
Since the decline of GH correlates with the onset of aging-related symptoms, scientists have investigated whether synthetic GH replacement may prove beneficial.
Some of the most compelling evidence that somatopause may respond favorably to synthetic GH replacement therapy comes from investigations involving patients suffering from total or near total absence of GH secretion as a result of pituitary disease. Without treatment, adults suffering from pituitary disease are both physically and psychologically less healthy than their age-matched peers, demonstrating significantly reduced muscle mass, bone density, exercise performance, thyroid function, and collagen production, with a concurrent escalation of central fat mass (especially fat accumulation in the abdominal organs) and insulin resistance, as well as an increased risk for cerebrovascular accidents (strokes) and cardiac events.10 Psychologically, they tend to experience more emotional lability (abrupt changes in mood in response to everyday events), depression, and social isolation,11-14 and their average life expectancy is measurably reduced.15,16
In the late 1980s and early 1990s, GH replacement studies in adults with poor pituitary function were designed with the goal of restoring normal GH levels. However, the doses used in these chronically GH-deficient individuals produced IGF-1 concentrations that greatly exceeded the expected range, resulting in unacceptably high rates of adverse reactions. In subsequent work, with GH doses adjusted to produce age-appropriate IGF-1 concentrations, negative side effects were largely eliminated or reduced to tolerable levels. Study subjects demonstrated significant and sustained improvements in body composition, physical performance, bone density, and psychological well-being, as well as substantial reductions in biomarkers for cardiac disease.17-24
In light of these results, researchers felt cautiously optimistic that men and women with partial GH deficiency secondary to advancing age might also reap the benefits of GH replacement therapy. However, following a landmark study by Rudman and colleagues in 1990, which provided the first evidence that GH supplementation in the elderly could diminish—and potentially reverse—some of the physical symptoms associated with somatopause,25 exogenous GH therapy has been controversial10,26-37 and associated with high costs.
Fortunately, scientists are discovering that the benefits of youthful GH levels can also be harnessed safely by naturally increasing the body’s own hormone levels with the right nutrients and lifestyle practices.
Nutritional Strategies for Optimizing GH
Nutritional strategies can offer targeted support for individuals seeking to enhance their endogenous production of GH. Such nutrients may work either by directly enhancing GH release from the pituitary gland or by enhancing the efficacy of sleep or exercise, the two activities that best support GH secretion.
CDP-Choline Boosts GH, Supports Brain Health
A growing body of research suggests that the compound cytidine-5’-diphosphate choline (CDP-choline) may boost GH secretion while conferring an array of brain health benefits for aging adults.
As adults grow older, GH secretion from the anterior pituitary gland declines precipitously. Exciting scientific research suggests that decreased GH release results in part from increasing levels of somatostatin with aging. Somatostatin produced by the hypothalamus inhibits the release of GH from the anterior pituitary.
This innovative idea has led researchers to search for agents that inhibit somatostatin and thus potentially increase the release of GH. Experimental research shows that treatment with cholinergic agonists increases GH release by inhibiting somatostatin release from the hypothalamus.38
These findings were soon supported by a human study. This compelling investigation showed that administration of CDP-choline to healthy elderly adults resulted in a dramatic four-fold increase in serum GH levels, compared with baseline values.39 These findings build upon evidence from an earlier study showing that CDP-choline administration in healthy men increased serum GH levels.40
In addition to its effects on GH release, CDP-choline acts through other mechanisms to promote brain cell integrity and health. CDP choline acts as an intermediate in the synthesis of neuronal membranes, promoting healthy brain cell membrane structure and function. CDP-choline counteracts the deposition of amyloid-beta, a pathological protein found in the brains of patients with Alzheimer’s disease. Human research suggests that CDP-choline supports release of the essential neurotransmitter norepinephrine, while animal studies show that CDP-choline increases brain levels of key neurotransmitters including dopamine and serotonin.41
In clinical trials, CDP-choline has shown promise in improving age-associated memory impairment, boosting cognitive performance in the early stages of Alzheimer’s disease, and supporting recovery from both ischemic and hemorrhagic stroke.41
These findings combine to suggest a powerful role for CDP-choline in supporting healthy GH levels and in optimizing brain health with aging.
Protein, Amino Acids Enhance GH Release, Lean Body Mass
Protein (especially protein derived from animal sources) provides important essential and conditionally essential amino acids known to assist endogenous GH secretion.42-44 An added bonus: these same essential amino acids are vital for supporting muscle growth and recovery in active men and women.
The most abundant amino acid in the body is glutamine. Consuming even a relatively small amount of glutamine (2,000 mg) has been shown to increase plasma GH levels.45 Glutamine has also been shown to help preserve muscle mass in individuals vulnerable to losing lean body mass due to inactivity following surgery.46 This suggests that glutamine may provide important benefits in maintaining lean body tissue.
Like glutamine, oral intake of the amino acid arginine increases the release of GH at rest. The combination of arginine intake with exercise produces even greater increases in GH levels.47 In addition to its anabolic (tissue-building) effects,48 ornithine alpha-ketoglutarate has also been reported to increase GH secretion.49
Compelling evidence demonstrates that the combination of arginine and ornithine augments the results of resistance training by helping to increase lean body mass and strength. The investigation also indicated that oral doses as relatively small as 1 gram of ornithine and arginine were effective in enhancing strength and lean tissue mass.50