Monday, February 15, 2010


Bodybuilders and other athletes have a continuing fascination with human growth hormone(HGH). HGH itself is nothing more than a long string of amino acids chained together in a specific sequence, thus making it a polypeptide hormone as opposed to steroid-based hormones, such as testosterone and estrogen, that are synthesized from a cholesterol precursor. The reputed anabolic and fat-mobilizing effects of HGH are what attracts bodybuilders to the idea of stimulating an increased HGH response in the body. Other uses for HGH include a suggested antiaging effect, based on the fact that HGH does decline with age in humans.

The surest route to increasing HGH levels in the body involves administering the hormone in injectable form. In fact, this is the only way to take straight HGH, since taking it in an oral or pill form would result in the hormone being broken down into its amino acid constituents. What you’d then have is an extremely expensive amino acid supplement. Commercial HGH injections are sold under various trade names, such as Protropin and Humatrope.

While the only approved medical use of HGH is to treat dwarfism, its antiaging and anabolic properties have led to it being used as a putative “fountain of youth” hormone. This use is based on studies conducted by Dr.Daniel Rudman in 1992, in which he gave HGH to a group of men with established GH deficiency (as confirmed by low plasma IGF-1 levels), leading to a reversal of various age-induced degenerative changes in the study subjects. These effects included increased muscle mass coupled with fat-losses. While it’s still difficult to get a doctor to write a prescription for GH injections, the proliferation of “anti-aging clinics” freely gives out the injections for a hefty price.

A more rational way to maximize HGH secretion would involve natural means, since the injectable forms are linked to long-term side effects, including carpel tunnel syndrome (an impingement of wrist nerves), water retention, and in some men, gynecomastia or male breast formation. The nutritional methods of promoting HGH secretion have generally involved various combinations of amino acids, such as arginine or ornithine, or lately, glutamine.

The amino acid route to increasing natural GH secretion has met with varying success. Providing arginine in 30-gram intravenous doses is indeed a reliable way of provoking a potent GH release, But taking it orally is more like a biochemical crap shoot. Attempting to duplicate a 30-gram intravenous dose orally would likely lead to nausea rather than higher levels of GH in the body.

The actual release of GH in the body depends on an interplay between various substances in the brain. GH itself is synthesized, stored, and released from the pituitary gland in the brain. What determines the release of GH from the pituitary gland is the balance between growth-hormone releasing hormone (GHRH) and somatostatin. GHRH promotes the release of GH, while somatostatin inhibits it. But it’s not as simple as it appears. Other brain chemicals enter the picture because they control the balance between the two primary GH control substances, GHRH and somatostatin.

These other brain chemicals that orchestrate GH release are called neurotransmitters. This is still an intense area of research for scientists, but we do know that various neurotransmitters are involved in GH release. These include dopamine, norepinephrine, GABA, and acetylcholine. Acetylcholine is particularly important in this regard, and many scientists think that this may be the most potent GH-promoting brain neurotransmitter.

Growth hormone release declines with advancing age, yet the production and actual synthesis of the hormone in the pituitary gland appears to be unaffected by aging. So what causes this slowdown in GH release in older people? Several theories are offered by scientists to explain the relative GH deficit with age. Two of the more interesting suggestions in this regard involve a age-related dominance of somatostatin over GHRH, leading to a blunted GH release. This effect also commonly occurs in people with higher body fat levels, explaining why such people show a blunted GH release. Excess free fatty acids in the blood will also blunt GH release, as will high blood glucose levels.

The second theory of why people over age 40 show lower GH levels involves a gradual decrease with age in the synthesis of acetylcholine activity in the brain. The extent of this impairment varies with individuals, with the most extreme cases involving a loss of cells that synthesize acetylcholine in the brain, or upgraded activity of the enzyme that degrades acetylcholine. These more extreme cases are typical seen with degenerative brain diseases, such as Alzheimer’s disease or multi-infarct dementias, with the latter usually the result of long-standing untreated high blood pressure leading to brain neuron destruction.

The loss of acetylcholine is especially devastating to brain functions involving memory and intelligence, since acetylcholine is the primary brain neurotransmitter in the hippocampus section of the brain, considered the site of memory storage, although other brain areas are also involved in the memory process. The link between acetylcholine and brain function is readily apparent in the proliferation of so-called smart drugs, more properly known as “nootropics.” Many of these drugs work by potentiating either the synthesis or release of acetylcholine in the brain. All the current drugs available to treat Alzheimer’s disease also work by attempting to increase existing levels of acetylcholine in the brain through inhibiting the enzyme that degrades acetylcholine.

Acetylcholine itself is nothing more than a combination of an acetyl group and the nutrient, choline. Until recently, choline, which occurs naturally in foods such as liver and egg yolk, was not considered an essential nutrient because it can be synthesized in the body from the amino acid methionine. However, recent research has reevaluated the need for choline, and its status has been upgraded to essential.

As noted, in the brain choline is enzymatically combined with an acetyl group to form acetylcholine. The acetyl group needed for this process can be obtained from other nutrients, such as the B-complex vitamin, pantothenic acid, or acetyl groups may also derive from acetyl L-carnitine, a specialized form of L-carnitine, itself an amino acid-derivative. The free access of acetyl L-carnitine through the protective blood-brain barrier makes it an especially useful acetyl donor for acetylcholine synthesis, explaining the studies that show it to be useful in the treatment of various cognitive or brain defects.

Would ingesting oral choline supplements also increase brain acetylcholine levels? Studies show mixed results when straight choline is provided orally. Choline itself doesn’t easily get past the blood-brain barrier, which exists to prevent the entrance of potentially noxious substances into the brain. Studies show that in older people, even choline ingested in food doesn’t get into the brain, though phosphatidylcholine, found in lecithin, does get more easily absorbed into the brain of older people.

Another problem with choline relates to intestinal absorption. Studies show that 50% of ingested choline is converted into betaine in the gut. However, in many people, especially those with a genetic predisposition, nearly all ingested oral choline is converted into methyl compounds, such as trimethylamine. This substance can lead to a disgusting body odor similar to rotting fish. The good news is that under such conditions, you will never have trouble getting a seat on the bus--though your social life won’t be anything to rave about, either.

What about taking granular or concentrated lecithin supplements? These supplements have been around for years, and do contain the desirable phosphatidylcholine form of choline, which is both absorbed easier than straight choline and isn’t prone to the rotting fish syndrome described earlier. However, upon contact with the intestinal lining, granular lecithin supplements are converted into lysolecithin. If the lysolecithin gets attached to a acetyl group, it becomes phosphatidylcholine. If it then gets deacetylated, it becomes Alpha-GPC, perhaps the most desirable form of choline available. If neither of these events occur, however, the lysolecithin can promote such undesirable effects as a destruction of red blood cells and gastrointestinal ulcer formation.

The interesting aspect of this is that lysolecithin is actually sold as a supplement. Lyso is often combined with either glutamine or prohormone supplements with the idea that lyso has the ability to “spread open” intestinal cells, which would have the effect of promoting an increased uptake of nutrients. This property of lysolecithin has never been shown in any studies. But considering that animal studies do show that lysolecithin does promote ulcer formation, which is a pathological opening in the intestinal wall, it’s not difficult to figure out where its reputation as a “spreading” agent came from.

As suggested, the most desirable form of supplemental choline would avoid all the potential problems discussed with the more common forms of choline supplements. In addition, such a improved choline supplement should have easy access through the protective blood-brain barrier to act as an efficient substrate for acetylcholine synthesis. One form of oral choline supplement does meet these standards: L-alpha glycerylphosphorylcholine, also known as choline alfoscerate or simply, alpha-GPC.

What is alpha-GPC and how does it work?

Alpha-GPC is classified as a phospholipid, since it’s composed of choline, glycerol, and phosphate. In the body, alpha-GPC acts as a storage form of choline within cells, and is thus found throughout the body. Alpha-GPC also occurs naturally in foods, such as animal or vegetable lecithins, cow’s milk, and cruciferous vegetables including cabbage, cauliflower, brusssel sprouts.

The primary role of alpha-GPC in the body is to serve as an immediate source of choline, which in turn is available for conversion into acetylcholine. As noted earlier, acetylcholine is a vital neurotransmitter in the brain, involved in arousal, learning, and sleep mechanisms. Acetylcholine is also the chemical secreted in the myoneural junctions found in skeletal muscle, which controls muscular contraction. Without acetylcholine, you couldn’t contract your muscles, which would make training a bit difficult--not to mention breathing.

Emerging research shows that under intense conditions, including severe exercise, the body’s synthesis of acetylcholine may not keep up with the needs of the body. This can lead to a relative deficit of acetylcholine, which may be apparent as muscular fatigue. Controversy exists over whether consuming supplemental choline may alleviate this deficit, although it is known to exist.

Several studies have shown that alpha-GPC, through improving acetylcholine synthesis in the brain, is capable of improving cognitive decline under both pathological, i.e., dementia, and normal conditions associated with aging. It does this by easily entering through the blood-brain barrier to act as a substrate for acetylcholine synthesis, and also by contributing to phospholipid synthesis, important for maintaining cellular membrane integrity.

The readily accessible choline provided by alpha-GPC also works in concert with other methyl donors, such as S-adenosyl-L-methionine (SAMe), folic acid, vitamin B12, and B6 to facilitate vital methyl reactions on the body. These reactions include nucleic acid synthesis, and at least 30 other vital biochemical reactions such as the synthesis in the liver of lipotropic factors needed to transport fat and cholesterol in the blood.

From a bodybuilding perspective, alpha-GPC may be one of the most effective nutrient GH boosters available. It increases growth hormone release through two known mechanisms: 1) Increased synthesis of acetylcholine, which inhibits the release of the GH-blunting somatostatin; 2) promotes increased secretion of GHRH through increased activity of various cellular second messenger systems that result in increased hormonal secretion--in this case, GHRH.

Alpha-GPC helps in the treatment of brain dementia by not only supplying readily available choline, but also by increasing the activity of enzymes involved in acetylcholine synthesis in the brain. As noted, a hallmark of dementia is the decreased activity of these same brain enzymes. Alpha-GPC also appears to promote the increased expression of nerve growth factor, which as the name implies is needed for both the building and repair of existing neurons or brain cells. In Italy, Alpha-GPC has been marketed as a treatment for brain dementia syndromes under various trade names, such as Gliatilan, Delecit, and Brazal.

Older people often have an imbalance between the two primary substances that control GH secretion, somatostain and GHRH. In such older people, somatostatin dominates, thus blunting GH release. This is thought to be the major reason that older people generally secrete less growth hormone. However, one study showed that providing Alpha-GPC to a group of older people led to a 3-fold increase in GH release. This effect was verified in several other studies.

When Alpha-GPC was compared to another easily absorbed form of oral choline supplement called citicholine, the Alpha-GPC proved superior in elevating free choline levels in the brain. Another study showed that alpha-GPC may be an effective therapeutic aid in the recovery from head injuries and strokes.

Alpha-GPC has a low side effect profile, with most side effects occurring when provided in parenteral (injectable) form. Some older people who’ve taken oral doses of alpha-GPC over 1,200 milligrams have had symptoms of heartburn, diarrhea, dizziness, skin rash, insomnia. Luckily, however, alpha-GPC isn’t subject to the dreaded “rotten fish” body odor effect seen with other oral choline supplements.

Based on published studies, alpha-GPC may help to correct various brain deficits involving acetylcholine, may boost and optimize growth hormone release, and may even improve athletic performance as a fast-acting source of choline.

. Ceda GP, et al. Alpha-GPC administration increases the GH responses to GHRH of young and elderly subjects.Hormone Metab Res 1992;24:119-121.
. DiPerri R, et al. A multicentre trial to evaluate the efficiency and tolerability of alpha-glycerylphosphorylcholine versus cytosine diphosphocholine in patients with vascular dementia.J Int Med Research 1991;19:330-41.

©,2013 Jerry Brainum. Any reprinting in any type of media, including electronic and foreign is expressly prohibited.

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