Are Growth Hormones And Growth Factors Myth Or Muscle?

Does a formula exist that can stimulate GH-releasing hormones, mildly increase acetylcholine levels and decrease somastatin levels in order to maximise GH release? Thomas Incledon investigates.

Bodybuilders and athletes are known to use growth hormone (GH) and insulin-like growth factor-1 (IGF-1), despite these agents being banned by most international sports federations, including the International Olympic Committee (IOC). Since 1990, anti-ageing adherents have spiked the use of these ingredients. Reports of gains in lean body mass and strength with concurrent losses in fat mass have created even more interest amongst the general public.

Human growth hormone is a protein hormone secreted into the blood by the anterior pituitary gland. It is the major hormone responsible for growth after birth in humans and acts on a variety of tissues including bone, cartilage and muscle. Two hormones, produced in the hypothalamus, are primarily responsible for modulating the secretion of GH: somastatin and growth hormone-releasing hormone (GHRH). GH, in turn, stimulates the liver to produce IGF-1. This is referred to as the GH/IGF-1 axis. Once produced, IGF-1 travels in the blood and can exert anabolic actions on a variety of tissues.

Exercise, deep sleep, hypoglycaemia, fasting, a high-protein meal and the infusion of amino acids can stimulate GH. Supplement companies, sensing the public demand for GH and IGF-1, have released many products that allegedly elevate these anabolic hormones. Unfortunately, claims are often made while drawing the reader's attention to studies on GH instead of research that involves the GH-releasing products directly. In most cases, supplements alleged to elevate GH and IGF-1 do not hold up to scientific scrutiny.

The following assesses some ingredients currently being studied or marketed for their potential to elevate GH levels.

Amino Acids
Arginine is a popular GH releaser, primarily based off infusion studies. Some studies on oral arginine supplementation show no effects on GH or IGF-1 levels,^1,2,3 while others do show an increase in GH and/or IGF-1 levels.^2,4,5,6 Differences in these results may be because of differences in dosages, delivery methods (eg, capsules vs liquid drink), type of arginine (arginine hydrochloride vs arginine aspartate), the subjects (age or training status) and calorie intakes of the subjects. Most studies also used small numbers of subjects, making it difficult to reliably detect effects.

Since most people looking to boost GH and/or IGF-1 levels are older, it makes sense to see if there is an effect on GH/IGF-1 release for these subjects. Research on 30 elderly people administered 17g free arginine from arginine aspartate found that IGF-1 and nitrogen balance increased significantly (2.0 ± 0.41g) over 15 people taking a placebo (0.11 ± 0.47g).⁶

From this simple review, two other findings seem solid: Arginine ingestion by itself shows greater success with dosages higher than 8g/day arginine, and arginine aspartate may be preferred to arginine hydrochloride.

Lysine has been shown to increase GH levels, at least via injections or infusions. However, research is lacking on the effects of lysine administered orally. Only one published study looked at oral lysine by itself (without other amino acids).⁷ In it, 1,200mg lysine hydrochloride elevated GH three times over baseline. However, the researchers used only eight subjects and did not describe their statistical techniques. Interpretation of this information is difficult and by itself does not support the use of lysine as a GH stimulator.

Ornithine can be synthesised in the body from the amino acids arginine or citrulline. It became a popular dietary supplement because of claims that it could stimulate GH and/or insulin. Ornithine is often taken as a salt consisting of two molecules of ornithine and one molecule of alpha-keto-glutarate. This supplement is known as ornithine alpha-ketoglutarate (OKG). OKG has been successfully used in clinical settings to treat burn, trauma, malnourished and surgical patients.⁸ In most cases, OKG was infused directly into the blood or into the GI tract.⁸ These same studies showed that OKG decreased muscle protein catabolism, promoted wound healing and/or increased muscle protein synthesis.⁸ One possible mechanism is that OKG increased GH levels in these patients.⁸ Oral ornithine taken separately from alpha-keto glutarate found no effect on GH levels.⁹

Tryptophan, unlike most other amino acids, has been shown to elevate GH levels in healthy subjects.¹⁰ In normal patients, 10g tryptophan increased GH levels, as well as levels of glucose, insulin and glucagon.¹¹ Tryptophan also lowered cortisol levels, although the response was quite variable. Since tryptophan sales are prohibited in many countries, companies have since started selling a similar compound, 5-hydroxytryptophan (5-HTP). GH release research on the effects of oral doses of 5-HTP is lacking. Most studies involve intravenous administration and indicate that 5-HTP can increase GH, but unfortunately, also cortisol and prolactin. (Elevating cortisol and prolactin may counter the effects of GH.) Taking 5-HTP for GH does not appear to be a prudent decision at this time.

Combinations of amino acids are used by supplement companies to maximise the effects of single supplements that have been shown to exert a physiological effect. While synergism among different amino acids is possible in the case of GH release, amino acids can travel many different biochemical pathways, so synergism is not guaranteed. Fortunately, several studies exist on combinations of various amino acids.

One of the first studies compared the effects of 1,200mg arginine-2-pyrrolidone-5-carboxylate plus 1,200mg lysine hydrochloride vs each separately vs 2,400mg arginine-2-pyrrolidone-5-carboxylate to stimulate GH release.¹⁶ The results indicated 1,200mg arginine-2-pyrrolidone-5-carboxylate plus 1,200mg lysine hydrochloride was better than either amino acid separately or 2,400mg arginine-2-pyrrolidone-5-carboxylate at stimulating GH in 15 male volunteers.⁷ This study failed to report the statistical methods used, so the value of the results is debatable. One point to consider is that researchers used a unique form of arginine and not L-arginine (the free-form version of the amino acid).

Another study tested the effects of three commercially available oral GH-releasing products.¹¹ Product A contained 2.4g L-arginine and L-lysine. Product B contained 1.1g L-ornithine, 750mg tyrosine, 750mg pyridoxine hydrochloride (vitamin B6) and 125mg ascorbic acid. Product C was 20g Bovril that contained 7.8g protein (438mg arginine, 412mg lysine, 362mg leucine, 312mg valine, 238mg phenylalanine, 200mg isoleucine) and 580mg carbohydrate. None of the supplements worked as well as GHRH, which was also used for comparison purposes and as evidence that each subject had a functional pituitary relative to GH release.

In competitive weightlifters, 1g each of L-arginine, L-ornithine and L-lysine taken once after lunch and again after dinner did not affect GH levels.¹³ In another study, 1,500mg L-arginine and 1,500mg L-lysine stimulated an increase in GH release at rest. In these 16 weight-trained men, the same mixture did not further increase the elevations in GH due to exercise.¹⁴ Other low-dose studies using branched-chain amino acids also found no effect on GH release.^19,20,15,16 In contrast, 20g glutamate arginine salts increased GH and lowered cortisol in highly trained cyclists.¹⁷

Athletes are not the only group that researchers have studied using amino acid mixtures. Older men who ingested 3g L-arginine plus 3g L-lysine or placebo capsules twice daily for 14 days did not have significantly altered GHRH-stimulated GH levels or serum IGF-I.⁹

Overall, the data point to variable effects of amino acid mixtures for raising GH levels in physically active people. As with some of the individual amino acids, the trend appears to be that fairly high doses are needed to have an effect.

It's All In The Brain
Glycerylphosphorylcholine (GPC) in-creases acetylcholine levels in the brains of rats. An increase in this neurotransmitter inhibits somatostatin and could indirectly elevate GH. GPC also is a precursor for the synthesis of phosphatidylcholine, which has been speculated to lead to changes in the cell membranes of anterior pituitary cells that enhance the stimulatory effect of GHRH on GH release.

In a 1992 study using human subjects, GPC and GHRH were shown to stimulate GH in both younger and older subjects.¹⁸ When GPC and GHRH were combined, the resulting increase in GH levels was greater than with either agent alone. Given this evidence, GPC looks like a viable supplement. There are a few problem areas, though. By itself, GPC did not increase GH levels very much. Also, the 1,000mg of GPC was injected. While injectable GPC enhanced the effect of GHRH on stimulating GH, there are no published studies on oral GPC and GH release. However, unpublished work in our lab indicates that oral GPC will not stimulate GH release unless taken prior to exercise or in conjunction with other supplements.

Choline deficiency leads to the formation of fat deposits in the liver. The term lipotropic was then coined to describe choline and other substances that prevented fat deposition in the liver. Unfortunately, companies convinced the general public that 'lipotropic' meant agents would accelerate fat loss. This is hardly the case.

Recently, some supplement companies have made claims that choline supplementation would increase acetylcholine production and lead to elevated GH levels. Research using rats indicates that choline does increase acetylcholine levels and that this leads to increased prolactin levels.¹⁹However, in one human study, 14g choline in four divided doses had only transient effects on acetylcholine levels.²⁰

Other Agents
Ascorbic acid has been touted to elevate GH/IGF-1 levels. There is no direct evidence that this occurs in humans. In studies using cultured cells, vitamin C has been shown to act as a cofactor to suppress prolactin levels and elevate dopamine levels.^12,21 Since dopamine can stimulate GH release, some companies may have figured that adding vitamin C to their formula will help. There doesn't appear to be any negatives to having vitamin C in the mix; there is just no support for its use at this time.

Colostrum, sold as a nutritional supplement, is derived from cows' milk. It contains predominantly casein and whey protein. The whey protein includes immun-oglobulins IgG, IgA and IgM, growth factors (IGF-1), lactoferrin, lysozyme, lactoperoxidase, serum albumin, alpha-lactalbumin and beta-lactoglobulin. The detection of IGF-1 and other growth factors led to it being banned in international sports. Endocrinologist Peter Sonksen, studying human growth hormone on behalf of the International Olympic Committee (IOC), indicated that IGF-1 is broken down and inactivated when ingested orally.²² There is, therefore, no mechanism by which ingested IGF-1 could act directly on the body as a growth factor. This is consistent with abstracts that have been presented at international conferences indicating that colostrum can increase performance, yet serum IGF-1 levels did not differ between colostrum and placebo groups.^23,24 It is possible that the gains in lean body mass and performance are secondary to improvements in immune function. Despite the research in this area, the IOC has banned colostrum simply because it contains IGF-1, a prohibited substance.

Colostrum is slowly building up evidence that it can increase lean body mass in athletes. The only disadvantage with colostrum so far, outside of Olympic competition, is that the doses are about 60g/day. This may be cost prohibitive.

St John's wort (Hypericum perforatum), in addition to its efficacy in mild forms of depression, can also stimulate GH release.²⁵ Twelve healthy male volunteers who ingested a single dose of a methanolic extract experienced a significant increase in GH and a significant decrease in prolactin levels, while cortisol levels were unchanged.

Miscellaneous agents have been touted to increase GH levels but with absolutely no proof this can occur in cells, animals or people. Among these are chromium poly-nicotinate, Ginkgo biloba, inosine, kelp, licorice, Macuna pruriens, monosodium glutamate (MSG), Muira puama, naringenin, niacin, selenium, Shilajit and Tribulus terrestris.

A World Of Potential
After looking at many studies on various agents that stimulate GH release, some clear points can be made to describe the ideal GH-releasing agent. First, it has to cross the GI tract intact or break down into bioactive components. The ideal product needs to have components that can stimulate GHRH, mildly increase acetylcholine levels and decrease somastatin levels in order to maximise GH release. All this has to be done without increasing prolactin or cortisol or suppressing other important hormones like testosterone or thyroid hormones. So far, nothing on the market can accomplish this menu of actions, but the goal seems worth pursuing and studies so far are sufficiently tantalizing that the near future of research will likely be quite lively.

References

1. Corpas E, et al. Oral arginine-lysine does not increase growth hormone or insulin-like growth factor-I in old men. J Gerontology 1993;48(4):128-33.

2. Moore T, et al. Growth hormone response to oral arginine supplementation. Med Sci Sports Exer 1998;30(5):S18,Abstr 98.

3. Walberg-Rankin J. The effect of oral arginine during energy restriction in male weight trainers. J Strength Condit Res 1994;8(3):170-7.

4. Besset A, et al. Increase in sleep related GH and Prl secretion after chronic arginine aspartate administration in man. Acta Endocrinol 1982;99(1):18-23.

5. Colombani PC, et al. Chronic arginine aspartate supplementation in runners reduces total plasma amino acid level at rest and during a marathon run. Euro J Nutr 1999;38(6):263-70.

6. Hurson M, et al. Metabolic effects of arginine in a healthy elderly population. JPEN J Parenter Enteral Nutr 1995 May-Jun;19(3):227-30.

7. Isidori A, et al. A study of growth hormone release in man after oral administration of amino acids. Curr Med Res Opin 1981;7(7):475-81.

8. Cynober L. Ornithine alpha-ketoglutarate in nutritional support. Nutrition 1991;7(5):313-22.

9. Bucci L, et al. Ornithine ingestion and growth hormone release in bodybuilders. Nutr Res 1990;10:239-45.

10. Hedo JA, et al. Elevation of plasma glucose and glucagon after tryptophan ingestion in man. Metab: Clin Exper 1977;26(10):1131-44.

11. Lambert MI, et al. Failure of commercial oral amino acid supplements to increase serum growth hormone concentrations in male body-builders. Inter J Sport Nutr 1993;3(3):298-305.

12. Shin SH, et al. Dopamine requires ascorbic acid to be the prolactin release-inhibiting factor. Am J Physiol 1997;273(3 Pt 1):E593-8.

13. Fogelholm GM, et al. Low-dose amino acid supplementation: no effects on serum human growth hormone and insulin in male weightlifters. Inter J Sport Nutr 1993;3(3):290-7.

14. Suminski RR, et al. Acute effect of amino acid ingestion and resistance exercise on plasma growth hormone concentration in young men. Inter J Sport Nutr 1997;7(1):48-60.

15. Bigard AX, et al. Branched-chain amino acid supplementation during repeated prolonged skiing exercises at altitude. Inter J Sport Nutr 1996;6(3):295-306.

16. Fry AC, et al. Endocrine and performance responses to high volume training and amino acid supplementation in elite junior weightlifters. Inter J Sport Nutr 1993;3(3):306-22.

17. Eto B, et al. Glutamate-arginine salts and hormonal responses to exercise. Arch Physiol Biochem 1995;103(2):160-4.

18. Ceda G, et al. alpha-Glycerylphosphorylcholine administration increases the GH responses to GHRH of young and elderly subjects. Hormone Metabolic Res 1992;24(3):119-21.

19. Gurun MS, et al. Centrally administered choline increases plasma prolactin levels in conscious rats. Neurosci Lett 1997;232(2):79-82.

20. Mohs RC, Davis KL. Interaction of choline and scopolamine in human memory. Life Sci 1985;37(2):193-7.

21. Shin SH, Stirling R. Ascorbic acid potentiates the inhibitory effect of dopamine on prolactin release in primary cultured rat pituitary cells. J Endocrinol 1988;118(2):287-94.

22. Australian Sports Drug Agency, Drugs in Sport Update (Vol 2, issue 3), 1998, ASDA Newsletters.

23. Buckley JD, et al. Oral supplementation with bovine colostrum (IntactÔ ) improves rowing performance in elite female rowers. In: 5th IOC World Congress on Sport Sciences 1999. Sydney, Australia.

24. Buckley J, et al. Effect of an oral bovine colostrum supplement (intact TM) on running performance. Abstract in: Australian Conference of Science and Medicine in Sport 1998. Adelaide Convention Centre, Adelaide: Canberra, Sports Medicine Australia.

25. Franklin M, et al. Neuroendocrine evidence for dopaminergic actions of hypericum extract (LI 160) in healthy volunteers. Biol Psychiat 1999;46(4):581-4.

Thomas Incledon is a scientist, nutritionist, writer and athlete. He is director of performance research and nutrition at Athletes' Performance—a world-class training facility for athletes.
Email: www.thomasincledon.com