Body building, weight loss, and nutrition: Arginine, Nitric oxide and Human Growth Hormone

When do people need more arginine, or HGH?

Most of the time, your body produces enough arginine but sometimes it cannot make enough. The truth is that certain amino acids are Conditionally Essential amino acids. There are some situations that make it hard for the body to make as much as is needed. For example, trauma (damaging large amounts of tissue). Some examples of how trauma happens are: a heavy large muscle workout in a weight room, football practice, a bad sunburn, catching the flu or other infection, food poisoning, or having an unhealthy organ- kidneys, liver, intestine.

So what? Well if L-arginine gets low, then the blood vessels remain small, and organs get too little blood flow. That means not enough oxygen or glucose, and too much carbon dioxide, waste and lactic acid (makes muscles ache when muscle oxygen demand is more than the blood flow can supply). The red muscle fibers lack oxygen, so white fibers take over using glycolysis alone, shifting into emergency mode anaerobic respiration. These white fibers still make some energy. One glucose allows formation of two ATP's in oxygen-starved white fibers, but the normal pyruvic acid by-product cannot be processed further without oxygen, so instead it is fermented into lactic acid. Eventually, the acids start to close down the tiny valves(pre-capillary sphincters) that let blood into the smallest capillary channels, making things worse. Normally the liver would convert some acid, but only if the liver's blood supply had enough oxygen.

Exercise uses up nitric oxide

A big change happens when someone starts doing heavy exercise. Lots of adrenaline is produced, putting the body in a "fight or flight" condition, in which blood flow is diverted to the muscles, brain, heart and lungs, so it is drastically reduced to the intestines and kidneys. Losing blood flow, along with oxygen and glucose means a huge drop in the intestine and kidney supply of ATP energy molecules. As a result, this drastically lowers the total blood supply of arginine. Soon, the body runs out of nitric oxide and the blood vessels start getting smaller, cutting back energy in the muscles. This is one reason a sprint race is a short distance. More like a cheetah dash or quarter horse race, and less like a throughbred racehorse contest.

Faster Healing of Burns and Certain other Injuries with Arginine

After sunburn, the body needs extra amino acids to repair the skin, so the body’s nitrogen balance(at bottom of webage) can become negative, taking a long time to heal. Vacationers might do well to take arginine supplements after a burn for faster healing. Over the last dozen years, burns have been reported to heal more rapidly. Also, arginine helped surgical skin wounds to heal: the tissue contained more PMN (polymorphnuclear) white cells, collagen-forming fibroblasts contained more NO, and new skin was less likely to pull apart (more tensile strength). People with foot ulcers from diabetes, who used arginine healed in 6 months. Plus, the amount of protein leaking past their kidneys was only half as much. It is hard enough to take in enough dietary protein, when it is constantly leaking out of the body, especially as many mature folks have less stomach acid to digest the protein.

Arginine must be made using the body stores of L-citrulline. This is a two stage job using the enzyme argininosuccinate synthetase (ASS), then the enzyme argininosuccinate lyase (ASL). Plenty of energy is required ( 2 ATP energy molecules.) Lots of oxygen allows the cell’s energy plants, the mitochondria, to make plenty of ATP). Adenosine TriPhosphate has lots of electrons on it (stored electricity), and is like a tiny battery fully charged.

Compare that with exhausted tissue, or damaged tissue with low ATP, low oxygen and high acidity that cannot spare the energy to produce much arginine. Obviously muscle with lots of little tears has a partly wrecked blood supply and is swollen and congested, making it hard for blood to move through the area, like a traffic jam. Finally, arginine makes nitric oxide (sort of like nitrous for a racing engine).

Thus, the blood-starved, oxygen poor tissue cannot make nitric oxide, with almost no enlargement of blood vessels, so it takes longer for the tissue to recover and heal. Beside oxygen and glucose, the amino acids (basic bricks for building new proteins) are carried in by the blood vessels.

Blood vessels "know" when they are too small to do the job. Flow Modulated Dilation (FMD) in small vessels of muscle happens when fast moving blood causes nitric oxide release from the inside epithelial wall of vessels, causing them to enlarge and feed more blood to the muscle, by analogy, turbocharging the blood flow.

The bottom line is that when the body starts making lots of nitric oxide, the stores of raw material- citrulline, are also used up. It looks as if pure L-arginine is a more useful supplement. Left handed arginine is the one that matters in the body, as it fits the other chemicals used to make nitric oxide, just like a left shoe only fits on the left foot.

While the body is relaxed and well-nourished, most arginine is made by combined work of the intestines and kidneys: endothelial cells lining the small intestine produce citrulline( from dietary glutamine, ) then the proximal tubule cells of the kidney remove citrulline from the blood and convert it to arginine, which is returned to the blood.

So, intestinal disease can cause a citrulline deficit, leading to an arginine deficit. Plus, sick kidneys can't make enough arginine from citrulline.

After-exercise benefits of arginine- also boosts your own HGH

In one scientific study, the increase in HGH ( human growth hormone- up to 18.5 ug/l) lasted 90 to 120 minutes after a 30 second sprint exercise. About half (44-60%) of that peak was still reached after 6 weeks of endurance training.

Heavy exercise can increase HGH by 7 times over resting levels. Arginine alone (no exercise) can increase HGH by 2 times normal. However, the exercise only raises HGH for a few hours. This writer concludes that oral arginine given later in the exercise day would be expected to produce another spike in HGH. This is analogous to spiking blood levels of medication when given in multiple daily doses. It is further conjectured that the arginine is delivering a pseudo-signal of tissue injury causing HGH to be secreted as a way to augment healing. Arginine helps control division of newly growing cells, helps heal tissue tears and wounds in general, especially in bone, helps clean waste (such as ammonia) from the body, keep the immune system working properly, and helps release hormones.

Sampling of current literature on HGH stimulation by arginine

Arginine may stimulate the secretion of human growth hormone, and is used in growth hormone stimulation tests.

However, more recent research suggests that oral capsule or powder types of L-arginine, given before exercise, provide no HGH benefit- even though it increases plasma levels of L-arginine. This proves that oral arginine enters the blood, but that it will not produce HGH level increase more than those from exercise alone.

Fortunately, exercise has been reported to cause a large increase of HGH in the blood. It is reported that this increase in HGH will result in gains in muscle mass and strength, Additionally, the intravenous infusion of arginine in men and women created large increases in HGH (8- and 20-fold, respectively). Arginine has been shown to increase baseline HGH secretion by the mechanism of suppressing normal somatostatin release from the pituitary gland. HGH can be stimulated by "HGH-RH(releasing hormone) by clonidine and levodopa, as it is by arginine. A long acting HGH derivative, now in Phase II trials in adults and children, may be injected once every 7 days, thanks to addition of a Carboxy Terminal Peptide, according to Prolor Biotech. The same CTP technology was approved in the EU for a Merck product (FSH derivative).

How Exercise changes the body

Walking 10 minutes, 3 times a day produces increased muscle in legs, waist and upper arms. Even at rest, that extra muscle consumes more calories than fat, like a large V8 engine idling. (skeletal muscle =13.0 kcal/kg daily, adipose tissue (fat)=4.5 kcal/kg). Fat mostly stores calories. A daily walker with identical measurements as a couch potato has more dense calorie-burning muscle, and less fat. Muscle is about 15% denser than fat. The walker can eat more and weigh the same, or eat less and lose weight- However, the walker must absorb enough amino acids from her diet, to protect the muscle from being used for energy. Mature people usually have much less stomach acid and extract and absorb less digested amino acids, iron, minerals and B12 from their food. Low acid only partially forms stomach pepsin. Fortunately, eggs or egg whites are well digested even with a low-acid stomach, thanks to a second enzyme in people that works with low acidity. .Many younger people use acid blockers, with the same results. Amino acids supplements are another option, with the usual caution about normal dosing and health kidneys.

Arginine Cautions, and Warnings: pregnancy, delicate liver or kidney

Some is good, but more is not always better. Many studies on healthy people find 5 grams daily to be sufficient, which is taken as a scoop of powder, dissolved in liquid. Large amounts of arginine, or any amino acid can create problems for persons with kidney impairment, as they would be overloaded, just as in the case of earthquake victims or a fallen person who remains down for hours. The constant un-relieved weight makes pressure high enough to stop blood flow into the squashed muscle. Extensive tissue damage can happen from crushing injuries that kill muscle cells, breaking open the membranes and allowing large amounts of internal proteins and amino acids to enter the blood. So, normal doses and measuring are important. This is especially true for those with no spleen, as they cannot store up amino acids for gradual release as needed. For this and other reasons, adequate water intake is required.

HGH- Human Growth Hormone Cautions, safety question

There is a legal problem (potential criminal charges) with bringing it from outside the US without a prescription, and it is expensive here, providing a doctor would prescribe HGH despite the potential side effects: diabetes, heart disease, gigantism (acromegaly) and high blood pressure. Dosing must be individually tailored by the physician. Over time, larger doses may cause exaggerated growth of jaw, nose, lips, tongue, ears, hands feet and internal organs, plus "growing pains." Excessive amounts may cause the pituitary gland to enlarge, pressing on the optic nerve with vision reduction, or reducing LH and FSH, lowering testosterone levels or halting menses. One might take baseline photos and measurements, plot the changes over time, and modify doses to avoid unwanted effects. Lastly, a rare, unproven rumor is that if a person had a tumor, maybe it would grow faster if they were taking growth hormone. Many take it, and there is not much press about that risk. In the past, women using contraceptives with high doses of estrogen showed similar physical changes, with accelerated physical maturation. Normal growth does produces a general broadening and thickening in most people, probably due to the long term influence of natural growth hormone.

Healthy people need about 1 gram per kilogram of lean body weight. People who work hard use more (cane sugar workers use 10,000 calories per day, a person with tetanus infection about the same as all large muscles are in spasm). More is needed by growing kids, people recovering from extensive sunburns, food poisoning, professional bodybuilders and athletes and the like. People who cannot digest well (low stomach acid), or have leaky kidneys (proteinuria) need more, while those with sick kidneys must restrict protein intake. Vegetarians must be smart about combining different sources to get all the essential amino acids

Anti-aging and Rejuvenation

Can you take a reasonable and effective dose of HGH without getting disfigurement and enlarged nose, ears, jaw and other organs? One clue is to ask people to give testimonials, then judge for yourself.

Alba-Roth J, Müller O, Schopohl J, von Werder K (1988). "Arginine stimulates growth hormone secretion by suppressing endogenous somatostatin secretion". J Clin Endocrinol Metab 67 (6): 1186–9

Andrew, P.J.; Myer, B. (August 15 1999). "Enzymatic function of nitric oxide synthases". Cardiovascular Research 43 (3): 521–531 REVIEW

Chromiak J and Antonio J.Use of amino acids as growth hormone-releasing agents by athletes. Nutrition 18: 657–661, 2002

Collier, S.R., Collins, E., and Kanaley, J.A., J. Applied Physiology 10, 1152 2006 Oral arginine attenuates the growth hormone response to resistance exercise

Cen Y, Luo X, Ren L, Liu X, Hua Xi Yi Ke Da Xue Xue Bao, 1999 Jun;30(2):198-201.

Debats, I.B.J.G., T.G.A.M. Wolfs, J.P.M. Cleutjens, and C.J. Peutz- Kootstra. "Role of Arginine in Superficial Wound Healing in Man." Web. 12 Dec. 2011. <http://www.ncbi.nlm.nih.gov/pubmed/19638312>}.

Kanaley JA, Weatherup-Dentes MM, Jaynes EB, and Hartman ML. Obesity attenuates the growth hormone response to exercise. J Clin Endocrinol Metab 84: 3156–3161, 1999.

Kanaley JA, Weltman JY, Pieper KS, Weltman A, and Hartman ML. Cortisol and growth hormone responses to exercise at different times of day. J Clin Endocrinol Metab 86: 2881–2889, 2001.

Low LC (1991). "Growth hormone-releasing hormone: clinical studies and therapeutic aspects". Neuroendocrinology 53 Suppl 1: 37–40.

Patrizio P, Masselli L., Annalisa Pipicelli A., and Barber A., "Effect of a Nutritional Supplement Used for Diabetic Foot Ulcers on Microalbuminuria." Mediterranian Journal of Nutrition Metabolism 9 (2011).

Peng, X., H. Yan, Z. You, P. Wang, and S. Wang. "Glutamine Granule- supplemented Enteral Nutrition Maintains Immunological Function in }Severely Burned Patients." Burns 32.5 (2006): 589-93.

Pritzlaff CJ, Wideman L, Weltman JY, Abbott RD, Gutgesell ME, Hartman ML, Veldhuis JD, and Weltman A. Impact of acute exercise intensity on pulsatile growth hormone release in men. J Appl Physiol 87: 498–504, 1999

Stechmiller, J.K.; et al. (February 2005). "Arginine supplementation and wound healing". Nutrition in Clinical Practice 20 (13): 52–61 REVIEW.

Stokes KA, Nevell ME, Hall GM, Lakomy HK, J Sports Sci . 2002 Jun;20(6):487-94.

The time course of the human growth hormone response to a 6 s and a 30 s cycle ergometer sprint.

The Mayo Clinic, Arginine (monograph), accessed 11-28-2011, http://www.mayoclinic.com/health/l-arginine/NS_patient-arginine

U.S.National Library of Medicine (September 2009). Growth hormone stimulation test.

Witte, M.B.; Barbul, A (Nov-Dec 2003). "Arginine physiology and its implication for wound healing". Wound Repair and Regeneration 11 (6): 419–423 REVIEW.

Tapiero, H.; et al. (November 2002). "L-Arginine". Biomedicine and Pharmacotherapy 56 (9): 439–445 REVIEW.

The Mayo Clinic, Arginine (monograph), accessed 11-28-2011, http://www.mayoclinic.com/health/l-arginine/NS_patient-arginine

Weltman JY, Weltman A, van der Heijden M, Janssen Y, Metzger D, Veldhuis JD, Keizer HA, and Rogol AD. Effect of intensity of exercise on 24-hour growth hormone release. Med Sci Sports Exerc 26: S37, 1994.

Wideman L, Weltman JY, Shah N, Story S, Veldhuis JD, and Weltman A. Effects of gender on exercise-induced growth hormone release. J Appl Physiol 87: 1154–1162, 1999