A combination of arginine, citrulline, and certain
antioxidants are shown to help preserve physical fitness
Exercise Capacity Decline
By Will Block
n the development of life on the planet, the amino acid arginine has proven to be invaluable. This is because its special chemistry and metabolism is crucial for the evolution of the metabolic and structural features of animals. Arginine and its derivative compounds act in muscle tissue as a major reserve for adenosine triphosphate (ATP)—the “molecular unit of currency” of intracellular energy transfer—and as a regulatory sink for phosphate. That’s because, after its addition and utilization, the removal of phosphate from cellular protein is a pivotal strategy in the regulation of metabolic processes.
In animals less complex than ourselves, the metabolism of arginine has been extended to produce urea, initially as an osmotic regulator, and subsequently as a means for terrestrial animals to excrete surplus nitrogen. Arginine is broken down by the enzyme arginase to produce urea and another amino acid, ornithine, which is metabolized to form important polyamines, and also proline. For maximum rates of growth, cells require polyamines. Proline (along with hydroxyproline) is an essential constituent of collagen and related proteins. What we see in animals as metabolic variations (e.g., synthesis of urea, creatine and polyamines) are exaggerations of enzymic steps that occurred early in evolutionary history. The change from phosphoarginine to phosphocreatine may have been an accommodating step in the development of the vertebrates which are rich in connective tissue. In other words, without the evolutionary development of arginine, we would not exist.
The history of arginine starts way back in 1886 when a Swiss chemist named Ernst Schultze isolated it from a seedling extract of the legume, lupin. Following that, not much happened until 1932, when scientists at the University of Freiburg, Germany discovered the urea cycle. This series of cellular reactions occurs in our bodies when ammonia is converted into a less toxic substance called urea. We then excrete urea out of our bodies through urination. Arginine was found to have a significant role in the creation of urea, showing that it’s needed to help detoxify our bodies. Then, in 1939, it was proven that arginine aided in the creation of creatine, a nitrogenous organic acid that occurs naturally in vertebrates—including ourselves—and helps to supply energy to muscle. This has led to the widespread use of creatine to help preserve and build muscles. Creatine is useful also as an osmolyte, to protect against amyloid in the brain and other types of protein aggregation throughout the body.
Long-term Use of Arginine for Erectile Effects
Goes On and On
A very recent study using arginine as a significant part of a nutritional supplement—designed to help men achieve erections—has found that it apparently does not lose efficacy, even when used for several months. This new research was funded by the supplement’s maker. A serving of the supplement contains the amino acid L-arginine, L-aspartate, and pine bark extract, as a proprietary blend (720 mg/serving).*
Three additional studies lasting up to six weeks have shown that the formulation improves erectile function in men with mild to moderate erectile problems, improves fertility, increases e-NOS in spermatozoa, significantly raises testosterone levels in blood, and lowers both cholesterol levels and blood pressure. Other studies have shown these benefits for arginine use, alone or in other formulations.
The goal of the supplement maker’s study was to determine if the formulation could help men (who took it for up to six months), without a drop-off in benefits. Researchers gave 124 men (aged 30–50 years) two doses of the formulation twice daily (total of 2,840 mg), or an inactive placebo, for six months. The treated problems—erectile dysfunction—were thought to be related to untreated hypertension (high blood pressure). Both treated and placebo groups had moderately high blood pressure and total cholesterol levels on the verge of hypercholesterolemia. None had diabetes. In in addition to taking the supplement or placebo pills, the subjects were instructed to lose weight, cut down on their salt intake, and exercise.
At the beginning of the study, the researchers scored the men in both groups an average of 15 on a 30-point standardized score measuring erectile function, indicating mild to moderate erectile dysfunction. After three months, average scores were 25 for the treated group (a 25–30 point score signifies no dysfunction) and 19 in the placebo group (higher than at the start, but still mild dysfunction). However, at six months, average scores were 27 for the treated group, yet still 19 for the placebo group.
Importantly, the subjects in the treated group also had better sexual desire, orgasmic function, intercourse satisfaction, and overall satisfaction. These were judged to be significant, yet this was not so with the placebo group.
As with other studies using arginine in this regard, erectile dysfunction was tied to poor vascular function—a man’s blood vessels need to be in good working order to achieve erection. And furthermore, bad heart health predicts loss of erectile function. Arginine and aspartate work by helping to restore and even enhance the ability of the blood vessels to produce nitric oxide, which dilated blood vessels through smooth muscle relaxation. On the other hand, Viagra works through a similar mechanism, but later in the process, by amplifying nitric oxide’s effects. Viagra does not increase nitric oxide production.
The pine bark extract used in the study exerts antioxidant effects, which are thought to improve spermatozoa function. Some research suggests that it may enhance production of nitric oxide. No studies have shown any direct effect on erectile dysfunction.
- Ledda A, Belcaro G, Cesarone MR, Dugall M, Schönlau F. Investigation of a complex plant extract for mild to moderate erectile dysfunction in a randomized, double-blind, placebo-controlled, parallel-arm study. BJU Int 2010 Feb 22. [Epub ahead of print]
- Stanislavov R, Nikolova V, Rohdewald P. Improvement of seminal parameters with Prelox: a randomized, double-blind, placebo-controlled, cross-over trial. Phytother Res 2009 Mar;23(3):297-302.
- Nikolova V, Stanislavov R, Vatev I, Nalbanski B, Punevska M. [Sperm parameters in male idiopathic infertility after treatment with prelox]. Akush Ginekol (Sofiia) 2007;46(5):7-12.
- Stanislavov R, Nikolova V, Rohdewald P. Improvement of erectile function with Prelox: a randomized, double-blind, placebo-controlled, crossover trial. Int J Impot Res 2008 Mar-Apr;20(2):173-80.
A Nobel Prize for “The Molecule of the Year”
In the Parthenon of amino acids, arginine has won Athena’s commanding position with the awarding of the Nobel Prize in 1998 to Drs. Robert F. Furchgott, Louis J. Ignarro, and Ferid Murad for their discoveries that nitric oxide serves as a signaling molecule in the cardiovascular system. If a lot of research preceded the award, a plethora followed. Rarely has a molecule been given such attention. Why? Because nitric oxide is a great boon for cardiovascular health, a bonus for better memory function, and—here’s the real clamor—it has also made possible the revolution in erectile dysfunction drugs and nutrients. By the way, nitric oxide is made from arginine in our bodies.
What we see in animals as metabolic
variations (e.g., synthesis of urea,
creatine and polyamines) are
exaggerations of enzymic steps that
occurred early in evolutionary history.
Also in 1997, a group of Italian scientists discovered that arginine helped reduce blood pressure in their patients. In short order, arginine appeared so beneficial that doctors started to take it and then started recommending it to their patients. Hospitals caught on to papers that had actually been published over several decades and started giving it to their patients to heal their infectious wounds quicker. Already in the 1990s, a surge of arginine supplements had begun showing up in the market. Slowly at first, and then quicker as the word got out.
The Changes to GH Activity with Age
Among the changes that occur during aging are the degradation of immune functions and wound healing, and the loss of lean body mass and strength. Altogether, these are the result of the age-related loss of growth hormone activity that occurs as we age. We simply release less GH from exercise and less when we sleep. Even the way it’s released changes; it become more of a slow dribble at night rather than the cyclic pulses of youth.
Arginine Helps Restore GH Release
At the University of Torino, Italy in 1994 researchers reported that even though the responsiveness of somatotrope cells (cells in the anterior pituitary that produce growth hormone) to growth hormone releasing hormone (GHRH) is reduced in elderly humans, it is totally restored by arginine which probably acts by inhibiting hypothalamic release of somatostatin. Somatostatin (also known as growth hormone-inhibiting hormone) is a peptide hormone that regulates endocrine and nervous system functions by inhibiting the secretion of several other hormones such as insulin, gastrin, and growth hormone.
High doses of arginine were used in this study, with the iv administration of 30, 10 and 5 g as well as oral administration of 8 g of arginine. The researchers compared the effects of the arginine on the GH response to 1 mcg/kg iv GHRH in 27 healthy elderly subjects (11 men and 16 women, age 70–86 years, BMI 21–25 kg/m).
Without the evolutionary
development of arginine,
we would not exist.
In the group (n = 7) given 30 g of arginine iv, there was a striking enhancement of the GHRH-induced GH rise. Similarly, in the second group (n = 6) and third group (n = 7) receiving 10 g of arginine iv and 8 g oral arginine, respectively, there was also enhanced GH response to GHRH. In contrast, the group receiving the 5 g of iv arginine failed to see a GHRH-induced GH rise.
Surprisingly, GH responses to GHRH alone did not significantly differ amongst groups, except for the low-dose iv group which didn’t respond. These results show that the GH response to GHRH in elderly subjects is enhanced even by a range of iv doses of arginine and by the orally administered amino acid of only 8 g. Significantly, the results suggest that the combined administration of GHRH and arginine may be a useful approach to restore the impaired function of the GH-IGF axis in aging.
We now know that oral arginine alone can reverse GH decline.
Reversing One of Aging’s Downward Courses
Human exercise capacity declines with advancing age, with the concomitant loss of physical fitness and the speed-up of senescence. Some studies have implicated nitric oxide in the ability to improve exercise capacity through vascular smooth muscle relaxation in both coronary and skeletal muscle arteries; so too via independent mechanisms. Other studies have found that certain antioxidants may prevent nitric oxide inactivation by oxygen free radicals, especially vitamins C and E. A new study investigated the effects of an L-arginine and antioxidant supplement on exercise performance in elderly male cyclists.
Nitric oxide has also made possible
the revolution in erectile dysfunction
drugs and nutrients.
In a two-arm double-blinded and placebo-controlled trial, 16 male cyclists were randomized to receive either a proprietary supplement, containing 5.2 g L-arginine in a blend with L-citrulline, 500 mg ascorbic acid, 400 IU vitamin E, 400 µg folic acid, 300 mg L-taurine, and 10 mg alpha lipoic acid in a lemon-flavored powder form, or a placebo powder. The measure of the effects were assessed by maximal incremental exercise testing performed on a stationary cycle ergometer using breath-by-breath analysis at baseline, week one and week three.
At the start of the study there was no difference in baseline exercise parameters. In the supplemented group, anaerobic threshold increased by 16.7% at week 1, and the effect was sustained by week 3 with a 14.2%. In the control group, there was no change in anaerobic threshold at weeks 1 and 3 compared to baseline. Importantly, the anaerobic threshold for the supplement groups was significantly higher than that of placebo group at week 1 and week 3. There were no significant changes noted in VO2 max between control and intervention groups at either week 1 or week 3 by comparison to baseline.
In conclusion, an arginine and antioxidant-containing supplement increased the anaerobic threshold at both week one and week three in elderly cyclists. No effect on VO2 max was observed. This study suggests that an L-arginine and antioxidant supplementation can improve exercise performance in the elderly.
Studies done to date suggest that supplementation with the amino acid arginine can yield many benefits. Arginine may help:
- Stimulate growth hormone release
- Improve exercise capacity
- Boost exercise tolerance in weakened hearts
- Enhance cardiovascular health
- Fight coronary artery disease
- Counter atherosclerosis
- Improve fasting vascular endothelial function
- Protect against ischemia/reperfusion injury, the result of heart attacks and strokes
- Enhance blood flow
- Improve blood pressure
- Enhance sexual performance
- Maintain vein health
- Prevent high levels of C-reactive protein
Blood Sugar Metabolism
- Improve glucose metabolism
- Boost insulin sensitivity
- Prevent metabolic effects of high glucose in diabetic mice
- (Along with L-citrulline and antioxidants) Prevent high-glucose-induced cellular senescence
Protect and preserve kidney function
- Accelerate wound healing
- Reduce healing time of injuries (particularly bone)
- Quicken repair time of damaged tissue
- Enhance memory
- Improve brain function in the elderly
The Best Growth Hormone Releaser
World renown life extension researchers Durk Pearson & Sandy Shaw have been on the case of GH releasers for over 30 years, and about which they have continuously written in their Life Extension News™.* In the early 1980s, it was the work they did under a grant from the Paul F. Glenn Foundation (see www.americanaging.org/awards.html) that put GH releasers on the map. Finding initially for arginine and ornithine, Durk & Sandy have gone through a number of developments that have led to their current formulation, which is arginine-based, but far beyond their earlier versions. Their advanced formulation contains, along with 6 g of L-arginine, 500 mg L-citrulline, 500 mg ascorbic acid, 120 IU vitamin E, 100 mg vitamin E as mixed tocopherols with gamma tocopherol, 700 µg folic acid, 200 mg L-taurine, 1 g betaine HCl, 670 g choline, 1 g malic acid, and much more (23 nutrients altogether), and within this formulation they embrace many new discoveries. For further details, please see their articles previously published in this magazine (e.g.,
“Putting More Power into Your Life” in the April 2006 issue).
"I tested all the other stuff on
one side, and Durk & Sandy’s
formulation on this side."
The formulation used in the elderly cyclists study mentioned in this article has been endorsed by Nobel Prize winner Louis J. Ignarro, one of the three scientists who did much of the work that helped put nitric oxide on the map. As previously stated, it is comprised of 5.2 g L-arginine in a proprietary blend with L-citrulline, 500 mg ascorbic acid, 400 IU vitamin E, 400 µg folic acid, 300 mg L-taurine, and 10 mg alpha lipoic acid per serving. It bears a striking resemblance to Durk & Sandy’s formulation, but is nowhere near as complete or prescient.
- Hird FJR. The importance of arginine in evolution. Comp Biochem Physiol 1986; 85B(2):285-8.
- Maccario M, Oleandri SE, Procopio M, Grottoli S, Avogadri E, Camanni F, Ghigo E. Comparison among the effects of arginine, a nitric oxide precursor, isosorbided initrate and molsidomine, two nitric oxide donors, on hormonal secretions and blood pressure in man. J Endocrinol Invest 1997 Sep;20(8):488-92.
- Ghigo E, Ceda GP, Valcavi R, Goffi S, Zini M, Mucci M, Valenti G, Cocchi D, Müller EE, Camanni F. Low doses of either intravenously or orally administered arginine are able to enhance growth hormone response to growth hormone releasing hormone in elderly subjects. J Endocrinol Invest 1994 Feb;17(2):113-7.
- Collier SR, Collins E, Kanaley JA. Oral arginine attenuates the growth hormone response to resistance exercise. J Appl Physiol 2006 Sep;101(3):848-52.
- Chen S, Kim W, Henning SM, Carpenter CL, Li Z. Arginine and antioxidant supplement on performance in elderly male cyclists: a randomized controlled trial. J Int Soc Sports Nutr 2010 Mar 23;7(1):13.
Will Block is the publisher and editorial director of Life Enhancement magazine.