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L-Arginine Potentiates Fat Loss
Weight loss is becoming an increasingly frustrating barometer of body change. Physicians and their patients not only struggle to see the scale numbers drop, but are discouraged when the weight inevitably comes back on. A 2007 review from the American Psychological Association looked at the success rate of diets and came to a sobering conclusion: within 2 years, 66% of dieters end up weighing more than they did before they started the diet.¹

The issue may be the consequences of low-calorie diets and a sole focus on weight. It has long been known that low-calorie diets can have negative and sometimes unintended results, namely reduction of active muscle mass. It has been shown that sudden low-calorie diets can induce insulin insensitivity in susceptible populations, a fact that many physicians are not aware of.⁷

The muscle mass of an individual determines 40% of his or her insulin sensitivity and 70% to 90% of blood glucose clearance.^5,6 This makes muscle a valuable asset in sustained body change. Low-calorie diets deplete muscle tissue, significantly reduce metabolic rate, and create a progressive resistance to further weight loss after each month.⁹

Adding exercise to a low-calorie diet can help attenuate the decline in muscle mass, as long as that exercise is resistance training. A 2008 study in the journal Obesity showed that resistance training, but not aerobic exercise, was better at sparing muscle loss during low-calorie dieting.⁸ It also showed sustainability of basal metabolic rate (BMR), an important consideration for weight maintenance.

BMR can be decreased by 10% to 20% in response to dietary reduction.¹¹ And a slowed BMR is a predictor of future fat gain. Dieters with the slowest metabolic declines have a 4-fold increase in gaining 15 or more pounds over the next 2 years.¹²

Help from a Cardiac Nutrient
From the above data, it is obvious that we need better solutions to combine with exercise to assure that fat is lost rather than muscle. L-arginine, often thought of as a cardiovascular nutrient, may offer help through several unique mechanisms.

L-arginine is a well-known precursor to nitric oxide (NO). While NO is celebrated in the cardiovascular world, it is less well known in the exercise world. Nitric oxide synthase, the enzyme that catalyzes the reaction of L-arginine into NO, is highly expressed in muscle tissue. It turns out that NO acts as a powerful modulator of metabolic activity in several beneficial ways. L-arginine has been shown to stimulate mitochondrial biosynthesis, activate brown adipose tissue, enhance growth hormone production, and activate multiple genes responsible for fat and glucose oxidation.^4,13-16

The impact on fat loss is exciting enough, but L-arginine's ability to affect muscle mass as well makes it a potential game-changer in turning weight loss to fat loss. One of the most interesting aspects of L-arginine's impact may come from the ability of NO to affect muscle satellite cells, which are responsible for maintaining and growing muscle. A study by Kartashkina et al. showed that NO can stop the atrophy of muscle mass that normally comes with muscle disuse through affecting satellite cells.¹⁵

A 2009 rat study showed that L-arginine supplementation for 12 weeks resulted in substantial loss of fat tissue and a 14% improved rate of glucose metabolism. Surprisingly, it also increased muscle weight by 14%.¹³ Similar effects have been shown in human studies incorporating L-arginine.^2,3

In one of the more striking L-arginine studies, Lucotti et al. studied 33 obese type 2 diabetic subjects undergoing an extensive lifestyle intervention.² All subjects were put on a 1000 kcal diet along with 90 minutes of daily exercise including cardiovascular and resistance training. One group was given 8.3 g L-arginine and the other group was treated with placebo. The intervention lasted 3 weeks.

The results of the study showed that the placebo group lost 8.6 pounds (4.6 pounds of fat and 3.7 of which was muscle). The L-arginine group lost 6.6 pounds of fat and no muscle. Despite the rigorous exercise program, the placebo group's losses were well over a third muscle (43% muscle loss). The L-arginine group lost fat exclusively, a very difficult task to pull off.

Clinical Implications
Given the profound ramifications of indiscriminate weight loss, it is important to look for interventions that do not simply aid fat reduction, but maintain muscle mass at the same time. Resistance training has been the most reliable intervention in this regard to date, but the addition of the research on L-arginine is promising. Along with other amino acids, including branched chain amino acids (BCAA), we should add L-arginine to the list of lean mass builders. The realization that L-arginine has such positive benefits on body composition should make it a first-line consideration in weight loss and obesity management.

Notes

1. Mann et al. Medicare's search for effective obesity treatments: diets are not the answer. Am Psychologist. 2007 April;62(3):220–233.
2. Lucotti et al. Beneficial effects of a long-term oral L-arginine treatment added to a hypocaloric diet and exercise training program in obese, insulin-resistant type 2 diabetic patients. Am J Physiol Endocrinol Metab. 2006 Nov;291(5):E906–912.
3. Michishita et al. Evaluation of the anti-obesity effects of an amino acid mixture and conjugated linoleic acid on exercising overweight humans: a randomized double-blind, placebo-controlled trial. J Int Med Res. 2010;38:844–859.
4. Steensberg et al. Nitric oxide production is a proximal signaling event controlling exercise-induced mRNA expression in human skeletal muscle. FASEB J. 2007 Sep;21(11):2683–2694.
5. Nastala et al. Skeletal muscle insulin resistance is fundamental to the cardiometabolic syndrome. J Cardiometab Syndr. 2006;1(1):47–52.
6. Jens et al. A muscle-specific insulin receptor knockout exhibits features of the metabolic syndrome of NIDDM without altering glucose tolerance. 1998;2(5):559–569.
7. Koffler et al. Starvation diets and very low calorie diets may induce insulin resistance and overt diabetes mellitus. J Diabetes Complications. 1996;10(2):109–112.
8. Hunter et al. Resistance training conserves fat-free mass and resting energy expenditure following weight loss. Obesity. Mar 2008;16:1045–1051.
9. Heilbronn et al. Effect of 6-month calorie restriction on biomarkers of longevity, metabolic adaptation, and oxidative stress in overweight individuals: a randomized controlled trial. JAMA. 2006;295:1539–1548.
10. Redman et al. Metabolic and behavioral compensations in response to caloric restriction: implications for the maintenance of weight loss. PLoS ONE . Feb 2009;4(2): e4377.
11. Hansen et al. The effects of exercise training on fat-mass loss in obese patients during energy restriction. Sports Med. Jan 2007;37(1):31–46.
12. Ravussin et al. Reduced rate of energy expenditure as a risk factor for body-weight gain. N Engl J Med. Feb. 25, 1988;318(8):467–472.
13. Jobgen et al. Dietary L-arginine supplementation reduces white fat gain and enhances skeletal muscle and brown fat masses in diet-induced obese rats. J Nutr. 2009;139:230–237
14. Jobgen et al. Regulatory role for the arginine-nitric oxide pathway in metabolism of energy substrates. J Nutr Biochem. 2006;17:571–588.
15. Kartashkina et al. Effect of NO on satellite cell proliferation during functional unloading and muscle stretching. Dokl Biol Sci. 2010;432(1):167–170.
16. McKnight et al. Beneficial effects of L-arginine on reducing obesity: potential mechanisms and important implications for human health. Amino Acids. July 2010;39(2):349–357.