Innovations & Applications

Recycling Natural Gas
Much attention has been directed to the amino acid L-arginine, the precursor to the biological gas called nitric oxide that mediates changes in blood vessel diameter, blood pressure and blood flow. However, when nitric oxide is formed from L-arginine, the amino acid L-citrulline is formed. L-citrulline also can be recycled back into L-arginine. L-citrulline is not found in dietary proteins but is produced in notable amounts by the liver and intestines, in part from L-arginine. Controversy exists whether L-citrulline itself may serve as a blood vessel/pressure regulator.1,2

A study published in November 2001 offers additional evidence that L-citrulline may indeed act as a vasodilator, at least in the rat aorta. Researchers found that L-citrulline—via recycling back into L-arginine—substantially relaxed blood vessels and increased nitric oxide production.3 One research group has suggested that L-citrulline may be a preferable way to provide L-arginine to the body and could enhance blood flow and erectile function and even reduce sickle cell anemia symptoms.4 This theory has not yet been tested in humans, but studies may soon get under way.

NAC Breakthroughs
A family member is rushed to the hospital, having overdosed on acetaminophen (Tylenol). What is the antidote of choice in most medical centres around the world? N-acetylcysteine (NAC). This amino acid also has been widely used in Europe to treat bronchitis because it reduces symptoms as well as the risk of worsening the condition.5 NAC is both a direct antioxidant and a precursor to the most abundant miniprotein or peptide antioxidant found in cells—glutathione.

HIV patients, who typically display low glutathione levels, responded to sustained use of 8g NAC/day for up to 32 weeks, with elevated blood and immune T cell glutathione content, while those receiving placebo did not.6 An equally intriguing result was found when 37 smokers, who exhibited dysfunctional blood vessel function, were given 600mg NAC/day for two weeks. In measuring blood flow into fingernail beds, researchers found a significant improvement.7 NAC may protect the lungs, blood vessels and other tissues of chronic and frequent smokers. Additional studies are needed to confirm the long-term effects of NAC and its safety in asthmatics.8

In hundreds of studies, researchers have investigated green tea (Camellia sinensis) for its anticancer and anti-oxidant effects. Much of the plant's bioactivity has been assigned to the polyphenols found in brews and extracts. A precursor of green tea is white tea, which is steamed and fermented to various degrees and then dried to produce green, oolong and black teas.

A less-processed material such as white tea may have more active polyphenols. Recent studies using the Ames test to assess the ability of coloured or brewed teas to reverse bacterial mutation showed white tea to be more potent than green tea.9 In this study, concentrations of the most potent polyphenol, epigallocatechin gallate (EGCG), were similar between the teas, but white tea had more methylxanthines, caffeine and theobromine as well as other polyphenols including gallic acid and epicatechin-3-gallate (ECG).

Recently, researchers found that white tea added to the drinking water of mice with a high risk for developing colon polyps resulted in those mice developing smaller tumours and less anemia than mice receiving plain water.10 White tea is likely to be hitting store shelves soon. What is still brewing in the minds of scientists is whether this purest of teas is a more potent antioxidant in humans than the green variety.

Anthony Almada is a nutritional and exercise biochemist and has collaborated on more than 50 university-based clinical trials. He is the co-founder of EAS and founder and chief scientific officer of IMAGINutrition (


1. Ruiz E, Tejerina T. Relaxant effects of L-citrulline in rabbit vascular smooth muscle. Br J Pharmacol 1998;125:186-92.

2. Marx S, et al. Citrulline does not relax isolated rat and rabbit vessels. Br J Pharmacol 2000;130:713-6.

3. Raghavan SAV, Dikshit M. L-Citrulline mediated relaxation in the control and lipopolysaccharide-treated rat aortic rings. Eur J Pharmacol (in press).

4. Waugh WH, et al. Evidence that L-arginine is a key amino acid in sickle cell anemia—a preliminary report. Nutr Res 1999;19:501-18.

5. Stey C, et al. The effect of oral N-acetylcysteine in chronic bronchitis: a quantitative systematic review. Eur Respir J 2000;16:253-62.

6. De Rose SC, et al. N-acetylcysteine replenishes glutathione in HIV infection. Eur J Clin Invest 2000;30:915-29.

7. Qing L, et al. N-acetylcysteine improves microcirculatory flow during smoking: new effects of an old drug with possible benefits for smokers. Clin Cardiol 2001;24:511-5.

8. Schmidt LE, Dalhoff K. Risk factors in the development of adverse reactions to N-acetylcysteine in patients with paracetamol poisoning. Br J Clin Pharmacol 2001;51:87-91.

9. Santana-Rios G, et al. Potent antimutagenic activity of white tea in comparison with green tea in the Salmonella assay. Mutat Res 2001;495:61-74.

10. Orner GA, et al. Effect of white tea on intestinal tumor progression in the APCM in mouse. Environ Molec Mutagen 2001;37(Suppl32):59.

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