The surge in the products that can affect mood has grown rapidly over the past five years. We now have a plethora of products that stimulate the mind, enhance alertness or relax the mind, such as L-theanine. The latest developments in the mood-health market are addiction treatment, mental stress and anxiety, with research papers in 2007 showcasing the potential benefit of N-acetyl cysteine, L-lysine, L-arginine, L-cirtrulline, and the granddaddy of them all, L-carnitine. It is said that all a company needs are two trials with consumer-relevant benefit in order to launch a new product. If that is so, the new research detailed below should open doors to new product development efforts.

Addiction

One premise regarding the chemical mechanisms that reinforce addictive behaviour is a chemical cascade that influences the glutamate system. As such researchers from University of Minnesota School of Medicine recently investigated the use of the amino acid N-acetyl Cysteine (NAC) and its ability to restore glutamate concentrations and reduce addictive behavior.1

In a six-week, double-blind, placebo-controlled trial, 13 subjects diagnosed as pathological gamblers were supplemented with a mean dose of 1.5g NAC or placebo (following a two-week open-label trial on NAC to identify responders). Of the 13 subjects in the pre-trial shown to have lower scores following a pathological gambling assessment, 83.3 per cent continued to meet responder criteria compared to 28.6 per cent in the placebo group.

The authors of this unique study suggest NAC's efficacy support the hypothesis for the glutamate system as a target for reward-seeking behaviors such as gambling. Additional work in other areas where chemical rewards for behaviour are associated, such as obesity, would be interesting and offer unique IP opportunities.

Easing stress

A study utilising amino acids for mood modification was recently carried out by Japanese researchers.2 The study examined the effect of two amino acids on anxiety and stress hormones. The premise behind this work was that supplementation with the essential amino acid L-lysine has been shown to reduce chronic anxiety in humans with low dietary intake of L-lysine. Furthermore, the combination of L-lysine and L-arginine has also been documented to normalize the hormonal stress responses in humans. The present study, with 108 healthy Japanese adults, investigated the ability of 2.64g/day L-lysine and 2.64g/day L-arginine for seven days to reduce anxiety and associated stress-hormone levels.

Results showed that the amino-acid treatments significantly reduced both trait and state anxiety induced by a cognitive-stress battery. In addition, supplementation also decreased the basal levels of salivary cortisol and chromogranin-A (a salivary marker of the sympatho-adrenal system) in male subjects. The take-home message from this study is the beneficial potential of supplemental amino acids in healthy humans with high levels of mental stress and anxiety.

Watermelon: nature's nitric oxide

The push to natural products that offer an alternative to synthesised powders and pills can provide a distinct competitive advantage. Arginine is a conditionally essential amino acid that has applications within the ingredients market, thanks to its influence on nitric-oxide levels and the associated application in blood pressure, diabetes and blood clotting. Researchers in 2007 investigated the influence of watermelon pomace juice, a rich source of L-citrulline (a precursor of arginine) on plasma arginine levels.3

In this controlled trial, subjects consumed either 0 (control), 780g or 1,560g watermelon juice per day for three weeks in a crossover design. These latter doses provided 1g and 2g citrulline per day, respectively. Following three weeks of supplementation with watermelon, plasma arginine increased 12 per cent and 22 per cent for the low- and high-dose intakes, demonstrating that the citrulline contained within watermelon can increase arginine levels.

Previous work utilising watermelon in rodents with metabolic syndrome demonstrated reduced fat accretion; lowered serum concentrations of glucose, freed fatty acids and homocysteine; and improved acetylcholine-induced vascular relaxation.4 Further human investigations with this natural arginine enhancer may provide effective results in areas of sports performance, obesity and cardiovascular disease.

Carnitine: multi-functional amino

The trimethylated amino acid L-carnitine is a co-enzyme, a water-soluble vitamin-like compound classified as an amino acid. It has been a hot ingredient over the past year because of a big push from the sports and weight-loss sectors of the market. However, carnitine's functions within the human body extend far beyond these latter categories, and many have not been exploited to any significant degree. One big trend throughout the supplement market is a synergy and chemical bonding between complementary ingredients. Carnitine is no exception, as such the following gives a brief overview of some of the novel applications for carnitine over the coming months and years.

Endurance enhancement — Researchers from India have taken a slight diversion from the power and weight-loss market for carnitine and recently evaluated the effect of L-carnitine supplementation on improving endurance exercise in normobaric/normoxic and hypobaric/hypoxic environments.5

Following six weeks of endurance training, 24 male rats were randomly divided into two groups. Group A supplemented with 100mg x kg(-1) body weight L-carnitine, and group B had no supplement. Over 25 days of supplementation in a normobaric/normoxic environment, a run to exhaustion was carried out on day one (pre-supplementation) and on days seven, 14 and 21 of supplementation. The same run test was also carried out on day 28 following 72 hours of hypoxic exposure equivalent to an altitude of 6100m.

The L-carnitine group experienced a significant improvement in endurance performance under normobaric/normoxia conditions (36-39 per cent) and hypobaric/hypoxia conditions (50 per cent). L-carnitine had no effect on plasma glucose levels either at sea level or after hypoxic exposure. Total cholesterol was decreased in normoxic and HDL cholesterol was increased in normoxic and hypoxic conditions, indicating a beneficial effect of exercise.

This study suggests L-carnitine supplementation improved exercise endurance in rats exposed to normobaric/normoxic and hypobaric/hypoxic conditions. The potential of L-carnitine taken at high altitude would also make for an interesting study. Further clinical work in disease states defined by local and systemic hypoxia such as pulmonary diseases and intermittent claudication observed in patients suffering cardiovascular disease offers potentially new revenue opportunities.

Mental energy — It has been aptly demonstrated that L-carnitine is an important contributor to cellular energy metabolism — the reason the ingredient has seen success in the sports-performance sector. Among all the substances whose concentration decreases with age, L-carnitine diminution is fundamentally important, given its function in the production of energy. Accordingly, researchers in Italy assessed the effects of L-carnitine supplementation on fatigue, both mental and physical, on 100-year-olds living in Sicily.6

The double-blind, placebo-controlled, randomised study of 66 centenarians found that 2g/day L-carnitine for six months resulted in increased blood levels of carnitine, and significantly increased capacity for physical and cognitive activity, as well as significant improvements in total fat mass and total muscle mass.

The study, published in the December 2007 issue of American Journal of Clinical Nutrition, used Sigma-tau's L-carnitine and represented part of the commitment to carnitine research and rollout of novel carnitine forms in 2007 by the Italian supplier.

Neuroprotection — Another December 2007 study looked at an area of benefit akin to that of carnitine's influence on the brain — neuroprotection, in this case, from assault caused from methamphetamine use and its attendant behavioural sensitisation.7
In this rodent study, carnitine was the equal to valproate, a mood-stabilising and anticonvulsant drug used in inhibiting methamphetamine-induced hyperactivity. The study raises the possibility of beneficial effects of carnitine in abuse behaviour.

Hair Growth — Researchers at the University of Hamburg, Germany, have taken an interest in the functions of carnitine in energy metabolism and hair growth. With the personal-care category rapidly expanding, the following study offers exciting and unique insights. The authors of the study hypothesized that L-carnitine may stimulate hair growth by increasing energy supply to the rapidly proliferating and energy-consuming anagen hair matrix (the growth phase of the hair follicle's life cycle).8

Hair follicles (HFs) in the anagen stage of the hair cycle were cultured in the presence of of L-carnitine-L-tartrate (CT) for nine days. At day nine, HFs treated with CT showed a moderate but significant stimulation of hair-shaft elongation compared with nontreated controls. These findings suggest that L-carnitine stimulates human scalp-hair growth by up-regulation of proliferation and reduced death rate of hair follicles in vitro. Further work with pure L-carnitine given as a dietary supplement should be directed toward androgenetic alopecia and other forms of hair loss, as it could offer market potential.

Carnitine joins the heart-health Q — There is now an ocean of evidence regarding carnitine and coenzyme Q10's (co-Q10) importance for optimal functioning of myocardial mitochondria. Those that are deficient, as with congestive heart failure, can be afflicted with excessive inflammation. The research in the following study suggest that supplemental co-Q10 and L-carnitine may protect these patients from further tissue damage by decreasing inflammation.⁹

Over a 12-week period, a randomised, double-blind, placebo-controlled trial assessed the effects of supplementation with 2,250mg/day L-carnitine and 270mg/day hydrosoluble co-Q10 (Carni Q-Gel, supplied by Tishcon). Two groups totaling 62 patients participated in the study with 31 patients with heart failure receiving the co-Q10 plus L-carnitine (group A) and another 31 patients serving as controls (group B).

After 12 weeks, there was a marked reduction in IL-6, which indicates inflammation activity, in the intervention group without such changes in the control group. IL-10, which indicates anti-inflammatory activity, showed only the nonsignificant decrease in both groups from the baseline levels. TNF-alpha, which amplifies inflammatory responses, was comparable at baseline and also showed a greater decline in the supplement group compared to placebo.

Baseline serum co-Q10 levels were low; however, after 12 weeks, serum co-Q10 showed a significant increase in the intervention group compared to control. The quality-of-life visual analogous scale revealed that shortness of breath, palpitation and fatigue, present at rest in all patients at baseline, showed beneficial changes in the intervention group compared to placebo. Furthermore, results from a six-minute walk test showed significantly greater increase in walking distance from baseline in the intervention than the placebo group.

These findings indicate that supplementation with co-Q10 plus L-carnitine can cause a significant reduction in pro-inflammatory cytokines, and a significant improvement in quality of life in patients with heart failure. Further work is required to define optimal dosing and to provide support for the conclusions found in this trial, though this early data look to offer the functional- and medical-foods market an intriguing opportunity.

Unfortunately, the constraints of this article do not allow further discussion into additional areas of carnitine research, such as L-carnitine L-tartrate reducing muscle damage after exercise.10

However, results from the above studies demonstrate the vibrancy the amino acids-ingredient category is currently experiencing. As a result of research, new opportunities are opening. With functional on everyone's lips, aminos look set to take full advantage.

Mark J Tallon, PhD, is chief science officer of NutriSciences, a London-based consultancy firm specialising in health-claim substantiation, product development and technical writing. www.NutriSciences.net. Respond: [email protected]

For more on carnitine and sports performance, see 'Science Review.'

References
1. Grant JE, et al. N-acetyl cycteine, a glutamate-modulating agent, in the treatment of pathological gambling: a pilot study. Biol Psychiatry 2007;62(6): 652-7.
2. Collins JK, et al. Watermelon consumption increases plasma arginine concentrations in adults. Nutrition 2007; 23(3): 261-6.
3. Smriga M, et al. Oral treatment with L-lysine and L-arginine reduces anxiety and basal cortisol levels in healthy humans. Biomed Res 2007;28(2):85-90.
4. Wu G, et al. Dietary supplementation with watermelon pomace juice enhances arginine availability and ameliorates the metabolic syndrome in Zucker diabetic fatty rats. J Nutr 2007;137(12):2680-5.
5. Panjwani U, et al. Effect of L-carnitine supplementation on endurance exercise in normobaric/normoxic and hypobaric/hypoxic conditions. Wilderness Environ Med 2007;18(3):169-76.
6. Malaguarnera M, et al. L-carnitine treatment reduces severity of physical and mental fatigue and increases cognitive functions in centenarians: a randomized and controlled clinical trial. Am J Clin Nutr 2007;86:1738-44.
7. Coccurello R, et al. Valproate and acetyl-L-carnitine prevent methamphetamine-induced behavioural sensitization in mice. Ann NY Acad Sci 2007 Dec;1122:260-75.
8. Foitzik K, et al. L-carnitine-L-tartrate promotes human hair growth in vitro. Exp Dermatol 2007;16(11):936-45.
9. Kumar A, et al. Effect of carni Q-gel (ubiquinol and carnitine) on cytokines in patients with heart failure in the Tishcon study. Acta Cardiol 2007;62(4):349-54.
10. Spiering BA, et al. Responses of criterion variables to different supplemental doses of L-carnitine L-tartrate. J Strength Cond Res 2007;21(1):259-64