Featured Amino Acids

What are amino acids?

Amino acids are relatively simple molecules containing both amino (NH2) group and carboxyl (COOH) functional groups. They are ancient, from an evolutionarily viewpoint, and, alongside carbohydrates and fatty acids, basic nutrients. Twenty amino acids provide minimal requirements for growth, nitrogen equilibrium, maintenance of host defenses, neural (Fernstrom, 2000; Young et al., 1994) and muscular functions, as well as gene expression regulation (Fafournoux et al., 2000). The catabolism of amino acids contributes an energy source via intermediate products of glycolytic pathways and the citric acid cycle. The body is incapable of storing large amounts of amino acids and their homeostasis must be finely maintained by the integrated action of all the tissue and organs. For this reason, the dietary requirement for amino acids has important health consequences (Rose, 1957; Millward, 1994; Young, 1998; Young and Borongha, 2000). Nine amino acids are considered essential to diet, but demarcation between essentiality and non-essentiality is blurred by discoveries that have revealed effects of age (Baertl et al., 1974; Schober et al., 1989), nutritional status (Kurpad et al., 2003), and psycho-behavioral conditions, such as exposure to severe stress (Lacey and Wilmore, 1990; Obled et al., 2002). Indeed, the 2007 report of a joint WHO/FAO/UNU expert consultation on “Proteins and Amino Acids Requirements in Human Nutrition” led to a dramatic increase in the requirements for almost all essential amino acids, reflecting the recent shift towards to the quality of protein human dietary supply.

Amino acids are also the biochemical building blocks of proteins (large, naturally occurring polypeptides). The protein chains are made by linking the amino group of one amino acid with the carboxyl group of another. The amino acids absorbed into the body are utilized for the reconstitution of the body’s own proteins. It is therefore essential that the amino acids, as substrates of proteins, exist in sufficient quantity and a proper balance. The history of the discovery of amino acids began with the isolation of asparagine from an extract of asparagus shoot in 1806 and came to an end with the discovery of threonine in 1935. The beginning of the industrial production goes back to 1909 when glutamic acid was first obtained by extraction from wheat gluten hydrolysate to be used as a flavor enhancer. In the 1950s, a progress in the technology of purification and isolation enlarged the scope of applications for numerous amino acids, especially for those amino acids produced by fermentation. Presently, four methods of production are being used, extraction, fermentation, enzymatic method and chemical synthesis.

Since 1956, crystalline amino acids have been used in the medical and pharmaceutical fields as components of parenteral and later also enteral nutrition. For example, high quality amino acids have been employed for nutritional therapy in the treatment of patients with inflammatory bowel disease, Crohn’s disease or food allergies. Some amino acids are being utilized as ACE inhibitors, HIV protease inhibitors, anti-viral agents or anti-diabetic drugs.

In many developed countries, amino acids have been long utilized as dietary supplements or important constituents of cosmetics among the general healthy population in sport nutrition, cardiovascular health, hematopoietics and so on.

References:

1. Baertl, J. M., Placko, R. P. & Graham, G. G. (1974). American Journal of Clinical Nutrition, 27, 733-742.
2. Fernstrom, J. D. (2000). American Journal of Clinical Nutrition, 71, 1669S-1673S.
3. Kurpad, A. V., Regan, M. M., Raj, T., Vasudevan, J., Kuriyan, R., Gnanou, J. & Young, V. R. (2003). American Journal of Clinical Nutrition, 77, 101-8.
4. Lacey, J. M. & Wilmore, D. W. (1990). Nutritional Reviews, 48, 297-309.
5. Obled, C., Papet, I. & Breuille, D. (2002). Current Opinions in Clinical Nutrition and Metabolic Care, 5, 189-97.
6. Rose, W. C. (1957). Nutritional Abstracts and Reviews, 27, 489-497.
7. Millward, J. (1994). Journal of Nutrition, 124, 1509S-1516S.
8. Schober, P. H., Kurz, R., Musil, H. E. & Jarosch, E. (1989). Infusionstherapie, 16, 68-74.
9. Young, V. R., El-Khoury, A. E., Melchor, S. & Castillo, L. (1994). Nestle Nutrition Workshop Series, 33, 1-28, Vevey/Raven Press, New York.
10. Young, V. R. (1998). Journal of Nutrition, 128, 1570-1573.
11. Young, V. R. & Borgonha, S. (2000). Journal of Nutrition, 130, 1841S-1849S.

Lysine

Lysine is an essential amino acid because the human body cannot synthesize it in the body and therefore its breakdown is irreversible. Lysine is produced by fermentation from carbohydrate sources as a white crystalline powder, odorless but with a slight bitter taste. Lysine is readily soluble in water and practically insoluble in alcohol.

In the pharmaceutical field, lysine (usually in the format of monohydrochloride) is used as a component for integral amino acid preparations and therapeutics for herpes simplex (Griffith, 1987).

In agro-business, lysine is an indispensable component for lifestock feed, especially for pigs and chickens.

In human nutrition, lysine has been recognized as the first limiting essential amino acid in predominantly cereal diets and is inadequate among the poor in most developing regions (Scrimshaw, 1973). A significant improvement in protein quality by lysine fortification and a subsequent enhancement of growth in children has been documented in ethnically and culturally diverse populations living on diets marginally deficient in lysine (Pellet & Ghosh, 2004; Hussain, 2004; Zhao, 2004). Recent studies indicate that requirements for lysine and other essential amino acids may be increased in acute infectious disease states (Kurpad, 2003, Smriga, 2004). The most recent human studies in Western African showed that dietary supplementation with lysine could reduce diarrheal morbidity in children and respiratory morbidity in men (Ghosh, 2010). One of the ICAAS member companies is actively pursuing research and development in Western Africa, building upon the above clinical data (Fig.)

In respect to upper levels in human diet, few data indicate adverse effects caused by lysine ingestion (the 6th ICAAS Workshop on the Assessment of Adequate Intake of Dietary Amino Acids). In the US population, the main intake of lysine from foods was 5.3 gram per person per day. The scientific literatures contain several studies with added doses of approximately 3 – 6 gram free lysine per day in herpes simplex treatment, without any side effects reported.

Most of the lysine intake from dietary supplements is in the form of a hydrochloride. Because high chloride intake may induce hyperchloremic acidosis, which is deleterious in patients with renal failure who cannot handle excessive loads of acids, a certain attention to chloride intake in that subgroup of people is warranted. However, The presently available literature indicates that there are no clear hazards identified for an excessive dietary intake of lysine and that a metabolic limit could be the only real approach to setting up an upper limit (if one is needed). This approach would be in parallel to the FAO/WHO Nutrient Risk Assessment Workshop approach which proposed the use of the highest observed intake concept for endogenous substances with no known adverse health effects.

References:

1. Ghosh, S., Smriga, S., Vuvor, S., Suri, D., Mohammed, H., Armah, S., Scrimshaw, N. S. (2010). Am J Clin Nutrition, 92, 928-939.
2. Griffith, R. S., Walsh, D. E., Myrmel, K. H., Thompson, R.W., Behforooz, A. (1987). Dermatologica, 175, 183-190.
3. Hussain, T., Abbas, S., Khan, M. A., Scrimshaw, N. S. (2004). Food and Nutrition Bulletin, 25(2):114-22.
4. Kurpad, A. V., Regan, M. M., Raj, T., Vasudevan, J., Kuriyan, R., Gnanou, J. (2003). Am J Clin Nutrition, 77, 101-108.
5. Pellett, P.L., Ghosh, S. (2004). Food and Nutrition Bulletin, 25, 7.
6. Scrimshaw, N. S., Taylor, Y., Young, V. R. (1973). Am J Clin Nutrition, 26, 965-972.
7. Smriga, M., Ghosh, S., Mouneimne, Y., Pellett, P. L., Scrimshaw, N. S. (2004). Proceedings of the National Academy of Sciences of the United States of America, 101, 8285-8288.
8. The 6th Workshop on the Assessment of Adequate Intake of Dietary Amino Acids (2007). J. Nutrition, 137, Supplement.
9. Zhao, W., Zhai, F., Zhang, D., An, Y., Liu, Y., He, Y., Scrimshaw, N. (2004). Food and Nutrition Bulletin, 25, 123-129.

Branched-Chain Amino Acids (BCAA)

BCAA are a group of three ketogenic essential amino acids (leucine, valine and isoleucine). They are called branched-chain because their structure has a “branch” off the main body of the molecule. The combination of these three essential amino acids makes up approximately one-third of skeletal muscle in the human body in form of protein, even though BCAA are present in the skeletal muscle in free (non-protein) form only in marginal amounts. Commercial form of BCAA is a white crystal or crystalline powder, odorless and with slightly bitter taste. All of the BCAA are readily soluble in formic acid, sparingly in water and practically insoluble in alcohol.

Differently from many other amino acids, BCAA are metabolized only in the muscle, since the enzyme BCAA amino-transferase is not present in the liver where many other amino acids are converted. The rate-limiting enzyme of BCAA metabolism is branched-chain alpha-ketodehydrogenase is also located in the muscle and effectively activated by physical exercise or fasting. BCAA are used in various combinations and amounts, among them, leucine is the most readily oxidized one and therefore the most effective at secreting insulin from the pancreas. It lowers elevated blood sugar levels and aids in growth hormone production.

In the pharmaceutical field, BCAA are being used in gastrectomized patients to maintain nitrogen in the body and treat various forms of hepatic injury. Three possible targets of BCAA supplementation in hepatic diseases are: (1) hepatic encephalopathy, (2) liver regeneration, and (3) liver cirrhosis (i.e., Urata, 2007, Kawamura, 2009). The BCAA may ameliorate hepatic encephalopathy by promoting ammonia detoxification, correction of the plasma amino acid imbalance, and by reduced brain influx of aromatic amino acids. The influence of BCAA supplementation on hepatic encephalopathy could be especially effective in chronic hepatic injury with hyperammonemia and low concentrations of BCAA in blood. The favorable effect of BCAA on liver regeneration and nutritional state of the body is related to their stimulatory effect on protein synthesis, secretion of hepatocyte growth factor, glutamine production and inhibitory effect on proteolysis (Holecek, 2010).

There is substantial scientific debate on whether BCAA have an anabolic effect during/after exercise in healthy humans, with some recent clinical studies indicating that exercise-induced muscle damage and muscle soreness may be suppressed by oral load of BCAA (Shimomura, 2010; Jackman, 2010), leading to an improved long-term muscle performance. However, the subject of anabolism is still insufficiently studied, also due to disparity of methodologies applied to study muscle performance and differences in BCAA dose, respectively the ratio among leucine, isoleucine and valine.

In respect to upper levels in human diet, no human data indicate adverse effects caused by an increased ingestion of BCAA in healthy humans (the 4th Workshop on the Assessment of Adequate Intake of Dietary Amino Acids). The only “model” of extremely high BCAA exposure is a very rare genetic disorder, maple syrup urine disease, a feature of which is substantial brain dysfunction, but that cannot serve as a useful model of excessive BCAA intake in general population (for review see, Fernstrom, 2005). In patients with liver cirrhosis, high doses (app. 12 gram BCAA per day) were applied for prolonged periods of severl months without any reports of side effects (for review, see, Marchesini, 2005). A recent project sponsored by ICAAS (Elango, 2010) has indicated that the mean upper metabolic limit to oxidize leucine in healthy humans was as high as 0.56 gram per kg body weight per day, which would indicate that the homeostatic control of the intake of one of the BCAA, leucine, is very well developed in humans.

Reference:

1. Elango, R., Chapman, K., Rafii, M., Ball, R. O., Pencharz, P. B. (2010). Abstract for the Experimental Biology.
2. Fernstrom, J. D. (2005). J. Nutrition, 135S, 1539 – 1546.
3. Holecek, M. (2010). Nutrition, 26, 482-490.
4. Jackman, S. R., Witard, O. C., Jeukendrup, A. E., Tipton, K. D. (2010). Med Sci Sports Exercice,  42, 962-970.
5. Kawamura, E., Habu, D., Morikawa, H., Enomoto, M., Kawabe, J., Tamori, A., Sakaguchi, H., Saeki, S., Kawada, N., Shiomi. S. (2009). Liver Transpl., 15, 790-797.
6. Marchesini, G., Marzocchi, R., Noia, M., Bianchi, G. (2005). J. Nutrition, 135S, 1596 – 1601.
7. Shimomura, Y., Inaguma, A., Watanabe, S., Yamamoto, Y., Muramatsu, Y., Bajotto, G., Sato, J., Shimomura, N., Kobayashi, H., Mawatari, K. (2010). Int J Sport Nutr Exerc Metabolism,  20, 236-244.
8. The 4th Workshop on the Assessment of Adequate Intake of Dietary Amino Acids (2005). J. Nutrition, 135S.
9. Urata, Y., Okita, K., Korenaga, K., Uchida, K., Yamasaki, T., Sakaida, I. (2007). Hepatol Research, 37, 510-516.

Tryptophan

Tryptophan (Trp) is one of the nine essential amino acids that need to be ingested daily in the diet. The adult male requirement for Trp in diet is 4.0 mg per kg body weight. The idea of using Trp to reduce mental stress and improve sleeping has been implemented since 1970s, since the time medical scientists discovered that Trp influenced the rate at which neuronal endings formed the neurotransmitter serotonin and that Trp was a precursor of melatonin. The brain Trp co-depends on the plasma supply of Trp and carbohydrates (Fernstrom, 1983 & 1991), and it is inversely affected by the circulating levels of other large neutral amino acids (LNAA: tyrosine, phenylalanine, leucine, isoleucine and valine), making the availability of Trp dependent on nutritional aspects. Deficiency of Trp dietary supply results in rapid and severe decline in the brain serotonin activity. Trp deficiency worsens seasonal depression, anxiety, carbohydrate craving, the premenstrual syndrome, and the ability to deal with daily stresses (Blokland et al., 2002).

Human applications of the Trp deficiency model have suggested that the negative results of the deficiency originate not only from serotonin deficiency, but mainly from complex interactions between monoaminergic systems (Reilly et al., 1997; Van der Does, 2001; Delgado, 2000). Yet, the controversy on Trp use in supplements continues. Controlled clinical studies indicate that Trp supplements, alone, or in a combination with carbohydrates, alleviate stress-induced mood (Maes et al., 1999), and some milder forms of cognitive deterioration (Markus et al., 2002).

Moreover, Trp is necessary for the production of vitamin B3 and requires B6, zinc as well as vitamin C to make the conversion enzyme. Some suggest that Trp or 5-hydroxytryptamine (the demi-product in the conversion of tryptophan to serotonin) may help in controling hyperactivity in children (Rucklidge et al., 2009).

Unfortunately, human research on the Trp supplements suddenly shrank 21 years ago, when nonprescription Trp preparations made by a single maker were linked to deadly outbreak of eosinophilia myalgia syndrome (EMS), most probably due to impurities caused by insufficient quality control management. Consequently, Trp was banned from the US and UK markets until 2005, when it was again reintroduced.

ICAAS is currently intensively working on quality control methods that would help in preventing such disasters in the future and provide the consumers with an access to potentially useful amino acid. In addition, ICAAS is supporting both animal and human research models that may help to establish the upper intake limits for Trp.

Finally, Trp tends to be deficient in livestock feed for chicken and pigs, if the feed is mainly composed of maize. Livestock farming productivity is therefore increased by fortifying Trp to maize feed.

References

1. Blokland, A., Lieben, C. & Deutz, N. E. (2002). Anxiogenic and depressive-like effects, but no cognitive deficits, after repeated moderate tryptophan depletion in the rat. Journal of Psychopharmacology, 16, 39-49.
2. Delgado, P. L. (2000) Depression: the case for a monoamine deficiency. Journal of Clinical Psychiatry, 61, 7-11.
3. Fernstrom, J. D. (1991). Effects of the diet and other metabolic phenomena on brain tryptophan uptake and serotonin synthesis. Advances in Experimental Medicine and Biology, 294, 369-76.
4. Fernstrom, J. D. (1983). Role of precursos availability in control of monoamine biosynthesis in brain. Physiological Reviews, 63, 484-486.
5. Maes, M., Lin, A. H., Verkerk, R., Delmeire, L., Van Gastel, A., Van der Planken, M. & Scharpe, S. (1999). Serotonergic and noradrenergic markers of post-traumatic stress disorder with and without major depression. Neuropsychopharmacology, 20, 188-97.
6. Markus, C. R., Olivier, B. & de Haan, E. H. F. (2002). Whey protein rich in lactalbumine increases the ration of plasma tryptophan to the sum of the other large neutral amino acids and improves cognitive performance in stress-vulnerable subjects. American Journal of Clinical Nutrition, 75, 1051-1056
7. Reilly, J. G., MCTavish, S. F. & Young, A. H. (1997). Rapid depletion of plasma tryptophan: a review of studies and experimental methodology. Journal of Psychopharmacology, 11, 381-392.
8. Rucklidge, J. J., Johnstone, J., Kaplan, B. J. (2009). Nutrient supplementation approaches in the treatment of ADHD. Expert. Rev. Neurother. 9, 461-76.
9. Van der Does, A. J. (2001). The effect of tryptophan depletion on mood and psychiatric symptoms. Journal of Affective Disorders, 64, 107-119.

Arginine