BCAA NTLC

Branched Chain Amino AcidsBranched Chain Amino Acids

Tasneem ShaikhTasneem Shaikh

MSc SN IMSc SN I

Roll No:19Roll No:19

Nutrition through lifecycleNutrition through lifecycle

What are Branched Chain Amino Acids(BCAAs)?

BCAAs in human body

BCAAs account for-35–40% of the dietary essential amino acids in body protein-14–18% of the total amino acids(essential and non-essential) in muscle proteins

The total concentration of BCAA in human blood (0.3–0.4 mM) is relatively high compared with that of the other amino acids (except glutamine)

Also present in the free amino acid pool.(0.1g/kg muscle)

Metabolism of BCAAs

1,7,13. Branched Chain AminoTransferase; 2,8,14. Branched Chain Keto-Acid Dehydrogenase;3. Isovaleryl-CoA Dehydrogenase; 4. 3-Methylcrotonyl-CoA Carboxylase; 5. 3-Methylglutaconyl-CoA Hydratase; 6. 3-Hydroxy-3-Methylglutaryl-CoA lyase; 9. 2-Methylbutyryl-CoA Dehydrogenase; 10. Enol-CoA Dehydrogenase; 11. 2-Methylhydroxybutyryl CoA Thiolase;12. 3-Methylacetoacetyl-CoA Thiolase;; 15. 2-Methylbutyryl-CoA Dehydrogenase; 16. Enol-CoA Dehydrogenase; 17. 3-Hydroxyisobutyryl-CoA Deacylase; 18. 3-Hydroxyisobutyryl-CoA Dehydrogenase; 19. Methylmalonic semialdehyde Dehydrogenase; 20. Propionyl-CoA Carboxylase; 21. Methylmalonyl-CoA Mutase.

Distribution of BCAA MetabolismThe cellular and tissue distribution of their primary metabolizing enzymes(BCAT and BCKD) that gives leucine, isoleucine and valine such an important role in nitrogen metabolism.

Neither isoform of BCAT is expressed in the liver. BCATc is expressed primarily in the brain, testes and ovaries, while BCATm is found throughout the body.

Its primary catabolism occurs in the skeletal muscle.

A key function of the BCAAs in the skeletal muscle is to provide the nitrogen needed to maintain muscle pools of glutamate, alanine and glutamine.In the skeletal muscle, BCAT activity is substantially higher than BCKD activity for efficiently transferring nitrogen from BCAAs to alpha-ketoglutarate and also possibility of a high release of BCKAs from the tissue instead of their being oxidized.

Despite the extensive release of BCKAs from the skeletal muscle, the concentrations of circulating BCKAs are exceptionally low. This is due to the complete absence of BCAT isozymes in the liver, while the hepatocytes demonstrate an extremely high level of BCKD activity. This allows virtually complete oxidation of BCKAs and maintains low levels.

The brain is the only tissue (along with the ovaries and testes) that express BCATc, BCATm and BCKD

The BCAAs can be obtained from one of 4 possible sources:1. Whole-food proteins2. Protein supplements3. Solutions of protein hydrolysates and4. Free amino acids.

•On average, the BCAA content of food proteins is about 15% of the total amino acid content. •BCAA are found in all protein-containing foods, but egg and poultry, meat and milk (particularly whey) have notable BCAA content (BCAA to total protein ratio).•Among plant food sources, oats, soy, lentils and wheat germ have respectable leucine levels.•Isoleucine is found in especially high amounts in meats, fish, cheese, most seeds and nuts, eggs, chicken and lentils.•Important sources of valine include soy flour, cottage cheese, fish, meats and vegetables.•The typical adult diet might contain BCAA at a level of 50 to 150 mg/kg of weight, with the level and type of protein consumed being the primary determinant.•Meanwhile, the recommended dietary allowances (RDA) for the BCAA are 12, 14 and 16 mg/kg for isoleucine, valine and leucine.

Sources of BCAA

Example:

Given Cow’s Milk contains 0.51 grams of nitrogen/ 100 ml

Therefore nitrogen in one serving(200ml)= 0.51 * 2= 1.02 grams of nitrogen

Given Leucine content= 600mg/ gram of nitrogen

Therefore leucine content in one serving(200ml) of cow’s milk= 600*1.02= 612 mg of leucine

Functions/Role of BCAAsMetabolic roles:

1.Provide carbon source of oxidation for production of energy in muscles2.Act as a precursor for muscle protein synthesis3.BCAAs are more energy efficient than glucose

4.Oxidation of BCAAs increases under various physiological conditions to meet the energy demand including the demand at starvation

5.BCAAs regulate the turnover of protein in muscles by inhibiting protein degradation and enhancing protein synthesis.

6.BCAAs can cover the elevated demands for alanine and glutamine by the body during clinical conditions such as such as starvation, surgery, trauma, sepsis, liver disease, and cancer that lead to protein loss especially muscle protein.

7.BCAAs facilitate glucose uptake by liver and SK muscle as well as enhances glycogen synthesis.

8.BCAAs have large influence on energy metabolism as well as on reducing risks of obesity.(increases lipid oxidation)

Functions/Role of BCAAsPhysiological role:

1.Immunity: BCAAs are absolutely required for lymphocytes growth and proliferation. BCAAs are also important for cytotoxic T lymphocyte and natural killer cell activity.

2. Sepsis: BCAAs have a beneficial effect in septic patients.(decreases mortality)

3. Diabetes:The BCAAs maintain glucose homeostasis by stimulating insulin secretion. Complex relationship between BCAAs and insulin regulation. While Wang et al. (2011) showed that elevation of circulating BCAAs is a significant risk factor for diabetes and insulin resistance, another study reported that supplementation of BCAAs actually improves glucoses homeostasis and insulin resistance in hepatic cirrhosis patients. Further investigation needed.

4. Brain function: BCAAs may also play important roles in brain function. BCAAs may influence brain protein synthesis and production of energy and may influence synthesis of different neurotransmitters, that is, serotonin, dopamine, norepinephrine, and so forth, directly or indirectly.

Functions/Role of BCAAs5. Liver diseases:i.Liver cirrhosis: positive effect improved serum albumin concentration, improved liver function and overall health.

ii.Hepatic encephalopathy: BCAAs administration can improve hepatic encephalopathy, but it does not have any effect on mortality.

iii.Liver cancer: Decrease of postoperative morbidity, decreased use of diuretic therapy to control ascites in preoperative group, no weight loss, shorter hospital stay and quicker improvement of liver function in the early postoperative period.

iv.Nonalcoholic Steatohepatitis(NASH/NAFLD): BCAAs can lower fat deposition in rats fed a high-fat diet which might be a potential strategy to treat NASH in humans. 6. Cancer prevention: BCAAs possibly contribute to tumor suppression by enhancing cellular senescence mediated through the mTOR signalling pathway. 7. Skeletal muscles: Supplementation of BCAAs with glucose decreases the onset of exercise induced muscle soreness in young females.

Functions/Role of BCAAs

8. Fatigue: BCAAs supplementation was able to reduce perceived exertion(reduces serotonin central fatigue)

9. Burns : no positive result yet. More research required.

10. Trauma: Ingestion of BCAAs improves nitrogen balance in trauma and surgically stressed patients. BCAAs supplementation improves cognitive functions in TBI(traumatic Brain Injury) patients.

11. Cardiovascular disease: BCAAs and its related metabolites are independently associated with CAD severity. BCAAs are independently related to ambulatory BP and cIMT in individuals with high HbA1c levels

12. Renal disease: In chronic hemodialysis, six months of BCCAs supplementation reduced anorexia and improved overall nutritional status.

BCAAs as nutritional ergogenic aid

Branched-Chain Amino Acid Supplementation:BCAA can be found in classic supplemental form (pills, capsules, etc.) as well as formulated into sport drinks, bars and shakes (powder and ready-to-drink (RTD)).

It is sometimes recommended that the BCAA be taken together and in a balance of 2 to 2 to 1 (leucine:valine:iso-leucine) although supportive information is scarce.Recommended levels of consumption seem to depend on training intensity, and manufacturers generally advise that individuals take from 1 gram/day on rest days and easy days to about 3 grams on heavy training days. Dosage: 5-10gms-1-2 times/day (max 30g/day)

BCAAs as nutritional ergogenic aid

Liquid BCAAHigh ratio BCAA

Flavored BCAA

BCAA tablets

Unflavored BCAA

Side effects of BCAA supplementation

Safe to use in children and adults according to studies lasting for up to 6 months.Side effects may include fatigue, nausea and muscle incoordination.Allergic reactions to BCAAs supplements are possible but would be much more likely

caused by added substances than BCAAs themselves.Pregnant and breastfeeding women should avoid BCAAs supplements since their safety

during these periods has not been studied well. One should avoid BCAA supplements if they are-Anyone drinking a lot of alcohol - BCAAs triggered hepatic encephalopathy in one

research study,-Individuals with amyotrophic lateral sclerosis (ALS, Lou Gehrig’s disease)-Individuals with branched-chain keto aciduria- also known as maple syrup urine disease

(MSUD)-Infants with idiopathic hypoglycaemia-Individuals scheduled for surgery in the next two weeks.

BCAAs as nutritional ergogenic aid

Deficiency:Deficiency of BCAAs usually occurs along with protein malnutrition. Deficiency of BCAAs alone is rare and may occur in individuals with chronic kidney failure and liver cirrhosis. The main symptom is anorexia (poor appetite).

Toxicity:At this time very little is known regarding the potential toxicity of BCAA and the upper limits (UL) have not been set.

Deficiency and Toxicity

Conclusion BCAAs have unique characteristics as they are not primarily oxidized in liver and

they regulate protein synthesis and degradation in muscle as well as other tissues.

They have diverse metabolic and physiological roles.

It is important and necessary to explore whether BCAAs have other therapeutic effects on other tissues. Future investigations may be directed to fully understand the diverse effects of BCAA in different tissues and associated signaling pathways.

Our current knowledge regarding the role of BCAA in insulin regulation is still not

clear. It has been reported that increased BCAAs level is associated with CVD, diabetes, and MSUD.

But if an individual gets a diet which is low in BCAAs it can affect the overall body protein synthesis, insulin regulation, glucose homeostasis, glutamate-glutamine pool, and antioxidant level. Therefore, further studies are needed to fill up the knowledge gap between BCAAs metabolism and the related regulation of these amino acids.

ResearchExercise-induced muscle damage is reduced in resistance-trained males by branched chain amino acids: a randomized, double-blind, placebo controlled studyGlyn Howatson, Michael Hoad, Stuart Goodall, Jamie Tallent, Phillip G Bell andDuncan N FrenchCorresponding author: Glyn [email protected] Journal of the International Society of Sports Nutrition 2012, 9:20 doi:10.1186/1550-2783-9-20AbstractBackgroundIt is well documented that exercise-induced muscle damage (EIMD) decreases muscle function and causes soreness and discomfort. Branched-chain amino acid (BCAA) supplementation has been shown to increase protein synthesis and decrease muscle protein breakdown, however, the effects of BCAAs on recovery from damaging resistance training are unclear. Therefore, the aim of this study was to examine the effects of a BCAA supplementation on markers of muscle damage elicited via a sport specific bout of damaging exercise in trained volunteers.MethodsTwelve males (mean ± SD age, 23 ± 2 y; stature, 178.3 ± 3.6 cm and body mass, 79.6 ± 8.4 kg) were randomly assigned to a supplement (n = 6) or placebo (n = 6) group. The damaging exercise consisted of 100 consecutive drop-jumps. Creatine kinase (CK), maximal voluntary contraction (MVC), muscle soreness (DOMS), vertical jump (VJ), thigh circumference (TC) and calf circumference (CC) were measured as markers of muscle damage. All variables were measured immediately before the damaging exercise and at 24, 48, 72 and 96 h post-exercise.ResultsA significant time effect was seen for all variables. There were significant group effects showing a reduction in CK efflux and muscle soreness in the BCAA group compared to the placebo (P<0.05). Furthermore, the recovery of MVC was greater in the BCAA group (P<0.05). The VJ, TC and CC were not different between groups.

ConclusionConclusionThe present study has shown that BCAA administered before and following damaging resistance The present study has shown that BCAA administered before and following damaging resistance exercise reduces indices of muscle damage and accelerates recovery in resistance-trained males. exercise reduces indices of muscle damage and accelerates recovery in resistance-trained males. It seems likely that BCAA provided greater bioavailablity of substrate to improve protein It seems likely that BCAA provided greater bioavailablity of substrate to improve protein synthesis and thereby the extent of secondary muscle damage associated with strenuous synthesis and thereby the extent of secondary muscle damage associated with strenuous resistance exercise.resistance exercise.

ResearchEfficacy and safety of oral branched-chain amino acid supplementation in patients undergoing interventions for hepatocellular carcinoma: a meta-analysisLing Chen, Yaqin Chen, Xiwei Wang, Hong Li, Hongmin Zhang, Jiaojiao Gong, Shasha Shen, Wenwei Yin and Huaidong Hu*Abstract: Most hepatocellular carcinoma (HCC) patients have complications, including cirrhosis and malnutrition. The efficacy of dietary supplementation with oral branched-chain amino acids (BCAAs) in HCC patients undergoing interventions has not been confirmed. Relevant publications on the efficacy and safety of oral BCAA supplementation for HCC patients undergoing anti-HCC interventions through September, 2014 were searched for identification in the PubMed, Embase, Web of Science, and the Cochrane Library databases. The pooled risk ratio (RR) and standardized mean difference (SMD) were used to assess the supplementation effects. A total of 11 eligible studies (974 patients in total) were evaluated and included in our analysis. Oral BCAA supplementation helped to maintain liver reserve with higher serum albumin (SMD = 0.234, 95 % CI: 0.033–0.435, P = 0.022), and lower rates of ascites (RR = 0.545, 95 % CI: 0.316–0.938, P = 0.029) and edema (RR = 0.494, 95 % CI: 0.257–0.952, P = 0.035) than in the control group. BCAA supplementation seemed to be effective in improving mortality, especially in Child-Pugh class B patients, but the efficacy was not confirmed. Apparent effects were not found in improving HCC recurrence, total bilirubin, ALT, or AST. BCAA supplementation was relatively safe without serious adverse events. BCAA supplementation may be clinically applied in improving liver functional reserve for HCC patients and further improving the quality of life.

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Bibliography7. G. L. Blackburn, L. L. Moldawer, S. Usui, A. Bothe Jr., S. J. D. O’Keefe, and B. R. Bistrian, “Branched chain amino acid administration and metabolism during starvation, injury, and infection,” Surgery, vol. 86, no. 2, pp. 307–315, 1979.  8. H. Mochizuki, O. Trocki, L. Dominioni, and J. W. Alexander, “Effect of a diet rich in branched chain amino acids on severely burned guinea pigs,” Journal of Trauma, vol. 26, no. 12, pp. 1077– 1085, 1986.  9. K. Tajiri and Y. Shimizu, “Branched-chain amino acids in liver diseases,” World Journal of Gastroenterology, vol. 19, no. 43, pp. 7620–7629, 2013.  10. K. Sugiyama, L. Yu, and N. Nagasue, “Direct effect of branched-chain amino acids on the growth and metabolism of cultured human hepatocellular carcinoma cells,” Nutrition and Cancer, vol. 31, no. 1, pp. 62–68, 1998. 11. T. Kawaguchi, Y. Nagao, H. Matsuoka, T. Ide, and M. Sata, “Branched-chain amino acid-enriched supplementation improves insulin resistance in patients with chronic liver dis-ease,” International Journal of Molecular Medicine, vol. 22, no. 1, 105–112, 2008 12. M. Arakawa, T. Masaki, J. Nishimura, M. Seike, and H. Yoshi-matsu, “The effects of branched-chain amino acid granules on the accumulation of tissue triglycerides and uncoupling pro-teins in diet-induced obese mice,” Endocrine Journal, vol. 58, no. 3, pp. 161–170, 2011.

Bibliography

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Bibliography

17. M. G. Buse and S. S. Reid, “Leucine: a possible regulator of protein turnover in muscle,” Journal of Clinical Investigation, vol. 56, no. 5, pp. 1250–1261, 1975.  18. J. de Bandt and L. Cynober, “Therapeutic use of branched-chain amino acids in burn, trauma, and sepsis,” Journal of Nutrition, vol. 136, supplement, no. 1, pp. 308S–313S, 2006.  19. E. Blomstrand, “Potential role of branched-chain amino acid catabolism in regulating fat oxidation,” Journal of Nutrition, vol. 41, no. 4, pp. 194–200, 2006. 20. T. M. O’Connell, “The complex role of branched chain amino acids in diabetes and cancer,” Metabolites, vol. 3, no. 4, pp. 931– 945, 2013.

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