FUNCTION OF BCAAS AS IMMUNE-NUTRIENTS

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FUNCTION OF BCAAS AS IMMUNE-NUTRIENTS

  • Moderate intensity exercise leads to positive health effects. Although exercise stimulates the production of reactive oxygen species, their intracellular concentration does not reach damaging levels due to activation of antioxidant responses. After all, single bout of high intensity exercise may result in oxidative stress, muscle fatigue and muscle injury. Furthermore, impaired immunity has been noted during the recovery period as shown by severe inflammation and compensatory immunosuppression.1
  • Although moderate intensity exercise is essential for the general population to reduce the risk of chronic inflammatory diseases, athletes engaged in high-intensity exercise are more susceptible to a number of adverse effects, such as high rates of protein catabolism, a pro-inflammatory state, accompanied by muscle damage, soreness, chronic oxidative stress and immune suppression (Overtraining syndrome).2-4
  • During moderate intensity exercise, pro-inflammatory cytokines are downregulated and anti-inflammatory cytokines are upregulated.5-7
  • In 2002, a study was done on Olympic Triathlon participants. They were divided into two groups; the first were supplemented with BCAAs and the other supplemented with placebo. Peripheral blood samples were collected prior to and immediately after the triathlon. Lymphocyte proliferation, cytokine production by cultured cells, and plasma glutamine were measured. After the exercise bout, athletes from the placebo group showed a decreased plasma glutamine concentration which was abolished by BCAAs supplementation and an increased proliferative response in their peripheral blood mononuclear cells. After exercise, those cells also produced less TNF-α, IL-1 and IL-4, and interferon and 48% more interleukin-2. Supplementation stimulated the production of interleukin-2 and interferon after exercise and a more pronounced decrease in the production of interleukin-4, indicating a diversion toward a Th1 type immune response. BCAAs supplementation recovers the ability of peripheral blood mononuclear cells proliferate in response to mitogens after a long distance intense exercise, as well as plasma glutamine concentration.8
  • A study was done in 2010 to discover the effects of squat exercise induced delayed onset muscle soreness (DOMS) using young, healthy, untrained female participants. In the morning on the exercise-session day, the participants ingested either BCAA or placebo before the squat exercise. DOMS showed a peak on Days 2 and 3 in both groups, but the level of soreness was significantly lower in the BCAA group than in the placebo group. Plasma BCAA concentrations, which decreased after exercise in the placebo group, were markedly elevated during 2 hours after exercise in the BCAA group. Serum myoglobin concentration was increased by exercise in the placebo but not in the BCAA group. The change in the elastase level was significant only in the placebo group. These results suggest that muscle damage may be suppressed by BCAA supplementation.9
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BCAAs supplementation in patients with advanced liver disease and hepatocellular carcinoma

  • A study was done in 2014 to investigate the role of BCAAs in the prognosis of hepatocellular carcinoma patients by comparing patients treated with BCAAs for at least 2 weeks before TACE or RFA and those not receiving such pre-treatment. A total of 270 patients with hepatocellular carcinoma complicated by cirrhosis were included in the study. Mean changes from baseline (Δ) in serum albumin (Alb), C-reactive protein (CRP), and transaminase levels, and peak body temperature were compared at days 2, 5, and 10 after the start of TACE or RFA. pre-intervention BCAA significantly suppressed the development of post-intervention hypoalbuminemia and reduced inflammatory reactions during the subsequent clinical course. In patients who underwent TACE or RFA, the ΔAlb peaked on day 2, remained constantly lower in BCAA-treated patients, compared to the control group. The ΔCRP was also significantly lower in BCAA-treated patients on days 2, 5 and 10. The changes in serum Alb level were inversely correlated with CRP changes; therefore, a possible involvement of the anti-inflammatory effect of BCAAs was inferred as a factor contributory to the suppression of decrease in serum Alb level.10
  • In patients with advanced liver disease, serum levels of BCAAs decrease, while the levels of the aromatic amino acids AAAs, such as phenylalanine and tyrosine, increase resulting in a low ratio of BCAAs to AAAs which is associated with hepatic encephalopathy (HE).11
  • BCAA supplementation was shown to delay the progression of CCl4-induced chronic liver injury in a rat model by reducing hepatic apoptosis.12On the other hand, BCAAs promoted hepatocyte regeneration in a rat model of hepatectomy.13 In addition, BCAAs were reported to stimulate the production of hepatocyte growth factor.14
  • The effects of BCAAs on liver cancer cells have been analysed in culture systems. Increased concentrations of BCAAs in culture medium were reported to suppress the proliferation of HCC cell lines.15 Moreover, BCAAs were found to accelerate insulin-induced vascular endothelial growth factor (VEGF) mRNA degradation, downregulating VEGF expression during the development of HCCs.16 BCAAs were also shown to induce apoptosis of liver cancer cell lines. Moreover, BCAAs may inhibit obesity-related hepatocarcinogenesis by suppressing the stimulatory effect of visfatin, an adipokine with a critical role in HCC proliferation.17
  • HE frequently occurs after gastrointestinal bleeding, perhaps due to an absence of isoleucine and an abundance of leucine in hemoglobin molecules, leading to HE by BCAA antagonism. Treatment with BCAAs may therefore have a beneficial effect on patients with hepatic encephalopathy mainly by compensating decreased ratio of BCAAs to AAAs, but not by reducing serum ammonia levels.18
  • A systematic review was conducted in 2013 to investigate the effects of oral BCAAs on patients with cirrhosis and recurrent overt or minimal HE. Analyses included data from 8 trials (n = 382 patients). Random effects meta-analysis showed that improvements in HE manifestations were registered for 87 of 172 patients in the BCAA group compared with 56 of 210 controls. The effect of BCAAs differed for patients with overt and minimal HE. BCAAs supplements had no effect on mortality and did not induce adverse events. In conclusion, oral BCAA supplements improve manifestations of HE but have no effect on survival.19
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BCAAs supplementation and risk of diabetes mellitus

  • Increased levels of circulating BCAAs in blood are associated with worse metabolic outcomes. They were found to be associated with increased insulin resistance which by time could cause type 2 diabetes mellitus.20
  • Metabolite profiles were investigated and followed among 2,422 normoglycemic individuals for 12 years. 201 developed diabetes. Amino acids, amines and other polar metabolites were profiled in baseline specimens by liquid chromatography-tandem mass spectrometry (LC-MS). Five branched-chain and aromatic amino acids had highly significant associations with future diabetes: isoleucine, leucine, valine, tyrosine and phenylalanine.21
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BCAAs supplementation in Cachexia

  • One of the most severe sequelae of cancers is cachexia. It is a major cause of morbidity and mortality in up to 50% of patients with advanced cancer.22 Cachexia is characterized by extensive loss of both adipose and skeletal muscle tissue which reduces the quality. Alterations in amino acid metabolism appear to play a major role in cachexia pathogenesis.23 Cancer patients are often anorexic due to the disease or the treatment, so reduced dietary intake of amino acids likely plays a role. The progression of cachexia appears to involves a net increase in protein catabolism along with activation of proteolysis and a significant reduction in protein synthesis.
  • Under normal circumstances, BCAA oxidation in skeletal muscle provides 6%–7% of the energy requirements, but under highly catabolic circumstances such as cancer cachexia, the contribution can be as high as 20%.24 Myofibrillar proteins are composed of approximately 18% BCAAs and therefore, breakdown of skeletal muscle can yield significant increases in BCAAs.25 It might be expected that the increased proteolysis would lead to an increase in the circulating BCAAs, but this increase leads to an increase in the oxidative pathway. The tumor itself also uses the catabolized BCAAs along with the other amino acids for protein synthesis.
benefits

REFERENCES

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