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The effect of branched chain amino acids on skeletal muscle mitochondrial function in young and elderly adults.

ABSTRACT: A reduction in maximal mitochondrial ATP production rate (MAPR) and mitochondrial DNA (mtDNA) abundance occurs with age in association with muscle weakness and reduced endurance in elderly people. Branched chain amino acids (BCAA) have been extensively used to improve physical performance.The objective was to determine whether an 8-h infusion of BCAA enhances MAPR equally in healthy young and elderly adults.Using a crossover study design, we compared the effect BCAA vs. saline infusion in 12 young (23.0 +/- 0.8 yr) and 12 elderly (70.7 +/- 1.1 yr) participants matched for sex and body mass index. Skeletal muscle MAPR and mtDNA abundance were measured in muscle biopsy samples obtained before and at the end of the 8-h infusion.In young participants, MAPR with the substrates glutamate plus malate (supplying electrons to complex I) and succinate plus rotenone (complex II) increased in response to BCAA infusion, relative to a decline in MAPR in response to the saline infusion. In contrast, MAPR was unaffected by BCAA infusion in the elderly participants. Moreover, mtDNA abundance was lower in the elderly compared with the young participants but was unaffected by the BCAA infusion. Insulin and C-peptide concentrations declined over time during the saline infusion, but these declines were prevented by the BCAA infusion.BCAA increased skeletal muscle MAPR in the young participants in comparison with saline, but this effect was not seen in the elderly participants indicating, that unlike in the young, BCAA does not increase muscle mitochondrial function in the elderly.

SUBMITTER: Tatpati LL

PROVIDER: S-EPMC2840857 | biostudies-other | 2010 Feb

REPOSITORIES: biostudies-other

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The effect of branched chain amino acids on skeletal muscle mitochondrial function in young and elderly adults.

Tatpati Laura L LL Irving Brian A BA Tom Andrea A Bigelow Maureen L ML Klaus Katherine K Short Kevin R KR Nair K Sreekumaran KS

The Journal of clinical endocrinology and metabolism 20091218 2

<h4>Context</h4>A reduction in maximal mitochondrial ATP production rate (MAPR) and mitochondrial DNA (mtDNA) abundance occurs with age in association with muscle weakness and reduced endurance in elderly people. Branched chain amino acids (BCAA) have been extensively used to improve physical performance.<h4>Objective</h4>The objective was to determine whether an 8-h infusion of BCAA enhances MAPR equally in healthy young and elderly adults.<h4>Methods</h4>Using a crossover study design, we comp ...[more]

PMID: 20022987

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Project description:BACKGROUND:A previous clinical study reported that the addition of an amylopectin/chromium complex (ACr; Velositol®) to 6?g of whey protein (WP) significantly enhanced muscle protein synthesis (MPS). Branched-chain amino acids (BCAAs) are also well-known to enhance MPS. The aim of this study was to determine if the addition of ACr to BCAAs can enhance MPS and activate expression of the mammalian target of the rapamycin (mTOR) pathway compared to BCAAs and exercise alone in exercise-trained rats. METHODS:Twenty-four male Wistar rats were randomly divided into three groups (n?=?8 per group): (I) Exercise control, (II) Exercise plus BCAAs (0.465?g/kg BW, a 6?g human equivalent dose (HED)), and (III) Exercise plus BCAAs (0.465?g/kg BW) and ACr (0.155?g/kg BW, a 2?g HED). All animals were trained with treadmill exercise for 10?days. On the day of the single-dose experiment, rats were exercised at 26?m/min for 2?h and then fed, via oral gavage, study product. One hour after the consumption of study product, rats were injected with a bolus dose (250?mg/kg BW, 25?g/L) of phenylalanine labeled with deuterium to measure the fractional rate of protein synthesis (FSR). Ten minutes later, muscle tissue samples were taken to determine MPS measured by FSR and the phosphorylation of proteins involved in the mTOR pathway including mTOR, S6K1, and 4E-BP1. RESULTS:ACr combined with BCAAs increased MPS by 71% compared to the exercise control group, while BCAAs alone increased MPS by 57% over control (p?<?0.05). ACr plus BCAAs significantly enhanced phosphorylation of mTOR, S6K1 and 4E-BP1 compared to exercise control rats (p?<?0.05). The addition of ACr to BCAAs enhanced insulin levels, mTOR and S6K1 phosphorylation compared to BCAAs alone (p?<?0.05). Serum insulin concentration was positively correlated with the levels of mTOR, (r?=?0.923), S6K1 (r?=?0.814) and 4E-BP1 (r?=?0.953). CONCLUSIONS:In conclusion, the results of this study provide evidence that the addition of ACr to BCAAs significantly enhances exercise-induced MPS, and the phosphorylation of mTOR signaling proteins, compared to BCAAs and exercise alone.

Project description:BACKGROUNDElevated circulating branched chain amino acids (BCAAs), measured at a single time point in middle life, are strongly associated with an increased risk of developing type 2 diabetes mellitus (DM). However, the longitudinal patterns of change in BCAAs through young adulthood and their association with DM in later life are unknown.METHODSWe serially measured BCAAs over 28 years in the Coronary Artery Risk Development in Young Adults (CARDIA) study, a prospective cohort of apparently healthy Black and White young adults at baseline. Trajectories of circulating BCAA concentrations from years 2-30 (for prevalent DM) or years 2-20 (for incident DM) were determined by latent class modeling.RESULTSAmong 3,081 apparently healthy young adults, trajectory analysis from years 2-30 revealed 3 distinct BCAA trajectory groups: low-stable (n = 1,427), moderate-stable (n = 1,384), and high-increasing (n = 270) groups. Male sex, higher body mass index, and higher atherogenic lipid fractions were more common in the moderate-stable and high-increasing groups. Higher risk of prevalent DM was associated with the moderate-stable (OR = 2.59, 95% CI: 1.90-3.55) and high-increasing (OR = 6.03, 95% CI: 3.86-9.43) BCAA trajectory groups in adjusted models. A separate trajectory group analysis from years 2-20 for incident DM after year 20 showed that moderate-stable and high-increasing trajectory groups were also significantly associated with higher risk of incident DM, after adjustment for clinical variables and glucose levels.CONCLUSIONBCAA levels track over a 28-year span in most young adults, but serial clinical metabolomic measurements identify subpopulations with rising levels associated with high risk of DM in later life.FUNDINGThis research was supported by the NIH, under grants R01 HL146844 (JTW) and T32 HL069771 (MRC). The CARDIA study is conducted and supported by the NIH National Heart, Lung, and Blood Institute in collaboration with the University of Alabama at Birmingham (HHSN268201800005I and HHSN268201800007I), Northwestern University (HHSN268201800003I), the University of Minnesota (HHSN268201800006I), and Kaiser Foundation Research Institute (HHSN268201800004I).

Project description:BackgroundCirculating branched-chain amino acid (BCAA) levels reflect metabolic health and dietary intake. However, associations with breast cancer are unclear.MethodsWe evaluated circulating BCAA levels and breast cancer risk within the Nurses' Health Study (NHS) and NHSII (1997 cases and 1997 controls). A total of 592 NHS women donated 2 blood samples 10 years apart. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) of breast cancer risk in multivariable logistic regression models. We conducted an external validation in 1765 cases in the Women's Health Study (WHS). All statistical tests were 2-sided.ResultsAmong NHSII participants (predominantly premenopausal at blood collection), elevated circulating BCAA levels were associated with lower breast cancer risk (eg, isoleucine highest vs lowest quartile, multivariable OR = 0.86, 95% CI = 0.65 to 1.13, P trend = .20), with statistically significant linear trends among fasting samples (eg, isoleucine OR = 0.74, 95% CI = 0.53 to 1.05, P trend = .05). In contrast, among postmenopausal women, proximate measures (<10 years from blood draw) were associated with increased breast cancer risk (eg, isoleucine OR = 1.63, 95% CI = 1.12 to 2.39, P trend = .01), with stronger associations among fasting samples (OR = 1.73, 95% CI = 1.15 to 2.61, P trend = .01). Distant measures (10-20 years since blood draw) were not associated with risk. In the WHS, a positive association was observed for distant measures of leucine among postmenopausal women (OR = 1.23, 95% CI = 0.96 to 1.58, P trend = .04).ConclusionsNo statistically significant associations between BCAA levels and breast cancer risk were consistent across NHS and WHS or NHSII and WHS. Elevated circulating BCAA levels were associated with lower breast cancer risk among predominantly premenopausal NHSII women and higher risk among postmenopausal women in NHS but not in the WHS. Additional studies are needed to understand this complex relationship.

Dataset Information

The effect of branched chain amino acids on skeletal muscle mitochondrial function in young and elderly adults.

Publications

The effect of branched chain amino acids on skeletal muscle mitochondrial function in young and elderly adults.

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