Altered oxidative stress profile in the cortex of mice fed an enriched branched‐chain amino acids diet: Possible link with amyotrophic lateral sclerosis?

Abstract

Branched-chain amino acids (BCAAs), valine, isoleucine, and leucine, are widely used among athletes as dietary integrators. Although the occurrence of untoward effects of BCCA supplementation, with particular regard to neurological disturbances, cannot be excluded, no specific studies have been performed so far. The aim of this work was to evaluate the effects of a diet enriched in BCAAs on the expression of oxidative stress pathway genes in the brain of C57Bl/6J mice. Animals were fed a standard or a BCAA diet for 95 days starting from postnatal day 21 until sacrifice. BCAA treatment, at doses comparable to human usage, significantly down-regulated the expression of some antioxidant genes, while up-regulating the expression of some oxygen transporters. In conclusion, it appears that BCAAs administered by diet could alter some specific oxidative stress pathways in the brain. Caution should thus be exercised in the widespread use of BCAAs as dietary integrators in sports practice.

Voluntary Exercise Prevents Oxidative Stress in the Brain of Phenylketonuria Mice

“…Moreover, as concentrations of Phe and other large neutral amino acids did not change in the brain due to exercise, competition between aromatic amino acids and BCAA might not have hampered BCAA uptake in ExePKU in comparison to SedPKU. This observation could indicate an increased amino acid metabolism to yield energy, as the brain has high activity of the key enzymes especially for BCAA catabolism (Piscopo et al 2011). Furthermore, brain proline levels show a positive correlation with the daily distance run only for PKU mice (r ¼ 0.817; p ¼ 0.004); therefore, the amount of running, and hence the amount of training, might have influenced this result.…”

Prediagnostic plasma branched-chain amino acids and the risk of amyotrophic lateral sclerosis

“…Still, it is possible that these amino acids affect disease processes at a later stage, which could be consistent with the results from previous metabolomics studies, the possible adverse effects reported in clinical trials, 4,5 and the findings from in vivo and in vitro studies suggesting that BCAAs affect pathways relevant to the disease. 6,7 BCAAs contribute both to de novo synthesis and buffering of glutamate, which in excessive amounts may contribute to excitotoxicity in ALS. The amino acids, in particular leucine, rapidly cross into the CNS, 28 and provide approximately 25% of the amino groups of brain glutamate.…”

“…In an Italian trial, there was an excess of deaths in the group treated with BCAAs, 4 and in a later US trial, the estimated decline in forced vital capacity, one of the a priori selected outcomes, was 2.5 times greater in the treatment group as compared to placebo. 5 As BCAAs may affect pathways relevant to ALS, including downregulation of antioxidant genes associated with familial ALS and induction of hyperexcitability in cortical neurons, 6,7 it has been proposed that dietary supplements containing BCAAs, which are commonly used by Italian soccer players, 8 could be one of the factors that contributed to their elevated ALS risk. 9,10 Whether BCAAs increase the risk of ALS is currently not known.…”

Amyotrophic lateral sclerosis and environmental factors

“…They have therefore been investigated as risk factors for ALS. Piscopo et al (2011) examined the effect of a diet enriched with BCAAs in C57BI/6J mice and demonstrated that BCAAs are able to down-regulate the expression of some antioxidant genes and can alter oxidative stress pathways in the brain; the authors concluded that caution should be exercised in the use of these dietary supplements by athletes. Venerosi et al (2011) demonstrated that BCAA supplements can exacerbate motor deficits in G39A mice.…”