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Correlation of plasma amino acids to obesity and cardiovascular disease: what they don’t mean

Several clinical studies published during the last five years reported a positive correlation between blood level of branched-chain amino acids (BCAA; leucine, isoleucine, valine) and metabolic disorders, mainly obesity and cardiovascular disease. Among others, see: www.ncbi.nlm.nih.gov/pubmed/19356713 or www.ncbi.nlm.nih.gov/pubmed/20173117. Other case-control observational studies found positive associations between cardiovascular disease and a score of other amino acids measured at baseline. See, www.ncbi.nlm.nih.gov/pubmed/23242195.

What does it all mean? There are twenty protein-building amino acids present in our body and circulating in our blood. It is therefore not surprising that synthesis or breakdown of some amino acids may go up (down) during a long-term observational study in specific sub-populations. Does such a correlation indicate causative effects linking the intake of the said amino acids to some metabolic diseases? It definitively does not, as reasoned below in 4 steps applied to the case of BCAA, which are the best studied group of amino acids in that respect.

1. Interventional clinical studies indicated that BCAA improve metabolic health and even benefit a specifically susceptible group of patients with heart failure. See, www.ncbi.nlm.nih.gov/pubmed/25287287 and www.ncbi.nlm.nih.gov/pubmed/24925377.

2. Patients with obesity and/or cardiovascular disease were reported to have somehow elevated plasma levels of BCAA (see references in the 1st paragraph).

3. Dietary intake of BCAA (from foods or dietary supplements) does not correlate to plasma BCAA levels (see, www.ncbi.nlm.nih.gov/pubmed/26277881).

4. People with metabolic syndrome have a decreased capacity to break-down BCAA in the adipose tissue. Consequently, BCAA may accumulate in plasma of such subgroups of patients, when compared to healthy population (see, www.ncbi.nlm.nih.gov/pubmed/22560213).

As a conclusion; above points 1 – 4 demonstrate that, (A) BCAA circulating in the blood do not serve as biomarkers of their dietary intake, and (B) plasma BCAA may serve as one of the biomarkers for metabolic diseases, because cardiovascular pathologies and obesity influence BCAA break-down and overall homeostasis.