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ARS Home » Pacific West Area » Davis, California » Western Human Nutrition Research Center » Obesity and Metabolism Research » Research » Publications at this Location » Publication #310083
Title: Whey protein supplementation does not alter plasma branched-chained amino acid profiles but results in unique metabolomics patterns in obese women enrolled in an 8-week weight loss trial

Author
item Piccolo, Brian
item COMERFORD, KEVIN - University Of California
item KARAKAS, SIDIKA - University Of California
item KNOTTS, TRINA - University Of California
item FIEHN, OLIVER - University Of California
item Adams, Sean

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/30/2014
Publication Date: 2/4/2015
Citation: Piccolo, B.D., Comerford, K.B., Karakas, S.E., Knotts, T.A., Fiehn, O., Adams, S.H. 2015. Whey protein supplementation does not alter plasma branched-chained amino acid profiles but results in unique metabolomics patterns in obese women enrolled in an 8-week weight loss trial. Journal of Nutrition. 145(4):691-700. doi: 10.3945/jn.114.203943.

Interpretive Summary: Elevations of plasma concentrations of branched-chain amino acids (BCAAs) are correlated with insulin resistance and type 2 diabetes (T2D), but the origins of this are not yet established. It is possible that these conditions impair normal amino acid metabolism in the body, alongside the more commonly-considered effects on blood glucose. Reduction in the activity of BCAA-breakdown enzymes such as branched-chain ketoacid dehydrogenase complex (BCKDC) activity and impaired complete mitochondrial BCAA catabolism may contribute to the phenomenon, and in turn contribute to disease or disease risk. The current study evaluated if a simple alteration in diet might normalize BCAA metabolism in insulin-resistant women, through provision of a BCAA-rich supplement, hypothesized to increase enzyme activities in the tissues. We investigated changes in the plasma metabolome (catalog of hundreds of metabolites in the blood) of 27 obese women with metabolic syndrome before and after weight loss, with a diet complemented with either a 20 g/d whey- (BCAA-rich) or gelatin- (BCAA-poor) protein supplement. When matched for total protein by gram weight, whey has three times the amount of BCAAs compared to gelatin. All BCAAs were significantly correlated with an insulin resistance score pre-intervention, consistent with altered BCAA metabolism in the pre-diabetic state. Post-intervention plasma leucine, isoleucine, and valine (BCAAs) trended lower in the whey protein-supplemented group compared to gelatin protein-supplemented controls. Multivariate statistical analysis of untargeted plasma metabolomics provided evidence of specific alterations of proline- and cysteine-related pathways following whey-protein- versus gelatin-protein supplementation. The results suggest that a whey-protein supplement has potential to modify the body’s ability to metabolize BCAA and some other amino acids, which in turn could influence metabolic health. More studies are warranted to understand dose amount and timing to determine if a whey protein regimen in women with metabolic syndrome and diabetes risk can improve blood glucose regulation and normalize metabolite patterns in the blood.

Technical Abstract: Background. Elevations of plasma concentrations of branched-chain amino acids (BCAA) are correlated with insulin resistance. Reduction in the activity of branched-chain ketoacid dehydrogenase complex (BCKDC) activity and impaired complete mitochondrial BCAA catabolism may contribute to this phenotype. Evidence in animals suggests dietary protein consumption can increase BCKDC activity, but there is limited evidence in humans. Objective. We hypothesize that a diet rich in BCAA will elicit an adaptive increase in BCKDC expression and activity, which will manifest in a reduction of overnight-fasted plasma BCAA concentrations. Methods. We investigated changes in the plasma metabolome of 27 obese women with metabolic syndrome before and after weight loss to identify changes in BCAA metabolism. Subjects were enrolled in an 8-week weight loss study complemented with either a 20 g/d whey- or gelatin-protein supplement. When matched for total protein by gram weight, whey has three times the amount of BCAAs compared to gelatin. Results. Post-intervention plasma leucine, isoleucine, and valine trended lower in the whey protein-supplemented group compared to gelatin protein-supplemented controls (P = 0.07, treatment effect for total BCAA). All BCAAs were significantly correlated with HOMA at baseline (r = 0.52; 0.43; 0.49 for leucine, isoleucine, valine, respectively: P < 0.05), but these relationships weakened after weight loss. Multivariate statistical analysis of untargeted plasma metabolomics provided evidence of specific alterations of proline- and cysteine-related pathways following whey-protein- versus gelatin-protein supplementation. Conclusion. An 8-week supplementation of 20 g/d whey-protein in women with metabolic syndrome moderately decreased plasma BCAA abundance, and additional studies are warranted to determine if this phenotype associates with increased tissue BCKDC activity as per our working model. Furthermore, BCAAs were associated with insulin resistance before, but not after, weight loss, suggesting that factors associated with calorie restriction (i.e., or reduced visceral adiposity), impact how plasma BCAAs relate to insulin sensitivity indices.