title: A pilot, short-term dietary manipulation of branched chain amino acids has modest influence on fasting levels of branched chain amino acids.
abstract: BACKGROUND
  Elevated fasting levels of branched chain amino acids (BCAAs: valine, isoleucine, leucine) in venous blood are associated with a variety of metabolic impairments, including increased risk of type 2 diabetes (T2D). Fasting BCAA levels are influenced by non-dietary factors. However, it is unknown whether fasting BCAAs can be altered through manipulation of dietary intake alone.
  
  
  OBJECTIVE
  To test whether a specific dietary intervention, using differences in BCAA intake, alters fasting BCAA levels independent of other factors.
  
  
  METHODS
  Five healthy male volunteers underwent 4 days of a low and 4 days of a high BCAA content dietary intervention (ClinicalTrials.gov [NCT02110602]). All food and supplements were provided. Fasting BCAAs were measured from venous blood samples by mass spectrometry at baseline and after each intervention.
  
  
  RESULTS
  Diets were isocaloric; contained equal percentages of calories from carbohydrate, fats, and protein; and differed from each other in BCAA content (1.5±0.1 vs. 14.0±0.6 g for valine; 4.5±0.9 g vs. 13.8±0.5 g for isoleucine; 2.1±0.2 g vs. 27.1±1.0 g for leucine; p<0.0001 for all). Fasting valine was significantly lower (p=0.02) and fasting isoleucine and leucine were numerically lower following the low BCAA content vs. the high BCAA content diet levels. The inter-individual response to the dietary interventions was variable and not explained by adherence.
  
  
  CONCLUSIONS
  Short-term dietary manipulation of BCAA intake led to modest changes in fasting levels of BCAAs. The approach from our pilot study can be expanded to test the metabolic implications of dietary BCAA manipulation.
authors.affiliation: Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Nicole Landa
authors.initials: NL
authors.lastname: Cavallaro
authors.affiliation: Metabolism & Nutrition Research, Clinical Research Center, Massachusetts General Hospital, Boston, MA, USA.|Harvard Catalyst Clinical Translational Science Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Jamie
authors.initials: J
authors.lastname: Garry
authors.affiliation: Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Xu
authors.initials: X
authors.lastname: Shi
authors.affiliation: Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA.|Cardiology Division, Massachusetts General Hospital, Boston, MA, USA.|Harvard Medical School, Boston, MA, USA.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Gerszten
authors.affiliation: Metabolism & Nutrition Research, Clinical Research Center, Massachusetts General Hospital, Boston, MA, USA.|Harvard Catalyst Clinical Translational Science Center, Harvard Medical School, Boston, MA, USA.|Diabetes Research Center, Diabetes Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Ellen J
authors.initials: EJ
authors.lastname: Anderson
authors.affiliation: Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA.|Harvard Medical School, Boston, MA, USA.|Diabetes Research Center, Diabetes Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA; gwalford@partners.org.
authors.forename: Geoffrey A
authors.initials: GA
authors.lastname: Walford
keywords: branched chain amino acids; cross-over clinical trial; dietary intervention; insulin sensitivity; metabolism; nutritional modulation