OBJECTIVE: (-)-Hydroxycitric acid
((-)-HCA) is available as a herbal supplement, and promoted as a weight
loss agent. It is hypothesized that (-)-HCA can increase fat oxidation by
inhibiting citrate lyase, an enzyme which plays a crucial role in energy
metabolism during de novo lipogenesis. The indirect inhibition of the
cytosolic pool of citrate by (-)-HCA and the subsequent reduction in
acetyl coenzyme A and oxaloacetate alters steps in the citric acid cycle
that promote fat oxidation. The objective of this study was to determine
the effect of (-)-HCA on marker substrates of altered metabolism, as well
as on respiratory quotient (RQ) and energy expenditure (EE) in humans,
following an overnight fast and during a bout of exercise.
HYPOTHESIS OF STUDY: We hypothesized
that supplementation with (-)-HCA would result in an increase in fat
oxidation and metabolic rate, reflected by an increase in beta-hydroxybutyrate
and EE and/or a decrease in RQ. Furthermore, during moderately intense
exercise, we hypothesized that (-)-HCA supplementation would increase the
rate of lactate conversion to glucose in the liver, with a subsequent
reduction of circulating lactate and an elevation of circulating ketone
bodies due to the increased partial oxidation of fatty acids (FA) in
mitochondria. Studies have examined the fat regulating action of (-)-HCA
on steps of the citric acid cycle in rodents showing reductions in body
weight and food intake. No studies have investigated the effects of
(-)-HCA supplementation in conjunction with a typical daily dietary
composition (that is approx 30-35% fat) on metabolic processes which could
influence body weight regulation in humans.
DESIGN: This was a double blind,
placebo controlled, randomized, crossover study involving three days of
(-)-HCA (3.0 g/d) or placebo supplementation. The effects of (-)-HCA
supplementation on metabolic parameters with or without moderately intense
exercise was studied over four laboratory visits.
SUBJECTS: Sedentary
adult male subjects (n = 10, age: 22-38 y, body mass index (BMI) 22.4-37.6
kg/m2).
MEASUREMENTS: Two of the four visits
involved no exercise (Protocol A) with and without (-)-HCA treatment,
while the remaining two visits included a moderately intense exercise bout
(Protocol B; 30 min at 40% maximal aerobic fitness (VO2max) and 15 min at
60% VO2max) with and without (-)-HCA treatment. EE (by indirect
calorimetry) and RQ were measured for 150 min following an overnight fast.
Blood samples were collected for the determination of glucose, insulin,
glucagon, lactate, and beta-hydroxybutyrate concentrations.
RESULTS: In a fasted state and
following 3 d of (-)-HCA treatment, RQ was not significantly lowered
during rest (Protocol A) nor during exercise (Protocol B) compared with
the placebo treatment. Treatment with (-)-HCA did not affect EE, either
during rest or during moderately intense exercise. Furthermore, the blood
substrates measured were not significantly different between treatment
groups under the fasting conditions of this study.
CONCLUSION: These results do not
support the hypothesis that (-)-HCA alters the short-term rate of fat
oxidation in the fasting state during rest or moderate exercise, with
doses likely to be achieved in humans while subjects maintain a typical
Western diet (approx 30-35% total calories as fat).
