Novel nutritional interventions in the manipulation of energy expenditure and blood glucose regulation in humans

The purpose of the studies described in this thesis was to study the purported metabolic effects of two dietary agents, L-Histidine and Epigallocatechingallate (EGCG). Supplementation of both LHistidine and pure EGCG in animal models has previously shown effects on components of energy balance and blood glucose regulation. Studies of their supplementation among humans are none (in case of L-Histidine) or very limited (in case of EGCG supplementation). The studies presented herein are novel as there have been no previous studies conducted to measure their effects on thermogenesis in humans and the present studies are the first to do. Three studies were performed to investigate metabolic effects of L-Histidine and two studies were performed to investigate metabolic effects of EGCG among healthy men. Duration of supplementation and varying doses were considered in different studies which led to the variation in study designs and protocols. Effects of L-Histidine: The metabolic effects of the essential amino acid L-Histidine (25 mg/kg) on healthy and overweight men were investigated in a series of studies. A pilot study was conducted to develop a protocol for measurement of resting metabolic rate (RMR), mean skin (MST), core temperature (CT) simultaneously. The protocol implemented was successful and was applied in all further studies. This study also examined the effect of L-Histidine supplementation (25 mg/kg) on RMR, MST, CT over a short period (3.25 hours). No conclusive results were obtained from this study. A single blind, placebo controlled cross-over study was then conducted to examine the effects of 10-day supplementation of L-Histidine on RMR, MST, CT and fasting blood glucose (FBG) in healthy male subjects (n = 9). Following L-Histidine ingestion, mean body weight (p = 0.008) and FBG (p = 0.04) were significantly reduced compared to baseline measurements. A randomised, parallel, single blinded and placebo controlled study was conducted following on from this to examine the effects of long-term (8 week, 25 mg/kg/day) intake of L-Histidine on RMR, MST, CT, lipid profile, FBG, insulin, leptin, non-esterified fatty acid (NEFA) and body fat composition in overweight and obese but otherwise healthy men (n = 18 (9 participants each in placebo and L-Histidine group)). Results of this study showed significantly decreased weight after 8 weeks (p = 0.007) compared to baseline, irrespective of the type of supplementation. Oral supplementation of L-Histidine improved FBG concentrations and reduced body weight after 10 days’ ingestion, however, no effects of long-term supplementation was established. Effects of EGCG: The second part of this thesis presents studies performed to investigate metabolic effects of pure EGCG. The first study was randomised, cross-over, placebo controlled and singleblinded in design. the effects of an oral intake of 150 mg pure EGCG over an acute period (2.5 hours), on key metabolic parameters and following an oral glucose challenge was measured (n = 8, healthy men). Results of this study were inconclusive on RMR, MST, CT plasma insulin, leptin and NEFA concentrations and appetite regulation. The second study tested the effects of varying doses (75, 150 and 300 mg/day) of pure EGCG on afore mentioned key metabolic parameters when supplemented over a period of 7 days each (n = 8, male). No significant changes in measured parameters were found. The results of these two studies indicate the need for further studies to investigate effects of EGCG on weight loss / weight maintenance possibly in combination with caffeine and/or other green tea flavanols. Both L-Histidine and EGCG supplmentations have previously shown to influence regulators of energy balance, blood glucose and cardiovascular risk factors via activation of the sympathetic nervous system in animal models. The present studies however did not provide any definitive conclusions following EGCG ingestion in healthy humans. L-Histidine supplementation brought about significant decrease in FBG and body weight after 10 days’ ingestion but its effect after 3.25 hours and 8 weeks was inconclusive. The effects following supplementation of both L-Histidine and EGCG ingestion needs to be further studied to clarify any potential metabolic consequences in humans.