Mechanism for the Increase in Human Growth Hormone with Administration of a Novel Test Supplement and Results Indicating Improved Physical Fitness and Sleep Efficiency

Abstract

An oral test supplement increases serum human growth hormone (hGH) levels after acute administration in healthy adults. We investigated the mechanism for the increase in hGH and the effect of continued daily administration of the test supplement on measures of physical fitness and sleep efficiency. In Study 1, serum triiodothyronine (T3) was measured in samples from a prior placebo-controlled, double-blind study in which 16 healthy participants received both placebo and the test supplement in a crossover design; treatment order was randomized, and treatments were separated by a 1-week washout. In Study 2, physical fitness (VO2 max) was measured at baseline and after 2 weeks of daily administration of the test supplement (N = 12 healthy participants). Study 3 assessed daily sleep onset latency and time awake during 3 weeks of daily administration of the test supplement (N = 15 healthy participants). A fall from baseline in T3 was observed with placebo (-6.1 ± 8.5 ng/dL, P = .01). Of note, the change in T3 was smaller with the test supplement (-3.3 ± 10.7 ng/dL, P = not significant) but was not statistically different from placebo. Mean VO2 max increased by 6% from baseline after 2 weeks (P = .02). Sleep-onset latency and time awake during the night were reduced from baseline to week 3 by 22% and 65%, respectively (P = .01 and P = .02). The conservation of T3 levels suggests that the mechanism for increased hGH secretion by the test supplement is through somatostatin inhibition. Furthermore, pilot studies indicated that daily administration of the supplement improved physical fitness and sleep efficiency from baseline, effects consistent with increased endogenous hGH release. Clinical Trial Registration No. NCT02987868.

Keywords: growth hormone; growth hormone secretagogue; insulin-like growth factor-1; somatostatin.

Conflict of interest statement

A.L.H. is an employee of Bydex Management, LLC. C.K. is a consultant for Basic Research, LLC. F.L.G. is a consultant for Beachbody, Basic Research, LLC, Eisai, Inc., General Nutrition Corporation, Melior Discoveries, and Techenterprises, is on advisory boards for Baronova, Inc., Curves-Jenny Craig, Gelesis, Microbiome Therapeutics, Novo Nordisk, Novartis, Plensat, and Zafgen, holds stock or stock options in Microbiome Therapeutics, Plensat, and Zafgen, and holds patents in Neuroquest. C.S.T. and J.R. have no conflict of interest.

Figures

FIG. 1.

Pathways involved in regulation of hGH and downstream effects. hGH exerts direct and indirect (i.e., via IGF-1) effects on CNS and peripheral tissues. Neurons that release GHRH and somatostatin act directly on pituitary cells to influence hGH release. Somatostatin inhibits hGH and TSH release from the pituitary. TSH stimulates production of T4 by the thyroid gland, which is then converted to T3. Ghrelin, a peptide hormone produced by the stomach, stimulates hGH release. hGH stimulates release of IGF-1 from liver and other tissues. CNS, central nervous system, GHRH, growth hormone releasing hormone; hGH, human growth hormone; IGF-1, insulin-like growth factor 1; T3, triiodothyronine; T4, thyroxine; TSH, thyroid-stimulating hormone.

FIG. 2.

Effect of the test supplement on T3, VO2 max, and sleep quality. (A) Mean ± SEM change from baseline (t = 0) to endpoint (t = 120 min) in T3 observed following administration of placebo or the test supplement (treatment was a crossover design in which all individuals, N = 16, received the placebo or test supplement, treatment order was randomized and separated by a 1-week washout period). (B) Mean ± SD VO2 max observed in the same individuals, N = 12, at baseline before treatment and after 14 days of administration of the test supplement. (C) Geometric mean for sleep onset latency and time awake are shown for each day from day 0 to week 3 in healthy individuals, N = 15. Lines represent the population-level predicted regression lines. Mixed-effect Poisson models were fit to the individual data per night. Sleep onset latency model: log(μ(t)) = 2.905 – 0.091t, where μ is the mean sleep onset latency at time t. Time awake model: log(μ(t)) = 1.657 – 0.390t, where μ is the mean sleep onset latency at time t. *p < 0.05 vs. baseline. SD, standard deviation; SEM, standard error of the mean.