Sport Physiology

Sport Physiology

The Effect of Hydroxy-Beta-Methylbutyrate and Caffeine Supplementation on Growth Hormone Levels Following Resistance Exercise in Obese Women

Document Type : Research Paper

Authors
1 Department of Physical Education and Sport Sciences, Marivan Branch, Islamic Azad University, Marivan, Iran
2 Department of Physical Education and Sport Sciences, Faculty of Humanities and Social Sciences, University of Kurdistan, Sanandaj, Iran
Abstract
Background and Purpose
Growth hormone (GH) is a potent anabolic hormone that affects multiple systems in the body and plays an important role in lipid metabolism in various locations such as the liver, skeletal muscle, and visceral adipose tissue. Exercise is a potent physiological stimulus for GH secretion, and both aerobic and resistance exercise result in significant, acute increases in GH secretion. The administration of exercise as a stimulus to elicit a GH response in obese individuals is of considerable importance, as it may offer a non-pharmacological approach to reduce adipose tissue deposits and increase lean muscle mass. However, studies have shown that resistance exercise is less able to increase circulating GH in obese individuals than in normal or lean individuals. B hydroxy-b-methylbutyrate (HMB), a metabolite of the amino acid leucine, has been shown to promote strength and lean muscle mass when supplemented in conjunction with resistance training. HMB administration has been shown to increase GH and IGF-I mRNA levels in in vitro and in vivo models, and acute and chronic HMB administration has been reported to increase serum GH levels in normal individuals. The higher bioavailability may rationalize acute supplementation with HMB as a means to enhance the anabolic response resulting from heavy resistance training. Some studies have reported that caffeine is associated with a decrease in GH levels, while others have reported an increase. Our secondary aim was to investigate the effect of caffeine consumption on GH levels after resistance exercise in obese individuals. Therefore, the present study investigated the effect of HMB and caffeine supplementation on GH levels following a single session of resistance exercise in obese individuals.
Materials and Methods
The statistical population consisted of inactive obese women aged 28 to 44 years and without any disease (diabetes, cardiovascular disease, motor disorders, etc.). Among 16 eligible volunteers, 11 volunteers were selected by simple random sampling. All subjects gave their written consent before their inclusion in the study. At least ten days before the experiments, anthropometric and 1-repetition maximum (1RM) measurements were collected, and the subjects were familiarized with the exercise scheme. Percent body fat was calculated by using the equation of Brozek et al. Subjects performed a resistance exercise test in four conditions of placebo (P), HMB (H), caffeine (C), and a combination of HMB and caffeine (HC) in a within-group design with reciprocal balancing. Subjects in condition H consumed 3 g of HMB, 6 mg per kilogram of body weight of caffeine in condition C and condition HC in a combined amount of both conditions, and in condition P also consumed maltodextrin. HMB was consumed 30 minutes and caffeine one hour before the test. The interval between test sessions was one week. Subjects were engaged in a standardized pre-prepared breakfast for 15 minutes in the morning of each session. Blood samples were taken from the subjects after 180 minutes of rest. After consuming the relevant supplement and after the required time, they started to perform sports activities with a predetermined intensity. The next blood sample was taken immediately after the exercise and the third blood sample was taken 30 minutes after the end of the exercise. The serum samples were placed at room temperature for 20min after being transferred to the tubes. The serum was obtained after 20min of centrifugation (3,000 rpm, 4°C) and stored at -20°C until further analysis. Two-way analysis of variance with repeated measures and Tukey's post hoc test were used to examine the differences within and between groups with a prespecified experimental type I error rate of 0.05 was used to maintain a type I error rate of 0.05. All calculations were analyzed with SPSS21 software at a statistical level of p<0.05. Normal distribution for all variables was verified with the Shapiro-Wilk test. For all repeated-measures ANOVAs, Mauchly’s test of sphericity was performed to assess the equality of variances between groups. All the data were expressed as means ± SD, and the statistical significance was accepted for p<0.05.
Findings
All subjects completed the acute resistance exercise session. The data had a normal distribution, and the assumption of homogeneity of variance was violated. In different test conditions, the difference in mean GH levels was significant only in condition H (F=23.27, p=0.001), in which GH levels were significantly higher than resting levels (p=0.001) and 30 minutes after exercise (p=0.003). GH levels immediately after exercise were higher than levels of this hormone in other conditions (p<0.05). GH levels in other conditions including conditions C, P and HC did not change significantly (p>0.05). Changes in mean insulin and glucose levels in different test conditions were not significant (p>0.05).
Conclusion
In summary, these results appear to be the first study to demonstrate that three grams of HMB can significantly increase GH following acute, high-intensity resistance exercise compared with placebo in obese women. This finding makes important contributions to our understanding of how HMB affects endocrine function in obese individuals. Caffeine does not appear to make a difference in circulating GH levels following resistance exercise.
Article message 
Considering our results regarding the lack of GH increase in obese women during resistance exercise but its increase with HMB consumption, it seems that HMB consumption before resistance exercise can increase GH in obese individuals. On the other hand, caffeine, either alone or in combination with HMB, has no effect on GH levels in obese individuals.
Funding
The present study did not receive any financial support.
Authors’ Contributions
All authors contributed to the design, implementation, and writing of all parts of this study.
Conflicts of Interest
The authors declare no conflict of interest.
Acknowledgement
We would like to thank the subjects of the present study.
Keywords
Subjects

1.       de Sá-Caputo DdC, Bernardo-Filho M, Taiar R, de Oliveira Maranhão TM. Obesity: The Relationship between Growth Hormone and Exercises.  Growth Hormone-Impact and Insights in Human Beings: IntechOpen; 2023.
2.       Verheggen R, Maessen M, Green DJ, Hermus A, Hopman M, Thijssen D. A systematic review and meta‐analysis on the effects of exercise training versus hypocaloric diet: distinct effects on body weight and visceral adipose tissue. Obesity reviews. 2016;17(8):664-90.
3.       Dehkhoda F, Lee CM, Medina J, Brooks AJ. The growth hormone receptor: mechanism of receptor activation, cell signaling, and physiological aspects. Frontiers in endocrinology. 2018;9:35.
4.       Wideman L, Weltman JY, Hartman ML, Veldhuis JD, Weltman A. Growth hormone release during acute and chronic aerobic and resistance exercise: recent findings. Sports medicine. 2002;32:987-1004.
5.       Iranmanesh A, Lizarralde G, Veldhuis JD. Age and relative adiposity are specific negative determinants of the frequency and amplitude of growth hormone (GH) secretory bursts and the half-life of endogenous GH in healthy men. The Journal of Clinical Endocrinology & Metabolism. 1991;73(5):1081-8.
6.       Vijayakumar A, Yakar S, LeRoith D. The intricate role of growth hormone in metabolism. Frontiers in endocrinology. 2011;2:32.
7.       Nicholls AR, Holt RI. Growth hormone and insulin-like growth factor-1. Sports Endocrinology. 2016;47:101-14.
8.       Saxton SN, Clark BJ, Withers SB, Eringa EC, Heagerty AM. Mechanistic links between obesity, diabetes, and blood pressure: role of perivascular adipose tissue. Physiological reviews. 2019;99(4):1701-63.
9.       Thomas GA, Kraemer WJ, Comstock BA, Dunn-Lewis C, Maresh CM, Volek JS. Obesity, growth hormone and exercise. Sports medicine. 2013;43:839-49.
10.   Scacchi M, Pincelli A, Cavagnini F. Growth hormone in obesity. International journal of obesity. 1999;23(3):260-71.
11.   Kanaley J, Weatherup-Dentes M, Jaynes E, Hartman M. Obesity attenuates the growth hormone response to exercise. The Journal of Clinical Endocrinology & Metabolism. 1999;84(9):3156-61.
12.   Zanchi NE, Gerlinger-Romero F, Guimaraes-Ferreira L, de Siqueira Filho MA, Felitti V, Lira FS, et al. HMB supplementation: clinical and athletic performance-related effects and mechanisms of action. Amino acids. 2011;40:1015-25.
13.   Arazi H, Rohani H, Ghiasi A, Keikanloo NA. Resistance training & beta-hydroxy-beta-methylbutyrate supplementation on hormones. Revista Brasileira de Medicina do Esporte. 2015;21(5):386-9.
14.   Wilson JM, Lowery RP, Joy JM, Andersen J, Wilson SM, Stout JR, et al. The effects of 12 weeks of beta-hydroxy-beta-methylbutyrate free acid supplementation on muscle mass, strength, and power in resistance-trained individuals: a randomized, double-blind, placebo-controlled study. European journal of applied physiology. 2014;114:1217-27.
15.               Townsend J, Stout J, Hoffman J, Gonzalez A, Jajtner A, Wells A, et al. Acute anabolic response to β-hydroxy-β-methylbutyrate (HMB)-free acid supplementation following heavy resistance exercise. Journal of the International Society of Sports Nutrition. 2014;11(1):1-.
16.               Townsend JR, Hoffman JR, Gonzalez AM, Jajtner AR, Boone CH, Robinson EH, et al. Effects of β‐hydroxy‐β‐methylbutyrate free acid ingestion and resistance exercise on the acute endocrine response. International journal of endocrinology. 2015;2015(1):856708.
17.               Durkalec-Michalski K, Jeszka J, Podgórski T. The effect of a 12-week beta-hydroxy-beta-methylbutyrate (HMB) supplementation on highly-trained combat sports athletes: A randomised, double-blind, placebo-controlled crossover study. Nutrients. 2017;9(7):753.
18.               Starling-Soares B, Pereira M, Renke G. Extrapolating the Coffee and Caffeine (1, 3, 7-Trimethylxanthine) Effects on Exercise and Metabolism—A Concise Review. Nutrients. 2023;15(24):5031.
19.               Jankowski-Wilkinson AF. The Effects of Caffeine Gum Administration on Reaction Time and Lower Body Pain During Cycling to Exhaustion: University of Akron; 2008.
20.               Beck TW, Housh TJ, Malek MH, Mielke M, Hendrix R. The acute effects of a caffeine-containing supplement on bench press strength and time to running exhaustion. The Journal of Strength & Conditioning Research. 2008;22(5):1654-8.
21.               Wu B-H, Lin J-C. Caffeine attenuates acute growth hormone response to a single bout of resistance exercise. Journal of Sports Science & Medicine. 2010;9(2):262.
22.               Rahimi MR, Semenova EA, John G, Fallah F, Larin AK, Generozov EV, et al. Effect of ADORA2A Gene Polymorphism and Acute Caffeine Supplementation on Hormonal Response to Resistance Exercise: A Double-Blind, Crossover, Placebo-Controlled Study. Nutrients. 2024;16(12):1803.
23.               Rahimi R, Khodamoradi M, Falah F. Effects of caffeine consumption before resistance exercise on blood levels of testosterone and growth hormones in male athletes. Koomesh. 2019;21(4):679-85.
24.               Wilson GJ, Wilson JM, Manninen AH. Effects of beta-hydroxy-beta-methylbutyrate (HMB) on exercise performance and body composition across varying levels of age, sex, and training experience: A review. Nutrition & metabolism. 2008;5:1-17.
25.               Health UDo, Services H. 2018 Physical activity guidelines advisory committee. 2018 Physical activity guidelines advisory committee scientific report. 2018.
26.               Portal S, Eliakim A, Nemet D, Halevy O, Zadik Z. Effect of HMB supplementation on body composition, fitness, hormonal profile and muscle damage indices. Journal of Pediatric Endocrinology and Metabolism. 2010;23(7):641-50.
27.               Rahimi R, Qaderi M, Faraji H, Boroujerdi SS. Effects of very short rest periods on hormonal responses to resistance exercise in men. The Journal of Strength & Conditioning Research. 2010;24(7):1851-9.
28.               Asadi A, Arazi H, Suzuki K. Effects of Nutrients. 2017;9(12):1316.
29.               Rahimi MR, Faraji H, Khodamoradi M. CYP1A2 genotype and acute effects of caffeine intake on growth hormone and testosterone response to resistance exercise. Sport Sciences and Health Research. 2024;16(2).
30.               Hallworth JR, Copeland JL, Doan J, Hazell TJ. The Effect of Exercise Intensity on Total PYY and GLP-1 in Healthy Females: A Pilot Study. Journal of nutrition and metabolism. 2017;2017.
31.               Sabag A, Chang D, Johnson NA. Growth hormone as a potential mediator of aerobic exercise-induced reductions in visceral adipose tissue. Frontiers in physiology. 2021;12:623570.
32.               Oliver SR, Rosa JS, Minh TD, Pontello AM, Flores RL, Barnett M, et al. Dose-dependent relationship between severity of pediatric obesity and blunting of the growth hormone response to exercise. Journal of Applied Physiology. 2010;108(1):21-7.
33.               Weltman A, Weltman JY, Watson Winfield DD, Frick K, Patrie J, Kok P, et al. Effects of continuous versus intermittent exercise, obesity, and gender on growth hormone secretion. The Journal of Clinical Endocrinology & Metabolism. 2008;93(12):4711-20.
34.               Thomas GA, Kraemer WJ, Kennett MJ, Comstock BA, Maresh CM, Denegar CR, et al. Immunoreactive and bioactive growth hormone responses to resistance exercise in men who are lean or obese. Journal of applied physiology. 2011;111(2):465-72.
35.               Gerlinger-Romero F, Guimarães-Ferreira L, Giannocco G, Nunes MT. Chronic supplementation of beta-hydroxy-beta methylbutyrate (HMβ) increases the activity of the GH/IGF-I axis and induces hyperinsulinemia in rats. Growth Hormone & IGF Research. 2011;21(2):57-62.
36.               Peng L-N, Cheng Y-C, Yu P-C, Lee W-J, Lin M-H, Chen L-K. Oral nutritional supplement with β-hydroxy-β-methylbutyrate (HMB) improves nutrition, physical performance and ameliorates intramuscular adiposity in pre-frail older adults: a randomized controlled trial. The Journal of nutrition, health and aging. 2021;25(6):767-73.
37.               Kraemer WJ, Ratamess NA. Hormonal responses and adaptations to resistance exercise and training. Sports medicine. 2005;35(4):339-61.
38.               Guessous I, Dobrinas M, Kutalik Z, Pruijm M, Ehret G, Maillard M, et al. Caffeine intake and CYP1A2 variants associated with high caffeine intake protect non-smokers from hypertension. Human molecular genetics. 2012;21(14):3283-92.
39.               Fulton JL, Dinas PC, Carrillo AE, Edsall JR, Ryan EJ, Ryan EJ. Impact of genetic variability on physiological responses to caffeine in humans: A systematic review. Nutrients. 2018;10(10):1373.
40.               Keijzers GB, De Galan BE, Tack CJ, Smits P. Caffeine can decrease insulin sensitivity in humans. Diabetes care. 2002;25(2):364-9.
41.               Thong FS, Derave W, Kiens B, Graham TE, Ursø B, Wojtaszewski JF, et al. Caffeine-induced impairment of insulin action but not insulin signaling in human skeletal muscle is reduced by exercise. Diabetes. 2002;51(3):583-90.
42.               Tsuda S, Egawa T, Kitani K, Oshima R, Ma X, Hayashi T. Caffeine and contraction synergistically stimulate 5′‐AMP‐activated protein kinase and insulin‐independent glucose transport in rat skeletal muscle. Physiological reports. 2015;3(10):e12592.
43.               Hauck D, Braun W, editors. The Influence of Caffeine on Resistance Exercise Performance and Post-Exercise Glucose Control. International Journal of Exercise Science: Conference Proceedings; 2018.
44.               Zaharieva DP, Riddell MC. Caffeine and glucose homeostasis during rest and exercise in diabetes mellitus. Applied Physiology, Nutrition, and Metabolism. 2013;38(8):813-22.
45.               Herrod PJ, Gharahdaghi N, Rudrappa SS, Phillips HG, Ranat RA, Hardy EJ, et al. The impact of acute beta-hydroxy-beta-methylbutyrate (HMB) ingestion on glucose and insulin kinetics in young and older men. Journal of Functional Foods. 2020;73:104163.
46.               Leelarungrayub D, Sallepan M, Charoenwattana S. Effects of acute caffeinated coffee consumption on energy utilization related to glucose and lipid oxidation from short submaximal Treadmill exercise in sedentary Men. Nutrition and metabolic insights. 2011;4:NMI. S8299.
Volume 16, Issue 64
Summer 2025
Pages 91-72

  • Receive Date 09 March 2025
  • Revise Date 16 June 2025
  • Accept Date 05 July 2025