Studies analyzing the effects of VLCKD-induced WL on metabolic and hormonal profile, SF and reproductive health in males. Both mean weight (kg) and BMI (kg/m2) refer to baseline
n: number of subjects; age: mean age (years); weight: mean weight (kg); BMI: mean body mass index (kg/m2); D: vitamin D; PSA: prostate-specific antigen; RF: reproductive function; NA: not available; AMS: Aging Males’ Symptoms Scale. ↓: decrease; ↑: increase; -: none; =: unchanged
Declarations
Author contributions
GI: Conceptualization, Investigation, Writing—original draft, Writing—review & editing. CI: Investigation, Writing—original draft. PM and MV: Validation, Writing—review & editing, Supervision. All authors read and approved the submitted version.
Conflicts of interest
The authors declare that they have no conflicts of interest.
Caprio M, Infante M, Moriconi E, Armani A, Fabbri A, Mantovani G, et al.; Cardiovascular Endocrinology Club of the Italian Society of Endocrinology. Very-low-calorie ketogenic diet (VLCKD) in the management of metabolic diseases: systematic review and consensus statement from the Italian Society of Endocrinology (SIE).J Endocrinol Invest. 2019;42:1365–86. [DOI] [PubMed]
Chooi YC, Ding C, Magkos F. The epidemiology of obesity.Metabolism. 2019;92:6–10. [DOI] [PubMed]
Xu H, Li X, Adams H, Kubena K, Guo S. Etiology of metabolic syndrome and dietary intervention.Int J Mol Sci. 2019;20:128. [DOI] [PubMed] [PMC]
Van Dyken P, Lacoste B. Impact of metabolic syndrome on neuroinflammation and the blood-brain barrier.Front Neurosci. 2018;12:930. [DOI] [PubMed] [PMC]
La Vignera S, Cannarella R, Galvano F, Grillo A, Aversa A, Cimino L, et al. The ketogenic diet corrects metabolic hypogonadism and preserves pancreatic β-cell function in overweight/obese men: a single-arm uncontrolled study.Endocrine. 2021;72:392–9. [DOI] [PubMed] [PMC]
Mongioì LM, Cimino L, Condorelli RA, Magagnini MC, Barbagallo F, Cannarella R, et al. Effectiveness of a very low calorie ketogenic diet on testicular function in overweight/obese men.Nutrients. 2020;12:2967. [DOI] [PubMed] [PMC]
Bellastella G, Menafra D, Puliani G, Colao A, Savastano S, Obesity Programs of nutrition, Education; Research and Assessment (OPERA) Group. How much does obesity affect the male reproductive function?Int J Obes Suppl. 2019;9:50–64. [DOI] [PubMed] [PMC]
Chambers TJ, Richard RA. The impact of obesity on male fertility.Hormones (Athens). 2015;14:563–8. [DOI] [PubMed]
Ilacqua A, Francomano D, Aversa A. Obesity and testicular function. In: Lenzi A, Migliaccio S, Donini LM, editors. Multidisciplinary approach to obesity.Cham: Springer. 2014. pp. 99–106.
Derby CA, Zilber S, Brambilla D, Morales KH, McKinlay JB. Body mass index, waist circumference and waist to hip ratio and change in sex steroid hormones: the Massachusetts Male Ageing Study.Clin Endocrinol (Oxf). 2006;65:125–31. [PubMed]
Pivonello R, Menafra D, Riccio E, Garifalos F, Mazzella M, de Angelis C, et al. Metabolic disorders and male hypogonadotropic hypogonadism.Front Endocrinol (Lausanne). 2019;10:345. [DOI] [PubMed] [PMC]
Aversa A, Morgentaler A. The practical management of testosterone deficiency in men.Nat Rev Urol. 2015;12:641–50. [DOI] [PubMed]
Barbosa-Desongles A, Hernández C, Simó R, Selva DM. Testosterone induces cell proliferation and cell cycle gene overexpression in human visceral preadipocytes.Am J Physiol Cell Physiol. 2013;305:C355–9. [DOI] [PubMed]
Xu W, Morford J, Mauvais-Jarvis F. Emerging role of testosterone in pancreatic β cell function and insulin secretion.J Endocrinol. 2019;[Epub ahead of print]. [DOI] [PubMed] [PMC]
Könner AC, Brüning JC. Selective insulin and leptin resistance in metabolic disorders.Cell Metab. 2012;16:144–52. [DOI] [PubMed]
Oh JY, Barrett-Connor E, Wedick NM, Wingard DL; Rancho Bernardo Study. Endogenous sex hormones and the development of type 2 diabetes in older men and women: the Rancho Bernardo study.Diabetes Care. 2002;25:55–60. [DOI] [PubMed]
Haring R, Ittermann T, Völzke H, Krebs A, Zygmunt M, Felix SB, et al. Prevalence, incidence and risk factors of testosterone deficiency in a population-based cohort of men: results from the study of health in Pomerania.Aging Male. 2010;13:247–57. [DOI] [PubMed]
Russell SH, Small CJ, Stanley SA, Franks S, Ghatei MA, Bloom SR. The in vitro role of tumour necrosis factor-alpha and interleukin-6 in the hypothalamic-pituitary gonadal axis.J Neuroendocrinol. 2001;13:296–301. [DOI] [PubMed]
Watanobe H, Hayakawa Y. Hypothalamic interleukin-1β and tumor necrosis factor-α, but not interleukin-6, mediate the endotoxin-induced suppression of the reproductive axis in rats.Endocrinology. 2003;144:4868–75. [DOI]
Laaksonen DE, Niskanen L, Punnonen K, Nyyssönen K, Tuomainen TP, Valkonen VP, et al. The metabolic syndrome and smoking in relation to hypogonadism in middle-aged men: a prospective cohort study.J Clin Endocrinol Metab. 2005;90:712–9. [DOI] [PubMed]
Saboor Aftab SA, Kumar S, Barber TM. The role of obesity and type 2 diabetes mellitus in the development of male obesity-associated secondary hypogonadism.Clin Endocrinol (Oxf). 2013;78:330–7. [DOI] [PubMed]
Bellastella G, Maiorino MI, Bizzarro A, Giugliano D, Esposito K, Bellastella A, et al. Revisitation of autoimmune hypophysitis: knowledge and uncertainties on pathophysiological and clinical aspects.Pituitary. 2016;19:625–42. [DOI] [PubMed] [PMC]
Bellastella A, Bizzarro A, Coronella C, Bellastella G, Sinisi AA, De Bellis A. Lymphocytic hypophysitis: a rare or underestimated disease?Eur J Endocrinol. 2003;149:363–76. [DOI] [PubMed]
Teerds KJ, de Rooij DG, Keijer J. Functional relationship between obesity and male reproduction: from humans to animal models.Hum Reprod Update. 2011;17:667–83. [DOI] [PubMed]
Isidori AM, Caprio M, Strollo F, Moretti C, Frajese G, Isidori A, et al. Leptin and androgens in male obesity: evidence for leptin contribution to reduced androgen levels.J Clin Endocrinol Metab. 1999;84:3673–80. [DOI] [PubMed]
Simó R, Sáez-López C, Barbosa-Desongles A, Hernández C, Selva DM. Novel insights in SHBG regulation and clinical implications.Trends Endocrinol Metab. 2015;26:376–83. [DOI] [PubMed]
Martins AD, Majzoub A, Agawal A. Metabolic syndrome and male fertility.World J Mens Health. 2019;37:113–27. [DOI] [PubMed] [PMC]
Eisenberg ML, Kim S, Chen Z, Sundaram R, Schisterman EF, Buck Louis GM. The relationship between male BMI and waist circumference on semen quality: data from the LIFE study.Hum Reprod. 2014;29:193–200. [DOI] [PubMed] [PMC]
Stewart TM, Liu DY, Garrett C, Jørgensen N, Brown EH, Baker HW. Associations between andrological measures, hormones and semen quality in fertile Australian men: inverse relationship between obesity and sperm output.Hum Reprod. 2009;24:1561–8. [DOI] [PubMed]
Tsao CW, Liu CY, Chou YC, Cha TL, Chen SC, Hsu CY. Exploration of the association between obesity and semen quality in a 7630 male population.PLoS One. 2015;10:e0119458. [DOI] [PubMed] [PMC]
Hammiche F, Laven JS, Twigt JM, Boellaard WP, Steegers EA, Steegers-Theunissen RP. Body mass index and central adiposity are associated with sperm quality in men of subfertile couples.Hum Reprod. 2012;27:2365–72. [DOI] [PubMed]
Leisegang K, Bouic PJ, Henkel RR. Metabolic syndrome is associated with increased seminal inflammatory cytokines and reproductive dysfunction in a case-controlled male cohort.Am J Reprod Immunol. 2016;76:155–63. [DOI] [PubMed]
Esposito K, Ciotola M, Giugliano F, Maiorino MI, Autorino R, De Sio M, et al. Effects of intensive lifestyle changes on erectile dysfunction in men.J Sex Med. 2009;6:243–50. [DOI] [PubMed]
Corona G, Rastrelli G, Monami M, Saad F, Luconi M, Lucchese M, et al. Body weight loss reverts obesity-associated hypogonadotropic hypogonadism: a systematic review and meta-analysis.Eur J Endocrinol. 2013;168:829–43. [DOI] [PubMed]
Kaukua J, Pekkarinen T, Sane T, Mustajoki P. Sex hormones and sexual function in obese men losing weight.Obes Res. 2003;11:689–94. [DOI] [PubMed]
Khoo J, Piantadosi C, Worthley S, Wittert GA. Effects of a low-energy diet on sexual function and lower urinary tract symptoms in obese men.Int J Obes (Lond). 2010;34:1396–403. [DOI] [PubMed]
Khoo J, Piantadosi C, Duncan R, Worthley SG, Jenkins A, Noakes M, et al. Comparing effects of a low-energy diet and a high-protein low-fat diet on sexual and endothelial function, urinary tract symptoms, and inflammation in obese diabetic men.J Sex Med. 2011;8:2868–75. [DOI] [PubMed]
Niskanen L, Laaksonen DE, Punnonen K, Mustajoki P, Kaukua J, Rissanen A. Changes in sex hormone-binding globulin and testosterone during weight loss and weight maintenance in abdominally obese men with the metabolic syndrome.Diabetes Obes Metab. 2004;6:208–15. [DOI] [PubMed]
Hoffer LJ, Beitins IZ, Kyung NH, Bistrian BR. Effects of severe dietary restriction on male reproductive hormones.J Clin Endocrinol Metab. 1986;62:288–92. [DOI] [PubMed]
Klibanski A, Beitins IZ, Badger T, Little R, McArthur JW. Reproductive function during fasting in men.J Clin Endocrinol Metab. 1981;53:258–63. [DOI] [PubMed]
Colling C, Bredella MA, Fazeli PK, Pachón-Peña G, Singh RJ, Rosen CJ, et al. Changes in serum cortisol levels after 10 days of overfeeding and fasting.Am J Physiol Endocrinol Metab. 2023;324:E506–13. [DOI] [PubMed]
Stanik S, Dornfeld LP, Maxwell MH, Viosca SP, Korenman SG. The effect of weight loss on reproductive hormones in obese men.J Clin Endocrinol Metab. 1981;53:828–32. [DOI] [PubMed]
Strain GW, Zumoff B, Miller LK, Rosner W, Levit C, Kalin M, et al. Effect of massive weight loss on hypothalamic-pituitary-gonadal function in obese men.J Clin Endocrinol Metab. 1988;66:1019–23. [DOI] [PubMed]
Håkonsen LB, Thulstrup AM, Aggerholm AS, Olsen J, Bonde JP, Andersen CY, et al. Does weight loss improve semen quality and reproductive hormones? Results from a cohort of severely obese men.Reprod Health. 2011;8:24. [DOI] [PubMed] [PMC]
Jaffar M, Ashraf M. Does weight loss improve fertility with respect to semen parameters—results from a large cohort study.Int J Infertil Fetal Med. 2017;8:12–7. [DOI]
Caruso P, Caputo M, Cirillo P, Scappaticcio L, Longo M, Maiorino MI, et al. Effects of Mediterranean diet on semen parameters in healthy young adults: a randomized controlled trial.Minerva Endocrinol. 2020;45:280–7. [DOI] [PubMed]
Ilacqua A, Izzo G, Emerenziani GP, Baldari C, Aversa A. Lifestyle and fertility: the influence of stress and quality of life on male fertility.Reprod Biol Endocrinol. 2018;16:115. [DOI] [PubMed] [PMC]
Silva T, Jesus M, Cagigal C, Silva C. Food with influence in the sexual and reproductive health.Curr Pharm Biotechnol. 2019;20:114–22. [DOI] [PubMed]
Renck A, Thiago TA, Souza MRd, Cardoso PdN, Trarbach EB, Hallak J, et al. Effect of significant weight loss by very low calorie ketogenic diet on male obesity secondary hypogonadism and sexual function.Bioscientifica. 2020;70:EP380. [DOI]
Renck A, Thiago TA, Pariz JR, Trarbach EB, Hallak J, Costa EMF. Semen quality improvement after weight loss by very low-calorie ketogenic dietary: a report of two cases.Bioscientifica. 2020;70:EP379. [DOI]
Cignarelli A, Santi D, Genchi VA, Conte E, Giordano F, Di Leo S, et al. Very low-calorie ketogenic diet rapidly augments testosterone levels in non-diabetic obese subjects.Andrology. 2023;11:234–44. [DOI] [PubMed]
El Shabrawy AM, Elbana KA, Abdelsalam NM. Proinsulin/insulin ratio as a predictor of insulin resistance and B-cell dysfunction in obese Egyptians ((insulin resistance & B-cell dysfunction in obese Egyptians)).Diabetes Metab Syndr. 2019;13:2094–6. [DOI] [PubMed]
El-Messallamy FAF, El-Ashmawy HM, El Shabrawy AM, Radwan SE. Proinsulin/insulin ratio as a predictor of insulin resistance in patients with diabetic nephropathy.Diabetes Metab Syndr. 2019;13:2057–60. [DOI] [PubMed]
Condorelli RA, Aversa A, Basile L, Cannarella R, Mongioì LM, Cimino L, et al. Beneficial effects of the very-low-calorie ketogenic diet on the symptoms of male accessory gland inflammation.Nutrients. 2022;14:1081. [DOI] [PubMed] [PMC]
Furini C, Spaggiari G, Simoni M, Greco C, Santi D. Ketogenic state improves testosterone serum levels—results from a systematic review and meta-analysis.Endocrine. 2023;79:273–82. [DOI] [PubMed]
Liu CY, Chang TC, Lin SH, Tsao CW. Is a ketogenic diet superior to a high-fat, high-cholesterol diet regarding testicular function and spermatogenesis?Front Nutr. 2022;9:805794. [DOI] [PubMed] [PMC]
Milder J, Patel M. Modulation of oxidative stress and mitochondrial function by the ketogenic diet.Epilepsy Res. 2012;100:295–303. [DOI] [PubMed] [PMC]
Boguenet M, Bouet PE, Spiers A, Reynier P, May-Panloup P. Mitochondria: their role in spermatozoa and in male infertility.Hum Reprod Update. 2021;27:697–719. [DOI] [PubMed]
