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Cited by 36Diet and metabolism studiesDietary Effects on HealthHormonal and reproductive studies

The ketogenic diet corrects metabolic hypogonadism and preserves pancreatic ß-cell function in overweight/obese men: a single-arm uncontrolled study

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La Vignera, Sandro, Cannarella, Rossella, Galvano, Fabio, Grillo, Agata, Aversa, Antonio, Cimino, Laura, Magagnini, Cristina M., Mongioì, Laura M. +2 more·2021·Endocrine
DOI 10.1007/s12020-020-02518-8PMC PMC8128723
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Abstract

BACKGROUND: Overweight and obesity are increasingly spread in our society. Low testosterone levels are often present in these patients, the so-called metabolic hypogonadism, that further alters the metabolic balance in a sort of vicious cycle. Very low-calorie ketogenic diet (VLCKD) has been reported to efficiently reduce body weight, glycaemia, and the serum levels of insulin, glycated hemoglobin, but its effects on β-cell function and total testosterone (TT) levels are less clear. AIM: To evaluate the effects of VLCKD on markers suggested to be predictive of β-cell dysfunction development, such as proinsulin or proinsulin/insulin ratio, and on TT values in a cohort of overweight or obese nondiabetic male patients with metabolic hypogonadism. METHODS: Patients with overweight or obesity and metabolic hypogonadism underwent to VLCKD for 12 weeks. Anthropometric parameters, blood testing for the measurement of glycaemia, insulin, C-peptide, proinsulin, TT, calculation of body-mass index (BMI), and HOMA index were performed before VLCKD and after 12 weeks. RESULTS: Twenty patients (mean age 49.3 ± 5.2 years) were enrolled. At enrollement all patients presented increased insulin, HOMA index, C-peptide, and proinsulin levels, whereas the proinsulin/insulin ratio was within the normal values. After VLCKD treatment, body weight and BMI significantly decreased, and 14.9 ± 3.9% loss of the initial body weight was achieved. Glycaemia, insulin, HOMA index, C-peptide, and proinsulin significantly decreased compared to pre-VLCKD levels. Serum glycaemia, insulin, C-peptide, and proinsulin levels returned within the normal range in all patients. No difference in the proinsulin/insulin ratio was observed after VLCKD treatment. A mean increase of 218.1 ± 53.9% in serum TT levels was achieved and none of the patients showed TT values falling in the hypogonadal range at the end of the VLCKD treatment. CONCLUSIONS: This is the first study that evaluated the effects of VLCKD on proinsulin, proinsulin/insulin ratio, and TT levels. VLCKD could be safely used to improve β-cell secretory function and insulin-sensitivity, and to rescue overweight and obese patients from β-cell failure and metabolic hypogonadism.

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  • A small study in 20 patients with overweight or obesity and functional hypogonadism showed that a very low-calorie ketogenic diet during 12 weeks resulted in a mean increase in total testosterone levels of around 218% (±53.9%).

    “A small study in 20 patients with overweight or obesity and functional hypogonadism showed that a very low-calorie ketogenic diet during 12 weeks resulted in a mean increase in total testosterone levels of around 218% (± 53.9%) [24].”

    From Treatment of Men with Central Hypogonadism: Alternatives for Testosterone Replacement Therapy (2020) · cites this paper as [24]

  • Several studies with a very low-calorie ketogenic diet showed a positive effect of this diet on body mass index, glycemic control and insulin resistance.

    “Several studies with a very low-calorie ketogenic diet showed a positive effect of this diet on body mass index, glycemic control and insulin resistance.”

    From Treatment of Men with Central Hypogonadism: Alternatives for Testosterone Replacement Therapy (2020) · cites this paper as [24]

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  1. [10]Wilder RM The effects of ketonemia on the course of epilepsy Mayo. Clin. Proc. 1921 2 307 308
  2. [13]Nagy R Dr. Atkins’ diet revolution: a review. Va Med. Mon. 1974 101 5 383 385 4826189
  3. [24]von Berghes C Brabant G Biebermann H Krude H Wiegand S Proinsulin and the proinsulin/insulin ratio in overweight and obese children and adolescents: relation to clinical parameters, insulin resistance, and impaired glucose regulation Pediatr. Diabetes 2011 12 3 Pt 2 242 249 10.1111/j.1399-5448.2010.00734.x 21518412 · DOI
  4. [33]Pfützner A Kann PH Pfützner AH Kunt T Larbig M Weber MM Forst T Intact and total proinsulin: new aspects for diagnosis and treatment of type 2 diabetes mellitus and insulin resistance Clin. Lab. 2004 50 9-10 567 573 15481632

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Authors
La Vignera, S., Cannarella, R., Galvano, F., Grillo, A., Aversa, A., Cimino, L., Magagnini, C. M., Mongioì, L. M., Condorelli, R. A., & Calogero, A. E.
Affiliations
University of Catania (IT)
Corresponding author
Condorelli, Rosita A.
ORCID
Venue
Endocrine
Publisher
Springer Science and Business Media LLC
Published
2020-10-15
Volume
72
Issue
2
Pages
392-399
ISSN
  • 0969-711X (ISSN-L)
  • 1355-008X
  • 1559-0100
DOI
10.1007/s12020-020-02518-8
PMC
PMC8128723
OpenAlex
W3093273105
Cited by
36
References
53
Citations by year
2026: 3 · 2025: 3 · 2024: 5 · 2023: 6 · 2022: 13 · 2021: 4 · 2020: 1 · 2014: 1
FWCI
3.61
Type
journal article
Language
en
Open access
Licence
Locations
  • Endocrine (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
Ministry of Education, University and Research (PRIN 2017XLFJAX)
Topics
  • Health Sciences › Medicine › Physiology › Diet and metabolism studies
  • Health Sciences › Medicine › Physiology › Dietary Effects on Health
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
Keywords
ketogenic diet, very low-calorie ketogenic diet, testosterone, beta-cell function, proinsulin, proinsulin/insulin ratio, insulin resistance, obesity, overweight men, weight loss, HOMA index, C-peptide, insulin secretion, insulin sensitivity, hyperinsulinemia, hyperandrogenism, male infertility, male hypogonadism
MeSH terms
Adult, Humans, Hypogonadism, Male, Middle Aged, Obesity, Body Mass Index, Overweight, Diet, Ketogenic

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