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Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2020

Open Access 01-12-2020 | Insulins | Research

Effects of a ketogenic diet in overweight women with polycystic ovary syndrome

Authors: Antonio Paoli, Laura Mancin, Maria Cristina Giacona, Antonino Bianco, Massimiliano Caprio

Published in: Journal of Translational Medicine | Issue 1/2020

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Abstract

Background

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women during reproductive age. It is characterised clinically by oligo-ovulation or anovulation, hyper-androgenism, and the presence of polycystic ovaries. It is associated with an increased prevalence of metabolic syndrome, cardiovascular disease and type 2 diabetes. The onset of PCOS has been associated to several hereditary and environmental factors, but insulin resistance plays a key pathogenetic role. We sought to investigate the effects of a ketogenic diet (KD) on women of childbearing age with a diagnosis of PCOS.

Methods

Fourteen overweight women with diagnosis of PCOS underwent to a ketogenic Mediterranean diet with phyoextracts (KEMEPHY) for 12 week. Changes in body weight, body mass index (BMI), fat body mass (FBM), lean body mass (LBM), visceral adipose tissue (VAT), insulin, glucose, HOMA-IR, total cholesterol, low density lipoprotein (LDL), high density lipoprotein (HDL), triglycerides (TGs), total and free testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH); dehydroepiandrosterone sulfate (DHEAs), estradiol, progesterone, sex hormone binding globulin (SHBG) and Ferriman Gallwey score were evaluated.

Results

After 12 weeks, anthropometric and body composition measurements revealed a significant reduction of body weight (− 9.43 kg), BMI (− 3.35), FBM (8.29 kg) and VAT. There was a significant, slightly decrease of LBM. A significant decrease in glucose and insulin blood levels were observed, together with a significant improvement of HOMA-IR. A significant decrease of triglycerides, total cholesterol and LDL were observed along with a rise in HDL levels. The LH/FSH ratio, LH total and free testosterone, and DHEAS blood levels were also significantly reduced. Estradiol, progesterone and SHBG increased. The Ferriman Gallwey Score was slightly, although not significantly, reduced.

Conclusions

Our results suggest that a KD may be considered as a valuable non pharmacological treatment for PCOS. Longer treatment periods should be tested to verify the effect of a KD on the dermatological aspects of PCOS.
Trial registration Clinicaltrial.gov, NCT04163120, registrered 10 November 2019, retrospectively registered, https://​clinicaltrials.​gov.
Literature
1.
2.
3.
Palomba S, Falbo A, Chiossi G, Muscogiuri G, Fornaciari E, Orio F, et al. Lipid profile in nonobese pregnant women with polycystic ovary syndrome: a prospective controlled clinical study. Steroids. 2014;88:36–43.CrossRefPubMed
4.
5.
6.
De Leo V, Musacchio MC, Cappelli V, Massaro MG, Morgante G, Petraglia F. Genetic, hormonal and metabolic aspects of PCOS: an update. Reprod Biol Endocrinol. 2016;14(1):38.PubMedPubMedCentralCrossRef
7.
Wallace IR, McKinley MC, Bell PM, Hunter SJ. Sex hormone binding globulin and insulin resistance. Clin Endocrinol. 2013;78(3):321–9.CrossRef
8.
Homburg R, Pariente C, Lunenfeld B, Jacobs HS. The role of insulin-like growth factor-1 (IGF-1) and IGF binding protein-1 (IGFBP-1) in the pathogenesis of polycystic ovary syndrome. Hum Reprod. 1992;7(10):1379–83.CrossRefPubMed
9.
Barrea L, Marzullo P, Muscogiuri G, Di Somma C, Scacchi M, Orio F, et al. Source and amount of carbohydrate in the diet and inflammation in women with polycystic ovary syndrome. Nutr Res Rev. 2018;31(2):291–301.CrossRefPubMed
10.
Ceriello A. Acute hyperglycaemia and oxidative stress generation. Diab Med. 1997;14(Suppl 3):S45–9.CrossRef
11.
Barrea L, Arnone A, Annunziata G, Muscogiuri G, Laudisio D, Salzano C, et al. Adherence to the mediterranean diet, dietary patterns and body composition in women with polycystic ovary syndrome (PCOS). Nutrients. 2019;11(10):2278.PubMedCentralCrossRef
12.
Legro RS, Arslanian SA, Ehrmann DA, Hoeger KM, Murad MH, Pasquali R, et al. Diagnosis and treatment of polycystic ovary syndrome: an endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2013;98(12):4565–92.PubMedPubMedCentralCrossRef
13.
Norman RJ, Dewailly D, Legro RS, Hickey TE. Polycystic ovary syndrome. Lancet. 2007;370(9588):685–97.CrossRefPubMed
14.
Hoeger KM, Oberfield SE. Do women with PCOS have a unique predisposition to obesity? Fertil Steril. 2012;97(1):13–7.CrossRefPubMed
15.
Stamets K, Taylor DS, Kunselman A, Demers LM, Pelkman CL, Legro RS. A randomized trial of the effects of two types of short-term hypocaloric diets on weight loss in women with polycystic ovary syndrome. Fertil Steril. 2004;81(3):630–7.CrossRefPubMed
16.
Moran LJ, Noakes M, Clifton PM, Wittert GA, Williams G, Norman RJ. Short-term meal replacements followed by dietary macronutrient restriction enhance weight loss in polycystic ovary syndrome. Am J Clin Nutr. 2006;84(1):77–87.CrossRefPubMed
17.
Tsagareli V, Noakes M, Norman RJ. Effect of a very-low-calorie diet on in vitro fertilization outcomes. Fertil Steril. 2006;86(1):227–9.CrossRefPubMed
18.
Frary JM, Bjerre KP, Glintborg D, Ravn P. The effect of dietary carbohydrates in women with polycystic ovary syndrome: a systematic review. Minerva Endocrinol. 2016;41(1):57–69.PubMed
19.
20.
Paoli A, Bianco A, Grimaldi KA. The ketogenic diet and sport: a possible marriage? Exerc Sport Sci Rev. 2015;43(3):153–62.CrossRefPubMed
21.
Muscogiuri G, Barrea L, Laudisio D, Pugliese G, Salzano C, Savastano S, et al. The management of very low-calorie ketogenic diet in obesity outpatient clinic: a practical guide. J Transl Med. 2019;17(1):356.PubMedPubMedCentralCrossRef
22.
Rubini A, Bosco G, Lodi A, Cenci L, Parmagnani A, Grimaldi K, et al. Erratum to: effects of twenty days of the ketogenic diet on metabolic and respiratory parameters in healthy subjects. Lung. 2017;195(1):155.CrossRefPubMed
23.
Draznin B, Wang C, Adochio R, Leitner JW, Cornier MA. Effect of dietary macronutrient composition on AMPK and SIRT1 expression and activity in human skeletal muscle. Horm Metab Res. 2012;44(9):650–5.CrossRefPubMed
24.
Ruderman NB, Xu XJ, Nelson L, Cacicedo JM, Saha AK, Lan F, et al. AMPK and SIRT1: a long-standing partnership? Am J Physiol Endocrinol Metab. 2010;298(4):E751–60.PubMedPubMedCentralCrossRef
25.
Erickson N, Boscheri A, Linke B, Huebner J. Systematic review: isocaloric ketogenic dietary regimes for cancer patients. Med Oncol. 2017;34(5):72.CrossRefPubMed
26.
Paoli A, Rubini A, Volek JS, Grimaldi KA. Beyond weight loss: a review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets. Eur J Clin Nutr. 2013;67(8):789–96.PubMedPubMedCentralCrossRef
27.
Bueno NB, de Melo IS, de Oliveira SL, da Rocha Ataide T. Very-low-carbohydrate ketogenic diet v. low-fat diet for long-term weight loss: a meta-analysis of randomised controlled trials. Br J Nutr. 2013;110(7):1178–87.CrossRefPubMed
28.
Caprio M, Infante M, Moriconi E, Armani A, Fabbri A, Mantovani G, et al. 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(11):1365–86.CrossRefPubMed
29.
Mavropoulos JC, Yancy WS, Hepburn J, Westman EC. The effects of a low-carbohydrate, ketogenic diet on the polycystic ovary syndrome: a pilot study. Nutr Metab. 2005;2:35.CrossRef
30.
Douglas CC, Gower BA, Darnell BE, Ovalle F, Oster RA, Azziz R. Role of diet in the treatment of polycystic ovary syndrome. Fertil Steril. 2006;85(3):679–88.PubMedPubMedCentralCrossRef
31.
Kulak D, Polotsky AJ. Should the ketogenic diet be considered for enhancing fertility? Maturitas. 2013;74(1):10–3.CrossRefPubMed
32.
McGrice M, Porter J. The effect of low carbohydrate diets on fertility hormones and outcomes in overweight and obese women: a systematic review. Nutrients. 2017;9(3):204.PubMedCentralCrossRef
33.
Rotterdam EA-SPCWG. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril. 2004;81(1):19–25.CrossRef
34.
Wang J, Thornton JC, Bari S, Williamson B, Gallagher D, Heymsfield SB, et al. Comparisons of waist circumferences measured at 4 sites. Am J Clin Nutr. 2003;77(2):379–84.CrossRefPubMed
35.
Klein S, Allison DB, Heymsfield SB, Kelley DE, Leibel RL, Nonas C, et al. Waist circumference and cardiometabolic risk: a consensus statement from SHAPING America’s health: association for weight management and obesity prevention; NAASO, The obesity society; the American Society for Nutrition; and the American Diabetes Association. Am J Clin Nutr. 2007;85(5):1197–202.CrossRefPubMed
36.
Voulgari C, Tentolouris N. The performance of a glucose-ketone meter in the diagnosis of diabetic ketoacidosis in patients with type 2 diabetes in the emergency room. Diab Technol Ther. 2010;12(7):529–35.CrossRef
37.
Paoli A, Cenci L, Grimaldi KA. Effect of ketogenic mediterranean diet with phytoextracts and low carbohydrates/high-protein meals on weight, cardiovascular risk factors, body composition and diet compliance in italian council employees. Nutr J. 2011;10(1):112.PubMedPubMedCentralCrossRef
38.
Paoli A, Bianco A, Grimaldi KA, Lodi A, Bosco G. Long term successful weight loss with a combination biphasic ketogenic mediterranean diet and mediterranean diet maintenance protocol. Nutrients. 2013;5(12):5205–17.PubMedPubMedCentralCrossRef
39.
Paoli A, Cenci L, Fancelli M, Parmagnani A, Fratter A, Cucchi A, et al. Ketogenic diet and phytoextracts comparison of the efficacy of Mediterranean, zone and tisanoreica diet on some health risk factors. Agro Food Ind Hi-Tech. 2010;21(4):24–9.
40.
Paoli A, Grimaldi K, D’Agostino D, Cenci L, Moro T, Bianco A, et al. Ketogenic diet does not affect strength performance in elite artistic gymnasts. J Int Soc Sports Nutr. 2012;9(1):34.PubMedPubMedCentralCrossRef
41.
Paoli A, Moro T, Bosco G, Bianco A, Grimaldi KA, Camporesi E, et al. Effects of n-3 polyunsaturated fatty acids (omega-3) supplementation on some cardiovascular risk factors with a ketogenic Mediterranean diet. Mar Drugs. 2015;13(2):996–1009.PubMedPubMedCentralCrossRef
42.
Bosco G, Rizzato A, Quartesan S, Camporesi E, Mangar D, Paganini M, et al. Effects of the Ketogenic diet in overweight divers breathing enriched air nitrox. Sci Rep. 2018;8(1):2655.PubMedPubMedCentralCrossRef
43.
Lodi A, Karsten B, Bosco G, Gomez-Lopez M, Brandao PP, Bianco A, et al. The effects of different high-protein low-carbohydrates proprietary foods on blood sugar in healthy subjects. J Med Food. 2016;19(11):1085–95.CrossRefPubMed
44.
Armani A, Berry A, Cirulli F, Caprio M. Molecular mechanisms underlying metabolic syndrome: the expanding role of the adipocyte. FASEB J. 2017;31(10):4240–55.CrossRefPubMed
45.
Fauser BC, Tarlatzis BC, Rebar RW, Legro RS, Balen AH, Lobo R, et al. Consensus on women’s health aspects of polycystic ovary syndrome (PCOS): the Amsterdam ESHRE/ASRM-Sponsored 3rd PCOS Consensus Workshop Group. Fertil Steril. 2012;97(1):28–38 e25.CrossRefPubMed
46.
47.
Kim JY, Tfayli H, Michaliszyn SF, Arslanian S. Impaired lipolysis, diminished fat oxidation, and metabolic inflexibility in obese girls with polycystic ovary syndrome. J Clin Endocrinol Metab. 2018;103(2):546–54.CrossRefPubMed
48.
Di Sarra D, Tosi F, Bonin C, Fiers T, Kaufman JM, Signori C, et al. Metabolic inflexibility is a feature of women with polycystic ovary syndrome and is associated with both insulin resistance and hyperandrogenism. J Clin Endocrinol Metab. 2013;98(6):2581–8.CrossRefPubMed
49.
Carmina E. Oral contraceptives and cardiovascular risk in women with polycystic ovary syndrome. J Endocrinol Invest. 2013;36(5):358–63.PubMed
50.
Orio F, Palomba S. Reproductive endocrinology: new guidelines for the diagnosis and treatment of PCOS. Nat Rev Endocrinol. 2014;10(3):130–2.CrossRefPubMed
51.
52.
Sumithran P, Prendergast LA, Delbridge E, Purcell K, Shulkes A, Kriketos A, et al. Ketosis and appetite-mediating nutrients and hormones after weight loss. Eur J Clin Nutr. 2013;67:759–64.CrossRefPubMed
53.
Sumithran P, Prendergast LA, Delbridge E, Purcell K, Shulkes A, Kriketos A, et al. Long-term persistence of hormonal adaptations to weight loss. New Engl J Med. 2011;365(17):1597–604.CrossRefPubMed
54.
Fery F, Balasse EO. Ketone body production and disposal in diabetic ketosis. A comparison with fasting ketosis. Diabetes. 1985;34(4):326–32.CrossRefPubMed
55.
56.
Veech RL, Chance B, Kashiwaya Y, Lardy HA, Cahill GF Jr. Ketone bodies, potential therapeutic uses. IUBMB Life. 2001;51(4):241–7.CrossRefPubMed
57.
Taboulet P, Deconinck N, Thurel A, Haas L, Manamani J, Porcher R, et al. Correlation between urine ketones (acetoacetate) and capillary blood ketones (3-beta-hydroxybutyrate) in hyperglycaemic patients. Diab Metab. 2007;33(2):135–9.CrossRef
58.
Harvey C, Schofield GM, Williden M. The use of nutritional supplements to induce ketosis and reduce symptoms associated with keto-induction: a narrative review. PeerJ. 2018;6:e4488.PubMedPubMedCentralCrossRef
59.
Laffel L. Sick-day management in type 1 diabetes. Endocrinol Metab Clin North Am. 2000;29(4):707–23.CrossRefPubMed
60.
Mesa J, Salcedo D, Calle Hde L, Delgado E, Novoa J, Hawkins F, et al. Detection of ketonemia and its relationship with hyperglycemia in type 1 diabetic patients. Diab Res Clin Pract. 2006;72(3):292–7.CrossRef
61.
Krebs HA. The regulation of the release of ketone bodies by the liver. Adv Enzyme Regul. 1966;4:339–54.CrossRefPubMed
62.
63.
Perez-Guisado J. Ketogenic diets: additional benefits to the weight loss and unfounded secondary effects. Arch Latinoam Nutr. 2008;58(4):323–9.PubMed
64.
Sharman MJ, Kraemer WJ, Love DM, Avery NG, Gomez AL, Scheett TP, et al. A ketogenic diet favorably affects serum biomarkers for cardiovascular disease in normal-weight men. J Nutr. 2002;132(7):1879–85.CrossRefPubMed
65.
Volek JS, Gomez AL, Kraemer WJ. Fasting lipoprotein and postprandial triacylglycerol responses to a low-carbohydrate diet supplemented with n-3 fatty acids. J Am Coll Nutr. 2000;19(3):383–91.CrossRefPubMed
66.
Xiong YL, Liang XY, Yang X, Li Y, Wei LN. Low-grade chronic inflammation in the peripheral blood and ovaries of women with polycystic ovarian syndrome. Eur J Obstet Gynecol Reprod Biol. 2011;159(1):148–50.CrossRefPubMed
67.
Gonzalez F. Inflammation in polycystic ovary syndrome: underpinning of insulin resistance and ovarian dysfunction. Steroids. 2012;77(4):300–5.CrossRefPubMed
68.
Youm YH, Nguyen KY, Grant RW, Goldberg EL, Bodogai M, Kim D, et al. The ketone metabolite beta-hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory disease. Nat Med. 2015;21(3):263–9.PubMedPubMedCentralCrossRef
69.
70.
Sengupta S, Peterson TR, Sabatini DM. Regulation of the mTOR complex 1 pathway by nutrients, growth factors, and stress. Mol Cell. 2010;40(2):310–22.PubMedPubMedCentralCrossRef
71.
Canto C, Auwerx J. Calorie restriction: is AMPK a key sensor and effector? Physiology. 2011;26(4):214–24.CrossRefPubMed
72.
73.
Klepper J, Scheffer H, Leiendecker B, Gertsen E, Binder S, Leferink M, et al. Seizure control and acceptance of the ketogenic diet in GLUT1 deficiency syndrome: a 2- to 5-year follow-up of 15 children enrolled prospectively. Neuropediatrics. 2005;36(5):302–8.CrossRefPubMed
74.
Bergqvist AG. Long-term monitoring of the ketogenic diet: do’s and don’ts. Epilepsy Res. 2012;100(3):261–6.CrossRefPubMed
75.
Bertoli S, Trentani C, Ferraris C, De Giorgis V, Veggiotti P, Tagliabue A. Long-term effects of a ketogenic diet on body composition and bone mineralization in GLUT-1 deficiency syndrome: a case series. Nutrition. 2014;30(6):726–8.CrossRefPubMed
76.
De Amicis R, Leone A, Lessa C, Foppiani A, Ravella S, Ravasenghi S, et al. Long-term effects of a classic ketogenic diet on ghrelin and leptin concentration: a 12-month prospective study in a cohort of Italian children and adults with GLUT1-deficiency syndrome and drug resistant epilepsy. Nutrients. 2019;11(8):1716.PubMedCentralCrossRef
77.
Dressler A, Stocklin B, Reithofer E, Benninger F, Freilinger M, Hauser E, et al. Long-term outcome and tolerability of the ketogenic diet in drug-resistant childhood epilepsy–the Austrian experience. Seizure. 2010;19(7):404–8.CrossRefPubMed
78.
Heussinger N, Della Marina A, Beyerlein A, Leiendecker B, Hermann-Alves S, Dalla Pozza R, et al. 10 patients, 10 years—long term follow-up of cardiovascular risk factors in Glut1 deficiency treated with ketogenic diet therapies: a prospective, multicenter case series. Clin Nutr. 2018;37:2246–51.CrossRefPubMed
79.
Patel A, Pyzik PL, Turner Z, Rubenstein JE, Kossoff EH. Long-term outcomes of children treated with the ketogenic diet in the past. Epilepsia. 2010;51(7):1277–82.CrossRefPubMed
Metadata
Title
Effects of a ketogenic diet in overweight women with polycystic ovary syndrome
Authors
Antonio Paoli
Laura Mancin
Maria Cristina Giacona
Antonino Bianco
Massimiliano Caprio
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2020
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-020-02277-0

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