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

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

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.

Keywords: Hyperinsulinemia; Ketogenic diet; Ketone bodies; LCKD; Low carbohydrate diet; Overweight; PCOS.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Flow chart of experimental design. Recruitment of patients. Further details are reported in the text
Fig. 2
Fig. 2
Changes in anthropometric variables after 12 weeks of KD. BMI body mass index, FBM fat body mass, LBM mean body mass. Standard deviation is represented in the figure. ***p < 0.0001; **p = 0.0015; *p = 0.0205
Fig. 3
Fig. 3
Changes in hormonal variables after 12 weeks of KD. LH luteinizing hormone, FSH follicle stimulating hormone, DHEAs dehydroepiandrosterone sulfate, SHBG sex hormone binding globulin. Standard deviation is represented in the figure. ***p < 0.0001; **#p = 0.009; **P = 0.0082; *p = 0.0258

References

    1. Trikudanathan S. Polycystic ovarian syndrome. Med Clin North Am. 2015;99(1):221–235. doi: 10.1016/j.mcna.2014.09.003.
    1. Sirmans SM, Pate KA. Epidemiology, diagnosis, and management of polycystic ovary syndrome. Clin Epidemiol. 2013;6:1–13. doi: 10.2147/CLEP.S37559.
    1. 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. doi: 10.1016/j.steroids.2014.06.005.
    1. El Hayek S, Bitar L, Hamdar LH, Mirza FG, Daoud G. Poly cystic ovarian syndrome: an updated overview. Front Physiol. 2016;7:124. doi: 10.3389/fphys.2016.00124.
    1. Larner J, Brautigan DL, Thorner MO. D-chiro-inositol glycans in insulin signaling and insulin resistance. Mol Med. 2010;16(11–12):543–552. doi: 10.2119/molmed.2010.00107.
    1. 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. doi: 10.1186/s12958-016-0173-x.
    1. Wallace IR, McKinley MC, Bell PM, Hunter SJ. Sex hormone binding globulin and insulin resistance. Clin Endocrinol. 2013;78(3):321–329. doi: 10.1111/cen.12086.
    1. 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):1379–1383. doi: 10.1093/oxfordjournals.humrep.a137577.
    1. 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. doi: 10.1017/S0954422418000136.
    1. Ceriello A. Acute hyperglycaemia and oxidative stress generation. Diab Med. 1997;14(Suppl 3):S45–S49. doi: 10.1002/(SICI)1096-9136(199708)14:3+<S45::AID-DIA444>;2-I.
    1. 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. doi: 10.3390/nu11102278.
    1. 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):4565–4592. doi: 10.1210/jc.2013-2350.
    1. Norman RJ, Dewailly D, Legro RS, Hickey TE. Polycystic ovary syndrome. Lancet. 2007;370(9588):685–697. doi: 10.1016/S0140-6736(07)61345-2.
    1. Hoeger KM, Oberfield SE. Do women with PCOS have a unique predisposition to obesity? Fertil Steril. 2012;97(1):13–17. doi: 10.1016/j.fertnstert.2011.11.026.
    1. 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):630–637. doi: 10.1016/j.fertnstert.2003.08.023.
    1. 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. doi: 10.1093/ajcn/84.1.77.
    1. Tsagareli V, Noakes M, Norman RJ. Effect of a very-low-calorie diet on in vitro fertilization outcomes. Fertil Steril. 2006;86(1):227–229. doi: 10.1016/j.fertnstert.2005.12.041.
    1. 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.
    1. Paoli A. Ketogenic diet for obesity: friend or foe? Int J Environ Res Public Health. 2014;11(2):2092–2107. doi: 10.3390/ijerph110202092.
    1. Paoli A, Bianco A, Grimaldi KA. The ketogenic diet and sport: a possible marriage? Exerc Sport Sci Rev. 2015;43(3):153–162. doi: 10.1249/JES.0000000000000050.
    1. 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. doi: 10.1186/s12967-019-2104-z.
    1. 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. doi: 10.1007/s00408-016-9958-0.
    1. 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):650–655. doi: 10.1055/s-0032-1312656.
    1. 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–E760. doi: 10.1152/ajpendo.00745.2009.
    1. Erickson N, Boscheri A, Linke B, Huebner J. Systematic review: isocaloric ketogenic dietary regimes for cancer patients. Med Oncol. 2017;34(5):72. doi: 10.1007/s12032-017-0930-5.
    1. 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):789–796. doi: 10.1038/ejcn.2013.116.
    1. 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):1178–1187. doi: 10.1017/S0007114513000548.
    1. 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):1365–1386. doi: 10.1007/s40618-019-01061-2.
    1. 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. doi: 10.1186/1743-7075-2-35.
    1. 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):679–688. doi: 10.1016/j.fertnstert.2005.08.045.
    1. Kulak D, Polotsky AJ. Should the ketogenic diet be considered for enhancing fertility? Maturitas. 2013;74(1):10–13. doi: 10.1016/j.maturitas.2012.10.003.
    1. 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. doi: 10.3390/nu9030204.
    1. 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. doi: 10.1016/j.fertnstert.2003.10.004.
    1. 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):379–384. doi: 10.1093/ajcn/77.2.379.
    1. 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):1197–1202. doi: 10.1093/ajcn/85.5.1197.
    1. 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):529–535. doi: 10.1089/dia.2010.0011.
    1. 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. doi: 10.1186/1475-2891-10-112.
    1. 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):5205–5217. doi: 10.3390/nu5125205.
    1. 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):24–29.
    1. 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. doi: 10.1186/1550-2783-9-34.
    1. 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. doi: 10.3390/md13020996.
    1. 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. doi: 10.1038/s41598-018-20933-w.
    1. 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):1085–1095. doi: 10.1089/jmf.2016.0072.
    1. Armani A, Berry A, Cirulli F, Caprio M. Molecular mechanisms underlying metabolic syndrome: the expanding role of the adipocyte. FASEB J. 2017;31(10):4240–4255. doi: 10.1096/fj.201601125RRR.
    1. 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. doi: 10.1016/j.fertnstert.2011.09.024.
    1. Kelley DE. Skeletal muscle fat oxidation: timing and flexibility are everything. J Clin Invest. 2005;115(7):1699–1702. doi: 10.1172/JCI25758.
    1. 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):546–554. doi: 10.1210/jc.2017-01958.
    1. 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):2581–2588. doi: 10.1210/jc.2013-1161.
    1. Carmina E. Oral contraceptives and cardiovascular risk in women with polycystic ovary syndrome. J Endocrinol Invest. 2013;36(5):358–363.
    1. Orio F, Palomba S. Reproductive endocrinology: new guidelines for the diagnosis and treatment of PCOS. Nat Rev Endocrinol. 2014;10(3):130–132. doi: 10.1038/nrendo.2013.248.
    1. Paoli A, Bosco G, Camporesi EM, Mangar D. Ketosis, ketogenic diet and food intake control: a complex relationship. Front Psychol. 2015;6:27. doi: 10.3389/fpsyg.2015.00027.
    1. 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;67:759–764. doi: 10.1038/ejcn.2013.90.
    1. 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):1597–1604. doi: 10.1056/NEJMoa1105816.
    1. Fery F, Balasse EO. Ketone body production and disposal in diabetic ketosis. A comparison with fasting ketosis. Diabetes. 1985;34(4):326–332. doi: 10.2337/diab.34.4.326.
    1. Cahill GF., Jr Fuel metabolism in starvation. Annu Rev Nutr. 2006;26:1–22. doi: 10.1146/annurev.nutr.26.061505.111258.
    1. Veech RL, Chance B, Kashiwaya Y, Lardy HA, Cahill GF., Jr Ketone bodies, potential therapeutic uses. IUBMB Life. 2001;51(4):241–247. doi: 10.1080/152165401753311780.
    1. 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):135–139. doi: 10.1016/j.diabet.2006.11.006.
    1. 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. doi: 10.7717/peerj.4488.
    1. Laffel L. Sick-day management in type 1 diabetes. Endocrinol Metab Clin North Am. 2000;29(4):707–723. doi: 10.1016/S0889-8529(05)70160-2.
    1. 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):292–297. doi: 10.1016/j.diabres.2005.10.008.
    1. Krebs HA. The regulation of the release of ketone bodies by the liver. Adv Enzyme Regul. 1966;4:339–354. doi: 10.1016/0065-2571(66)90027-6.
    1. Paoli A. Booster ketones: battling hunger. Obesity. 2018;26(2):252–253. doi: 10.1002/oby.22099.
    1. Perez-Guisado J. Ketogenic diets: additional benefits to the weight loss and unfounded secondary effects. Arch Latinoam Nutr. 2008;58(4):323–329.
    1. 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):1879–1885. doi: 10.1093/jn/132.7.1879.
    1. 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):383–391. doi: 10.1080/07315724.2000.10718935.
    1. 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):148–150. doi: 10.1016/j.ejogrb.2011.07.012.
    1. Gonzalez F. Inflammation in polycystic ovary syndrome: underpinning of insulin resistance and ovarian dysfunction. Steroids. 2012;77(4):300–305. doi: 10.1016/j.steroids.2011.12.003.
    1. 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):263–269. doi: 10.1038/nm.3804.
    1. Puchalska P, Crawford PA. Multi-dimensional roles of ketone bodies in fuel metabolism, signaling, and therapeutics. Cell Metab. 2017;25(2):262–284. doi: 10.1016/j.cmet.2016.12.022.
    1. Sengupta S, Peterson TR, Sabatini DM. Regulation of the mTOR complex 1 pathway by nutrients, growth factors, and stress. Mol Cell. 2010;40(2):310–322. doi: 10.1016/j.molcel.2010.09.026.
    1. Canto C, Auwerx J. Calorie restriction: is AMPK a key sensor and effector? Physiology. 2011;26(4):214–224. doi: 10.1152/physiol.00010.2011.
    1. Paoli A, Cancellara P, Pompei P, Moro T. Ketogenic diet and skeletal muscle hypertrophy: a frenemy relationship? J Hum kinet. 2019;68:233–247. doi: 10.2478/hukin-2019-0071.
    1. 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):302–308. doi: 10.1055/s-2005-872843.
    1. Bergqvist AG. Long-term monitoring of the ketogenic diet: do’s and don’ts. Epilepsy Res. 2012;100(3):261–266. doi: 10.1016/j.eplepsyres.2011.05.020.
    1. 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):726–728. doi: 10.1016/j.nut.2014.01.005.
    1. 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. doi: 10.3390/nu11081716.
    1. 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):404–408. doi: 10.1016/j.seizure.2010.06.006.
    1. 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;37:2246–2251. doi: 10.1016/j.clnu.2017.11.001.
    1. 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):1277–1282. doi: 10.1111/j.1528-1167.2009.02488.x.

Source: PubMed

스폰서 및 공동 작업자

건강 상태

약물 개입

3
구독하다