Presented By: Camille Frances Hanginan , M.D.

1. Oral Carnitine Supplementation Reduces Body Weight And Insulin Resistance In Women With Polycystic Ovary Syndrome: A Randomized, Double-blind, Placebo-controlled Trial MansoorehSamimi, MehriJamilian, FaranehAfsharEbrahimi, Maryam Rahimi‡, BanafshehTajbakhsh and ZatollahAsemi • Presented By: • Camille Frances Hanginan, M.D. SOURCE: Clinical Endocrinology (2016) 84, 851–857

2. Introduction

3. POLYCYSTIC OVARIAN SYNDROME • one of the most common endocrine disorders • can affect up to 10% of women around the world • Diagnosis: • anovulatorycycles or irregular periods • signs of hyperandrogenism • enlarged ovaries (> 10 cm3 ) and the presence of 10 or more peripherally oriented cystic structures (2 to 8 mm) surrounding a dense stroma. • Lentz, G., Lobo, R., Gershenson D., Katz, V., (2012). Comprehensive Gynecology. 6th edition

4. POLYCYSTIC OVARIAN SYNDROME • 30-70% are overweight • Up to 70% have insulin resistance • Can lead to diabetes mellitus • Lentz, G., Lobo, R., Gershenson D., Katz, V., (2012). Comprehensive Gynecology. 6th edition

5. POLYCYSTIC OVARIAN SYNDROME • Addressing metabolic and weight concerns • diet • exercise regimens • metformin • Lentz, G., Lobo, R., Gershenson D., Katz, V., (2012). Comprehensive Gynecology. 6th edition

6. CARNITINE • endogenous compound that has a role in energy metabolism • transfers long-chain fatty acids to the mitochondria for subsequent beta oxidation in order to produce energy • can help lose weight • can help treat insulin resistance • Longo, N., Frigeni, M., & Pasquali, M. (2016). Carnitine transport and fatty acid oxidation. Biochimica et biophysicaacta, 1863(10), 2422–2435. doi:10.1016/j.bbamcr.2016.01.023

7. Relevance

8. RELEVANCE • A substantial amount of information on carnitine’s effects on glucose homeostasis and weight loss can readily be found. • The effect of this compound on women with PCOS, a condition highly associated with weight gain and insulin resistance has not yet been widely studied.

9. Objectives

10. OBJECTIVE • to determine the effects of oral supplementation of carnitine on weight loss, fasting blood sugar, insulin concentrations, lipid profiles, and androgen hormones on women with PCOS

11. Highlights

12. Study Design • A randomized, double-blind, placebo-controlled clinical trial to determine the effects of oral carnitine supplementation on weight loss and metabolic profiles of women with PCOS

13. Sample Population • Eligible for the study: • Diagnosis of PCOS using the Rotterdam criteria • Aged 18-40 • those with a body mass index of >25kg/m2 with phenotypes A(oligo/anovulation + hyperandrogenism + polycystic ovary morphology) and D (oligo/anovulation + polycystic ovary morphology) • No hyperprolactinemia, DM, thyroid disease, not having a special diet or intake of a drug with a known effect on hormones, no intake of ovulation induction agents, and those not on anti-obesity therapies in the last 3 months prior to the start of the study

15. Methodology & Intervention • Half of the 60 women included in the study received 250mg carnitine supplements for 12 weeks while the other half received placebo containing cellulose, also for 12 weeks. • Participants’ compliance was checked through counting of unused capsules.

16. Methodology & Intervention • The variables assessed in the study: • the participants’ body weight, BMI, waist circumference, hip circumference(HC) • fasting plasma glucose(FPG), lipid profiles, serum insulin levels, and androgenic hormones. • Blood samples for the biochemical assessment were taken at the beginning and end of the study for which commercial kits and ELISA kit were used.

17. Results • 12 weeks of carnitine supplementation was found to decrease FPG, serum insulin levels, as well as reduction in weight, BMI, and HC. • No significant changes on lipid profiles nor free testosterone

19. Limitations of the Study • quantification of carnitine concentration was not done due to limited funding. • small sample size • the markers of inflammation, oxidative stress, and sex hormone-binding globulin were not assessed. • the reduction of FPG seen in the carnitine group may have been caused by regression to mean due to the 4g dose used in the study.

20. Conclusion

21. CONCLUSION • Among women with PCOS, carnitine can have beneficial effects on weight, BMI, WC, HC, FPG, and serum insulin levels. • It was not found to have influence on lipid profiles nor free testosterone. • A longer period of clinical trial with higher doses of carnitine supplementation are recommended to further establish its effect on insulin resistance, lipid concentrations, an hormonal outcomes.

22. References • Lentz, G., Lobo, R., Gershenson D., Katz, V., (2012). Comprehensive Gynecology. 6th edition • Dunaif A, Xia J, Book CB, Schenker E, Tang Z., (1995).Excessive insulin receptor serine phosphorylation in cultured fibroblasts and in skeletal muscle. A potential mechanism for insulin resistance in the polycystic ovary syndrome. J Clin Invest.; 96(2):801-10. • Longo, N., Frigeni, M., & Pasquali, M. (2016). Carnitine transport and fatty acid oxidation. Biochimica et biophysicaacta, 1863(10), 2422–2435. doi:10.1016/j.bbamcr.2016.01.023 • Kalpana, Aruna, (2012). Effects of L-Carnitine (Neutraceutical) In Weight Management among Overweight and Obese Adults of Age between 20 – 45yrs – A Comparative Study in Chennai and Tirupathi. International Journal of Scientific and Research Publications, Volume 2, Issue 9 • Lopaschuk G, (2016). Fatty Acid Oxidation and Its Relation with Insulin Resistance and Associated Disorders. Ann NutrMetab; 68(suppl 3):15-20. doi: 10.1159/000448357