Journal Article | Cardio-Metabolic

September 21, 2020



Introduction

 

Polycystic ovarian syndrome (PCOS) is one of the most common endocrine disorders which can affect up to 10% of women around the world.1 Women with PCOS have anovulatory cycles or irregular periods and signs of hyperandrogenism in addition to ultrasound findings of enlarged ovaries with peripherally-oriented cystic structures around a dense stroma.

 

It has long been established that women with PCOS suffer from metabolic problems. Thirty to seventy percent are overweight depending on their country of origin, and up to 70% have insulin resistance (which is thought to enhance ovarian androgen production).2

 

The cause of insulin resistance (IR) remains unclear, but is thought to be due to a specific abnormal pattern of insulin receptor phosphorylation. This can eventually lead to diabetes mellitus (DM), one of the long-term consequences of PCOS. Other serious consequences of PCOS are infertility, ovarian cancer, and cardiovascular disease, with its risk greatly enhanced by obesity.

 

The metabolic and weight concerns of women with PCOS are primarily addressed by diet, metformin, and exercise regimens to reduce weight which can lead to improvement in metabolic parameters.

 

Carnitine, an endogenous compound derived from amino acids lysine and methionine has a role in energy metabolism.3 It is largely popular as an add-on to weight loss regimens. Its role is the transfer of long-chain fatty acids to the mitochondria for subsequent beta oxidation in order to produce energy.

 

Carnitine has been found to be an effective adjunct to regular and adequate physical exercise among overweight and obese adults seeking to lose weight.4 Moreover, carnitine has been found to be beneficial in treating insulin resistance. This is due to its ability to stimulate glucose utilization and to prevent accumulation of fatty acid metabolites which can lead to impaired insulin signaling.5

 

In overweight and obese women seeking effective weight loss strategies, sufficient data on the effectiveness of carnitine is yet to be established.

 

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.

 

Objectives

 

The 2015 study conducted by Samimi, et al. aims 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.6

 

Highlights

 

This is a randomized, double-blind, placebo-controlled clinical trial done in Arak, Iran from July 2015 to September 2015. Those who were involved in the study were women with PCOS referred to Taleghani Clinic.

 

The Rotterdam criteria was used to establish a diagnosis of PCOS. Those who were eligible for the study were women with PCOS who were aged 18-40, and 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).

 

Excluded from the study were women with hyperprolactinemia, DM, thyroid disease, having a special diet or intake of a drug with a known effect on hormones, intake of ovulation induction agents, and those on anti-obesity therapies in the last 3 months prior to the start of the study.

 

A total of 60 women were included in the study. Half of them received 250mg carnitine supplements for 12 weeks while the other half received placebo containing cellulose. Participants’ compliance was checked through counting of unused capsules.

 

The variables assessed in the study were markers of insulin metabolism (the primary outcome), 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.

 

The researchers utilized Kolmogrov-Smirnov test to assess the normal distribution of variables; student’s t-test to detect differences in the general characteristics and dietary intakes between the two groups; paired-samples t-test to detect within-group changes; and analysis of covariance to check for confounding variables. The intention-to-treat principle was used to perform analysis.

 

At the end of the study, 12 weeks of carnitine supplementation was found to decrease FPG, serum insulin levels, as well as reduction in weight, BMI, and HC. It did not, however, lead to any significant changes on lipid profiles nor free testosterone.

 

Better evaluation of compliance through quantification of carnitine concentration which would have added strength to the study was not done due to limited funding. Other limitations included a small sample size. Furthermore, the markers of inflammation, oxidative stress, and sex hormone-binding globulin were not assessed.

 

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, and hormonal outcomes.

 

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 biophysica acta, 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 Nutr Metab; 68(suppl 3):15-20. doi: 10.1159/000448357

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