PCOS & the role of dietary supplements in supporting lifestyle changes

Polycystic ovary syndrome (PCOS) is a major cause of menstrual irregularity and excess androgen hormones (hormones that give men their male characteristics) in women.  The condition is characterized by the presence of hyperandrogenism that manifests as hirsutism (male pattern hair growth on a female’s face, chest and back) and acne; irregular menstrual cycles; and a polycystic appearance of the ovaries on transvaginal ultrasound¹.

PCOS is one of the most common endocrine disorders in women, affecting between 5 to 10% of women. Whilst the defining symptoms negatively impact quality of life, of great concern are the increased risks of metabolic issues associated with the syndrome¹.  It is estimated that between 40 to 85% of women with PCOS are overweight or obese and women with PCOS are at increased risk of type-2 diabetes, non-alcoholic fatty liver disease/non-alcoholic steatohepatitis, and sleep apnoea².

Central to the metabolic issues associated with PCOS is hyperinsulinaemia and insulin resistance. Whilst a systematic, controlled study has not been performed to determine the exact prevalence³ most investigators find that compared with normal women, at least half of women with PCOS are obese and most are also hyperinsulinaemic and insulin resistant^{4, 5}.  Hyperinsulinaemia contributes to hyperandrogenism both directly through the stimulation of androgen biosynthesis, and indirectly by suppressing sex hormone-binding globulin (SHBG) production by the liver.  SHBG binds to hormones like testosterone and reduces their bioavailability in the bloodstream. Hyperinsulinaemia also increases production of insulin-like growth factor 1 (IGF-1), which can contribute to the development of acne and hirsutism.

With multiple abnormalities that require attention, treatment of PCOS is multifactorial.  The overall goals of treatment are to manage the underlying metabolic disorders and reduce risks for cardiometabolic diseases, to ameliorate the hyperandrogenic features of the syndrome, and to prevent thickening and cancers in the endometrium layer.  For most women, lifestyle changes that lead to weight loss is the first treatment option, and according to the American Society for Reproductive Medicine’s 2018 Guidelines, lifestyle modification including changes to diet and more exercise is the recommended first-line treatment⁶.  Diet and exercise can improve insulin sensitivity, reduce weight and other metabolic risks, which curtails increased androgen production⁷.

Insulin resistance and hyperinsulinaemia is strongly implicated in PCOS and presents in a considerable proportion of both lean and obese cases and consequently diets that target carbohydrate intake and carbohydrate quality are often recommended. A meta-analysis showed that low carbohydrate diets increased SHBG levels by increasing insulin sensitivity, leading to decreased androgen levels and improvements in symptoms⁸. Similarly, diets that improve the quality of carbohydrate, such as low glycaemic index diet are also beneficial for women with PCOS, and reductions in postprandial glucose and subsequent hyperinsulinaemic improves metabolic profiles in the PCOS population⁸.

One of the challenges with lifestyle interventions is that making significant changes to our habits are difficult to achieve and maintain.  There are multiple factors that make change difficult, especially when we’re trying to make changes to our diet.  These factors include cultural norms, economic impacts (it is more expensive to eat healthily), personal flavour preferences, and influences from third parties such as advertising and marketing^9-11.  For these reasons, people often require further intervention to improve treatment outcomes.  Anti-diabetic medications are often used due to their impact on insulin sensitivity, alongside oral hormone treatment.

Two of the most used anti-diabetic medications for PCOS are metformin and acarbose.  Acarbose is an alpha-glucosidase inhibitor that prevents the breakdown of dietary carbohydrates, resulting in significant reductions in post-meal glucose rises with consequent reductions in hyperinsulinaemia¹².  The undigested carbohydrates further stimulate GLP-1 in the ileum, which helps improve insulin responses, increase oxidation of fatty acids, and increase satiety¹³.  Acarbose does not cause hypoglycaemia and lowers cardiovascular risk factors¹³, however it is poorly tolerated due to gastrointestinal side-effects¹².

A systematic review evaluated the efficacy of acarbose in the treatment of women with PCOS, and it was shown to be a safe and effective treatment. VLDL, triglycerides, luteinizing hormone, testosterone, and dehydroepiandrosterone sulphate all decreased compare with placebo, whilst HDL was significantly increased¹⁴.  Metformin is also used to treat PCOS, especially in combination with clomiphene. In a study comparing metformin and acarbose in combination with clomiphene, both combinations led to improvements in symptoms, however acarbose was more effective in inducing ovulation and decreasing body mass index in infertile women¹⁵.

Acarbose and metformin are however relatively poorly tolerated.  Common metformin side-effects include nausea, vomiting, upset stomach, and diarrhoea, and population-based studies have shown that it is contra-indicated for use in one in four individuals due to these side-effects¹⁶.  Acarbose has a similar side-effect profile, with flatulence being the most reported side-effect affecting up to 50% of individuals¹².

Nutritional support in the form of dietary supplements can help overcome the challenges in making lifestyle changes, promote a healthy insulin response and improve insulin sensitivity, helping women maintain a normal menstrual cycle.  One such solution is Reducose®, a proprietary mulberry leaf extract that has been shown across nine clinical trials to significantly reduce postprandial glucose and insulin levels.  Reducose, inhibits the digestive enzymes that break down carbohydrates and prevents their absorption into the body.  Clinical trials have shown that Reducose lowers glucose and insulin spikes after eating by more than 40%¹⁷.  Reducose® is well tolerated with no difference in frequency or severity of GI symptoms compared with a placebo¹⁸. The undigested carbohydrates continue to travel through the GI tract, where they will stimulate GLP-1, and an unpublished pilot study has shown that Reducose® improves blood lipid profile, lowering LDL and total cholesterol by 11% and 14% respectively.  These undigested nutrients ultimately reach the microbiome, where they are fermented to short chain fatty acids¹⁹, which have further metabolic health supporting benefits. A recent study similarly reported that high fibre diet or a high fibre diet in combination with acarbose alleviated metabolic inflammation, reproductive function, gut-brain peptides in women with PCOS through remodelling of gut microbiota²⁰.

Reducose® has a small dose, 250mg, which gives great flexibility for combining it with other functional ingredients that may be beneficial for supporting overall health and promoting a normal cycle for women with PCOS.  It is estimated that between 67%-85% of women with PCOS have vitamin D deficiency (compared with 48% in the general population)²¹, and emerging data suggests vitamin D supplementation may improve glycaemic control, stimulates insulin production and improves insulin sensitivity²². D-Chiro-inositol (DCI) is another example of a dietary supplement ingredient that would pair well in combination with Reducose®.  Reducose® is stable, and easy to formulate into a range of dietary supplement dosage forms including tablets, capsules, powders, gummies, stick-packs, beverages, and fast melts.

References

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