PCOS Nutrition: A Practical Approach PDF

Table of Contents Overview........................................................................................................................... 2 Causes of PCOS.................................................................................................................. 3 Obesity & PCOS.....

Table of Contents Overview........................................................................................................................... 2 Causes of PCOS.................................................................................................................. 3 Obesity & PCOS................................................................................................................. 6 Inflammation & PCOS........................................................................................................ 8 Microbiome & PCOS.......................................................................................................... 9 Traditional Treatments.................................................................................................... 11 Nutrition & Lifestyle Management for PCOS.................................................................... 14 Supplements & PCOS....................................................................................................... 19 Physical Activity & PCOS.................................................................................................. 21 Role of the dietitian......................................................................................................... 24 PCOS: Fertility & Pregnancy............................................................................................. 31 1 Overview Polycystic ovary syndrome (PCOS) is the most common endocrinopathy affecting reproductive aged women, with a prevalence of between 8 and 13% depending on the population studied and definitions used. Clinical practice in the assessment and management of PCOS is inconsistent, with key evidence practice gaps, whilst women internationally have highlighted delayed diagnosis and dissatisfaction with care. In this graphic, we see that PCOS is both, a reproductive and metabolic disorder, with clinical signs of both beginning in adolescence, continuing into the reproductive years of adulthood which persists into adulthood and menopausal years. The metabolic outcomes of PCOS as women age is under studied yet risk for chronic disease (especially T2DM and CVD) is higher in this population. While there is little is shown in the Egyptian history regarding the antiquity of PCOS, an examination of later ancient medical records provides clues. Hippocrates (460 BC-377 BC) notes that “But those women whose menstruation is less than three days or is meagre, are robust, with a healthy complexion and a masculine appearance; yet they are not concerned 2 about bearing children nor do they become pregnant.” Most directly, the celebrated renaissance surgeon and obstetrician Ambroise Pare (1510-1590 AD) observed that “Many women, when their flowers or tearmes be stopped, degenerate after a manner into a certaine manly nature, whence they are called Viragines, that is to say stout, or manly women; therefore their voice is loud and bigge, like unto a mans, and they become bearded.” (The 24th Book-Of the Generation Of Man). The prevalence of PCOS appears to be only minimally affected by the increasing rates of obesity and the excessive consumption of Western-type food. In a recent interesting analysis, Corbett et al propose that the BMI-fecundity relationship of PCOS is simply shifted leftward, such that patients with PCOS would have „normal’ fertility at the very low BMIs experienced by hunter-gatherers (and including populations through the 1800s) during periods of food scarcity, while their non-PCOS counterparts would experience subnormal fertility during that period of time. the BMI-fecundity relationship in PCOS is simply decreased at all BMIs. Thus, patients with PCOS should be considered sub-fertile, not infertile. Figure 1: Proposed BMI-Fecundity relationship in PCOS (Obtained from Fertil Steril. 2011 Apr; 95(5): 1544–1548. Causes of PCOS PCOS is likely the result of a myriad of genetic variations resulting in a complex genetic trait. In fact, mathematical modeling has suggested that Mendelian-disease genes appear to be under 3 widespread purifying selection, especially when the disease mutations are dominant (rather than recessive); in contrast, the class of genes that influence complex disease risk show little signs of negative selection, possibly because this category includes targets of both purifying and positive selection. Symptoms of PCOS arise during the early pubertal years. Both normal female pubertal development and PCOS are characterized by irregular menstrual cycles, anovulation, and acne. Owing to the complicated interwoven pathophysiology, discerning the inciting causes is challenging. Most available clinical data communicate findings and outcomes in adult women. Whereas the Rotterdam criteria are accepted for adult women, different diagnostic criteria for PCOS in adolescent girls have been delineated. Diagnostic features for adolescent girls are menstrual irregularity, clinical hyperandrogenism, and/or hyperandrogenemia. Pelvic ultrasound findings are not needed for the diagnosis of PCOS in adolescent girls. Even before definitive diagnosis of PCOS, adolescents with clinical signs of androgen excess and oligomenorrhea/amenorrhea, features of PCOS, can be regarded as being “at risk for PCOS.” 4 PCOS reflects the interactions among multiple proteins and genes influenced by epigenetic and environmental factors. Figure 2: Factors contributing to PCOS phenotype 5 Obesity & PCOS The recent International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome (PCOS) has emphasized the importance of diet and physical activity for managing the signs and symptoms of PCOS and preventing the metabolic complications associated with the syndrome. The recommendations support weight management across the life course for all women with PCOS, including weight loss for women with comorbid overweight or obesity and the prevention of weight gain for women within a healthy weight range. A focus on weight management practices is predicated based on substantial evidence that obesity worsens reproductive and metabolic profiles in PCOS. According to the adipose tissue expandability hypothesis, adipocyte hypertrophy establishes a microenvironment characterized by hypoxia, proinflammatory cytokine secretion, free fatty acid “spillover,” macrophage invasion, and IR. IR decreases suppression of adipocyte lipolysis, resulting in increased serum free fatty acids and triglycerides, ultimately leading to increased hepatic de novo lipogenesis and hyperlipidemia. Another consequence is increased fat storage in skeletal muscle, liver, and pancreas because the adipose tissue capacity to store lipid is exceeded. In the liver, ectopic fat storage is labeled hepatic steatosis, which can develop into nonalcoholic fatty liver disease. Investigation of normal-weight women with PCOS showed 6 increased total abdominal fat mass due to preferential deposition of intra-abdominal fat with an increased population of small subcutaneous abdominal adipocytes. The higher your body mass index, the lower your LH (due to obesity’s effect on GnRH) therefore you are less likely to have an elevated LH to FSH ratio in women with very high BMI. Ideal insulin 25 kg/m2: “Multi-component lifestyle interventions should be recommended for reductions in weight and insulin resistance.” In addition, A variety of balanced dietary approaches could be recommended to reduce dietary energy intake. Achievable weight loss (5% to 10% within 6 months) yields significant clinical improvements and weight loss does improve menstrual regularity. To achieve weight loss in those with excess weight, an energy deficit of 30% or 500-750 kcal/day (1,200 to 1,500 kcal/day) could be prescribed for women. Also consider individual energy requirements, body weight and physical activity levels. In women with PCOS, there is no or limited evidence that any specific energy equivalent diet type is better than another, or 14 that there is any differential response to weight management intervention, compared to women without PCOS. Tailoring of dietary changes to food preferences, allowing for a flexible and individual approach to reducing energy intake and avoiding unduly restrictive and nutritionally unbalanced diets, are important, as per general population recommendations. As a critical clinical key summary, the following points are to be considered: In a study by Marsh K et al in 2010 and published in the American Journal of Clinical Nutrition, a comparison for the Low glycemic index (GI) vs. Conventional Diet (CD) was done using 50% CHO, 23% protein, 27% fat. 96 fat women with PCOS were enrolled for 12 months. The results showed Low GI had better menstrual regularity (95% vs. 63% on CD), better insulin sensitivity. Those with high insulin levels had a 2-fold reduction in body fat (modest weight loss) vs. CD. Some strategic foods for a low GI diet are included in the table below. 15 Many diets were tested for PCOS patients with not much significant evidence to support an effective use due to the challenge faced with this patient population. Compared with women without PCOS, women with the condition have higher levels of insulin and inflammatory markers. In a 2015 study, researchers investigated the use of an anti-inflammatory diet in women with PCOS. In this study, 100 overweight women with PCOS ate a reduced-calorie diet for 12 weeks. The diet consisted of five small meals with 25% proteins, 25% fat, and 50% carbohydrates. The diet was designed to include moderate to high amounts of fiber with an emphasis on anti-inflammatory foods such as fish, legumes, green tea, and low-fat dairy. Chicken, red meat, and added sugars were limited. The results were encouraging. The mean weight loss was 7.2% with significant reductions in cholesterol, blood pressure, and fasting blood glucose. Levels of C-reactive protein (CRP) were reduced by 35%, and 63% of the women regained menstrual cyclicity. Examples of antioxidant rich foods include: cold water fish (at least 2x/week), nuts (daily), avocados (daily), whole grains (daily), beans (2-3x/week), legumes (2-3x/week), fruits (2-3 per day), vegetables (2-5/ day) and green tea (daily). 16 The DASH (Dietary Approaches to Stop Hypertension) diet, which also is designed to be rich in antioxidants, has been investigated in women with PCOS as well. Women who followed the DASH diet for eight weeks saw significant reductions in insulin and CRP levels, along with improvements in waist circumference measurements. The “low-carbohydrate diet” is typically defined as having 45% of energy from carbohydrates) may have detrimental effects in people with impaired glucose regulation and it should be avoided. There is no optimum amount of carbohydrate intake for women with PCOS, and, therefore, any range of dietary carbohydrates may be adopted, according to the individuals’ dietary assessment, metabolic goals, dietary habits and preferences. However, it may be advantageous to consume the majority of carbohydrates at 17 lunch time, with the second best option, ie, their equal distribution in meals throughout the day, and to avoid a high-carbohydrate breakfast. Although some studies support that higher protein diets may result in several positive health outcomes, including lean mass preservation during weight loss and maintenance, better glycemic control and amelioration of other cardiovascular disease risk factors, such as blood pressure, it is not clear yet whether these effects are due to the higher protein or lower carbohydrate intake, and no recommendations can be made currently. Nevertheless, the addition of 7–15 g of dietary protein in meals and snacks may offer some additional health benefits for women with PCOS, including amelioration of insulin sensitivity and lower postprandial glucose fluctuations, but this still needs to be confirmed. Replacement of dietary carbohydrate with MUFA and/or PUFA in a reduced energy diet may offer additional health benefits in the management of PCOS. The adoption of healthy dietary patterns such as DASH or the Mediterranean-style diets should be encouraged among women with PCOS, as they are rich in dietary fiber, antioxidants and anti-inflammatory nutrients, lead to greater satiety and have anti-hyperlipidemic, antihypertensive and antidiabetic properties. Although some studies have reported some beneficial health effects of PUFAS, particularly n- 3 marine PUFAs, there is still a lot of controversy and no conclusions can be drawn at this point. The timing of food intake has gained considerable interest in the past few years as it is found to affect metabolism and insulin secretion. It has been suggested that postprandial glycemia is under circadian regulation and that its misalignment may lead to glucose intolerance. Eating late during the day was associated with decreased resting-energy expenditure, decreased fasting carbohydrate oxidation, decreased glucose tolerance, blunted daily profile in free cortisol concentrations and decreased thermal effect of food on wrist temperature in normal weight, 18 healthy females. People with prediabetes preferring to consume their main meal in the evening (later chronotype) had higher HbA1c compared to those consuming their main course at lunch time, and thus, had higher risk of developing type 2 diabetes sooner. The American Heart Association in their recent scientific statement concluded that meal frequency and timing may be important parameters in the nutrition management of chronic diseases, leading to healthier lifestyle and reduction in cardiometabolic risk factors. Supplements & PCOS Research is expanding to determine with highlights on the benefits of nutritional supplements for women with PCOS. N-acetylcysteine (NAC) is a powerful antioxidant and amino acid. NAC is a derivative of L-cysteine, a precursor to glutathione, and is involved in fighting oxidative stress and inflammation. NAC also has been shown to protect insulin receptors and influence insulin receptor activity and insulin secretion from pancreatic cells. NAC improved BMI, total testosterone, insulin, and lipid levels equally as well as metformin did in women with PCOS. Also NAC showed evidence to produce significant improvements in pregnancy and ovulation rates compared with placebo among women with PCOS. Both myo-inositol (MYO) and D-chiro-inositol (DCI) have been well studied in women with PCOS and are showing promising results as first-line treatment. MYO in particular has been shown to improve insulin sensitivity as well as egg quality and ovulation. Newer research is showing that a combination of MYO and DCI in the ideal 40:1 ratio that mimics the body's own tissue levels works better than inositol alone for improving metabolic aspects and restoring hormone balance. MYO and DCI work as inositol-phosphoglycan mediators, or "secondary messengers" that regulate activities of hormones, including follicle-stimulating hormone, thyroid-stimulating hormone, and insulin. The therapeutic dosage is 2 to 4 g MYO daily with 50 to 100 mg DCI daily. Inositol is well tolerated with minimal side effects. It may have the 19 potential to lower blood sugar, especially in those taking insulin sensitizers or other supplements that also may lower blood sugar. Studies on PCOS show an inverse relationship between vitamin D and metabolic and hormonal disorders. Studies found no evidence that vitamin D supplementation reduced or mitigated metabolic and hormonal dysregulations in women with PCOS. Vitamin D receptors have been located on oocytes, immature ova or egg cells involved in reproduction. Vitamin D supplementation (100,000 IU/month) has been shown to improve fertility in women with PCOS by increasing the number of mature follicles and improving menstrual regularity, but the results weren't statistically significant. Fish oil offers many benefits to women with PCOS, including helping to reduce elevated triglyceride levels, improving fatty liver, and decreasing inflammation. Omega-3 oil also has been found to lower testosterone and regulate menstrual cycles in both overweight and lean women with PCOS. Results from the Diabetes Prevention Program Outcomes Study show that metformin affects the absorption of vitamin B12 by causing alterations of the vitamin B12-intrinsic factor 20 complex in the ileum. Vitamin B12 deficiency is progressive over time in metformin users. Consequences of decreased vitamin B12 concentrations—such as macrocytic anemia, neuropathy, and mental changes—can be profound. Since the average dose of metformin in the PCOS population is high (1,500 mg to 2,000 mg per day), it's recommended that patients who take metformin have their vitamin B12 levels checked annually and supplement with vitamin B12. The sublingual methyl-cobalamin form is best absorbed. In conclusion for supplements, it is important to familiarize with the benefits of these supplements and optimal dosages although what supplement to use will depend on the symptom, problem and patient readiness. All these supplements can be taken with metformin and together. In addition, educate patients when appropriate. If possible, depending on the supplement, start slow to check for side effects and benefits. Physical Activity & PCOS Exercise training has shown significant improvement in irregularity of menstrual cycles and ovulation in about 50% women diagnosed with PCOS which improves body composition. Further weight loss may reduce pulse amplitude of luteinizing hormone (LH) in turn reducing androgen production. The key factor responsible for these effects is the reduction of hyperinsulinemia and IR. Exercise has shown to modulate insulin sensitivity and lipid metabolism in skeletal muscle. Exercise improves insulin sensitivity by increasing 21 intramyocellular triacylglycerol concentration. Improvement in insulin sensitivity could be due to more efficient lipid turnover resulting in increased muscle lipid uptake, transport, utilization, and oxidation. The literature states the efficacy of exercise training in combating metabolic syndrome in PCOS patients by marking improvements in apolipoprotein, adiponectin in the process of lipid turnover, and uptake in skeletal muscles. Endurance exercise also increases capillary density, mitochondrial density, number, hyperplasia of muscle fibers, neural sensitization, motor learning, and adaptations thereby increasing exercise capacity and reducing exercise intolerance in PCOS individuals. Exercise recommendations for preventing weight gain and maintenance of health include in adults from 18 – 64 years, a minimum of 150 min/week of moderate intensity physical activity or 75 min/week of vigorous intensities or an equivalent combination of both, including muscle strengthening activities on 2 non-consecutive days/week. Activity be performed in at least 10- minute bouts or around 1,000 steps is recommended, and the aim to achieve at least 30 minutes daily on most days. A minimum of 250 min/week of moderate intensity activities or 150 min/week of vigorous intensity or an equivalent combination of both, and muscle strengthening through activities involving major muscle groups on 2 non-consecutive days/ week and minimize sedentary, screen or sitting time. Physical activity includes leisure time physical activity, transportation such as walking or cycling, occupational work, household chores, games, sports or planned exercise, in the context of daily, family and community activities. Daily, 10000 steps is ideal, including activities of daily living and 30 minutes of structured physical activity or around 3000 steps. Structuring of recommended activities need to consider women’s and family routines as well as cultural preferences. Below are two examples for Aerobic training versus a resistance exercise training. 22 Figure 3: Exercise prescription for aerobic training versus resistance exercise training Some tips to enhance exercise compliance would focus on realistic physical activity using SMART (Specific, Measurable, Achievable, Relevant, Time limited) goals could include 10 minute bouts, progressively increasing physical activity 5% weekly, up to and above recommendations. Self-monitoring including with fitness tracking devices and technologies for step count and exercise intensity, could be used as an adjunct to support and promote active lifestyles and minimize sedentary behaviors. 23 Role of the dietitian Dietitians may be the first health care provider to recognize the syndrome among their patients and they must have the knowledge and skills to recognize and treat patients with PCOS. Diet and its effect on metabolic outcomes should be more thoroughly examined in women with PCOS. Women with PCOS seem to have a greater appetite, consume more energy-dense high glycemic index (GI) foods and saturated fat, have inadequate fiber intake and have low scores for PCOS-related quality of life, although their overall energy intake, physical activity and resting metabolic rate are similar to controls. Reduction in IR has been suggested as the principal goal of PCOS treatment. Lifestyle changes (diet plus physical activity), along with weight loss (5–10%), are proposed as the first-line strategy for amelioration of IR, ovulatory function and decreased free testosterone levels in women with PCOS. Trunk fat, waist circumference (WC) and BMI are the best predictors of IR in PCOS. Other dietary interventions, including carbohydrate distribution, meal frequency and timing, adequate intake of n-3 fatty acids and/or vitamin D supplementation, have been suggested to offer some additional benefits for markers of glucose and energy metabolism and reproductive hormonal 24 regulation. In a study on the effects of exercise and nutritional counseling in women with PCOS, Bruner et al. found that nutritional counseling, with or without exercise, decreased insulin levels and improved both metabolic and reproductive abnormalities associated with PCOS. Overall, there is little variation in weight loss with different diets, and this variation may be due to the differences in compliance and not how the body handles different macro- or micronutrients. Negative energy balance (with a deficit of 350–1000 kcal/day) seems to be the 25 key factor leading to successful body weight and fat loss and amelioration of menstrual cycle and insulin sensitivity, irrespectively of the adopted dietary pattern. Results of a 1-month trial by Stamets K et al published in Fertil Steril in 2004 comparing the effects of two hypocaloric diets, differing in macronutrients, on a variety of clinical measures in women with PCOS, showed that negative energy balance alone resulted in significant weight loss (–4 kg) and decreased testosterone (–9 ng/dL), fasting insulin (–5 mIU/L), area under the curve (AUC) for insulin (–5.823 mIU/L⋅min), fasting leptin (–11 ng/mL), AUC for leptin (–1.854 ng/mL⋅min), total cholesterol (–22 mg/dL) and low-density lipoprotein (LDL) cholesterol (–12 mg/dL), independently of macronutrient composition of the tested diets. Similarly, results from another trial comparing the effects of two hypocaloric diets with different macronutrient composition and GI in women with PCOS showed that negative energy balance resulted in successful weight loss (–4%), decreased dehydroepiandrosterone sulfate (DHEAS) and increased SHBG concentrations. Moreover, results from a 6-month study by Marzouk TM et al published in J Pediatr Adolesc Gynecol in 2015 comparing the effects of two hypocaloric diets (energy deficit –500 kcal/day), differing in macronutrient composition, showed that negative energy balance per se resulted in body weight and fat loss, amelioration of menstrual dysfunction (more regular menstrual episodes reported after weight loss) and hirsutism. In conclusion, negative energy balance is a key strategy for the management and treatment of PCOS. The size of the caloric deficit should be determined according to the individuals’ needs (dietary preferences, habits, culture and metabolic goals) and physical activity patterns. Gluten free diets can be considered for PCOS patients with GI issues such as constipation, diarrhea, gas and bloating, joint pain and fatigue (brain fog). 26 Accordingly, the role of the dietitian can be highlighted in the following points: Provide empathetic, supportive, encouraging approach; Provide education on PCOS, insulin resistance and inflammation; Provide education and support on healthy diet, supplements, sleep, stress, and exercise; Encourage a healthy, sustainable approach to eating and exercise rather than focusing on weight loss; Assess symptom severity (including eating disorder behaviors); Assess medication and supplement compliance. Below is a chart published by the PCOS 27 Nutrition Center on how food affects insulin levels with simple or sugary carbs, refined carbs and processed foods to be avoided. The PCOS plate helps dietitians in education on how food affects insulin and in the use of food journals and intuitive eating scale. A balanced PCOS plate consists of half non-starchy vegetables, one quarter protein, and a quarter of carbs, and some fat is included in the middle to incorporate into the meal. 28 Among the helpful strategies for PCOS patients include the education about the disease and the role of insulin as appetite stimulant. Taking inositol and other supplements to help regulate 29 insulin and cravings can be helpful. It is important to avoid long hours without eating. Mindful eating is considered an effective strategy where patients are taught to trust body cues (food records) and to cope with emotions pertaining to foods, promote enjoyable exercise as well as to work on sleep hygiene and stress management. The intuitive eating scale used for PCOS patients is a helpful tool for dietitians to exercise on their patients. 30 PCOS: Fertility & Pregnancy Infertility is a prevalent presenting feature of PCOS with 75% of these women experiencing infertility due to anovulation, making PCOS the most common cause of anovulatory infertility. The treatment of infertility in PCOS includes lifestyle changes (diet, exercise, and behavioural strategies), pharmacological therapies (oral agents such as clomiphene citrate, letrozole or metformin or injectable agents, such as gonadotrophins), surgical therapy (laparoscopic ovarian surgery) or in vitro fertilization (IVF). In vitro maturation (IVM) has been proposed to offer a promising alternative to conventional IVF. When looking at diet for infertility, carb amount didn’t make a difference, while the quality of carbs did. Foods with high GI values correlated more with infertility. Women who ate the highest HI categories had 92% more ovulatory infertility. As for trans-fatty acids increase risk of infertility at a rate of 4gm per day or more. Unsaturated fats decreased risk for infertility. When carbs were added at the expense of fat, risk of infertility increased. One serving a day of full-fat dairy product reduced infertility risk. One serving a day of low or fat-free dairy products increased the risk. 31 Oocytes and granulosa cells have transferrin receptors; can store iron for future use. Women who took MVI or iron supplement had 40% less trouble conceiving. 40 to 80 mg iron (non- heme) day was effective. Women who received majority of iron from heme sources had more ovulatory infertility. Women with PCOS tend to have some degree of chronic inflammation. This makes you more resistant to insulin, chronically fatigued and prone to gaining weight – even when trying desperately to shed kilos. Eating a diet rich in anti-inflammatory foods – such as dark leafy greens including kale and spinach, blueberries, blackberries, cherries, dark red grapes, nutrition-dense vegetables such as broccoli and cauliflower – can help combat some of these symptoms. Some other anti-inflammatory foods to include are beans, lentils, green tea, red wine (in moderation), avocado, coconut, olives, nuts, turmeric, cinnamon, dark chocolate. Using a variety of spices and herbs to flavor your food can help as well. Accordingly, antioxidant foods improves egg quality, involved with egg maturity, helps with ovulation, reduce inflammation and insulin resistance, and is required for healthy pregnancy. 32 Unique concerns for PCOS and lactation include: Link with insufficient milk production; Failure of breast tissue to develop; Insulin resistance, high androgens; Overabundance of milk production. Some guidelines to establish adequate milk supply in PCOS include: Pump after feedings for 10-15 minutes on each breast in the first 2 weeks of initiating nursing; Frequent feedings with full drainage; Adequate diet and fluid intake; Extra breast stimulation by frequent nursing or pumping sessions is crucial; Resources prior to birth. 33