This review was written by our regular contributor; dietitian – Maeve Hanan.
Study: Chudzicka-Strugała et al. “Effects of synbiotic supplementation and lifestyle modifications on women with polycystic ovary syndrome”. J Clin Endocrinol Metab. 2021 May 29;dgab369. doi: 10.1210/clinem/dgab369.
What was the study investigating?
This study was investigating the effects of lifestyle modifications (diet and exercise) and synbiotic supplementation for women with polycystic ovary syndrome (PCOS).
Synbiotics are supplements that contain both probiotics (live microorganisms that provide health benefits when consumed) and prebiotics (food for probiotics).
The main outcomes that were measured in this study were BMI and body fat percentage.
Secondary outcomes that were measured included:
- Hormone levels relevant to PCOS including: testosterone, dehydroepiandrosterone sulphate (DHEAS), sex hormone binding globulin (SHBG), luteinizing hormone (LH), follicle-stimulating hormone (FSH) and insulin
- Ovarian volume – as high ovarian volume can form part of PCOS diagnosis
- Hirsutism i.e. thick, dark hair on the face, neck, chest, stomach, lower back, buttocks or thighs
- Level of acne
- Blood glucose, glucose tolerance and insulin sensitivity
- Cholesterol and triglyceride level
- Waist, hip, and thigh circumference
Overview of the study
This randomised controlled trial was carried out in Poznan University of Medical Sciences in Poland. This means that participants in the study were randomly divided between a treatment group and a placebo group. This study was also double-blinded, so neither the participants nor the researchers know which group participants are in to reduce the risk of bias.
This study included women with PCOS between the age of 18 – 40 (average age ~29 years old) with a BMI above 25 kg/m2 (average BMI ~34.4). There were originally 65 women involved, but 26 dropped out during the course of the study, so only 39 women were included in the final results; with 19 in the Synbiotic Group and 20 in the Placebo Group.
Women were excluded from the study if they had certain conditions that could impact the results of the study. Participants also avoided antibiotics, laxatives, hormone therapy, weight loss supplements, synbiotics or probiotics for 2 months before the study began.
Both groups received the same lifestyle advice and support that included:
- Restricting dietary intake to 1,400-1,800 kcal per day based on body composition analysis
- Individualized advice about food composition
- Avoiding alcohol
- 30-40 minutes of walking each day
- In person follow-up with a Dietitians every 2-3 weeks
The Placebo Group took 4 placebo capsules each day, whereas the Synbiotic group took 4 SANPROBI Super Formula synbiotics each day. The synbiotic supplement contains a multi-strain probiotic and the prebiotics inulin and fructooligosaccharides.
After 3 months, the collected data was analysed using statistical methods (mainly a paired t-test).
What did they find?
The Synbiotic Group experienced an 8% decrease in BMI which was significantly greater than the 5% BMI decrease in the Placebo Group (P=0.03)*.
*Put simply, ‘statistically significant’ means that a result is more likely to be due to the study intervention rather than occurring randomly or by chance. A p-value is used to determine how strong or weak this statistical significance is, if P is less than 0.05 a result is usually deemed to be significant, and the lower this value is (e.g. P<0.001) the more reliable the result is considered to be.
Percentage body fat also reduced significantly in both groups, by 10% in the Synbiotic Group (P<0.0001) and by 7% in the Placebo Group (P<0.0001). In this case there was no significant difference between the two groups (P=0.12).
In terms of secondary outcomes, waist, hip and thigh circumference reduced significantly in both groups, and the reduction in waist circumference was significantly higher in the Synbiotic Group (P=0.03).
Triglycerides reduced by 23% in the Synbiotic Group (P=0.022), and by 15% in the Placebo Group (P=0.034).
Testosterone level significantly reduced by 32% in the Synbiotic Group (P<0.0001), which was significantly higher than the 6% decrease in the Placebo Group (P=0.016).
All other changes in hormone levels were not significant, with the exception of:
- DHEAS increased by 14% in the Synbiotic Group (P=0.012)
- LH reduced by 26% in the Placebo Group (P=0.039)
There was no significant change in ovarian volume. There was also a non-significant trend towards reduced hirsutism (6% decrease, P=0.06) and improved insulin sensitivity (25% increase, P=0.12) in the Synbiotic Group. Data for acne score was not included in the results, despite being mentioned in the study procedure.
What does this mean?
The addition of synbiotics to this diet and exercise intervention led to a significantly higher reduction in BMI and body fat (3% higher in both cases) in this group of women with PCOS.
Some weight loss studies have reported an improvement in PCOS symptoms for women in the higher weight categories (1). However, there are numerous barriers to weight loss and there is a lack of long-term evidence as to whether maintaining weight loss is realistic (2). It’s important to add that pursuing weight loss is not in everyone’s best interest, and women with PCOS have been found to have a high risk of body image issues and disordered eating (3). Improvements in PCOS symptoms can also occur independent of weight loss, and women can develop PCOS at any weight or size (3).
Secondary to the main findings related to weight and fat percentage, a 32% reduction in testosterone was found in the Synbiotic Group. This is relevant because testosterone is one of the main androgens (male hormones involved in male traits and reproduction) which can be raised in women with PCOS.
Interestingly, a 14% increase in the androgen DHEAS was seen in the Synbiotic Group. Furthermore, LH is reduced by 26% in the Placebo Group, and high levels of LH are associated with PCOS. Therefore, these 2 secondary findings do not support the hypothesis of this study.
The reduction in triglyceride levels, by 23% in the Synbiotic Group and by 15% in the Placebo Group, suggest that synbiotics may add an additional benefit on top of diet and exercise changes in terms of cardiovascular health. This is promising to see, especially as women with PCOS have a higher risk of developing high triglyceride levels (a substance made of fat and a form of glucose that is found in the bloodstream) (4).
The findings of this study support previous studies which have found that probiotic or synbiotic supplementation may help to reduce testosterone and triglyceride levels in women with PCOS (5, 6). But contrary to the current study, these studies also found an improvement in blood glucose and insulin sensitivity and no significant changes in terms of weight loss (5, 6).
Strengths and limitations
Strengths of this study include:
- Strong study design that included randomisation, double-blinding and measurement of relevant factors like body composition, hormone levels and markers of metabolic health
- Exploring an interesting and important topic
- Both the synbiotic and placebo groups were similar at the beginning of the study in terms of age, body composition, hirsutism, ovarian volume, hormone, cholesterol and glucose levels. This makes the results more reliable due to comparing like with like
- Inclusion of diet and exercise support as part of the lifestyle intervention – with additional support from a dietitian
Limitations of this study include:
- Small sample size – this impacts the reliability of the results
- High drop-out rate of 40% – this impacts the sample size and also raises a question about how realistic the lifestyle intervention was to maintain
- Some of the outcomes such as hirsutism and lipids often need longer than 3 months to assess the impact of an intervention
- Using bioelectrical impedance analysis to measure body fat percentage has been found to be unreliable in some studies (7, 8)
- Some participants were taking medroxyprogresterone (a progesterone derivative) which may impact some of the results
- The study included limited information about the lifestyle intervention, however some people were advised to reduce their kcal intake to 1400 kcals which is very low for an adult, particularly in a population at increased risk of disordered eating as discussed above
- An acne score was mentioned in the study protocol, but the results for this were not presented. Similarly, menstrual regularity and microbiome changes were listed as secondary outcomes when the trial was registered, but these were not included in the final study
- This double-blinded randomised controlled trial investigated the effects of lifestyle modifications (diet and exercise) and synbiotic supplementation for women with PCOS
- Taking synbiotic supplements (i.e. containing prebiotics and probiotics) was found to improve the impact of diet and lifestyle changes for women with PCOS in terms of weight loss and body fat reduction
- Those in the Synbiotic group also saw greater improvements in testosterone and triglyceride levels
- Other hormone changes were less favourable, as DHEAS significantly increased in the Synbiotic Group and LH significantly reduced in the Placebo Group
- This study was well designed overall, but it had a small sample size, only lasted 3 months and had a 40% dropout rate
(1) Kim et al. “Effects of lifestyle modification in polycystic ovary syndrome compared to metformin only or metformin addition: A systematic review and meta-analysis”. Sci Rep 10, 7802 (2020). https://doi.org/10.1038/s41598-020-64776-w
(2) Bacon & Aphramore “Weight Science: Evaluating the Evidence for a Paradigm Shift”. Nutrition Journal 2011, 10:9.
(3) Monash University “International evidence based guideline for the assessment and management of polycystic ovary syndrome”. 2018. [accessed June 2021 via: https://www.monash.edu/__data/assets/pdf_file/0004/1412644/PCOS_Evidence-Based-Guidelines_20181009.pdf]
(4) Wild et al. “Lipid levels in polycystic ovary syndrome: systematic review and meta-analysis”. Fertility and Sterility. 2011;95 (3)L1073-1079.
(5) Liao et al. “Meta-analysis of the effects of probiotic supplementation on glycemia, lipidic profiles, weight loss and C-reactive protein in women with polycystic ovarian syndrome”. Minerva Med. 2018;109(6):479-487.
(6) Hadi et al. “Effect of probiotics and synbiotics on selected anthropometric and biochemical measures in women with polycystic ovary syndrome: a systematic review and meta-analysis”. European journal of clinical nutrition. 2020;74(4):543-547.
(7) Coppini et al. “Limitations and validation of bioelectrical impedance analysis in morbidly obese patients”. Curr Opin Clin Nutr Metab Care. 2005 May;8(3):329-32.
(8) Gaba et al. “Comparison of multi- and single-frequency bioelectrical impedance analysis with dual-energy X-ray absorptiometry for assessment of body composition in post-menopausal women: effects of body mass index and accelerometer-determined physical activity”. Journal of Human Nutrition and Dietetics. 2014. https://doi.org/10.1111/jhn.12257