Changes in bone turnover markers, biochemical profile and gut microbiota in response to chronic flaxseed consumption in postmenopausal women

Osteoporosis remains one of the leading causes of morbidity particularly among postmenopausal women. Currently dietary guidelines advocate for adherence to a plant-based diet, as this has been associated with many health benefits, partly due to the abundance of phytoestrogens. Studies of phytoestrogens have primarily focused on the ability of soy isoflavones to prevent several hormone related diseases, particularly postmenopausal bone loss. Lignans are the most common type of phytoestrogen in Western diets and are the focus of this thesis. In a literature review we explore the known effects of flaxseed lignan consumption on postmenopausal associated bone loss and highlight current evidence linking gut microbiota composition and activity to lignan bioavailability and potentially to bone health. Habitual diet has been largely shown to influence both bone health and the gut microbiota but only a few studies have investigated the impact of dietary patterns and dietary interventions on bone turnover markers and gut microbiota in terms of bone health. In order to address this knowledge gap, a sub-sample of participants from an observational cohort study in Omani adults was used to investigate the dietary habits amongst this population, and associations with markers of bone health status. Dietary pattern analysis was performed which identified four main patterns: ‘Processed Foods’, ‘Healthy Foods’, ‘Omani Junk Foods’ and ‘Omani traditional Foods’. No associations were found between the identified dietary patterns and markers of bone health in the Omani men and women aged 20-60 years. These findings led to a more in-depth nutritional analysis to investigate these dietary patterns in relation to bone health and associations with sex, body mass index (BMI) and age groups. Both age and sex influenced the preference for each dietary pattern, especially ‘Traditional Omani Foods’. However, there was a limited impact of the dietary pattern on BMI and markers of bone health. Findings from this cohort study were used to design a human randomised controlled trial (FLAX study) which aimed to address the effect of a dietary intervention on postmenopausal bone turnover. Forty-six postmenopausal women were given either 40 g /day flaxseed in the form of a flapjack, which provided an average of 1.38% of the plant lignan, secoisolariciresinol diglucoside (SDG), or a matched control flapjack without flaxseed, for 12 weeks. At baseline and the end of the dietary intervention, blood, urine and faecal samples were collected as well as anthropometric and blood pressure measurements including data on dietary intake. The investigation of flaxseed consumption on bone metabolism, lipid profile and gut microbiota was performed using bone turnover markers, clinical chemistry analysis, nuclear magnetic resonance (NMR) and 16S rRNA gene sequencing. Consumption of flaxseed for 12 weeks led to a tendency (p= 0. 27) for a favourable reduction in the bone-resorption marker, urinary N-Telopeptide Type I Collagen (NTX-I) in the flaxseed group compared to baseline. Significant intervention group*time interactions were observed for serum low density lipoprotein (LDL)-cholesterol (P=0.04) and uric acid (P=0.003) concentrations. In particular, there was a greater increase in serum uric acid after 12 weeks of consuming the flaxseed than placebo flapjacks, and evidence of a beneficial effect of the flaxseed flapjacks in attenuating the rise in LDL-cholesterol observed with the control flapjacks. In addition, after 12 weeks, 16S rRNA amplicon sequencing revealed a non-significant increase in the abundance of the phyla Bacteroidetes and the Bacteroidetes/Firmicutes ratio, suggestive of a beneficial effect of our interventions on gut microbiota composition. Additionally, chronic flaxseed intake showed to impact on urinary creatinine levels compared to baseline which might be indicative of a positive effect of flaxseed on bone health. In summary, the research presented in this thesis has provided novel insights into the common dietary patterns of an Omani population and their relationship with bone health markers according to sex, BMI and age group. Furthermore, findings from the randomised controlled trial has contributed evidence to the literature that intake of 40 g/day of flaxseed appears to have a beneficial impact on LDL-cholesterol and serum uric acid but limited effects on bone turnover markers in postmenopausal women living in the UK. Favourable changes in gut microbiota composition and urinary creatinine over the intervention period may be indicative of positive benefits on bone health and are worthy of further investigation