Endocannabinoids, endocannabinoid-like molecules and their precursors in human small intestinal lumen and plasma: does diet affect them?

PURPOSE: To determine the small intestinal concentration of endocannabinoids (ECs), N-acylethanolamines (NAEs) and their precursors N-acylphosphatidylethanolamines (NAPEs) in humans. To identify relationships between those concentrations and habitual diet composition as well as individual inflammatory status. METHODS: An observational study was performed involving 35 participants with an ileostomy (18W/17M, aged 18-70 years, BMI 17-40 kg/m2). Overnight fasting samples of ileal fluid and plasma were collected and ECs, NAEs and NAPEs concentrations were determined by LC-HRMS. Dietary data were estimated from self-reported 4-day food diaries. RESULTS: Regarding ECs, N-arachidonoylethanolamide (AEA) was not detected in ileal fluids while 2-arachidonoylglycerol (2-AG) was identified in samples from two participants with a maximum concentration of 129.3 µg/mL. In contrast, mean plasma concentration of AEA was 2.1 ± 0.06 ng/mL and 2-AG was 4.9 ± 1.05 ng/mL. NAEs concentrations were in the range 0.72-17.6 µg/mL in ileal fluids and 0.014-0.039 µg/mL in plasma. NAPEs concentrations were in the range 0.3-71.5 µg/mL in ileal fluids and 0.19-1.24 µg/mL in plasma being more abundant in participants with obesity than normal weight and overweight. Significant correlations between the concentrations of AEA, OEA and LEA in biological fluids with habitual energy or fat intakes were identified. Plasma PEA positively correlated with serum C-reactive protein. CONCLUSION: We quantified ECs, NAEs and NAPEs in the intestinal lumen. Fat and energy intake may influence plasma and intestinal concentrations of these compounds. The luminal concentrations reported would allow modulation of the homeostatic control of food intake via activation of GPR119 receptors located on the gastro-intestinal mucosa. CLINICAL TRIAL REGISTRY NUMBER AND WEBSITE: NCT04143139; www.clinicaltrials.gov .

Consumption of a soy drink has no effect on cognitive function but may alleviate vasomotor symptoms in post-menopausal women; a randomised trial.

PURPOSE: Cognitive decline is commonly reported during the menopausal transition, with memory and attention being particularly affected. The aim of this study was to investigate the effects of a commercially available soy drink on cognitive function and menopausal symptoms in post-menopausal women. METHODS: 101 post-menopausal women, aged 44-63 years, were randomly assigned to consume a volume of soy drink providing a low (10 mg/day; control group), medium (35 mg/day), or high (60 mg/day) dose of isoflavones for 12 weeks. Cognitive function (spatial working memory, spatial span, pattern recognition memory, 5-choice reaction time, and match to sample visual search) was assessed using CANTAB pre- and post-the 12 week intervention. Menopausal symptoms were assessed using Greene's Climacteric Scale. RESULTS: No significant differences were observed between the groups for any of the cognitive function outcomes measured. Soy drink consumption had no effect on menopausal symptoms overall; however, when women were stratified according to the severity of vasomotor symptoms (VMS) at baseline, women with more severe symptoms at baseline in the medium group had a significant reduction (P = 0.001) in VMS post-intervention (mean change from baseline score: - 2.15 ± 1.73) in comparison to those with less severe VMS (mean change from baseline score: 0.06 ± 1.21). CONCLUSIONS: Soy drink consumption had no effect on cognitive function in post-menopausal women. Consumption of ~ 350 ml/day (35 mg IFs) for 12 weeks significantly reduced VMS in those with more severe symptoms at baseline. This finding is clinically relevant as soy drinks may provide an alternative, natural, treatment for alleviating VMS, highly prevalent among western women.

The effect of a randomized 12-week soy drink intervention on everyday mood in postmenopausal women.

OBJECTIVE: Dietary soy may improve menopausal symptoms, and subsequently mediate mood. This novel study examines various doses of dietary soy drink on everyday mood stability and variability in postmenopausal women. METHODS: Community-dwelling women (n = 101), within 7 years postmenopause, consumed daily either a low (10 mg, n = 35), medium (35 mg, n = 37), or high (60 mg, n = 29) dose of isoflavones, for 12 weeks. Menopausal symptoms and repeated measures of everyday mood (positive [PA] and negative [NA] affect) (assessed at four time points per day for 4 consecutive days, using The Positive and Negative Affect Schedule) were completed at baseline and follow-up. RESULTS: The dietary soy intervention had no effect on everyday mood stability (for PA [F{2,70} = 0.95, P = 0.390] and NA [F{2,70} = 0.72, P = 0.489]) or variability (for PA [F{2,70} = 0.21, P = 0.807] and for NA [F{2,70} = 0.15, P = 0.864]), or on menopausal symptoms (for vasomotor [F{2,89} = 2.83, P = 0.064], psychological [F{2,88} = 0.63, P = 0.535], somatic [F{2,89} = 0.32, P = 0.729], and total menopausal symptoms [F{2,86} = 0.79, P = 0.458]). There were between-group differences with the medium dose reporting higher PA (low, mean 24.2, SD 6; and medium, mean 29.7, SD 6) and the low dose reporting higher NA (P = 0. 048) (low, mean 11.6, SD 2; and high, mean 10.6, SD 1) in mood scores. Psychological (baseline M = 18 and follow-up M = 16.5) and vasomotor (baseline M = 4.2 and follow-up M = 3.6) scores declined from baseline to follow-up for the overall sample. CONCLUSIONS: Soy isoflavones had no effect on mood at any of the doses tested. Future research should focus on the menopause transition from peri to postmenopause as there may be a window of vulnerability, with fluctuating hormones and increased symptoms which may affect mood.

The effect of weight change over a 2-year period on inflammatory status in postmenopausal women.

BACKGROUND/OBJECTIVES: Body fat distribution has been shown to be a predictor of adhesion molecule and inflammatory marker expression albeit the effect of modest weight change on concentrations of adhesion molecules and inflammatory markers in postmenopausal women are not fully understood. The primary aim was to investigate the effects of weight change on adhesion molecules and inflammatory markers over 24 months in postmenopausal women. SUBJECTS/METHODS: Body composition was assessed in 254 healthy postmenopausal women using dual-energy X-ray absorptiometry (DXA). Adhesion molecules and inflammatory markers were analysed by multiplex ELISA. Participants weight gain/loss at 24 months was defined as any value that was either above/below the weight value recorded at baseline. RESULTS: Postmenopausal women with an average weight loss of 3% had significantly decreased leptin concentrations by 18% at 24 months (P < 0.01). A 4% increase in body weight or a 9% increase in FMI significantly increased intercellular adhesion molecule-1 (ICAM-1), tumour necrosis factor-α (TNF-α) and leptin concentrations in postmenopausal women at 24 months (P < 0.01). CONCLUSIONS: Modest weight loss in postmenopausal women has a lowering effect on leptin concentrations over 24 months which may improve inflammatory status whilst modest weight gain increases ICAM-1, leptin and TNF-α, markers which are associated with a pro-inflammatory state and vascular complications.

Effects of supplementation with a calcium-rich marine-derived multi-mineral supplement and short-chain fructo-oligosaccharides on serum lipids in postmenopausal women.

Recent literature suggests that Ca supplements have adverse effects on cardiovascular health. The effects of a Ca-rich supplement administered alone or in combination with short-chain fructo-oligosaccharides (scFOS) on serum lipids in postmenopausal women were examined using secondary data from a 24-month double-blind randomised controlled study. A total of 300 postmenopausal women were randomly assigned to daily supplements of 800 mg of Ca (2·4 g Aquamin) (Ca), 800 mg of Ca with 3 g of scFOS (CaFOS) or control (maltodextrin) (MD). A full lipid profile, body composition, blood pressure and a range of cytokines were measured at baseline and after 24 months. Intention-to-treat ANCOVA assessed treatment effects between the groups. A significant time-by-treatment effect was observed for LDL and total cholesterol for the Ca and CaFOS groups, with both groups having lower LDL and total cholesterol concentrations compared with MD after 24 months. The control group had mean (5·2 mmol/l) total cholesterol concentrations above the normal range (≤ 5 mmol/l) at 24 months, whereas values remained within the normal range in the treatment groups. There was no significant treatment effect on HDL-cholesterol, TAG, body composition, blood pressure or cytokine concentrations at 24 months, with the exception of IL-4, where there was a significant increase in the CaFOS group compared with the placebo. This study demonstrates a lipid-lowering effect of both the Ca-rich supplement alone and the supplement with scFOS. At the 4-year follow-up, there was no significant difference between the groups for reported diagnosed cardiovascular conditions.

Supplementation with calcium and short-chain fructo-oligosaccharides affects markers of bone turnover but not bone mineral density in postmenopausal women.

This 24-mo randomized, double-blind, controlled trial aimed to examine whether supplementation with a natural marine-derived multi-mineral supplement rich in calcium (Ca) taken alone and in conjunction with short-chain fructo-oligosaccharide (scFOSs) has a beneficial effect on bone mineral density (BMD) and bone turnover markers (BTMs) in postmenopausal women. A total of 300 non-osteoporotic postmenopausal women were randomly assigned to daily supplements of 800 mg of Ca, 800 mg of Ca with 3.6 g of scFOS (CaFOS), or 9 g of maltodextrin. BMD was measured before and after intervention along with BTMs, which were also measured at 12 mo. Intention-to-treat ANCOVA identified that the change in BMD in the Ca and CaFOS groups did not differ from that in the maltodextrin group. Secondary analysis of changes to BTMs over time identified a greater decline in osteocalcin and C-telopeptide of type I collagen (CTX) in the Ca group compared with the maltodextrin group at 12 mo. A greater decline in CTX was observed at 12 mo and a greater decline in osteocalcin was observed at 24 mo in the CaFOS group compared with the maltodextrin group. In exploratory subanalyses of each treatment group against the maltodextrin group, women classified with osteopenia and taking CaFOS had a smaller decline in total-body (P = 0.03) and spinal (P = 0.03) BMD compared with the maltodextrin group, although this effect was restricted to those with higher total-body and mean spinal BMD at baseline, respectively. Although the change in BMD observed did not differ between the groups, the greater decline in BTMs in the Ca and CaFOS groups compared with the maltodextrin group suggests a more favorable bone health profile after supplementation with Ca and CaFOS. Supplementation with CaFOS slowed the rate of total-body and spinal bone loss in postmenopausal women with osteopenia-an effect that warrants additional investigation. This trial was registered at www.controlled-trials.com as ISRCTN63118444.