The Effects of Vitamin D Supplementation on C-Reactive Protein and Systolic and Diastolic Blood Pressure in Postmenopausal Women: A Meta-Analysis and Systematic Review of Randomized Controlled Trials.

BACKGROUND: An inverse relationship between vitamin D supplementation and C-reactive protein (CRP) and hypertension has been reported, mostly through observational data. This inverse relationship, however, has not been confirmed in randomized controlled trials (RCTs). A meta-analysis of RCTs is needed to provide more robust evidence. OBJECTIVE: This systematic review of RCTs was conducted to assess the effect of vitamin D supplementation on CRP, systolic blood pressure (SBP), and diastolic blood pressure (DBP) in postmenopausal women. METHODS: Four databases (PubMed, Web of Science, Embase, and Scopus) were systemically searched to identify relevant RCTs published in international scientific journals up to January 2023. Changes from baseline and SDs of CRP, SBP, and DBP were compared between postmenopausal women who received vitamin D supplementation and those who did not (controls). These parameters were applied to compute the overall effect sizes using the random-effects model. Data were summarized as mean difference (MD) with 95% CI. Heterogeneity among arms was scrutinized using the Cochrane's Q test and I2 statistic. Publication bias was judged by means of funnel plots and Egger's test. RESULTS: Seven studies with 6 arms on CRP, 6 arms on SBP, and 6 arms on DBP were included in the meta-analysis. Combined effect sizes suggested a significant effect of vitamin D supplementation on CRP (MD = -0.65 mg/L; 95% CI -0.93 to -0.37 mg/L; P < .001). In addition, CRP concentrations were significantly reduced after vitamin D supplementation in studies with a duration of more than 3 months (MD = -0.91 mg/L; 95% CI -1.37 to -0.45 mg/L; P < .001) and studies involving doses of ≤1,000 IU/d (MD = -2.10 mg/L; 95% CI -2.51 to -1.68 mg/L; P < .001). Vitamin D supplementation did not reduce SBP significantly (MD = -1.06 mm Hg; 95% CI -2.43 to 0.30 mm Hg; P = .127) and DBP (MD = 0.003 mm Hg; 95% CI -0.86 to 0.86 mm Hg; P = .994) levels compared with control groups. CONCLUSIONS: This meta-analysis concluded that vitamin D supplementation is associated with reduced CRP concentrations among postmenopausal women.

Effects of Multispecies Probiotic Supplementation on Serum Bone Turnover Markers in Postmenopausal Women with Osteopenia: A Randomized, Double-Blind, Placebo-Controlled Trial.

Probiotics have been found to have beneficial effects on bone metabolism. In this randomized, double-blind, placebo-controlled trial, the effects of multispecies probiotic supplementation on bone turnover markers were evaluated after 12 weeks. Forty postmenopausal women with osteopenia were included and randomly divided into two groups. The intervention group received multispecies probiotics, while the control group received identical placebo sachets daily. The baseline characteristics of both groups were similar. Still, the median serum bone resorption marker C-terminal telopeptide of type I collagen (CTX) was slightly higher in the multispecies probiotic group than in the placebo group (0.35 (0.12, 0.53) vs. 0.16 (0.06, 0.75); p-value = 0.004). After 12 weeks, the mean difference in serum CTX at baseline versus 12 weeks was significantly different between the multispecies probiotic and placebo groups (-0.06 (-0.29, 0.05) vs. 0.04 (-0.45, 0.67); p-value < 0.001). The multispecies probiotic group showed a significant decrease in serum CTX at 12 weeks compared with baseline (p-value 0.026). However, the placebo group showed no significant change in serum CTX (p-value 0.18). In conclusion, multispecies probiotics may have a preventive effect on bone through their antiresorptive effect in osteopenic postmenopausal women.

Effects of melatonin on blood pressure, arterial stiffness and quality of life in postmenopausal women: A randomized controlled trial.

OBJECTIVES: Studies suggest that melatonin may promote cardiovascular protection. Previous trials have primarily been performed on co-morbid patients. Little information exist on the effect in postmenopausal women with general good health. DESIGN, PARTICIPANTS AND INTERVENTION: In a double-blinded placebo-controlled study, we randomized 41 postmenopausal women to either 10 mg melatonin per day or placebo for 3 months. OUTCOME MEASURES: Outcomes of the trial was changes in blood pressure, pulse wave velocity (PWV), and quality of sleep evaluated by Pittsburgh Sleep Quality Index (PSQI). RESULTS: Thirty-nine women completed the study. Mean age was 63 years (range 55-75 years). Over the 3 months of the trial, PWV did not differ between groups: Placebo 1.1% (IQR -2.1;9.9) vs. melatonin 0.0% (IQR-9.8;4.1), p = 0.43). The were no significant differences in blood pressure bewteen melatonin and placebo group. Both groups had a pour quality of sleep at baseline (placebo: PSQI 6.0 (IQR 3.3; 8.8) vs. melatonin PSQI 6.0 (IQR 3.0; 10.0), p = 0.94), which did not change in response to treatment. CONCLUSION: In healthy postmenopausal women, supplementation with 10 mg melatonin was well-tolerated, but we did not observe any significant improvements in pulse wave velocity, blood pressure or quality of sleep compared with placebo.

L-Citrulline supplementation attenuates aortic pressure and pressure waves during metaboreflex activation in postmenopausal women.

Postmenopausal women have augmented pressure wave responses to low-intensity isometric handgrip exercise (IHG) due to an overactive metaboreflex (postexercise muscle ischaemia, PEMI), contributing to increased aortic systolic blood pressure (SBP). Menopause-associated endothelial dysfunction via arginine (ARG) and nitric oxide deficiency may contribute to exaggerated exercise SBP responses. L-Citrulline supplementation (CIT) is an ARG precursor that decreases SBP, pulse pressure (PP) and pressure wave responses to cold exposure in older adults. We investigated the effects of CIT on aortic SBP, PP, and pressure of forward (Pf) and backward (Pb) waves during IHG and PEMI in twenty-two postmenopausal women. Participants were randomised to CIT (10 g/d) or placebo (PL) for 4 weeks. Aortic haemodynamics were assessed via applanation tonometry at rest, 2 min of IHG at 30 % of maximal strength, and 3 min of PEMI. Responses were analysed as change (Δ) from rest to IHG and PEMI at 0 and 4 weeks. CIT attenuated ΔSBP (−9 ± 2 v. −1 ± 1 mmHg, P = 0·006), ΔPP (−5 ± 2 v. 0 ± 1 mmHg, P = 0·03), ΔPf (−6 ± 2 v. −1 ± 1 mmHg, P = 0·01) and ΔPb (−3 ± 1 v. 0 ± 1 mmHg, P = 0·02) responses to PEMI v. PL. The ΔPP during PEMI was correlated with ΔPf (r = 0·743, P < 0·001) and ΔPb (r = 0·724, P < 0·001). Citrulline supplementation attenuates the increase in aortic pulsatile load induced by muscle metaboreflex activation via reductions in forward and backward pressure wave amplitudes in postmenopausal women.

Association Study between Antioxidant Nutrient Intake and Low Bone Mineral Density with Oxidative Stress-Single Nucleotide Variants: GPX1 (rs1050450 and rs17650792), SOD2 (rs4880) and CAT (rs769217) in Mexican Women.

Oxidative stress is essential in developing multiple bone metabolism diseases, including osteoporosis. Single-nucleotide variants (SNVs) have been associated with oxidative stress, promoting an imbalance between the production of reactive oxygen species and the ability to neutralize them, and it has been reported that antioxidant nutrient intake can influence bone mineral density (BMD). This work reports the association between oxidative stress-related SNVs (GPX1-rs1050450, rs17650792, SOD2-rs4880, and CAT-rs769217), BMD, and antioxidant nutrient intake. The study included 1269 Mexican women from the Health Workers Cohort Study. Genotyping was performed using predesigned TaqMan assays. Dietary data were collected using a 116-item semi-quantitative food frequency questionnaire. A dietary antioxidant quality score (DAQS) was used to estimate antioxidant-nutrient intake. Association analysis was estimated via linear, logistic, or quantile regression models. The results showed an association of the rs1050450-A and rs17650792-A alleles with femoral neck BMD (p = 0.038 and p = 0.017, respectively) and the SNV rs4880-A allele with total hip BMD (p = 0.026) in respondents aged 45 years or older. In addition, antioxidant-nutrient intake was associated with the rs4880-GG genotype, being significant for fiber (p = 0.007), riboflavin (p = 0.005), vitamin B6 (p = 0.034), and vitamin D (p = 0.002). The study showed an association between oxidative stress-related SNVs, BMD, and antioxidant-nutrient intake in Mexican women. Therefore, treatments for low BMD could be developed based on antioxidant supplementation.

Vitamin D Supplementation During COVID-19 Lockdown and After 20 Months: Follow-Up Study on Slovenian Women Aged Between 44 and 66.

Introduction: The main objective was to assess the impact of the COVID-19 pandemic on vitamin D supplementation habits and their changes in the follow-up, 20 months after the study in Slovenian premenopausal and postmenopausal women. Methods: A cross-sectional study was conducted between March and May 2021. 176 healthy women aged 44 to 65 from the Central Slovenian region were included in the final analysis. Vitamin D status was determined by measuring 25(OH)D concentration. After 20 months an online follow-up questionnaire was sent out, to which 123 participants responded with complete data. Results: Between March and May 2021, 61% of the participants were supplementing vitamin D. 55% of the supplementers and 88% of the non-supplementers had insufficient levels (total 25(OH)D <75 nmol/L). After 20 months in the follow-up, it was found that 62% of participants were taking vitamin D supplements, but only 70% of those who had initially reported taking supplements were still doing so. In the follow-up 61% of participants stated that they started or increased vitamin D intake due to COVID-19. Conclusions: Vitamin D supplementation increased 7-fold compared to pre-pandemic levels and remained at a high level after 20 months. However, a significant number of participants discontinued supplementation, and only one-fifth were taking vitamin D throughout the entire year. Supplementation is effective for vitamin D deficiency prevention only at the individual level, however due to low compliance it should not be the only strategy for preventing vitamin D deficiency in the population.

Tai Chi exercise reduces circulating levels of inflammatory oxylipins in postmenopausal women with knee osteoarthritis: results from a pilot study.

Background: Tai Chi (TC) controls pain through mind-body exercise and appears to alter inflammatory mediators. TC actions on lipid biomarkers associated with inflammation and brain neural networks in women with knee osteoarthritic pain were investigated. Methods: A single-center, pre- and post-TC group (baseline and 8 wk) exercise pilot study in postmenopausal women with knee osteoarthritic pain was performed. 12 eligible women participated in TC group exercise. The primary outcome was liquid chromatography tandem mass spectrometry determination of circulating endocannabinoids (eCB) and oxylipins (OxL). Secondary outcomes were correlations between eCB and OxL levels and clinical pain/limitation assessments, and brain resting-state function magnetic resonance imaging (rs-fMRI). Results: Differences in circulating quantitative levels (nM) of pro-inflammatory OxL after TC were found in women. TC exercise resulted in lower OxL PGE1 and PGE2 and higher 12-HETE, LTB4, and 12-HEPE compared to baseline. Pain assessment and eCB and OxL levels suggest crucial relationships between TC exercise, inflammatory markers, and pain. Higher plasma levels of eCB AEA, and 1, 2-AG were found in subjects with increased pain. Several eCB and OxL levels were positively correlated with left and right brain amygdala-medial prefrontal cortex functional connectivity. Conclusion: TC exercise lowers pro-inflammatory OxL in women with knee osteoarthritic pain. Correlations between subject pain, functional limitations, and brain connectivity with levels of OxL and eCB showed significance. Findings indicate potential mechanisms for OxL and eCB and their biosynthetic endogenous PUFA precursors that alter brain connectivity, neuroinflammation, and pain. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT04046003.

Association between equol and non-alcoholic fatty liver disease in Japanese women in their 50s and 60s.

BACKGROUND AND AIM: Equol is a metabolite of soy isoflavone and has estrogenic activity. The incidence of non-alcoholic fatty liver disease (NAFLD) increases after menopause in women, which is thought to result in a decrease in estrogen. This study aimed to evaluate the association between equol and NAFLD. METHODS: We evaluated 1185 women aged 50-69 years who underwent health check-ups at four health centers in Fukushima, Japan. Equol producers were defined by a urinary equol concentration of 1.0 µM or more. In addition to comparison between equol producers and non-producers, the association between equol and NAFLD was estimated using logistic regression analysis adjusting for fast walking and eating habits. RESULTS: Of the 1185 participants, 345 (29.1%) women were equol producers. The proportions of women who had NAFLD (34.8% vs 45.2%) were significantly lower in the equol-producing group than in the non-producing group. Multivariable logistic regression analysis showed that equol production was significantly associated with NAFLD (odds ratio = 0.66, 95% confidence interval: 0.51-0.86). CONCLUSIONS: Equol production was significantly associated with NAFLD in women in their 50s and 60s.

Predictors of osteoporotic fracture in postmenopausal women: a meta-analysis.

Osteoporosis affects more than 200 million women worldwide, with postmenopausal women being particularly susceptible to this condition and its severe sequelae disproportionately, such as osteoporotic fractures. To date, the current focus has been more on symptomatic treatment, rather than preventive measures. To address this, we performed a meta-analysis aiming to identify potential predictors of osteoporotic fractures in postmenopausal women, with the ultimate goal of identifying high-risk patients and exploring potential therapeutic approaches. We searched Embase, MEDLINE and Cochrane with search terms (postmenopausal AND fracture) AND ("risk factor" OR "predictive factor") in May 2022 for cohort and case-control studies on the predictors of osteoporotic fracture in postmenopausal women. Ten studies with 1,287,021 postmenopausal women were found eligible for analyses, in which the sample size ranged from 311 to 1,272,115. The surveyed date spanned from 1993 to 2021. Our results suggested that age, BMI, senior high school and above, parity ≥ 3, history of hypertension, history of diabetes mellitus, history of alcohol intake, age at menarche ≥ 15, age at menopause < 40, age at menopause > 50, estrogen use and vitamin D supplements were significantly associated with osteoporotic fracture in postmenopausal women. Our findings facilitate the early prediction of osteoporotic fracture in postmenopausal women and may contribute to potential therapeutic approaches. By focusing on preventive strategies and identifying high-risk individuals, we can work toward reducing the burden of osteoporosis-related fractures in this vulnerable population.

Plasma fatty acid composition and some markers of dietary habits are associated with cardiovascular disease risk determined by an atherogenic plasma index in postmenopausal women.

It is hypothesized that plasma proportion of selected fatty acids (FAs) and dietary habits are linked with the risk of cardiovascular disease (CVD) in postmenopausal women. Therefore, this study was designed to determine the association of plasma FA composition and markers of dietary habits with an atherogenic index of plasma (AIP), a predictor of CVD risk in postmenopausal women. In total, 87 postmenopausal women with an average age of 57 ± 7 years were recruited and their dietary intake, anthropometric and biochemical parameters, and FA status in total plasma lipid proportions were determined, showing that 65.5% of the participants had a high risk of CVD according to their AIP value. After adjusting for some confounders (age, body mass index, and physical activity level), the risk of CVD was only positively associated with the frequency of consumption of animal fat spreads (butter and lard) of terrestrial origin. Regarding the FA profile, CVD risk was positively associated with the percentages of vaccenic acid, dihomo-γ-linolenic acid, and monounsaturated fatty acids (MUFA; mainly n-7) in total FA, as well as the MUFA/SFA ratio in total plasma and stearoyl-CoA desaturase-16 activity (16:1/16:0 ratio). In contrast, the risk of CVD was negatively associated with percentages of α-linolenic acid, total polyunsaturated fatty acids (PUFA), and PUFA/MUFA ratio in total plasma lipid, and the estimated activity of Δ5-desaturase (20:4/20:3 n-6 ratio). These results support the current recommendations to decrease the frequency of animal fat spread intake because it is associated with a reduced CVD risk based on AIP in postmenopausal women. In accordance with these plasma percentages of ALA, vaccenic acid, dihomo-γ-linolenic acid, PUFA, PUFA/MUFA ratio, and 16:1/16:0 ratio may be important parameters in CVD risk assessment.

Optimal Serum 25(OH)D Levels and Vitamin D Intake in Korean Postmenopausal Women.

Vitamin D plays a crucial role in regulating the growth and maintenance of the musculoskeletal system. Postmenopausal women are vulnerable to bone fractures because of the decrease in bone mineral density (BMD). Therefore, this study aimed to identify the determinants that influence BMD and the 25(OH)D levels in Korean postmenopausal women. This study collected general and dietary intake information, measured biochemical indices, and conducted BMD tests in 96 postmenopausal women residing in a metropolitan area in Korea. This study analyzed factors that influenced serum 25-hydroxyvitamin D (25(OH)D) and BMD, as well as the correlation between the intact parathyroid hormone (iPTH) and serum 25(OH)D levels. The serum 25(OH)D levels increased by 0.226 ng/mL in the summertime, 0.314 ng/mL in the wintertime, and 0.370 ng/mL on annual average when vitamin D intake rose by 1 µg/1000 kcal. When the serum 25(OH)D levels were ≥18.9 ng/mL, the iPTH levels did not rapidly increase. To maintain the serum 25(OH)D levels at ≥18.9 ng/mL, a daily vitamin D intake of ≥13.21 µg was required. Consequently, consuming vitamin D-fortified foods or vitamin D supplements is necessary to improve both bone health and vitamin D nutritional status.

Effect of Vitamin E Supplementation on Chronic Insomnia Disorder in Postmenopausal Women: A Prospective, Double-Blinded Randomized Controlled Trial.

Chronic insomnia disorder is one of the most common problems in postmenopausal women, exacerbated by underdiagnosis and improper treatment. This double-blinded, randomized, placebo-controlled trial was conducted to evaluate the potential of vitamin E to treat chronic insomnia as an alternative to sedative drugs and hormonal therapy. The study enrolled 160 postmenopausal women with chronic insomnia disorder, divided randomly into two groups. The vitamin E group received 400 units of mixed tocopherol daily, while the placebo group received an identical oral capsule. The primary outcome of this study was sleep quality assessed by the Pittsburgh Sleep Quality Index (PSQI), a self-evaluated and standardized questionnaire. The secondary outcome was the percentage of participants using sedative drugs. There were no significant differences in baseline characteristics between the study groups. However, the median PSQI score at baseline was slightly higher in the vitamin E group compared with the placebo (13 (6, 20) vs. 11 (6, 20); p-value 0.019). After one month of intervention, the PSQI score was significantly lower (indicating better sleep quality) in the vitamin E group compared with the placebo (6 (1, 18) vs. 9 (1, 19); p-value 0.012). Moreover, the improvement score was significantly higher in the vitamin E group compared with the placebo (5 (-6, 14) vs. 1 (-5,13); p-value < 0.001). In addition, there was a significant reduction in the percentage of patients using sedative drugs in the vitamin E group (15%; p-value 0.009), while this reduction was not statistically significant in the placebo group (7.5%; p-value 0.077). This study demonstrates vitamin E's potential as an excellent alternative treatment for chronic insomnia disorder that improves sleep quality and reduces sedative drug use.

Vitamin D, Menopausal Health and COVID-19: Critical Appraisal of Current Data.

Inconsistency exists across studies conducted in postmenopausal women regarding the effect of vitamin D deficiency (VDD) and supplementation on several aspects of menopausal health, such as fractures, vasomotor symptomatology, cardiovascular disease (CVD), cancer and infections, including coronavirus disease 2019 (COVID-19). The aim of this review is to critically summarize the evidence provided by observational studies and randomized controlled trials (RCTs) of vitamin D supplementation in postmenopausal women with VDD. Observational studies have found that VDD is associated with an increased risk of falls and fractures after the menopause. VDD also has a negative effect on menopausal symptomatology. VDD, especially its severe form, is associated with an increased risk of CVD risk factors and CVD events. VDD is associated with increased risk and mortality from several cancer types and risk of infections. The evidence from RCTs regarding the effect of vitamin D supplementation on falls, fractures, menopausal symptoms, cardiovascular disease, cancer and infections is not robust. Thus, skeletal health may benefit only when vitamin D is co-administered with calcium, especially in those ≥70 years old and with severe VDD. There is no evidence of a favorable effect on menopausal symptoms or risk of CVD or cancer, except for a modest reduction in cancer-related mortality. Inconsistency still exists regarding its effect on infection risk, disease severity and mortality due to COVID-19.

Association of calcium and vitamin D supplementation with cancer incidence and cause-specific mortality in Black women: Extended follow-up of the Women's Health Initiative calcium-vitamin D trial.

Low circulating vitamin D levels are more prevalent in Black than White individuals. We analyzed the Women's Health Initiative (WHI) calcium plus vitamin D (CaD) randomized clinical trial extended follow-up data to evaluate associations between calcium plus vitamin D supplementation and incident cancer, cardiovascular disease (CVD), and cause-specific mortality endpoints among Black women. Intent-to-treat analysis was performed. Among 3325 Black women in the CaD trial who were randomized into either daily calcium (1000 mg of calcium carbonate) plus vitamin D (400 IU D3) or placebos for an average of 7 years, there were 813 deaths, 588 incident cancers, and 837 CVD events during an average of 15.7 years of follow up (52 230 total person-years). Using Cox's proportional hazards models, we calculated hazard ratios and their confidence intervals for outcomes ascertained during the trial period, posttrial follow-up period and overall periods combined. We found that total mortality, cause-specific mortality, and total cancer incidence were almost identical between CaD and placebo groups. These results suggest that calcium plus vitamin D supplementation does not reduce risks of cancer, CVD, or other major causes of death in Black women overall and, thus, other medical, behavioral or social interventions should be considered to narrow health disparities related to these outcomes. However, other finer endpoints, such as colorectal cancer, warrants further investigation.

The Effect of Palm Pollen Extract on Sexual Disorders in Postmenopausal Women: A Randomized Clinical Trial.

Background: Considering the numerous nutritional and estrogenic compounds of palm pollen and their effect on sexual function, this study was performed to investigate the effect of palm pollen extract on sexual disorders in postmenopausal women. Methods: In this three-blind clinical trial, 110 postmenopausal women from December 2019 to December 2020 from Rafsanjan comprehensive health service centers were randomly assigned to two groups, using a lottery method. The intervention group received 300 mg capsule of palm pollen extract, and the control group received placebo for 4 weeks. Sexual disorders were assessed with a 6-item female sexual function index before, at the end of the intervention, and 4 weeks after the end of the intervention. Independent t-test, Chi-square and repeated measures ANOVA were used to analyze the data through SPSS software version 21. The statistically significant level was considered P value less than 0.05. Results: The mean scores of sexual disorders before the intervention in the intervention and control groups were 15.36±5.01 and 14.13±4.67 (P=0.68); at the end of the intervention, they were 15.18±4.50 and 14.22±3.91 (P=0.43) and 4 weeks after the end of the intervention we obtained 15.7±4.77 and 14.44±3.78, respectively (P=0.90). Conclusions: According to the results, daily consumption of 300 mg of date pollen extract had no effect on improving sexual disorders in postmenopausal women. Further studies in this field are suggested.Trial Registration Number: IRCT20160308026971N1.

Impact of Qigong exercises on the severity of the menopausal symptoms and health-related quality of life: A randomised controlled trial.

The aim of the present study was to analyze the effects of a Qigong exercise programme on the severity of the menopausal symptoms and health-related quality of life (HRQoL) of community-dwelling postmenopausal women. This was done by means of a randomised clinical trial with a sample of 125 women who were assigned to either a control (n = 62) or an experimental group (n = 63). The severity of their menopause-related symptoms and HRQoL were assessed through the Menopause Rating Scale (MRS) and the 36-item Short-Form Health Survey (SF-36) respectively, before and after the intervention period. The main findings of our study reveal significant improvement in the severity of menopausal symptoms at the somatic, psychological, and urogenital levels, as well as in the total score of the MRS. Additionally, participants assigned to the Qigong group experienced improvement in the general health, physical functioning, role-physical, bodily pain, vitality, and mental health domains of the 36-item Short-Form Health Survey, as well as in its physical component and mental component summaries. We can therefore conclude that, among Spanish postmenopausal women, a twelve-week Qigong exercise programme has beneficial effects on the severity of menopausal symptoms and HRQoL.HighlightsWe have studied the effects of Qigong on menopause-related quality of life.Qigong is a useful tool in the management of the severity of menopausal symptoms.A 12-week Qigong programme showed benefits on health-related quality of life.Trial registration: ClinicalTrials.gov identifier: NCT03989453.

The Effects of Oral Probiotic Supplementation in Postmenopausal Women with Overweight and Obesity: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

Gut microbiota has been identified as a unique endocrine organ linked to the development of cardiovascular disease and other illnesses, especially deteriorated in overweight and obese postmenopausal women. The object of this systematic review and meta-analysis aimed to assess the effects of oral supplementation with probiotics for overweight and obese postmenopausal women. We performed a systematic search for randomized controlled trials (RCTs) from inception to April 2022 in MEDLINE, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov. We also performed a hand search by reviewing reference lists to identify trials. The risk of bias in individual studies was assessed with the Cochrane risk of bias tool for randomized trials (RoB). Two reviewers independently selected studies and collected data. There were 6 studies from 5 RCTs with 281 participants in this systematic review. Compared with the placebo, the probiotics supplementation group had reductions in insulin (MD - 4.20 IU/L (95% CI - 8.11 to - 0.30 IU/L), I2 = 54%), HOMA-IR (MD - 1.25 (95% CI - 2.49 to - 0.01), I2 = 50%), and TNF-α (MD - 0.12 pg/mL (95% CI - 0.22 to - 0.01 pg/mL), I2 = 44%). Improvements were also shown in body adiposity and lipid profile, but these effects were nonsignificant. In addition to body adiposity and cardiovascular risk markers, one trial showed the administration of probiotics also had an effect on iron metabolism. In conclusion, probiotics have a potential benefit on glucose metabolism and inflammatory process in overweight and obese postmenopausal women, but this effect is mild. It demonstrates that oral probiotics supplementation can be a complementary treatment for improving the fitness of postmenopausal women with overweight and obesity.

EMAS position statement: Vitamin D and menopausal health.

INTRODUCTION: There is increasing evidence that vitamin D has widespread tissue effects. In addition to osteoporosis, vitamin D deficiency has been associated with cardiovascular disease, diabetes, cancer, infections and neurodegenerative disease. However, the effect of vitamin D supplementation on non-skeletal outcomes requires clarification, especially in postmenopausal women. AIM: This position statement provides an evidence-based overview of the role of vitamin D in the health of postmenopausal women based on observational and interventional studies. MATERIALS AND METHODS: Literature review and consensus of expert opinion. RESULTS AND CONCLUSIONS: Vitamin D status is determined by measuring serum 25-hydroxyvitamin D levels. Concentrations <20 ng/ml (<50 nmol/l) and <10 ng/ml (<25 nmol/l) are considered to constitute vitamin D deficiency and severe deficiency, respectively. Observational data suggest an association between vitamin D deficiency and adverse health outcomes in postmenopausal women, although they cannot establish causality. The evidence from randomized controlled trials concerning vitamin D supplementation is not robust, since many studies did not consider whether people were deficient at baseline. Moreover, high heterogeneity exists in terms of the population studied, vitamin D dosage, calcium co-administration and duration of intervention. Concerning skeletal health, vitamin D deficiency is associated with low bone mass and an increased risk of fractures. Vitamin D supplementation at maintenance doses of 800-2000 IU/day (20-50 µg/day), after repletion of vitamin D status with higher weekly or daily doses, may be of benefit only when co-administered with calcium (1000-1200 mg/day), especially in the elderly populations and those with severe vitamin D deficiency. Concerning cardiovascular disease, vitamin D deficiency is associated with an increased prevalence of cardiovascular risk factors, mainly metabolic syndrome, type 2 diabetes mellitus and dyslipidemia. Vitamin D deficiency, especially its severe form, is associated with an increased risk of cardiovascular events (coronary heart disease, stroke, mortality), independently of traditional risk factors. Vitamin D supplementation may have a modestly beneficial effect on lipid profile and glucose homeostasis, especially in obese individuals or those ≥60 years old and at doses of ≥2000 IU/day (≥50 µg/day). However, it has no effect on the incidence of cardiovascular events. Concerning cancer, vitamin D deficiency is associated with increased incidence of and mortality from several types of cancer, such as colorectal, lung and breast cancer. However, the data on other types of gynecological cancer are inconsistent. Vitamin D supplementation has no effect on cancer incidence, although a modest reduction in cancer-related mortality has been observed. Concerning infections, vitamin D deficiency has been associated with acute respiratory tract infections, including coronavirus disease 2019 (COVID-19). Vitamin D supplementation may decrease the risk of acute respiratory tract infections and the severity of COVID-19 (not the risk of infection). Concerning menopausal symptomatology, vitamin D deficiency may have a negative impact on some aspects, such as sleep disturbances, depression, sexual function and joint pains. However, vitamin D supplementation has no effect on these, except for vulvovaginal atrophy, at relatively high doses, i.e., 40,000-60,000 IU/week (1000-1500 IU/week) orally or 1000 IU/day (25 µg/day) as a vaginal suppository.

Associations of long chain polyunsaturated fatty acids with bone mineral density and bone turnover in postmenopausal women.

PURPOSE: The immunomodulatory properties of n-3 long chain polyunsaturated fatty acids (LCPUFA) are reported to reduce bone loss through alteration of bone remodelling and n-3 LCPUFA, therefore, may benefit bone health in post-menopausal women, a vulnerable group at high risk of osteoporosis. METHODS: Measures of bone mineral density (BMD) were determined using dual energy X-ray absorptiometry (DEXA) in 300 post-menopausal women. The bone turnover markers osteocalcin (OC), C-terminal telopeptides of type 1 collagen (CTX) and total alkaline phosphatase were quantified in serum along with urinary creatinine corrected deoxypyridinoline (DPD/Cr) and CTX/Cr and the CTX:OC ratio calculated. Total serum n-6 PUFA (LA + AA) and n - 3 LCPUFA (ALA + EPA + DPA + DHA) were measured and the n - 6:n - 3 ratio was calculated. RESULTS: Mean (SD) age and body mass index (BMI) were 61 (6.4) years and 27.4 (4.8) kg/m2, respectively with participants being 12.6 (7.6) years post-menopause. Multiple regression analysis identified no association between n-3 LCPUFA and any of the measures of T-score or BMD albeit a significant positive association between total n - 3 LCPUFA and femur BMD (ß = 0.287; p = 0.043) was observed within those women with a low n - 6:n - 3 ratio. There was a significant inverse association between ALA and urinary DPD/Cr (ß = - 0.141; p = 0.016). CONCLUSION: A favourable low n - 6:n - 3 ratio was associated with higher femur BMD and a higher n - 3 LCPUFA (ALA) was associated with lower bone resorption. These results support a beneficial role for n - 3 LCPUFA in reducing postmenopausal bone resorption and favourably influencing BMD. TRIAL NUMBER & DATE OF REGISTRATION: ISRCTN63118444, 2nd October 2009, "Retrospectively registered".

Effects of L-Citrulline Supplementation on Endothelial Function and Blood Pressure in Hypertensive Postmenopausal Women.

Aging and menopause are associated with decreased nitric oxide bioavailability due to reduced L-arginine (L-ARG) levels contributing to endothelial dysfunction (ED). ED precedes arterial stiffness and hypertension development, a major risk factor for cardiovascular disease. This study investigated the effects of L-citrulline (L-CIT) on endothelial function, aortic stiffness, and resting brachial and aortic blood pressures (BP) in hypertensive postmenopausal women. Twenty-five postmenopausal women were randomized to 4 weeks of L-CIT (10 g) or placebo (PL). Serum L-ARG, brachial artery flow-mediated dilation (FMD), aortic stiffness (carotid-femoral pulse wave velocity, cfPWV), and resting brachial and aortic BP were assessed at 0 and 4 weeks. L-CIT supplementation increased L-ARG levels (Δ13 ± 2 vs. Δ−2 ± 2 µmol/L, p < 0.01) and FMD (Δ1.4 ± 2.0% vs. Δ−0.5 ± 1.7%, p = 0.03) compared to PL. Resting aortic diastolic BP (Δ−2 ± 4 vs. Δ2 ± 5 mmHg, p = 0.01) and mean arterial pressure (Δ−2 ± 4 vs. Δ2 ± 6 mmHg, p = 0.04) were significantly decreased after 4 weeks of L-CIT compared to PL. Although not statistically significant (p = 0.07), cfPWV decreased after L-CIT supplementation by ~0.66 m/s. These findings suggest that L-CIT supplementation improves endothelial function and aortic BP via increased L-ARG availability.