Vitamin D deficiency in nursing home residents: a systematic review.

CONTEXT: Vitamin D deficiency is a global public health issue, particularly in nursing home residents. OBJECTIVE: This review critically summarizes the prevalence of vitamin D deficiency in nursing home residents worldwide. In addition, it outlines the effect of vitamin D intervention, alone or in combination with other nutrients or therapies, on improving vitamin D status and associated health outcomes in nursing home residents. DATA SOURCES, EXTRACTION, AND ANALYSIS: Searches were conducted of electronic databases for articles published from 2010 to May 2021. After screening of the 366 papers initially identified, 58 articles were included. CONCLUSIONS: A paucity of observational studies in nursing homes suggests a high prevalence of vitamin D deficiency ranging from 8% [25(OH)D <25 nmol/L], up to 94% [25(OH)D <50 nmol/L] in some cohorts where supplement use was low. Reported factors associated with deficiency and suboptimal vitamin D status include lack of sunlight exposure, poor dietary intake of vitamin D, limited vitamin D food fortification, frailty, poor renal function, and low use of vitamin D supplements. Residents who are severely deficient, deficient, or insufficient in vitamin D require remedial vitamin D supplementation prior to maintenance supplementation at doses >800 IU/day. High-dose vitamin D supplementation may reduce respiratory illness; however, supportive data are limited. Oral nutritional supplements, in combination with exercise, may benefit physical function and performance, whereas supplementation with vitamin D- and calcium-fortified foods has been associated with improved quality of life and reduced bone resorption. Globally, vitamin D deficiency is highly prevalent in nursing home residents. There is an urgent need for standardized dietary and supplementation guidelines to prevent deficiency in this vulnerable group.

Vitamin D and Bone Health of Older Adults within Care Homes: An Observational Study.

Limited studies have reported vitamin D status and health outcomes in care home residents, a group at risk of vitamin D deficiency. This study investigated serum 25-hydroxyvitamin D (25-OHD) concentrations in older adults within care homes in Northern Ireland (NI) and its association with musculoskeletal health (ultrasound T-score, muscle strength, Timed Up & Go test (TUG)), bone turnover markers (BTMs), and immune function markers. A total of 87 participants were recruited with mean ± SD age 83.2 ± 7.9 years. Mean ± SD serum 25-OHD concentration (n 69) was 49.52 ± 35.58 nmol/L. Vitamin D deficiency (25-OHD <25 nmol/L) was observed in 34.8% (n 24) of participants with 17.4% (n 12) classified as insufficient (25-OHD 25−50 nmol/L) and 47.8% (n 33) as sufficient (25-OHD >50 nmol/L). 25-OHD concentration was not an independent predictor of T-score, muscle strength, TUG, or inflammatory cytokines. After adjusting for covariates, a significant negative association was observed between 25-OHD concentration and the BTMs; osteocalcin (ß = −0.395; p = 0.001), procollagen type 1 N propeptide (P1NP) (ß = −0.320; p = 0.012), and C-terminal telopeptide of type 1 collagen (CTX) (ß = −0.377; p = 0.003). Higher 25-OHD concentration was positively associated with use of vitamin D ± calcium supplementation (ß = 0.610; p < 0.001). Vitamin D deficiency and insufficiency were highly prevalent in this sample of care home residents in NI. Higher 25-OHD concentration was associated with greater supplement use and with reduced bone turnover, which in this population is linked with reduced bone loss. These findings emphasize the need for a mandatory vitamin D ± calcium supplementation policy specific for care home residents.

Vitamin D Status and Health Outcomes in School Children in Northern Ireland: Year One Results from the D-VinCHI Study.

(1) Background: Vitamin D status has never been investigated in children in Northern Ireland (UK). (2) Methods: Children (4-11 years) (n = 47) were recruited from November 2019 to March 2020 onto the cross-sectional study. Anthropometry was assessed. Plasma 25-hydroxyvitamin D (25(OH)D) was analysed. Vitamin D intake, parental knowledge and perceptions, participant habits, physical activity and sedentary behaviour were established via questionnaire. Muscle strength was assessed via isometric grip strength dynamometry and balance via dominant single-leg and tandem stance. Parathyroid hormone, bone turnover markers (OC, CTX and P1NP), glycated haemoglobin and inflammatory markers (CRP, IFN-γ, IL-10, IL-12p70, IL-13, IL-1ß, IL-2, IL-4, IL-6, IL-8 and TNF-α) were analysed. (3) Results: Mean (SD) 25(OH)D was 49.17 (17.04) nmol/L (n = 47); 44.7% of the children were vitamin D sufficient (25(OH)D >50 nmol/L), 48.9% were insufficient (25-50 nmol/L) and 6.4% were deficient (<25 nmol/L). 25(OH)D was positively correlated with vitamin D intake (µg/day) (p = 0.012, r = 0.374), spring/summer outdoor hours (p = 0.006, r = 0.402) and dominant grip strength (kg) (p = 0.044, r = 0.317). Vitamin D sufficient participants had higher dietary vitamin D intake (µg/day) (p = 0.021), supplement intake (µg/day) (p = 0.028) and spring/summer outdoor hours (p = 0.015). (4) Conclusion: Over half of the children were vitamin D deficient or insufficient. Wintertime supplementation, the consumption of vitamin D rich foods and spring/summer outdoor activities should be encouraged to minimise the risk of vitamin D inadequacy.

Micronutrient deficiencies: current issues.

Micronutrient deficiencies are of growing public health concern. An understanding of how micronutrient deficiencies affect health and measures that can be taken to improve micronutrient status are essential to improve population health. The main purpose of the 2018 Irish Section Meeting 'Targeted approaches to tackling current nutritional issues' was to provide an overview of current issues in relation to micronutrient status at various stages of the lifecycle. Novel biomarkers of nutrient status, global strategies to improve micronutrient status and implications for policy were also considered. The papers presented demonstrated recent advancements in this field and highlighted areas that warrant priority at the public health level, on both a national and global scale. Novel methods and biomarkers are being developed that will enhance the assessment of micronutrient status in specific population groups. It is evident that mild-to-moderate deficiency, or low status (in the absence of deficiency), of some micronutrients have important ramifications for public health that should be considered alongside the implications of severe deficiency. It is imperative that policy makers, public health workers and scientists work together to ensure that sustainable programmes are implemented to address micronutrient deficiencies at the population level.

Risks and benefits of consuming edible seaweeds.

Recent interest in seaweeds as a source of macronutrients, micronutrients, and bioactive components has highlighted prospective applications within the functional food and nutraceutical industries, with impetus toward the alleviation of risk factors associated with noncommunicable diseases such as obesity, type 2 diabetes, and cardiovascular disease. This narrative review summarizes the nutritional composition of edible seaweeds; evaluates the evidence regarding the health benefits of whole seaweeds, extracted bioactive components, and seaweed-based food products in humans; and assesses the potential adverse effects of edible seaweeds, including those related to ingestion of excess iodine and arsenic. If the potential functional food and nutraceutical applications of seaweeds are to be realized, more evidence from human intervention studies is needed to evaluate the nutritional benefits of seaweeds and the efficacy of their purported bioactive components. Mechanistic evidence, in particular, is imperative to substantiate health claims.

Vitamin D3 supplementation using an oral spray solution resolves deficiency but has no effect on VO2 max in Gaelic footballers: results from a randomised, double-blind, placebo-controlled trial.

PURPOSE: Vitamin D inadequacy is a global health concern in athletes as well as the general population. Whilst the role of vitamin D in skeletal health is well defined, there remains uncertainty over whether vitamin D supplementation has an added benefit beyond bone health. METHODS: This randomised placebo-controlled trial in healthy male and female Gaelic footballers (n = 42) investigated the effect of vitamin D3 supplementation [3000 IU (75 µg) daily for 12 weeks, via an oral spray solution] on VO2 max which was the primary outcome measure. Secondary outcomes included skeletal muscle and lung function. RESULTS: Supplementation significantly increased total 25-hydroxyvitamin D concentrations compared to the placebo group (mean ± SD change from baseline, 36.31 ± 32.34 vs. 6.11 ± 23.93 nmol/L, respectively; P = 0.006). At baseline, 50 and 22 % of footballers presented with vitamin D insufficiency (31-49 nmol/L) and deficiency (<30 nmol/L), respectively. Total 25-hydroxyvitamin D concentration did not significantly correlate with any measure of physical performance. Analysis of covariance (ANCOVA) models demonstrated that vitamin D supplementation over 12 weeks had no significant effect on VO2 max (P = 0.375), vertical jump height (P = 0.797), left and right handgrip strength (P = 0.146 and P = 0.266, respectively), forced vital capacity (P = 0.573) or forced expiratory volume at 1 s (P = 0.665), after adjusting for confounders. The high prevalence of vitamin D inadequacy observed in this cohort of collegiate Gaelic footballers supports the need for vitamin D supplementation during wintertime to avoid being at risk of poor bone health. CONCLUSIONS: Twelve-week daily supplementation with 3000 IU (75 µg) vitamin D3 successfully resolved deficiency but did not have any significant effect on VO2 max, skeletal muscle or lung function.

Vitamin D3 supplementation in healthy adults: a comparison between capsule and oral spray solution as a method of delivery in a wintertime, randomised, open-label, cross-over study.

Vitamin D is typically supplied in capsule form, both in trials and in clinical practice. However, little is known regarding the efficacy of vitamin D administered via oral sprays - a method that primarily bypasses the gastrointestinal absorption route. This study aimed to compare the efficacy of vitamin D3 liquid capsules and oral spray solution in increasing wintertime total 25-hydroxyvitamin D (25(OH)D) concentrations. In this randomised, open-label, cross-over trial, healthy adults (n 22) received 3000 IU (75 µg) vitamin D3 daily for 4 weeks in either capsule or oral spray form. Following a 10-week washout phase, participants received the opposite treatment for a final 4 weeks. Anthropometrics and fasted blood samples were obtained before and after supplementation, with samples analysed for total 25(OH)D, creatinine, intact parathyroid hormone and adjusted Ca concentrations. At baseline, vitamin D sufficiency (total 25(OH)D>50 nmol/l), insufficiency (31-49 nmol/l) and clinical deficiency (<30 nmol/l) were evident in 59, 23 and 18 % of the participants, respectively. Overall, baseline total mean 25(OH)D concentration averaged 59·76 (sd 29·88) nmol/l, representing clinical sufficiency. ANCOVA revealed no significant difference in the mean and standard deviation change from baseline in total 25(OH)D concentrations between oral spray and capsule supplementation methods (26·15 (sd 17·85) v. 30·38 (sd 17·91) nmol/l, respectively; F=1·044, adjusted r 2 0·493, P=0·313). Oral spray vitamin D3 is an equally effective alternative to capsule supplementation in healthy adults.

The effect of consuming Palmaria palmata-enriched bread on inflammatory markers, antioxidant status, lipid profile and thyroid function in a randomised placebo-controlled intervention trial in healthy adults.

PURPOSE: Palmaria palmata (P. Palmata) is reported to contain anti-inflammatory and antioxidant compounds albeit no study has investigated these effects in humans. METHODS: A randomised parallel placebo-controlled human intervention study was carried out to investigate the effect of consuming P. Palmata (5 g/day) incorporated into a bread on serum markers of inflammation [C-reactive protein (CRP); cytokine analysis] with secondary analysis investigating changes in lipids (cholesterol, triglycerides), thyroid function [thyroid-stimulating hormone (TSH)] and antioxidant status ferric reducing antioxidant power. ANCOVA with baseline values as covariates, controlling for age, BMI, sex and smoking status, was used to compare differences between treatment groups over time . In vitro studies investigated the inflammatory activity of P. Palmata extracts (hot water, cold water and ethanol extract), protein extracts and associated protein hydrolysates using a Caco-2 inflammation cell model. RESULTS: Consumption of P. Palmata-enriched bread significantly increased serum CRP (+16.1 %, P = 0.011), triglycerides (+31.9 %, P = 0.001) and TSH (+17.2 %, P = 0.017) when compared to the control group. In vitro evaluation of P. palmata extracts and protein hydrolysates identified a significant induction of IL-8 secretion by Caco-2 cells, and the hot water P. palmata extract was shown to increase adipocyte glycerol release (P < 0.05). CONCLUSION: Evidence from this human study suggests that P. palmata stimulates inflammation, increases serum triglycerides and alters thyroid function; however, these changes are not likely to impact health as changes remained within the normal clinical range. The data from the in vitro study provided indications that IL-8 may contribute to the apparent immunostimulation noted in the human study.

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.

Vitamin D: recent advances and implications for athletes.

Athletes may be predisposed to low vitamin D concentrations, with studies reporting a high prevalence of athletes with a vitamin D concentration below 50 nmol/L across a range of sports and geographical locations, particularly over the winter months. It is well documented that vitamin D is important for osseous health by enhancing calcium absorption at the small intestine; however, emerging research suggests that vitamin D may also benefit a plethora of extra-skeletal target tissues and systems. There is strong evidence that vitamin D is capable of regulating both innate and adaptive immune processes via binding of active vitamin D to its complementary receptor. Supplementation with vitamin D may also enhance skeletal muscle function through morphological adaptations and enhanced calcium availability during cross-bridge cycling; however, an exact mechanism of action is yet to be elucidated. Such findings have prompted research into the importance of maintaining vitamin D concentrations over wintertime and the possible physiological and immunological benefits of vitamin D supplementation in athletes. The following review critically evaluates existing literature and presents novel perspectives on how vitamin D may enhance athletic performance.

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.

Vitamin D status and supplementation in elite Irish athletes.

BACKGROUND: A high prevalence of vitamin D insufficiency/deficiency, which may impact on health and training ability, is evident among athletes worldwide. This observational study investigated the vitamin D status of elite Irish athletes and determined the effect of wintertime supplementation on status. METHODS: Serum 25-hydroxyvitamin D [25(OH)D], calcium, and plasma parathyroid hormone were analyzed in elite athletes in November 2010 (17 boxers, 33 paralympians) or March 2011 (34 Gaelic Athletic Association [GAA] players). A subset of boxers and paralympians (n = 27) were supplemented during the winter months with either 5,000 IU vitamin D3/d for 10-12 weeks or 50,000 IU on one or two occasions. Biochemical analysis was repeated following supplementation. RESULTS: Median 25(OH)D of all athletes at baseline was 48.4 nmol/L. Vitamin D insufficiency/deficiency (serum 25(OH)D <50 nmol/L) was particularly evident among GAA players (94%) due to month of sampling. Wintertime supplementation (all doses) significantly increased 25(OH)D (median 62.8 nmol/L at baseline vs. 71.1 nmol/L in April or May; p = .001) and corrected any insufficiencies/deficiencies in this subset of athletes. In contrast, 25(OH)D significantly decreased in those that did not receive a vitamin D supplement, with 74% of athletes classed as vitamin D insufficient/deficient after winter, compared with only 35% at baseline. CONCLUSIONS: This study has highlighted a high prevalence of vitamin D insufficiency/ deficiency among elite Irish athletes and demonstrated that wintertime vitamin D3 supplementation is an appropriate regimen to ensure vitamin D sufficiency in athletes during winter and early spring.

Chickpea (Cicer arietinum) and other plant-derived protease inhibitor concentrates inhibit breast and prostate cancer cell proliferation in vitro.

The soybean-derived protease inhibitor, Bowman-Birk inhibitor (BBI), is currently showing great promise as a novel cancer chemopreventive agent. In contrast to the wealth of research conducted on this compound, the anticancer effects of protease inhibitors isolated from other leguminous sources have received limited attention. In the current study, 7 protease inhibitor concentrates (PICs) were isolated from various leguminous sources (including soybean) and characterized. The effects of PICs on the proliferation of breast and prostate cancer cells were investigated in vitro. Chickpea PIC significantly inhibited the viability of MDA-MB-231 breast cancer and PC-3 and LNCaP prostate cancer cells at all concentrations tested (25-400 µg/ml). In addition, kidney bean (200, 400 µg/ml), soybean (50, 100 µg/ml), and mungbean (100, 200 µg/ml) PICs inhibited LNCaP cell viability. These findings suggest that leguminous PICs may possess similar anticancer properties to that of soybean BBI and deserve further study as possible chemopreventive agents.

Effect of adiposity on vitamin D status and the 25-hydroxycholecalciferol response to supplementation in healthy young and older Irish adults.

There is increasing epidemiological evidence linking sub-optimal vitamin D status with overweight and obesity. Although increasing BMI and adiposity have also been negatively associated with the change in vitamin D status following supplementation, results have been equivocal. The aim of this randomised, placebo-controlled study was to investigate the associations between anthropometric measures of adiposity and the wintertime serum 25-hydroxycholecalciferol (25(OH)D) response to 15 µg cholecalciferol per d in healthy young and older Irish adults. A total of 110 young adults (20-40 years) and 102 older adults ( ≥ 64 years) completed the 22-week intervention with >85 % compliance. The change in 25(OH)D from baseline was calculated. Anthropometric measures of adiposity taken at baseline included height, weight and waist circumference (WC), along with skinfold thickness measurements to estimate fat mass (FM). FM was subsequently expressed as FM (kg), FM (%), FM index (FMI (FM kg/height m2)) and as a percentage ratio to fat-free mass (FFM). In older adults, vitamin D status was inversely associated with BMI (kg/m2), WC (cm), FM (kg and %), FMI (kg/m2) and FM:FFM (%) at baseline (r - 0·33, - 0·36, - 0·33, - 0·30, - 0·33 and - 0·27, respectively, all P values < 0·01). BMI in older adults was also negatively associated with the change in 25(OH)D following supplementation (ß - 1·27, CI - 2·37, - 0·16, P = 0·026); however, no such associations were apparent in younger adults. Results suggest that adiposity may need to be taken into account when determining an adequate wintertime dietary vitamin D intake for healthy older adults residing at higher latitudes.

An evaluation of vitamin D status in individuals with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a multi-system inflammatory disease where genetic susceptibility coupled with largely undefined environmental factors is reported to underlie the aetiology of the disease. One such factor is low vitamin D status. The primary source of vitamin D is endogenous synthesis following exposure of the skin to UVB light. Photosensitivity, sunlight avoidance and the use of sun protection factor in combination with medications prescribed to treat the symptoms of the disease, puts SLE patients at increased risk of vitamin D deficiency. Decreased conversion of 25-hydroxyvitamin D to the metabolically active form, 1,25-dihydroxyvitamin D3, is possible, due to renal impairment common in SLE putting additional stress on vitamin D metabolism. The majority of studies have identified low 25-hydroxyvitamin D in SLE patients, albeit using varying cut-offs (<25 to <80 nmol/l). Of these studies, fifteen have investigated a link between status and disease activity with conflicting results. Variation with disease activity index measures used alongside methodological limitations within the study design may partially explain these findings. This review discusses the importance of optimal vitamin D status in SLE, critically evaluates research carried out to date that has investigated vitamin D in SLE, and highlights the need for a well-designed observational study that controls for diet, medication use, dietary supplements, UV exposure and seasonality, that uses sensitive methods for measuring vitamin D status and disease activity in SLE to conclusively establish the role of vitamin D in SLE.

Maintenance of wintertime vitamin D status with cholecalciferol supplementation is not associated with alterations in serum cytokine concentrations among apparently healthy younger or older adults.

Epidemiological studies have shown that low vitamin D status results in impaired immune function and is associated with the prevalence of autoimmune and inflammatory conditions. Vitamin D supplementation has been shown to reduce circulating concentrations of inflammatory markers in such conditions. However, the possible beneficial effect of vitamin D supplementation in the general population, particularly for those individuals living at high latitudes where hypovitaminosis D is common during wintertime, remains unclear. The aim of this study was to assess the effect of vitamin D supplementation using doses of 5, 10, and 15 µg/d cholecalciferol (D3) compared with placebo on cytokine concentrations throughout winter in apparently healthy younger (aged 20-40 y) and older (aged ≥64 y) adults. A total of 211 younger and 202 older adults completed the 22-wk intervention (from October to March) with >85% compliance. Serum concentrations of 25-hydroxycholecalciferol [25(OH)D3], high sensitivity C-reactive protein, IL-6, IL-10, soluble CD40 ligand, TGFß, TNFα, and fibrinogen were measured using ELISA. 25(OH)D3 concentrations significantly decreased in the placebo and 5 and 10/d µg D3 groups in the younger cohort and in the placebo group in the older cohort. Whereas 15 µg/d D3 supplementation maintained 25(OH)D3 concentrations in the younger cohort (baseline, 75.9 nmol/L; postintervention, 69.0 nmol/L) and significantly increased concentrations in the older cohort (baseline, 55.1 nmol/L; postintervention, 73.9 nmol/L), it had no significant effect on cytokine concentrations (ANCOVA, P > 0.05). The long-term effects of low vitamin D status remain to be elucidated and optimization of vitamin D status in otherwise healthy individuals may potentially have lasting beneficial effects on the immune system.

Is equol production beneficial to health?

The health benefits associated with soya food consumption have been widely studied, with soya isoflavones and soya protein implicated in the protection of CVD, osteoporosis and cancers such as those of the breast and prostate. Equol (7-hydroxy-3-(4'-hydroxyphenyl)-chroman), a metabolite of the soya isoflavone daidzein, is produced via the formation of the intermediate dihydrodaidzein, by human intestinal bacteria, with only approximately 30-40% of the adult population having the ability to perform this transformation following a soya challenge. Inter-individual variation in conversion of daidzein to equol has been attributed, in part, to differences in the diet and in gut microflora composition, although the specific bacteria responsible for the colonic biotransformation of daidzein to equol are yet to be identified. Equol is a unique compound in that it can exert oestrogenic effects, but is also a potent antagonist of dihydrotestosterone in vivo. Furthermore, in vitro studies suggest that equol is more biologically active than its parent compound, daidzein, with a higher affinity for the oestrogen receptor and a more potent antioxidant activity. Although some observational and intervention studies suggest that the ability to produce equol is associated with reduced risk of breast and prostate cancer, CVD, improved bone health and reduced incidence of hot flushes, others have reported null or adverse effects. Studies to date have been limited and well-designed studies that are sufficiently powered to investigate the relationship between equol production and disease risk are warranted before the clinical relevance of the equol phenotype can be fully elucidated.

Equol: a comparison of the effects of the racemic compound with that of the purified S-enantiomer on the growth, invasion, and DNA integrity of breast and prostate cells in vitro.

It has been postulated that the R- and S-equol enantiomers have different biological properties given their different binding affinities for the estrogen receptor. S-(-)equol is produced via the bacterial conversion of the soy isoflavone daidzein in the gut. We have compared the biological effects of purified S-equol to that of racemic (R and S) equol on breast and prostate cancer cells of varying receptor status in vitro. Both racemic and S-equol inhibited the growth of the breast cancer cell line MDA-MB-231 (> or = 10 microM) and the prostate cancer cell lines LNCaP (> or = 5 microM) and LAPC-4 (> or = 2.5 microM). The compounds also showed equipotent effects in inhibiting the invasion of MDA-MB-231 and PC-3 cancer cells through matrigel. S-equol (1, 10, 30 microM) was unable to prevent DNA damage in MCF-7 or MCF-10A breast cells following exposure to 2-hydroxy-4-nonenal, menadione, or benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide. In contrast, racemic equol (10, 30 microM) prevented DNA damage in MCF-10A cells following exposure to 2-hydroxy-4-nonenal or menadione. These findings suggest that racemic equol has strong antigenotoxic activity in contrast to the purified S-equol enantiomer implicating the R-, rather than the S-enantiomer as being responsible for the antioxidant effects of equol, a finding that may have implications for the in vivo chemoprotective properties of equol.

Phyto-oestrogens, their mechanism of action: current evidence for a role in breast and prostate cancer.

The incidence of hormone-dependent cancers, such as those of the breast and prostate, is much lower in Eastern countries such as China and Japan in comparison with the Western world. Diet is believed to have a major effect on disease risk and one group of compounds, the phyto-oestrogens, which are consumed in large amounts in Asian populations, have been implicated in cancer protection. This view follows the finding that plasma and urinary levels of phyto-oestrogens are much higher in areas where cancer incidence is low in comparison with areas of high cancer incidence. The phyto-oestrogens are comprised of two main groups; the isoflavones and lignans. Of the isoflavones, genistein and daidzein have been the most widely studied. These compounds have been shown to possess anticancer properties; however their precise mechanism of action remains to be elucidated. In comparison, few studies have investigated the effects of lignans in breast and prostate cancer. In vitro studies have shown that genistein exerts biphasic effects on cancer cell growth, stimulating growth at low concentrations (<10 microm) and inhibiting growth at high concentrations (>10 microm), which suggests that low phyto-oestrogen levels may stimulate cancer growth in vivo. Plasma phyto-oestrogen concentrations of >10 microm cannot be achieved by dietary intake and therefore the timing of exposure to phyto-oestrogens may be of the utmost importance in determining their chemopreventive effects. The present paper reviews the effects of phyto-oestrogens on breast and prostate cancer in vivo and in vitro and discusses possible mechanisms of action via which these compounds may exert their effects.