The Relationship between Mental and Physical Minor Health Complaints and the Intake of Dietary Nutrients.

Presenteeism is a problem that needs to be solved urgently, both for individual workers and for society overall. In this report, we propose the concept of MHC, which refers to mild mental and physical complaints subjectively perceived by individuals that are not caused by illness. We also planned to examine what kind of physical and mental disorder MHC is and whether food is effective as a method of self-care for MHC. First, we conducted "the comprehensive survey to establish an integrated database of food, gut microbiome, and health information" (the "Sukoyaka Health Survey") and obtained data on psychosomatic disorders and intakes of dietary nutrients. As a result, through factor analysis and item response theory analysis, we found the following specific examples of MHC: lack of vigor, irritability, fatigue, and somatic complaints. In addition, analysis of the relationship between these four MHC levels and the intake dietary nutrients indicated that they are closely related and that MHC levels can be improved by consuming sufficient amounts of multiple nutrients.

Safety assessment of herbal supplement components targeting hepatotoxicity and CYP3A4 induction in cell-based assay using HepG2 cells.

Herbal supplements can cause hepatotoxicity and drug interactions via hepatic cytochrome P-450 (CYP) in some cases. However, there is no simple and stable cell-based assay to conduct a screening for hepatotoxicity and CYP induction. In the present study, we selected 14 components of the herbal supplement based on our previous reports and investigated the safety of the herbal supplement components focusing on toxicity and CYP3A4 induction in a cell-based assay using HepG2. The toxicity of the components was examined by lactate dehydrogenase (LDH) and cell proliferation assays. Then, the CYP3A4 induction of the components were examined by a reporter assay using reporter vectors of CYP3A4. The vector includes the CYP3A4 proximal promoter (CYP3A4PP) and the xenobiotic-responsive enhancer module (XREM) regions. Luteolin (LU) significantly increased LDH activity and decreased cell proliferation activity that suggests LU may cause toxicity in HepG2 cells. Quercetin (QU) increased the transcriptional activity of CYP3A4 (1.5-fold of control) in the reporter assay. However, the induction of QU was slightly in comparison to the validation of the transcriptional activity of CYP3A4 treated with CYP3A4 inducers. The CYP3A4 induction of QU may not involve CYP3A4PP but involves the XREM response. Throughout our results, the method in the present study may be useful for a safety assessment of herbal supplements, primarily focusing on hepatotoxicity and CYP3A4 induction. PRACTICAL APPLICATION: Even though there are problems with herbal supplements, studies related to toxicity are not actively carried out. The present methods may apply to the safety assessment for herbal supplements and be useful for the prevention and verification of health hazards caused by herbal supplements (the summary is shown in Figure S2).

The Prevalence of Dietary Supplements That Claim Estrogen-like Effects in Japanese Women.

Recently, adverse events, such as irregular vaginal bleeding and menstrual disorders, associated with the use of dietary supplements containing Pueraria mirifica, have been reported in Japan. P. mirifica contains phytoestrogens, such as deoxymiroestrol and miroestrol. Therefore, we investigated the use of supplements that claim to have estrogen-like effects (i.e., estrogen-like supplements) in Japanese women aged from 15 to 69 years old in an online survey. The prevalence of estrogen-like supplement use was 5%, accounting for approximately 15% of the sample, including ex-users. The majority of the users were in their 40s and 50s, mainly using these supplements for the treatment of menopausal symptoms. In contrast, the younger generation mainly used them for beauty purposes, such as weight loss, mastogenic effects, and skin care. Many of them visited a clinic or took medicines for menstrual-related troubles. In all age groups, soybeans/isoflavones were the most commonly used, followed by equol and placenta. Participants in their teens and 20s also used P. mirifica. Among them, 16.2% had experienced adverse events, including irregular vaginal bleeding, breast swelling and pain, and heavy menstruation. In conclusion, estrogen-like supplement use is associated with adverse events; thus, it is necessary to pay attention to the use of these supplement. Furthermore, because the purpose of use differs depending on generation, caution according to each generation is necessary.

Identification of Factors Necessary for Enabling Technology-Based Dietary Record Surveys: A Qualitative Focus Group Interview with Japanese Dietitians.

Weighed food records together with an in-person interview approach constitute the most basic methods used to estimate energy and nutrient intakes in dietary surveys. In the background of the coronavirus disease-2019 pandemic, the need for non-face-to-face dietary surveys using information and communication technology (ICT) is increasing. We aimed to evaluate ICT-based dietary record surveys and identify factors that may enable this survey method to become more widely used in the future. We conducted a non-face-to-face survey of dietary records of 44 Japanese individuals, maintained by dietitians using dietary photography and video conferencing services. We conducted a focus group interview with the six dietitians who conducted that survey. Their opinions on the factors necessary to popularize ICT-based dietary survey method were analyzed. In the focus group interview, dietitians highlighted fewer restrictions on time and place as positive aspects. Negative aspects included insufficient skills to operate computers, difficulty in hearing, and understanding facial expressions using ICT. We identified three main factors for enabling widespread use of ICT-based dietary record survey: individual skill, device and technology, and social environmental factors. This suggests that a comprehensive approach is necessary for popularizing the use of ICT in dietary surveys.

Short-chain fatty acids, acetate and propionate, directly upregulate osteoblastic differentiation.

Short-chain fatty acids, including acetate, propionate, and butyrate are metabolites of dietary fibre produced by microbiota in the large intestine, have been proposed to contribute to effects on bone homeostasis. However, it is unclear whether they are used in osteoblasts and directly affect bone formation. We investigated whether short-chain fatty acids are absorbed in osteoblast cells and influence early osteoblastic differentiation using MC3T3-E1 cells. Acetate and propionate upregulated alkaline phosphatase activity, which is an osteoblast differentiation marker, and acetate upregulated alkaline phosphatase mRNA expression after treatment for 9 days, whereas butyrate did not in MC3T3-E1 cells. Butyrate was absorbed more rapidly and to a greater extent than acetate and propionate. These results indicate that short-chain fatty acids were used in osteoblastic cells, and particularly acetate and propionate directly upregulated differentiation in primary osteoblasts. Therefore, acetate and propionate might be useful for maintaining a positive balance of bone turnover.

Reliability in viscosity measurement of thickening agents for dysphagia management: Are results obtained by cone-and-plate rheometers reproducible between laboratories?

Viscosity measurement using a cone-and-plate rheometer is considered to provide an objective and reliable evaluation of thickening agents for dysphagia management. Here, we showed its measurement uncertainty in the context of an inter-laboratory study. Eight test samples (i.e., four viscosity standard liquids, one xanthan gum reagent powder, and three commercial thickening agent powders) were distributed to 10 laboratories in a blinded manner. According to the same standard operating procedure, each laboratory dissolved the xanthan gum or thickening agents at four concentrations (0.5-4.0 g/100 g) and then measured their viscosity (35-803 mPa∙s). As for the viscosity of the standard liquids, the grand means were 98-100% of the certified values, and the relative standard deviations for repeatability (RSDr ) and reproducibility (RSDR ) were ca. 1% and ca. 5%, respectively, suggesting good accuracy in the measurement process. On the other hand, as for the viscosity of the thickening agents, RSDr and RSDR were ca. 2-6% and ca. 5-8%, respectively; however, heterogeneity in the preparation process comprising a manual dissolving step may increase these to near 60%. Furthermore, RSDr and RSDR of estimated additive concentrations to achieve targeted viscosities (50-500 mPa∙s) based on concentration-viscosity curves were ca. 1-3% and ca. 3-5%, respectively, with a few exceptions. These findings suggest that a strictly standardized procedure provides reliable data on the viscosity measurements for thickening agents.

[A literature review on the relationship between questionnaires for assessing minor health complaints and health status indices among Japanese people].

Objectives　Minor health complaints related to stress, mental health, sleep, and fatigue are closely associated with each other, and their deterioration may cause lifestyle diseases. The health status of people can be predicted through a questionnaire by exploring the relationship between their state of minor health complaints and objective health status indices. Therefore, we conducted a systematic review of the relationship between a questionnaire on the state of minor health complaints and health status indices among Japanese people who have a high level of stress, which they experience on a daily basis, using epidemiological literature. Additionally, we considered items for the questionnaire which were necessary for an index development.Methods　The PubMed database was searched for papers on "autonomic nervous system," "sleep disorders," "mental health and stress," and "fatigue," using keywords mentioned in previous studies on minor health complaints.　The extracted research papers were screened according to the following inclusion criteria: 1) the participants were healthy Japanese people; 2) descriptions included characteristics of the target population; 3) use of analytic epidemiological study design, intervention studies, and systematic reviews; 4) minor health complaints assessed by a questionnaire; 5) evaluation of the relationship between the questionnaires for minor health complaints and the health index; and 6) written in Japanese or English. Based on this, ten papers were adopted.Results　Of the 10 papers collected, one was a cohort study, three were case-control studies, and six were cross-sectional studies. The participants in five of them were working adults. Reports on three out of six questionnaires on stress, four out of seven on sleep, and all two on comprehensive health status showed significant associations between minor health complaints assessed by the questionnaires and the index for health status. The increase in responses about work-related stress from the questionnaire was associated with an increase in the "risk of developing depression" [odds ratio 2.96 (confidence interval: 1.04-8.42)]. Poor sleep quality was associated with an increase in "changes in autonomic index," "number of comorbidities and the rate of depression," and the "risk of work-related injuries." Moreover, the health score was associated with the "autonomic nervous system index".Conclusion　These results suggest that a questionnaire evaluating minor health complaints should include questions about "stress," "sleep quality," and "comprehensive health status." Since studies that appropriately adopted for risk of bias were limited, it is necessary to further examine these relationships by applying prospective studies such as cohort studies and intervention studies.

The Combination of Soy Isoflavones and Resveratrol Preserve Bone Mineral Density in Hindlimb-Unloaded Mice.

It is well known that physical inactivity during space flight or prolonged bed rest causes rapid bone loss. Soy isoflavones (ISOs) and resveratrol (RES) have been reported to be useful to maintain a positive balance for bone turnover. Therefore, we examined the combined effects of ISO and RES on bone loss that was induced by hindlimb-unloading in mice. Female eight-week-old ddY mice were divided into the following six groups (n = 6-8 each): normally housed mice, loading mice, hindlimb-unloading (UL) mice fed a control diet, UL mice fed a 0.16% ISO conjugates, UL mice fed a 0.15% RES diet, and UL mice fed a 0.16% ISO and 0.15% RES diet. After three weeks, femoral bone mineral density was markedly decreased in unloading mice. The combination of ISO and RES prevented bone loss and especially maintained the trabecular bone mineral density more effectively compared with cortical bones. ISO and/or RES inhibited the increase in the RANKL/OPG expression ratio in bone marrow cells in UL mice. These results suggest that the combination of ISO and RES had a preventive effect against bone loss induced by hindlimb-unloading in mice. These osteoprotective effects of ISO and RES may result from the inhibition of bone resorption.

Assessment of safety and efficacy of pine bark extract in normal and ovariectomized mice.

We evaluated the influence of pine bark extract (PBE) on organs, the cytochrome-P450 (CYP) activities in liver and estrogenic effects in normal and ovariectomized (OVX) female mice. The PBE did not affect organ weights and liver-function indexes (activities of alkaline phosphatase, aspartate amino transferase, and alanine amino transferase) at doses; 0.04%, 0.4%, and 2.0% PBE in the diet, in normal and OVX female mice. In the OVX mice, CYP1A1 activity was significantly higher in the 0.4% and 2.0% PBE groups than in the OVX control group, and in the 0.4% and 2.0% PBE groups were significantly higher than in the 0.04% PBE group. CYP1A2 and 3A4 activities were significantly higher in the 2.0% PBE group than in all other groups. The PBE did not affect uterine weight and femoral bone mineral density at all PBE doses. These results showed that the dose of PBE at the recommended human intake, had no toxic and estrogenic effects in normal female and OVX mice, however, it may need attention to use the excess intake of PBE with some drugs in postmenopausal women.

Safety and Efficacy Assessment of Isoflavones from Pueraria (Kudzu) Flower Extract in Ovariectomised Mice: A Comparison with Soy Isoflavones.

Numerous Foods with Function Claims that contain the extract of Pueraria flower (kudzu) isoflavones (PFI) are available in the Japanese market. These are labelled with function claims of reducing visceral fat. However, these foods have not undergone proper safety assessment such as the evaluation of their oestrogenic activity and effects on drug-metabolising enzymes (cytochrome P-450: CYP) in the liver. This study evaluated the estrogenic effect and the hepatic CYP activity and mRNA expression in normal female mice as a safety assessment of PFI (Experiment 1). In addition, the bone mineral density and visceral fat weight in ovariectomised mice (OVX) compared to soy isoflavones (SI) was evaluated to assess the efficacy of PFI (Experiment 2). OVX control fed a control diet, OVX fed a PFI diet (the recommended human intake of PFI), OVX fed a PFI20 diet (20- times the recommended PFI), OVX fed an SI diet (the recommended human intake of SI), and OVX fed an SI20 diet (20 -times the recommended intake of SI) for 28 days in Experiment 2. Body, liver, and visceral fat weights were not affected by the PFI, PFI20, SI, or SI20 diets. The hepatic CYP1A and CYP3A activities were elevated by the SI20 treatment. Ovariectomy-induced bone loss was inhibited by the SI20 treatment, but not by the PFI20 treatment. These results suggest that (1) PFI intake in human doses had no oestrogenic properties and did not affect CYP activity in the liver; (2) there was no evidence that PFI affects the amount of visceral fat in OVX mice.

Resistant Starch Attenuates Bone Loss in Ovariectomised Mice by Regulating the Intestinal Microbiota and Bone-Marrow Inflammation.

The intestinal microbiota may regulate bone metabolism by reducing levels of pro-inflammatory cytokines, and T cells in bone tissues of oestrogen-deficient mice have been reported. Resistant starch (RS) is a type of dietary fibre and results in changes in the composition of the gut microbiota. We evaluated the effects of RS supplemented in diets on intestinal microbial composition, bone mineral density, and inflammatory-gene expression in the colon and bone marrow of ovariectomised (OVX) mice. OVX mice were divided randomly into three groups: OVX control, OVX fed a 20% high amylose corn starch (HAS) diet, and OVX fed a 20% acid-hydrolysed HAS (AH-HAS) diet. HAS and AH-HAS diets contained 6.8% and 12% of RS, respectively. After 6 weeks, treatment with HAS or AH-HAS increased the abundance of Bifidobacterium spp. in faeces. The AH-HAS diet tended to upregulate mRNA expression of interleukin (IL)-10 in the colon, and downregulate expression of receptor activator of nuclear factor kappa-B ligand and IL-7 receptor genes in the bone marrow of OVX mice. AH-HAS treatment attenuated ovariectomy-induced bone loss. These findings suggest that AH-HAS might change the microbiota and immune status of the bone marrow, resulting in attenuated bone resorption in OVX mice.

ß-Carotene prevents bone loss in hind limb unloading mice.

ß-Carotene has been reported to be useful to maintain a positive balance of bone turnover. However, the effects of ß-carotene on bone loss remain to be elucidated in mice with hind limb unloading. Therefore, we investigated whether ß-carotene prevented bone loss induced by skeletal hind limb unloading in mice. Female 8-week-old ddY mice were divided into six groups (n = 6-8 each) and subjected to: (1) normal housing, (2) sham unloading fed a control diet, (3) hind limb unloading fed a control diet, (4) hind limb unloading fed a 0.025% ß-carotene-containing diet, (5) hind limb unloading fed a 0.05% ß-carotene-containing diet, and (6) hind limb unloading fed a 0.25% ß-carotene-containing diet. After 3 weeks, bone mineral density of the tibia was markedly reduced by unloading, which was prevented by 0.025% ß-carotene. Histological analysis revealed a hind limb unloading-induced decrease in the calcified bone of the femur, which was slightly prevented by 0.025% ß-carotene. The 0.025% ß-carotene-containing diet increased the gene expression of osteoprotegerin in the bone marrow cells in unloading mice. These results suggest that a ß-carotene-containing diet may preserve bone health in subjects with disabilities as well as in astronauts.

The effects of green kiwifruit combined with isoflavones on equol production, bone turnover and gut microflora in healthy postmenopausal women.

BACKGROUND AND OBJECTIVES: Isoflavone (daidzein and genistein) interventions in postmenopausal women have produced inconsistent skeletal benefits, partly due to population heterogeneity in daidzein metabolism to equol by enteric bacteria. This study assessed changes in microflora and bone turnover in response to isoflavone and ki-wifruit supplementation in New Zealand postmenopausal women. METHODS AND STUDY DESIGN: Healthy women 1-10 years post-menopause were randomly allocated to group A (n=16) or B (n=17) for a 16-week crossover trial. Two consecutive 6-week treatment periods had a 2-week lead-in period at intervention commencement and a 2-week washout period between treatments. Treatments prescribed either (1) daily isoflavone supplementation (50 mg/day aglycone daidzein and genistein) alone, or (2) with two green kiwifruit. At treatment baseline and end-point (four time points) the serum bone markers C Telopeptide of Type I collagen (CTx), undercarboxylated os-teocalcin (unOC), and serum and urinary daidzein and equol, were measured. Changes in gut microflora were monitored in a subgroup of the women. RESULTS: Equol producers made up 30% of this study population (equol producers n=10; non-equol producers n=23) with serum equol rising significantly in equol producers. Serum ucOC decreased by 15.5% (p<0.05) after the kiwifruit and isoflavone treatment. There were no changes in serum CTx or in the diversity of the gut microflora. CONCLUSIONS: 50 mg/day isoflavones did not reduce bone resorption but kiwifruit and isoflavone consumption decreased serum ucOC levels, possibly due to vitamin K1 and/or other bioactive components of green kiwifruit.

Effect of daidzein and equol on DNA replication in MCF-7 cells.

It has been reported that daidzein and equol stimulate DNA replication and proliferation of MCF-7 cells. However, their molecular mechanisms of action are still unclear. We examined the effects of daidzein and equol on DNA replication of MCF-7 cells, focusing on MCM2-7 proteins, which function as the replicative helicase. In the presence of either 1 µM of daidzein or equol, the number of cells in S-phase, which was determined by detecting bromodeoxyuridine incorporated into replicated DNA, almost doubled. The total amounts of MCM7 protein and chromatin-bound MCM7 protein increased in the presence of daidzein. The data suggest that phytoestrogens facilitate cell cycle progression in G1-phase by increasing the level of MCM proteins. In the presence of phytoestrogens, phosphorylation of Rb and levels of MCM2, 3 and 7 mRNA increased, suggesting that stimulation of MCM2-7 transcription is involved in the cell cycle progression. Under the same conditions, double-stranded DNA breakage in logarithmically growing MCF-7 cells, which was detected using anti-γ-H2AX antibodies, did not increase in the presence of equol.

The combined effects of soya isoflavones and resistant starch on equol production and trabecular bone loss in ovariectomised mice.

Equol is a metabolite of the soya isoflavone (ISO) daidzein that is produced by intestinal microbiota. Equol has greater oestrogenic activity compared with other ISO, and it prevents bone loss in postmenopausal women. Resistant starch (RS), which has a prebiotic activity and is a dietary fibre, was reported to promote equol production. Conversely, the intestinal microbiota is reported to directly regulate bone health by reducing inflammatory cytokine levels and T-lymphocytes in bone. The present study evaluated the combined effects of diet supplemented with ISO and RS on intestinal microbiota, equol production, bone mineral density (BMD) and inflammatory gene expression in the bone marrow of ovariectomised (OVX) mice. Female ddY strain mice, aged 8 weeks, were either sham-operated (Sham, n 7) or OVX. OVX mice were randomly divided into the following four groups (seven per group): OVX control (OVX); OVX fed 0·05 % ISO diet (OVX+ISO); OVX fed 9 % RS diet (OVX+RS); and OVX fed 0·05 % ISO- and 9 % RS diet (OVX+ISO+RS). After 6 weeks, treatment with the combination of ISO and RS increased equol production, prevented the OVX-induced decline in trabecular BMD in the distal femur by modulating the enteric environment and altered OVX-induced inflammation-related gene expression in the bone marrow. However, there were no significant differences in bone parameters between the ISO+RS and ISO-alone groups in OVX mice. Our findings suggest that the combination of ISO and RS might alter intestinal microbiota and immune status in the bone marrow, resulting in attenuated bone resorption in OVX mice.

Combined effects of soy isoflavones and milk basic protein on bone mineral density in hind-limb unloaded mice.

We examined whether the combination of isoflavone and milk basic protein both are reported to be effective for bone metabolism, prevents bone loss induced by skeletal hind-limb unloading in mice. Female ddY strain mice, aged 8 weeks, were divided into six groups (n = 6-8 each): (1) normally housed group, (2) loading group, (3) hind-limb unloading group fed a control diet, (4) hind-limb unloading group fed a 0.2% isoflavone conjugates diet, (5) hind-limb unloading group fed a 1.0% milk basic protein diet, and (6) hind-limb unloading group fed a 0.2% isoflavone conjugates and 1.0% milk basic protein diet. After 3 weeks, femoral bone mineral density was markedly reduced in unloading mice. The combination of isoflavone and milk basic protein showed cooperative effects in preventing bone loss and milk basic protein inhibited the increased expression of osteogenic genes in bone marrow cells in unloading mice. These results suggest that the combination of soy isoflavone and milk basic protein may be useful for bone health in subjects with disabling conditions as well as astronauts.

Combined Effects of Soy Isoflavones and ß-Carotene on Osteoblast Differentiation.

Soy isoflavones, genistein, daidzein and its metabolite equol, as well as ß-carotene have been reported to be effective for maintaining bone health. However, it remains to be elucidated whether combining soy isoflavones with ß-carotene is beneficial to bone formation. This study investigated the combined effect of soy isoflavones and ß-carotene on the differentiation of MC3T3-E1 preosteoblastic cells. Daidzein and genistein alone did not affect cell growth but increased alkaline phosphatase (ALP) activity. Beta-carotene alone inhibited cell growth and markedly enhanced ALP activity. Soy isoflavones combined with ß-carotene resulted in higher ALP activity than treatment with isoflavones or ß-carotene alone. We observed significant main effects of ß-carotene on the enhanced expression of Runx2, ALP, and ostepontin mRNA, whereas there was a significant main effect of soy isoflavones on the expression of osterix mRNA. To investigate how ß-carotene affected osteoblast differentiation, MC3T3-E1 cells were treated with retinoic acid receptor (RAR) pan-antagonist combined with ß-carotene. Osteopontin and ALP mRNA expression levels, which were increased following treatment with ß-carotene, were significantly suppressed by the RAR pan-antagonist. This suggests treatment with ß-carotene enhanced early osteoblastic differentiation, at least in part via RAR signaling. These results indicate that a combination of isoflavones and ß-carotene may be useful for maintaining a positive balance of bone turnover by inducing osteoblast differentiation.

Effect of Kiwifruit on Bone Resorption in Ovariectomized Mice.

Kiwifruit is a good source of dietary components and has beneficial effects for health. In this study, we investigated the effects of two types of kiwifruit, green kiwifruit (GRK) and gold kiwifruit (GOK), on bone metabolism in ovariectomized (OVX) mice. Seven-week-old female Balb/c-strain mice were divided into four groups: sham-operated (sham) group, OVX group, and OVX mice that were fed a GRK-supplemented diet or GOK-supplemented diet. Freeze-dried GRK and GOK were prepared and added in the diet at a concentration of 3 g/100 g. After 9 wk, the mice were sacrificed, and the serum, uterus, and femurs were obtained. Final body weight did not differ significantly among the four groups. Compared to the sham group, uterine weight was significantly lower and serum C-terminal telopeptide of type I collagen (CTx) levels and receptor activator of NF-κB ligand (RANKL) mRNA expression of the whole femur were significantly higher in the OVX group. Compared to the OVX group, GRK, but not GOK, reduced serum CTx concentrations and RANKL mRNA expression of the whole femur without changes in uterine weight. These results suggest that the GRK inhibited bone resorption, which might be due to a decrease in RANKL mRNA expression in OVX mice.

Equol, a Metabolite of Daidzein, Is More Efficient than Daidzein for Bone Formation in Growing Female Rats.

Few studies have examined the effects of isoflavones and particularly equol, a metabolite of the isoflavone daidzein, on bone formation during the growth period in animals. The present study investigated the effects of orally administered daidzein or equol on bone formation and bone mineral density in growing female rats. Female Sprague-Dawley rats, aged 3 weeks, were divided into four groups (n = 8 per group) as follows: rats were orally administered a corn oil, 8 mg/day of daidzein, 4 mg/day of equol or 8 mg/day of equol in corn oil for 4 weeks. Daidzein and equol increased the bone mineral density of growing female rats by stimulating bone formation without exhibiting a substantial effect on the weight of their reproductive organs. Bone growth caused by increased bone mineralizing surface and bone formation rate in rats administered with equol was approximately twice that of rats administered with daidzein. These results suggest that equol might be more efficient than daidzein for bone formation in growing female rats. Copyright © 2015 John Wiley & Sons, Ltd.

Assessment of safety and efficacy of perinatal or peripubertal exposure to daidzein on bone development in rats.

Neonatal exposure to isoflavones improved bone health in thereafter in previous animal studies. However, since isoflavones possess hormonal activity, it may interfere with reproductive development. In the present study, we assessed the safety and efficiency of perinatal or peripubertal exposure to daidzein on bone and reproductive organ development at early adulthood in rats. Sprague-Dawley pregnant rats (n = 18) were divided into 3 groups: (1) dams and their offspring were fed the control diet. (2) Dams were fed the daidzein diet (0.5 g daidzein/kg diet) during pregnancy and then the control diet at postnatal day 13 and their offspring were fed the control diet. (3) Dams and their offspring were fed the daidzein diet through the experiment. While perinatal exposure to daidzein did not confer a positive effect on bone mineral density on postnatal day 35, peripubertal exposure to daidzein protected against a decline in bone mineral density. Meanwhile, exposure to daidzein during the perinatal or peripubertal period did not affect reproductive organ weights at early adulthood in rats. Further investigations should assess the mechanisms underlying these responses of bone metabolism to daidzein, as well as the safety of daidzein exposure during the perinatal period and throughout life.