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Background Inflammation is a major risk factor for frailty, but n-3 polyunsaturated fatty acids (PUFA) has been suggested as an anti-inflammatory agent. The present study aimed to investigate the hypothesis that the higher erythrocyte levels of long-chain n-3 PUFA were associated with lower odds of frailty and frailty criterion. Methods Cross-sectional analysis from the Korean Frailty and Aging Cohort Study, a total of 1,435 people aged 70–84 years were included. Sex- and age-stratified community residents, drawn in urban and rural regions nationwide, were eligible for participation in the study. All participants were categorized as frail and nonfrail according to the Cardiovascular Health Study index. Results The likelihood of frailty was inversely associated with the erythrocyte levels of eicosapentaenoic acid (EPA; odds ratio [OR] per unit 0.33; 95% confidence interval [CI] 0.14–0.77; p for trend = .002) and docosahexaenoic acid (DHA; OR per unit 0.42; 95% CI 0.20–0.87; p for trend = .018). Among each frailty criterion, the likelihood of slow walking speed was associated with erythrocyte levels of EPA and DHA, and the likelihood of exhaustion was inversely associated with the erythrocyte levels of DHA. Conclusions The present study showed that the frailty and frailty criterion were significantly associated with lower erythrocyte levels of long-chain n-3 PUFA, suggesting that lower n-3 PUFA could be a marker for the risk of frailty. more...

The association between obesity and erythrocyte fatty acids (FAs) has been suggested; however, there have been no studies on the effects of onion peel extract (OPE) on the composition of erythrocyte FAs. This study aimed to investigate the effects of OPE on the composition of erythrocyte FAs in overweight and obese subjects. This was a randomized, double-blind, and placebo-controlled trial conducted in overweight and obese Korean subjects. The placebo and OPE groups were taking placebo capsule or OPE capsule twice per day for 12 weeks. Body composition and fat distribution were measured using dual-energy X-ray absorptiometry. The OPE group showed significantly reduced body weight, body mass index, body fat mass, and percentage of body fat mass. After 12 weeks, eicosapentaenoic acid and monounsaturated FAs of the placebo group were significantly lower at baseline. Consumption of OPE ameliorated the decreasing polyunsaturated n-3 polyunsaturated FA (PUFA) n-3 and increasing PUFA n-6, which prevented an increased n-6/n-3 ratio. The changes in arm fat percentage (ARFATP), trunk fat percentage, and total fat percentage (FATP) were negatively correlated with the change in PUFA n-3. In addition, increased erythrocyte docosahexaenoic acid was associated with decreased ARFATP and FATP. These results suggest that OPE has beneficial effects on obesity by regulating erythrocyte n-6/n-3 ratio and preventing fat accumulation in various body regions. more...

Intake of flavonoids is associated with the incidence of breast cancer, but the association between the intake of flavonoids and cancer recurrence is unclear. This study aimed to investigate the hypothesis that intake of flavonoids and flavonoid-rich foods is negatively associated with cancer recurrence. Among 572 women who underwent breast cancer surgery, 66 patients had a cancer recurrence. Dietary data were collected using a structured 24-h dietary recall, and intake of flavonoids was calculated based on the Korea Rural Development Administration flavonoid database. Among overweight and obese patients, disease-free survival was associated with intake of flavonoids (p = 0.004) and flavonoid-rich foods (p = 0.003). Intake of flavonoids (hazard ratio (HR) = 0.249, 95% confidence interval (CI): 0.09–0.64) and flavonoid-rich foods (HR = 0.244, 95% CI: 0.09–0.66) was negatively associated with cancer recurrence after adjusting for confounding factors in overweight and obese patients. Consumption of flavonoids and flavonoid-rich foods was lower in overweight and obese patients with cancer recurrence than those without recurrence and in normal-weight patients. This study suggests that intake of flavonoids and flavonoid-rich foods could have beneficial effects on cancer recurrence in overweight and obese breast cancer survivors. more...

Antioxidant intake has been suggested to be associated with a reduced osteoporosis risk, but the effect of dietary total antioxidant capacity (TAC) on bone health and the risk of osteoporosis remains unclear. We aimed to assess the hypothesis that dietary TAC is positively associated with bone mass and negatively related to the risk of osteoporosis in Korean women. This cross-sectional study was performed using data from the Korea National Health and Nutrition Examination Survey. Dietary TAC was estimated using task automation and an algorithm with 24-h recall data. In total, 8230 pre- and postmenopausal women were divided into four groups according to quartiles of dietary TAC. Dietary TAC was negatively associated with the risk of osteoporosis (odds ratio, 0.73, 95% confidence interval, 0.54–0.99, p-value = 0.045) in postmenopausal women, but not in premenopausal women. Dietary TAC was positively associated with bone mineral content (BMC) and bone mineral density of the femoral neck and lumbar spine in postmenopausal women and BMC of the total femur and lumbar spine in premenopausal women. Our study suggests that dietary TAC is inversely associated with the risk of osteoporosis in postmenopausal women and positively associated with bone mass in both pre- and postmenopausal women. more...

Aging is associated with changes in hormones, slowing of metabolism, diminished physiological processes, chronic inflammation and high exposure to oxidative stress factors, generally described as the biological cost of living. Lifestyle interventions of diet and exercise can improve the quality of life during aging and lower diet-related chronic disease. The endocannabinoid system (ECS) has important effects on systemic metabolism and physiological systems, including the central and peripheral nervous systems. Exercise can reduce the loss of muscle mass and improve strength, and increase the levels of endocannabinoids (eCB) in brain and blood. Although the ECS exerts controls on multiple systems throughout life it affords benefits to natural aging. The eCB are synthesized from polyunsaturated fatty acids (PUFA) and the primary ones are produced from arachidonic acid (n-6 PUFA) and others from the n-3 PUFA, namely eicosapentaenoic and docosahexaenoic acids. The eCB ligands bind to their receptors, CB1 and CB2, with effects on appetite stimulation, metabolism, immune functions, and brain physiology and neuroplasticity. Dietary families of PUFA are a primary factor that can influence the types and levels of eCB and as a consequence, the downstream actions when the ligands bind to their receptors. Furthermore, the association of eCB with the synthesis of oxylipins (OxL) is a connection between the physiological actions of eCB and the lipid derived immunological OxL mediators of inflammation. OxL are ubiquitous and influence neuroinflammation and inflammatory processes. The emerging actions of eCB on neuroplasticity, well-being and pain are important to aging. Herein, we present information about the ECS and its components, how exercise and diet affects specific eCB, their role in neuroplasticity, neuroinflammation, pain, mood, and relationship to OxL. Poor nutrition status and low nutrient intakes observed with many elderly are reasons to examine the role of dietary PUFA actions on the ECS to improve health. more...

Background: Statin treatment has decreased the risk of cardiovascular events in patients with chronic kidney disease (CKD). Erythro-cyte membrane oleic acid level is higher in patients with acute coronary syndrome. This study aimed to evaluate the effect of pravas-tatin on the erythrocyte membrane fatty acid (FA) contents in patients with CKD. Methods: Sixty-two patients were enrolled from January 2017 to March 2019 (NCT02992548). Pravastatin was initially administered at a dose of 20 mg for 24 weeks. The pravastatin dose was increased to 40 mg after 12 weeks if it was necessary to control dyslipid-emia. The primary outcome was change in erythrocyte membrane FA, including oleic acid, after pravastatin treatment for 24 weeks. Results: Forty-five patients finished this study, and there was no adverse effect related to pravastatin. Compared with baseline, total cholesterol and low-density lipoprotein cholesterol levels were significantly decreased after pravastatin treatment. Compared with baseline, saturated FA, oleic acid, and arachidonic acid levels were significantly increased and polyunsaturated FA and linoleic acid (LA) levels were significantly decreased after pravastatin treatment. There was also a decrease in eicosapentaenoic acid after pravas-tatin treatment in CKD patients with estimated glomerular filtration rate < 60 mL/min/1.73㎡. Conclusion: Administration of pravastatin in patients with CKD leads to a decrease in FA known to be protective against the risk of CVD. Omega-3 FA or LA supplementation might be necessary to recover changes in erythrocyte membrane FA contents when pravas-tatin is used for treating dyslipidemia in patients with CKD. more...

The gut microbiota has been suggested as an important factor in the pathogenic mechanisms of amyotrophic lateral sclerosis (ALS). This study aimed to investigate whether the intake of different kinds of dietary fiber was related to the disease progression rate (∆FS) and survival time. In total, 272 Korean sporadic ALS patients diagnosed according to the revised EI Escorial criteria were recruited starting in March 2011 and were followed until the occurrence of events or the end of September 2020. The events included percutaneous endoscopic gastrostomy, tracheostomy, and death. Dietary fiber intake was calculated based on a 24-h dietary recall and classified according to five major fiber-rich foods: vegetables, fruits, grains, legumes, and nuts/seeds. Among the total participants, the group with ∆FS values lower than the mean ∆FS (0.75) was noted in the highest tertiles of total and vegetable fiber intake. Participants in the highest tertile for vegetable fiber intake showed longer survival in the Kaplan&ndash, Meier analysis (p = 0.033). Notably, vegetable fiber intake was negatively correlated with pro-inflammatory cytokine (interleukin (IL)-1&beta, IL-6, and monocyte chemoattractant protein-1) levels in the cerebrospinal fluid. This study showed that vegetable fiber intake could influence the disease progression rate and survival time. Further clinical trials are needed to confirm whether dietary fiber supplementation improves the prognosis of ALS. more...

Early life maternal separation (MS) increases the vulnerability to depression in rats with chronic mild stress (CMS). N-3 polyunsaturated fatty acids (PUFA) improved depressive behaviors in rats with acute stress; however, their effects on rats with MS+CMS were not apparent. The purpose of the present study was to investigate the hypothesis that lifetime n-3 PUFA supplementation improves post-menopausal depression through the serotonergic and glutamatergic pathways while modulating n-3 PUFA-derived metabolites. Female rats were fed diets of either 0% n-3 PUFA during lifetime or 1% energy n-3 PUFA during pre-weaning, post-weaning, or lifetime periods. Rats were allocated to non-MS or MS groups and underwent CMS after ovariectomy. N-3 PUFA increased brain n-3 PUFA-derived endocannabinoid/oxylipin levels, and reversed depressive behaviors. N-3 PUFA decreased blood levels of adrenocorticotropic hormone and corticosterone, and brain expressions of corticotropin-releasing factor and miRNA-218, which increased the expression of the glucocorticoid receptor. N-3 PUFA decreased the expression of tumor necrosis factor-α, interleukin (IL)-6, IL-1β, and prostaglandin E2, while increased the expression of miRNA-155. N-3 PUFA also increased brainstem serotonin levels and hippocampal expression of the serotonin-1A receptor, cAMP response element-binding protein (CREB), phospho-CREB, and brain-derived neurotrophic factor. However, n-3 PUFA did not affect brain expression of α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor subtype 1, N-methyl-D-aspartate receptor subtype 2B, or miRNA-132. Moreover, n-3 PUFA exposure during lifetime caused greater effects than pre- and post-weaning periods. The present study suggested that n-3 PUFA improved depressive behaviors through serotonergic pathway while modulating the metabolites of n-3 PUFA in post-menopausal depressed rats with chronic stress. more...

Increased protein intake has been suggested as an effective strategy to treat age-related loss of muscle mass and function, but the amount of protein required to improve muscle and function without exercise in older adults remains unclear. Thus, this secondary data analysis aimed to assess what amount of protein from habitual protein intake was positively associated with changes in muscle mass and gait speed in older women and men. Ninety-six community-dwelling older adults consumed 0.8, 1.2, or 1.5 g/kg/day of protein and maintained their usual physical activity for 12 weeks. Increased protein intake of &gt, 0.54 g/kg/day was positively associated with changes in appendicular skeletal muscle mass (ASM)/weight (B = 0.591, p = 0.026), ASM/body mass index (B = 0.615, p = 0.023), and ASM:fat ratio (B = 0.509, p = 0.030) in older men. However, change in protein intake was not associated with change in muscle mass in older women. Additionally, change in protein intake was not associated with change in gait speed in older women and men. The present study suggested that an increased absolute protein amount of &gt, 0.54 g/kg/day from habitual protein intake was positively associated with change in muscle mass in older men. more...

OBJECTIVES: Inflammation is a major risk factor for frailty, and n-3 polyunsaturated fatty acids (PUFA) are well known as an anti-inflammatory agent. The purpose of present study was to investigate the hypothesis that the higher erythrocyte levels of long-chain n-3 PUFA were associated with lower odds of frailty and frailty criterion in community-dwelling older people. METHODS: Cross-sectional analysis from the data of the Korean Frailty and Aging Cohort Study, a total of 1435 older people aged 70–84 years were included in the analysis. Sex- and age-stratified community residents, drawn in urban and rural regions nationwide, were eligible for participation in the study. All participants were categorized as frail and non-frail according to the Cardiovascular Health Study index, and analyzed for erythrocyte fatty acid composition by gas chromatography. The erythrocyte levels of PUFA were expressed as a % of total erythrocyte PUFAs. RESULTS: After adjusting for confounding factors, the risk of frailty was negatively associated with the erythrocyte levels of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and Omega-3 Index, but positively associated with erythrocyte levels of arachidonic acid/EPA ratio. Consistently, the frailty score was negatively correlated with erythrocyte levels of EPA, DHA, and Omega-3 Index, but positively correlated with erythrocyte levels of arachidonic acid/EPA ratio. In addition, for each frailty criterion, the risk of slow walking speed, low handgrip strength, exhaustion, and low physical activity were negatively associated with erythrocyte levels of n-3 PUFA. CONCLUSIONS: The present study showed that the risk of frailty and frailty criteria were significantly associated with lower erythrocyte levels of long-chain n-3 PUFAs, suggesting that lower erythrocyte levels of long-chain n-3 PUFAs could be a marker for the risk of frailty. FUNDING SOURCES: This research was supported by a grant of the Korea Health Technology R&D Project through the Korean Health Industry Development Institute (KHIDI) funded by the Ministry of Health and Welfare, Republic of Korea (grant No. HI15C3153), and the National Research Foundation (NRF) of Korea grant funded by the Korea government (NRF-2018R1A2B6002486). more...

OBJECTIVES: The purpose of the present study was to investigate the hypothesis that lifetime n-3 polyunsaturated fatty acids (PUFA) intake improved depression through serotonergic pathway in post-menopausal rats with chronic mild stress (CMS) and maternal separation (MS). METHODS: Female rats were fed diets with 0% or 1 energy % n-3 PUFA during lifetime from embryonic day (ED) 0 to postnatal day (PND) 112, or 1% n-3 PUFA before weaning (ED 0-PND 20), or after weaning (PND 20–112). The rats in four diet group were allocated to brief separation from dam (non-MS group) or long-term separation (MS group) on PND 2–14, and then underwent CMS on PND 91–105 after ovariectomy. Thus, there were eight groups in total (n = 8/group). RESULTS: MS + CMS increased depressive behaviors, and modified hypothalamic-pituitary-adrenal (HPA) axis activity, inflammation, serotonergic and glutamatergic neurotransmission, and related miRNAs as compared to CMS alone. N-3 PUFA decreased depressive behaviors by decreasing immobility while increasing swimming during forced swim test, and increasing sucrose preference in rats with MS + CMS and with CMS. N-3 PUFA decreased HPA axis activity by modifying expressions of corticotrophin releasing factor and glucocorticoid receptor, and levels of adrenocorticotropic hormone and corticosterone. N-3 PUFA also reduced levels of TNF-α, IL-1β, IL-6, PGE(2), and miRNA-218, and increased serotonergic neurotransmission, including expressions of cAMP response element binding protein, brain-derived neurotrophic factor and serotonin 1A receptor, and serotonin level, and expression of miRNA-155. In addition, lifetime supplementation of n-3 PUFA had greater effect than pre- or post-supplementation. N-3 PUFA had no effect on glutamatergic pathway including α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor and N-methyl-D-aspartate receptor. CONCLUSIONS: The present study suggested that lifetime n-3 PUFA improved depression in post-menopausal rats with MS + CMS through modulation of serotonergic pathway by decreasing HPA axis activity but not glutamatergic pathway. FUNDING SOURCES: This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (NRF-2018R1A2B6002486). more...

Aim: Stearoyl-CoA desaturase (SCD)-1 and elongase-6 (Elovl-6) are associated with fatty acid (FA) synthesis. We evaluated the effect of omega-3 FA on erythrocyte membrane FA contents through SCD-1 and Elovl-6 expression in the liver and kidney of a cyclosporine (CsA)-induced rat model. Methods: Male Sprague Dawley rats were divided into control, CsA, and CsA treated with omega-3 FA groups. We measured SCD-1 and Elovl-6 expression levels via western blot and immunohistochemistry analysis. Results: Erythrocyte membrane oleic acid content was lower in the CsA with omega-3 FA group compared to the CsA group. Compared to the control group, CsA-induced rats showed elevated SCD-1 expression in the kidney and liver, which omega-3 FA treatment reversed. Elovl-6 expression was increased in the liver, but decreased in the kidney in CsA group compared to control, which omega-3 FA treatment also reversed. Conclusions: Omega-3 FA supplementation decreased erythrocyte membrane oleic acid content by modulating SCD-1 and Elovl-6 expression in the kidney and liver of CsA-induced rats. more...

Background Depression induced by chronic mild stress (CMS) reduced bone mass in ovariectomized (OVX) rats, and maternal separation (MS) during early life aggravated depression-induced bone mass destruction. N-3 polyunsaturated fatty acids (PUFA) have been shown to improve bone mass and depression, but the bone-protecting effects of n-3 PUFA were unclear in CMS+MS-induced depression models. The purpose of this study was to determine whether n-3 PUFA improved CMS+MS-induced postmenopausal bone loss via its antidepressant-like action. Methods Rats were fed diets containing 0% of total energy intake (en %) of n-3 PUFA during lifetime or 1 en % n-3 PUFA during pre-weaning or post-weaning periods, or their entire lifetimes and were allocated to CMS or CMS+MS groups after OVX. Results Lifetime supply of n-3 PUFA enhanced bone mass and microarchitecture, and expression of runt-related transcription factor 2, while decreasing blood levels of amino-terminal cross-linked telopeptide of type 1 collagen and the expression of receptor activator of nuclear factor kappa Β ligand/osteoprotegerin, activating transcription factor 4, and adrenergic receptor β2. Lifetime supply of n-3 PUFA decreased levels of adrenocorticotropic hormone and corticosterone and the expression of corticotropin-releasing factor in the brain but increased expression of the glucocorticoid receptor, serotonin-2C receptor, cAMP response element-binding protein (CREB), and calmodulin kinase IV and serotonin levels. Supply of n-3 PUFA during the pre-and post-weaning periods had beneficial effects on the brain but not on the bones. Conclusion Lifetime supply of n-3 PUFA ameliorated bone loss induced by chronic stress by regulating hypothalamic-pituitary-adrenal axis activity and serotonin-CREB signaling. more...

Early life and adulthood stress increase vulnerability for mental illness, and eventually trigger depression. N-3 polyunsaturated fatty acids (PUFA) have antidepressant effects, but their effect on rats exposed to combined stress has been not investigated. This study aimed to investigate whether n-3 PUFA supplementation had antidepressant-like effects in rat models of depression induced by a combination of chronic mild stress (CMS) and maternal separation (MS) through the modulation of the hypothalamic-pituitary-adrenal (HPA) axis and neurotransmission. Rats were fed the n-3 PUFA diet during the pre-weaning or post-weaning period or for lifetime, and allocated to different groups based on the type of induced stress: non-stress (NS), CMS + MS, or CMS alone. N-3 PUFA improved the depressive behaviors of the CMS alone and CMS + MS groups and modulated the HPA-axis by reducing the circulating adrenocorticotropic hormone, corticosterone, and corticotropin-releasing factor expression, and increasing glucocorticoid receptor expression. N-3 PUFA also modulated brain phospholipid fatty acid concentration, thus reducing inflammatory cytokines; improved the serotonergic pathway, thus increasing the expression of the brain-derived neurotrophic factor (BDNF), cAMP response element-binding protein (CREB), serotonin-1A receptor, and serum levels of serotonin; but did not affect glutamatergic neurotransmission. Furthermore, n-3 PUFA decreased the hippocampal expression of microRNA-218 and -132, increased that of microRNA-155, and its lifetime supplementation was more beneficial than pre- or post-weaning supplementation. This study suggests that n-3 PUFA has an antidepressant effect in rats exposed to combined stress, through the improvement of the HPA-axis abnormalities, the BDNF-serotonergic pathway, and the modulation of microRNAs. more...

OBJECTIVES: The purpose of the present study was to investigate the hypothesis that n-3 polyunsaturated fatty acids (PUFAs) had antidepressant effects through microRNA (miR)-regulated neurobiological systems in dams with postpartum depression (PPD) induced by pup separation (PS). METHODS: After mating, the female rats were fed a modified AIN-93 G diet with 0% or 1% n-3 PUFAs relative to total energy intake during gestation and lactation periods. After birth, dams were separated from their pups for 15 min (control) or 180 min (PS) every day on postpartum day 2–14. There were four groups (n = 8/group): control, PS, n-3 PUFAs and PS + n-3 PUFAs. RESULTS: PS increased latencies to contact first pup and to retrieve all pup increased immobility but decreased climbing during forced swimming test, and decreased sucrose preference. PS increased activity of hypothalamic-pituitary-adrenal (HPA) axis including expression of corticotrophin releasing factor and glucocorticoid receptor, and levels of adrenocorticotropic hormone and corticosterone. PS also decreased serotonergic neurotransmission including expressions of cAMP response element binding protein (CREB), pCREB, brain-derived neurotrophic factor (BDNF) and serotonin 1A receptor, and level of serotonin. In addition, PS increased inflammation including expressions of TNF-α, IL-6, PGE(2), and N-methyl-D-aspartate receptor (NMDAR) 2B. PS modified HPA-axis, serotonergic neurotransmission, inflammation and NMDAR 2B through miR-218, miR-132, miR-182 and miR-155. N-3 PUFAs modified depressive behaviors, HPA axis activity, serotonergic neurotransmission, inflammation through miR-218, miR-182 and miR-155. However, n-3 PUFAs had no effect on miR-17, miR-132, and NMDAR 2B. CONCLUSIONS: The present study suggested that the antidepressant-like effects of n-3 PUFAs could be due to regulation of HPA axis activity, serotonergic neurotransmission and inflammation via miR-218, miR-182 and miR-155, rather than NMDAR. FUNDING SOURCES: This work was supported by the National Research Foundation of Korea grant funded by the Korea government (NRF-2018R1A2B6002486). more...

OBJECTIVES: Flavonoid intakes have been shown to associate with breast cancer incidence, but it is not clear the association between flavonoids and cancer recurrence. The purpose of the present study was to investigate the hypothesis that intakes of flavonoids and flavonoid-rich foods were negatively associated with cancer recurrence. METHODS: Among 572 women after breast cancer surgery, 66 patients had cancer recurrence during follow–up until 114 months with a median period of disease-free survival of 43 months ranged 6–103 months. Dietary data were collected using structured 24-h dietary recall, and the intake of flavonoid was calculated based on the Korea Rural Development Administration flavonoid database. RESULTS: There was no significant association of flavonoid and flavonoid-rich food intake with cancer recurrence and disease-free survival among all patients. On the other hand, among overweight and obese patients, Kaplan-Meier survival curves revealed a significant effect of dietary flavonoids (P = 0.04) and flavonoid-rich foods (P = 0.03) on disease-free survival, but not overall survival. Intakes of flavonoid (HR = 0.244, 95% CI: 0.09–0.66) and flavonoid-rich food (HR = 0.223, 95% CI: 0.08–0.59) were also negatively associated with cancer recurrence after adjusting for confounding factors in overweight and obese patients. Consumption of flavonoids and flavonoid-rich foods was lower in overweight and obese patients with cancer recurrence than those without recurrence. CONCLUSIONS: To the best of our knowledge, this was the first study to examine the association between flavonoid intake and cancer recurrence/disease-free survival in breast cancer patients. The present study suggested that intakes of flavonoids and flavonoid-rich foods could have a beneficial effect on cancer recurrence among overweight and obese breast cancer survivors. Further clinical studies are needs to confirm whether supplementation of flavonoids reduces cancer recurrence. FUNDING SOURCES: This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (NRF-2018R1A2B6002486). more...

OBJECTIVES: Antioxidant intake has been suggested to be associated with the risk of osteoporosis. However, the effect of dietary total antioxidant capacity (TAC) on bone health is not clear. The aim of the present study was to assess the hypothesis that dietary TAC was positively associated with bone mass and negatively with the risk of osteoporosis in Korean women. METHODS: This cross-sectional study was performed using data from the Korea National Health and Nutrition Examination Survey, 2008–2011. Dietary TAC was estimated by using task automation technique and algorithm to calculate the theoretical TAC from one day of 24-hour recall data using a TAC database comprising antioxidant capacities of 42 dietary antioxidants, developed for common Korean foods. In total, 8230 women were divided into a postmenopausal and premenopausal group, and each group was subdivided into four groups according to quartiles of dietary TAC. Multiple regression analysis was performed to assess relationships between dietary TAC with bone mass and the risk of osteoporosis risk. RESULTS: Dietary TAC was negatively associated with the risk of osteoporosis (odds ratio: 0.73, 95% confidence interval: 0.54–0.99; p-trend = 0.045) in postmenopausal women, but not in premenopausal women. Dietary TAC was positively associated with bone mineral content (BMC) and bone mineral density of the femoral neck and lumbar spine in postmenopausal women, and BMC of total femur and lumbar spine in premenopausal women. CONCLUSIONS: The present study suggested that dietary TAC was inversely associated with the risk of osteoporosis in postmenopausal women, and positively associated with bone mass in pre- and post-menopausal women. Further long-term cohort or intervention study will be necessary to confirm the effect of a high dietary TAC diet on bone health. FUNDING SOURCES: This research was supported by the Basic Science Research Program through the National Research Foundation of Korea funded by the Korean government. more...

OBJECTIVES: The gut microbiota has been suggested to associate with the pathophysiology of amyotrophic lateral sclerosis (ALS), and thus prebiotic effect of fiber could play an important role on pathophysiology of ALS. The present study aimed to investigate the effect of dietary fiber intake on the disease progression rate (∆FS) and survival time among Korean ALS patients. METHODS: A total of 272 Korean sporadic ALS patients diagnosed according to the revised EI Escorial criteria were recruited during 2011–2019, and were followed until the occurrence of events or the end of September 2020. The events were defined as percutaneous endoscopic gastrostomy, tracheostomy, or death. Intake of dietary fibers was calculated based on 24-hour dietary recall, and divided into five major fiber-rich foods: vegetables, fruits, grains, legumes, and nuts/seeds. RESULTS: There were higher proportion of participants with lower than the mean value of ∆FS (0.75) in the highest tertile of total fiber and vegetable fiber intake than those in the lowest tertile. Kaplan–Meier analysis showed that participants in the highest tertile for vegetable fiber intake had longer survival. Cox regression analysis showed that intake of vegetable fiber was negatively associated with risk for events after adjustment. Notably, vegetable fiber intake was negatively correlated with pro-inflammatory cytokine such as interleukin (IL)-1β, IL-6, and monocyte chemoattractant protein-1 in the cerebrospinal fluid. CONCLUSIONS: In conclusion, this study showed that vegetable fiber intake was negatively associated to the ∆FS and shorter survival time, suggesting that vegetable fiber intake could influence the prognosis of ALS. Further clinical trials are needed to confirm whether supplementation of dietary fiber improves the prognosis in ALS. FUNDING SOURCES: This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT). more...

Oestrogen and n-3 PUFA, especially EPA and DHA, have been reported to have beneficial effects on bone loss. Thus, the purpose of the present study was to investigate the synergistic bone-protective mechanism of combined treatments of EPA+DHA supplementation and oestrogen injection in ovariectomised rats. Rats were fed a modified American Institute of Nutrition-93G diet with 0 %, 1 % or 2 % n-3 PUFA (EPA+DHA) relative to the total energy intake for 12 weeks. Rats were surgically ovariectomised at week 8, and after a 1-week recovery period rats were injected with either 17β-oestradiol-3-benzoate (E2) or maize oil for the last 3 weeks. Combined use of n-3 PUFA and E2 synergistically increased femoral cortical bone volume, bone mineral content and the bone expression of runt-related transcription factor 2 (RUNX2), but decreased the bone expression of IL-1β. Both n-3 PUFA and E2 decreased the bone expressions of IL-7, TNF-α and PPAR-γ, and increased the bone expression of oestrogen receptor-α. n-3 PUFA in the presence of E2 and E2 alone significantly decreased the bone expressions of IL-1β and IL-6 and increased the bone expression of RUNX2. E2 significantly decreased the serum levels of bone turnover markers and the bone expression of receptor activator of NF-κB ligand, but decreased the bone expression of osteoprotegerin. The combined use of n-3 PUFA and E2 exerted synergistic bone-protective efficacy through up-regulation of RUNX2, an essential transcription factor for bone formation, as well as the suppression of bone-resorbing cytokine IL-1β. more...

Triple-negative breast cancer (TNBC) is a common subtype of breast cancer among women with dense breasts and is associated with a poor prognosis. Diet is a modifiable risk factor for breast cancer, but the association between the risk of TNBC and diet has not been studied. The present study investigated the hypothesis that a healthy dietary pattern was negatively associated with risk of TNBC in women with dense breasts (density types 3 and 4). After total mastectomy or breast conserving surgery, patients with TNBC (n = 38) and non-TNBC (n = 178) were recruited. The risk of TNBC was negatively associated with a healthy dietary pattern involving consumption of seafood and vegetables, and positively associated with a dietary pattern of consuming grains, meats, and eggs. Additionally, intake of animal fat, eggs, and meat was positively associated with the risk of TNBC, but intake of vegetable fats, nuts, and vegetables showed a negative association. Patients with TNBC had higher proportion of obesity or abdominal obesity than those with non-TNBC. The present study is the first to show a negative association between risk of TNBC and a healthy dietary pattern in women with dense breasts and suggests the importance of diet in the prevention of TNBC. more...

Objective Epidemiologic and clinical studies have suggested that hormone therapy (HT) and n-3 polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), exert antidepressant effects through regulation of the serotonergic pathway. The present study was conducted to evaluate the hypothesis that erythrocyte levels of n-3 PUFAs and depression were negatively associated in postmenopausal women, particularly those using HT. Methods A total of 214 postmenopausal women were divided into groups defined by depression and HT status. Depression was defined as a Beck Depression Inventory score of at least 14, and the types and durations of HT were obtained from medical records. Results Erythrocyte levels of EPA, docosapentaenoic acid (DPA), DHA, omega-3 index (sum of EPA + DHA), total n-3 PUFA, and arachidonic acid were significantly higher in women using HT than in those not using HT. There were significant negative correlations between depression and erythrocyte levels of alpha-linolenic acid (r = -0.310), DPA (r = -0.272), DHA (r = -0.209), and total n-3 PUFA (r = -0.234) in women using HT. Multivariate-adjusted logistic regression analysis also showed that depression was negatively associated with the erythrocyte levels of alpha-linolenic acid (P for trend = 0.018), DPA (P for trend = 0.014), and DHA (P for trend = 0.036), only in women using HT. Conclusions Negative associations between erythrocyte levels of n-3 PUFAs and depression were found in Korean postmenopausal women using HT but not in those not using HT, suggesting a synergistic effect of HT and n-3 PUFAs on depression. more...

Stress and ovarian hormone fluctuation are risk factors for postpartum depression (PPD). Previous studies suggested antidepressant-like effects of n-3 polyunsaturated fatty acids (PUFA), but their effect on dam animal with additional stress were not clear. The purpose of the present study was to investigate the hypothesis that n-3 PUFA improved PPD through the serotonergic and glutamatergic pathways by modulating miRNA. Rats were fed n-3 PUFA or control diet from gestation, with pup separation (PS) on postpartum days 2-14 and non-PS controls. N-3 PUFA reversed PS-induced depressive behaviors, including increased immobility, latencies to contact first pup and retrieve all pups, and decreased sucrose preference. N-3 PUFA also modulated the hypothalamic-pituitary-adrenal (HPA) axis by decreasing circulating levels of adrenocorticotropic hormone and corticosterone and expression of hypothalamic corticotrophin releasing factor and hippocampal miRNA-218 but increasing the hippocampal expression of glucocorticoid receptor. N-3 PUFA inhibited neuroinflammation by decreasing circulating levels of prostaglandin E2 and hippocampal expression of tumor necrosis factor-α, interleukin-6, and miRNA-155. In addition, n-3 PUFA up-regulated the serotonergic pathway by increasing circulating levels of serotonin and hippocampal expression of serotonin-1A receptor, cAMP response element binding protein (CREB), pCREB, brain-derived neurotrophic factor, and miRNA-182 but did not affect the glutamatergic pathway according to the hippocampal expression of N-methyl-D-aspartate receptor-2B. The present study suggested that n-3 PUFA improved PPD through the serotonergic pathway by modifying the HPA axis, neuroinflammation, and related miRNAs. more...

Conversion ofα-linolenic acid (ALA) into the longer chainn-3 PUFA has been suggested to be affected by the dietary intake of linoleic acid (LA), but the mechanism is not well known. Therefore, the purpose of this study was to evaluate the effect of a low-LA diet with and without oestrogen on the fatty acid conversion enzymes and transcription factors. Rats were fed a modified American Institute of Nutrition-93G diet with 0%n-3 PUFA or ALA, containing low or high amounts of LA for 12 weeks. At 8 weeks, the rats were injected with maize oil with or without 17β-oestradiol-3-benzoate (E) at constant intervals for the remaining 3 weeks. Both the low-LA diet and E significantly increased the hepatic expressions of PPAR-α, fatty acid desaturase (FADS) 2, elongase of very long chain fatty acids 2 (ELOVL2) and ELOVL5 but decreased sterol regulatory element binding protein 1. The low-LA diet, but not E, increased the hepatic expression of FADS1, and E increased the hepatic expression of oestrogen receptor-αandβ. The low-LA diet and E had synergic effects on serum and liver levels of DHA and on the hepatic expression of PPAR-α. In conclusion, the low-LA diet and oestrogen increased the conversion of ALA into DHA by upregulating the elongases and desaturases of fatty acids through regulating the expression of transcription factors. The low-LA diet and E had a synergic effect on serum and liver levels of DHA through increasing the expression of PPAR-α. more...

Our previous study showed that n-3 polyunsaturated fatty acid (PUFA) and estrogen (E) had synergistic hypocholesterolemic effects by inhibiting cholesterol synthesis and enhancing bile acid synthesis. The purpose of the present study was to investigate the hypothesis that α-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) decrease low-density lipoprotein cholesterol (LDL-C), synergistically with E, via hepatic cholesterol synthesis and clearance. Rats were fed a diet with either 0% n-3 PUFA or 1% ALA, EPA, or DHA, relative to total energy consumption, for the entire 12-week study. After ovariectomy, rats were injected with either corn oil or E every 4 days for the last 3 weeks of the study. In combination with E, dietary supplementation with EPA or DHA increased the phosphorylated adenosine monophosphate–activated protein kinase/adenosine monophosphate–activated protein kinase ratio and LDL receptor expression, and it decreased the expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase, sterol regulatory element-binding protein-2, and proprotein convertase subtilisin/kexin type 9 in the liver. In addition, dietary supplementation with EPA or DHA increased hepatic expression of cholesterol 7α-hydroxylase, sterol 12α-hydroxylase, and sterol 27-hydroxylase. However, E decreased the expression of cholesterol 7α-hydroxylase and sterol 12α-hydroxylase and increased the expression of estrogen receptor α and β in the liver. ALA had no significant effects on cholesterol metabolism. In conclusion, the present study suggests that dietary supplementation with EPA and DHA decreased LDL-C synthesis and increased bile acid synthesis and LDL-C clearance by LDL receptor, synergistically with E. more...

Both inflammation and poor nutritional status are major risk factors of frailty, and the dietary inflammatory index (DII) has been suggested as being associated with the risk of frailty. The present study aimed to investigate whether DII scores were positively associated with the risk of frailty in older individuals, particularly those with poor nutritional status. In total, 321 community-dwelling older individuals aged 70&ndash, 85 years were recruited and categorized as non-frail, pre-frail, and frail according to the Cardiovascular Health Study index. DII scores were calculated based on 24-h dietary recall, and nutritional status was assessed using the Mini Nutritional Assessment. Multinomial logistic regression analysis showed that DII scores were positively associated with the risk of frailty in older individuals (odds ratio, OR 1.64, 95% confidence interval, 95% CI 1.25&ndash, 2.17), particularly those with poor nutritional status (OR 1.68, 95% CI 1.21&ndash, 2.34). Among the frailty criteria, weight loss (OR 1.29, 95% CI 1.03&ndash, 1.60), low walking speed (OR 1.33, 95% CI 1.10&ndash, 1.61), and low grip strength (OR 1.34, 95% CI 1.13&ndash, 1.60) were associated with DII scores. In addition, the optimal DII cut-off score for frailty was &ge, 0.93 (sensitivity 71%, specificity: 72%, area under the receiver operating characteristic curve, AUC = 0.792). The present study showed that a pro-inflammatory diet was associated with increased risk of frailty, particularly in older individuals with poor nutritional status. Future randomized controlled trials with a low DII diet for the prevention of frailty are needed to confirm our finding. more...

The dietary inflammatory index (DII) has been associated with breast cancer incidence and survival. However, the association between DII and cancer recurrence and mortality among patients with breast cancer has not been investigated. Therefore, the present study aimed to investigate whether DII was positively associated with risk for cancer recurrence and overall mortality among patients with breast cancer. Among 511 women (51.9 &plusmn, 10.7 years, stage 0&ndash, 3) who underwent breast cancer surgery, 88 had cancer recurrence, and 44 died during follow&ndash, up until 213 months (average disease free survival of 84.3 &plusmn, 42.4 months and overall survival of 69.3 &plusmn, 38.9 months). The DII assessed after surgery (5.4 &plusmn, 5.2 months after diagnosis) was significantly higher in patients with recurrence than those without recurrence, and Cox proportional hazards regression analysis showed that it was positively associated with the risk for cancer recurrence (hazard ratio (HR) 2.347, confidence interval (CI) 1.17&ndash, 4.71) and overall mortality (HR 3.049, CI 1.08&ndash, 8.83) after adjusting for confounding factors. Disease-free survival and overall survival rates were significantly lower in patients with higher DII scores. In addition, the DII was positively associated with the risk for cancer recurrence according to prognostic factors, such as age (&lt, 50 years), premenopausal status, body mass index (&ge, 25 kg/m2), HR+, tumor size (&gt, 2 cm), and presence of lymph node metastasis. The present study showed that anti-inflammatory diets may decrease the risk of cancer recurrence and overall mortality in patients with breast cancer, particularly those with prognostic factors, such as younger age, premenopausal status, obesity, HR+ breast cancer, tumor size &gt, 2 cm, and presence of lymph node metastasis. more...

Objectives: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease, and the nutritional state of ALS patients is associated with survival. The purpose of the present study was to investigate whether macronutrient intake at early stage of the disease was positively associated with survival and duration from symptom onset to death, tracheostomy, or non-invasive ventilation (NIV) in ALS.Methods: ALS patients diagnosed according to EI Escorial criteria were recruited from 2011 to 2016 and followed up until 2017, when they reached the endpoint of death, tracheostomy, or NIV use. Dietary intake was estimated based on a 24-hour recall conducted less than 2 years from symptom onset, and the survival time was defined as the duration from symptom onset to the endpoint.Results: ALS patients were categorized as short-term group (n=79) and long-term group (n=69) according to the mean survival time (33.03±14.01 months). Short-term survival was negatively associated with fat, protein, and meat intake, and positively associated with carbohydrate intake after adjustment for confounders. In addition, the survival time was positively associated with fat, protein, and meat intake but was not associated with carbohydrate intake.Discussion: The present study suggested that higher intake of fat and protein, particularly from meat at early stage of the disease, could prolong the survival of ALS patients. However, further clinical trials are necessary to confirm the beneficial effects of higher fat and protein intake on mortality in ALS patients. more...

n-3 PUFA such as EPA and DHA as well as oestrogen have been reported to decrease blood levels of cholesterol, but their underlying mechanism is unclear. The purpose of this study was to determine the effects of the combination ofn-3 PUFA supplementation and oestrogen injection on hepatic cholesterol metabolism. Rats were fed a modified AIN-93G diet with 0, 1 or 2 %n-3 PUFA (EPA+DHA) relative to the total energy intake for 12 weeks. Rats were surgically ovariectomised at week 8, and, after 1-week recovery, rats were injected with 17β-oestradiol-3-benzoate (E2) or maize oil for the last 3 weeks. Supplementation withn-3 PUFA and E2injection significantly increased the ratio of the hepatic expression of phosphorylated AMP activated protein kinase (p-AMPK):AMP activated protein kinase (AMPK) and decreased sterol regulatory element-binding protein-2, 3-hydroxy-3-methylglutaryl coenzyme A reductase and proprotein convertase subtilisin/kexin type 9. Supplementation withn-3 PUFA increased hepatic expression of cholesterol 7α-hydroxylase (CYP7A1), sterol 12α-hydroxylase (CYP8B1) and sterol 27-hydroxylase (CYP27A1); however, E2injection decreased CYP7A1 and CYP8B1 but not CYP27A1. Additionally, E2injection increased hepatic expression of oestrogen receptor-αandβ. In conclusion,n-3 PUFA supplementation and E2injection had synergic hypocholesterolaemic effects by down-regulating hepatic cholesterol synthesis (n-3 PUFA and oestrogen) and up-regulating bile acid synthesis (n-3 PUFA) in ovariectomised rats. more...

Previous studies have suggested that estrogen and n-3 polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have antidepressant-like effects. The purpose of the present study was to determine the interaction between n-3 PUFAs and estrogen, and their neurotrophic mechanism in rats after the forced swimming test (FST). Rats were fed a modified American Institute of Nutrition 93G diet with 0%, 1% or 2% EPA+DHA relative to the total energy intake during 12 weeks. At 8 weeks, rats were ovariectomized and injected with either 17β-estradiol-3-benzoate (E2) or corn oil during the last 3 weeks. Both n-3 PUFA supplementation and E2 injection increased climbing and decreased immobility during the FST. Serum serotonin concentration was also increased by both n-3 PUFA and E2. N-3 PUFA and E2 decreased hippocampal expressions of interleukin (IL)-6 and tumor necrosis factor-α, and increased cAMP response element binding protein (CREB), phosphorylated CREB and brain-derived neurotrophic factor (BDNF). N-3 PUFA supplementation decreased hippocampal expression of IL-1β only in rats injected with E2. Both n-3 PUFA supplementation and E2 injection increased estrogen receptor (ER)-α in the hippocampus, but ER-β was increased only by E2 injection. Additionally, there was a significant interaction between n-3 PUFA supplementation and E2 injection on the hippocampal expression of pCREB, suggesting membrane-mediated interaction of n-3 PUFAs and E2. In conclusion, both n-3 PUFA and E2 had antidepressant-like effects by regulating serotonergic neurotransmission through BDNF and inflammatory cytokines. more...

Background Age-related loss of muscle mass and function is a major component of frailty. Nutrition supplementation with exercise is an effective strategy to decrease frailty by preventing sarcopenia, but the effect of protein alone is controversial. Objective The present study was performed to investigate a dose-dependent effect of protein supplementation on muscle mass and frailty in prefrail or frail malnourished elderly people. Design A 12-wk double-blind randomized controlled trial was conducted in elderly subjects aged 70-85 y with ≥1 of the Cardiovascular Health Study frailty criteria and a Mini Nutritional Assessment score ≤23.5 (n = 120). Participants were randomly assigned to 1 of 3 groups: 0.8, 1.2, or 1.5 g protein · kg-1 · d-1, with concealed allocation and intention-to-treat analysis. Primary outcomes were appendicular skeletal muscle mass (ASM) and skeletal muscle mass index (SMI) measured by dual-energy X-ray absorptiometry. Results After the 12-wk intervention, the 1.5-g protein · kg-1 · d-1 group had higher ASM (mean ± SD: 0.52 ± 0.64 compared with 0.08 ± 0.68 kg, P = 0.036) and SMI (ASM/weight: 0.87% ± 0.69% compared with 0.15% ± 0.89%, P = 0.039; ASM/BMI: 0.02 ± 0.03 compared with 0.00 ± 0.04, P = 0.033; ASM:fat ratio: 0.04 ± 0.11 compared with -0.02 ± 0.10, P = 0.025) than the 0.8-g protein · kg-1 · d-1 group. In addition, gait speed was improved in the 1.5-g protein · kg-1 · d-1 group compared with the 0.8-g protein · kg-1 · d-1 group (0.09 ± 0.07 compared with 0.04 ± 0.07 m/s, P = 0.039). There were no significant differences between the 1.2- and 0.8-g protein · kg-1 · d-1 groups in muscle mass and physical performance. No harmful adverse effects were observed. Conclusions The present study indicates that protein intake of 1.5 g · kg-1 · d-1 has the most beneficial effects in regard to preventing sarcopenia and frailty compared with protein intakes of 0.8 and 1.2 g · kg-1 · d-1 in prefrail or frail elderly subjects at risk of malnutrition. This trial was registered at cris.nih.go.kr as KCT0001923. more...

Background The prevalence of cholesterol gallstones is high in Western populations, while pigment gallstones are common in Asian populations. Dietary factors are suggested to be associated with gallstone risk, but their relationship with gallstone type has not been evaluated. This study investigated the association between diet and risk of cholesterol gallstone or pigment gallstone in a Korean population whose dietary pattern and type of gallstone were changed during the last 30 years. Methods Patients with cholesterol (n = 40) and pigment (n = 59) gallstones were recruited after laparoscopic cholecystectomy and were compared with those of age- and sex-matched controls without gallstones (n = 99). Dietary intakes were assessed by trained dietitians using a semi-quantitative food frequency questionnaire. Multinomial logistic regression analysis was performed to calculate odds ratios and 95% confidence intervals to examine the associations between diet and risk for type of gallstones adjusted by potential confounders. Results Patients with cholesterol gallstone consumed more lipid, animal lipid, beef, pork, and fried food than those with pigment gallstones and control, while patients with pigment gallstone consumed more carbohydrate and noodles than patients with cholesterol gallstone and control. In multinomial logistic regression analysis using control as reference group, dietary pattern with high consumption of beef, pork, and fried food was associated with risk of cholesterol gallstones, while there was no association between the risk of pigment gallstone and dietary pattern. In addition, control consumed more alcohol than patients with cholesterol and pigment gallstones. Conclusions The present study suggested consumption of fat from meat and fried foods increased the risk of cholesterol gallstone, and intake of carbohydrate from noodles increased the risk of pigment gallstone. Electronic supplementary material The online version of this article (10.1186/s41043-017-0116-y) contains supplementary material, which is available to authorized users. more...

Background Modifications of erythrocyte membrane fatty acid (FA) contents may affect cellular function or transmembrane receptors. One cross-sectional study has shown that kidney transplant (KTP) recipients have lower erythrocyte membrane oleic acid content than dialysis patients do. Therefore, we prospectively tested whether erythrocyte membrane contents of FA including oleic acid change after KTP. Methods We recruited 23 KTP recipients (September 2011 through May 2014). Blood samples were obtained immediately before KTP and 6 months after. Erythrocyte membrane FA contents were measured by gas chromatography. Results Mean age of the enrolled KTP recipients was 45.3 ± 10.9 years, and men represented 66.7% of the cases. ABO-incompatible KTPs constituted 14.3% and cadaver donors 42.9% of the cases. Steroids, mycophenolate mofetil, and tacrolimus were used as immunosuppressive treatment. There was no significant difference in dietary consumption between time points before and 6 months after KTP. Total cholesterol and low-density lipoprotein cholesterol levels were significantly higher at 6 months after KTP as compared with baseline. Erythrocyte membrane contents of polyunsaturated FA, ω-3 FA, ω-6 FA, and the ω-3 index were significantly higher, but erythrocyte membrane contents of total saturated FAs, total monounsaturated FAs, including oleic acid, total trans-FA, palmitoleic acid, and the ω-6-to-ω-3 ratio were significantly lower at 6 months after KTP. Conclusions Erythrocyte membrane FA contents significantly changed toward a more favorable cardiovascular profile after KTP. These changes in erythrocyte membrane FA contents may be related to improved renal function because of the absence of significant dietary changes. more...

Kochujang, a Korean fermented soybean-based red pepper paste, has been reported to have beneficial health effects. The aim of this study was to examine the antiobesity effects of Kochujang as a supplement in overweight/obese subjects according polymorphisms in the obesity-linked gene, peroxisome proliferator activator receptor γ (PPARγ2). Sixty overweight/obese subjects, who had body mass indexes (BMI, kg/m2) ≥23 or waist/hip ratios (WHR) ≥0.90 for males or ≥0.85 for females, were randomly assigned to either taking 32 g/day of placebo or Kochujang for 12 weeks. Before and after the intervention, anthropometric and metabolic parameters and body fat distribution (by computed tomography) were measured. After PPARγ2 C1431T polymorphism was analyzed by PCR-restriction fragment length polymorphism, the differences among the four groups (wild and mutant alleles in Kochujang and placebo groups) were determined. Between the Kochujang (n = 26) and placebo (n = 27) groups, there were no differences in body ... more...

Associations between n-3 polyunsaturated fatty acids (PUFAs), inflammation, oxidative stress and the risk of depression have been suggested. We hypothesize that erythrocyte n-3 PUFAs are inversely associated with biomarkers for inflammation and oxidative stress in Koreans with and without depression. Study participants comprised 80 cases diagnosed with depression based on the Center for Epidemiological Studies Depression Scale Korea version (CES-D-K) scores ≥25 and psychiatrist confirmation and 80 age- and sex-matched healthy controls without histories of depression. Depressed patients had lower levels of n-3 PUFAs and higher circulating levels of inducible nitric oxide synthase (iNOS), superoxide dismutase, interferon-γ, and nitrotyrosine compared to the controls. CES-D-K scores and levels of iNOS and tumor necrosis factor (TNF)-α were negatively associated with Omega-3 Index (erythrocyte levels of eicosapentaenoic acid and docosahexaenoic acid) after adjusting for confounding factors. Concentrations of iNOS, TNF-α, thiobarbituric acid reactive substances, and nitrotyrosine were negatively correlated with erythrocyte levels of n-3 PUFAs, but positively with erythrocyte levels of n-6 PUFAs. Erythrocyte levels of n-3 PUFAs were inversely associated with circulating markers of inflammation and oxidative stress in Koreans with and without depression in this case control study. Future randomized controlled trials are needed to determine whether dietary or supplemental n-3 PUFAs can reduce inflammation and oxidative stress, and reduce depressive symptoms in humans. more...

Background/Aims: The relationship between diet and non-alcoholic fatty liver disease (NAFLD) in patients with gallstone disease and in those who have a high risk for NAFLD has not been investigated. This study was conducted to investigate the association between the risk of NAFLD and dietary pattern in patients who underwent cholecystectomy. Additionally, we assessed the association between erythrocyte fatty acid composition, a marker for diet, and the risk of NAFLD. Methods: Patients (n = 139) underwent liver ultrasonography to determine the presence of NAFLD before laparoscopic cholecystectomy, reported dietary intake using food frequency questionnaire, and were assessed for blood fatty acid composition. Results: Fifty-eight patients were diagnosed with NAFLD. The risk of NAFLD was negatively associated with 2 dietary patterns: consuming whole grain and legumes and consuming fish, vegetables, and fruit. NAFLD was positively associated with the consumption of refined grain, meat, processed meat, and fried foods. Additionally, the risk of NAFLD was positively associated with erythrocyte levels of 16:0 and 18:2t, while it was negatively associated with 20:5n3, 22:5n3, and Omega-3 Index. Conclusion: The risk of NAFLD was negatively associated with a healthy dietary pattern of consuming whole grains, legumes, vegetables, fish, and fruit and with an erythrocyte level of n-3 polyunsaturated fatty acids rich in fish. more...

Our previous studies found that n-3 polyunsaturated fatty acids (PUFAs) and estrogen had synergistic antidepressant-like effects. The purpose of the present study was to investigate the hypothesis that three major n-3 PUFAs, α-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), individually had antidepressant effects combined with 17β-estradiol-3-benzoate (E) through a neurobiological pathway in ovariectomized rats. Rats were fed a modified American Institute of Nutrition-93G diet with 0% n-3 PUFAs and 1% ALA, EPA and DHA relative to total energy intake for 12 weeks and were injected with corn oil or E every 4 days during the last 3 weeks. Supplementation of EPA, DHA and E increased serum concentrations of serotonin and climbing behavior, and decreased immobility during a forced swimming test. Supplementation with EPA, DHA and E also decreased hippocampal expressions of interleukin-6 and tumor necrosis factor-α, and increased cAMP response element binding protein, brain-derived neurotrophic factor (BDNF) and estrogen receptor-α. Immunofluorescence staining consistently showed elevated expressions of BDNF. Magnetic resonance spectroscopy showed that E increased glucose and decreased glutamate, glutamine and myo-inositol concentrations regardless of n-3 PUFA supplementation. In addition, supplementation with EPA, DHA and E decreased levels of nitrite and nitrate. However, ALA had no antidepressant effect. The present study suggested that the antidepressant-like effects of EPA and DHA supplementation and E injection could be due to the regulation of serotonergic neurotransmission and inflammatory cytokines rather than due to the antioxidative system. Supplementation with n-3 PUFA and E had the additional function of modulating neurometabolites in the hippocampus. more...

Anthocyanin-rich black soybeans have been used in traditional East Asian medicine to cure diseases related to oxidative stress and carcinogens, but not obesity. Our objective was to investigate the effects of anthocyanin-rich black soybean testa extracts (BBT), Glycine max (Chongja No. 3), on obesity. In total, 63 participants defined as overweight or obese by their body mass index (BMI23) or waist circumference (WC90 cm for males,85 cm for females) were sorted into two groups: 32 receiving the trial medication (BBT, 2.5 g/d) and 31 receiving the placebo (starch, 2.5 g/d). Participants completed an 8-week, randomized, double-blinded, and placebo-controlled clinical trial. There were no significant differences between the two groups at the beginning of the trial, and both required the same safety assessments. Significant decreases in abdominal fat, described according to WC and hip circumference, and lipid profiles such as triacylglycerols (TG), low density lipoprotein cholesterol (LDLc), and non-high density lipoprotein cholesterol (non-HDLc) were observed in the BBT group at the conclusion of the clinical trial. The indicators for arteriosclerosis such as total cholesterol (TC)/HDLc and LDLc/HDLc were significantly decreased in the BBT group, but had not changed in the placebo group. With no difference between the two groups in energy-adjusted dietary intakes and physical activity, BBT was shown to strongly improve plasma lipid profiles, related to the reduction of WC (an indicator of abdominal fat) as long as high dietary fiber and low cholesterol diets were maintained. In conclusion, BBT can potentially be developed as a functional food for preventing abdominal obesity with high fiber and low cholesterol diets. more...

Inadequate calcium and vitamin D intake is a possible risk factor of osteoporosis. Our purposes were to estimate calcium and vitamin D intake in Korean women, and to determine associated risk factors for low calcium and vitamin D intake. This is a multicenter, hospital-based, and cross-sectional study on osteoporosis. In this study, 1516 women of 50 years or older were involved. Dietary calcium and vitamin D intake were evaluated using the self-reporting KCAT questionnaire. Average daily calcium intake was 662.8 ± 473.8 mg, and vitamin D intake 9.5 ± 10.7 μg. In multivariate analysis, older age (OR 1.02, 95 % CI 1.00–1.04, p = 0.001), and rural residence (OR 2.43, 95 % CI 1.34–4.43, p = 0.004) were significant risk factors for lower calcium intake, and older age (OR 1.03, 95 % CI 1.02–1.04, p < 0.001), and rural residence (OR 1.85, 95 % CI 1.10–3.11, p < 0.001) were significant risk factors for lower vitamin D intake. About 70 % of women aged 50 years or older had calcium and vitamin D intake below the recommended dietary intake. Older age and rural residence were significant risk factors for lower calcium and vitamin D intake in Korean women. more...

Background. Alterations of erythrocyte membrane fatty acid (FA) composition play important roles in cellular function because they change the membrane microenvironment, including transmembrane receptors. The erythrocyte membrane oleic acid content is higher among patients with acute coronary syndrome and also in dialysis patients. However, available data are limited concerning erythrocyte membrane FA content in kidney transplant recipients (KTP). We sought to test the hypothesis that erythrocyte membrane FA content among KTP were different from those in dialysis patients. Methods. In this cross-sectional study, we recruited 35 hemodialysis, 33 peritoneal dialysis 49 KTP, and 33 normal control subjects (CTL). Their erythrocyte membrane FA content were measured by gas chromatography. Results. The mean ages of the enrolled dialysis patients, KTP, and CTL were 56.4 10.1, 48.9 10.4, and 49.5 8.3 years, respectively. Mean kidney transplant duration was 89.8 64.8 months and mean dialysis duration, 49.0 32.6 months. The intakes of vegetable lipid and vegetable protein including total calories were significantly increased among KTP versus dialysis patients. Total cholesterol (P .001) and high density lipoprotein cholesterol (HDL; P .001) levels were significantly higher and C-reactive protein was significantly lower among KTP compared with dialysis patients. The erythrocyte membrane content of palmitoleic acid (P .001) was significantly higher but oleic acid (P .001) significantly lower in KTP compared with dialysis patients. The erythrocyte membrane contents of arachidonic acid and docosahexaenoic acid were significantly higher, and linoleic acid and the omega-6 FA to omega-3 FA ratio (P .001) significantly lower in KTP compared with dialysis patients. The erythrocyte membrane content of oleic acid was independently associated with monounsaturated fatty acid (beta 0.771, P.001), eicosapentaeonic acid (beta0.244, P.010), and HDL (beta 0.139, P .049) in KTP. Conclusions. FA contents of erythrocyte membranes were significantly different in KTP compared with dialysis patients. These differences may have been associated with improved dietary intake and immunosuppression after kidney transplantation. more...

Vitamin D deficiency, low levels of fetuin-A, and fibroblast growth factor 23 (FGF-23) are related to vascular calcification, which is associated with cardiovascular disease. We hypothesized that omega-3 fatty acid (FA), which has cardioprotective properties, modifies vitamin D status, fetuin-A, and FGF-23 levels in dialysis patients. In a randomized, open-label, controlled study, a total of 47 patients treated with dialysis for at least 1 year were randomized to treatment for 6 months with omega-3 FAs (Omacor, 3 g/d; Pronova, Sandefjord, Norway) or a control group. Levels of fetuin-A and FGF-23 were measured by enzyme-linked immunoassay, 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D were measured by radioimmunoassay. The mean age of the enrolled patients was 57.4 ± 10.4 years, and mean dialysis duration was 46.5 ± 28.1 months. Twenty-seven hemodialysis patients and 16 peritoneal dialysis patients finished this trial. After 6 months, the levels of 1,25-dihydroxyvitamin D and fetuin-A were significantly increased in the group taking the omega-3 FA supplement compared with baseline. Levels of calcium, phosphorous, parathyroid hormone, 25-hydroxyvitamin D, FGF-23, and lipid profiles were not significantly changed in the omega-3 FA-supplemented group after 6 months compared with baseline. The erythrocyte membrane contents of eicosapentaenoic acid and docosahexaenoic acid were significantly increased, and oleic acid content was significantly decreased in the omega-3 FA-supplemented group after 6 months compared with baseline. Regarding vascular calcification and cardiovascular disease, omega-3 FA supplementation may have a clinical benefit caused by activating vitamin D, increasing fetuin-A levels, and modifying erythrocyte membrane FA contents in dialysis patients. more...

Soy isoflavones have been suggested to improve bone loss and lipid profile in postmenopausal women and ovariectomized rats. In present study, we investigated the hypothesis that consumption of soybean, mung bean, cowpea and azuki bean has a beneficial effect on lipid profile which associates with bone mass in ovariectomized rats. Forty two female Sprague-Dawley rats were either sham-operated (Sham) or surgically ovariectomized (OVX). Sham and OVX groups were fed a regular AIN-93M diet, but ovariectomized rats with soybean (OS), mung bean (OM), cowpea (OC) or adzuki bean (OA) were fed AIN-93M diet replacing 35% of corn starch with powdered OS, OM, OC or OA for 10 weeks. Total- and LDL-cholesterol concentrations were significantly lower in Sham and OC groups than other OVX groups. There was significant negative association between total cholesterol concentration and bone mineral density (BMD) of tibia in only OC group. In conclusion, total-cholesterol concentration was significantly and negatively correlated with BMD in rats consumed cowpea, suggesting that the reduced cholesterol concentration may have a beneficial effect on bone mass. more...

The purpose of this study was to examine the hypothesis that the antiobesity effect of doenjang, a Korean fermented soy paste is different between the mutant and the wild-type alleles of a polymorphism upstream of the uncoupling protein-1 (UCP-1) gene in overweight subjects. In our randomized, double-blind, placebo-controlled trial, a total of 51 subjects with a body mass index of 23 kg/m(2) or greater and a waist-to-hip ratio of 0.90 or greater for men or 0.85 or greater for women were randomly assigned to take 9.9 g/d of either a placebo or doenjang for 12 weeks. The relative frequency of the mutant G allele of the UCP-1 polymorphism was 0.60 in the placebo group and 0.62 in the doenjang group. Supplementation of doenjang had no significant effect on the visceral fat area compared with that of the placebo group, but there was a significantly reduced amount of visceral fat in subjects with the G allele of UCP-1 polymorphism. Doenjang supplementation was found to significantly increase the free fatty acid concentration in subjects with both the A allele and the G allele. There was a significant association between visceral fat and age in study subjects with both the wild-type and mutant alleles of the UCP-1 gene. Doenjang supplementation significantly reduced visceral fat and increased the free fatty acid concentrations in subjects with the G allele of the UCP-1 polymorphism, which suggests that doenjang may be related to increased free fatty acid levels caused by elevated lipolysis in these subjects. more...

Objective Vascular calcification (VC) scores determined by using simple plain radiographic films are known to be associated with coronary artery disease and mortality in patients undergoing hemodialysis (HD). Omega-3 fatty acid (FA) has been shown to reduce ectopic calcifications in an animal model, and it has also been shown that erythrocyte membrane omega-3 FA content is an independent discriminator of coronary artery disease. The present study was designed to demonstrate relations between VC scores and erythrocyte membrane FA contents in patients undergoing HD. Design A cross-sectional study was carried out. Setting The study was carried out at an outpatient hemodialysis unit at Dong-A University Hospital, Busan, Republic of Korea. Patients A total of 31 patients undergoing HD were recruited. Patients with significant malnutrition, a short duration of dialysis ( Main Outcome Measures Plain radiographic films of the feet, hands, pelvis, and lateral lumbar spine were examined and VC scores were determined using previously reported methods. Erythrocyte membrane FA contents were analyzed by gas chromatography. Results The erythrocyte membrane contents of eicosapentaenoic acid and docosahexaenoic acid were not found to be related with VC on simple plain radiographic films. However, erythrocyte membrane contents of oleic acid and total monounsaturated FA (MUFA) were significantly higher in patients with significant VC scores. Furthermore, erythrocyte membrane contents of MUFA and oleic acid were found to be negatively associated with high-density lipoprotein cholesterol level and positively associated with triglyceride level. Conclusion Erythrocyte membrane contents of MUFA and oleic acid were found to be associated with VC scores determined using plain radiographs and with dyslipidemia in patients undergoing HD. more...

Increasing evidence suggests that the status of vitamin D and n-3 PUFA is associated with the risk of CVD. Major dietary sources of vitamin D include fish and fish products, which are also rich in n-3 PUFA; however, the relationship between serum 25-hydroxyvitamin D levels and tissue contents of n-3 PUFA remains unknown. The present study investigates the hypothesis that serum 25-hydroxyvitamin D and erythrocyte n-3 PUFA levels are positively correlated in patients with CVD. We recruited sixty CVD cases and matched them with sixty healthy controls based on age, sex and season during which blood was drawn for the study. As serum 25-hydroxyvitamin D levels increased, erythrocyte levels of docosapentaenoic acid, DHA, omega-3 index and total n-3 PUFA increased significantly, while erythrocyte levels of stearic acid and total SFA decreased significantly, after adjusting for age, sex, BMI and smoking. Partial correlation analysis also showed that erythrocyte n-3 PUFA levels were positively correlated (r 0·215; P = 0·021) and total SFA content was negatively correlated (r − 0·263; P = 0·004) with serum 25-hydroxyvitamin D levels. However, multiple logistic regression analysis showed that serum 25-hydroxyvitamin D levels were not significantly associated with the risk of CVD, after adjusting or not adjusting for age, sex, BMI and smoking. In conclusion, the results of our case–control study suggest that serum 25-hydroxyvitamin D levels are positively related to erythrocyte n-3 PUFA levels, but are not associated with the risk of CVD in this population. more...

Soybeans are known to protect against osteoporosis, but other legumes frequently consumed in Asia have not been studied to learn if they have a similar protective effect. This study investigated the hypothesis that consumption of soybean, mung bean, cowpea, and adzuki bean has beneficial effects on bone biomarkers in ovariectomized rats. Female Sprague-Dawley rats were either sham operated (sham; n = 7) or surgically ovariectomized and then fed a regular AIN-93M diet (OVX; n = 7) or AIN-93M containing soybean (n = 7), mung bean (n = 7), cowpea (n = 7), or adzuki beans (n = 7) for 10 weeks. No bean consumption significantly altered the body, subcutaneous fat, or uterus weight; however, consumption significantly increased the serum calcium/phosphorous ratio and decreased urinary calcium excretion compared with those of the OVX group. Serum concentration of 17β-estradiol was significantly lower in the OVX group compared with that of the sham group and was lowest in the group fed OVX diet containing soybean. Serum osteocalcin concentration was significantly higher in all OVX rats given a diet with beans compared with the same diet without, but urinary deoxypyridinoline excretion was lowest in the group fed OVX diet containing cowpea. There were no significant differences in bone mineral density or bone mineral content of the right femur, tibia, or lumbar spine or in the trabecular bone volume of the tibia among the diet groups. In conclusion, the consumption of soybean, mung bean, cowpea, and adzuki bean in OVX rats improved osteocalcin, but only those fed cowpea showed decreased bone resorption biomarker, suggesting that cowpea may have the most protective effect on bone in OVX rats. more...

Salt sensitivity is a risk factor for cardiovascular morbidity and mortality. To date, only a few genetic variations have been identified as being associated with salt sensitivity. This study aimed to estimate the prevalence of salt sensitivity in the Korean population and to identify genetic variants affecting its development. A total of 101 Korean participants consumed a low-salt diet for 7 days followed by a high-salt diet for 7 additional days. Salt sensitivity was determined by noting any significant elevation in the 24-h mean arterial blood pressure. To determine genetic variants affecting salt sensitivity, 36 single-nucleotide polymorphisms (SNPs) that were previously reported to be associated with hypertension were tested for any associations with salt sensitivity. Of the 101 subjects, 28 (27.7%) were determined to have salt sensitivity. Out of the 36 SNPs tested, four were significantly associated with salt sensitivity after adjusting for confounding factors: rs2681472 in ATPase, Ca(++) transporting, plasma membrane 1 (ATP2B1), rs7961152 in branched chain aminotransferase 1 (BCAT1), rs16998073 in fibroblast growth factor 5 (FGF5) and rs2398162 in LOC100132798. For rs3754777 in serine threonine kinase 39 (STK39) and rs1937506, associations with salt sensitivity were observed before adjusting for confounding factors. Haplotype analysis revealed that the A-C haplotype of rs3754777-rs6749447 in STK39 was more frequent in the salt-sensitive group compared with the salt-resistant group, and was associated with salt sensitivity. This study estimates the prevalence of salt sensitivity in the Korean population and demonstrates a novel association between salt sensitivity and the ATP2B1, BCAT1, FGF5, LOC100132798 and STK39 genetic variations. more...

Osteoporosis, which has become a serious public health concern, is influenced by diet, especially calcium intake. Dairy products are a good source of calcium, but plant calcium may also be important in populations that do not consume a large amount of milk. The purpose of the present study was to examine the hypothesis that calcium from vegetable sources is associated with osteoporosis risk and bone mineral density in postmenopausal Korean women with osteoporosis and age-matched controls (N = 144). The results of multivariate-adjusted regression analyses indicated that the intake of calcium, plant calcium, potassium, vitamin A, carotene, vitamin B(1), niacin, vitamin E, vitamin C, and vegetables was associated with significantly reduced risk of osteoporosis after adjusting for age, body mass index, hormone replacement therapy, and energy intake. In addition, intake of vegetables alone, as well as calcium, plant calcium, potassium, and antioxidant vitamins (vitamin C, vitamin E, β-carotene), which are abundant in vegetables, was significantly and positively associated with bone mineral density. However, in this population of low-dairy consumers, intake of calcium from meat and dairy products was not related to risk of osteoporosis and bone mineral density. Our results suggest that high dietary intake of calcium, especially plant calcium, reduces the risk of osteoporosis and increased bone mineral density in postmenopausal Korean women. Vegetables may be an important source of calcium and may also provide vitamins and minerals that exert additional beneficial effects on the bone. more...