Association of Plasma n-3 Polyunsaturated Fatty Acid Levels and the Prevalence of Frailty in Older Adults: A Cross-Sectional Analysis of UK Biobank.

BACKGROUND: Circulating levels of n-3 polyunsaturated fatty acids (PUFAs) have been associated with frailty among Koreans (a population with a high intake of fish), but whether this association exists in Western populations with low fish intake is unknown. The present study examined the hypothesis that the prevalence of frailty was inversely associated with plasma levels of n-3 PUFAs, with the intake of oily fish, and with fish oil supplementation in older adults in the United Kingdom. METHODS: UK Biobank including 79 330 adults aged ≥65 years with dietary data, and 18 802 participants with plasma fatty acid data were used. Frailty was defined using the Cardiovascular Health Study index, plasma levels of n-3 PUFAs were measured by nuclear magnetic resonance, and intake of oily fish and/or fish oil supplements was collected via food frequency questionnaire. RESULTS: Frailty prevalence was inversely associated with n-3 PUFA levels [odds ratios (OR) per SD: 0.86, 95% confidence interval (CI) 0.79-0.94; p < .001], with oily fish intake (never vs ≥2 servings per week; OR 0.59, 95% CI 0.52-0.68, p < .001), and with the use of fish oil supplements (OR 0.72; 95% CI 0.66-0.78; p < .001) after adjusting for confounding factors. All 3 exposures were also associated with each frailty criterion, particularly low physical activity and walking pace. CONCLUSIONS: Inverse associations between plasma n-3 PUFA levels and measures of frailty suggest that higher intakes of oily fish or the use of fish oil supplements may help prevent frailty in older adults in the United Kingdom.

Synergistic antidepressant-like effect of n-3 polyunsaturated fatty acids and probiotics through the brain-gut axis in rats exposed to chronic mild stress.

N-3 polyunsaturated fatty acids (PUFA) and probiotics have antidepressant-like effects, but the underlying mechanisms are unclear. We hypothesized that n-3 PUFA combined with live and dead probiotics synergistically improves depression by modulating the hypothalamic-pituitary-adrenal (HPA) axis and serotonergic pathways through the brain-gut axis. Rats were randomly divided into seven groups (n = 8/group): nonchronic mild stress (CMS) with n-6 PUFA, CMS with n-3 PUFA, n-6 PUFA, live probiotics, dead probiotics, n-3 PUFA, and live probiotics, and n-3 PUFA and dead probiotics. Diets of n-6 and n-3 PUFA and oral supplementation of live and dead probiotics were provided for 12 weeks, and CMS was performed for the last 5 weeks. N-3 PUFA and probiotics improved depressive behaviors and modulated the brain and gut HPA axis by synergistically increasing glucocorticoid receptor expression and decreasing corticotropin-releasing factor expression and blood levels of adrenocorticotropic hormone and corticosterone. N-3 PUFA and probiotics upregulated the brain serotonergic pathway through serotonin levels and expression of brain-derived neurotrophic factor, phosphorylated cAMP response binding protein, and 5-hydroxytryptamine 1A receptor while downregulating the gut serotonergic pathway. Furthermore, n-3 PUFA and probiotics increased the abundance of Ruminococcaceae, brain and gut short chain fatty acid levels, and occludin expression while decreasing the expression of tumor necrosis factor-α, interleukin-1ß, and prostaglandin E2 and blood lipopolysaccharides levels. There was no significant difference between the live and dead probiotics. In conclusion, n-3 PUFA and probiotics had synergistic antidepressant-like effects on the HPA axis and serotonergic pathways of the brain and gut through the brain-gut axis.

Position Statement: Vitamin D Intake to Prevent Osteoporosis and Fracture in Adults.

Adequate vitamin D status is essential for bone health. New randomized controlled trials investigating the effect of vitamin D supplementation on bone health have recently been published. This position statement updates and expands on the previous 2015 position statement of the Korean Society for Bone and Mineral Research on the adequate vitamin D status for healthy older adults (age ≥ 70 years) and those at high risk of osteoporosis and fracture (adults on osteoporosis medications) to maintain serum 25-hydroxy-vitamin D (25[OH]D) levels ≥ 20 ng/mL but < 50 ng/mL. A serum 25(OH)D level of 30 ng/mL may be beneficial for those on anti-resorptives. Vitamin D can be obtained from ultraviolet light exposure and diet. To reach the target vitamin D status through intake, adults must consume at least 400 IU/day to reach 20 ng/mL and 800 to 1,000 IU/day to reach 30 ng/mL. Foods familiar to the Korean diet that are high in vitamin D content or consumed frequently enough to positively impact vitamin D status are introduced in addition to the amount required to help reach one's target vitamin D status.

Association between Omega-3 Index and Hyperglycemia Depending on Body Mass Index among Adults in the United States.

There is inconsistency regarding the association between long-chain n-3 polyunsaturated fatty acids such as eicosapentaenoic acid (EPA; 20:5n3) and docosahexaenoic acid (DHA; 22:6n3) and the risk of type 2 diabetes. The present study aimed to investigate the association between the Omega-3 Index (erythrocyte EPA + DHA) and glycemic status as a function of body mass index (BMI). Cross-sectional data from routine clinical laboratory testing with a total of 100,572 people aged over 18 years and BMI ≥ 18.5 kg/m2 were included. Of the patients, 10% were hyperglycemic (fasting plasma glucose levels ≥ 126 mg/dL) and 24.7% were of normal weight, 35.0% were overweight, and 40.3% were obese. Odds ratios (ORs) of being hyperglycemic were inversely associated with the Omega-3 Index, but weakened as BMI increased. Thus, ORs (95% CI) comparing quintile 5 with quintile 1 were 0.54 (0.44-0.66) in the normal weight group, 0.70 (0.61-0.79) in the overweight group, and 0.74 (0.67-0.81) in the obese group. Similar patterns were seen for EPA and DHA separately. The present study suggested that a low Omega-3 Index is associated with a greater risk of disordered glucose metabolism and this is independent of BMI.

Dietary PUFAs and Exercise Dynamic Actions on Endocannabinoids in Brain: Consequences for Neural Plasticity and Neuroinflammation.

The brain and peripheral nervous system provide oversight to muscle physiology and metabolism. Muscle is the largest organ in the body and critical for glucose sensitivity, prevention of diabetes, and control of obesity. The central nervous system produces endocannabinoids (eCBs) that play a role in brain neurobiology, such as inflammation and pain. Interestingly, studies in humans and rodents show that a moderate duration of exercise increases eCBs in the brain and blood and influences cannabinoid receptors. Cannabinoid actions in the nervous system have advanced our understanding of pain, well-being, and disease. Nutrition is an important aspect of brain and eCB physiology because eCBs are biosynthesized from PUFAs. The primary eCB metabolites are derived from arachidonic acid, a 20:4n-6 (ω-6) PUFA, and the n-3 (ω-3) PUFAs, EPA and DHA. The eCBs bind to cannabinoid receptors CB1 and CB2 to exert a wide range of activities, such as stimulating appetite, influencing energy metabolism, supporting the immune system, and facilitating neuroplasticity. A diet containing different essential n-6 and n-3 PUFAs will dominate the formation of specific eCBs, and subsequently their actions as ligands for CB1 and CB2. The eCBs also function as substrates for cyclooxygenase enzymes, including potential substrates for the oxylipins (OxLs), which can be proinflammatory. Together, the eCBs and OxLs act as modulators of neuroinflammation. Thus, dietary PUFAs have implications for exercise responses via synthesis of eCBs and their effects on neuroinflammation. Neurotrophins also participate in interactions between diet and the eCBs, specifically brain-derived neurotrophic factor (BDNF). BDNF supports neuroplasticity in cooperation with the endocannabinoid system (ECS). This review will describe the role of PUFAs in eCB biosynthesis, discuss the ECS and OxLs in neuroinflammation, highlight the evidence for exercise effects on eCBs, and describe eCB and BDNF actions on neuroplasticity.

N-3 PUFA ameliorated bone loss induced by postmenopausal depression following exposure to chronic mild stress and maternal separation by regulating neuronal processes.

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. 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. 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 ß2. 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. Lifetime supply of n-3 PUFA ameliorated bone loss induced by chronic stress by regulating hypothalamic-pituitary-adrenal axis activity and serotonin-CREB signaling.

Allium hookeri Extracts Improve Scopolamine-Induced Cognitive Impairment via Activation of the Cholinergic System and Anti-Neuroinflammation in Mice.

Allium hookeri (AH) is a medicinal food that has been used in Southeast Asia for various physiological activities. The objective of this study was to investigate the activation of the cholinergic system and the anti-neuroinflammation effects of AH on scopolamine-induced memory impairment in mice. Scopolamine (1 mg/kg body weight, i.p.) impaired the performance of the mice on the Y-maze test, passive avoidance test, and water maze test. However, the number of error actions was reduced in the AH groups supplemented with leaf and root extracts from AH. AH treatment improved working memory and avoidance times against electronic shock, increased step-through latency, and reduced the time to reach the escape zone in the water maze test. AH significantly improved the cholinergic system by decreasing acetylcholinesterase activity, and increasing acetylcholine concentration. The serum inflammatory cytokines (IL-1ß, IL-6, and IFN-γ) increased by scopolamine treatment were regulated by the administration of AH extracts. Overexpression of NF-κB signaling and cytokines in liver tissue due to scopolamine were controlled by administration of AH extracts. AH also significantly decreased Aß and caspase-3 expression but increased NeuN and ChAT. The results suggest that AH extracts improve cognitive effects, and the root extracts are more effective in relieving the scopolamine-induced memory impairment. They have neuroprotective effects and reduce the development of neuroinflammation.

Effect of pravastatin on erythrocyte membrane fatty acid contents in patients with chronic kidney disease.

BACKGROUND: Statin treatment has decreased the risk of cardiovascular events in patients with chronic kidney disease (CKD). Erythrocyte membrane oleic acid level is higher in patients with acute coronary syndrome. This study aimed to evaluate the effect of pravastatin 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 dyslipidemia. 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 pravastatin treatment in CKD patients with estimated glomerular filtration rate <60 mL/min/1.73 m2. 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 pravastatin is used for treating dyslipidemia in patients with CKD.

N-3 PUFA improved post-menopausal depression induced by maternal separation and chronic mild stress through serotonergic pathway in rats-effect associated with lipid mediators.

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-1ß, 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.

Association Between Erythrocyte Levels of n-3 Polyunsaturated Fatty Acids and Risk of Frailty in Community-Dwelling Older Adults: The Korean Frailty and Aging Cohort Study.

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.

N-3 PUFA Have Antidepressant-like Effects Via Improvement of the HPA-Axis and Neurotransmission in Rats Exposed to Combined Stress.

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.

N-3 PUFA improved pup separation-induced postpartum depression via serotonergic pathway regulated by miRNA.

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.

Onion Peel Extract Increases Erythrocyte Membrane n-3 Fatty Acids in Overweight and Obese Korean Subjects.

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.

Eicosapentaenoic acid and docosahexaenoic acid, but not α-linolenic acid, decreased low-density lipoprotein cholesterol synergistically with estrogen via regulation of cholesterol synthesis and clearance in ovariectomized rats.

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 ß 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.

Omega-3 fatty acid decreases oleic acid by decreasing SCD-1 expression in the liver and kidney of a cyclosporine-induced nephropathy rat model.

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.

Protein supplementation improves muscle mass and physical performance in undernourished prefrail and frail elderly subjects: a randomized, double-blind, placebo-controlled trial.

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.

EPA and DHA, but not ALA, have antidepressant effects with 17ß-estradiol injection via regulation of a neurobiological system in ovariectomized rats.

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 17ß-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.

PPARγ2 C1431T Polymorphism Interacts with the Antiobesogenic Effects of Kochujang, a Korean Fermented, Soybean-Based Red Pepper Paste, in Overweight/Obese Subjects: A 12-Week, Double-Blind Randomized Clinical Trial.

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 composition, insulin resistance, or antioxidant biomarkers before and after intervention. Compared to placebo, Kochujang significantly decreased plasma triglyceride (TG), TG/high-density lipoprotein (HDL), and dietary intakes of protein, sodium, and potassium after age, sex, and BMI were adjusted. The beneficial effects of Kochujang on lowering of TG and TG/HDL were weakened in subjects with the PPARγ2 mutant T allele with increasing subcutaneous fat area. However, the interaction between Kochujang and the PPARγ2 T allele improved insulin sensitivity. The obesogenic variables affected by the T mutant allele of PPARγ2 C1431T SNP were different in overweight/obese subjects in response to Kochujang.

Association of Blood Fatty Acid Composition and Dietary Pattern with the Risk of Non-Alcoholic Fatty Liver Disease in Patients Who Underwent Cholecystectomy.

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.

Synergistic attenuation of ovariectomy-induced bone loss by combined use of fish oil and 17ß-oestradiol.

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 17ß-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-1ß. 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-1ß 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-1ß.