Vasorelaxant Effect of Trachelospermi caulis Extract on Rat Mesenteric Resistance Arteries.

BACKGROUND: Trachelospermi caulis (T. caulis) has been used as a traditional herbal medicine in Asian countries. Although it is well known that T. caulis has beneficial effects, no sufficient research data are available on the cardiovascular effect of T. caulis. We investigated whether T. caulis extract has vascular effects in rat resistance arteries in this study. METHODS: To examine whether T. caulis extract affects vascular reactivity, we measured isometric tension of rat mesenteric resistance arteries using a multi-wire myograph system. T. caulis extract was administered after arteries were pre-contracted with high K+ (70 mM) or phenylephrine (5 µM). Vanillin, a single active component of T. caulis, was used to treat mesenteric arteries. RESULTS: T. caulis extract caused vascular relaxation in a concentration-dependent manner, which was endothelium-independent. To further identify the mechanism, we incubated the arteries in Ca2+-free solution containing high K+, followed by a cumulative administration of CaCl2 (0.01-2.0 mM) with or without T. caulis extract (250 µg/mL). The treatment of T. caulis extract decreased contractile responses induced by the addition of Ca2+, which suggested that the extracellular Ca2+ influx was inhibited by the T. caulis extract. Moreover, an active compound of T. caulis extract, vanillin, also induced vasodilation in mesenteric resistance arteries. CONCLUSION: T. caulis extract and its active compound, vanillin, concentration-dependently induced vascular relaxation in mesenteric resistance arteries. These results suggest that the administration of T. caulis extract could help decrease blood pressure.

Vasodilatory Effect of Alpinia officinarum Extract in Rat Mesenteric Arteries.

BACKGROUND: Alpinia officinarum (A. officinarum) is known to exhibit a beneficial effect for anti-inflammatory, anti-oxidant, and anti-hyperlipidemic effects. However, no sufficient research data are available on the cardiovascular effect of A. officinarum. Thus, in this study, we investigate whether A. officinarum extract has direct effects on vascular reactivity. METHODS: To examine whether A. officinarum extract affects vascular functionality, we measured isometric tension in rat mesenteric resistance arteries using a wire myograph. After arteries were pre-contracted with high-K+ (70 mM), phenylephrine (5 µM), or U46619 (1 µM), A. officinarum extract was treated. RESULTS: A. officinarum extract induced vasodilation in a concentration-dependent manner, and this effect was endothelium independent. To further investigate the mechanism, we incubated arteries in a Ca2+-free and high-K+ solution, followed by the cumulative addition of CaCl2 (0.01-2.5 mM) with or without A. officinarum extract (30 µg/mL). Pre-treatment of A. officinarum extract reduced the contractile responses induced by cumulative administration of Ca2+, which suggests that extracellular Ca2+ influx was inhibited by the treatment of A. officinarum extract. These results were associated with a reduction in phosphorylated MLC20 in VSMCs treated with A. officinarum extract. Furthermore, eucalyptol, an active compound of A. officinarum extract, had a similar effect as A. officinarum extract, which causes vasodilation in mesenteric resistance arteries. CONCLUSION: A. officinarum extract and its active compound eucalyptol induce concentration-dependent vasodilation in mesenteric resistance arteries. These results suggest that administration of A. officinarum extract could exert beneficial effects to treat high blood pressure.

Vasodilatory Effect of Phellinus linteus Extract in Rat Mesenteric Arteries.

Phellinus linteus is a well-known medicinal mushroom that is widely used in Asian countries. In several experimental models, Phellinus linteus extracts were reported to have various biological effects, including anti-inflammatory, anti-cancer, hepatoprotective, anti-diabetic, neuroprotective, and anti-angiogenic activity. In the present study, several bioactive compounds, including palmitic acid ethyl ester and linoleic acid, were identified in Phellinus linteus. The intermediate-conductance calcium-activated potassium channel (IKCa) plays an important role in the regulation of the vascular smooth muscle cells' (VSMCs) contraction and relaxation. The activation of the IKCa channel causes the hyperpolarization and relaxation of VSMCs. To examine whether Phellinus linteus extract causes vasodilation in the mesenteric arteries of rats, we measured the isometric tension using a wire myograph. After the arteries were pre-contracted with U46619 (a thromboxane analogue, 1 µM), Phellinus linteus extract was administered. The Phellinus linteus extract induced vasodilation in a dose-dependent manner, which was independent of the endothelium. To further investigate the mechanism, we used the non-selective K+ channel blocker tetraethylammonium (TEA). TEA significantly abolished Phellinus linteus extract-induced vasodilation. Thus, we tested three different types of K+ channel blockers: iberiotoxin (BKca channel blocker), apamin (SKca channel blocker), and charybdotoxin (IKca channel blocker). Charybdotoxin significantly inhibited Phellinus linteus extract-induced relaxation, while there was no effect from apamin and iberiotoxin. Membrane potential was measured using the voltage-sensitive dye bis-(1,3-dibutylbarbituric acid)-trimethine oxonol (DiBAC4(3)) in the primary isolated vascular smooth muscle cells (VSMCs). We found that the Phellinus linteus extract induced hyperpolarization of VSMCs, which is associated with a reduced phosphorylation level of 20 KDa myosin light chain (MLC20).

Efficacy and safety of biological agents in patients with giant cell arteritis: A meta-analysis of randomized trials.

OBJECTIVE: This study assessed the efficacy and safety of biological agents in patients with giant cell arteritis (GCA). MATERIALS AND METHODS: A meta-analysis of 6 randomized clinical trials (RCTs) (260 patients and 193 controls) to examine the efficacy and safety of tocilizumab, tumor necrosis factor (TNF) inhibitors, and abatacept relative to that of placebo in GCA patients was performed. RESULTS: The remission rate was significantly higher for tocilizumab-treated patients than that for placebo-treated controls (odds ratio (OR) 7.009, 95% confidence interval (CI) 3.854 - 12.75, p < 0.001). In addition, the relapse rate was significantly lower for the tocilizumab group than that for the placebo group (OR 0.222, 95% CI 0.129 - 0.381, p < 0.001). Further, no significant difference in remission and relapse was observed between groups treated with TNF inhibitors, abatacept, and placebo. The number of serious adverse events (SAEs) was significantly lower in tocilizumab-treated patients than that in placebo-treated controls (OR 0.539, 95% CI 0.296 - 0.982, p = 0.044). However, there was no significant difference in SAEs among patients treated with TNF inhibitors, abatacept, and placebo. The infection rate was significantly higher in TNF inhibitor-treated patients than in those treated with placebo (OR 2.407, 95% CI 1.168 - 4.960, p = 0.017), while there was no significant difference in infection rate between individuals treated with tocilizumab, abatacept, and placebo. CONCLUSION: Tocilizumab was found to be more effective than placebo in GCA patients, but TNF inhibitors and abatacept were not. Further, TNF inhibitors were associated with a higher risk of infection.

Traditional Medicine (Mahuang-Tang) Improves Ovarian Dysfunction and the Regulation of Steroidogenic Genes in Letrozole-Induced PCOS Rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Mahuang-Tang (MHT) has traditionally been used in Asia to treat a variety of diseases, such as fever without sweating, joint pain, lower back pain, asthma, and gynecological conditions. Polycystic ovary syndrome (PCOS) is a kind of gynecological disease that causes amenorrhea, infertility, and menopausal and urogenital disorders that could benefit from MHT treatment. AIM OF THE STUDY: In this study, we examined the effects of MHT on ovarian hormones and steroidogenic enzymes in female PCOS rats. METHODS AND RESULTS: The PCOS rat model was induced by Letrozole, and an in vivo evaluation of whether the dietary consumption of MHT improved the PCOS-like symptoms was conducted. The luteinizing hormone (LH) level and luteinizing hormone/follicular-stimulating hormone (LH/FSH) ratio increased in PCOS rats but decreased following MHT treatment. In the PCOS rats, the reduced estrogen level was restored to that of normal controls with MHT treatment in serum. The transcription level(s) of gonadotropin receptors (Fshr and Lhr), steroid receptors (Pgr, and Esr1) and steroidogenic enzymes (Cyp19a1, Hsd3b1, Hsd17a1, and Cyp11a1) changed under the PCOS condition, and were regulated by MHT treatment in the ovaries of PCOS rats. The reproductive tissues of Letrozole-induced PCOS rats were restored into estrogenic condition from androgen environments. CONCLUSION: These results suggest that MHT ameliorates the symptoms of PCOS by improving the dysregulation of ovarian steroids and steroidogenic enzymes in PCOS rats.

N,N'-Diacetyl-p-phenylenediamine restores microglial phagocytosis and improves cognitive defects in Alzheimer's disease transgenic mice.

As a central feature of neuroinflammation, microglial dysfunction has been increasingly considered a causative factor of neurodegeneration implicating an intertwined pathology with amyloidogenic proteins. Herein, we report the smallest synthetic molecule (N,N'-diacetyl-p-phenylenediamine [DAPPD]), simply composed of a benzene ring with 2 acetamide groups at the para position, known to date as a chemical reagent that is able to promote the phagocytic aptitude of microglia and subsequently ameliorate cognitive defects. Based on our mechanistic investigations in vitro and in vivo, 1) the capability of DAPPD to restore microglial phagocytosis is responsible for diminishing the accumulation of amyloid-ß (Aß) species and significantly improving cognitive function in the brains of 2 types of Alzheimer's disease (AD) transgenic mice, and 2) the rectification of microglial function by DAPPD is a result of its ability to suppress the expression of NLRP3 inflammasome-associated proteins through its impact on the NF-κB pathway. Overall, our in vitro and in vivo investigations on efficacies and molecular-level mechanisms demonstrate the ability of DAPPD to regulate microglial function, suppress neuroinflammation, foster cerebral Aß clearance, and attenuate cognitive deficits in AD transgenic mouse models. Discovery of such antineuroinflammatory compounds signifies the potential in discovering effective therapeutic molecules against AD-associated neurodegeneration.

Curcumae Radix Extract Decreases Mammary Tumor-Derived Lung Metastasis via Suppression of C-C Chemokine Receptor Type 7 Expression.

Curcumae radix is the dry root of Curcuma longa L. (turmeric) that can be used either as a spice or traditional medicine. The aim of this study was to investigate the survival benefits and the anti-metastatic activity of curcumae radix extract (CRE) in MCF7 cells and in MMTV-PyMT transgenic mice-a mouse model of breast cancer metastasis. In vitro wound scratch assay revealed that CRE treatment inhibited cell motility and cell migration in a dose-dependent manner. To investigate the effect of CRE in breast cancer metastasis, MMTV-PyMT transgenic female virgin mice were used and randomly divided into two groups. For survival curve analysis, CRE was administered in a dose of 50 mg/kg to 8⁻20-week-old mice. Interestingly, CRE treatment significantly increased the median and prolonged survival of MMTV-PyMT mice. Furthermore, CRE treatment decreased tumor burden and inhibited cell proliferation in primary breast tumor, and also suppressed mammary tumor-derived lung metastasis. The size of the lung metastases substantially decreased in the CRE-treated group compared with the ones in the control group. Curcumae radix extract showed anti-metastatic activity through regulating the expression of metastasis markers including C-C Chemokine Receptor Type 7, Matrix Metalloproteinase 9 and the proto-oncogenes c-fos and c-jun. We demonstrated that these metastatic regulators were decreased when CCR7 expression was suppressed in MCF7 cells transfected with CCR7 siRNA. The results of this study show that curcumae radix exerts antitumor and anti-metastatic activities, and we suggest that curcumae radix might be a potential supplement for the treatment and prevention of breast cancer metastasis.

Welsh Onion Root (Allium fistulosum) Restores Ovarian Functions from Letrozole Induced-Polycystic Ovary Syndrome.

Polycystic ovarian syndrome (PCOS) is an endocrine, metabolic, and systemic disease. It is mainly characterized by hyperandrogenism, oligomenorrhea, and high levels of luteinizing hormone (LH). There is no obvious therapy for PCOS, so patients have received symptomatic therapy. Welsh onion (Allium fistulosum) is well-known in Asian countries for its usage in food ingredients and traditional medicines. It is also studied for its many effects. These include activation of immune responses, antihypertensive effects, and antioxidant effects. Using letrozole-induced PCOS rats, we focused on herbal therapy using extract of Allium fistulosum (AF; A. fistulosum) roots to improve ovarian functions. As a nonsteroidal aromatase inhibitor, letrozole blocks conversion of testosterone to estrogen and subsequently induces PCOS phenomenon. We divided six-week-old female rats into four groups, including control, letrozole, letrozole + AF extract, and temporary letrozole groups. In our study, treatment with AF extract shows a low plasma LH/FSH ratio, and reveals high estrogen levels, ovarian morphology, folliculogenesis-related genes, and aromatase expression under PCOS mimic conditions. We concluded that AF extract administration influenced aromatase production, enhanced the estrogen steroid synthesis, and consequently restored the estrogenic feedback mechanism on the pituitary-ovary system.

Coffee consumption and the risk of rheumatoid arthritis and systemic lupus erythematosus: a Mendelian randomization study.

We aimed to analyze the causal association between coffee consumption and the risk of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). We performed a two-sample Mendelian randomization (MR) analysis using the inverse-variance weighted (IVW), MR-Egger regression, and weighted median methods. We used publicly available summary statistics datasets of coffee consumption genome-wide association studies (GWASs) as an exposure variable and RA and SLE GWASs as outcomes. Four single-nucleotide polymorphisms (SNPs) from GWASs of coffee consumption were selected as instrumental variables (IVs) to improve inference: NCARD (rs16868941), POR (rs17685), CYP1A1 (rs2470893), and LAMB4 (rs382140). The IVW method showed a causal association between coffee consumption and RA (beta = 0.770, SE = 0.279, p = 0.006). MR-Egger regression revealed that directional pleiotropy was unlikely to be biasing the result (intercept = - 0.145, p = 0.451). While the MR-Egger analysis showed no causal association between coffee consumption and RA (beta = 2.744, SE = 1.712, p = 0.355), the weighted median approach demonstrated a causal association between coffee consumption and RA (beta = 0.751, SE = 0.348, p = 0.031). However, the associations based on the weighted median analyses after the Bonferroni correction were not significant (adjusted p values = 0.091). The IVW, MR-Egger analysis, and weighted median methods showed no causal association between coffee consumption and SLE risk (beta = 0.594, SE = 0.437, p = 0.209; beta = 3.100, SE = 3.632, p = 0.550; beta = 0.733, SE = 0.567, p = 0.196). MR analysis results do not support causal associations between coffee consumption and the development of RA and SLE.

Investigating the possible causal association of coffee consumption with osteoarthritis risk using a Mendelian randomization analysis.

This study examined whether coffee consumption is causally associated with osteoarthritis. A two-sample Mendelian randomization (MR) analysis using inverse-variance weighted (IVW) and weighted median estimates, and the MR-Egger regression method were performed. The publicly available summary statistical datasets of coffee consumption genome-wide association studies (GWASs) meta-analyses on coffee intake from eight Caucasian cohorts (n = 18,176), GWAS meta-analyses of predominately regular-type coffee consumers of European ancestry (n = up to 91,462), and a GWAS in 7410 patients with osteoarthritis in the arcOGEN study with 11,009 controls of European ancestry were evaluated. Four single-nucleotide polymorphisms (SNPs) from GWASs of coffee consumption as instrumental variables (IVs) to improve inference were selected. These SNPs were located at neurocalcin delta (NCALD) (rs16868941), cytochrome p450 oxidoreductase (POR) (rs17685), cytochrome p450 family 1 subfamily A member 1 (CYP1A1) (rs2470893), and neuronal cell adhesion molecule (NRCAM) (rs382140). The IVW method (beta = 0.381, SE = 0.170, p = 0.025) and the weighted median approach (beta = 0.419, SE = 0.206, p = 0.047) showed evidence to support a causal association between coffee consumption and osteoarthritis. MR-Egger regression revealed that directional pleiotropy was unlikely to be biasing the result (intercept = 0.064; p = 0.549), but showed no causal association between coffee consumption and osteoarthritis (beta = - 0.518, SE = 1.270, p = 0.723). Cochran's Q test and the funnel plot indicated no evidence of heterogeneity between IV estimates based on the individual variants. The results of MR analysis support the observation that coffee consumption is causally associated with an increased risk of osteoarthritis.

Comparison of Vitamin D Levels in Patients with and without Acne: A Case-Control Study Combined with a Randomized Controlled Trial.

BACKGROUND: Vitamin D plays an important role in the immune system, and its deficiency has been implicated in various skin diseases, including atopic dermatitis and psoriasis. Acne is a common inflammatory skin disease; however, the association with vitamin D remains unclear. OBJECTIVES: We evaluated vitamin D levels in patients with acne to determine the effect of vitamin D supplementation. METHODS: This study included 80 patients with acne and 80 healthy controls. Serum 25-hydroxyvitamin D (25(OH)D) levels were measured, and demographic data were collected. Vitamin D-deficient patients were treated with oral cholecalciferol at 1000 IU/day for 2 months. RESULTS: Deficiency in 25(OH)D was detected in 48.8% of patients with acne, but in only 22.5% of the healthy controls. The level of 25(OH)D was inversely associated with the severity of acne, and there was a significant negative correlation with inflammatory lesions. In a subsequent trial, improvement in inflammatory lesions was noted after supplementation with vitamin D in 39 acne patients with 25(OH)D deficiency. LIMITATIONS: Limitations of the study include the small number of patients in the supplementation study and the natural fluctuation of acne. CONCLUSIONS: Vitamin D deficiency was more frequent in patients with acne, and serum 25(OH)D levels were inversely correlated with acne severity, especially in patients with inflammatory lesions.

X-ray Structure and Nuclear Magnetic Resonance Analysis of the Interaction Sites of the Ga-Substituted Cyanobacterial Ferredoxin.

In chloroplasts, ferredoxin (Fd) is reduced by Photosystem I (PSI) and oxidized by Fd-NADP(+) reductase (FNR) that is involved in NADP(+) reduction. To understand the structural basis for the dynamics and efficiency of the electron transfer reaction via Fd, we complementary used X-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy. In the NMR analysis of the formed electron transfer complex with Fd, the paramagnetic effect of the [2Fe-2S] cluster of Fd prevented us from detecting the NMR signals around the cluster. To solve this problem, the paramagnetic iron-sulfur cluster was replaced with a diamagnetic metal cluster. We determined the crystal structure of the Ga-substituted Fd (GaFd) from Synechocystis sp. PCC6803 at 1.62 Šresolution and verified its functional complementation using affinity chromatography. NMR analysis of the interaction sites on GaFd with PSI (molecular mass of ∼1 MDa) and FNR from Thermosynechococcus elongatus was achieved with high-field NMR spectroscopy. With reference to the interaction sites with FNR of Anabaena sp. PCC 7119 from the published crystal data, the interaction sites of Fd with FNR and PSI in solution can be classified into two types: (1) the core hydrophobic residues in the proximity of the metal center and (2) the hydrophilic residues surrounding the core. The former sites are shared in the Fd:FNR and Fd:PSI complex, while the latter ones are target-specific and not conserved on the residual level.

Inhibitory effect of Paeonia lactiflora Pallas extract (PE) on poly (I:C)-induced immune response of epidermal keratinocytes.

Epidermal keratinocytes provide protective role against external stimuli by barrier formation. In addition, kertinocytes exerts their role as the defense cells via activation of innate immunity. Disturbance of keratinocyte functions is related with skin disorders. Psoriasis is a common skin disease related with inflammatory reaction in epidermal cells. We attempted to find therapeutics for psoriasis, and found that Paeonia lactiflora Pallas extract (PE) has an inhibitory potential on poly (I:C)-induced inflammation of keratinocytes. PE significantly inhibited poly (I:C)-induced expression of crucial psoriatic cytokines, such as IL-6, IL-8, CCL20 and TNF-α, via down-regulation of NF-κB signaling pathway in human keratinocytes. In addition, PE significantly inhibited poly (I:C)-induced inflammasome activation, in terms of IL-1ß and caspase-1 secretion. Finally, PE markedly inhibited poly (I:C)-increased NLRP3, an important component of inflammasome. These results indicate that PE has an inhibitory effect on poly (I:C)-induced inflammatory reaction of keratinocytes, suggesting that PE can be developed for the treatment of psoriasis.

Regulation of lipid production by light-emitting diodes in human sebocytes.

Light-emitting diodes (LED) have been used to treat acne vulgaris. However, the efficacy of LED on sebaceous lipid production in vitro has not been examined. This study investigated the efficacy of 415 nm blue light and 630 nm red light on lipid production in human sebocytes. When applied to human primary sebocytes, 415 nm blue light suppressed cell proliferation. Based on a lipogenesis study using Oil Red O, Nile red staining, and thin-layered chromatography, 630 nm red light strongly downregulated lipid production in sebocytes. These results suggest that 415 nm blue light and 630 nm red light influence lipid production in human sebocytes and have beneficial effects on acne by suppressing sebum production.

Coffee or tea consumption and the risk of rheumatoid arthritis: a meta-analysis.

Meta-analysis of the cohort studies revealed a trend of an association between total coffee intake and RA incidence (RR of the highest vs. the lowest group = 1.309, 95 % confidence interval [CI] = 0.967-1.771, p = 0.085). Meta-analysis of case-control studies showed a significant association between total coffee intake and RA incidence (RR = 1.201, 95 % CI =1.058-1.361, p = 0.005). There were differences in the reference groups (all categories of coffee) between the case-control meta-analysis that showed a significant association and the cohort studies where meta-analysis results were non-significant. In addition, the highest category of coffee intake varied between Heliovaara et al. cohort study from Finland where the highest category included drinking up to 13 cups per day, compared to US studies where it was very unusual to have > 4 cups coffee intake per day. Combining the data of the cohort and case-control studies showed a significant association between total coffee intake and RA incidence (RR = 1.217, 95 % CI = 1.083-1.368,p = 0.001). Meta-analysis stratified by seropositivity indicated a significant association between coffee consumption and seropositive RA risk (RR=1.309, 95 % CI=1.142-1.499, p=1.1x10-5), but not seronegative RA risk (RR=1.097, 95 % CI=0.886-1.357, p=0.396). There was no significant association between decaffeinated coffee consumption and RA incidence (RR=1.709, 95 % CI 0.786-3.715), or between caffeinated coffee consumption and RA incidence (RR=1.055, 95 % CI 0.782-1.421). [corrected].

Regulation of TREM-1 expression by 1,25-dihydroxyvitamin D3 in human monocytes/macrophages.

Triggering receptor expressed on myeloid cells-1 (TREM-1) is a recently identified cell surface receptor that is expressed mainly on monocytes and neutrophils, and acts as an amplifier of immune responses. In this study, 1,25(OH)2D3 strongly upregulated the expression of TREM-1 in human monocytes and macrophages. 1,25(OH)2D3 stimulated TREM-1 mRNA expression by augmenting transcription, and not by inhibiting mRNA degradation. The upregulated expression of TREM-1 by 1,25(OH)2D3 was dependent on the NF-κB signaling pathway and required new protein synthesis in differentiated U937 macrophages. Our results show that 1,25(OH)2D3 can affect the innate and inflammatory responses by upregulating TREM-1 expression, and suggest that 1,25(OH)2D3 may function as an enhancer of the innate immune response by upregulating TREM-1 expression, in addition to inducing the antimicrobial peptide cathelicidin.

Evaluation of vitamin D level and grip strength recovery in women with a distal radius fracture.

PURPOSE: Vitamin D is known to contribute to muscular function. The purpose of this study was to determine whether the level of vitamin D is associated with grip strength recovery in women after a distal radius fracture. METHODS: We analyzed grip strength recovery after a distal radius fracture in 70 women over age 50 years. We measured vitamin D levels and grip strength recovery, which we analyzed as a function of age, surgical care, baseline vitamin D level, vitamin D supplementation, wrist range of motion, pain level, and radiographic results at 6 months. We performed multivariate analysis to identify factors that independently predicted grip strength recovery at 6 months after injury. RESULTS: Grip strength of affected hands averaged 65% of the contralateral sides (range, 25% to 100%) at 6 months after injury. We found no significant correlation between baseline vitamin D level and grip strength recovery. However, baseline vitamin D level correlated with the grip strengths of uninjured sides. Multivariate analysis indicated that younger age, vitamin D supplementation, and greater wrist range of motion were independently associated with better grip strength recovery at 6 months after injury. CONCLUSIONS: This study demonstrated that in women with a distal radius fracture, baseline vitamin D level is not associated with grip strength recovery in the injured hand. However, baseline vitamin D level correlated with grip strength in the uninjured hand. In addition, vitamin D supplementation may help grip strength recovery in the injured hand. Further prospective, comparative studies are warranted to confirm the effect of vitamin D supplementation on grip strength recovery.

Association between vitamin D intake and the risk of rheumatoid arthritis: a meta-analysis.

The aim of this study was to summarize published results on the association between vitamin D intake and the development of rheumatoid arthritis (RA) and between serum vitamin D levels and RA activity. Evidence of a relationship between vitamin D intake and the development of RA and between serum vitamin D levels and RA activity was studied by summarizing published results using a meta-analysis approach. Three cohort studies including 215,757 participants and 874 incident cases of RA were considered in this meta-analysis, and eight studies on the association between serum vitamin D levels and RA activity involving 2,885 RA patients and 1,084 controls were included. Meta-analysis showed an association between total vitamin D intake and RA incidence (relative risk (RR) of the highest vs. the lowest group = 0.758, 95 % confidence interval (CI) 0.577-0.937, p = 0.047), without between-study heterogeneity (I(2) = 0 %, p = 0.595). Individuals in the highest group for total vitamin D intake were found to have a 24.2 % lower risk of developing RA than those in the lowest group. Subgroup meta-analysis also showed a significant association between vitamin D supplement intake and RA incidence (RR 0.764, 95 % CI 0.628-0.930, p = 0.007), without between-study heterogeneity. All studies, except for one, found that vitamin D levels are inversely associated with RA activity. One study found no correlation between vitamin D levels and disease activity among 85 RA patients, but these patients had a high incidence of vitamin D deficiency, which might have influenced the study outcome. Meta-analysis of 215,757 participants suggests that low vitamin D intake is associated with an elevated risk of RA development. Furthermore, available evidence indicates that vitamin D level is associated with RA activity.

Omega-3 polyunsaturated fatty acids and the treatment of rheumatoid arthritis: a meta-analysis.

BACKGROUND AND AIMS: We undertook this study to assess the effects of omega-3 polyunsaturated fatty acids (PUFAs) (administered at ≥2.7 g/day) for a minimum duration of 3 months on clinical outcomes in patients with rheumatoid arthritis (RA). METHODS: The authors surveyed randomized controlled trials (RCTs) that examined the effects of omega-3 PUFAs on clinical outcomes in RA patients using Medline and the Cochrane Controlled Trials Register and by performing manual searches. Meta-analysis of RCTs was performed using fixed and random effects models. Outcomes are presented as standardized mean differences (SMD). RESULTS: Ten RCTs involving 183 RA patients and 187 placebo-treated RA controls were included in this meta-analysis. The analysis showed that omega-3 PUFAs clearly reduced nonsteroidal anti-inflammatory drug (NSAID) consumption (SMD -0.518, 95% CI -0.915 to -0.121, p = 0.011) without between-study heterogeneity (I(2) = 0%). Tender joint count (SMD -0.214, 95% CI-0.489-0.062, p = 0.128), swollen joint count (SMD -0.170, 95% CI-0.454-0.114, p = 0.241), morning stiffness (SMD -0.224, 95% CI-0.955-0.212, p = 0.221), and physical function (SMD 0.264, 95% CI-0.232-0.724, p = 0.314) showed a trend to improve more in patients treated with omega-3 PUFAs than in placebo-treated controls, but they did not reach statistical significance. CONCLUSIONS: This meta-analysis suggests that the use of omega-3 PUFAs at dosages >2.7 g/day for >3 months reduces NSAID consumption by RA patients. Further studies are needed to explore the clinical and NSAID-sparing effects of omega-3 PUFAs in RA.