BACKGROUND: Vitamin D serum levels and the presence and activity of rheumatic conditions have been associated. However, many studies are merely observational, and the existent randomized clinical trials were never systematically analyzed. Therefore, this study aims to provide a systematic review and meta-analysis of such a topic.

METHODS: MEDLINE, EMBASE, LILACS, COCHRANE, and CINAHL were explored to identify randomized trials that investigated clinical repercussions of vitamin D (or analogs) supplementation for at least 3 months in rheumatic diseases. Standardized clinical and/or laboratorial outcomes related to disease activity were analyzed according to each disease before and after supplementation.

RESULTS: Database searches rendered 668 results; 9 were included-5 on rheumatoid arthritis, 3 on systemic lupus erythematosus, and 1 on systemic sclerosis. Seven of the studies were meta-analyzed. After vitamin D supplementation, rheumatoid arthritis recurrence decreased; however, not significantly (risk difference = -0.10, 95% CI = -0.21, 0.00, P = .05). No statistical significance was observed regarding visual analog scale (mean difference = 2.79, 95% CI = -1.87, 7.44, P = .24) and disease activity score28 (mean difference = -0.31, 95% CI = -0.86, 0.25, P = .28). Regarding systemic lupus erythematosus, anti-dsDNA positivity was significantly reduced (risk difference = -0.10, 95% CI = -0.18, -0.03; P = .005).

CONCLUSION: Vitamin D supplementation reduced anti-dsDNA positivity on systemic lupus erythematosus and could possibly reduce rheumatoid arthritis recurrence, although novel randomized clinical trials are needed to confirm and extend the benefits of this hormone in immune-mediated rheumatic diseases.

BACKGROUND: Vitamin D serum levels and the presence and activity of rheumatic conditions have been associated. However, many studies are merely observational, and the existent randomized clinical trials were never systematically analyzed. Therefore, this study aims to provide a systematic review and meta-analysis of such a topic.

METHODS: MEDLINE, EMBASE, LILACS, COCHRANE, and CINAHL were explored to identify randomized trials that investigated clinical repercussions of vitamin D (or analogs) supplementation for at least 3 months in rheumatic diseases. Standardized clinical and/or laboratorial outcomes related to disease activity were analyzed according to each disease before and after supplementation.

RESULTS: Database searches rendered 668 results; 9 were included-5 on rheumatoid arthritis, 3 on systemic lupus erythematosus, and 1 on systemic sclerosis. Seven of the studies were meta-analyzed. After vitamin D supplementation, rheumatoid arthritis recurrence decreased; however, not significantly (risk difference = -0.10, 95% CI = -0.21, 0.00, P = .05). No statistical significance was observed regarding visual analog scale (mean difference = 2.79, 95% CI = -1.87, 7.44, P = .24) and disease activity score28 (mean difference = -0.31, 95% CI = -0.86, 0.25, P = .28). Regarding systemic lupus erythematosus, anti-dsDNA positivity was significantly reduced (risk difference = -0.10, 95% CI = -0.18, -0.03; P = .005).

CONCLUSION: Vitamin D supplementation reduced anti-dsDNA positivity on systemic lupus erythematosus and could possibly reduce rheumatoid arthritis recurrence, although novel randomized clinical trials are needed to confirm and extend the benefits of this hormone in immune-mediated rheumatic diseases.

OBJECTIVES: Cognitive dysfunction has been reported in 20-80% of SLE patients. Converging evidence has indicated the importance of vitamin D as a neuroimmunomodulator for cognitive function. In this study, we evaluated the relationship between vitamin D and cognitive dysfunction.

METHODS: Consecutive age- and gender-matched SLE patients and healthy controls (HCs) were administered Automated Neuropsychological Assessment Metrics in this cross-sectional study. The primary outcome was the total throughput score (TTS). Anxiety and depression were measured using the Hospital Anxiety and Depression Scale (HADS). Levels of 25-hydroxyvitamin D [25(OH)D3 and total 25(OH)D] were measured using Liquid Chromatography-Tandem Mass Spectrometry.

RESULTS: In total, 61 SLE patients and 61 HCs were studied. SLE patients scored significantly lower than HCs in the TTS (p = 0.004). There were no statistically significant differences in 25(OH)D3 levels, total 25(OH)D levels and total 25(OH)D deficiency between SLE patients and HCs. However, more SLE patients had 25(OH)D3 deficiency compared to HCs [12 (19.7%) versus 2 (3.3%), p = 0.003]. Deficiency of 25(OH)D3 (β = -63.667, SE = 27.456, p = 0.025), but not other vitamin D variables, independently predicted worse TTS after adjusting for age, education, gender, ethnicity, HADS-Total, duration of SLE, SELENA-SLEDAI, SLICC/ACR Damage Index and cumulative steroid dose in SLE patients. Age (β = -4.261, SE = 0.866, p<0.001) was the only predictor of TTS after adjusting for education, gender, ethnicity, HADS-Total, vitamin D levels or status in HCs.

CONCLUSIONS: Deficiency of 25(OH)D3, a potentially modifiable risk factor, independently predicted cognitive impairment in SLE patients.

OBJECTIVE: To examine in women with systemic lupus erythematosus (SLE) who participated in a clinical trial the relationship between daily dose of dehydroepiandrosterone (DHEA), serum levels of DHEA and DHEA sulfate (DHEAS), clinical effectiveness, and side effects. METHODS: Twenty-three women with mild to moderate SLE were treated with DHEA for a 6 month period. The starting dose was 50 mg/day, and monthly stepwise increases were allowed. Subjects were assessed monthly by the Systemic Lupus Erythematosus Disease Activity Index, Systemic Lupus Activity Measure (SLAM), Health Assessment Questionnaire, and other outcomes. Serum testosterone, DHEA, and DHEAS levels were obtained and side effects noted monthly. RESULTS: Statistically significant improvements were found in all lupus outcomes over 6 months. Serum DHEA and DHEAS levels correlated with the dose of DHEA. Serum DHEA and DHEAS correlated negatively with SLAM score. A second order regression analysis of serum DHEAS level versus SLAM score suggested that the optimal serum level of DHEAS was 1000 microg/dl. The most common side effect was acne. CONCLUSION: The clinical response to DHEA was not clearly dose dependent. Serum levels of DHEA and DHEAS correlated only weakly with lupus outcomes, but suggested an optimum serum DHEAS of 1000 microg/dl. Monitoring these serum levels appears to have limited clinical utility.

OBJECTIVE: To determine whether long-term therapy (up to 1 year) with the weakly androgenic adrenal steroid dehydroepiandrosterone (DHEA) is feasible and beneficial in patients with mild to moderate systemic lupus erythematosus (SLE).

METHODS: In a prospective, open label, uncontrolled longitudinal study 50 female patients (37 premenopausal, 13 postmenopausal) with mild to moderate SLE were treated with oral DHEA 50-200 mg/day. RESULTS: DHEA therapy was associated with increases in the serum levels of DHEA, DHEA sulfate, and testosterone and, for those patients who continued DHEA, with decreasing disease activity measured by SLE Disease Activity Index score (p < 0.01), patient global assessment (p < 0.01), and physician global assessment (p < 0.05), compared to baseline. Concurrent prednisone doses were reduced (p < 0.05). These improvements were sustained over the entire treatment period. Thirty-four patients (68%) completed 6 months of treatment and 21 patients (42%) completed 12 months. Mild acneiform dermatitis was the most common adverse event (54%). Pre and postmenopausal women experienced similar efficacy and adverse effects from DHEA.

CONCLUSION: DHEA was well tolerated and appeared clinically beneficial, with the benefits sustained for at least one year in those patients who maintained therapy.

OBJECTIVE: To evaluate the efficacy and tolerability of dehydroepiandrosterone (DHEA) at a dosage of 200 mg/day in adult women with active systemic lupus erythematosus (SLE). METHODS: In a multicenter randomized, double-blind, placebo-controlled trial, 120 adult women with active SLE received oral DHEA (200 mg/day; n = 61) or placebo (n = 59) for 24 weeks. The primary end point was the mean change from baseline in the Systemic Lupus Activity Measure (SLAM) score at 24 weeks of therapy. Secondary end points included time to first flare, change in SLE Disease Activity Index (SLEDAI) score, and physician’s and patient’s global assessment scores at week 24.

RESULTS: The two groups were well balanced for baseline characteristics. Mean reductions in SLAM scores from baseline were similar and were not statistically significantly different between treatment groups (DHEA -2.6 +/- 3.4 versus placebo -2.0 +/- 3.8, mean +/- SD). The number of patients with flares was decreased by 16% in the DHEA group (18.3% of DHEA-treated patients versus 33.9% of placebo-treated patients; P = 0.044, based on time to first flare). The mean change in the patient’s global assessment was statistically significant between the two groups (DHEA -5.5 versus placebo 5.4; P = 0.005). The number of patients with serious adverse events, most of which were related to SLE flare, was significantly lower in DHEA-treated patients compared with placebo-treated patients (P = 0.010). Expected hormonal effects, including increased testosterone levels and increased incidence of acne, were observed. No life-threatening reactions or serious safety issues were identified during this study.

CONCLUSION: The overall results confirm that DHEA treatment was well-tolerated, significantly reduced the number of SLE flares, and improved patient’s global assessment of disease activity

OBJECTIVE. To determine if dehydroepiandrosterone (DHEA) has clinical benefits in patients with systemic lupus erythematosus (SLE). METHODS. Ten female patients with mild to moderate SLE and various disease manifestations were given DHEA (200 mg/day orally) for 3-6 months.

The patients were given other medications as clinically indicated, and followed with respect to overall disease activity and specific outcome parameters.

RESULTS. After 3-6 months of DHEA treatment, indices for overall SLE activity including the SLEDAI (SLE Disease Activity Index) score and physician’s overall assessment were improved, and corticosteroid requirements were decreased.
Of 3 patients with significant proteinuria, 2 showed marked and 1 modest reductions in protein excretion. DHEA was well tolerated, the only frequently noted side effect being mild acneiform dermatitis.

CONCLUSION. DHEA shows promise as a new therapeutic agent for the treatment of mild to moderate SLE. Further studies of DHEA in the treatment of SLE are warranted.

Objective: This systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to determine the effect of alpha-lipoic acid (ALA) supplementation on the inflammatory markers among patients with metabolic syndrome (MetS) and related disorders.

Methods: We searched the following databases until November 2017: PubMed, MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials. Three reviewers independently assessed study eligibility, extracted data, and evaluated risk of bias of included primary studies. Statistical heterogeneity was assessed using Cochran’s Q test and I-square (I) statistic. Data were pooled by using the random-effect model and standardized mean difference (SMD) was considered as the summary effect size.

Results: Eighteen trials out of 912 potential citations were found to be eligible for our meta-analysis. The findings indicated that ALA supplementation significantly decreased(CRP) (SMD = - 1.52; 95% CI, - 2.25, - 0.80; < 0.001),-6 (IL-6) (SMD = - 1.96; 95% CI, - 2.60, - 1.32; < 0.001), and tumor necrosis factor alpha levels (TNF-α) (SMD = - 2.62; 95% CI, - 3.70, - 1.55; < 0.001) in patients diagnosed with metabolic diseases.

Conclusion: In summary, the current meta-analysis demonstrated the promising impact of ALA administration on decreasing inflammatory markers such as CRP, IL-6 and TNF-α among patients with MetS and related disorders.

BACKGROUND AND AIM: The aim of this meta-analysis was to assess effects of alpha-lipoic acid supplementation on C-reactive protein (CRP) levels in clinical trial studies.

METHODS AND RESULTS: A systematic search was carried out on clinical trial studies published in PubMed, ISI Web of Science, Cochrane Library and Scopus databases completed by manual search on reference list of eligible studies accomplished by November 4, 2017. Of a total number of 508 studies found in the first step of literature search, only 11 were included with 264 participants in supplementation groups and 287 in control groups. Estimated pooled random effects size analysis showed a significant reducing effect of alpha-lipoic acid supplementation on CRP level (-0.72 mg/l, 95% CI; -1.4, -0.04; P = 0.03) with a significant heterogeneity between the selected studies. Sub-group analysis showed that alpha-lipoic acid supplementation could significantly reduce serum CRP level when the baseline CRP level was greater than 3 mg/l (-1.02 mg/l, 95% CI: -1.3, -0.73)and when trial duration was>8 weeks (-0.99 mg/l, 95% CI: -1.29, -0.70). Results of subgroup analysis also showed that alpha lipoic acid supplementation could decrease CRP level only in non-diabetic patients (-1.02 mg/l, 95% CI: -1.31, -0.74).

CONCLUSIONS: Results of the current meta-analysis study showed that alpha-lipoic acid supplementation could significantly decrease CRP level in patients with elevated levels of this inflammatory marker.

OBJECTIVE: Vegetarian diets contain various anti-inflammatory components. We aimed to investigate the effects of vegetarianism on inflammatory biomarkers when compared with omnivores.

DESIGN: Systematic review and meta-analysis.

SETTING: Literature search was conducted in Science Direct, Proquest, MEDLINE and Google Scholar up to June 2016. Summary estimates and corresponding 95 % CI were derived via the DerSimonian and Laird method using random effects, subgroup analyses were run to find the source of heterogeneity and a fixed-effect model examined between-subgroup heterogeneity.

SUBJECTS: Studies were included if they evaluated effects of any type of vegetarianism compared with omnivores on circulating levels of inflammatory biomarkers. No restriction was made in terms of language or the date of study publications.

RESULTS: Eighteen articles were included. Pooled effect size showed no difference in high-sensitivity C-reactive protein (hs-CRP) levels in vegetarians v. omnivores (Hedges’ g=-0·15; 95 % CI -0·35, 0·05), with high heterogeneity (I 2=75·6 %, P<0·01). A subgroup analysis by minimum duration of vegetarianism showed that a minimum duration of 2 years vegetarianism was associated with lower hs-CRP levels v. omnivores (Hedges’ g=-0·29; 95 % CI -0·59, 0·01), with moderate heterogeneity (I 2=68·9 %, P<0·01). No significant effect was found in studies using a minimum duration of 6 months of vegetarianism, with low heterogeneity. Vegetarianism was associated with increased IL-6 concentrations (0·21 pg/ml; 95 % CI 0·18, 0·25), with no heterogeneity (I 2=0·0 %, P=0·60).

CONCLUSIONS: The meta-analysis provides evidence that vegetarianism is associated with lower serum concentrations of hs-CRP when individuals follow a vegetarian diet for at least 2 years. Further research is necessary to draw appropriate conclusions regarding potential associations between vegetarianism and IL-6 levels. A vegetarian diet might be a useful approach to manage inflammaging in the long term.