Effect of Crocus sativus (Saffron) Intake on Top of Standard Treatment, on Disease Outcomes and Comorbidities in Patients with Rheumatic Diseases: Synthesis without Meta-Analysis (SWiM) and Level of Adherence to the CONSORT Statement for Randomized Controlled Trials Delivering Herbal Medicine Interventions.

Rheumatic diseases (RDs) are often complicated by chronic symptoms and frequent side-effects associated with their treatment. Saffron, a spice derived from the Crocus sativus L. flower, is a popular complementary and alternative medicine among patients with RDs. The present systematic review aimed to summarize the available evidence regarding the efficacy of supplementation with saffron on disease outcomes and comorbidities in patients with RD diagnoses. PubMed, CENTRAL, clinicaltrials.gov and the grey literature were searched until October 2021, and relevant randomized controlled trials (RCTs) were screened for eligibility using Rayyan. Risk of bias was assessed using the Cochrane's Risk of Bias-2.0 (RoB) tool. A synthesis without meta-analysis (SWiM) was performed by vote counting and an effect direction plot was created. Out of 125 reports, seven fulfilled the eligibility criteria belonging to five RCTs and were included in the SWiM. The RCTs involved patients with rheumatoid arthritis, osteoarthritis and fibromyalgia, and evaluated outcomes related to pain, disease activity, depression, immune response, inflammation, oxidative stress, health, fatigue and functional ability. The majority of trials demonstrated some concerns regarding overall bias. Moreover, the majority of trialists failed to adhere to the formula elaborations suggested by the CONSORT statement for RCTs incorporating herbal medicine interventions. Standardization of herbal medicine confirms its identity, purity and quality; however, the majority of trials failed to adhere to these guidelines. Due to the great heterogeneity and the lack of important information regarding the standardization and content of herbal interventions, it appears that the evidence is not enough to secure a direction of effect for any of the examined outcomes.

Peeking into the future: Transdermal patches for the delivery of micronutrient supplements.

Adhesive transdermal delivery devices (patches) are the latest advancement in the delivery of micronutrients. A common challenge in this mode of delivery includes surpassing the physical barrier of the skin, while the use of microneedle (MN) arrays, or pretreatment of the skin with MNs can be used for a more successful outcome. Limited evidence from human non-randomized trials point to a sub-optimal delivery of iron through skin patches, although no MNs were used in those trials. Moreover, the use of patches proved inefficient in reducing the prevalence of micronutrient deficiencies in post-bariatric surgery patients. The delivery of minerals was tested in animals using reservoir-type patches, gel/foam patches, MNs and iontophoresis. Results from these studies indicate a possible interplay between the dietary manipulation of mineral intake and the trandermal delivery through patches, as reduced, or regular dietary intake seems to increase absorption of the delivered mineral. Moreover, intervention duration could be an additional factor affecting absorption. Possible adverse events from animal studies include redness or decolorization of skin. In vitro and ex vivo studies revealed an increase in vitamin K, vitamin D and iron delivery, however a variety of methodological discrepancies are apparent in these studies, including the models used, the length of the MNs, the duration of application, temperature control and total micronutrient load in the patches. Data indicate that pre-treating the skin with MNs might enhance delivery; however, a source of variability in the observed effectiveness might include the different molecular weights of the nutrients used, skin factors, the ideal tip radius and MN wall thickness. Non-human studies indicate a potential benefit in combining MN with iontophoresis. Presently, the transdermal delivery seems promising with regard to nutritional supplementation, however limited evidence exists for its efficacy in humans. Future research should aim to control for both intervention duration, possible deficiency status and for the dietary intake of participants.

Effectiveness of oral vitamin D supplementation in lessening disease severity among patients with psoriasis: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: Many treatment modalities have been used to manage psoriasis; however, there is, to our knowledge, no pooled estimate for the effectiveness of oral vitamin D supplements in patients with psoriasis. Hence, the aim of the present study was to systematically review and meta-analyze the efficacy of oral vitamin D supplementation in lessening disease severity of patients with psoriasis. METHODS: A systematic literature review was performed on the electronic databases PubMed, Embase, and Cochrane Central and the gray literature for retrieving randomized controlled trials comparing oral vitamin D supplementation with placebo. The primary outcome was the change of Psoriasis Area and Severity Index (PASI) score. We used the random effects model for synthesizing the evidence. RESULTS: Of the total 5018 search results, 4 studies were included in the qualitative and 3 studies in quantitative analysis. Vitamin D supplementation was effective in ameliorating the PASI score after 6 mo of intervention (mean difference [MD] = -0.92, 95% confidence interval [CI] = -1.72 to -0.11). However, after the Hartung-Knapp adjustment, the results became non-significant (MD = -0.92, 95% CI = -2.21 to 0.38). CONCLUSIONS: A favorable effect of oral vitamin D supplementation in patients with psoriasis could not be verified. More randomized controlled trials with larger sample sizes are needed to produce robust results.

Let Food Be Thy Medicine: The Case of The Mediterranean Diet in Rheumatoid Arthritis.

The role of diet in rheumatoid arthritis (RA) has been the topic of extensive research. The present review aimed to present and appraise the studies assessing adherence to the Mediterranean diet (MD) and the primary/secondary prevention of rheumatoid arthritis. Based on the available studies, the evidence appears low and adherence to the MD does not appear to affect RA indices.

Autologous Whole-blood Injections in Chronic Spontaneous Urticaria: Assessment of Efficacy Biomarkers.

No abstract.

Curcumin mediates attenuation of pro-inflammatory interferon γ and interleukin 17 cytokine responses in psoriatic disease, strengthening its role as a dietary immunosuppressant.

Curcumin exhibits anti-inflammatory properties and has been used for centuries in traditional medicine and as dietary supplement. Data from clinical trials has strengthened the notion that curcumin may exert an anti-inflammatory and immunosuppressive role in patients with psoriatic disease, but its mode of action has remained elusive. We hypothesized that curcumin could inhibit interferon (IFN)-γ and interleukin (IL)-17 production in peripheral blood mononuclear cells from patients with psoriasis and psoriatic arthritis (PsA). To this end, we assessed the in vitro effect of curcumin on IFN-γ production by cluster differentiation (CD)4(+), CD8(+) T cells, natural killer (NK) and NKT cells and on IL-17 production by CD4(+) T cells from 34 patients with psoriatic disease (22 with psoriasis and 12 with PsA); 15 normal subjects were included as healthy controls. We also assessed the effect of curcumin on signal transducer and activator of transcription (STAT)3 activation. Curcumin significantly decreased, in a dose dependent manner, IFNγ-production by CD4(+) and CD8(+) T cells, and NK and NKT cells in patients with psoriatic disease and healthy controls. It also decreased IL-17 production by CD4(+) T cells (Th17). At the molecular level, curcumin increased STAT3 serine 727 phosphorylation intensity and p-STAT3(+) CD4(+) T cells in patients with PsA and psoriasis. In conclusion, curcumin in vitro inhibits pro-inflammatory IFN-γ and IL-17 production in psoriatic disease, and this may strengthen its role as a dietary immunosuppressant in patients with this disease.

Effectiveness of Autologous Whole-Blood Injections in Patients with Refractory Chronic Spontaneous Urticaria.

BACKGROUND: Nonsedating antihistamines are the treatment of choice for chronic spontaneous urticaria (CSU), while omalizumab and immunosuppressants have also been approved as an add-on treatment. Autologous whole-blood injection (AWBI) has been used in previous studies with ambiguous results. The aim of our study was to evaluate changes in the Urticaria Activity Score (UAS7), Dermatology Life Quality Index (DLQI), and Chronic Urticaria Quality of Life (CU-Q2oL) score, and also the association of serologic markers with disease severity measures after AWBI. METHODS: In this observational study, AWBIs were performed (8 courses on a weekly basis) in adults with refractory CSU, who refused an add-on treatment with either omalizumab or immunosuppressants. UAS7, DLQI, and CU-Q2oL questionnaires and serum concentrations of total IgE, C-reactive protein (CRP), and D-dimer were evaluated before and after the intervention. RESULTS: Nineteen patients (12 females; mean age 54 ± 20.8 years) completed the protocol. Following AWBI, significant improvements in the UAS7 (34.26 ± 8.04 vs. 12.52 ± 10.83, p < 0.001), DLQI (11.63 ± 5.51 vs. 3.47 ± 2.85, p < 0.001), and CU-Q2oL score (32.97 ± 18.71 vs. 10.94 ± 7.71, p < 0.001) were recorded. A negative correlation between the baseline D-dimer levels and UAS7 and DLQI variations (p = 0.002 and p = 0.001, respectively) was noted. D-dimer levels ≥292 ng/mL have been associated with poor responsiveness (sensitivity 75%; specificity 83.3%). No correlation with either total immunoglobulin E or CRP levels was observed. CONCLUSION: AWBI appears to be a safe, alternative, add-on therapeutic option in refractory CSU, particularly in patients with low plasma levels of D-dimer.