The Effect of L-Carnitine on Mortality Rate in Septic Patients: A Systematic Review and Meta-Analysis on Randomized Clinical Trials.

BACKGROUND: Recent clinical trial studies have reported that L-carnitine supplementation can reduce the mortality rate in patients with sepsis, but there are no definitive results in this context. The current systematic review and meta-analysis aimed to evaluate the effect of L-carnitine supplementation on 28-day and one-year mortality in septic patients. METHODS: A systematic search conducted on Pubmed, Scopus and Cochrane Library databases up to June 2019 without any language restriction. The publications were reviewed based on the Cochrane handbook and preferred reporting items for systematic reviews and meta-analyses (PRISMA). To compare the effects of L-carnitine with placebo, Risk Ratio (RR) with 95% confidence intervals (CI) were pooled according to the random effects model. RESULTS: Across five enrolled clinical trials, we found that L-carnitine supplementation reduce one-year mortality in septic patients with SOFA> 12 (RR: 0.68; 95% CI: 0.49 to 0.96; P= 0.03) but had no significant effect on reducing 28-day mortality ((RR: 0.93; 95% CI: 0.68 to 1.28; P= 0.65) compared to placebo. Finally, we observed that based on current trials, L-carnitine supplementation may not have clinically a significant effect on mortality rate. CONCLUSION: L-carnitine patients with higher SOFA score can reduce the mortality rate. However, the number of trials, study duration and using a dosage of L-carnitine are limited in this context and further large prospective trials are required to clarify the effect of L-carnitine on mortality rate in septic patients.

The Neuromodulatory Effects of ω-3 Fatty Acids and Nano-Curcumin on the COX-2/ iNOS Network in Migraines: A Clinical Trial Study from Gene Expression to Clinical Symptoms.

BACKGROUND: Migraine is a common neuroinflammatory disorder characterized by recurrent attacks of pain. Human and experimental models of migraine studies have demonstrated the role played by COX-2/ iNOS in migraine's neuroinflammatory pathogenesis. COX-2 and iNOS are closely linked and both contribute to inflammation and neurogenic pain in the central nervous system. Omega- 3 fatty acids and curcumin, an active polyphenol of turmeric, have anti-inflammatory and neuroprotective effects through several mechanisms, including the suppression of COX-2 and iNOS gene expression, as well as their serum levels. The aim of the present study is to evaluate the nutrigenomic effects of ω-3 fatty acids, nano-curcumin, and a combination of the two, on neuroinflammation and clinical symptoms in migraine patients. METHODS: This study reports the results of a clinical trial over a 2-month period, involving 74 episodic migraine patients who received ω-3 fatty acids, nano-curcumin, a combination of them, or a placebo. At the start and end of the study, the expression of COX-2/iNOS (in peripheral mononuclear blood cells isolated from patients) and COX-2/iNOS serum levels were measured, using real-time PCR and ELISA respectively. The frequency, severity and duration of pain attacks were also recorded. RESULTS: The results of the present trial showed that ω-3 fatty acids and nano-curcumin can reinforce each other's effects in the downregulation of COX-2/iNOS mRNA, as well as reduce their serum levels. In addition, the combination of ω-3 and nano-curcumin significantly reduced the frequency, severity and duration of headaches (P<0.05). CONCLUSION: These findings indicate that combination therapy of ω-3 fatty acids and nano-curcumin can be considered as a promising new approach in migraine prevention.

A Novel Combination of ω-3 Fatty Acids and Nano-Curcumin Modulates Interleukin-6 Gene Expression and High Sensitivity C-reactive Protein Serum Levels in Patients with Migraine: A Randomized Clinical Trial Study.

BACKGROUND: Migraine is a disabling neuroinflammatory condition characterized by increasing the levels of interleukin (IL)-6, a proinflammatory cytokine and C-reactive protein (CRP) which considered as a vascular inflammatory mediator, disrupting the integrity of blood-brain barrier and contributing to neurogenic inflammation, and disease progression. Curcumin and ω-3 fatty acids can exert neuroprotective effects through modulation of IL-6 gene expression and CRP levels. The aim of present study is the evaluation of combined effects of ω-3 fatty acids and nano-curcumin supplementation on IL-6 gene expression and serum level and hs-CRP levels in migraine patients. METHODS: Eighty episodic migraine patients enrolled in the trial and were divided into four groups as 1) combination of ω-3 fatty acids (2500 mg) plus nano-curcumin (80 mg), 2) ω-3 (2500 mg), 3) nanocurcumin (80 mg), and 4) the control (ω-3 and nano-curcumin placebo included oral paraffin oil) over a two-month period. At the beginning and the end of the study, the expression of IL-6 from peripheral blood mononuclear cells and IL-6 and hs-CRP serum levels were measured, using a real-time PCR and ELISA methods, respectively. RESULTS: The results showed that both of ω-3 and nano-curcumin down-regulated IL-6 mRAN and significantly decreased the serum concentration. hs-CRP serum levels significantly decrease in combination and nano-curcumin within groups (P<0.05). An additive greater reduction of IL-6 and hs-CRP was observed in the combination group suggested a possible synergetic relation. CONCLUSION: It seems that ω-3 fatty acids and curcumin supplementation can be considered a new promising target in migraine prevention.