A total of 241 studies were identified, of which 28 were included for meta-analysis. Overall standardized mean depression scores were reduced in response to fish oil supplementation as compared with placebo (standardized mean difference -0.291, 95% CI -0.463 to -0.120, p = 0.001). Subgroup analyses showed significant effects for: (1) diagnostic category (bipolar disorder and major depression showing significant improvement with omega3 LC-PUFA supplementation versus mild-to-moderate depression, chronic fatigue and non-clinical populations not showing significant improvement); (2) therapeutic as opposed to preventive intervention; (3) adjunctive treatment as opposed to monotherapy; and (4) supplement type. Symptoms of depression were not significantly reduced in 3 studies using pure DHA (p= 0.997) or in 4 studies using supplements containing greater than 50% DHA (p = 0.417), but were significantly reduced in 13 studies using supplements containing greater than 50% EPA (standardized mean difference -0.446, 95% CI -0.753 to -0.138, p = 0.005) and in 8 studies using pure ethyl-EPA (standardized mean difference -0.396, 95% CI -0.650 to -0.141, p = 0.002). The current meta-analysis provides evidence that EPA may be more efficacious than DHA in treating depression. (J Am Coll Nutr. 2009 Oct;28(5):525-42.) PMID: 20439549.

The study was a 12-week, double-blind, placebo-controlled, cross-over clinical trial of injectable methylcobalamin, after which subjects were given the option of entering a 6-month open-label trial. All subjects received 6 weeks of placebo and 6 weeks of methyl B12 at a dose of 64.5 mcg/kg every three days administered subcutaneously into the buttocks. Blood for GSH analysis and behavioral assessments were obtained at baseline, week 6, and week 12. Thirty (30) subjects completed the 12-week, double-blind study and 22 subjects completed the 6-month extension study. No statistically significant mean differences in behavior tests or in glutathione status were identified between active and placebo groups. However, 9 subjects (30%) demonstrated clinically significant improvement on the Clinical Global Impression Scale and at least two additional behavioral measures. More notably, these responders exhibited significantly increased plasma concentrations of GSH and GSH/GSSG. Although methylcobalamin was found to be ineffective overall in treating behavioral symptoms of autism, methylcobalamin may alleviate symptoms of autism in a subgroup of children. (J Altern Complement Med. 2010 May;16(5):555-60.) PMID: 20804367.

In a double-blind, randomized trial, 230 infants with HLA-conferred susceptibility to type 1 diabetes and at least one family member with type 1 diabetes were assigned to receive either a casein hydrolysate formula or a conventional, cow’smilk- based formula (control) whenever breast milk was not available during the first 6 to 8 months of life. Autoantibodies to insulin, glutamic acid decarboxylase (GAD), the insulinomaassociated 2 molecule (IA-2), zinc transporter 8, and islet-cell antibodies were analyzed during a median observation period of 10 years. The unadjusted hazard ratio for having a positive test for one or more autoantibodies was 0.54 (95% CI 0.29-0.95) in the casein hydrolysate group compared with the control group; the adjusted HR was 0.51 (95% CI 0.28-0.91). The unadjusted hazard ratio for positivity for two or more autoantibodies was 0.52 (95% CI 0.21-1.17), and the adjusted hazard ratio was 0.47 (95% CI 0.19-1.07). In the per-protocol cohort the hazard ratio for incidence type 1 diabetes with casein hydrolysate was 0.40 (95% CI, 0.11 to 1.51), incidence rate 4% versus 8%. Use of hydrolyzed whey protein in preference to other formula types may reduce risk of type 1 diabetes. (N Engl J Med. 2010 Nov 11;363(20):1900-8.) PMID: 21067382.

This study was designed to test the effects of n-3 polyunsaturated fatty acids (PUFAs) on left ventricular (LV) systolic function in chronic heart failure (HF) due to non-ischemic dilated cardiomyopathy (NICM). A total of 133 patients with NICM and minimal symptoms on standard therapy were randomized to receive n-3 PUFAs or placebo. For the first month, patients took 5 caps/d (~4250 mg combined EPA+DHA), after which they took 2 caps per day (1700 mg) for 11 months. Both groups were treated with an ACE inhibitor/angiotensin-receptor blocker, a beta blocker, and furosemide. LV function and functional capacity were assessed by echocardiography and cardiopulmonary exercise testing at baseline and at 12 months. After 12 months, the n-3 PUFAs group and the placebo group differed significantly (p <0.001) in regard to: 1) LV ejection fraction (increased by 10.4% and decreased by 5.0% respectively); 2) peak VO(2) (increased by 6.2% and decreased by 4.5% respectively); 3) exercise duration (increased by 7.5% and decreased by 4.8% respectively); and 4) mean New York Heart Association functional class (decreased from 1.88 ± 0.33 to 1.61 ± 0.49 and increased from 1.83 ± 0.38 to 2.14 ± 0.65 respectively). The hospitalization rates for heart failure were 6% in the n-3 PUFAs and 30% in the placebo group (p = 0.0002). (J Am Coll Cardiol. 2010 Dec 29.) PMID: 21215550.

Prevalence of coeliac disease was assessed among 100 autoimmune liver disease patients in Iran and compared it with the prevalence in healthy individuals. The study also sought to determine if rates of celiac disease among autoimmune liver patients had been evaluated in Western populations. Among Iranian participants in the study, elevated prevalence of coeliac disease (10-15%) was observed compared to the general population (0.1-1%). To a lesser extent, the prevalence was high in patients with autoimmune hepatitis (2-4%). In our systematic review, prevalence of coeliac disease in autoimmune hepatitis in the majority of studies was 4% or more; several studies also reported such prevalence in primary biliary cirrhosis. CONCLUSIONS: Since coeliac disease is common among patients with autoimmune liver disease, screening autoimmune liver disease patients for coeliac disease is indicated. Although the magnitude of benefit from a gluten-free diet in reversing autoimmune liver disease in patients with coeliac disease is controversial, it may reduce the risk of further complications of coeliac disease. (Dig Liver Dis. 2010 Sep;42(9):620-3.) PMID: 20236872

During stage 1, 72 Danish children aged 4 to 11 years were assigned to GFCF diet (A) or no-diet (B) groups. Participants were assessed at baseline, 8, and 12 months using the Autism Diagnostic Observation Schedule (ADOS) and the Gilliam Autism Rating Scale (GARS) to assess core autism behaviours; Vineland Adaptive Behaviour Scales (VABS) to ascertain developmental level; and Attention-Deficit Hyperactivity Disorder – IV scale (ADHD-IV) to determine inattention and hyperactivity. Based on per protocol analysis, data for 26 diet children and 29 controls were available at 12 months. At this point, there was a significant improvement in the GFCF diet group on sub-domains of ADOS, GARS and ADHD-IV measures. At this point, given the improvement seen in the treatment group (A), the control group (B) was also offered treatment. Data from18 group A and 17 group B participants were available at 24 months. Analysis based on inter- and intra-group comparisons showed evidence of sustained clinical group improvements with a possible plateau effect for diet. Further studies are required to ascertain potential best- and non-responders to intervention. (Nutr Neurosci. 2010 Apr;13(2):87-100.) PMID: 20406576

This study examined whether inositol in combination with melatonin improves oocyte quality, fertilization rate, and pregnancy rate compared to inositol alone in women undergoing in vitro fertilizaiton (IVF). Starting on the day of GnRH administration, 65 women undergoing IVF were randomized into two groups to receive either myo-inositol + folic acid + melatonin, or myo-inositol plus folic acid alone, administered continuously. The mean number of oocytes retrieved did not differ between the two groups (P=0.65). The group cotreated with melatonin had a significantly greater mean number of mature oocytes (P=0.047) and a lower mean number of immature oocytes (P=0.001). The mean number of high quality embyos was higher in the melatonin group (=0.01). Fertilization rates did not differ between the two groups, but the clinical pregnancy rate and implantation rate tended to be higher in the group cotreated with melatonin. There were a total of 22 pregnancies: 13 in the melatonin group and 9 in the control group; P=0.26). Biochemical pregnancy rate and miscarriage rate were similar in both groups. Melatonin augments the activity of myo-inositol and folic acid by improving oocyte quality and pregnancy outcome in women with a history of low oocyte quality. (Eur Rev Med Pharmacol Sci. 2010 Jun;14(6):555-61.) PMID: 20712264.

Steatohepatitis is characterized by abnormal liver lipid metabolism and altered mitochondrial function. Carnitine is an essential cofactor for mitochondrial beta oxidation of fatty acids. This study examined the effect of carnitine supplementation on liver function and peripheral blood mitochondria copy number in patients with non alcoholic fatty liver disease (NAFLD). Forty-five NAFLD patients were assigned to a carnitine group or a control group. Liver function tests and analysis of peripheral blood mitochondrial DNA were performed before and following three months of treatment. Carnitine treatment was associated with reduction of ALT, AST, and total bilirubin. In comparison, there was no change in AST, ALT, and total bilirubin associated with treatment in the control group. Peripheral mitochondrial DNA copy number was significantly increased from 158.8+/- 69.5 copies to 241.6+/-180.6 copies (p=0.025) in the carnitine group, but not in the control group. Carnitine improved liver function and mitochondrial numbers in NAFLD. (Korean J Gastroenterol. 2010 Jun;55(6):384-9.) PMID: 20571306.

The effect of vitamin B6 on inflammation was investigated in randomized controlled trial of patients with rheumatoid arthritis (RA). A total of 35 patients were randomly allocated to receive either 5 mg folic acid only, or 100 mg vitamin B6 plus 5 mg folic acid daily for 12 weeks. The following parameters were measured at baseline and after 12 weeks: Plasma pyridoxal 5’-phosphate (PLP), serum folate, inflammatory parameters (hs-CRP, ESR, IL-6, TNF-alpha), and immune parameters (WBC count, total lymphocytes, T-cells (CD3), B-cells (CD19), T-helper cells (CD4), and T-suppressor cells(CD8)). In the vitamin B6 group, plasma IL-6 and TNF-alpha levels significantly decreased at week 12. There were no significant changes with respect to immune responses in either group, except for the percentage of total lymphocytes in the vitamin B(6) group compared to baseline. Plasma IL-6 levels were significantly inversely related to plasma PLP after adjusting for confounders (P=0.01). High dose vitamin B6 suppresses pro-inflammatory cytokines IL-6 and TNF-alpha in patients with RA. (Eur J Clin Nutr. 2010 Sep;64(9):1007-13.) PMID: 20571496.

The VITATOPS-DEP study was a randomized, double-blind, placebo-controlled trial of daily folic acid (2 mg), vitamin B6 (25 mg), and vitamin B12 (0.5 mg) for 1 to 10.5 years in stroke survivors. The primary endpoint was the onset of major depression, as defined by the DSM-IV, after randomization. Secondary outcomes were the prevalence of DSM-IV major or minor depression at the end of treatment. Among 273 people who completed the final assessment after 7.1 ± 2.1 years (mean ± standard deviation) of follow up, B-vitamins were associated with a significantly lower risk of major depression compared with placebo (18.4% vs 23.3%, adjusted hazard ratio 0.48, 95% CI 0.31-0.76). There was also a trend toward a lower risk of major or minor depression at the end of the trial compared with placebo (19.1% vs 27.7%; adjusted odds ratio 0.58; 95%CI 0.31-1.09). Long-term treatment of poststroke survivors with B-vitamin supplementation may be an effective, safe, and affordable intervention to reduce the burden of poststroke depression. (Ann Neurol. 2010 Oct;68(4):503-10.) PMID: 20976769.