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European Journal of Neurology Jun 2021Peripheral neuropathy (PN) is common in patients with diseases that are in turn associated with deficiency of the B-vitamins, and vitamin treatment has shown mixed... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Peripheral neuropathy (PN) is common in patients with diseases that are in turn associated with deficiency of the B-vitamins, and vitamin treatment has shown mixed results.
METHODS
This systematic review and meta-analysis studied the association between PN/pain and B-vitamin biomarkers and investigated whether vitamin treatment can ameliorate the symptoms. PubMed and Web of Science were searched according to the study protocol.
RESULTS
A total of 46 observational and seven interventional studies were identified and included in the data synthesis. The presence of PN was associated with lowered B12 levels (pooled estimate [95% CIs] = 1.51 [1.23-1.84], n = 34, Cochran Q Test I = 43.3%, p = 0.003) and elevated methylmalonic acid (2.53 [1.39-4.60], n = 9, I = 63.8%, p = 0.005) and homocysteine (3.48 [2.01-6.04], n = 15, I = 70.6%, p < 0.001). B12 treatment (vs. the comparators) showed a non-significant association with symptom improvement (1.36 (0.66-2.79), n = 4, I = 28.9%). Treatment with B1 was associated with a significant improvement in symptoms (5.34 [1.87-15.19], n = 3, I = 64.6%, p = 0.059). Analysis of seven trials combined showed a non-significant higher odds ratio for improvement under treatment with the B-vitamins (2.58 [0.98-6.79], I = 80.0%, p < 0.001).
CONCLUSIONS
PN is associated with lowered plasma vitamin B12 and elevated methylmalonic acid and homocysteine. Overall, interventional studies have suggested that B-vitamins could improve symptoms of PN. Available trials have limitations and generally did not investigate vitamin status prior to treatment. Well-designed studies, especially in non-diabetes PN, are needed. This meta-analysis is registered at PROSPERO (ID: CRD42020144917).
Topics: Dietary Supplements; Folic Acid; Homocysteine; Humans; Peripheral Nervous System Diseases; Vitamin B 12; Vitamin B Complex
PubMed: 33619867
DOI: 10.1111/ene.14786 -
Pharmacopsychiatry May 2022Partial response to pharmacotherapy is common in major depressive disorder (MDD) and many patients require alternative pharmacotherapy or augmentation, including... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Partial response to pharmacotherapy is common in major depressive disorder (MDD) and many patients require alternative pharmacotherapy or augmentation, including adjunctive L-methylfolate. Given that L-methylfolate augmentation is rarely included in major clinical practice guidelines, we sought to systematically review evidence for L-methylfolate augmentation in adults with MDD and to examine its efficacy meta-analytically.
METHODS
We systematically searched PubMed for articles up to December 31, 2020, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. Included studies were published in peer-reviewed, English-language journals and examined L-methylfolate adjunctive therapy in depressive disorders or its effect on antidepressant response. A fixed- and random-effects meta-analysis and risk of bias assessment using the Cochrane Risk of Bias Tool were conducted.
RESULTS
Qualitative assessment of nine articles (N=6,707 patients) suggests that adjunctive L-methylfolate improved antidepressant response. In the meta-analysis of categorical Hamilton Rating Scale for Depression-17 response, (three studies, 483) adjunctive L-methylfolate was associated with a small effect versus antidepressant monotherapy (relative risk: 1.25, 95% confidence interval [CI]=1.08 to 1.46, 0.004). A meta-analysis of four studies (507) using a continuous measure of depressive symptoms showed a similar effect of adjunctive L-methylfolate (standardized mean difference=- 0.38, 95% CI=- 0.59 to-0.17, 0.0003).
CONCLUSION
Adjunctive L-methylfolate may have modest efficacy in antidepressant-treated adults with MDD.
Topics: Adult; Antidepressive Agents; Depressive Disorder, Major; Humans; Tetrahydrofolates
PubMed: 34794190
DOI: 10.1055/a-1681-2047 -
Journal of the American College of... Dec 2022Healthy dietary patterns are rich in micronutrients, but their influence on cardiovascular disease (CVD) risks has not been systematically quantified.
BACKGROUND
Healthy dietary patterns are rich in micronutrients, but their influence on cardiovascular disease (CVD) risks has not been systematically quantified.
OBJECTIVES
The goal of this study was to provide a comprehensive and most up-to-date evidence-based map that systematically quantifies the impact of micronutrients on CVD outcomes.
METHODS
This study comprised a systematic review and meta-analysis of randomized controlled intervention trials of micronutrients on CVD risk factors and clinical events.
RESULTS
A total of 884 randomized controlled intervention trials evaluating 27 types of micronutrients among 883,627 participants (4,895,544 person-years) were identified. Supplementation with n-3 fatty acid, n-6 fatty acid, l-arginine, l-citrulline, folic acid, vitamin D, magnesium, zinc, α-lipoic acid, coenzyme Q10, melatonin, catechin, curcumin, flavanol, genistein, and quercetin showed moderate- to high-quality evidence for reducing CVD risk factors. Specifically, n-3 fatty acid supplementation decreased CVD mortality (relative risk [RR]: 0.93; 95% CI: 0.88-0.97), myocardial infarction (RR: 0.85; 95% CI: 0.78-0.92), and coronary heart disease events (RR: 0.86; 95% CI: 0.80-0.93). Folic acid supplementation decreased stroke risk (RR: 0.84; 95% CI: 0.72-0.97), and coenzyme Q10 supplementation decreased all-cause mortality events (RR: 0.68; 95% CI: 0.49-0.94). Vitamin C, vitamin D, vitamin E, and selenium showed no effect on CVD or type 2 diabetes risk. β-carotene supplementation increased all-cause mortality (RR: 1.10; 95% CI: 1.05-1.15), CVD mortality events (RR: 1.12; 95% CI: 1.06-1.18), and stroke risk (RR: 1.09; 95% CI: 1.01-1.17).
CONCLUSIONS
Supplementation of some but not all micronutrients may benefit cardiometabolic health. This study highlights the importance of micronutrient diversity and the balance of benefits and risks to promote and maintain cardiovascular health in diverse populations. (Antioxidant Supplementation in the Prevention and Treatment of Cardiovascular Diseases; CRD42022315165).
Topics: Humans; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Risk Factors; Heart Disease Risk Factors; Vitamin D; Folic Acid; Stroke
PubMed: 36480969
DOI: 10.1016/j.jacc.2022.09.048 -
Annals of the Rheumatic Diseases Jan 2023To update the evidence on efficacy of DMARDs (disease-modifying antirheumatic drugs) and inform the taskforce of the 2022 update of the European Alliance of Associations...
Efficacy of synthetic and biological DMARDs: a systematic literature review informing the 2022 update of the EULAR recommendations for the management of rheumatoid arthritis.
OBJECTIVES
To update the evidence on efficacy of DMARDs (disease-modifying antirheumatic drugs) and inform the taskforce of the 2022 update of the European Alliance of Associations for Rheumatology (EULAR) recommendations for management of rheumatoid arthritis (RA).
METHODS
This systematic literature review (SLR) investigated the efficacy of conventional synthetic (cs), biological (b), biosimilar and targeted synthetic (ts)DMARDs in patients with RA. Medline, EMBASE, Cochrane CENTRAL and Web of Science were used to identify all relevant articles published since the previous update in 2019 to 14 January 2022.
RESULTS
Of 8969 search results, 169 articles were selected for detailed review and 47 were finally included. Trials investigated the efficacy of csDMARDs, bDMARDs and tsDMARDs, DMARD switching, tapering and trials investigating different treatment strategies. The compounds investigated were csDMARDs (methotrexate (MTX), leflunomide, sulfasalazine, hydroxychloroquine), bDMARDs (abatacept, adalimumab, certolizumab-pegol, denosumab, etanercept, infliximab, levilimab, olokizumab, opineracept, rituximab, sarilumab, tocilizumab) and tsDMARDs (baricitinib, filgotinib, tofacitinib, upadacitinib). The efficacy of csDMARDs+ short-term glucocorticoids in early RA was confirmed and similar to bDMARD+MTX combination therapy. Interleukin-6 pathway inhibition was effective in trials on olokizumab and levilimab. Janus kinase inhibitor (JAKi) was efficacious in different patient populations. After insufficient response to JAKi, patients could respond to TNFi treatment. Tapering of DMARDs was feasible for a proportion of patients, who were able to taper therapy while remaining in low disease activity or remission.
CONCLUSION
The results of this SLR, together with one SLR on safety of DMARD and one on glucocorticoids, informed the taskforce of the 2022 update of the EULAR recommendations for pharmacological management of RA.
Topics: Humans; Glucocorticoids; Rheumatology; Biological Products; Antirheumatic Agents; Arthritis, Rheumatoid; Methotrexate; Biosimilar Pharmaceuticals; Janus Kinase Inhibitors
PubMed: 36368906
DOI: 10.1136/ard-2022-223365 -
Cells Aug 2021Folic acid has been identified to be integral in rapid tissue growth and cell division during fetal development. Different studies indicate folic acid's importance in...
Folic acid has been identified to be integral in rapid tissue growth and cell division during fetal development. Different studies indicate folic acid's importance in improving childhood behavioral outcomes and underline its role as a modifiable risk factor for autism spectrum disorders. The aim of this systematic review is to both elucidate the potential role of folic acid in autism spectrum disorders and to investigate the mechanisms involved. Studies have pointed out a potential beneficial effect of prenatal folic acid maternal supplementation (600 µg) on the risk of autism spectrum disorder onset, but opposite results have been reported as well. Folic acid and/or folinic acid supplementation in autism spectrum disorder diagnosed children has led to improvements, both in some neurologic and behavioral symptoms and in the concentration of one-carbon metabolites. Several authors report an increased frequency of serum auto-antibodies against folate receptor alpha (FRAA) in autism spectrum disorder children. Furthermore, methylene tetrahydrofolate reductase (MTHFR) polymorphisms showed a significant influence on ASD risk. More clinical trials, with a clear study design, with larger sample sizes and longer observation periods are necessary to be carried out to better evaluate the potential protective role of folic acid in autism spectrum disorder risk.
Topics: Autism Spectrum Disorder; Autoantibodies; Dietary Supplements; Folate Receptor 1; Folic Acid; Humans; Methylenetetrahydrofolate Reductase (NADPH2); Polymorphism, Single Nucleotide; Risk Factors
PubMed: 34440744
DOI: 10.3390/cells10081976 -
Nutrition Reviews Mar 2022Elevation of homocysteine (Hcy) levels is well-established as a risk factor for dementia, yet controversy exists regarding whether B-vitamin-mediated reduction of... (Meta-Analysis)
Meta-Analysis
CONTEXT
Elevation of homocysteine (Hcy) levels is well-established as a risk factor for dementia, yet controversy exists regarding whether B-vitamin-mediated reduction of homocysteine levels can benefit cognitive function.
OBJECTIVE
To investigate whether B vitamin supplementation can reduce the risk of cognitive decline and incident dementia.
DATA SOURCES
The PubMed, EMBASE, Cochrane Library, and Web of Science were systematically searched for articles published from the inception dates to March 1, 2020. Randomized controlled trials (RCT) were included if B vitamins were supplied to investigate their effect on the rate of cognitive decline. Cohort studies investigating dietary intake of B vitamins and the risk of incident dementia were eligible. Cross-sectional studies comparing differences in levels of B vitamins and Hcy were included.
DATA EXTRACTION
Two reviewers independently performed data extraction and assessed the study quality.
DATA ANALYSIS
Random-effect or fixed-effect models, depending on the degree of heterogeneity, were performed to calculate mean differences (MDs), hazard ratios (HRs), and odds ratios (ORs).
RESULTS
A total of 95 studies with 46175 participants (25 RCTs, 20 cohort studies, and 50 cross-sectional studies) were included in this meta-analysis. This meta-analysis supports that B vitamins can benefit cognitive function as measured by Mini-Mental State Examination score changes (6155 participants; MD, 0.14, 95%CI 0.04 to 0.23), and this result was also significant in studies where placebo groups developed cognitive decline (4211 participants; MD, 0.16, 95%CI 0.05 to 0.26), suggesting that B vitamins slow cognitive decline. For the > 12 months interventional period stratum, B vitamin supplementation decreased cognitive decline (3814 participants; MD, 0.15, 95%CI 0.05 to 0.26) compared to placebo; no such outcome was detected for the shorter interventional stratum (806 participants; MD, 0.18, 95%CI -0.25 to 0.61). In the non-dementia population, B vitamin supplementation slowed cognitive decline (3431 participants; MD, 0.15, 95%CI 0.04 to 0.25) compared to placebo; this outcome was not found for the dementia population (642 participants; MD, 0.20, 95%CI -0.35 to 0.75). Lower folate levels (but not B12 or B6 deficiency) and higher Hcy levels were significantly associated with higher risks of dementia (folate: 6654 participants; OR, 1.76, 95%CI 1.24 to 2.50; Hcy: 12665 participants; OR, 2.09, 95%CI 1.60 to 2.74) and cognitive decline (folate: 4336 participants; OR, 1.26, 95%CI 1.02 to 1.55; Hcy: 6149 participants; OR, 1.19, 95%CI 1.05 to 1.34). Among the population without dementia aged 50 years and above, the risk of incident dementia was significantly decreased among individuals with higher intake of folate (13529 participants; HR, 0.61, 95%CI 0.47 to 0.78), whereas higher intake of B12 or B6 was not associated with lower dementia risk.
CONCLUSIONS
This meta-analysis suggests that B vitamin supplementation is associated with slowing of cognitive decline, especially in populations who received early intervention and intervention of long duration; the study also indicates that higher intake of dietary folate, but not B12 or B6, is associated with a reduced risk of incident dementia in non-dementia aged population. Given the prevalence of dementia cases in many countries with aging populations, public health policies should be introduced to ensure that subgroups of the population at risk have an adequate B vitamin status.
Topics: Aged; Cognition; Cognitive Dysfunction; Dementia; Dietary Supplements; Folic Acid; Humans; Middle Aged; Vitamin B 12; Vitamin B Complex
PubMed: 34432056
DOI: 10.1093/nutrit/nuab057 -
Effect of Vitamin B2 supplementation on migraine prophylaxis: a systematic review and meta-analysis.Nutritional Neuroscience Sep 2022Migraine is a common disease worldwide and migraine prevention is primarily currently based on pharmaceuticals. The mechanism of Vitamin B2 may positively contribute to... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Migraine is a common disease worldwide and migraine prevention is primarily currently based on pharmaceuticals. The mechanism of Vitamin B2 may positively contribute to migraine. This systematic review and meta-analysis aimed to evaluate the impact of Vitamin B2 supplementation on the days, duration, frequency, and pain score of the migraine attack.
METHODS
: The PRISMA guideline was used for the studying process. Five electronic databases, PubMed, Embase, Cochrane, CINAHL, and CEPS were searched from 1990 to March 2019. The search terms were Vitamin B2, migraine, and prophylactic. A meta-analysis was performed using Comprehensive Meta-Analysis (CMA) version.
RESULTS
: Nine articles were included in systemic review and finally meta-analysis. Eight randomized controlled trials and one controlled clinical trial with 673 subjects were analyzed using meta-analysis. Vitamin B2 supplementation significantly decreased migraine days (= .005, = 89%), duration (= .003, = 0), frequency (= .001, = 65%), and pain score (= .015, = 84%).
CONCLUSIONS
A pooled analysis of available randomized controlled clinical trials demonstrated that Vitamin B2 400 mg/day for three months supplementation had significant effect on days, duration, frequency, and pain score of migraine attacks.
Topics: Dietary Supplements; Humans; Migraine Disorders; Pain; Randomized Controlled Trials as Topic; Riboflavin
PubMed: 33779525
DOI: 10.1080/1028415X.2021.1904542 -
The American Journal of Clinical... Dec 2022Circulating concentrations of homocysteine and folate are inconsistently associated with the risk of nonalcoholic fatty liver disease (NAFLD) in observational studies. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Circulating concentrations of homocysteine and folate are inconsistently associated with the risk of nonalcoholic fatty liver disease (NAFLD) in observational studies.
OBJECTIVES
We conducted a meta-analysis and Mendelian randomization (MR) analyses to examine these associations.
METHODS
We performed a meta-analysis of observational studies identified from 3 databases to evaluate the associations of serum homocysteine and folate concentrations with NAFLD from inception to 7 April 2022. We conducted MR analyses to strengthen the causal inference in these associations. Independent single-nucleotide polymorphisms without linkage disequilibrium (r2 < 0.01) that were strongly associated (P < 5 × 10-8) with serum homocysteine (n = 13) and folate (n = 2) concentrations were selected as instrumental variables from 2 meta-analyses of genome-wide association studies (GWASs) of 44,147 and 37,645 individuals of European ancestry, respectively. Data on NAFLD were obtained from a GWAS of 8434 NAFLD cases and 770,180 controls of European ancestry. We further included 4 liver enzymes as secondary outcomes from a GWAS of 361,194 individuals with European descent.
RESULTS
Twenty-two observational studies comprising 30,368 participants were included in the meta-analysis. There was a positive association between serum homocysteine and NAFLD risk (n = 20; OR: 1.96; 95% CI: 1.57, 2.45) and an inverse association between serum folate and NAFLD risk (n = 12; OR: 0.75; 95% CI: 0.58, 0.99). In MR analysis, the ORs of NAFLD were 1.17 (95% CI: 1.01, 1.36) and 0.75 (95% CI: 0.55, 1.02) per 1-SD increment of genetically predicted circulating concentrations of homocysteine and folate, respectively. Each 1-SD increase of genetically predicted circulating homocysteine and folate conferred a change in ALT concentrations of 0.62 U/L (95% CI: 0.20, 1.04) and -0.84 U/L (95% CI: -0.14, -1.54).
CONCLUSIONS
This study suggests a potential role of circulating homocysteine and possibly folate in NAFLD, which calls for future clinical exploration of the possibility of lowering homocysteine concentrations to prevent NAFLD. This systematic review was registered at PROSPERO as CRD42021296434.
Topics: Humans; Folic Acid; Mendelian Randomization Analysis; Non-alcoholic Fatty Liver Disease; Homocysteine; Genome-Wide Association Study; Polymorphism, Single Nucleotide
PubMed: 36205540
DOI: 10.1093/ajcn/nqac285 -
Medicine Dec 2021Ectopic pregnancy (EP) is a common cause of acute abdominal pain in the field of gynecology. Because the majority of women with EP are hemodynamically stable,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Ectopic pregnancy (EP) is a common cause of acute abdominal pain in the field of gynecology. Because the majority of women with EP are hemodynamically stable, non-surgical therapy is a viable option. The goal of this study was to determine the most effective non-surgical therapy for hemodynamically stable EP.
METHODS
We performed a systematic review and meta-analysis. We searched PubMed, LILACS, SciELO, CINAHL, Embase, and the Cochrane library in May 2020, with no starting date restrictions.Studies were restricted to randomized controlled trials, which were included if the target population contained women with tubal EP and the intervention was non-surgical management. The primary outcome measure was treatment success defined by a decrease in serum hCG to a level ranging from five mIU/mL to 50 mIU/mL. Secondary outcome measures were side effects, time needed to treat, number of injections and operative rate.
RESULTS
We conducted a meta-analysis of 15 studies that included 1573 women who were diagnosed with EP and managed non-surgically. There was no significant difference in treatment success in the matched groups; however, single-dose MTX was associated with fewer side effects than multiple-dose (relative risk 0.48, 95% confidence interval 0.28-0.80, P = .006) and two-dose therapies (relative risk 0.74, 95% confidence interval 0.55-1.00, P = .05).
CONCLUSIONS
We highly recommend that single-dose MTX without mifepristone be used first-line in patients who require conservative therapy due to the inherent negative effects of mifepristone. An EP woman with a low -hCG level that is falling or plateauing should receive expectant treatment to reduce adverse effects.
Topics: Adult; Female; Humans; Methotrexate; Mifepristone; Pregnancy; Pregnancy, Ectopic; Pregnancy, Tubal; Treatment Outcome
PubMed: 34918633
DOI: 10.1097/MD.0000000000027851 -
American Journal of Public Health Jan 2016Birth defects remain a significant source of worldwide morbidity and mortality. Strong scientific evidence shows that folic acid fortification of a region's food supply... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Birth defects remain a significant source of worldwide morbidity and mortality. Strong scientific evidence shows that folic acid fortification of a region's food supply leads to a decrease in spina bifida (a birth defect of the spine). Still, many countries around the world have yet to approve mandatory fortification through government legislation.
OBJECTIVES
We sought to perform a systematic review and meta-analysis of period prevalence of spina bifida by folic acid fortification status, geographic region, and study population.
SEARCH METHODS
An expert research librarian used terms related to neural tube defects and epidemiology from primary research from 1985 to 2010 to search in EMBASE and MEDLINE. We searched the reference lists of included articles and key review articles identified by experts.
SELECTION CRITERIA
Inclusion criteria included studies in English or French reporting on prevalence published between January 1985 and December 2010 that (1) were primary research, (2) were population-based, and (3) reported a point or period prevalence estimate of spina bifida (i.e., prevalence estimate with confidence intervals or case numerator and population denominator). Two independent reviewers screened titles and abstracts for eligible articles, then 2 authors screened full texts in duplicate for final inclusion. Disagreements were resolved through consensus or a third party.
DATA COLLECTION AND ANALYSIS
We followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses, or PRISMA, abstracting data related to case ascertainment, study population, folic acid fortification status, geographic region, and prevalence estimate independently and in duplicate. We extracted overall data and any subgroups reported by age, gender, time period, or type of spina bifida. We classified each period prevalence estimate as "mandatory" or "voluntary" folic acid fortification according to each country's folic acid fortification status at the time data were collected (as determined by a well-recognized fortification monitoring body, Food Fortification Initiative). We determined study quality on the basis of sample representativeness, standardization of data collection and birth defect assessment, and statistical analyses. We analyzed study-level period prevalence estimates by using a random effects model (α level of < 0.05) for all meta-analyses. We stratified pooled period prevalence estimates by birth population, fortification status, and continent.
RESULTS
Of 4078 studies identified, we included 179 studies in the systematic review and 123 in a meta-analysis. In studies of live births (LBs) alone, period prevalences of spina bifida were (1) lower in geographical regions with mandatory (33.86 per 100,000 LBs) versus voluntary (48.35 per 100,000 LBs) folic acid fortification, and (2) lower in studies of LBs, stillbirths, and terminations of pregnancy in regions with mandatory (35.22 per 100,000 LBs) versus voluntary (52.29 per 100,000 LBs) fortification. In LBs, stillbirths, and terminations of pregnancy studies, the lowest pooled prevalence estimate was in North America (38.70 per 100,000). Case ascertainment, surveillance methods, and reporting varied across these population-based studies.
CONCLUSIONS
Mandatory legislation enforcing folic acid fortification of the food supply lags behind the evidence, particularly in Asian and European countries. This extensive literature review shows that spina bifida is significantly more common in world regions without government legislation regulating full-coverage folic acid fortification of the food supply (i.e., Asia, Europe) and that mandatory folic acid fortification resulted in a lower prevalence of spina bifida regardless of the type of birth cohort. African data were scarce, but needed, as many African nations are beginning to adopt folic acid legislation.
Topics: Female; Folic Acid; Food, Fortified; Global Health; Humans; Pregnancy; Prevalence; Spinal Dysraphism; Vitamin B Complex
PubMed: 26562127
DOI: 10.2105/AJPH.2015.302902