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Low vitamin B12 has been associated with raised plasma homocysteines and the consumption of B vitamins has been shown to reduce homocysteines. Raised levels of homocysteines have been linked to causing symptoms of mental illness. B12 is also required in the synthesis of monoamines and is required to maintain neurological health. Aim: This study reviews research into the effects of the supplementation of B12 in the prevention and recovery of mental illness, and the potentiation of psychotropic medication. Methodology: This literature review follows a systematic approach to searching databases CINAHL, EMBASE, Medline, and PsycINFO where 287 non-duplicated articles results were received. Appropriate articles were identified through title and abstract screening and inclusion and exclusion criteria were applied. Five articles were chosen to address the research question following critical appraisal. Thematic analysis was then conducted. Findings: This review identified five randomised controlled trials into the supplementation of various doses of B12 in conjunction with folic acid and B6. The supplement was measured against post-stroke depression prevention, the reduction of symptoms of depression in woman with cardiovascular disease, the effect on negative symptoms in schizophrenia, the reduction and prevention of depression in older adults, and the potentiation of psychotropic interventions. The papers reviewed showed inconclusive results, but evidence to support sub-groups and specific high-risk groups. Strong evidence showed supplementation of B12, folic acid and B6 has high rates of preventing post-stroke depression. Conclusion: The findings show that this area of research is still to be developed. The effects of B12 supplementation with other B vitamins on mental health have shown to be inconclusive. There is a case for its use to be considered within certain patient groups to aid recovery of mental health or in some high-risk patient groups. Recommendations are made for further research into high-risk groups of people that may have symptoms or symptoms that could be improved through the supplementation of B12. [ABSTRACT FROM AUTHOR]

Purpose: Trials aiming to lower homocysteine by B-vitamin supplementation have reported mixed results on slowing cognitive decline. We investigated if efficacy of B-vitamin supplementation is affected by baseline plasma omega-3 fatty acid levels. Methods: This post-hoc analysis of the B-proof trial included 191 adults aged 65 years or older with baseline plasma total homocysteine ≥ 12 μmol/L, randomly assigned to 400 µg folic acid and 500 µg vitamin B12 or placebo daily for 2 years. Global and domain-specific cognitive functioning were assessed at baseline and after 2 years. The effect of B-vitamin supplementation was analyzed according to tertiles of baseline plasma omega-3 fatty acids concentrations combined, and eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) individually using multiple linear regression analyses. Results: The mean ± SD age of the participants was 71.6 ± 5.9 years and median [IQR] Mini-Mental State Examination was 29 [28–30]. The treatment effect of B-vitamins on global cognition was larger in participants in the high compared to the middle DHA tertile (difference in z-score, mean ± SE 0.22 ± 0.10, p = 0.03). There was no significant interaction between B-vitamin supplementation and combined omega-3 fatty acid (p = 0.49) and EPA (p = 0.99) tertiles. Similarly, the efficacy of B-vitamin treatment on domain-specific cognitive functioning did not link to omega-3 fatty acid, DHA, or EPA plasma levels. Conclusion: This post-hoc analysis indicated that efficacy of B-vitamin supplementation in slowing cognitive decline relates to DHA status, with individuals with higher plasma DHA levels benefitting more from vitamin B12 and folic acid use. The results support earlier observations that positive effects of B-vitamins in cognitive ageing may be subgroup-specific. Trial registration: Registered at clinicaltrials.gov (NCT00696514) on June 12, 2008. [ABSTRACT FROM AUTHOR]

A case study of a 15‑year‑old boy presented with complaints of intellectual decline and behavioral change for last 8 months due to Cobalamin C Disease. Topics include developed concomitant stiffness of both lower limbs with transient tremulousness of feet on standing from a recumbent position; and considering the child's age, presentation with cognitive dysfunction and spastic ataxic paraparesis, a positive family history.

Background: Vitamin B deficiency and elevated total plasma homocysteine have been associated with cognitive impairment and dementia in later life, although it is unknown if treatment with these vitamins improves cognitive outcomes. Objectives: The objectives of this study were to examine the efficacy of treatment with vitamin B12, vitamin B6, or folic acid in slowing cognitive decline amongst older adults with and without cognitive impairment. Methods: We summarized findings from previous systematic reviews of clinical trials and performed a new systematic review and meta-analysis of 31 English-language, randomized placebo-controlled trials of B-vitamin supplementation of individuals with and without existing cognitive impairment. Results: Previous reviews have generally reported no effect of B vitamins on cognitive function in older adults with or without cognitive impairment at study entry, although these vitamins effectively lowered total plasma homocysteine levels in participants. Ten randomized placebo-controlled trials of 1925 participants with pre-existing cognitive impairment and 21 trials of 15,104 participants without cognitive impairment have been completed to date but these generally confirmed findings from previous reviews with the exception of two trials that showed a modest but clinically uncertain benefit for vitamins in people with elevated plasma homocysteine. B-vitamin supplementation did not show an improvement in Mini-Mental State Examination scores for individuals with (mean difference 0.16, 95% confidence interval − 0.18 to 0.51) and without (mean difference 0.04, 95% confidence interval − 0.10 to 0.18) cognitive impairment compared to placebo. Conclusions: Raised total plasma homocysteine is associated with an increased risk of cognitive impairment and dementia, although available evidence from randomized controlled trials shows no obvious cognitive benefit of lowering homocysteine using B vitamins. Existing trials vary greatly in the type of supplementation, population sampled, study quality, and duration of treatment, thereby making it difficult to draw firm conclusions from existing data. Findings should therefore be viewed in the context of the limitations of the available data and the lack of evidence of effect should not necessarily be interpreted as evidence of no effect. [ABSTRACT FROM AUTHOR]

Objective To summarize the clinical manifestations, laboratory, electrophysiological and imaging features, treatment and prognosis of subacute combined degeneration of the spinal cord (SCD). Methods and Results The clinical data of 15 SCD patients from February 2014 to February 2018 were collected and analyzed retrospectively. The etiology of SCD is related to disorders in uptake, absorption, combination or transport of vitamin B12. The onset was chronic or subacute, and main initial symptoms were paresthesia of hands or feet. Laboratory examination showed elevated serum homocysteine (Hcy) levels, reduced vitamin B12 levels and positive anti - intrinsic factor and anti - parietal cell antibodies. Spinal MRI showed that the lesions often occurred in the posterior and lateral funiculus of cervical and thoracic spinal cord. The "inverted V sign" was considered to be the characteristic imaging manifestation. All patients showed improved symptoms and signs to different degrees after vitamin B12 treatment. Conclusions The pathogenesis of SCD is related to vitamin B12 deficiency. The clinical manifestations are diverse. Spinal "inverted V sign" is a strong evidence for clear diagnosis, and vitamin B12 is effective in the treatment of the disease. [ABSTRACT FROM AUTHOR]

Purpose: We compare the effect of 8-week oral supplementation with cyano-B12 (currently used in vitamin pills) and hydroxo-B12 (predominant form in the diet) in a population with nutritional vitamin B12 deficiency.Methods: Fifty-one healthy Indian adults with baseline serum cobalamin < 200 pmol/L were supplied for 8 weeks with daily oral supplements of 3-µg cyano-B12 (n = 15), 3-µg hydroxo-B12 (n = 16), or a placebo (n = 20). Blood at baseline, and each following week, was examined for total cobalamin, holotranscobalamin, methylmalonic acid, and homocysteine.Results: The study groups did not differ at baseline and were characterized by [median (range)] serum cobalamin [128 (68-191) pmol/L], holotranscobalamin [16 (6-41) pmol/L], methylmalonic acid [0.8 (0.3-1.7) µmol/L], homocysteine [17.9 (8.5-100.9) µmol/L], and a combined indicator of B12 status 4cB12 of − 1.65 (− 0.64 to − 4.07). The group supplemented with cyano-B12 showed a higher increase in total serum cobalamin than the group treated with hydroxo-B12, while other biomarkers changed comparably in the two groups. After 8 weeks of treatment, the biomarker values of the supplemented groups (pooled) differed significantly from the placebo group. Yet, the vitamin B12 status was still poor [cobalamin: 168 (87-302) pmol/L; holotranscobalamin: 19 (8-45) pmol/L; methylmalonic acid: 0.7 (0.2-1.7) µmol/L; homocysteine: 17.2 (2.6-96.8) µmol/L; 4cB12 = − 1.34 (− 0.33 to − 3.3)].Conclusion: 8-week supplementation with 3-µg cyano-B12 elevated serum cobalamin more than 3 µg hydroxo-B12, but all other biomarkers changed similarly in both groups. Supplementation with 3 µg vitamin B12 did not reverse the low status in individuals with nutritional vitamin B12 deficiency.Clinical Trial Registry of India: REF/2017/02/013343. [ABSTRACT FROM AUTHOR]

Objectives To examine the effects of oral maternal vitamin B12 supplementation during pregnancy and early lactation on cognitive development in children. Method We studied 218 children born to mothers enrolled in a placebo-controlled, randomized trial of vitamin B12 supplementation during pregnancy through 6 weeks post-partum. Cognitive functions were assessed at 30 months using the Bayley Scales of Infant Development- 3rd edition (BSID III). The association of maternal sociodemographic characteristics, maternal biochemical status during pregnancy, birth weight and home environment with each sub-domain of BSID-III was examined using linear regression analysis. Separate multiple linear regression analyses for each of the BSID-III sub-domains with maternal trimester specific nutritional biomarker status was conducted. Results Children of mothers who received oral vitamin B12 supplementation had significantly higher scores on expressive language compared to children of mothers who received placebo (β = 0.14, P = 0.03). Children of mothers with elevated serum total homocysteine (tHcy) in the second and third trimesters of pregnancy had significantly lower scores on expressive language (β = − 0.18, P = 0.03 and β = − 0.19, P = 0.02, respectively) and gross motor domains (β = − 0.23, P = 0.008 and β = − 0.30, P = 0.001, respectively) of BSID-III adjusted for treatment arm and multiple confounders, compared with children whose mothers did not have elevated tHcy. Conclusions for practice Maternal B12 supplementation during pregnancy was associated with higher expressive language scores in children at 30 months. Elevated maternal tHcy levels during pregnancy had negative associations with expressive language and gross motor domains of BSID-III. Larger trials of maternal B12 supplementation are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Background: Hemolytic uremic syndrome (HUS) is a clinical syndrome characterized by hemolytic anemia, thrombocytopenia, and acute kidney injury. Atypical hemolytic uremic syndrome (aHUS) is a devastating disease with significant mortality and high risk of progression to end-stage kidney disease. It is mostly caused by dysregulation of the alternative complement pathway. Cobalamin C (Cbl C) defect is a genetic disorder of cobalamin metabolism and is a rare cause of HUS.Case-diagnosis/treatment: We present a 6-month-old male infant who was admitted to the pediatric intensive care unit (PICU) due to restlessness, severe hypertension, anemia, respiratory distress, and acute kidney injury. Metabolic screening revealed elevated plasma homocysteine levels, low methionine levels, and methylmalonic aciduria, and the patient was diagnosed as having HUS secondary to Cbl C defect. Additionally, complement factor H (CFH) and complement C3 levels were decreased. The infant was treated with betaine, hydroxycobalamin, and folic acid. After treatment, the homocysteine and methylmalonic acid levels were normalized but hemolysis and acute kidney failure persisted. He required continued renal replacement treatment (CRRT) and plasma exchange due to thrombotic microangiopathy (TMA). Therefore, we considered a second mechanism in the pathogenesis as complement dysregulation and gave eculizumab to the patient. After eculizumab treatment, the renal and hematologic indices improved and he was free of dialysis.Conclusions: To the best of our knowledge, our patient is the first to have Cbl C defect-HUS accompanied by complement dysregulation, who responded well to eculizumab therapy. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this trial was to investigate the influence of a dietetic product consisting of a unique combination of l-arginine with the vitamins B6, folic acid and B12 (Telcor® Arginin plus) on endothelial dysfunction.Methods: Subjects aged 40-65 years with mild to moderate blood pressure (BP) elevation not treated with anti-hypertensive drugs were randomly assigned to either the dietetic product (n = 40) or a matching placebo (n = 41) for 3 months with open follow-up for a further 3 months. Postprandial change in endothelial function was assessed using the validated reactive hyperaemia index (RHI) at 3 months compared to the study onset (RHI post-pre, visit 3-visit 1; ΔΔRHI). Secondary parameters included BP and plasma homocysteine concentration.Results: The primary efficacy analysis revealed superiority of the nutritional intervention over placebo (p = 0.0349) in reducing the deterioration of endothelial function. While in the active group ΔΔRHI increased (0.371 ± 0.122), almost no change could be detected in the placebo group (0.031 ± 0.100), thus demonstrating a significant improvement in vascular function in the intervention group. Moreover, the intervention reduced BP and homocysteine levels. Non-serious adverse events were equally distributed in both groups, and none of the events were assessed as possibly intervention-related by the investigators.Conclusions: This trial confirmed the effective and safe use of dietary management with l-arginine in combination with B vitamins. The primary efficacy analysis demonstrated a statistically significant superiority of the combination of l-arginine with B vitamins over placebo in improving and restoring impaired endothelial function and lowering BP in patients with mild to moderate blood pressure elevation. [ABSTRACT FROM AUTHOR]

The effects of different doses of folic acid and vitamin B12 on rabbits with deep vein thrombosis (DVT) and hyperhomocysteinemia were investigated. In total, 60 New Zealand rabbits were divided into untreated control, low-dose and high-dose groups. After inducing DVT, hemorheology and coagulation indexes were measured 3 and 10 days later. We found that both treatment groups performed better than the control group, and the high-dose performed better than the low-dose. Ten days after thrombosis, the levels of Hcy and D-dimer were lower in the high-dose group. Moreover, the changes of lower extremity deep venous thrombosis were significantly reduced in both high- and low-dose groups, but the high-dose group showed the most improvement. The effective rate of the high-dose group was 100%, higher than the rate in the low-dose and control groups. Overall, high-dose of folic acid and vitamin B12 can significantly improve plasma Hcy, coagulation indexes, and pathological changes in the venous thrombosis of the lower extremity. [ABSTRACT FROM AUTHOR]

The efficacy of carbamazepine combined with vitamin B12 in epilepsy treatment by comparing levels of plasma homocysteine (Hcy), serum TNF-α and hs-CRP in patients with epilepsy before and after treatment was investigated. Fifty-eight patients with epilepsy who were admitted and received treatment in The First People's Hospital of Xuzhou were recruited as subjects, and fifty-eight healthy volunteers were recruited as the control group. Patients were treated with carbamazepine combined with vitamin B12 for a period of three months. The mRNA and protein levels of TNF-α and hs-CRP in serum were measured before and after treatment using semi-quantitative RT-PCR and western blotting, respectively. The plasma Hcy levels were measured as well. Within one year after the 3-month treatment, the frequency and duration of seizure were tracked. After treatment with carbamazepine combined with vitamin B12 for patients with epilepsy, the Hcy level was significantly higher than that before treatment and that in the control group (P<0.01). The mRNA and protein levels of TNF-α and hs-CRP in serum were significantly higher in patients than that in healthy people (P<0.01). After treatment these levels were reduced (P<0.01), but still higher than those in healthy people (P<0.05, P<0.01). After treatment, the frequency and duration of seizures were all reduced (P<0.05, P<0.01). The results suggested that carbamazepine combined with vitamin B12 was effective in treatment of epilepsy by reducing levels of TNF-α and hs-CRP in the serum, but had a risk of increasing the Hcy level. [ABSTRACT FROM AUTHOR]

Answers to a clinical quiz about a child with severe hypertension and circulatory failure is presented.

Background and Aim: Treatment of neuropathic pain and chemotherapy-induced peripheral neuropathy (CIPN) in patients with malignancy is often unsuccessful. Functional vitamin B12 deficiency, defined by elevated levels of the B12-dependent metabolites, methylmalonic acid (MMA), and/or homocysteine, despite normal B12 values, may cause neuropathy and is associated with disorders linked to increased oxidative stress. Since both cancer and neurotoxic antineoplastic agents increase oxidative stress, a role for functional B12 deficiency in CIPN was considered.Methods: A retrospective record review of 241 cancer subjects evaluated by the adult palliative care service for B12 deficiency in a university-based cancer center between October 2008 and September 2012 with measurement of B12, MMA, and/or homocysteine levels was performed.Results: B12 values were elevated (>900 pg/ml) in 30 % and low (≤300 pg/ml) in 17 % of subjects tested. Elevated MMA (>250 nmol/l) and homocysteine (>12.1 μmol/l) levels occurred in 38 and 23 % of subjects respectively and at least one metabolite was increased in 54 % of evaluable subjects. Even when B12 values were ≥1500 pg/ml (n = 36), increased MMA and homocysteine values occurred in 31 and 23 % of subjects, respectively. B12 therapy decreased MMA values in all four subjects studied and improved neurologic findings in the three subjects tested.Conclusions: Functional vitamin B12 deficiency is common in subjects with advanced malignancy. Further studies are needed to determine if this disorder is a risk factor for CIPN and if B12 therapy has a role in the management and/or prevention of neuropathy and neuropathic pain in this population. [ABSTRACT FROM AUTHOR]

​Impaired homocysteine metabolism plays an important role in alcoholic liver disease (ALD); however, there are limited data about its relationship with the risk and severity of patients with ALD in Taiwan. To understand plasma homocysteine and related vitamin concentrations in patients with ALD in Taiwan, we recruited 50 male patients with ALD from Cathay General Hospital, with 49 age-and gender-matched healthy adults as the control group. The Institutional Review Board for Human Studies approved the study, and informed consent was obtained from all patients prior to blood collection. Significantly higher plasma homocysteine concentrations but lower folate concentrations were obtained from patients with ALD. In addition, patients with ALD showed a significant lower erythrocyte reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio but higher plasma thiobarbituric acid-reactive substance (TBARS) concentration, which indicated that oxidative stress was occurring in patients with ALD. A negative correlation between plasma folate and homocysteine was observed in all subjects. There was also a negative correlation between plasma homocysteine and the erythrocyte GSH/GSSG ratio which indicated impaired homocysteine metabolism may have disrupted the antioxidative status. In addition, patients in Child-Pugh Class B and C showed higher plasma vitamin B12 concentrations than did patients without cirrhosis and patients in Child-Pugh Class A. These findings show that impaired homocysteine metabolism was observed in patients with ALD in Taiwan. In addition, the plasma vitamin B12 concentration may reflect the degree of liver injury. [ABSTRACT FROM AUTHOR]

Objectives: To report the association of lifestyle factors and plasma vitamin B-12 with hyperhomocysteinemia in a large sample of men and women living in a region of China where there is an increased risk of NTDs. Design: Community-based, cross-sectional study of Lvliang City, Shanxi Province, China. Setting: Hyperhomocysteinemia is an independent risk factor for cardiovascular disease (CVD) and a sensitive marker of vitamin B-12 and folate deficiency. Participants: A total of 2355 (1044 men and 1311 women) participants born before 1 January 1958 (≥55 years of age) and living in Lvliang City for at least 2 months a year were included. Measurements: The participants were assessed regarding demographic characteristics, height, weight, as well as having a physical examination and blood sampling for serum cholesterol, total homocysteine (tHcy), folate, and vitamin B12 levels. Results: The median (25th-75th percentile) tHcy concentration was 21.5 (15.8-33.6) µmol/L in men and 18.0 (13.4-24.8) µmol/L in women. The overall prevalence of hyperhomocysteinemia (tHcy ≥15 µmol/L) was 72.6% (84.3% in men and 63.2% in women), inversely correlated with folate (r=-0.230, P=0.006) and vitamin B-12 (r=-0.540, P<0.001), and positively correlated with uric acid (r=0.054, P<0.001). Vitamin B-12 and folate deficiency, older age, and male gender were associated with elevated tHcy; with vitamin B-12 deficiency being the strongest. Conclusions: Plasma tHcy concentration and hyperhomocysteinemia were significantly higher in this population than in previously studied populations. Vitamin B-12 and folate supplementation, concomitant lifestyle changes such as smoking cessation, and lipid-lowering treatments may help to decrease plasma tHcy concentrations and reduce the CVD risk in this population. [ABSTRACT FROM AUTHOR]

Objectives: Neuropathies often accompany vitamin B12 deficiency. Since many neuropathies are linked to oxidative stress and since B12 has both antioxidant and neurotrophic properties, B12 may also be effective treatment in non-deficient subjects. Thus, the characteristics and predictors of B12-responsive neuropathies and their relationship to disorders associated with increased oxidative stress (oxidant risks) were examined. Methods: Retrospective review of 78 subjects with neurological abnormalities treated with B12 and evaluated by the measurement of B12 and the B12-dependent metabolites, methylmalonic acid (MMA), and homocysteine. Results: Sixty-five subjects had neurological improvement (83%), including 35 with other known causes of neuropathy. Only two responders had B12-responsive macrocytosis. Pretherapy B12, MMA, and homocysteine values were normal in 72, 33 and 54% of responders, with all three normal in 23%. Moreover, B12 therapy did not significantly decrease elevated MMA and homocysteine levels in 20 and 37%, respectively, of responders tested but did decrease both metabolites in 75% of evaluable nonresponders. At least one oxidant risk was present in 41 of the 46 responders with normal B12 levels (89%). Oral therapy was effective, but parenteral B12 improved responses in four subjects. Discussion: B12-responsive neuropathies are thus (1) common even when confounding disorders are present; (2) dissociated from the presence of hematological abnormalities; (3) dissociated from the presence of B12-responsive metabolical abnormalities; and (4) associated with the presence of oxidant risks when B12 levels are normal. Since no predictors of responses to B12 therapy were identified, empiric trials with parenteral B12 should be considered in appropriate subjects. [ABSTRACT FROM AUTHOR]

Importance: Functional methionine synthase reductase deficiency, also known as cobalamin E disorder, is a rare autosomal recessive inherited disease that results in an impaired remethylation of homocysteine to methionine. It presents with macrocytic anemia, hyperhomocysteinemia, and hypomethioninemia, and may also be accompanied with neurological impairment. Clinical presentation: We describe two new cases of unrelated girls with megaloblastic anemia misclassified at first as congenital dyserythropoietic anemia with development of neurologic dysfunction in one of them. Intervention: The posterior finding of biochemical features (hyperhomocysteinemia and hypomethioninemia) focused the diagnosis on the inborn errors of intracellular vitamin B12. Subsequent molecular analysis of the methionine synthase reductase (MTRR) gene revealed compound heterozygosity for a transition c.1361C > T (p.Ser454Leu) and another, not yet described in literature, c.1677–1G > A (p.Glu560fs) in one patient, and a single homozygosis mutation, c.1361C > T (p.Ser545Leu) in the other one. These mutations confirmed the diagnosis of cobalamin E deficiency. Conclusion: Treatment with hydroxocobalamin in combination with betaine appears to be useful for hematological improvement and prevention of brain disabilities in CblE-affected patients. Our study widens the clinical, molecular, metabolic, and cytological knowledge of deficiency MTRR enzyme. [ABSTRACT FROM PUBLISHER]

Purpose: A vitamin B12 supplement is required in pemetrexed single agent therapy. Intramuscular administration is the method of choice; however, oral administration is simpler and easier and may be sufficiently effective. We conducted a Phase II study to evaluate the safety of oral administration of vitamin B12 in patients with advanced non-small cell lung cancer who received pemetrexed single agent therapy.Methods: Folic acid and vitamin B12 were given orally for ˃ 1 week before pemetrexed administration. The primary end-point was onset of a grade ≥ 3 neutropenia ratio (50% of threshold expression ratios; an expectation expression ratio of 21%; α, 0.05; β, 0.1). Blood concentration of folic acid and homocysteine which are markers of vitamin B12 deficiency were also examined (UMIN000003180).Results: A total of 25 cases were registered from February 2010 to July 2014. The ratio of grade ≥ 3 neutropenia was 36% (95% CI 22-52 %). Grade ≥ 3 non-hematologic toxicity and hematologic toxicity were seen in 20% (5 cases) and 44% (11 cases) of patients, respectively. In addition, the homocysteine blood concentration just before the first cycle dosage of pemetrexed was significantly elevated relative to the 2-3 cycle.Conclusion: This study failed to meet its primary endpoint. We could not demonstrate the safety and efficacy of the 1-week vitamin B12 oral administration protocol as compared with intramuscular administration. [ABSTRACT FROM AUTHOR]

The purpose of this narrative review is to highlight insights into the importance and frequency of metabolic vitamin B12 (B12) deficiency, reasons why it is commonly missed, and reasons for the widespread but mistaken belief that treatment of B12 deficiency does not prevent stroke or improve cognitive function. Metabolic B12 deficiency is common, being present in 10%-40% of the population; is frequently missed; is easily treated; and contributes importantly to cognitive decline and stroke in older people. Measuring serum B12 alone is not sufficient for diagnosis; it is necessary to measure holotranscobalamin or functional markers of B12 adequacy such as methylmalonic acid or plasma total homocysteine. B-vitamin therapy with cyanocobalamin reduces the risk of stroke in patients with normal renal function but is harmful (perhaps because of thiocyanate accumulation from cyanide in cyanocobalamin) in patients with renal impairment. Methylcobalamin may be preferable in renal impairment. B12 therapy slowed gray matter atrophy and cognitive decline in the Homocysteine and B Vitamins in Cognitive Impairment Trial. Undiagnosed metabolic B12 deficiency may be an important missed opportunity for prevention of dementia and stroke; in patients with metabolic B12 deficiency, it would be prudent to offer inexpensive and nontoxic supplements of oral B12, preferably methylcobalamin or hydroxycobalamin. Future research is needed to distinguish the effects of thiocyanate from cyanocobalamin on hydrogen sulfide, and effects of treatment with methylcobalamin on cognitive function and stroke, particularly in patients with renal failure. [ABSTRACT FROM AUTHOR]

Background: Exclusive breastfeeding for 6 months is assumed to ensure adequate micronutrients for term infants. Our objective was to investigate the effects of prolonged breastfeeding on B vitamin status and neurodevelopment in 80 infants with subnormal birth weights (2000-3000 g) and examine if cobalamin supplementation may benefit motor function in infants who developed biochemical signs of impaired cobalamin function (total homocysteine (tHcy) > 6.5 μmol/L) at 6 months.Methods: Levels of cobalamin, folate, riboflavin and pyridoxal 5´-phosphate, and the metabolic markers tHcy and methylmalonic acid (MMA), were determined at 6 weeks, 4 and 6 months (n = 80/68/66). Neurodevelopment was assessed with the Alberta Infants Motor Scale (AIMS) and the parental questionnaire Ages and Stages (ASQ) at 6 months. At 6 months, 32 of 36 infants with tHcy > 6.5 μmol/L were enrolled in a double blind randomized controlled trial to receive 400 μg hydroxycobalamin intramuscularly (n = 16) or sham injection (n = 16). Biochemical status and neurodevelopment were evaluated after one month.Results: Except for folate, infants who were exclusively breastfed for >1 month had lower B vitamin levels at all assessments and higher tHcy and MMA levels at 4 and 6 months. At 6 months, these infants had lower AIMS scores (p = 0.03) and ASQ gross motor scores (p = 0.01). Compared to the placebo group, cobalamin treatment resulted in a decrease in plasma tHcy (p < 0.001) and MMA (p = 0.001) levels and a larger increase in AIMS (p = 0.02) and ASQ gross motor scores (p = 0.03).Conclusions: The findings suggest that prolonged exclusive breastfeeding may not provide sufficient B vitamins for small infants, and that this may have a negative effect on early gross motor development. In infants with mild cobalamin deficiency at 6 months, cobalamin treatment significantly improvement cobalamin status and motor function, suggesting that the observed impairment in motor function associated with long-term exclusive breastfeeding, may be due to cobalamin deficiency.Clinical Trial Registration: ClinicalTrials.gov, number NCT01201005. [ABSTRACT FROM AUTHOR]

Background: Cobalamin C (CblC) defects are inherited autosomal recessive disorders of vitamin B12 metabolism due to mutations in the MMACHC gene. Renal manifestations include thrombotic microangiopathy (TMA), acute or chronic renal failure, tubulointerstitial nephritis, and proximal renal tubular acidosis. However, reports about glomerular pathologies are scarce. Case report: A 4-year-old boy presented with nephrotic syndrome, arterial hypertension, and chronic anemia but no signs of hemolysis. Renal biopsy showed TMA with ischemic glomerular collapse, foot process effacement, and tubulointerstitial fibrosis. Elevated serum levels of homocysteine suggested a cobalamin C disorder. This was confirmed by the identification of compound heterozygous mutations in the MMACHC gene. Initial therapy consisted of antihypertensive treatment including angiotensin converting enzyme inhibitor (ACEi) leading to blood pressure control and a significant reduction of proteinuria. After a definite diagnosis of CblC deficiency, hydroxocobalamin was introduced. Thereafter, homocysteine levels decreased, anemia resolved, and a further decline of proteinuria with normalization of serum protein levels was noted. Renal function remained stable. Conclusions: Although uncommon, the clinical picture of CblC defects may be ruled by nephrotic syndrome mimicking glomerulonephritis, minimal change disease, or primary focal and segmental glomerulosclerosis. Key to a correct diagnosis is elevated serum levels of homocysteine, and a definite diagnosis can be confirmed by genetic testing. [ABSTRACT FROM AUTHOR]

The article discusses the role of methylenetetrahydrofolate reductase (MTHFR) in regulating levels of homocysteine (HC) and mentions that MTHFR C677T gene is associated with an increased risk of cardiovascular (CV) disease. Topics discussed include association if MTHFR C677T polymorphism loci with increased venous thromboembolism (VTE) and study on association of folic acid supplementation and decreased HC levels.

Nutrition is far more important than most physicians and patients recognize. Maintaining a healthy weight, reducing dietary cholesterol, avoiding egg yolks, and consuming a Cretan Mediterranean diet substantially reduce the risk for stroke. Besides the very high cholesterol content of egg yolks (more than the recommended daily intake of 200 mg of cholesterol in a single large egg yolk), it is now apparent that phosphatidylcholine (lecithin, 250 mg per egg yolk) is converted by intestinal bacteria to trimethylamine, which in turn is oxidized in the liver to trimethylamine n-oxide (TMAO), which is pro-atherosclerotic in animal models and increases the risk for cardiovascular events in patients at risk for coronary disease. Unrecognized metabolic deficiency of vitamin B12 is very common, and frequently missed, because a 'normal' serum B12 is not a reliable test for adequacy of B12. Besides neuropathy, myelopathy, and dementia, B12 deficiency increases the risk for stroke by raising levels of total homocysteine (tHcy). Despite widespread misunderstanding of the complex issues, it is increasingly clear that B vitamin therapy to reduce homocysteine does reduce the risk for stroke. However adequacy of B12 dosing and renal impairment determine the response to B vitamin therapy: cyanocobalamin is beneficial in patients with normal kidney function, but harmful in those with renal impairment (GFR<50). Methylcobalamin should be used in patients with renal impairment. [ABSTRACT FROM AUTHOR]

Muscle strength plays an important role in determining risk for falls, which result in fractures and other injuries. While bone loss has long been recognized as an inevitable consequence of aging, sarcopenia-the gradual loss of skeletal muscle mass and strength that occurs with advancing age-has recently received increased attention. A review of the literature was undertaken to identify nutritional factors that contribute to loss of muscle mass. The role of protein, acid-base balance, vitamin D/calcium, and other minor nutrients like B vitamins was reviewed. Muscle wasting is a multifactorial process involving intrinsic and extrinsic alterations. A loss of fast twitch fibers, glycation of proteins, and insulin resistance may play an important role in the loss of muscle strength and development of sarcopenia. Protein intake plays an integral part in muscle health and an intake of 1.0-1.2 g/kg of body weight per day is probably optimal for older adults. There is a moderate inverse relationship between vitamin D status and muscle strength. Chronic ingestion of acid-producing diets appears to have a negative impact on muscle performance, and decreases in vitamin B and folic acid intake may also impair muscle function through their action on homocysteine. An adequate nutritional intake and an optimal dietary acid-base balance are important elements of any strategy to preserve muscle mass and strength during aging. [ABSTRACT FROM AUTHOR]

Objective: Vegetarians are more vascular-healthy but those with subnormal vitamin B-12 status have impaired arterial endothelial function and increased intima-media thickness. We aimed to study the impact of vitamin B-12 supplementation on these markers, in the vegetarians. Design: Double-blind, placebo controlled, randomised crossover study. Setting: Community dwelling vegetarians. Participants: Fifty healthy vegetarians (vegetarian diet for at least 6 years) were recruited. Intervention: Vitamin B-12 (500µg/day) or identical placebo were given for 12 weeks with 10 weeks of placebo-washout before crossover (n=43), and then open label vitamin B-12 for additional 24 weeks (n=41). Measurement: How-mediated dilation of brachial artery (FMD) and intima-media thickness (IMT) of carotid artery were measured by ultrasound. Results: The mean age of the subjects was 45+9 years and 22 (44%) were male. Thirty-five subjects (70%) had serum B-12 levels <150pmol/l. Vitamin B-12 supplementation significantly increased serum vitamin B-12 levels (p<0.0001) and lowered plasma homocysteine (p<0.05). After vitamin B-12 supplementation but not placebo, significant improvement of brachial FMD (6.3±1.8% to 6.9±1.9%; p<0.0001) and in carotid IMT (0.69±0.09mm to 0.67±0.09 mm, p<0.05) were found, with further improvement in FMD (to 7.4±1.7%; p<0.0001) and IMT (to 0.65±0.09mm; p<0.001) after 24 weeks open label vitamin B-12. There were no significant changes in blood pressures or lipid profiles. On multivariate analysis, changes in B-12 (β=0.25; p=0.02) but not homocysteine were related to changes in FMD, (R=0.32; F value=3.19; p=0.028). Conclusions: Vitamin B-12 supplementation improved arterial function in vegetarians with subnormal vitamin B-12 levels, proposing a novel strategy for atherosclerosis prevention. [ABSTRACT FROM AUTHOR]

The article explores the effect of folic acid supplementation on total plasma homocysteine (tHcy) concentrations in sedentary adult men, used to educe homocysteine levels found to be associated with an increased risk of cardiovascular disease. The study covered a period of 90 days of an oral liquid supplement containing folic acid and vitamin B12 following the recommended dosage set by the supplier. A comparison of homocysteine levels between a control group taking a placebo and the group taking the supplement are compared.

Abstract: Objective: The purpose of this study was to investigate the protective effects of combined treatment of folate and vitamin B12 against alcoholic liver disease. Methods: Male Wistar rats weighing about 160 g were divided into four groups: an ethanol group fed an ethanol liquid diet; a control group pair-fed an isoenergetic diet without ethanol; an ethanol and vitamin group fed an ethanol-containing diet that was supplemented with folate (10 mg/kg of body weight per day) and vitamin B12 (0.5 mg/kg of body weight per day); and a control and vitamin group fed an isoenergetic diet without ethanol, which was supplemented with folate (10 mg/kg of body weight per day) and vitamin B12 (0.5 mg/kg of body weight per day). Results: After 16 wk, the plasma folate concentration in the ethanol group was significantly lower than in the other three groups. The plasma homocysteine concentration in the ethanol group was significantly higher than in the other three groups. The hepatic matrix metalloproteinase-2 concentration in the ethanol group was significantly higher than in the control and ethanol/vitamin groups. Furthermore, the plasma homocysteine concentration at the 16th week and the hepatic matrix metalloproteinase-2 concentration showed a significant positive correlation in rats of each group. In addition, pathologic evidence of liver fibrosis was observed only in the ethanol group. Furthermore, hepatic cytochrome 2E1 protein expression in group E increased significantly. Conclusion: These results suggest that combined treatment of folate and vitamin B12 can alleviate alcoholic liver injury that may be related to normalization of plasma homocysteine levels. [Copyright &y& Elsevier]

Background: Evidence regarding the effectiveness of oral vitamin B12 in patients with serum vitamin B12 levels between 125-200 pM/l is lacking. We compared the effectiveness of one-month oral vitamin B12 supplementation in patients with a subtle vitamin B12 deficiency to that of a placebo. Methods: This multicentre (13 general practices, two nursing homes, and one primary care center in western Switzerland), parallel, randomised, controlled, closed-label, observer-blind trial included 50 patients with serum vitamin B12 levels between 125-200 pM/l who were randomized to receive either oral vitamin B12 (1000 μg daily, N = 26) or placebo (N = 24) for four weeks. The institution's pharmacist used simple randomisation to generate a table and allocate treatments. The primary outcome was the change in serum methylmalonic acid (MMA) levels after one month of treatment. Secondary outcomes were changes in total homocysteine and serum vitamin B12 levels. Blood samples were centralised for analysis and adherence to treatment was verified by an electronic device (MEMS; Aardex Europe, Switzerland). Trial registration: ISRCTN 22063938. Results: Baseline characteristics and adherence to treatment were similar in both groups. After one month, one patient in the placebo group was lost to follow-up. Data were evaluated by intention-to-treat analysis. One month of vitamin B12 treatment (N = 26) lowered serum MMA levels by 0.13 μmol/l (95%CI 0.06-0.19) more than the change observed in the placebo group (N = 23). The number of patients needed to treat to detect a metabolic response in MMA after one month was 2.6 (95% CI 1.7-6.4). A significant change was observed for the B12 serum level, but not for the homocysteine level, hematocrit, or mean corpuscular volume. After three months without active treatment (at four months), significant differences in MMA levels were no longer detected. Conclusions: Oral vitamin B12 treatment normalised the metabolic markers of vitamin B12 deficiency. However, a one-month daily treatment with1000 μg oral vitamin B12 was not sufficient to normalise the deficiency markers for four months, and treatment had no effect on haematological signs of B12 deficiency. [ABSTRACT FROM AUTHOR]

Objective. The aim of the study is to investigate the importance of serum vitamin B12 levels in pregnant women with foetal neural tube defect (NTD). Study design. This study consists of 31 pregnant women having fetuses with NTD. The pregnant women in the study group were selected among cases with normal folate levels. Serum vitamin B12 levels were investigated. Additionally, complete blood count, serum iron level, iron binding capacity, ferritin, folate, free T3, free T4, thyroid stimulating hormone and plasma homocysteine levels were measured. Control group consisted of 32 pregnant women who did not have a history of NTD in previous pregnancies and did not have fetuses with NTD in present pregnancy. NTD was diagnosed between14th and 20th gestational age. The mean gestational age of members of control group was the same as those of NTD group. Results. There was no statistically significant difference between pregnants with NTD and control group according to number of cases with vitamin B12 deficiency. Conclusion. It seems that vitamin B12 deficiency does not play a causative role in the development of foetal NTD. Monitoring maternal homocystein levels might be important in understanding the aetiologies of foetal NTD. [ABSTRACT FROM AUTHOR]

Vitamin B12 (cobalamin) ranks among the most useful, safe and effective orthomolecules when treating a diverse array of neuropsychiatric conditions. However, most clinicians do not consider vitamin B12 important unless the serum level is below laboratory reference ranges. Ten research reports, summarized here, indicate metabolic consequences from low-normal (but not deficient) serum B12 levels, and/or clinical improvements following therapy that markedly increased serum B12 levels. My clinical experience, along with the summarized reports, suggests that (1) serum levels of vitamin B12 not "classically" deficient by current laboratory standards are associated with neuropsychiatric signs and symptoms, and (2) clinical improvement results when serum vitamin B12 levels are optimized or markedly increased following vitamin B12 treatment. Vitamin B12's mechanisms of action are believed to include increased S- adenosylmethionine production, improved methylation, decreased plasma and brain homocysteine, compensation for inborn errors of metabolism, normalized gene expression, correction of long-latency vitamin B12 debt, and anti-inflammatory activity. Clinicians may wish to re-evaluate the importance of lower-than-optimal serum vitamin B12 levels, pursue additional testing such as urinary methylmalonic acid, and consider the potential benefits of vitamin B12 treatment. [ABSTRACT FROM AUTHOR]

Abstract: Oxidative stress is a feature of many chronic inflammatory diseases. Such diseases are associated with up-regulation of a vitamin B12 (cobalamin) blood transport protein and its membrane receptor, suggesting a link between cobalamin and the cellular response to inflammation. The ability of cobalamin to regulate inflammatory cytokines suggests that it may have antioxidative properties. Here we show that cobalamins, including the novel thiolatocobalamins N-acetyl-l-cysteinylcobalamin and glutathionylcobalamin, are remarkably effective antioxidants in vitro. We also show that thiolatocobalamins have superior efficacy compared with other cobalamin forms, other cobalamins in combination with N-acetyl-l-cysteine (NAC) or glutathione (GSH), and NAC or GSH alone. Pretreatment of Sk-Hep-1 cells with thiolatocobalamins afforded robust protection (>90% cell survival) against exposure to 30 μM concentrations of the pro-oxidants homocysteine and hydrogen peroxide. The compounds inhibited intracellular peroxide production, maintained intracellular glutathione levels, and prevented apoptotic and necrotic cell death. Moreover, thiolatocobalamins are remarkably nontoxic in vitro at supraphysiological concentrations (>2 mM). Our results demonstrate that thiolatocobalamins act as powerful but benign antioxidants at pharmacological concentrations. Because inflammatory oxidative stress is a component of many conditions, including atherosclerosis, dementia, and trauma, their utility in treating such disorders merits further investigation. [Copyright &y& Elsevier]

Objective: To investigate serum levels of folate, B12, and total homocysteine (tHcy) in elderly post-stroke patients, and the possible correlations with radiological markers of neuropathology.Design: Cross-sectional study.Setting: Department of Neurology, Cardinal Tien Hospital.Subjects: Eighty-nine elderly post-stroke patients were enrolled for dietary assessment and blood tests. Neuroradiological assessment was done in 62 of these patients.Main Outcome Measures: Dietary folate and vitamin B12 intakes were evaluated by a 24-h recall system using a semi-quantitative questionnaire. Circulating levels of folate, B12, and tHcy were measured. Magnetic resonance imaging (MRI) or computed tomography (CT) was used for evaluation of brain lesions including infarction and atrophy.Results: Mean folate and B12 intakes of these post-stroke patients were 69% and 261% of the recommended dietary allowances (RDA), respectively. Inadequate folate levels, defined as serum folate < 6 ng/mL, was noted in 68% of these patients. Hyperhomocysteinemia levels (tHcy >or=15 micromol/L) were observed in 48%. According to tertiles of serum tHcy and folate levels, the rate of brain atrophy, but not brain infarctions, are significantly associated with elevated tHcy (P = 0.0126) and decreased folate levels (P = 0.0273). After adjustments for age, sex, disease status, brain infarctions and carotid stenosis, the odds ratio of brain atrophy was 9.8 (95% CI: 1.7-56.4, P = 0.0101) in the hyperhomocysteinemia group and 9.6 (95% CI: 1.1-81.3, P = 0.0377) in the low folate group (serum folate < 3.0 ng/mL) compared with the group with normal tHcy and folate levels. No significant association was noted between vitamin B12 levels and brain lesions.Conclusions: Our data shows that folate deficiency and hyperhomocysteinemia are prevalent in elderly post-stroke patients. These two conditions are strongly and independently associated with the development of brain atrophy. [ABSTRACT FROM AUTHOR]

Introduction: Nitrous oxide is a commonly abused inhalant drug. It is known to precipitate vitamin B12 deficiency when used chronically and acutely, especially in people having marginal vitamin B12 reserve. Case report: We are presenting a case of nitrous oxide "whippit" abuse in a thirty-three-year-old male with bizarre behavior and delusions. The patient had low normal levels of vitamin B12 (202 pg/ml), but he had markedly high methylmalonyl CoA (1078 nmol/L) and homocysteine (48.4 mcmol/L). Treatment with intramuscular cobalamin led to a resolution of his psychosis. Discussion: This case report highlights the need to consider vitamin B12 deficiency in patients who arrive at a hospital with psychiatric manifestations and who report having a history of nitrous oxide exposure or abuse in the recent or remote past. A review of the literature on the neuropsychological manifestations of vitamin B12 deficiency is provided. [ABSTRACT FROM AUTHOR]

Fenofibrate is among the drugs of choice for treatment of hypertriglyceridaemia and low levels of high-density lipoprotein (HDL)-cholesterol, both recognised as risk factors for cardiovascular disease. Recently, a number of studies have shown an elevation of homocysteine levels with fenofibrate or bezafibrate therapy. Homocysteine is an atherogenic amino acid derived from the methionine cycle. At present, the underlying mechanism for this elevation has not been elucidated. While deterioration of vitamin status does not seem to be involved, impairment of renal function or changes in creatine metabolism are regarded as probable mechanisms. In patients not receiving lipid-lowering drugs, vitamin supplementation with folic acid and vitamin B12 effectively reduces the plasma homocysteine level. Two studies have shown that addition of folic acid or a vitamin combination to fenofibrate prevented most of the homocysteine increase associated with fenofibrate. Although the consequence of increasing homocysteine levels for cardiovascular risk has not been proven at present, it has to be considered that fenofibrate will be given for long-term treatment. Therefore, addition of folic acid and vitamin B12 to fenofibrate can be recommended to prevent the increase of homocysteine associated with fenofibrate, or treatment could be changed to gemfibrozil, which does not increase plasma homocysteine levels. [ABSTRACT FROM AUTHOR]

Objectives: There is uncertainty amongst clinicians about the definitions of cobalamin and folate deficiency and therefore about the indications for treatment. In this report we present the results of systematic cobalamin and folic acid treatment based upon serum cobalamin, total homocysteine (tHcy) and methylmalonic acid (MMA) analyses in a population-based sample.Subjects: A 20% random sample of persons 70 years or older in a defined geographical area were invited to a survey (n = 266). Sixty-nine persons who had serum cobalamin < 300 pmol L-1 and serum MMA >/=0.37 micromol L-1 or serum tHcy >/=15 micromol L-1 and who had no cobalamin or folic acid substitution were selected for treatment.Interventions: Initially all 69 patients were given cobalamin orally or intramuscularly. Those who remained high in tHcy were in addition given folic acid treatment.Main Outcome Measures: Serum cobalamin, serum MMA and serum tHcy.Results: After 6 months of cobalamin treatment, serum MMA became normal in 13 out of 15 persons. Mean serum tHcy decreased but was normalized in only 15 out of 56 persons. After 3 months of folic acid treatment added to those who still had an abnormal serum tHcy, serum tHcy had normalized in all but one person.Conclusions: Cobalamin treatment normalizes increased MMA values and combined cobalamin and folic acid treatment normalizes tHcy, suggesting a pretreatment deficiency of tissue cobalamin and folate in spite of normal serum cobalamin and folate values in the majority of cases. [ABSTRACT FROM AUTHOR]

Homocysteine, a product of the methionine cycle, is known to play an important role in cardiovascular diseases, neurological disorders and embryology, and in very important, fast growing fields concerning obstetrics and gynaecology. Therefore, we attempted an actual overview on possible obstetrical and gynaecological disorders as a consequence of an impaired methionine cycle. We tried to evaluate all mechanisms concerning homocysteine metabolism in order to look for hypothetical possibilities of therapeutic interventions. Using MEDLINE starting in January 1966, a search was conducted for articles published in which homocysteine was included as a subject heading or a text word. This search was also specified in combination with other key words such as obstetrics, pregnancy, gynaecology and cancer. Additional sources were identified through cross-referencing. All sources found were examined with regard to providing substantial information on our topic. The information obtained was divided into articles dealing with homocysteine and the methionine cycle itself, homocysteine and pregnancy, and homocysteine and hormones, including menopause, hormone replacement therapy and oral contraceptives. Another group was concerned with other special gynaecological aspects of the methionine cycle. We suggest that elevated concentrations of homocysteine could be a marker and perhaps a cause of, or contributive to, a wide range of obstetrical and gynaecological disorders. [ABSTRACT FROM AUTHOR]

Background: Stable renal transplant recipients have an excess prevalence of hyperhomocysteinemia, which is a risk factor for arteriosclerosis.Objective: To determine the effect of treatment with 1) vitamin B6 or 2) folic acid plus vitamin B12 on fasting and post-methionine-loading plasma total homocysteine levels in renal transplant recipients.Design: Block-randomized, placebo-controlled, 2 x 2 factorial study.Setting: University-affiliated transplantation program.Patients: 29 clinically stable renal transplant recipients.Intervention: Patients were randomly assigned to one of four regimens: placebo (n = 8); vitamin B6, 50 mg/d (n = 7); folic acid, 5 mg/d, and vitamin B12, 0.4 mg/d (n = 7); or vitamin B6, 50 mg/d, folic acid, 5 mg/d, and vitamin B12, 0.4 mg/d (n = 7).Measurements: Fasting and 2-hour post-methionine-loading plasma total homocysteine levels.Results: Vitamin B6 treatment resulted in a 22.1% reduction in geometric-mean post-methionine-loading increases in plasma total homocysteine levels (P = 0.042), and folic acid plus vitamin B12 treatment caused a 26.2% reduction in geometric-mean fasting plasma total homocysteine levels (P = 0.027). These results occurred after adjustment for age; sex; and pretreatment levels of total homocysteine, B vitamins, and creatinine.Conclusions: Vitamin B6 should be added to the combination of folic acid and vitamin B12 for effective reduction of both post-methionine-loading and fasting plasma total homocysteine levels in renal transplant recipients. [ABSTRACT FROM AUTHOR]

The article focuses on studies on the link between high levels of the amino acid homocysteine (HCy) and arteriosclerosis and coronary artery disease (CAD). It mentions prospective intervention trials which show that using folic acid and vitamins B12 and B6, also known as Triple B therapy, does not prevent heart attack, stroke or venous thrombosis. However, some clinical trials reveal that Triple B therapy reduces HCy elevation and prevents cardiovascular disease (CVD).

Background: Retinal vascular occlusions are uncommon in young people and require more in-depth investigation into the cause. Studies have revealed that a high level of circulating homocysteine poses a risk for retinal vaso-occlusive events across a wide age range. This case report reflects on how the interplay of genetic mutation and vitamin deficiency can cause a pathological level of homocysteine with resultant branch retinal artery occlusion in a young patient.Case Presentation: A 16-year-old boy presented to eye casualty with acute inferior visual field loss in the left eye. Visual acuity remained normal at 6/6 each eye and the event was painless. Initial assessment, and retinal photography revealed a left superior hemi-field branch retinal artery occlusion with macular sparing. Given the patient's age, extensive investigation into the cause was carried out. Positive findings were of an elevated level of homocysteine as a result of vitamin B12 and folic acid deficiency as well as a genetic mutation in the MTHFR gene (encoding MTHFR enzyme which is vital in normal homocysteine metabolism). Vitamin B12 and folic acid were replaced which in turn normalized the patient's homocysteine levels. At two months, the patient's visual fields had also improved, and no further vascular event had occurred.Conclusions: This case report has highlighted the link between hyperhomocysteinaemia and retinal artery occlusion. However, despite vitamin replacement being shown to normalize homocysteine levels, no evidence exists to date as to whether this will reduce the risk of further retinal vascular occlusion. [ABSTRACT FROM AUTHOR]

The single infusion of ketamine, an N -methyl- D -aspartic acid (NMDA) glutamate receptor antagonist, exerts a therapeutic effect in both unipolar and bipolar depression. Homocysteine (HCY) acts agonistically on the NMDA receptor, hyperhomocysteinemia is related to depression, and folic acid and vitamin B12 are associated with HCY system. We estimated the serum levels of these substances in 20 bipolar depressed patients before ketamine infusion. 10 patients responded favorably to this procedure, as their score on the Hamilton depression rating scale, compared to baseline, was reduced by more than 50 %, after 7 days. The vitamin B12 level was significantly higher in "responders" compared to the remaining patients. No differences between the 2 groups were found with regard to HCY, folic acid levels and such clinical factors as age, duration of illness and duration of current episode. These preliminary data suggest that the vitamin B12 level may be connected with the efficacy of ketamine infusion in bipolar depression [ABSTRACT FROM AUTHOR]

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The article discusses the results of the Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH) that was published in a 2010 issue of the "Journal of the American Medical Association." Results of the study failed to find a solution to treat cardiovascular diseases (CVD) using folic acid and vitamin B12. Results, however, indicated that folic acid and vitamin B12 could reduce homocysteine level.

Relates a study that examined a combination of daily low-dose folic acid supplement combined with vitamins B12 and B6 to reduce homocysteine levels in patients with coronary artery disease. Materials; Methodology; Results; Conclusion; Implication.

The article presents a study on the effects of daily supplements of B vitamins on the reduction of homocysteine levels and brain atrophy acceleration in older patients with mild cognitive impairment (MCI). It states that vitamins B6, B12 and folic acid can be used to reduce the rate of brain atrophy acceleration. It adds that whether elevated homocysteine is a direct cause of brain atrophy or only a marker for low-normal level of B vitamins remains unclear and requires further research.

Presents an abstract of the article `Reduction of Homocysteine Levels in Coronary Artery Disease by Low-Dose Folic Acid Combined With Vitamins B6 and B12,' by A. Lobo, A. Naso et al, which appeared in the March 15, 1999 issue of `American Journal of Cardiology.'