top Clinical Studies References
Vitamin B12 is necessary for carbohydrate, protein and fat metabolism. It is important to amino acid and fatty acid synthesis and is essential for hemoglobin and nerve cell growth and maintenance. It is an anti-stress vitamin sometimes prescribed for stress reduction.
Vitamin B12 is beneficial in pernicious anemia. It also may be used for treating high homocysteine levels, heart disease, chronic fatigue syndrome, male infertility, diabetes, memory loss, sleep disorders, Alzheimer's disease, bursitis, depression, psychiatric disorders, osteoporosis, tendonitis, immunosuppression, AIDS, inflammatory bowel disease, asthma, allergies, vitiligo and seborrheic dermatitis.
It may be beneficial in thyrotoxicosis, amyotrophic lateral sclerosis (Lou Gehrig's disease), multiple sclerosis, periodontal disease, tinnitus, hemorrhage, cancer, and liver and kidney disease. Vitamin B12 may be helpful in aging, improving concentration, mood elevation, boosting energy, maintaining fertility and protection against the toxins and allergens from tobacco smoke.
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Published Clinical Studiesclin
1 [Optimal use of markers for cobalamin/folate status. Results from a survey in a group of psychogeriatric patients]
Hultberg B, Isaksson A, Nilsson K, Gustafson L.
Kliniskt kemiska laboratoriet, Universitetssjukhuset i Lund. bjorn.hultberg@klinkem.lu.se
Cobalamin/folate deficiency may lead to neuropsychiatric symptoms. This review summarizes present findings concerning the different markers for cobalamin/folate deficiency in psychogeriatric patients. These findings suggest the use of plasma homocysteine, serum cobalamin and serum folate to evaluate cobalamin/folate status in psychogeriatric patients, whereas the use of serum methylmalonic acid and whole blood folate could be omitted.
Publication Types:
PMID: 14579665 [PubMed - indexed for MEDLINE]
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2 Reduction of plasma homocysteine and serum methylmalonate concentrations in apparently healthy elderly subjects after treatment with folic acid, vitamin B12 and vitamin B6: a randomised trial.
Lewerin C, Nilsson-Ehle H, Matousek M, Lindstedt G, Steen B.
Department of Haematology and Coagulation, Goteborg University, Goteborg, Sweden.
OBJECTIVES: To investigate, in an elderly population: (1) the effects of oral B-vitamin therapy on P-tHcys, S-MMA and Hb/MCV, (2) the appropriate decision limit for 'high' metabolite concentrations and (3) the estimated prevalence of vitamin B(12)/folate deficiency on the basis of different decision limits. DESIGN: Double-blind placebo-controlled intervention study. SETTING: Outpatient clinic. SUBJECTS: A total of 209 community-dwelling subjects, median age 76 y (range 70-93) y. INTERVENTION: Four months of oral daily supplementation with 0.5 mg cyanocobalamin, 0.8 mg folic acid and 3 mg vitamin B(6). RESULTS: High P- tHcys was found in 64% of men and 45% of women, high S-MMA in 11% of both. Vitamin B(12) deficiency was observed in 7.2% and folate deficiency in 11% of all subjects. Health-related upper reference limits for the metabolites at the start were higher than the laboratory's upper reference limits. The latter were, however, similar to those of the vitamin replete group. There was a significant decrease in P-tHcys (P<0.001) and S-MMA (P=0.009) after 4 months of vitamin treatment. In a multivariate analysis, the P-Hcys change correlated positively with baseline P-tHcys and inversely with baseline P-folate and transferrin saturation (Fe/TIBC ratio). The S-MMA change correlated with baseline S-MMA and inversely with baseline vitamin B(12) and age. CONCLUSIONS: Suboptimal vitamin status is an important cause of elevated P-tHcys and S-MMA in apparently healthy elderly subjects. Oral B-vitamin therapy is an effective and convenient way to normalise P-tHcys and S-MMA.
PMID: 14576756 [PubMed - in process]
Folic acid with or without vitamin B12 for cognition and dementia.3
Malouf M, Grimley EJ, Areosa SA.
Dept. of Clinical Geratology, Cochrane Dementia and Cognitive Improvement Group, Radcliffe Infirmary, Woodstock Road, Oxford, UK, OX2 6HE.
BACKGROUND: Folates are vitamins essential to the development of the central nervous system. Inusfficient folate activity at the time of conception and early pregnancy can result in congenital neural tube defects. In adult life folate deficiency has been known for decades to produce a characteristic form of anaemia ("megaloblastic"). More recently degrees of folate inadequacy, not severe enough to produce anaemia, have been found to be associated with high blood levels of the amino acid homocysteine. Such degrees of folate inadequacy can arise because of insufficient folates in the diet or because of inefficient absorption or metabolic utilisation of folates due to genetic variations. Conventional criteria for diagnosing folate deficiency may be inadequate for identifying people capable of benefiting from dietary supplementation. High blood levels of homocysteine have been linked with the risk of arterial disease, dementia and Alzheimer's disease. There is therefore interest in whether dietary supplements of folic acid (an artificial chemical analogue of naturally occurring folates) can improve cognitive function of people at risk of cognitive decline associated with ageing or dementia, whether by affecting homocysteine metabolism or through other mechanisms.There is a risk that if folic acid is given to people who have undiagnosed deficiency of vitamin B12 it may lead to neurological damage. Vitamin B12 deficiency produces both an anaemia identical to that of folate deficiency but also causes irreversible damage to the central and peripheral nervous systems. Folic acid will correct the anaemia of vitamin B12 deficiency and so delay diagnosis but will not prevent progression to neurological damage. For this reason trials of folic acid supplements may involve simultaneous administration of vitamin B12. Apparent benefit from folic acid given in the combination would therefore need to be "corrected" for any effect of vitamin B12 alone. A separate Cochrane review of vitamin B12 and cognitive function is being prepared. OBJECTIVES: To examine the effects of folic acid supplementation, with or without vitamin B12, on elderly healthy and demented people, in preventing cognitive impairment or retarding its progress. SEARCH STRATEGY: Trials were identified from a search of the Cochrane Dementia and Cognitive Improvement Specialized Register Group on 9 April 2003 using the terms: folic acid, folate, vitamin B9, leucovorin, methyltetrahydrofolate, vitamin B12, cobalamin, cyanocobalamin, dementia, cognitive function, cognitive impairment, Alzheimer's disease, vascular dementia, mixed dementia and controlled trials. MEDLINE and EMBASE (both all years) were searched for additional trials on healthy people. SELECTION CRITERIA: All double-blind placebo-controlled randomized trials, in which supplements of folic acid with or without vitamin B12 were compared with placebo for elderly healthy people or people with any type of dementia or cognitive impairment. DATA COLLECTION AND ANALYSIS: The reviewers independently applied the selection criteria and assessed study quality. One reviewer extracted and analysed the data. In comparing intervention with placebo, weighted mean differences, and standardized mean difference or odds ratios were estimated. MAIN RESULTS: Four randomized controlled trials fulfilled the inclusion criteria for this review. One trial (Bryan 2002) enrolled healthy women, and three (Fioravanti 1997; Sommer 1998; VITAL 2003) recruited people with mild to moderate cognitive impairment or dementia with or without diagnosed folate deficiency. Fioravanti 1997 enrolled people with mild to moderate cognitive impairment or dementia as judged by scores on the Mini-Mental State Examination (MMSE) and Global Deterioration Scale and with serum folate level<3ng/l. One trial (VITAL 2003) studied the effects of a combination of vitamin B12 and folic acid on patients with mild to moderate cognitive impairment due to Alzheimer's disease or mixed dementia.The analysis from the included trials found no benefit from folic acid with or withoic acid with or without vitamin B12 in comparison with placebo on any measures of cognition and mood for healthy or cognitively impaired or demented people: Folic acid effect and healthy participants: there was no benefit from of oral 750 mcg folic acid per day for five weeks compared with placebo on measures of cognition and mood of 19 healthy women aged 65 to 92. Folic acid effect and people with mild to moderate cognitive decline or dementia: there were no statistically significant results in favour of folic acid with or without vitamin B12 on any measures of cognitive function. Scores on the Mini-Mental State Examination (MMSE) revealed no statistically significant benefit from 2 mg per day folic acid plus 1mg vitamin B12 for 12 weeks when compared with placebo (WMD 0.39, 95% CI -0.43 to 1.21, P=0.35). Cognitive scores on the Alzheimer's Disease Scale (ADAS-Cog) showed no statistically significant benefit from 2 mg /day folic acid plus 1 mg /day vitamin B12 for 12 weeks compared with placebo (WMD 0.41, 95% -1.25 to 2.07, P=4.63). The Bristol Activities of Daily Living Scale (BADL) revealed no benefit from 2mg per day of folic acid plus 1 mg vitamin B12 for 12 weeks in comparison with placebo (WMD -0.57, 95%CI -1.95 to 0.81, P=0.42). None of the sub tests of the Randt Memory Test (RMT) showed statistically significant benefit from 15 mg of folic acid orally per day for 9 weeks when compared with placebo.One trial (Sommer 1998) reported a significant decline compared with placebo in two cognitive function tasks in demented patients who had received high doses of folic acid (10 mg /day) for unspecified periods. One trial (VITAL 2003) showed that 2 mg folic acid plus 1 mg vitamin B12 daily for 12 weeks significantly lowered serum homocysteine concentrations (P <0.0001). REVIEWER'S CONCLUSIONS: There was no beneficial effect of 750 mcg of folic acid per day on measures of cognition or mood in older healthy women. In patients with mild to moderate cognitive decline and different forms of dementia there was no benefit from folic acid on measures of cognition or mood. Folic acid plus vitamin B12 was effective in reducing the serum homocysteine concentrations. Folic acid was well tolerated and no adverse effects were reported. More studies are needed.
PMID: 14584018 [PubMed - in process]
4 Vitamin and homocysteine status of mothers and infants and the risk of nonsyndromic orofacial clefts.
van Rooij IA, Swinkels DW, Blom HJ, Merkus HM, Steegers-Theunissen RP.
Department of Epidemiology and Biostatistics, University Medical Center Nijmegen, the Netherlands.
OBJECTIVE: This study was undertaken to investigate the involvement of maternal and infant B vitamins and homocysteine as risk factors for orofacial clefting. STUDY DESIGN: Venous blood samples were taken from 96 infants with nonsyndromic orofacial clefts and 88 infants without a congenital malformation and from their mothers at approximately 14 months after the index pregnancy. Red blood cell and serum folate, serum vitamin B(12), whole blood vitamin B(6) as pyridoxal-5'-phosphate (PLP), and plasma homocysteine concentrations were measured. RESULTS: A vitamin B(12) concentration of 185 pmol/L or less and a PLP concentration of 44 nmol/L or less in mothers increased the risk of having a child with an orofacial cleft (odds ratio [OR]=3.1; 95% CI: 1.3-7.4, OR=2.9; 95% CI: 1.2-7.1, respectively). Infants with orofacial clefts had a 15% lower serum folate concentration compared with controls (P=.06). CONCLUSION: A low vitamin B(12) and PLP concentration in mothers increased the risk of orofacial clefts in the offspring. A possible role of the infant's folate status is suggested.
PMID: 14586370 [PubMed - indexed for MEDLINE]
5 Meta-analysis of plasma homocysteine, serum folate, serum vitamin B(12), and thermolabile MTHFR genotype as risk factors for retinal vascular occlusive disease.
Cahill MT, Stinnett SS, Fekrat S.
Duke University Eye Center, Durham, North Carolina 27710, USA. cahil005@mc.duke.edu
PURPOSE: To assess the role of plasma total homocysteine (tHcy) levels, serum folate and vitamin B(12)levels, and homozygosity for the thermolabile methylenetetrahydrofolate reductase genotype (TT) as risk factors for retinal vascular occlusive disease. DESIGN: Meta-analysis of literature. METHODS: A MEDLINE search was performed to identify all published case-control studies of plasma tHcy levels, serum folate and vitamin B(12) levels, and TT genotype in persons with retinal vascular occlusive disease. Main outcome measures included calculation of plasma tHcy, serum folate, and serum vitamin B(12) standard differences and odds ratios (OR) of TT genotype between cases and controls. RESULTS: In total, 614 patients with all types of retinal vein occlusion had higher plasma tHcy levels than 762 control subjects (standard difference, 0.867; 95% confidence interval [CI] = 0.735, 0.999; P <.001). Plasma tHcy levels were also higher in 154 patients with retinal artery occlusion compared with 358 control subjects (standard difference 1.174; 95% CI = 0.947, 1.402; P <.001). Serum folates, but not vitamin B(12) levels, were lower in 287 patients with retinal vascular occlusion than in the same number of control subjects (standard difference, 0.508; 95% CI = 0.340, 0.675; P <.001; and -0.060; 95% CI = -0.024, 0.104; P =.474, respectively). Similar proportions of 690 patients with retinal vein occlusion and 2754 control subjects demonstrated the TT genotype (OR = 1.332; 95% CI = 0.995, 1.783; P =.054) as did 152 patients with retinal artery occlusions and 435 control subjects (OR = 1.716; 95% CI = 0.977, 3.014; P =.060). CONCLUSIONS: Retinal vascular occlusion is associated with elevated plasma tHcy levels and low serum folate levels, but not serum vitamin B(12) levels and TT genotype. Until a prospective multicenter trial is undertaken, plasma tHcy levels and serum folate levels should be determined in patients with retinal vascular occlusions, and dietary supplementation with low doses of folate and vitamin B(12) should be considered for affected persons.
PMID: 14644226 [PubMed - indexed for MEDLINE]
6 [Nutrition and health--potential health benefits and risks of vegetarianism and limited consumption of meat in the Netherlands]
Dagnelie PC.
Universiteit Maastricht, capaciteitsgroep Epidemiologie, Postbus 616, 6200 MD Maastricht. dagnelie@epid.unimaas.nl
In the latest Dutch national food consumption survey (1998) just over 1% of subjects (about 150,000 persons) claimed to be vegetarians; however, a much larger group (6% or approximately 1 million persons) ate meat < or = once a week. Vegetarianism can be subdivided into lacto-vegetarianism (a diet without meat and fish) and veganism (a diet without any animal foods whatsoever, including dairy products and eggs). A recent meta-analysis showed that vegetarians had a lower mortality from ischaemic heart disease than omniovorous subjects; however, cancer mortality and total mortality did not differ. Although a high consumption of red meat, which is rich in haeme iron and saturated fat, may increase the risk of cardiovascular disease and some types of cancer, this does not apply to white meat and fish. In fact, the most important protective effect would seem to be derived from the consumption of unrefined vegetable products (whole-grain cereals, vegetables, fruits, nuts and legumes) and fish. In other words, a prudent, omnivorous diet with moderate amounts of animal products, in which red meat is partly replaced by white meat and fish (especially fatty fish), together with the consumption of ample amounts of unrefined vegetable products, is thought to be just as protective as a vegetarian diet. On the other hand, the omission of meat and fish from the diet increases the risk of nutritional deficiencies. A vegan diet, in particular, leads to a strongly increased risk of deficiencies of vitamin B12, vitamin B2 and several minerals, such as calcium, iron and zinc. However, even a lacto-vegetarian diet produces an increased risk of deficiencies of vitamin B12 and possibly certain minerals, such as iron. Data from the latest Dutch food consumption survey suggest that 5-10% of all inhabitants of the Netherlands (up to 1 million persons) actually have a vitamin B12 intake below recommended daily levels. In medical practice, the possibility of vitamin B12 deficiency in subjects consuming meat or fish < or = once a week deserves serious consideration. In case of doubt, evaluation is indicated using sensitive and specific deficiency markers such as the levels of methylmalonic acid in plasma or urine. Alternative dietary sources of vitamin B12 instead of meat are fish (especially fatty fish is a good source of vitamin B12), or a vitamin-B12-supplement.
PMID: 12868158 [PubMed - indexed for MEDLINE]
[In Process Citation]7
Behrens MI, Diaz V, Vasquez C, Donoso A.
Departamento de Neurologia y Neurocirugia, Hospital Clinico Universidad de Chile.
Cyanocobalamin (vitamin B12) deficiency can cause polyneuropathy, myelopathy, blindness, confusion, psychosis and dementia. Nonetheless, its deficiency as the sole cause of dementia is infrequent. We report a 59 years old man with a 6 months history of progressive loss of memory, disorientation, apathy, paranoid delusions, gait difficulties with falls, and urinary incontinence. He had suffered a similar episode 3 years before, with a complete remission. On examination there was frontal type dementia with Korsakoff syndrome, a decrease in propioception and ataxic gait. Cerebrospinal fluid examination showed a protein of 0.42 g/L. Brain computed tomography showed sequelae of a frontal left trauma. Brain single photon computed tomography (SPECT) was normal. Complete blood count showed a macrocytic anemia with a hematocrit 29% and a mean corpuscular volume of 117 micron3. Plasma vitamin B12 levels were undetectable, erythrocyte folate levels were 3.9 ng/ml and plasma folate was normal. The myelogram showed megaloblastosis and the gastric biopsy showed atrophic gastritis. Treatment with parenteral B12 vitamin and folic acid reverted the symptoms, with normalization of the neuropsychological tests and reintegration to work.
PMID: 14558247 [PubMed - in process]
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