Characterization of Vitamin B12 Supplementation and Correlation with Clinical Outcomes in a Large Longitudinal Study of Early Parkinson's Disease.

ObjectiveIn Parkinson's disease (PD), vitamin B12 levels are lower, and comorbid B12 deficiency has been associated with the development of neuropathy and early gait instability. Because little is known about B12 supplement use in PD, we sought to evaluate its use in a large PD cohort and, as an exploratory analysis, to determine whether baseline characteristics or disease progression differed according to B12 supplementation.MethodsWe utilized data collected as part of the National Institutes of Health Exploratory Trials in PD (NET-PD) Long-term Study (LS-1), a longitudinal study of 1,741 participants. We stratified subjects into 4 groups according to daily supplement use: no B12, multivitamin (MVI) containing < 100 μg B12, B12 ≥ 100 μg, and MVI + B12 ≥ 100 μg. Clinical outcomes were assessed at 3 years for each group using the Unified Parkinson's Disease Rating Scale (UPDRS), its subscores, and selected individual questions.ResultsOf the 1,147 participants who completed the 3-year visit, 41% took an MVI, 2% took B12, 3% took MVI + B12, and 54% reported taking no supplements. At 3 years, no significant differences in clinical outcomes were observed. However, there was a trend toward lower hazard ratios for developing sensory symptoms (UPDRS Item 17) in the MVI (p = 0.08) and B12 + MVI (p = 0.08) groups compared to that in the no supplement group.ConclusionThese results show that supplementation with vitamin B12 ≥ 100 μg is uncommon in early PD. The finding of a trend toward a lower hazard ratio for the development of sensory symptoms in those taking an MVI or B12 + MVI warrants further study

Transcobalamin C776G genotype modifies the association between vitamin B12 and homocysteine in older Hispanics.

Background/objectivesA common polymorphism, C776G, in the plasma B12 transport protein transcobalamin (TC), encodes for either proline or arginine at codon 259. This polymorphism may affect the affinity of TC for B12 and subsequent delivery of B12 to tissues.Subjects/methodsTC genotype and its associations with indicators of B12 status, including total B12, holotranscobalamin (holoTC), methylmalonic acid and homocysteine, were evaluated in a cohort of elderly Latinos (N=554, age 60-93 years) from the Sacramento Area Latino Study on Aging (SALSA).ResultsThe distribution of TC genotypes was 41.3% homozygous reference (776CC) and 11.6% homozygous variant (776GG). No differences between the homozygous genotypes were observed in total B12, holoTC, methylmalonic acid or homocysteine. The holoTC/total B12 ratio was lower in the 776GG group compared with the 776CC group (P=0.04). Significant interactions of TC genotype with total B12 (P=0.04) and with holoTC (P< or =0.03) were observed such that mean homocysteine concentrations and the odds ratios for hyperhomocysteinemia (>13 micromol/l) were higher in the 776CC subjects compared with all carriers of the G allele (776CG and 776GG combined) when total B12 (<156 pmol/l) or holoTC (<35 pmol/l) were low.ConclusionsThis population of older Latinos has a lower prevalence of the TC 776GG variant than reported for Caucasian populations. The association between vitamin B12 and homocysteine concentrations is modified by TC 776 genotype. It remains to be determined whether the TC C776G polymorphism has a significant effect on the hematological and neurological manifestations of B12 deficiency or on vascular and other morbidities associated with hyperhomocysteinemia

Human gut Bacteroides capture vitamin B12 via cell surface-exposed lipoproteins.

Human gut Bacteroides use surface-exposed lipoproteins to bind and metabolize complex polysaccharides. Although vitamins and other nutrients are also essential for commensal fitness, much less is known about how commensal bacteria compete with each other or the host for these critical resources. Unlike in Escherichia coli, transport loci for vitamin B12 (cobalamin) and other corrinoids in human gut Bacteroides are replete with conserved genes encoding proteins whose functions are unknown. Here we report that one of these proteins, BtuG, is a surface-exposed lipoprotein that is essential for efficient B12 transport in B. thetaiotaomicron. BtuG binds B12 with femtomolar affinity and can remove B12 from intrinsic factor, a critical B12 transport protein in humans. Our studies suggest that Bacteroides use surface-exposed lipoproteins not only for capturing polysaccharides, but also to acquire key vitamins in the gut

Deficiencies of the microelements, folate and vitamin B12 in women of the child bearing ages in Gorgan, Northern Iran

Background: The deficiencies of folic acid, vitamin B12, and microelements during pregnancy may affect the health of newborns. Objectives: To assess the serum levels of folate, vitamin B12, iron, zinc and copper in healthy women of the childbearing ages in Gorgan, northern Iran. Methodology: This descriptive, cross-sectional study was carried out on 100 women of childbearing ages in northern Iran during November 2007-March 2008. The serum levels of folate, vitamin B12, iron, copper and zinc were evaluated by laboratory tests. Results: Iron, copper, folate, vitamin B12 deficiencies and folate with vitamin B12 deficiency were detected in 13%, 32%, 13%, 32% and 11% women of the childbearing ages, respectively. According to the ethnicity, vitamin B12, folate and iron deficiencies in the Sistani group were observed in 38.3%, 12.9% and 12.9% of the women, respectively. In the native Fars group, the above mentioned deficiencies were found in 31.1%, 13.4% and 7.5% of the subjects. Folate and vitamin B12 deficiencies were observed in the urban habitant in 32.7% and 11.5% of the subjects as compared to those in the rural habitant (in 30.4% and 15.2%of the subjects respectively). The folate deficiencies in the under and above 18 years old subjects were 22.2% and 9.9%, respectively. Conclusions: This study showed that the deficiency of the micronutrients was considerable in women of the childbearing ages in Gorgan, northern Iran

Intakes, adequacy, food sources and biomarker status of iron, folate, and vitamin B₁₂ in Māori and non-Māori octogenarians : life and living in advanced age : a cohort study in New Zealand (LiLACS NZ) : a thesis presented in partial fulfilment of the requirements for the degree of Masters of Science in Nutrition and Dietetics, Massey University, Albany, New Zealand

Background: Iron, folate and vitamin B12 are the three key nutrients associated with the development of anaemia and have also been associated with the dietary patterns linked to higher malnutrition risk in older adults. Octogenarians may be at increased risk for iron, folate and vitamin B12 deficiency due to reduced food intake. Dietary factors, cooking methods, medications, presence of inflammation, and impaired gastrointestinal absorption may affect the availability and bioavailability of these nutrients. There are currently no specific nutrient reference values (NRVs) or biomarker cut-offs for adults in advanced age and little is known about the relationship between dietary intake and biomarkers for older adults. Aim: To investigate the intake, adequacy, food sources and biomarker status of iron, folate and vitamin B12 and the relationship between dietary intake and biomarkers. Methods: In the follow up assessment of LiLACS NZ, 216 Māori and 362 non-Māori participants completed a detailed dietary assessment using 2x 24-hr multiple pass recalls. Adequacy of iron, folate and vitamin B12 were determined by comparison to the Estimated Average Requirement (EAR) for adults aged 71+ years. Serum ferritin, serum iron, total iron binding capacity, transferrin saturation, red blood cell (RBC) folate, serum folate, serum vitamin B12 and haemoglobin were compared to recognised cut-offs for adults. Generalised linear models and binary regression estimated the association between dietary intake and biomarkers. Results: Most participants had adequate dietary iron intakes (88% Māori; 95% non-Māori above EAR) and biomarkers for iron (>94% above cut-offs). The EAR for vitamin B12 was met by 74% Māori; 78% non-Māori and folate met by 42% Māori; 49% non-Māori. Māori versus non-Māori had higher intakes of vitamin B12 (p=0.038) and serum vitamin B12 (p=0.026). Increased dietary folate intake was associated with increased RBC folate for Māori (p=0.001) and non-Māori (p=0.014) and with increased serum folate for Māori (p215μg/day was associated with reduced risk of deficiency in RBC folate for Māori (p=0.001). Conclusions: Dietary intake and stores of iron are largely adequate in this population. Strategies to optimise the intake and bioavailability of foods rich in folate and vitamin B12 may be beneficial

Influence of vitamin B12 and light on the formation of chlorosomes in green- and brown-colored Chlorobium species

The specific Bchl a and c content of the vitamin B12-dependent Chlorobium limicola strain 1230 decreased strongly under vitamin B12 limitation. In comparison to a regularly grown culture (20 g vitamin B12/l) the specific Bchl c content of a B12-limited culture was reduced to 20% and the specific Bchl a content to 42%. By ultrathin sections it could be clearly demonstrated that B12-deficient cells contained no chlorosomes. After the addition of vitamin B12 to a deficient culture, chlorosomes were formed and the Bchl a and c content increased again to the level of regularly grown cells. The brown-colored Chlorobium phaeobacteroides strain 2430 (type strain) and the extremely low-light-adapted strain MN1 were compared with respect to the influence of light on the formation of chlorosomes and the Bchl e and carotenoid content. By ultrathin sections it could be demonstrated that strain MN1 produced two-fold larger chlorosomes. Chlorosome dimensions of strain MN1 decreased with increasing light intensities. The number of chlorosomes per cell in both strains did not change with different light intensities. Strain MN1 formed twice as much Bchl e as the type strain when grown at 30 or below 1 mol · m-2 · s-1. Under comparable light conditions strain MN1 formed 14–57% more carotenoids than the type strain. Low light intensities aaused the carotenoid content to increase by 25% in strain 2430 in comparison to high light intensity

14C-Cobalamin Absorption from Endogenously Labeled Chicken Eggs Assessed in Humans Using Accelerator Mass Spectrometry.

Traditionally, the bioavailability of vitamin B-12 (B12) from in vivo labeled foods was determined by labeling the vitamin with radiocobalt (57Co, 58Co or 60Co). This required use of penetrating radioactivity and sometimes used higher doses of B12 than the physiological limit of B12 absorption. The aim of this study was to determine the bioavailability and absorbed B12 from chicken eggs endogenously labeled with 14C-B12 using accelerator mass spectrometry (AMS). 14C-B12 was injected intramuscularly into hens to produce eggs enriched in vivo with the 14C labeled vitamin. The eggs, which provided 1.4 to 2.6 μg of B12 (~1.1 kBq) per serving, were scrambled, cooked and fed to 10 human volunteers. Baseline and post-ingestion blood, urine and stool samples were collected over a one-week period and assessed for 14C-B12 content using AMS. Bioavailability ranged from 13.2 to 57.7% (mean 30.2 ± 16.4%). Difference among subjects was explained by dose of B12, with percent bioavailability from 2.6 μg only half that from 1.4 μg. The total amount of B12 absorbed was limited to 0.5-0.8 μg (mean 0.55 ± 0.19 μg B12) and was relatively unaffected by the amount consumed. The use of 14C-B12 offers the only currently available method for quantifying B12 absorption in humans, including food cobalamin absorption. An egg is confirmed as a good source of B12, supplying approximately 20% of the average adult daily requirement (RDA for adults = 2.4 μg/day)

Vitamin B12 measurements across neurodegenerative disorders.

Background:Vitamin B12 deficiency causes a number of neurological features including cognitive and psychiatric disturbances, gait instability, neuropathy, and autonomic dysfunction. Clinical recognition of B12 deficiency in neurodegenerative disorders is more challenging because it causes defects that overlap with expected disease progression. We sought to determine whether B12 levels at the time of diagnosis in patients with Parkinson's disease (PD) differed from those in patients with other neurodegenerative disorders. Methods:We performed a cross-sectional analysis of B12 levels obtained around the time of diagnosis in patients with PD, Multiple System Atrophy (MSA), Dementia with Lewy Bodies (DLB), Alzheimer's disease (AD), Progressive Supranuclear Palsy (PSP), Frontotemporal Dementia (FTD), or Mild Cognitive Impairment (MCI). We also evaluated the rate of B12 decline in PD, AD, and MCI. Results:In multivariable analysis adjusted for age, sex, and B12 supplementation, we found that B12 levels were significantly lower at time of diagnosis in patients with PD than in patients with PSP, FTD, and DLB. In PD, AD, and MCI, the rate of B12 decline ranged from - 17 to - 47 pg/ml/year, much greater than that reported for the elderly population. Conclusions:Further studies are needed to determine whether comorbid B12 deficiency affects progression of these disorders