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Background: Various definitions, criteria, tests, and cutoffs have been used to define vitamin B-12 status; however, a need exists for the systematic study of vitamin B-12 status in the United States because of concerns about high folic acid intakes and the potential for associated adverse effects. Objective: The objective was to determine the effect of different cutoff choices on outcomes and of the different degrees of serum vitamin B-12 status, definable by the concurrent use of a functional and circulating marker as the first steps to developing a data-based consensus on the biochemical diagnosis of vitamin B-12 deficiency. Design: Data from NHANES, a nationally representative cross-sectional survey, were examined for adults aged >19 y (mean ± SD age: 45 ± 1 y) from 1999 to 2004 (n = 12,612). Results: Commonly used cutoffs had a greater effect on prevalence estimates of low vitamin B-12 status with the use of vitamin B-12 than with the use of methylmalonic acid (MMA; 3-26% and 2-6%, respectively). A cutoff of >148 pmol/L for vitamin B-12 and of ≤210 nmol/L for MMA resulted in significant misclassifications. Approximately 1% of adults had a clear vitamin B-12 deficiency (low vitamin B-12 and elevated MMA); 92% of adults had adequate vitamin B-12 status. A high percentage of younger women characterized the group with low vitamin B-12 and normal MMA (2% of adults) and may have falsely reflected low vitamin B-12. Adults with elevated MMA (5%) only were demographically similar (ie, by age and race) to the deficient group and may have included some individuals with early vitamin B-12 deficiency. Conclusions: These analyses indicate the challenges of assessing vitamin B-12 status when uncertainties exist about the appropriate cutoffs. Future studies should determine definable endpoints to achieve this goal. [ABSTRACT FROM AUTHOR]

Background: Potential safety concerns relative to impaired cognitive function may exist when high folic acid exposures are combined with low vitamin B-12 status., Objectives: We aimed to examine the relation of the coexistence of high folate and low vitamin B-12 status with cognitive function, utilizing various definitions of "high" folate status., Methods: Cross-sectional data from older adults (≥60 y; n = 2420) from the 2011-2014 NHANES were analyzed. High folate status was defined as unmetabolized serum folic acid (UMFA) > 1 nmol/L or serum total folate > 74.1 nmol/L, and low vitamin B-12 status as methylmalonic acid > 271 nmol/L or serum vitamin B-12 < 150 pmol/L. Logistic regression models estimated ORs of scoring low on 1 of 4 cognitive tests: the Digit Symbol Substitution Test (DSST), the Consortium to Establish a Registry for Alzheimer's Disease Delayed Recall (CERAD-DR) and Word Learning tests, and the Animal Fluency test (AF)., Results: A significant interaction was observed relative to scoring low on the DSST (<34; UMFA; P-interaction = 0.0071) and AF (serum folate; P-interaction = 0.0078) for low vitamin B-12 and high folate status. Among those with low vitamin B-12, high UMFA or high serum total folate was associated with higher risk of scoring low on the DSST (OR: 2.16; 95% CI: 1.05, 4.47) and the AF (OR: 1.93; 95% CI: 1.08, 3.45). Among those with "normal" vitamin B-12, higher UMFA or serum total folate was protective on the CERAD-DR. In noninteraction models, when high folate and normal vitamin B-12 status was the reference group, low vitamin B-12 combined with high UMFA was associated with greater risk based on the DSST (<34, OR: 2.87; 95% CI: 1.85, 4.45; <40, OR: 2.22; 95% CI: 1.31, 3.75) and AF (OR: 1.97; 95% CI: 1.30, 2.97); but low vitamin B-12 and lower UMFA (OR: 1.69; 95% CI: 1.16, 2.47) was also significantly associated for DSST < 40 risk., Conclusions: Low vitamin B-12 was associated with cognitive impairment both independently and in an interactive manner with high folate for certain cognitive performance tests among older adults., (Published by Oxford University Press on behalf of the American Society for Nutrition 2020.)

Folate, an essential nutrient found naturally in foods in a reduced form, is present in dietary supplements and fortified foods in an oxidized synthetic form (folic acid). There is widespread agreement that maintaining adequate folate status is critical to prevent diseases due to folate inadequacy (e.g., anemia, birth defects, and cancer). However, there are concerns of potential adverse effects of excess folic acid intake and/or elevated folate status, with the original concern focused on exacerbation of clinical effects of vitamin B-12 deficiency and its role in neurocognitive health. More recently, animal and observational studies have suggested potential adverse effects on cancer risk, birth outcomes, and other diseases. Observations indicating adverse effects from excess folic acid intake, elevated folate status, and unmetabolized folic acid (UMFA) remain inconclusive; the data do not provide the evidence needed to affect public health recommendations. Moreover, strong biological and mechanistic premises connecting elevated folic acid intake, UMFA, and/or high folate status to adverse health outcomes are lacking. However, the body of evidence on potential adverse health outcomes indicates the need for comprehensive research to clarify these issues and bridge knowledge gaps. Three key research questions encompass the additional research needed to establish whether high folic acid or total folate intake contributes to disease risk. 1) Does UMFA affect biological pathways leading to adverse health effects? 2) Does elevated folate status resulting from any form of folate intake affect vitamin B-12 function and its roles in sustaining health? 3) Does elevated folate intake, regardless of form, affect biological pathways leading to adverse health effects other than those linked to vitamin B-12 function? This article summarizes the proceedings of an August 2019 NIH expert workshop focused on addressing these research areas., (Published by Oxford University Press on behalf of the American Society for Nutrition 2020.)

Since the introduction of folic acid fortification of flour 10 y ago, an initiative to consider fortifying flour with vitamin B-12 has gained momentum in the United States. The impetus for this move stems from several considerations, including some evidence that a proportion of neural tube defect pregnancies may be the result of vitamin B-12 rather than folate deficiency. However, no interventional trials have taken place to show the efficacy of vitamin B-12 supplementation or fortification in the primary prevention or recurrence of neural tube defect pregnancies, as was the case with folic acid. Other reasons put forward for the institution of vitamin B-12 fortification include the high prevalence of vitamin B-12 deficiency in certain demographic groups, including the elderly and the young in some countries. Much of this deficiency, however, is subclinical and not associated with manifest morbidity. Moreover, individuals affected by the most severe cases of vitamin B-12 deficiency that are associated with morbidity would not benefit from the concentrations of vitamin B-12 fortification that are practical or that are being considered, because such individuals suffer from malabsorption of vitamin B-12 rather than from an inadequacy of intake of the vitamin. In addition to the well-recognized complications of vitamin B-12 deficiency, such as macrocytic anemia and neurological complications affecting sensory and motor function, more subtle effects have also been described, including osteopenia, neurocognitive impairment, and increased vascular disease risk associated with elevated homocysteine. This analysis focuses on the research questions that are pertinent to the consideration of whether or not to introduce mandatory vitamin B-12 fortification in the United States.

We report how data from the University of California (UC) Davis mission-based reporting system (MBR) can be used to define contributions for each division within a Department of Pathology based on faculty rank and series, and to evaluate whether these contributions are in alignment with the missions of the department and the goals of the school's leadership. MBR summary reports were generated for each division within the Department of Pathology; these reports illustrated the average contribution for each faculty rank and series in each of the following missions: investigative/creative work (research), teaching, clinical service, and administrative/community service. All divisions contributed equally to the teaching mission, averaging approximately 1/3 of a faculty member's time. Research was the primary mission for faculty in both the Research and the Clinical Pathology divisions, whereas clinical service was the primary mission for Anatomic Pathology. Both Anatomic Pathology and Clinical Pathology also played a large role in the administration/community service mission. These roles were appropriate based on the division's distribution of faculty in each of the faculty series. The average contribution to both the research and administrative/community service missions were larger for the Department of Pathology than it was for the school as a whole. The Department of Pathology's average contribution to both the teaching and clinical service missions was less than the school's average. We conclude that MBR data creates unique profiles for divisions and the department and enables interdepartmental comparisons that would not be possible by other means. Within the context of our school, the present analysis illustrates that the Department of Pathology is fulfilling the expectations of the school's leadership. In a more general sense, these profiles allow appropriate monitoring of the workforce, funds flow analysis, allocation of resources, and strategic planning in an academic medical center.