Folate and vitamin B-12 status in relation to anemia, macrocytosis, and cognitive impairment in older Americans in the age of folic acid fortification

Morris, Martha Savaria; Jacques, Paul F.; Rosenberg, Irwin H.; Selhub, Jacob

doi:10.1093/ajcn/85.1.193

Cited by 528 publications

(428 citation statements)

References 75 publications

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“…2a) is 10-fold lower than that currently used in the above clinical trial, we anticipate that folate-labeling agents will generally be well tolerated. Third, consumption of high doses of folic acid could conceivably raise serum folate concentrations to levels that compete with folate-dye conjugates for binding to CTCs (29,30). Although no constraints were placed on vitamin utilization by the cancer patients tested in Fig.…”

Section: Discussionmentioning

confidence: 99%

In vivo quantitation of rare circulating tumor cells by multiphoton intravital flow cytometry

He¹,

Wang

Hartmann

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

271

276

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Quantitation of circulating tumor cells (CTCs) constitutes an emerging tool for the diagnosis and staging of cancer, assessment of response to therapy, and evaluation of residual disease after surgery. Unfortunately, no existing technology has the sensitivity to measure the low numbers of tumor cells (<1 CTC per ml of whole blood) that characterize minimal levels of disease. We present a method, intravital flow cytometry, that noninvasively counts rare CTCs in vivo as they flow through the peripheral vasculature. The method involves i.v. injection of a tumor-specific fluorescent ligand followed by multiphoton fluorescence imaging of superficial blood vessels to quantitate the flowing CTCs. Studies in mice with metastatic tumors demonstrate that CTCs can be quantitated weeks before metastatic disease is detected by other means. Analysis of whole blood samples from cancer patients further establishes that human CTCs can be selectively labeled and quantitated when present at Ϸ2 CTCs per ml, opening opportunities for earlier assessment of metastatic disease.folate conjugates ͉ in vivo imaging ͉ multiphoton microscopy ͉ metastasis ͉ cancer diagnosis

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Section: Discussionmentioning

confidence: 99%

In vivo quantitation of rare circulating tumor cells by multiphoton intravital flow cytometry

He¹,

Wang

Hartmann

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

271

276

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“…We classified elevated MMA using 2 concentrations: .376 nmol/L (31)(32)(33)(34)(35) and .271 nmol/L (24,28,32,(36)(37)(38)(39). We also examined 4 categories of MMA based on the above cutoffs (.376 and .271 nmol/L) and .210 nmol/L (14,23,40,41). We defined elevated tHcy as a concentration .13 lmol/L (4, 16).…”

Section: Biochemical Methodsmentioning

confidence: 99%

Monitoring of vitamin B-12 nutritional status in the United States by using plasma methylmalonic acid and serum vitamin B-12

Bailey¹,

Carmel²,

Green³

et al. 2011

The American Journal of Clinical Nutrition

136

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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 crosssectional survey, were examined for adults aged .19 y (mean 6 SD age: 45 6 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.Am J Clin Nutr 2011;94:552-61.

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“…The lack of effect found in this earlier trial has been partly attributed to the less-sensitive test used to assess cognitive function (mini-mental state examination) in the New Zealand trial (15) v. five separate tests of different cognitive domains used in the Dutch trial (14) . However, a recent analysis of the relationship between blood levels of folate and vitamin B 12 in older adult participants (> 60 years, n 1459) in the 1999-2002 US National Health and Nutrition Examination Survey and measures of cognitive function has found that the protective effects of folate on cognitive function are dependent on adequate vitamin B 12 status (16) . This study suggests that if vitamin B 12 status is adequate, then folic acid (even at high intake levels) seems to be protective of cognitive function (16,17) .…”

Section: Cognitive Functionmentioning

confidence: 99%

Session 1: Public health nutrition Folic acid food fortification: the Irish experience

et al. 2008

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Adequate intake of folic acid by women during very early pregnancy can markedly reduce risk of the development of neural-tube defects (NTD). The effectiveness of advice to women to take folic acid supplements is limited, mainly because 50 % of pregnancies are unplanned. However, mandatory folic acid food fortification programmes in North America have been very successful in reducing NTD rates. In Ireland higher rates of pregnancies are affected by NTD and the option of termination is illegal. Consequently, the much higher burden of disease makes primary prevention of NTD an important public health issue in Ireland. During 2006 a decision was taken in Ireland to initiate mandatory folic acid fortification of most bread to prevent NTD. Priority work was immediately undertaken to establish reliable and comprehensive baseline information on factors that will be affected by fortification. This information included data on: the national prevalence of pregnancies affected by NTD; the current extent of voluntary folic acid fortification of food on the Irish market and how it affects folic acid intakes; blood folate status indicators assessed for various subgroups of the Irish population. In addition, scientific developments that have arisen since 2006 relating to the risks and benefits of folic acid intake are under ongoing review. The present paper summarises the rationale for mandatory folic acid food fortification in Ireland and recent scientific developments relating to risks and benefits of folic acid intake. In this context, preliminary findings of baseline monitoring investigations in Ireland are considered.

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Folate and vitamin B-12 status in relation to anemia, macrocytosis, and cognitive impairment in older Americans in the age of folic acid fortification

Abstract: In seniors with low vitamin B-12 status, high serum folate was associated with anemia and cognitive impairment. When vitamin B-12 status was normal, however, high serum folate was associated with protection against cognitive impairment.

Cited by 528 publications

References 75 publications

In vivo quantitation of rare circulating tumor cells by multiphoton intravital flow cytometry

In vivo quantitation of rare circulating tumor cells by multiphoton intravital flow cytometry

Monitoring of vitamin B-12 nutritional status in the United States by using plasma methylmalonic acid and serum vitamin B-12

Session 1: Public health nutrition Folic acid food fortification: the Irish experience

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