Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2007 Dec 11;104(50):19995-20000.
doi: 10.1073/pnas.0709487104. Epub 2007 Dec 4.

In vitamin B12 deficiency, higher serum folate is associated with increased total homocysteine and methylmalonic acid concentrations

Jacob Selhub  1 , Martha Savaria Morris, Paul F Jacques
Affiliations

In vitamin B12 deficiency, higher serum folate is associated with increased total homocysteine and methylmalonic acid concentrations

Jacob Selhub et al. Proc Natl Acad Sci U S A. .

Abstract

In a recent study of older participants (age >/=60 years) in the 1999-2002 National Health and Nutrition Examination Survey (NHANES), we showed that a combination of high serum folate and low vitamin B(12) status was associated with higher prevalence of cognitive impairment and anemia than other combinations of vitamin B(12) and folate status. In the present study, we sought to determine the joint influence of serum folate and vitamin B(12) concentrations on two functional indicators of vitamin B(12) status, total homocysteine (tHcy) and methylmalonic acid (MMA), among adult participants in phase 2 of the NHANES III (1991-1994) and the NHANES 1999-2002. Exclusion of subjects who were <20 years old, were pregnant, had evidence of kidney or liver dysfunction, or reported a history of alcohol abuse or recent anemia therapy left 4,940 NHANES III participants and 5,473 NHANES 1999-2002 participants for the study. Multivariate analyses controlled for demographic factors, smoking, alcohol use, body mass index, self-reported diabetes diagnosis, and serum concentrations of creatinine and alanine aminotransferase revealed significant interactions between serum folate and serum vitamin B(12) in relation to circulating concentrations of both metabolites. In subjects with serum vitamin B(12) >148 pmol/liter (L), concentrations of both metabolites decreased significantly as serum folate increased. In subjects with lower serum vitamin B(12), however, metabolite concentrations increased as serum folate increased starting at approximately 20 nmol/L. These results suggest a worsening of vitamin B(12)'s enzymatic functions as folate status increases in people who are vitamin B(12)-deficient.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1.
Fig. 1.
Trends in serum MMA and Hcy concentrations with increasing serum folate in the United States population over the age of 20.
Fig. 2.
Fig. 2.
Creation of study datasets from NHANES datasets.
See this image and copyright information in PMC

Comment in

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Banerjee R. ACS Chem Biol. 2006;1:149–159. - PubMed
    1. Ludwig ML, Matthews RG. Annu Rev Biochem. 1997;66:269–313. - PubMed
    1. Savage DG, Lindenbaum J. In: Folate in Health and Disease. Bayley LB, editor. NY: Marcel Decker; 1995. pp. 237–285.
    1. Baik HW, Russell RM. Annu Rev Nutr. 1999;19:357–377. - PubMed
    1. Scott JM. Proc Nutr Soc. 1999;58:441–448. - PubMed

Publication types