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Table. 
Relationship Between Anemia and Elevated MCV and Homocysteine Level and Folate and Vitamin B12 Deficiency
Relationship Between Anemia and Elevated MCV and Homocysteine Level and Folate and Vitamin B12 Deficiency
1.
den Elzen  WPWestendorp  RGFrolich  Mde Ruijter  WAssendelft  WJGussekloo  J Vitamin B12 and folate and the risk of anemia in old age: the Leiden 85-Plus Study. Arch Intern Med 2008;168 (20) 2238- 2244
PubMedArticle
2.
Andrès  EFederici  LSerraj  KKaltenbach  G Update of nutrient-deficiency anemia in elderly patients. Eur J Intern Med 2008;19 (7) 488- 493
PubMedArticle
3.
Mitchell  PSmith  WAttebo  KWang  JJ Prevalence of age-related maculopathy in Australia: The Blue Mountains Eye Study. Ophthalmology 1995;102 (10) 1450- 1460
PubMedArticle
4.
Flood  VMWebb  KLSmith  W  et al.  Folate fortification: potential impact on folate intake in an older population. Eur J Clin Nutr 2001;55 (9) 793- 800
PubMedArticle
5.
Snow  CF Laboratory diagnosis of vitamin B12 and folate deficiency: a guide for the primary care physician. Arch Intern Med 1999;159 (12) 1289- 1298
PubMedArticle
6.
Metz  J A high prevalence of biochemical evidence of vitamin B12 or folate deficiency does not translate into a comparable prevalence of anemia. Food Nutr Bull 2008;29 (2) ((suppl)) S74- S85
PubMed
Research Letters
May 11, 2009

Association of Elevated Homocysteine Level and Vitamin B12 Deficiency With Anemia in Older Adults

Arch Intern Med. 2009;169(9):901-902. doi:10.1001/archinternmed.2009.75

A recent article in the Archives1 reported on the development of anemia in the Leiden 85-Plus Study. Folate deficiency and elevated serum homocysteine level were associated with anemia both at baseline and at the 5-year follow-up.1 However, the authors did not assess associations between anemia and dietary and red blood cell folate levels. It is important to investigate these relationships because folate deficiency generally develops as a result of inadequate dietary intake, and red blood cell folate concentration is more reliable than serum level.2 We therefore explored associations between anemia and elevated homocysteine level, as well as with vitamin B12 and serum, red blood cell, and dietary folate deficiencies, in a representative population of older adults.

Methods

The Blue Mountains Eye Study (BMES) is a population-based cohort study of sensory loss and other health outcomes, with methods previously reported.3 During 1992 to 1994, 3654 participants 49 years and older were examined (82.4% participation). At 5-year follow-up examinations (BMES-2), 2335 surviving participants (75.1% of survivors; 543 had died) and an additional 1174 subjects were examined as a result of a repeated door-to-door census. This provided a second cross-sectional population sample of 3509 subjects. Of these, venous blood samples were collected from 3015 subjects. Of the 2335 survivors in BMES-2, 1952 (75.6% of survivors; 1103 persons died) were re-examined at 10-year follow-up examinations (BMES-3).

Anemia, elevated mean corpuscular volume, elevated homocysteine level, and folate and vitamin B12 deficiencies were assessed using the same definitions described by den Elzen et al.1 All possible confounders listed in the Leiden 85-Plus Study were adjusted for in our study, with the exception of obstructive lung disease and Parkinson disease. We adjusted for fractures overall rather than specifically for hip fracture, as in the study by den Elzen et al.

Results

Of the 3015 subjects at BMES-2, 503 subjects who used any form of vitamin B12 and/or folic acid supplements were excluded, leaving 2512 subjects. Elevated serum homocysteine level and vitamin B12 deficiency were both associated with anemia (Table). Both serum and red blood cell folate deficiency and dietary folate less than the recommended daily intake were not associated with anemia but were associated with elevated mean corpuscular volume.

In an adjusted logistic regression model including elevated homocysteine level and serum folate and vitamin B12 deficiency, we observed an independent association between homocysteine and anemia (odds ratio, 3.78; 95% confidence interval, 2.12-6.74). At BMES-3, 21 subjects (7.0%) with elevated homocysteine levels had incident anemia (odds ratio, 2.09; 95% confidence interval, 1.01-4.30). Five-year incidence of anemia was not predicted by vitamin B12 or serum folate deficiencies.

Comment

Our study confirms the findings by den Elzen et al1 that elevated serum homocysteine level is associated with both prevalent and incident anemia, demonstrating that the Leiden 85-Plus Study findings extend down to persons 50 years and older. However, in contrast, we found that vitamin B12 deficiency rather than serum folate deficiency was associated with prevalent anemia. This is a valid finding because anemia is one of the most frequent consequences of vitamin B12 deficiency, and in developed countries, anemia due to folate deficiency is uncommon.5,6 Elevated mean corpuscular volume could be considered as a preanemia stage, which our study shows is associated with all the deficiencies we examined.

We provide evidence supporting screening and treatment of vitamin B12 deficiency, which may attenuate the occurrence of anemia in older adults. This contrasts with the recommendations by den Elzen et al1 for those 85 years and older. These conflicting results are not surprising, since a notable proportion of older anemic patients (30%-50%) are presumed to have multiple causes for their anemia.2 Hence, both the Blue Mountains and Leiden 85-Plus studies demonstrate that successful treatment of nutrient-deficiency anemia depends on focusing particular attention to discerning underlying causes.

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Article Information

Correspondence: Dr Mitchell, Centre for Vision Research, University of Sydney, Department of Opthalmology, Westmead Hospital, Hawkesbury Road, Westmead, New South Wales 2145, Australia (paul_mitchell@wmi.usyd.edu.au).

Author Contributions:Study concept and design: Gopinath and Mitchell. Acquisition of data: Mitchell. Analysis and interpretation of data: Gopinath, Rochtchina, and Flood. Drafting of the manuscript: Gopinath. Critical revision of the manuscript for important intellectual content: Rochtchina, Flood, and Mitchell. Statistical analysis: Rochtchina. Obtained funding: Mitchell. Administrative, technical, and material support: Gopinath, Flood, and Mitchell. Study supervision: Gopinath and Mitchell.

Financial Disclosure: None reported.

References
1.
den Elzen  WPWestendorp  RGFrolich  Mde Ruijter  WAssendelft  WJGussekloo  J Vitamin B12 and folate and the risk of anemia in old age: the Leiden 85-Plus Study. Arch Intern Med 2008;168 (20) 2238- 2244
PubMedArticle
2.
Andrès  EFederici  LSerraj  KKaltenbach  G Update of nutrient-deficiency anemia in elderly patients. Eur J Intern Med 2008;19 (7) 488- 493
PubMedArticle
3.
Mitchell  PSmith  WAttebo  KWang  JJ Prevalence of age-related maculopathy in Australia: The Blue Mountains Eye Study. Ophthalmology 1995;102 (10) 1450- 1460
PubMedArticle
4.
Flood  VMWebb  KLSmith  W  et al.  Folate fortification: potential impact on folate intake in an older population. Eur J Clin Nutr 2001;55 (9) 793- 800
PubMedArticle
5.
Snow  CF Laboratory diagnosis of vitamin B12 and folate deficiency: a guide for the primary care physician. Arch Intern Med 1999;159 (12) 1289- 1298
PubMedArticle
6.
Metz  J A high prevalence of biochemical evidence of vitamin B12 or folate deficiency does not translate into a comparable prevalence of anemia. Food Nutr Bull 2008;29 (2) ((suppl)) S74- S85
PubMed
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