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Reply to R Carmel

Institute of Health Sciences
Faculty of Earth and Life Sciences
Vrije Universiteit
De Boelelaan 1085
1081 HV Amsterdam
Netherlands

Petra Verhoef

Unilever Food and Health Research Institute
Olivier van Noortlaan 120
3133 AT Vlaardingen
Netherlands
E-mail: petra.verhoef{at}unilever.com

Dear Sir:

Dr Carmel states that mean corpuscular volume (MCV) is an important marker of serious vitamin B-12 deficiency. He also argues that it is important to distinguish clinical vitamin B-12 deficiency from subclinical deficiency when discussing possible adverse effects of supplemental folic acid. Furthermore, he makes the case that patients with severe vitamin B-12 deficiency are unlikely to benefit from fortification with vitamin B-12.

In our editorial, which ended with the suggestion that folic acid fortification be combined with vitamin B-12 fortification, we took the position that, despite a normal MCV, a person may still have vitamin B-12 deficiency. We do not contest the relevance of a high MCV value for diagnosis of vitamin B-12 deficiency, and we should have expressed ourselves more carefully. It would have been clearer had we said that every physician should know by now that a normal MCV does not mean that the person has no vitamin B-12 deficiency. We clearly recognize the value of an MCV measurement for diagnosis of vitamin B-12 deficiency and do consider it a valuable parameter for the detection of anemia in general.

We also agree with Carmel that the controversy surrounding the effects of folic acid in vitamin B-12–deficient persons may never be resolved. It is indeed not known whether the neurologic progression seen at folic acid supplementation in clinical deficiency also occurs in subclinical vitamin B-12 deficiency. However, it is not impossible that folic acid may also have detrimental health effects in persons with mild vitamin B-12 deficiency.

Carmel further states that patients who have progressive vitamin B-12 deficiency, including neurological deterioration, are unlikely to benefit from vitamin B-12 fortification because of malabsorption. We agree with him if this situation concerns patients who have reduced absorption due to lack of intrinsic factor, because these patients can passively absorb only 1% of crystalline vitamin B-12 (1). Therefore, they will still require intramuscular injections with vitamin B-12. Fortunately, this possibility affects only a relatively small group of patients. However, in most older persons, the absorption problem is caused by age-related gastric atrophy (2-4), which will lead to a reduced ability to extract vitamin B-12 from food protein. There is no reason to expect absorption problems for crystalline vitamin B-12 in this group.

We therefore expect that most older persons with low vitamin B-12 status will benefit from food fortification with vitamin B-12. When a food is already fortified with folic acid, additional vitamin B fortification may correct the otherwise unnoticed low vitamin B-12 status in elderly. Moreover, it may have other positive health effects, eg, on cognitive performance. Recent research shows that low vitamin B-12 status is associated with more rapid cognitive decline (5). However, randomized controlled clinical trials will have to show whether vitamin B-12 supplementation can indeed delay cognitive decline. In conclusion, although it is not a solution for patients who lack intrinsic factor, fortification with vitamin B-12 along with folic acid may have important health effects for a large group of elderly.

ACKNOWLEDGMENTS

Petra Verhoef is an employee of Unilever, which markets food products, some of which are enriched with B vitamins. Neither of the authors had any personal or financial conflict of interest.

REFERENCES

1. Baik HW, Russell RM. Vitamin B12 deficiency in the elderly. Annu Rev Nutr 1999;19:357–77.[Medline]
2. Hvas AM, Nexo E. Diagnosis and treatment of vitamin B12 deficiency—an update. Hematologica 2006;91:1506–12.[Abstract/Free Full Text]
3. Hin H, Clarke R, Sherliker P, et al. Clinical relevance of low serum vitamin B12 concentrations in older people: the Banbury B12 study. Age Aging 2006;35:416–22.[Abstract/Free Full Text]
4. Stabler SP, Allen RH. Vitamin B12 deficiency as a worldwide problem. Annu Rev Nutr 2004;24:299–326.[Medline]
5. Clarke R, Sherliker P, Hin H, et al. Detection of vitamin B12 deficiency in older people by measuring vitamin B12 or the active fraction of vitamin B12, holotranscobalamin. Clin Chem 2007;53:963–70.[Abstract/Free Full Text]

This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Brouwer, I. A Articles by Verhoef, P. Search for Related Content PubMed Articles by Brouwer, I. A Articles by Verhoef, P. Agricola Articles by Brouwer, I. A Articles by Verhoef, P.