Vitamin B12 Adequacy and Supplement Dose: When Conclusions Don’t Make Sense
Recently, MacFarlane, Shi and Greene-Finestone reported the effect that vitamin B12 supplements have on vitamin B12 levels in a Canadian population. Their conclusion was somewhat counter-intuitive, stating that high-dose vitamin B12 supplements do not improve vitamin B12 status compared to low-dose vitamin B12 supplements. As vitamin B12 absorption is somewhat dose-dependent (Doets et al. found that for every doubling in vitamin B12 dose, 30% less vitamin B12 was absorbed), their results are rather surprising. Surely, higher dose supplements should improve vitamin B12 status more than lower doses?
Vitamin B12 recommendations around the world vary between 1.4 and 3 µg. In countries with low levels of food insecurity, vitamin B12 intakes from foods are generally more than adequate for people consuming animal. The Micronutrient Calculator shows that vitamin B12 intakes in the USA exceed recommendations for most people, for example. This is presumably also the case in the Canadian population. In addition to vitamin B12 intakes from the diet, many people also take a dietary supplement that contains vitamin B12, as it is an essential micronutrient that is included in multivitamins, the most common type of dietary supplement taken.
The MacFarlane study reports that 23% of children, 12% of adolescents and 26% of adults from their representative sample of 5600 Canadians take a dietary supplement that includes vitamin B12. Around one quarter of adult users took “low dose” supplements of up to 10 µg per day, up to four times the recommended intake for adults in Canada. Doses of 10 to 25 µg, 25 to 100 µg, and above µg were taken by a little less than half, around one quarter, and around 9% of the population, respectively. As there are no known toxicity issues with very high doses of vitamin B12, there is no Tolerable Upper Limit for the vitamin and therefore very high doses should pose no health issues.
The authors compared use of any supplement containing vitamin B12 with non-vitamin B12 users and found both higher serum vitamin B12 levels and a low prevalence of inadequate serum levels (below 148 pmol/L) in vitamin B12 users. Overall, use of vitamin B12 supplements reduced the prevalence of inadequate levels from 6.4% to 1.6% in adults. The authors found in adults aged 20 to 79, vitamin B12 levels increased with increasing dose category, such that people consuming more than 25 µg had a higher serum vitamin B12 level than people consuming less than 10 µg. There was also a trend for a lower prevalence of inadequate vitamin B12 levels as dose increased, however there were no significant differences. When the results were broken down into age categories, including those for children, the sample size was rather small and there were fewer statistically significant differences between categories. The results of comparisons between low and high doses for age groups are reflected in the title of the publication, and the main conclusion. However, these statements do not mention that the authors did find an increase in serum vitamin B12 levels with higher dose supplement usage when looking at all adults, or adults aged 20 to 45, for which the sample size was presumably large enough to detect statistically significant differences.
The conclusions of this article do not tell the true story of the results. There are certain limitations used in the data analysis, including the use of categories for both age and dose, and low sample size in the subgroup analysis, that may have interfered with the intuitive conclusion. The authors chose to highlight the lack of association in age sub-groups in their title and conclusion, and did not draw attention to the results that do make sense: in the full adult dataset, and in the largest subgroup of adults aged 20 to 45, there was an increase in vitamin B12 levels with increasing dose categories.
Amanda J. MacFarlane, Yipu Shi, and Linda S. Greene-Finestone. High-Dose Compared with Low-Dose Vitamin B-12 Supplement Use Is Not Associated with Higher Vitamin B-12 Status in Children, Adolescents, and Older Adults. J. Nutr. 2014 144: 6 915-920; first published online April 3, 2014. doi:10.3945/jn.113.190256
Doets EL, In 't Veld PH, Szczecińska A, Dhonukshe-Rutten RA, Cavelaars AE, van 't Veer P, Brzozowska A, de Groot LC. Systematic review on daily vitamin B12 losses and bioavailability for deriving recommendations on vitamin B12 intake with the factorial approach. Ann Nutr Metab. 2013;62(4):311-22. doi: 10.1159/000346968. Epub 2013 Jun 20. http://www.ncbi.nlm.nih.gov/pubmed/23796635