Intended for healthcare professionals

Practice 10 Minute Consultation

Vitamin B-12 deficiency

BMJ 2010; 340 doi: (Published 01 June 2010) Cite this as: BMJ 2010;340:c2305

B12 deficiency may be more difficult to detect in people who exercise regularly

Herrmann and colleagues[1] found that the correlation between
methylmalonic acid (MMA) and serum B12 was -0.38 in sedentary subjects but
-0.01 in recreational athletes, suggesting that B12 metabolism in people
who exercise regularly differs from that in sedentary people. The same
group suggested that regular endurance training is associated with an
increase in B12 and folate requirements.[2] Herrmann and colleagues
suggest that people who exercise regularly can be functionally deficient
in B12 with normal or even high B12 levels.[1] In their study most of the
healthy recreational athletes they studied had elevated MMA levels,
suggesting critical intracellular B12 supply.[1] Possibly the best method
for detecting B12 deficiency is change in serum MMA after B12

In the early stages of my small fibre sensory neuropathy in 2005 my
lower extremity parasthesia was apparent 24-48 hours after a high
intensity 2 hour bicycle ride, lasted less than 12 hours and recurred only
after the next bike ride. At that time my B12 and folate levels were 460
pmol/L and 1624 nmol/L respectively (Roche method). When my neuropathy
started I was 53 and had a four-year history of proton pump inhibitor and
ant-acid use, but the neurologists I consulted did not consider B12
supplementation and advised that B12 deficiency was very unlikely.
Gastroscopy revealed mild chronic gastritis and helicobacter pylori
infection. A test for intrinsic factor anti-bodies was normal but was
within 10% of the cut-off value. The temporal relationship between my
early neuropathy symptoms and exercise might have been explained by the
prolonged recovery of acute exercise-induced elevation of homocysteine
observed in some endurance athletes.[2] Plasma concentration of MMA is
also acutely increased by strenuous exercise.[1] Both homocysteine and
MMA are implicated in neuronal injury.[4]

After much reading prompted by an anaesthetist colleague who had seen
neuropathy develop in a patient exposed to nitrous oxide on multiple
occasions, I started oral B12 supplementation at 3 mg of
methylcobalamin/day. My neuropathy stopped progressing and partially
resolved over the following few years. It is important to start B12
supplements early because delay may contribute to residual neurological
damage,[5] and the consequences of prolonged B12 deficiency can be
devastating.[6] No toxic or adverse effects have been associated with
large intakes of B12, so the threshold for prescribing B12 supplements
should be very much lower than it appears to be at present. Further
research is needed in B12 metabolism and measurement, particularly in
older people who exercise regularly.

1. Herrmann M, Obeid R, Scharhag J, Kindermann W, Herrmann W. Altered
vitamin B12 status in recreational endurance athletes. Int J Sport Nutr
Exerc Metab. Aug 2005;15(4):433-441.

2. Herrmann M, Schorr H, Obeid R, Scharhag J, Urhausen A, Kindermann
W, et al. Homocysteine increases during endurance exercise. Clin Chem Lab
Med. Nov 2003;41(11):1518-1524.

3. Bolann BJ, Solli JD, Schneede J, Grottum KA, Loraas A, Stokkeland
M, et al. Evaluation of indicators of cobalamin deficiency defined as
cobalamin-induced reduction in increased serum methylmalonic acid. Clin
Chem. Nov 2000;46(11):1744-1750.

4. Dharmarajan TS, Adiga GU, Norkus EP. Vitamin B12 deficiency.
Recognizing subtle symptoms in older adults. Geriatrics. Mar 2003;58(3):30
-34, 37-38.

5. Larner AJ. Missed diagnosis of vitamin B12 deficiency presenting
with paraesthetic symptoms. Int J Clin Pract. Jun 2002;56(5):377-378.

6. Dharmarajan TS, Norkus EP. Approaches to vitamin B12 deficiency.
Early treatment may prevent devastating complications. Postgrad Med. Jul

Competing interests:
None declared

Competing interests: No competing interests

10 June 2010
Martin J Turner
Honorary Principal Research Fellow
School of Public Health, University of Sydney, NSW 2006, Australia