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Rapid response to:

Clinical Review State of the Art Review

Prevention of falls in older people living in the community

BMJ 2016; 353 doi: (Published 28 April 2016) Cite this as: BMJ 2016;353:i1419

Rapid Response:

B12 deficiency is another modifiable falls risk factor

Vieira, Palmer, and Chaves, 2016 present an excellent article which addresses many of the issues that present a falls risk for elderly people. One important factor not addressed is vitamin B12 deficiency, which has a prevalence in the elderly of up to 24.8% (Moore et al, 2014), as a consequence of both ageing and co-morbidity. The literature has described the impact of B12 deficiency on the brain and spinal cord (demyelination) for over 100 years (McCaddon, 2013) and this can present clinically with paraesthesia of peripheral neuropathy to subacute combined cord degeneration. Neuropsychiatric symptoms may also present before anaemia (Smith, 1960). Signs can include: loss of vibration and/or position sense; ataxic gait; reduced sensation with a sensory level; positive Romberg’s test and muscle weakness. These symptoms and signs are obviously risk factors for falls in the elderly, even in the absence of anaemia. A large prospective Swedish study has also shown low cobalamin levels are associated with incident fractures (Lewerin et al, 2013).

The increased risk of falls with polypharmacy is well recognised but it is less well known that certain drugs commonly prescribed to the elderly, such as proton pump inhibitors (Au, Power and Gilmore, 2015) and metformin for type II diabetes (Niafar et al, 2014), are associated with vitamin B12 deficiency. Long term use of metformin is particularly associated with B12 deficiency (Aroda et al., 2016) and a recent systematic review and meta-analysis by Chapman, Darling, and Brown (2016) showed that patients on metformin had lower levels of B12 (by 57 pmol/l), which can lead to frank/borderline deficiency, so they recommend screening of patients on metformin. A recent study found that elderly patients over 75 years on metformin were less likely to be tested for vitamin B12 deficiency than their younger counterparts (Fogelman et al, 2016).

Orthostatic hypotension is a recognised risk factor for falls in the elderly and often cardiovascular causes are investigated, although it is recognised that B12 deficiency is also a prominent cause of autonomic dysfunction in the elderly (Kearney, Moore, and Donegan, 2007). Moreover, treatment of B12 deficiency in the elderly has been shown to be beneficial for orthostatic hypotension in a controlled trial (Moore et al, 2004). To complicate matters further, patients with B12 deficiency have been shown to have similar autonomic dysfunction to patients with diabetic neuropathy in a systematic case-controlled study (Beitzke et al., 2002).

B12 deficiency is common in the elderly but, if tested for, may be mistakenly overlooked as a potential risk factor for falls in the absence of the classical macrocytic anaemia. Twenty-five percent of patients with B12 deficiency may present with neurological symptoms and normal MCV (Devalia et al, 2014). A large population screening study conducted in Sweden of 1048 elderly patients discovered 97 cases of undiagnosed B12 deficiency, only 2 of whom would have been discovered if B12 levels were only checked after demonstration of macrocytic anaemia (Loikas et al, 2007).

Unfortunately there is no gold standard test to establish B12 deficiency, although methylmalonic acid and homocysteine can be used to confirm B12 deficiency in a hospital setting. It is recommended that treatment should be based on clinical symptoms/signs if there is ‘discordance of results’ as neurological impairment may be permanent after 6 months (Hunt et al, 2014).

I would suggest that the first step is thinking about B12 deficiency as a potential modifiable risk factor for falls. Testing B12 (and folate levels) and giving a treatment trial if the B12 level is <200ng/l (or if symptoms/signs are highly suggestive and the B12 result is borderline or MMA/homocysteine are elevated in the absence of other causes) using the neurological protocol of alternate day injections of hydroxocobalamin 1mg until no further improvement in neurological symptoms/signs (review after 3 weeks) followed by 2 monthly maintenance injections for life, when there has been a clinical response, is recommended by the British Committee for Standards in Haematology guidelines (Devalia et al, 2014).

Aroda, V.R., Edelstein, S.L., Goldberg, R.B., Knowler, W.C., Marcovina, S.M., Orchard, T.J., Bray, G.A., Schade, D.S., Temprosa, M.G., White, N.H. and Crandall, J.P. (2016) ‘Long-term Metformin use and vitamin B12 deficiency in the diabetes prevention program outcomes study’, The Journal of Clinical Endocrinology & Metabolism, 101(4), pp. 1754–1761. doi: 10.1210/jc.2015-3754.
Au, Minnie, Power, Jacinta, and Gilmore, David (2015) Proton pump inhibitors and vitamin B12 deficiency in older adults: a systematic review of clinical studies. Annals of the Australasian College of Tropical Medicine, 17 (1). p. 17.
Beitzke, M., Pfister, P., Fortin, J. and Skrabal, F. (2002) ‘Autonomic dysfunction and hemodynamics in vitamin B12 deficiency’, Autonomic Neuroscience, 97(1), pp. 45–54. doi: 10.1016/s1566-0702(01)00393-9.
Chapman, L.E., Darling, A.L. and Brown, J.E. (2016) ‘Association between metformin and vitamin B12 deficiency in patients with type 2 diabetes: A systematic review and meta-analysis’, Diabetes & Metabolism, . doi: 10.1016/j.diabet.2016.03.008.
Devalia, V., Hamilton, M.S. and Molloy, A.M. (2014) ‘Guidelines for the diagnosis and treatment of cobalamin and folate disorders’, British Journal of Haematology, 166(4), pp. 496–513. doi: 10.1111/bjh.12959.
Fogelman, Y., Kitai, E., Blumberg, G., Golan-Cohen, A., Rapoport, M. and Carmeli, E. (2016) ‘Vitamin B12 screening in metformin-treated diabetics in primary care: Were elderly patients less likely to be tested?’, Aging Clinical and Experimental Research, . doi: 10.1007/s40520-016-0546-1.
Hunt, A., Harrington, D. and Robinson, S. (2014) ‘Vitamin B12 deficiency’, BMJ, 349(sep04 1), pp. g5226–g5226. doi: 10.1136/bmj.g5226.
Kearney, F., Moore, A. and Donegan, C. (2007) ‘Orthostatic hypotension in older patients’, Reviews in Clinical Gerontology, 17(04), p. 259. doi: 10.1017/s0959259808002554.
Lewerin, C., Nilsson-Ehle, H., Jacobsson, S., Johansson, H., Sundh, V., Karlsson, M.K., Ljunggren, Ö., Lorentzon, M., Kanis, J.A., Lerner, U.H., Cummings, S.R., Ohlsson, C. and Mellström, D. (2013) ‘Low holotranscobalamin and cobalamins predict incident fractures in elderly men: The MrOS Sweden’, Osteoporosis International, 25(1), pp. 131–140. doi: 10.1007/s00198-013-2527-y.
Loikas, S., Koskinen, P., Irjala, K., Lopponen, M., Isoaho, R., Kivela, S.. and Pelliniemi, T.. (2007) ‘Vitamin B12 deficiency in the aged: A population-based study’, Age and Ageing, 36(2), pp. 177–183. doi: 10.1093/ageing/afl150.
McCaddon, A. (2013) ‘Vitamin B12 in neurology and ageing; clinical and genetic aspects’, Biochimie, 95(5), pp. 1066–1076. doi: 10.1016/j.biochi.2012.11.017.
Moore, A., Ryan, J., Watts, M., Pillay, I., Clinch, D. and Lyons, D. (2004) ‘Orthostatic tolerance in older patients with vitamin B12 deficiency before and after vitamin B12 replacement’, Clinical Autonomic Research, 14(2), pp. 67–71. doi: 10.1007/s10286-004-0142-x.
Moore, E., Pasco, J., Mander, A., Sanders, K., Carne, R., Jenkins, N., Black, M., Schneider, H., Ames, D. and Watters, D. (2014) ‘The prevalence of vitamin B12 deficiency in a random sample from the Australian population’, Journal of Investigational Biochemistry, 3(3), p. 95. doi: 10.5455/jib.20140716041521.
Niafar, M., Hai, F., Porhomayon, J. and Nader, N.D. (2014) ‘The role of metformin on vitamin B12 deficiency: A meta-analysis review’, Internal and Emergency Medicine, 10(1), pp. 93–102. doi: 10.1007/s11739-014-1157-5.
Smith, A.D.M. (1960) ‘Megaloblastic madness’, BMJ, 2(5216), pp. 1840–5. doi: 10.1136/bmj.1.5223.427-a.
Vieira, E.R., Palmer, R.C. and Chaves, P.H.M. (2016) ‘Prevention of falls in older people living in the community’, BMJ, , p. i1419. doi: 10.1136/bmj.i1419.

Competing interests: No competing interests

13 May 2016
Joanne Younge
Associate Specialist Old Age Psychiatry, Clinical Lecturer CBT.
South Eastern HSC Trust, Queen's university, Belfast
South Eastern HSC Trust, Newtownards Road, Dundonald, Northern Ireland