An epidemic of misdiagnoses and missed diagnosis
The BCA’s new strategic position has made it clear that as an Association we are to do the very best for our patients, to treat them well, in all senses, and to help them heal and be healthy. Understanding the role that Vitamin B12 deficiency plays in chronic pain, mood/behavioural issues and energy/fatigue, and how these are reflected in key parts of the guidance that the NHS provides, is, in my opinion, one true step forward to becoming integral to UK healthcare.
Vitamin B12 (cobalamin) is a non-toxic, water-soluble nutrient which is the rate limiting factor in two critical enzymes in the body. B12 can have a profound impact on energy production within the mitochondria and methylation, affecting the production of myelin and neurotransmitters and the accumulation of the toxic and highly inflammatory intermediary, homocysteine.
The inflammatory nature of homocysteine and the effects of decreased myelin production before the occurrence of overt demyelination create a sustained low grade inflammatory response with a relative hyperexcitation of the peripheral and central nervous system. In a clinical setting, this creates a relative exaggeration of existing symptomatic neuro-mechanical dysfunction and diagnosed/undiagnosed macro/micro connective tissue damage.
The effects of inflammation on neurotransmitter production (reduced serotonin production, increased quinolinic acid production) also create a tendency towards mood and behavioural changes, often diagnosed as depression and anxiety. Additionally, the decreased mitochondrial output creates low motivation which is often misdiagnosed as ‘depression’.
Deficiency/sub-optimal cellular levels of Vitamin B12, via its metabolic effects through two key enzymes, creates a unifying cause of persistent pain, depression/anxiety and fatigue. This gives us the opportunity to address the root cause of all three, rather than viewing them solely through the lens of association, as done with the biopsychosocial model.
The Vitamin B12 and back pain connection is reflected within the scientific literature in terms of treatment of acute and chronic spinal conditions with the administration of B12 (often with other B vitamins). Chiu et al. showed a 32% drop in chronic low back pain with B12 injections over a two-week period, compared to placebo (it is worth noting that the patients had no form of blood test to assess B12 status).
Critical issues around testing for B12 levels
In 1849, Thomas Addison described a lethal condition in which sufferers developed severe neurological symptoms (pins and needles, numbness, ataxia and eventually paralysis, psychosis and glossitis (sore tongue)). The patients also had obvious anaemia and thus it became known eventually as ‘pernicious anaemia’.
Due to its historical association with anaemia, it is common for medical doctors to screen indirectly for B12 deficiency via a full blood count, looking for megaloblastic anaemia (raised mean cell volume – MCV/macrocytosis).
Unfortunately, there are two key issues which make this unreliable:
- If the patient has been taking folic acid, this will normalise the blood cell appearance and create a false negative. This is not simply due to supplements but also due to the widespread fortification of foods with folic acid and has been shown by some authors to lower the rates of macrocytosis in patients with proven B12 deficiency (Wyckoff).
- Slowly reducing B12 levels will impact the energy production in the mitochondria and the methylation pathways, affecting myelin production before it can create macrocytic anaemia (if ever). Thus, many patients have been told they are not B12 deficient but never had their actual levels assessed.
This is reflected in the UK guidelines, “the absence of a raised MCV cannot be used to exclude the need for cobalamin testing because neurological impairment occurs with a normal MCV in 25% of cases”.
Blood testing for B12 directly hasn’t got a ‘gold standard’ either
Total/serum B12 contains both the active/useable fraction (holotranscobalamin) and the inactive fraction bound to a carrier (holohaptocorrin). The inactive fraction can be between 70-90% of the total Vitamin B12 measured.
Laboratory ranges can vary but many will consider under 160 pmol/L (216 ng/l, pg/L) to be a cut-off for confirming deficiency. However, many clinicians and some researchers feel there is a large grey zone between 160-500 pmol/L, which in some patients could represent functional deficiency on a cellular level. Therefore, patients with strong clinical symptoms of B12 deficiency and levels in the low normal range may well be physiologically deficient but declared ‘normal’.
We do not have the ability to measure the active fraction only and conclusive cut-off points to define deficiency are not currently possible.
One of the criticisms of blood testing for B12 is that it is just that, a reflection of B12 in the blood, not the cell. It is within the cell that it is used for energy production and methylation of myelin and neurotransmitters. Thus, the following two tests can be used to confirm B12 issues on a cellular level:
- Homocysteine is a valid and reliable intracellular/functional marker of methylation. However, it is not specific to B12 and can reflect reduced levels of B6 and folate. Levels over 10 umol/L are widely considered to be high and thus a reflection of low B12, B6 and/or folate.
- Methylmalonic acid (MMA) is an intermediary molecule in the mitochondria which builds up as B12 levels drop and spills out into the urine and blood, indicating a relatively low B12 level.
These frequently start to increase as B12 levels drop into the clinical grey zone of 160-500 pmol/L.
Thus, in my clinical practice, given the uncertainty about B12 blood levels, if a patient has symptoms suggestive of B12 levels affecting cellular function, unless he/she wishes to undertake further testing with homocysteine and MMA, a trial of sublingual B12 in the active form at 1-2000 mcg daily (to avoid malabsorption issues) is a reasonable course of action.
This is reflected in the UK guidelines, which state that “in the presence of discordance between the test results and strong clinical features of deficiency, treatment should not be delayed, to avoid neurological impairment.”
To us as chiropractors, missing a diagnosis of a functional B12 deficiency may mean the difference between a successful treatment for low back pain or a failure. But to the patient, as the deficiency progresses, it could be the difference between life, disability and death.
By Simon Billings
Founder of the Academy of Chiropractic Nutrition, a system of nutrition and functional medicine knowledge for chiropractors.