Tag Archives: methylmalonic acid

Serum levels of vitamin B12 are not accurate for brain health and cognition

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Numerous times over the past couple decades I’ve regrettably had to contradict a colleague when a patient has been told that their serum levels of vitamin B12 are adequate and supplementation is not warranted. A study just published in the journal Neurology offering yet more evidence that serum vitamin B12 levels within the typical normal range can mislead about serious consequences of B12 deficiency in the brain. The authors’ intent was to…

“…investigate the interrelations of serum vitamin B12 markers with brain volumes, cerebral infarcts, and performance in different cognitive domains in a biracial population sample cross-sectionally.”

They examined serum markers of vitamin B12 in relation to neuropsychological tests of 5 cognitive domains and brain MRI studies obtained on average 4.6 years later among 121 older community dwelling adults. The data paint an important picture:

“Concentrations of all vitamin B12–related markers, but not serum vitamin B12 itself, were associated with global cognitive function and with total brain volume. Methylmalonate levels were associated with poorer episodic memory and perceptual speed, and cystathionine and 2-methylcitrate with poorer episodic and semantic memory. Homocysteine concentrations were associated with decreased total brain volume. The homocysteine-global cognition effect was modified and no longer statistically significant with adjustment for white matter volume or cerebral infarcts. The methylmalonate-global cognition effect was modified and no longer significant with adjustment for total brain volume.”

In other words, the decrease in total brain volume due to vitamin B12 insufficiency appeared to the mediating the impact on function of the markers besides homocysteine (also associated with brains infarcts)—and serum B12 did not correlate with the MRI or cognitive testing results. For lay readers, your brain can be shrinking with concomitant loss of cognitive function due to B12 insufficiency and the blood test for B12 can still appear normal. The authors’ conclusion needs to become common knowledge among all practitioners:

“Methylmalonate, a specific marker of B12 deficiency, may affect cognition by reducing total brain volume whereas the effect of homocysteine (nonspecific to vitamin B12 deficiency) on cognitive performance may be mediated through increased white matter hyperintensity and cerebral infarcts. Vitamin B12 status may affect the brain through multiple mechanisms.”

Note: methylmalonate (methylmalonic acid) in urine or serum, while not perfect, are practicable. This study also adds more evidence to the importance of homocysteine and brain health.

More evidence that metformin can cause vitamin B12 deficiency

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British Medical JournalPatients with advanced diabetes whose insulin receptors have sustained years of damaging insult sometimes require the medication metformin. Clinicians and patients alike need to bear in mind that metformin tends to cause a deficiency of the critical nutrient cofactor vitamin B12. Research just published in the British Medical Journal reminds us that this is not in question or a matter of opinion. The authors set out to…

“…study the effects of metformin on the incidence of vitamin B-12 deficiency (<150 pmol/l), low concentrations of vitamin B-12 (150-220 pmol/l), and folate and homocysteine concentrations in patients with type 2 diabetes receiving treatment with insulin.”

Incidentally, this reference for vitamin B-12 is extremely low and far from optimal. After following 390 patients with type 2 diabetes who were treated with 850 mg metformin or placebo three times a day for 4.3 years, what did they conclude from their data?

“Long term treatment with metformin increases the risk of vitamin B-12 deficiency, which results in raised homocysteine concentrations. Vitamin B-12 deficiency is preventable; therefore, our findings suggest that regular measurement of vitamin B-12 concentrations during long term metformin treatment should be strongly considered.”

Do remember that serum B12 is not a reliable indicator. To ascertain that your genetic and circumstantial needs for this critical cofactor are actually being methylmalonic acid, measured in serum or urine, is much more reliable.