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

Posted on October 3, 2011 by Dr. Jonathan

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.

Vitamin C sometimes indicated to lower homocysteine

Posted on January 3, 2011 by Dr. Jonathan

As a practicing clinician (or knowledgeable layperson) have you encountered patients who continue to have higher plasma homocysteine levels than you’d like despite objective laboratory evidence (such as the relevant organic acids) that they are replete for vitamin B12, folic acid and vitamin B6? (I have.) A paper just published in the Annals of Nutrition & Metabolism throws some welcome light on the matter. The authors state:

“The factors influencing total plasma homocysteine levels (tHcy) are of special interest in the attempt to reduce cardiovascular risk…This investigation aimed to assess the independent effects of antioxidant vitamins on tHcy in elderly people.”

The authors examined 184 subjects in an aging population in Giessen (GISELA), Germany for the effects of plasma levels, intake and supplementation of vitamin C, vitamin E, and β-carotene on tHcy. What did their data show?

“Serum folate, the estimated glomerular filtration rate (eGFR), and plasma vitamin C showed a negative association with tHcy in simple regression analysis. In a subsequent multiple regression analysis, eGFR, serum folate, and plasma vitamin C were the relevant independent predictors of tHcy.”

In other words, higher plasma vitamin C was associated with lower homocysteine (along with the already recognized folic acid and eGFR as a metric for kidney function). There is good evidence for the importance of homocysteine in brain as well as cardiovascular health. The authors’ conclusion can be brought to mind when homocysteine levels fail to reach optimum despite the well-known interventions:

“Vitamin C may be an independent predictor of tHcy in free-living elderly people and, therefore, should be considered in attempts to reduce tHcy.“

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Another warning about metformin for diabetes and Vitamin B12

Posted on March 16, 2010 by Dr. Jonathan

Diabetes Care 0210 Judging from the tone of this paper just published in the journal Diabetes Care, there are still too few professionals and lay people alike who are not aware that Vitamin B12 must be attended to when taking the type 2 diabetes drug metformin. The authors focus on the varying severity of diabetic neuropathy and observe:

“Long-term use of metformin is associated with malabsorption of vitamin B12 (cobalamin [Cbl]) and elevated homocysteine (Hcy) and methylmalonic acid (MMA) levels, which may have deleterious effects on peripheral nerves.”

It won’t surprise any readers of these posts that their data showed…

“Metformin-treated patients had depressed Cbl levels and elevated fasting MMA and Hcy levels. Clinical and electrophysiological measures identified more severe peripheral neuropathy in these patients; the cumulative metformin dose correlated strongly with these clinical and paraclinical group differences.”

Their conclusion:

“Metformin exposure may be an iatrogenic cause for exacerbation of peripheral neuropathy in patients with type 2 diabetes. Interval screening for Cbl deficiency and systemic Cbl therapy should be considered upon initiation of, as well as during, metformin therapy to detect potential secondary causes of worsening peripheral neuropathy.”

Remember, when taking metformin you need to check your B12 levels, not by measuring it in the serum (blood) which is unreliable, but with methylmalonic acid in the blood or urine (not perfect but better) and keeping an eye on homocysteine.

Homocysteine and Brain Atrophy

Posted on October 12, 2009 by Dr. Jonathan

Homocysteine is a powerful risk factor for cardiovascular disease. Many of you have had it checked in your screening blood test for that reason, and because it is a nutritional marker for the vital process called methylation. Not surprisingly, we now have evidence that even smaller elevations of homocysteine are associated with neurodegeneration bad enough to cause brain shrinkage. Low stomach acid, estrogen supplementation and birth control pills are common causes of elevated homocysteine.