Vitamin B12. Don’t you love it? The pretty, bright red color? Sublingual or liquid B12 often has a tasty cherry flavor to match its natural color, making it fun to look at and to take.

The Merits of B12 are Legendary

It’s essential for normal neurological function, hematopoiesis, GI function, energy, and methylation. Recently, I read about B12-associated mitochondropathy, where the organelle itself becomes sub-functioning and hypertrophic as a result of the deficiency.

When you need “the 12,” it’s an honest-to-goodness, feel-good vitamin, is it not?

Research Emerging Regarding the Dire Consequences of B12 Deficiency

Recently, deficiency was associated with brain atrophy. However, deficiency wasn’t identified using serum B12 (not surprising, is it?), but rather methylmalonic acid (MMA) and homocysteine (Hcy). The IFM’s Joel Dahms summed it up:

 

“In a new study researchers found that higher levels of MMA and Hcy (indicating B12 deficiency), were associated with lower global cognitive function scores and lower total brain volume five years later. They found no relationship between serum vitamin B12 concentration and either global cognitive function or total brain volume…

“They found that 17.5% of participants had elevated Hcy levels, defined as higher than 14 μmol/L, and 15.2% had elevated MMA concentrations (>271 nmol/L). Serum Hcy and MMA concentrations were highly correlated... [n=121]”

 

The sensitivity of MMA over serum B12 was first established years ago using Framingham data. Around that time, MMA (specifically urine MMA) was endowed with the heady title of “gold standard” – though serum and urine are both used as specimens, and are arguably comparable.

Yet, clinicians still cling to serum B12.

In my practice, a patient’s data on MMA, mean cell volume, and homocysteine was recently ignored by a colleague. Instead he asked:  “where’s the serum B12 result?” 

But wait, many doctors are embracing MMA these days. One can readily obtain an insurance-reimbursed serum MMA from any standard reference laboratory.

However, when a doc finally makes the journey over to MMA, they are highly likely to find the test NOT POSITIVE. Indeed, they may actually find the serum B12 more sensitive.

You say: “Kara, are you serious?”

To quote the Directory of Services from an unnamed lab regarding MMA serum:

 

“the reference range has been set at +3 SD [standard deviations] above the mean for healthy blood bank donors. In the clinical assessment of patients with megaloblastic anemias a cutoff of +3 SD provides greater specificity in the diagnosis of the vitamin deficiency states, despite the sacrifice of some sensitivity.”

 

Well… Thanks for making tht decision for me! Have y'all had your brains weighed recently? (I say that as a friend.)

A Quick Look at a Bell Curve to Refresh Ourselves on Standard Deviations:

^{From Wikipedia (Petter Strandmark, based (in concept) on figure by Jeremy Kemp, on 2005-02-09}

Okay. At +3SD, exactly 0.1% of the population will be positive for MMA-diagnosed B12 deficiency using your assay. I’d say you’ve achieved a very high specificity. But sadly, we’ll miss almost all of those who need the nutrient.

Being a doctor who has “grown up” with nutrient (and functional nutrient marker) data ranked in quintiles flanked by 2 standard deviations, I am used to being in the driver’s seat when it comes to interpretation. It’s a perestroika of sorts. As Dr. Richard Lord says frequently, “let the data speak for itself!” However, we need to give it a voice with which to speak! And seeing the data completely, I can make good decisions regarding my patient’s nutrient needs. Yes, that can involve extra work, extra time in the research defining significance, but if health and disease prevention is the goal, it must be done. Period.

Look at it This Way

According to NHANES, less than 50% of the US population meets the DRI of magnesium (about 7% for potassium, 13% for vitamin E, 50% for vitamin C, and on and on). I need to see where my patient falls within the highly deficient population that is being employed to create reference ranges in the first place. The evidence is clear: Simply being “within normal limits” is not good enough with regard to nutrient status, let alone moving the normal limits to the outer limits of +3SD.

Incidentally, in the above referenced study, MMA cutoff is set lower than either of the two (most famous) reference labs. One would assume the study uses a more logical +2SD standard for clinical laboratory ranges (they don’t mention the SD, specifically). I wonder what the findings in the study would be if they ranked the data and investigated trends? How much disease could be easily prevented by increasing sensitivity for nutrient testing if only just a smidge?

~ Kara Fitzgerald, ND

Dr Fitzgerald is co-author of Case Studies in Integrative and Functional Medicine, and is on faculty for the Institute for Functional Medicine. She has a clinic and consulting practice in Sandy Hook CT. To schedule with Dr. Fitzgerald, or learn more about her work, visit www.drkarafitzgerald.com.

References

• Tangney C.C., et al. (2011). Vitamin B12, cognition, and brain MRI measures: A cross-sectional examination Neurology, 77 (13), 1276-1282.