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

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.

Choice of breakfast staple impacts brain size and cognition in children

A fascinating study conducted by Japanese researchers just published in PLoS One (Public Library of Science) demonstrates a significantly larger brain volume and a higher IQ in healthy children depending on whether their breakfast staple was rice or bread. The authors state:

Childhood diet is important for brain development. Furthermore, the quality of breakfast is thought to affect the cognitive functioning of well-nourished children. To analyze the relationship among breakfast staple type, gray matter volume, and intelligence quotient (IQ) in 290 healthy children, we used magnetic resonance images and applied voxel-based morphometry.”

They divided their study groups into those children who consumed rice, bread or both as their breakfast staple, controlled for a range of dietary, biological and socioeconomic variables, and analyzed the data.

“We showed that the rice group had a significantly larger gray matter ratio (gray matter volume percentage divided by intracranial volume) and significantly larger regional gray matter volumes of several regions, including the left superior temporal gyrus…The perceptual organization index (POI; IQ subcomponent) of the rice group was significantly higher than that of the bread group.”

Their study didn’t investigate what would be the underlying causes of such a difference, but they speculated that glycemic index may play a role:

“Although several factors may have affected the results, one possible mechanism underlying the difference between the bread and the rice groups may be the difference in the glycemic index (GI) of these two substances; foods with a low GI are associated with less blood-glucose fluctuation than are those with a high GI.”

However, the glycemic index of both rice and bread is relatively high compared to eggs. Drawing on a large body of published research, we can rationally advance the idea that gluten may be the decisive factor in the documented differences in brain volume and IQ. It is difficult to argue with their conclusion:

“Our study suggests that breakfast staple type affects brain gray and white matter volumes and cognitive function in healthy children; therefore, a diet of optimal nutrition is important for brain maturation during childhood and adolescence.”

Even mild anemia has a big impact

Because anemia degrades the ability of the blood to carry oxygen to every cell in the body it has a profound and global affect on function, especially for the brain. Sadly, this is often ‘written off’ in older folks who miss out on the care they need.

Haematologica 0109Here’s a paper published in the journal Haematologica that opens with…

Mild anemia is a frequent laboratory finding in the elderly usually disregarded in everyday practice as an innocent bystander.”

They took over three years to investigate the association of mild anemia with hospitalization and mortality in 7,536 subjects. Here’s what their data showed:

“The risk of hospitalization in the 3 years following recruitment was higher among the mildly anemic…Mortality risk in the following 3.5 years was also higher among the mildly anemic elderly…Similar results were found when slightly elevating the lower limit of normal hemoglobin concentration to 12.2 g/dL in women and to 13.2 g/dL in men.”

They conclude with this statement:

“After controlling for many potential confounders, mild grade anemia was found to be prospectively associated with clinically relevant outcomes such as increased risk of hospitalization and all-cause mortality.”

MedicineA study published not long ago in the journal Medicine also highlights the fact that even borderline anemia can have a big effect. First they note:

“The occurrence of anemia in older adults has been associated with adverse outcomes including functional decline, disability, morbidity, and mortality.”

In their study…

“Anemia was defined as hemoglobin <13 g/dL for men or <12g/dL for women.”

These levels are almost always ignored by most doctors. Here’s what their data showed:

“Anemia was associated with greater fatigue, lower handgrip strength, increased number of disabilities, and more depressive symptoms. Multivariate regression analysis…demonstrated strong associations for reduced hemoglobin, even within the “normal” range, and poorer health-related quality of life across multiple domains.”

Leading to the conclusion:

“Thus, anemia was independently associated with clinically significant impairments…Mildly low hemoglobin levels, even when above the World Health Organization (WHO) anemia threshold, were associated with significant declines in quality of life among the elderly.”

Current Opinion in HematologyAnother paper published in Current Opinion in Hematology begins with the familiar observation:

Anemia is common in older adults and is an independent predictor for increased morbidity and mortality in several disease states. Older persons with anemia suffer hospitalization, physical decline, and disability at higher rates than those people without anemia.”

In their study they found that a third of the cases were due to nutritional deficiencies (!), a third from chronic disease, and a third were unexplained (more on that in a future post). They too found that it predicted diminished physical performance and mobility, and reported the same finding that clarifies how we should understand ‘low’:

“The data suggest that the risk of mortality and loss of mobility even extends to levels of hemoglobin normally considered low normal by WHO criteria….”

Practitioners take note of their parting comment:

“Anemia is a common modifiable predictor of poor medical outcome in older adults and, as such, should be actively managed.”

PLoS OneI’ll introduce one more paper published in the Public Library of Science (PLoS One) that focuses on the damage to cognition and mood caused by mild anemia. In this study mood (depression), cognition, attention, memory and quality of life were all quantified for 4,068 individuals. Here’s what their data showed:

“In univariate analyses, mild anemic elderly persons had significantly worse results on almost all cognitive, functional, mood, and QoL (Quality of Life) measures. In multivariable logistic regressions…mild anemia remained significantly associated with measures of selective attention and disease-specific QoL.”

As in other studies, when the reference range was narrowed to a more precise ‘functional’ level, the deleterious effect of mild anemia was clear:

“When the lower limit of normal hemoglobin concentration according to WHO criteria was raised to define anemia (+0.2 g/dL), differences between mild anemic and non anemic elderly persons tended to increase on almost every variable.”

Here’s the bottom line: mild anemia has a profoundly negative impact on every aspect of function and should be investigated diligently as to its cause and treated accordingly.

Medium Chain Fatty Acids Improve Cognitive Function

You may remember that we use Medium Chain Triglycerides (MCT) in their pure form to make medical foods such as Clearvite® and Ultrameal® more complete. This form of fat is especially easy for the body to burn for energy, supports metabolism and stabilizes blood sugar. Two very interesting papers in the journals Diabetes and Neurobiology of Aging document that MCT oils also oppose neurodegeneration related to glucose dysregulation and improve cognition:

  1. Cognitive function improves in Type 1 Diabetes
  2. Memory improves with Alzheimer’s

MCT’s are abundant in coconut butter, and easily added to shakes in the form of MCT Oil which is liquid at room temperature.