B12: When Normal Isn't Enough

In this episode of Daily Value, we look at recent research suggesting that the B12 levels we’ve always accepted as "normal" might silently be failing our brains. New data reveals that standard B12 thresholds may not adequately shield us from subtle neurological decline. Are current diagnostics overlooking hidden deficiencies? We go into how B12 truly supports your nervous system, the overlooked significance of active B12, and why traditional treatments might need reconsideration, particularly for those struggling with absorption. Perhaps the path to preserving cognitive health lies in rethinking what we thought we knew about vitamin B12.

00:00 Introduction: Rethinking Vitamin B12 Levels

00:33 Understanding Vitamin B12

01:24 The Role of B12 in Neurological Health

01:57 Causes and Consequences of B12 Deficiency

03:00 Reevaluating B12 Sufficiency Standards

04:40 New Research Insights on B12 and Cognitive Health

07:30 Dietary Sources and Bioavailability of B12

08:50 Supplementation and Treatment Strategies

10:50 Challenges in Treating B12 Deficiency

11:55 Conclusion: Towards Optimal Cognitive Health

PMID: 39927551

PMID: 36774098

PMID: 38987879

Chapters

• 0:00 B12 and cognitive decline: new findings
• 0:45 Understanding B12: sources and function
• 2:12 Current thresholds and hidden brain changes
• 4:30 Effects of B12 levels on cognitive function
• 7:30 Dietary sources and bioavailability of B12
• 9:31 B12 supplementation and absorption issues
• 12:05 Treatment approaches and symptom resolution

Transcript

Speaker 1: 0:00

Are your vitamin B12 levels truly protecting your brain? Well, new research is challenging our assumptions, revealing that so-called normal B12 levels could quietly contribute to cognitive decline and hidden neurological changes. In today's episode, we'll explore why standard recommendations might not go far enough and how redefining optimal could transform your cognitive health as you age. Vitamin B12, scientifically known as cobalamin, is an essential water-soluble vitamin necessary for proper functioning of the nervous system, dna synthesis and the formation of healthy red blood cells. B12 is unique in that it is exclusively synthesized by microorganisms like bacteria and archaea. The latter are a group of single-celled microorganisms that, like bacteria, lack a nucleus, but they are genetically and biochemically distinct from bacteria. B12 is naturally found in animal-derived foods such as meat, fish, eggs and dairy, especially those of ruminant origin, meaning animals like cows, sheep, etc. That have specialized stomachs with microbes that synthesize B12 they store in their tissues and use. B12 plays a particularly important role in maintaining the myelin sheath, that's the protective coating around nerve fibers that acts as insulation on a wire ensuring efficient communication between nerve cells. As of now, it's not entirely known how exactly B12 contributes to myelination or prevents demyelination, but what we do know is that insufficient B12 can lead to neurological issues due to impaired myelin integrity, resulting in symptoms such as numbness, tingling, muscle weakness and difficulties. Deficiency typically arises from inadequate dietary intake or impaired absorption due to gastrointestinal issues, surgeries or conditions like pernicious anemia caused by atrophic gastritis. This is an autoimmune-like condition in which chronic inflammation of the intestines causes the loss of parietal cells. These are special cells that produce stomach acid, as well as a protein called intrinsic factor, which is essential for absorbing B12 in the small intestine. Without parietal cells, you can absorb B12 properly, which can lead to deficiency and conditions like pernicious anemia. This is a type of anemia where red blood cells are fewer in number but also larger than normal, but they're not as effective as carrying oxygen.

Speaker 1: 2:42

The body does store vitamin B12, as carrying oxygen. The body does store vitamin B12, approximately 1 to 5 milligrams, mainly in the liver. Most people only lose about 2 to 4 micrograms of B12 daily, which means that these reserves can delay symptoms for years, making early detection of deficiency syndrome challenging. Low B12 levels are associated with increased white matter hyperintensities in the brain, which are indicators of microstructural brain changes linked to cognitive decline. New research suggests that traditional testing for B12 sufficiency may deceive us by measuring only total serum levels, missing the very important active fraction known as holotranscobalamin. This is the form of B12 bound to protein in the bloodstream. This is the only form of B12 that has a specific receptor for cellular uptake. Thus it's considered the active fraction of bodily B12.

Speaker 1: 3:35

It turns out that the boundaries of normal might be dangerously narrow, particularly for aging brains. Current guidelines define deficiency as 148 picomoles per liter, that's 200 picograms per milliliter. These thresholds are coming under scrutiny as evidence mounts that our cognitive health requires levels far beyond what we've accepted as adequate. In fact, the threshold for vitamin B12 deficiency was developed as a simple calculation of three standard deviations below the average US intake. Interestingly, in 2010, the American Society for Nutrition argued that 5% of patients who have a syndrome consistent with B12 deficiency who respond positively to B12 supplementation, have levels of B12 over those considered to be adequate as of right now. Could it be that the standard definition of vitamin B12 sufficiency is failing us, quietly allowing neurological decline? Perhaps it's time to question these boundaries and redefine what truly constitutes optimal vitamin B12 status.

Speaker 1: 4:40

A very recent study published by Baudry, richard et al suggests that beneath the surface of what we consider normal vitamin B12 levels, there is a cognitive risk. Participants in this study with lower levels of active B12 showed greater volumes of white matter hyperintensities. Again, these are markers on brain scans that hint at subtle structural damage. These lesions could reflect unseen disruptions in vascular permeability and the quiet loss of oligodendrocytes. These are cells responsible for maintaining the brain's protective myelin sheath that we talked about.

Speaker 1: 5:15

The negative effects didn't end there. Older adults within the study demonstrated a clear functional link between lower B12 levels and slower cognitive processing speed. Interestingly, the study showed something unexpected Higher total B12, specifically the biologically inactive fraction, that's, b12 bound to haptocorin, correlated with elevated tau protein. That's a marker connected with neurodegenerative disease like Alzheimer's. The biological implications of this relationship remain elusive, raising questions. Does excess inactive B12 trapped by haptochorins somehow diminish the brain's ability to use active B12, inadvertently facilitating tau-mediated neuronal injury? Vitamin B12 is normally known for helping inhibit the formation of misfolded tau proteins. Thus, if haptochorin-bound B12 is indeed reducing the brain's access to usable B12, could it be silently contributing to these destructive accumulations?

Speaker 1: 6:17

These findings shine a new light on the limitations of traditional guidelines. Population-based definitions of micronutrient adequacy might have unknowingly overlooked subtle yet important neurological deficits appearing at both extremes of the B12 continuum levels, historically dismissed as clinically irrelevant Without sensitive diagnostic tools. These nuanced neurological symptoms have long remained hidden and unexplained, often leaving patients frustrated. Even after standard treatments seemingly succeed in addressing hematological or blood-related deficiency syndrome, it's actually a very common occurrence for people to request more B12 to deal with the neurological symptoms after the blood-related symptoms clear. So we have to ask why do some patients continue to demand higher B12 doses to manage lingering neurological symptoms, despite having fully resolved hematological issues? Perhaps it is time to reconsider what we truly understand as a normal vitamin B12 level? Perhaps the answer to safeguarding our cognitive futures lies hidden precisely in these subtler signals we've neglected to acknowledge.

Speaker 1: 7:23

So what does this all mean for you, especially if you're older, plant-based or simply assuming your level are fine? First let's talk diet. We know that what you eat and how much B12 it contains is only half the story. Bioavailability matters, and it's currently thought that approximately 50% of B12 is absorbed from food. Dairy, it turns out, leads the way in bioavailability. In a Quebec-based new age study, older adults consuming over 4 micrograms a day of food-derived B12 without any supplements had significantly reduced odds of biochemical deficiency using the current B12 thresholds. Notably dairy-derived B12, not-meat or organ meats had the strongest association with better B12, not meat or organ meats had the strongest association with better B12 status. Interestingly, dairy's B12 seems to be absorbed more efficiently approximately three times more bioavailable than B12 from meat or fish. This means that a cup of milk with 1.3 micrograms of B12 may actually be more useful than a three-ounce portion of beef containing 2.4 micrograms. In practical terms, a daily intake of 6 to 10 micrograms B12, mostly from natural food sources, appears to saturate biomarkers of sufficiency like holotranscobalamin. That intake of 6 to 10 micrograms is 2.5 to 4 times higher than the current US recommended dietary allowance of 2.4 micrograms per day.

Speaker 1: 8:48

And what about supplements? Here's where things get more nuanced. Supplements provide B12 in free form, not bound to protein, and bypass the need for gastric acid and pepsin. However, absorption efficiency drops dramatically with dose size due to intrinsic factor saturation. That's the protein that binds to B12 in the small intestine and helps it be absorbed. Below 2 micrograms of B12, absorption can reach 50%, but at higher doses, like 500 micrograms or 1 milligram, it plummets to 2 to 1.3%. This means a 500 microgram tablet delivers roughly 10 micrograms absorbed still enough to saturate knees, but far less efficient than most people think when it comes to correcting B12 deficiency, especially in the context of is roughly 10 micrograms absorbed still enough to saturate knees, but far less efficient than most people think.

Speaker 1: 9:31

When it comes to correcting B12 deficiency, especially in the context of malabsorption, food and oral supplements may not be enough. The preferred route is usually intramuscular hydroxycobalamin at 1,000 micrograms per. When it comes to correcting B12 deficiency, especially in the context of malabsorption, food and oral supplements may not be enough. The preferred route is usually intramuscular hydroxycobalamin, 1,000 micrograms per injection, or 1,000 to 2,000 micrograms a day orally for those that can absorb vitamin B12 in the small intestine.

Speaker 1: 10:07

According to US, british and even Dutch clinical practice, initial treatments often start with twice-weekly or alternate-day injections for five weeks until neurological symptoms stabilize. After that, injections are tapered based on clinical response, not lab markers. Importantly, symptom resolution may take months or even years and in many cases full resolution never even occurs. Up to 50% of patients require more frequent injections than the standard two-month maintenance dose. Many remain symptomatic unless treated every two to four weeks, with some people needing weekly injections long-term.

Speaker 1: 10:44

The idea that symptoms resolve in parallel with biomarker normalization is a bit misleading. Symptoms resolve in parallel with biomarker normalization is a bit misleading. B12 levels often normalize far earlier than clinical improvements and symptom relapse frequently does occur without any drop in serum B12 levels. Interestingly enough, this has sparked growing support for the therapeutic trial approach. If a patient presents with neurological or cognitive symptoms suggestive of B12 deficiency, even with normal serum B12, they may benefit from a 3-6 month trial of intramuscular B12 therapy. In such cases, holotranscobalamin, methylmalonic acid and even serum B12 are poor predictors of response. The only reliable endpoint is symptom resolution.

Speaker 1: 11:30

And what of oral therapy for malabsorption? While high doses may normalize labs through passive absorption, real-world efficacy varies dramatically. In fact, passive B12 absorption can be as low as 0.1 to 0.5 percent in some individuals. This is where there is currently no clinical consensus that oral therapy can safely replace injections in patients with confirmed malabsorption of B12. Today we've looked at the hidden complexities surrounding vitamin B12 status, uncovering evidence that challenges established thresholds and treatment guidelines. It appears increasingly clear that current normal reference ranges may inadequately reflect optimal cognitive and neurological health. To truly protect cognitive function across the lifespan, a more precise, individualized approach, considering dietary patterns, absorption capacity, supplementation strategy and clinical symptoms, may be necessary. Given these new insights, perhaps it's time to question whether conventional guidelines adequately protect our most vital asset, our cognitive health. Normal, it seems, may no longer be enough. Thank you for joining me today on Daily Value. As always, stay healthy.