In the world of integrative medicine and functional psychiatry, we talk a lot about the importance of nutrition and micronutrient status for mental health. Yet, one of the most overlooked and underdiagnosed deficiencies—one that can have a profound impact on mood, cognition, and overall well-being—is vitamin B12.
The Problem with Current B12 Testing
Most clinicians rely on standard serum B12 tests to assess levels, but this method is deeply flawed. A so-called “normal” B12 level, typically defined as above 200 pg/mL in the U.S., does not necessarily mean optimal. In fact, neurological symptoms can start appearing even in the lower end of the normal range. In a recent study, in a sample of older adults without any diagnosed cognitive disorders, those who had B12 levels in the lower end of the normal range were more likely to exhibit cognitive and neurological changes as well as structural changes in the brain indicative of neurodegeneration (Beaudry-Richard et al., 2025). The same authors concluded, “These findings suggest that current parameters for defining adequate B12 levels may be inappropriate when considering neurophysiological, neuropsychological, serological, and neuroradiological outcomes.”
Worse yet, serum B12 doesn’t tell us how well the body is actually utilizing the vitamin at the cellular level. Functional markers like methylmalonic acid (MMA) and homocysteine provide a clearer picture and can assist clinicians in identifying B12 inadequacy when a serum B12 is in the normal range. Unfortunately, these tests are rarely ordered in conventional settings and aren’t always covered by insurance companies. Holotranscobalamin (holoTC) is another biomarker that can provide insight into a person’s B12 status and ability to absorb it properly (Green, 2017). However, it is unavailable through conventional laboratories in the United States
How Many People Are Affected by a B12 Deficiency? More Than You Think…
B12 deficiency is often associated with strict vegan or vegetarian diets, but the reality is that many people—even omnivores—suffer from inadequate levels. Absorption issues are common, especially among older adults, those with gut health conditions (IBS, celiac, IBD, or low stomach acid), individuals on acid-blocking medications, exposure to certain toxins and chemicals. including nitrous oxide—commonly used as an anaesthetic—and even people with genetic variants that impact methylation, including the oft-discussed MTHFR mutations (Ankar & Kumar, 2024) (Shiran et al., 2015).
This isn’t just a minor nutritional gap. B12 is essential for red blood cell formation, nerve function, and DNA synthesis. Without it, the body—and the brain—suffers.
The Mental Health Connection
B12 plays a critical role in neurotransmitter production, myelin formation in the brain, and overall cognitive function. Deficiency has been linked to:
- Depression – Low B12 levels have often been found to correlate with levels of depression in patients (Fatima et al, 2023).
- Cognitive Decline – Memory issues, brain fog, and even early signs of dementia can be driven by inadequate B12 levels (Jatoi et al., 2020).
- Fatigue & Motivational Challenges – Many people struggling with persistent fatigue may actually be experiencing neurological effects of B12 deficiency (Pfnür, 2022).
- Psychosis & Paranoia – In severe cases, B12 deficiency has even been linked to psychotic symptoms that are sometimes misdiagnosed as primary psychiatric disorders (Sahu et al., 2022).
Why Are We Missing B12 Deficiencies?
The symptoms of B12 deficiency overlap with many common psychiatric and neurological conditions, leading to frequent misdiagnosis. Instead of identifying and treating the root cause, patients are often prescribed antidepressants, stimulants, or other medications—while the underlying deficiency goes unaddressed.
What Can We Do?
- Rethink Testing – Serum B12 alone isn’t enough. Clinicians should consider checking MMA, homocysteine, and in some cases, intrinsic factor antibodies to get a full picture of B12 status.
- Look Beyond Diet – While diet is a factor, absorption is often the bigger issue. Patients on metformin, PPIs, or those with gut inflammation may require B12 supplementation even if they eat animal products.
- Use the Right Form – Not all B12 supplements are created equal. Methylcobalamin, adenosylcobalamin, and hydroxycobalamin are the most bioavailable forms, whereas cyanocobalamin (the synthetic form used in many conventional supplements) is less effective, especially for those with methylation challenges (Paul & Brady, 2017).
- Consider Injections for Severe Deficiency – In cases of significant deficiency or absorption issues, intramuscular B12 injections can be a game changer.
The Bottom Line
B12 deficiency is more common than many realize and can be a hidden driver of mental health and cognitive issues. Since conventional testing often misses cases of suboptimal B12 levels, providers often need to take a more comprehensive approach—prioritizing thorough assessment and targeted treatment while also addressing the underlying causes. The right form and delivery method will vary based on individual needs, but ensuring adequate B12 is a simple yet powerful intervention we can’t afford to overlook.
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References
Ankar A, Kumar A. Vitamin B12 Deficiency. In: StatPearls. Treasure Island (FL): StatPearls Publishing; September 10, 2024.
Beaudry-Richard A, Abdelhak A, Saloner R, et al. Vitamin B12 Levels Association with Functional and Structural Biomarkers of Central Nervous System Injury in Older Adults. Ann Neurol. Published online February 10, 2025. doi:10.1002/ana.27200
Fatima A, Shah F, Khan HS, Rauf K, Ali S, Khan SA. Frequency Of Depression In Patients With Vitamin B12 Deficiency. JRMC [Internet]. 2023 Jun. 24 [cited 2025 Mar. 27];27(2). Available from: https://journalrmc.com/index.php/JRMC/article/view/2039
Green R. Vitamin B12 deficiency from the perspective of a practicing hematologist. Blood. 2017;129(19):2603-2611. doi:10.1182/blood-2016-10-569186
Jatoi S, Hafeez A, Riaz SU, Ali A, Ghauri MI, Zehra M. Low Vitamin B12 Levels: An Underestimated Cause Of Minimal Cognitive Impairment And Dementia. Cureus. 2020;12(2):e6976. Published 2020 Feb 13. doi:10.7759/cureus.6976
Paul C, Brady DM. Comparative Bioavailability and Utilization of Particular Forms of B12 Supplements With Potential to Mitigate B12-related Genetic Polymorphisms. Integr Med (Encinitas). 2017;16(1):42-49.
Pfnür IAH. Vitamin B12 Deficiency as the Cause. Dtsch Arztebl Int. 2022;119(12):216. doi:10.3238/arztebl.m2022.0053
Sahu P, Thippeswamy H, Chaturvedi SK. Neuropsychiatric manifestations in vitamin B12 deficiency. Vitam Horm. 2022;119:457-470. doi:10.1016/bs.vh.2022.01.001
Shiran A, Remer E, Asmer I, et al. Association of Vitamin B12 Deficiency with Homozygosity of the TT MTHFR C677T Genotype, Hyperhomocysteinemia, and Endothelial Cell Dysfunction. Isr Med Assoc J. 2015;17(5):288-292.
Zielińska M, Łuszczki E, Dereń K. Dietary Nutrient Deficiencies and Risk of Depression (Review Article 2018-2023). Nutrients. 2023;15(11):2433. Published 2023 May 23. doi:10.3390/nu15112433
