Vitamin B12 (AKA cobalamin)

Vitamin B12 is a water-soluble vitamin that your body cannot make on its own. This means you must get Vitamin B12 from food and/or supplements.

Why is it important?

In addition to providing energy, Vitamin B12 is important for many cellular processes including the creation of DNA and red blood cells. It is an important cofactor for certain enzymatic reactions in the body and is interdependent with other B vitamins, most notably VitaminsB2,B6, andB9 (folate). You need sufficient levels of Vitamin B12 for normal function of your nervous system, production of neurotransmitters and hormones, and forhealthy immune system function.(Think: sitting at work or in class and having no energy/focus/motivation to get a project done).

Symptoms of deficiency

Brain	Body
Mental fogginess Memory loss Disorientation Depression Apathy	Numbness/tingling of extremities Fatigue and lack of energy Muscle weakness Difficulty walking

Causes of deficiency

There are a variety of factors that can contribute to Vitamin B12 deficiency or insufficiency. We’re going to use some very medical terms for some of them, but the main thing you need to keep in mind is that Vitamin B12 deficiencies are most commonly caused by problems withabsorptionand/ormetabolism.Absorptionis how well your body “soaks up” the available B12 when it is released from its source, andmetabolismis how well your body can use that available B12.

Common medical conditions and diseases which can result in a Vitamin B12 deficiency due to decreasedabsorptionare:

Perniciousanemia, an autoimmune condition whereby the body’s own antibodies destroy the cells of the stomach. These cells produce an important protein calledintrinsic factor(IF). Thisintrinsic factor(IF) then grabs onto B12 and moves it through the small intestine where it can be absorbed into the bloodstream.Reduced IF = Reduce B12 absorption.(It should be noted that people withendocrine-related autoimmune disorders like diabetes or thyroid diseases may be athigher risk for developing pernicious anemia.)
Atrophic gastritis, a chronic inflammatory disease of the stomach which causes decreased stomach acid production which allows bacteria (H.pylori) in the stomach to flourish. These bacteria interfere with the absorption of Vitamin B12.Approximately 10% to 30% of people over the age of 50 have atrophicgastritis.
Celiac disease,ulcerative colitis,Crohn’s disease, andtropical sprueinterfere with absorption of Vitamin B12.
Bariatric surgeryincreases risk for B12 deficiency because the surgery itself may bypass the area whereintrinsic factor(IF) is produced.
Tapeworms from eating contaminated fish (totally gross!).

Risk factors

Age.B12 deficiencies notably worsen as people age. This is because the cells in the stomach that produce intrinsic factor (IF) are getting old and tired and aren’t producing as much as they used to when they were young and full of energy. This mostly occurs in individuals 60 years or older but can start in the 50s.

Diet.

Dietary factors can be HUGE when it comes to B12 deficiencies.

Vegetarian dietsare the most at risk particularly for pregnant women (62%), children (25% to 85%), adolescents (21% to 41%), and older adults (11% to 90%).

Alcoholismor excessive consumption of alcohol also reduces the body’s ability to absorb Vitamin B12 from food sources.

Medications.

Common Over-the-Counter (OTC)	Commonly Prescribed
Omeprazole (Prilosec) Lansoprazole (Prevacid) Someprazole (Nexium) Rabeprazole (Aciphex) Cimetidine (Tagamet) Famotidine (Pepcid) Ranitidine (Zantac)	Cholestyramine Chloramphenicol Neomycin Colchicine Metformin

Common Over-the-Counter (OTC) medications for the treatment of heartburn, ulcers, and reflux (GERD) like:

Proton-pump inhibitors (PPIs) likeomeprazole,lansoprazole,someprazole, andrabeprazolereduce the pH of stomach acid. Stomach acid is necessary for thereleaseof Vitamin B12 from food. Long-term use of these medications can interfere with thereleaseVitamin B12.
Histamine2-receptor antagonists likecimetidine,famotidine, andranitidine→ decrease theabsorptionof Vitamin B12 from food.

Other prescribed medications like cholestyramine, chloramphenicol, neomycin, colchicine, and metformin → decrease theabsorptionof Vitamin B12 from food.

Decreased release and absorption = decreased Vitamin B12 in your body!

Medical/Health Problems associated with B12 deficiency

Brain	Body	Potential Immune/Covid-19 vulnerabilities
Dementia Brain shrinkage Depression	Macrocytic anemia Megaloblastic anemia Cardiovascular disorders Decreasedimmune function	Elevated homocysteine (see our article on homocysteine) Increased reactive oxygen species (ROS) Metabolic syndrome Increased pro-inflammatory cytokines (IL-1b, IL6, TNF-a)

Natural Sources of Vitamin B12

Chicken	Beef	Fish	Oysters	Mussels	Clams
Milk	Cheese	Yogurt	Eggs	Yeast	Nuts

Notice what’s missing?Fruits and vegetables.Vitamin B12 is not found in plant foodsunless they’ve been fermented.The process of fermentation exposes them to bacteria that make (or synthesize) Vitamin B12. While the human Gastrointestinal (GI) tract is full of interesting bacteria, the kind of bacteria that can produce Vitamin B12 is located way, way down the GI tract in the colon and pretty much the only thing that gets absorbed here is water.

Supplementation

Supplementation with oral Vitamin B12 can be the “work around” if you don’t get enough B12 in your diet due to any of the medical diseases, conditions, or risk factors that are listed above. This is because supplements do not need stomach acid for thereleaseorabsorptionof B12.

There are 3 natural forms of Vitamin B12 and 1 synthetic form:

Natural → hydroxycobalamin (OHCbl)

Natural → methylcobalamin(MeCbl) – found in eggs and milk

Natural → adenosylcobalmin (AdCbl) – found in meats

Synthetic (not natural) →cyanocobalamin (CNCbl) – found in “enriched” foods(think white bread, all-purpose flour, crackers, cookies, and so on)and in many B complex vitamin supplements. To become active or “usable” in the body, this form of Vitamin B12 is broken down into cobalamin andcyanide.Yes, cyanide. There is concern that cyanide can accumulate in the body’s tissues with long-term use of this form of Vitamin B12, particularly forpeople who smoke. There is also some evidence that the cyanide that gets released from this more commonly used form of B12 can cause or contribute tokidneydysfunction.

How do I know what my B12 level is?

You can learn what your Vitamin B12 level is by asking your medical provider to order labs to assess your level. This means ablood draw. As psychiatric providers, we routinely order serum B12 levels on our patients. As a rule, we want our patients to have levels between 800 – 1000 pg/mL. This is the “goal range.” Although someone with a B12 level of 367 pg/mL might appear “normal” per their lab results, it is important to remember that this isactually a suboptimal levelthat will not get “flagged” as being “low”. As psychiatric providers, we believe in getting our patients to “optimal” levels. We also check ahomocysteine levelon our patients (see our article on homocysteine).

There are other labs that could be checked (MMA, TC1, TC2) but these are usually checked in research settings.

Summary

Vitamin B12 deficiencies are common in the general population. They are frequently undiagnosed and untreated. There are several factors that increase the risk for Vitamin B12 deficiency like excessive use of alcohol, vegetarian diets, advancing age, certain medications, and certain medical conditions. Symptoms that may indicate a Vitamin B12 deficiency includefatigue,lower energy,brain fog, memory problems, sad moods, numbness and tingling of the hands and feet, and muscle weakness. AtHealthyBrain, we believe Vitamin B12 is critical to many important processes in the body. Whether you get your B12 from food and/or supplements, make sure you’re getting enough.

“So what will happen when I start taking vitamin B-12? What will I notice?”

Good question! The answer depends on how significant your Vitamin B12 deficiency is (hence why we recommend getting a blood draw to check your level). It also depends on if you have deficiencies in other B vitamins as these will also need to be addressed. Most people with a significant B12 deficiency or insufficiency experience an increase in energy, less brain fog, improved memory, and more stable mood. If you also have numbness and tingling in your fingers and toes, this gets better, too. However, it is very important to understand thattaking Vitamin B12 by itself might not be enough to see asignificant change. This is becauseVitamin B12 works with other B vitamins (likeB2, B6, and B9)and these all need to be “balanced” to get the most benefit. Think of it like driving a car with unbalanced tires. Your car feels funny on the road. You might feel vibrations, it is more difficult to steer, and your tires wear unevenly. So, you take your car in to the shop and are told your tires are unbalanced and need to be rebalanced to fix the problem. You don’t just balance one tire; you have to balance all tires. Focusing on taking only one specific B vitamin can contribute to an imbalance in your body. That’s why we created ourImmune BoostandImmune +MoodBoostwhich have a good balance of important B vitamins. (For more information on individual B vitamins, check out our other blog posts!)

Remember:A HealthyBrain has “balanced Bs!”

References

1. Mitchell, E., Conus, N., Kaput, J. B vitamin polymorphisms and behavior: Evidence of associations with neurodevelopment, depression, schizophrenia, bipolar disorder, and cognitive decline. Neuroscience and Biobehavioral Reviews (2014); 47:307-320.
2. Paul, C., Brady, D. Comparative Bioavailability and Utilization of Particular Forms of B12 Supplements With Potential to Mitigate B12-related Genetic Polymorphisms. Integrative Medicine (2017); 16(1):42-49.
3. Surendran, S., Adaikalakoteswari, A., Saravanan, P., et al. An Update on vitamin B12-related gene polymorphisms and B12 status. Genes & Nutrition (2018); 13(2):1-35.
4. Thakkar, K. and Billa, G. Treatment of vitamin B12 dficiency—Methylcobalamine? Cyancobalamine? Hydroxocobalamin?—clearing the confusion. European Journal of Clinical Nutrition (2015); 69:1-2.
5. Vanita, R.A., Eldelstein, S.L., Goldbert, R.B., et al. Long-term Metformin Use and Vitamin B12 deficiency in the Diabetes Prevention Program Outcomes Study. Journal of Clinical Endocrinology & Metabolism; 101(4):1754-1761.
6. Young, L.M., Pipingas, A., White, D.J., et al. A Systematic Review and Meta-Analysis of B Vitamin Supplementation on Depressive Symptoms, Anxiety, and Stress: Effects on Healthy and ‘At-Risk’ Individuals. Nutrients (2019); 11, 2232:1-19.

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