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Why supplement with B12?

Like many nutrients, vitamin B12 plays a number of crucial roles within the human body. While a deficiency is most commonly associated with fatigue, signs and symptoms of tingling in the extremities, restless leg syndrome, anemia or homocysteinema can be indicative of a B12 deficiency. Moreover, many conditions show clinical improvements through supplementation with B12, even when serum B12 lab values may be considered ‘within normal limits’.

What are the different forms of B12?

There are generally 3 forms of supplemental B12: cyanocobalamin, hydroxycobalamin and methylcobalamin. Each of these forms has their own advantages and disadvantages, which we’ll discuss below.


Is the most common form of B12 found in supplements and is a synthetic molecule not naturally found in plants or animals. It is widespread in supplements because of its relatively cheap price and stability. AOR utilizes cyanocobalamin in its Eczema Creamfor this stability reason, as other B12 forms breakdown too quickly in a cream and are, therefore, not suitable as topicals.

The issue with using cyanocobalamin for oral supplementation is that, although it has demonstrated the ability to increase blood levels of B12, its ability to increase tissue levels is limited. In other words, there’s evidence to suggest that the body isn’t actually retaining the vitamin B12 efficiently. For this reason, cyanocobalamin is my least favorite B12 form for oral supplementation. Some people also express concern for cyanide toxicity from this form of supplementation (the “cyano” portion of the molecule is actually cyanide), although this is generally a non-issue in healthy individuals with no other chronic exposure to the compound.


If cyanide toxicity is suspected or a known concern, the best form of vitamin B12 to supplement with is hydroxycobalamin. Hydroxycobalamin is unique in that it has the ability to actually bind cyanide for excretion from the body. Hydroxycobalamin also increases detoxification by converting cyanide into the less toxic thiocyanate. Evidence of increased urinary excretion of thiocyanate has been demonstrated in animals supplemented with hydroxycobalamin.

Another significant advantage that hydroxycobalamin holds over cyanocobalamin is that it is much more readily converted to the most biologically active B12 form in the body. Hydroxycobalamin actually bypasses a conversion step and, therefore, can be activated and used faster! In summary, the two main advantages of supplementing with hydroxycobalamin include lowering possible cyanide toxicity and gaining improved utilization of B12 by the body. For these reasons, AOR offers Hydroxy B12 lozengesto those interested in a hydroxycobalamin supplement.


Finally, we get to methylcobalamin. Methylcobalamin is generally considered the preferred form of supplementation because it is the “co-enzyme form”, meaning that it is the form used to activate enzymatic reactions within the body (it is the form that we want cyanocobalamin and hydroxycobalamin to convert to!). It is the predominant form found in blood plasma and cerebral spinal fluid and research has shown that supplemental methylcobalamin is utilized more efficiently than cyanocobalamin to increase these levels.

Perhaps the most important feature of methylcobalamin is its affinity for the neurological system. Unlike other B12 forms, methylcobalamin is effective at protecting the brain and nervous tissue. This is evident by its ability to improve neurological function in those with multiple sclerosis and alzheimer’s disease, as well as in improving peripheral neuropathy symptoms. It has also shown the ability to normalize circadian rhythms, ultimately improving sleep parameters.

As a final feather in its cap, the methyl component of methylcobalamin is extremely important because it can be donated to regenerate methionine from homocysteine, thereby lowering levels of the potentially toxic amino acid. You may remember homocysteine is a biomarker for increased cardiovascular events, osteoporosis, cognitive impairments and many other diseases, therefore demonstrating the importance to lower its levels whenever possible.

It is for these many reasons that AOR includes the methylcobalamin form of B12 in the majority of its formulations. These include Methylcobalamin lozengesMethylcobalamin ultra lozengesMax MethylAdvanced B-Complex and Ortho-Prenatal (to name a few). By giving the most biologically active form of B12 directly to the body, we bypass enzymatic reactions that may not be working properly in the first place, thereby ensuring full delivery and utilization of the B12 vitamin.

What about administration routes?

When comparing absorption of oral B12, sublingual B12 and intramuscular injectable B12, we must first understand the barriers to absorption that our body must overcome. Our bodies rely on something called intrinsic factor (secreted by parietal cells in the stomach) to help our small intestines absorb B12 from food. In certain health conditions, this process can be impaired. For individuals with Crohn’s disease, inflammation of the small intestine (and subsequent surgical removal of a portion of the small intestine) may prevent proper absorption. Similarly, some individuals have an autoimmune form of atrophic gastritis, whereby parietal cells and intrinsic factor are actually destroyed by the body’s own immune system. Circumstances like these clearly make intramuscular B12 or sublingual B12 administration the better choice because they bypass the digestive tract.

However, in otherwise healthy individuals, research has suggested that oral and sublingual supplementation is comparable to injectable B12 in raising serum B12 concentrations. In other words, you don’t need to see your doctor for B12 injections and you can rely on oral lozenges or capsules. In addition, methylcobalamin is the best choice for most individuals, but hydroxycobalamin can be a close second for those with suspected cyanide toxicity.

So, what does this mean overall?

AOR offers a wide variety of oral or sublingual B12 supplements, either alone or in conjunction with other crucial B-vitamins and minerals. Speak to your physician about whether you may possibly benefit from B12 supplementation and, if you do decide to supplement, remember that forms matter!

You may also be interested in: “The Link Between Alzheimer’s Disease and Vitamin B”


Kelly, Gregory. The coenzyme forms of vitamin B12: Toward an understanding of their therapeutic potential. Alt Med Review 1997; 2(6): 459-471

Vidal-Alaball J, et al. Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency. Cochrane Database Syst Rev. 2005; 20(3)


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