Few vitamins and minerals receive the same amount of consumer attention and scientific research as vitamin B12.
Ask anyone who's even marginally interested in the topics of nutrition and diet hacking and they'll probably be able to tell you something about this key nutrient: from the dangers of not getting enough vitamin B12 to the shocking statistics about the prevalence of B12 deficiency, everybody seems to have an opinion on how the vitamin should be taken and what is the best way to optimize absorption.
In reality, the topic of what are the best forms of vitamin B12 to supplement remains largely under-researched and misunderstood, much like one of the active coenzyme forms of B12: adenosylcobalamin.
So, what is this form of B12 all about and why should you look into purchasing a high-quality B12 supplement that's going to deliver an adequate dosage of this form? Here's what we know so far!
What Is Adenosylcobalamin?
Even though vitamin B12 has become one of the most widely recognized nutrients to supplement, many consumers are not aware of the fact that there are four different forms of vitamin B12, some natural and some synthetic, each with its own unique characteristics: adenosylcobalamin, methylcobalamin, cyanocobalamin, and hydroxocobalamin.
Adenosylcobalamin is the natural, most common form of vitamin B12 found in the cells, organs, and tissues of the human body, as well as the most common form of B12 found in food. Interestingly enough, however, the adenosylcobalamin form of B12 is rarely ever talked about when discussing forms of vitamin B12 and their different benefits when supplemented.
Adenosylcobalamin is one of the two active coenzyme forms of B12, with methylcobalamin being the other, playing an important role (like all other B vitamins) in energy production and in maintaining stable energy levels. What makes adenosylcobalamin so crucial to energy is the fact that adenosylcobalamin is the main building block of the enzyme methylmalonyl-CoA mutase, the enzyme that is created in the cells' mitochondria before being transformed into succinyl-CoA, another crucial element for the metabolic process that provides energy to our body.
Adenosylcobalamin is just as important when it comes to the health and proper functioning of our nervous system. It reduces methylmalonic acid (MMA) levels in the body, an acid that can prevent normal fatty acid synthesis and lead to severe damages to the nervous system over time. Finally, adenosylcobalamin plays a key role in metabolizing certain amino acids and hormones, maintaining overall metabolic and endocrinal health.
So, why opt for the adenosylcobalamin form of vitamin B12 to cover your B12 needs?
When choosing what form of B12 to supplement, there are several factors one needs to take into account, such as vitamin bioavailability, product safety, market availability, and retail price.
Let's see how the adenosylcobalamin form of vitamin B12 compares with other forms of B12 sold on the market!
The Importance of Methylation (Adenosylcobalamin vs Methylcobalamin)
Comparing methylcobalamin and adenosylcobalamin doesn't leave us with a clear winner.
In fact, the two coenzyme forms of B12 work better as a unified team, complementing each other in a way that boosts each enzyme's unique properties.
Methylcobalamin is one of the most popular forms of cobalamin (B12), and it is generally considered the best option for those suffering from a methylation defect, as it plays a huge role in our body's methylation cycle.
Methylation is a biochemical process affecting DNA, believed to inhibit the occurrence of certain genes "turning on", most crucially for example, the genes that cause cancer cells to form or cardiovascular disease to develop. Research suggests that eating a diet rich in folate and vitamin B12 in the form of methylcobalamin can help improve DNA methylation, even as the process slows down with age.
Research suggests that adenosylcobalamin can support methylcobalamin's role in the methylation cycle better than the synthetic form of B12, cyanocobalamin, as it must be converted into adenosylcobalamin and methylcobalamin first, a process that may interfere with the cycle and make the methylation pathway less efficient for individuals with B12-related polymorphism.
And on that note...
The Pros and Cons of Cyanocobalamin (Adenosylcobalamin vs Cyanocobalamin)
Cyanocobalamin has long been the most popular form of vitamin B12 used in supplementation. For many years, cyanocobalamin B12 has been cheaper to produce than the two active forms, and as a result, its effects on the body have been studied extensively.
Does that mean that cyanocobalamin is the best form of vitamin B12 available? Not necessarily.
If we compare B12 adenosylcobalamin with the synthetic cyanocobalamin form, conversion seems to be the biggest potential issue when it comes to bioavailability and absorption: all forms of B12, once ingested, have to be broken down to their core cobalamin molecule, but cyanocobalamin will have to be transformed into adenosylcobalamin and methylcobalamin first.
According to the body of research on cyanocobalamin, this popular option is efficient as it is safe, but those with a MTHFR gene deficiency might fare better taking a mixture of adenosylcobalamin and methylcobalamin as their preferred B12 supplementation instead.
MTHFR reductase deficiency is a common genetic mutation resulting in higher levels of the amino acid homocysteine in the blood and low levels of folate and cobalamin. Women with MTHFR deficiency are believed to be at a higher risk of miscarriage when pregnant, and all individuals with this gene mutation are also believed to be at a higher risk of developing thyroid issues, Alzheimer's disease, and cardiovascular complications.
So, what role does MTHFR reductase gene mutation play in the methylation cycle?
Normally, homocysteine is quickly broken down during the cycle by the MTHFR gene, cobalamin (B12), vitamin B6, and folate, and then recycled to build other proteins. As the MTHFR mutation affects our body's ability to properly activate the MTHFR gene, leading to a build-up of homocysteine in the blood.
In order to prevent and treat this condition, folate and vitamin B12 levels must be adequate to quickly metabolize homocysteine and ensure the methylation cycle is unaffected. Using cyanocobalamin as vitamin B12 supplementation can slow down this process as an extra conversion step (from cyanocobalamin to methylcobalamin and adenosylcobalamin) is needed before the core cobalamin molecule is activated.
The suggested poorer bioavailability of cyanocobalamin might push some consumers away from taking this form to elevate their vitamin B12 status, but more research is needed to fully confirm this claim.
The b12 Injection (Adenosylcobalamin vs Hydroxocobalamin)
Hydroxocobalamin is often neglected when discussing the best type of B12 to supplement.
This is another natural form of B12, but unlike all the other options we have just explored, it is only available on prescription and given as an injection. Some research suggests that hydroxocobalamin may be more efficient in treating B12-related methylation issues if high doses of oral B12 are proven unsuccessful in improving B12 levels.
If we look at different studies, however, we can see that injecting hydroxocobalamin has not been proven to be more effective in treating B12 deficiency than ingesting oral tablets available over the counter.
In this case, getting a blood test after taking high regular doses of adenosylcobalamin and methycobalamin oral B12 might be a good option to try. In fact, if you suffer from gut-related issues and experience vitamin malabsorption, B12 injections might be an answer to the problem, though hydroxocobalamin is not considered an accessible option for the majority of the population due to the higher price and the required administration by a medical professional.
Adenosylcobalamin Deficiency Symptoms
Adenosylcobalamin deficiency presents many of the same symptoms of a general vitamin B12 deficiency, with chronic fatigue and weakness being the key tell-tale signs, since adenosylcobalamin plays a major role in energy production.
Not getting enough adenosylcobalamin can also lead to severe conditions like dementia, neuropathy and ataxia, two neurological deficits caused by elevated levels of MMA (methylmalonic acid). MMA is, in fact, normally converted into succinyl-CoA by cobalamin, a process that's crucial to amino acid metabolism and overall health of the nervous system.
So, if you're choosing to go ahead and give adenosylcobalamin a try as your next trusted B12 supplement, how much should you aim to take to avoid these dangerous side effects?
The answer is not as straightforward as you may think, as the recommended dosage varies greatly.
The often-cited dosage of 2000mcg weekly for those under 65 years old and 1000 mcg daily for those over 65 refers to the cyanocobalamin form, as studies on the correct dosage for natural forms of B12 are unfortunately lacking. Other experts, on the other hand, recommend a minimum of 1000mcg - 1500mcg of B12 daily for under 65, while the RDI is set at a mere minimum of 2.4mcg to 2.8mcg daily.
One thing to keep in mind when considering dosage is that our bodies tend to absorb B12 quite poorly, so going beyond the minimum amount is recommended, especially if you follow a 100% plant-based diet (as a water-soluble vitamin, any excess B12 will be excreted by your body instead of being stored in the liver!).
So, based on a balanced view of the current research, if you wish to take adenosylcobalamin or methylcobalamin (or better, a mixture of the two!) we recommend aiming to get between 400mcg to 500mcg daily if you are under 65 years old.
The best source of adenosylcobalamin vitamin B12 will be high-quality supplements, as rich dietary sources like meat, dairy, and eggs can be unreliable and those on a plant-based diet might have a hard time getting enough from fortified foods alone.
Methylcobalamin and Adenosylcobalamin Synergy
Throughout this article, we've been using adneosylcobalamin and methylcobalamin pretty much interchangeably to give recommendations on how to improve your status.
What makes adenosylcobalamin and methylcobalamin work better as a team?
Broadly speaking, adenosylcobalamin focuses on energy formation and metabolization as it carries out most of its work in the mitochondria, while methylcobalamin focuses on maintaining healthy homocysteine levels. As the two natural coenzymes playing a starring role in the methylation cycle, these forms of cobalamin depend on each other to cover both functions and are both essential for all facets of DNA health and beyond.
Up until recently, cyanocobalamin has been the most widely used form of cobalamin in supplements, while adeosylcobalamin has been largely neglected as an essential component of what makes our cells' metabolism work.
Pure methylcobalamin is definitely on the rise as a great alternative to the cyano form of B12 supplementation, but 99% of supplement brands have yet to take the leap and experiment with using the adenosylcobalamin and methylcobalamin synergy to boost bioavailability and absorption.
In this case, we are proud to be part of the 1%!
Methylcobalamin and Adenosylcobalamin b12 Supplements
The latest research informs everything we do as a supplements company, and with an increasing number of studies pointing to the mix of methylcobalamin and adenosylcobalamin as the best option for absorption and bioavailability, we have chosen to include the two active forms in our essential multivitamin for vegans (which of course, works great for non-vegans too!).
Most B12 supplements on the market won't include both and often fail to include methylcobalamin at all, which might present a problem to those who suffer from B12-related polymorphism or other gene-related methylation issues.
To this day, all of the four B12 forms are FDA-approved, considered safe, and regarded as efficient to treat deficiencies and low levels within the normal range, but we believe in providing a wider variety of options for those who wish to keep their health on track and their B12 status as good as it can be!