Vitamin B12 and ME/CFS

Last week, I wrote a post about methylation and its importance to people who have ME/CFS (and other immune disorders as well). If you haven’t read that post yet, I highly recommend you go back and read that one first because these two topics are inextricably intertwined. If you want even more detail than what I am providing here, ProHealth has an excellent article on B12 and Methylation that includes 225 scientific references!

So, with that basic knowledge of methylation, we already know that vitamin B12 is absolutely essential. It feeds a critical step in the methylation process, and without it, the whole process breaks down. That’s only the tip of the iceberg for B12 and ME/CFS, though.

Why is B12 so important to ME/CFS patients and what does it do?

We know that B12 is a critical component of the methylation cycle, which regulates detoxification, as well as critical processes in adrenal function, immune function, and the nervous system. Here are other facts about vitamin B12 and ME/CFS:

• Many people with ME/CFS and FM are actually deficient in B12

• Many people in the general population are deficient, including 78% of seniors in one study.
• People with ME/CFS often have low stomach acid and high bacterial growth in small intestine – both of which lead to B12 deficiency.
• Blood tests for B12 miss deficiencies 50% of the time (so if your blood tests show you have adequate B12 that is not necessarily true).
• B12 deficiency can cause IBS (Irritable Bowel Syndrome) symptoms that are very common in ME/CFS; IBS can lead to a B12 deficiency since nutrients are poorly absorbed – this is another of those vicious cycles present in ME/CFS.
• B12 helps regulate Natural Killer cells, a critical component of the immune system.

• In multiple studies, people with ME/CFS have been shown to have elevated levels of homocysteine, which can lead to cardiac problems; B12 helps to convert homocysteine to methionine.

• People with ME/CFS have been shown to have excess amounts of nitric oxide (NO) and peroxynitrite (-ONOO), a potent oxidant. Both of these lead to problems in multiple body systems that get progressively worse, as the high levels of NO and –ONOO in turn produce more of these compounds. NO also disrupts the methylation cycle. One form of B12, hydroxycobalamin, is a potent NO scavenger that can break this harmful cycle.

This was all news to me! Many years ago, when I first heard of doctors giving ME/CFS patients B12 shots, I thought it was an insignificant treatment, something done when doctors didn’t know what else to do because there was a myth that B12 improved energy. Wow, was I wrong!

What is Vitamin B12?

B12 consists of 4 different but related –cobalamin molecules (so named because they contain cobalt):

• Hydroxycobalamin –
• Scavenges excess NO
• Especially critical for neurological disorders and people with high levels of cyanide (smokers and those with certain metabolic defects)
• Methylcobalamin –
• Considered by many experts to be the most active form of B12
• Used directly in the methylation cycle
• Protects neurons against glutamate toxicity
• Promotes nerve cell regeneration
• Only form of B12 that helps in regulating circadian rhythms (sleep/wake cycle)
• Because it is directly used in the methylation cycle, it helps support production of serotonin, dopamine, and melatonin, which are directly responsible for good quality sleep.
• Adenosylcobalamin (dibencozide) –
• Another highly active form of B12
• Essential for energy metabolism
• Required for certain neurological processes
• Cyanocobalamin –
• Synthetic form of B12 not found in nature
• The most common form found in nutritional supplements
• Must be converted in the liver to other forms
• Lowest activity level of all forms of B12
• It is, however, essential in working together with hydroxycobalamin to quench NO

Dosing/Recommendations

The U.S. Institute of Medicine recommends that all adults over 50 use B12 supplements, so given everything listed above, it seems that every ME/CFS patient could benefit from B12 supplementation. What are the best ways to get it?

• Meat, eggs, fish, and shellfish contain the highest amounts of B12 in food but only about 50% of it is absorbed by the body (in a healthy GI tract) – IBS and other common GI symptoms in ME/CFS hamper absorption even further. Vegetarian sources of B12, like algae, are not bioavailable. So, supplementation is necessary.
• Most top ME/CFS doctors (Lapp, Cheney, Levine, DeMeirleir, others) routinely use B12 for their patients
• A study conducted by Dr. Charles Lapp (a renowned ME/CFS expert) found improved energy levels with B12 supplementation of 2500 – 5000 mcg every 2-3 days, even in ME/CFS patients who did not test deficient in B12.
• Though injections are the gold standard and are most easily absorbed by the body, there are some newer studies showing sublingual (under the tongue) types of B12 supplements to be as effective as injections. These come in tablets or sprays. We have still found injections to be most effective.
• Most direct benefits come from the hydroxycobalamin and methylcobalamin forms of B12, but the other two forms support and help these to work better, so all 4 forms can be helpful in ME/CFS.
• Studies show it can take 3-6 weeks or more to fully see the benefits of B12 supplementation.

 From what I have heard and seen myself, many doctors still feel that injections are the best way to get B12 into the body where it can be used effectively; others use sublingual or oral B12. 

Our Experiences

My son has been getting weekly hydroxycobalamin injections (1000 mcg) for several years now. We did not see an immediate effect, probably because his methylation process was so severely dysfunctional, and his system was overwhelmed by his three tick-borne infections when he started. Slowly, over time, as we addressed his methylation issues (see methylation post) and treated his infections, we saw that the B12 was having a positive effect. He feels a lot better, and we know the B12 is part of the reason why.  He also uses Black Bear Spray (a mouth spray form of B12) several times a day and finds that using it before or during a class, homework session, or a test helps to improve his mental energy and cognitive function.

He recently increased to 2 injections a week, and wow! He felt a huge burst of energy and improved cognitive function with that second weekly B12 shot. The effect was so positive that he now drives home from college twice a week to get a shot. Our next step – recently decided with the biochemist/dietician we consult with – is to switch him to daily shots that come pre-loaded so that he can do them himself at school, with hydroxycobalamin every day and methylcobalamin every third day.

As for me, last summer, I started using a product called B12 Extreme from ProHealth. I bought the product after reading that article they featured on B12 and ME/CFS because it is one of the few B12 products that contain all four types of B12. They are sublingual tablets, and, at first, I felt a mild improvement in energy when I took one each morning. I still take them every day, though I don’t notice that same burst of energy anymore, and blood tests done in December showed that I still had fairly low levels of B12. The biochemist/dietician we work with is reviewing my genetic test results to see if I have any problems metabolizing various forms of B12 and will make her recommendations based on that. I suspect injections may be in my future, too.

In summary, B12 seems to be essential to many body processes, and B12 supplementation should benefit anyone with ME/CFS. Just remember, though, that B12 is just one piece of a very complicated puzzle. If, like my son at first, you don’t see any benefits after a month or two of B12 supplementation, then you probably need to address other pieces of that puzzle, like other parts of the methylation cycle or treating underlying infections (if none of the typical ME/CFS treatments seem to work for you, then you almost certainly have underlying infections that need to be diagnosed and treated before you can move forward).

I will keep you up-to-date on my own B12 experiences, and I would love to hear about yours as well. Has B12 helped you? At what doses and in what forms? This seems to be a simple, inexpensive treatment that can help anyone with ME/CFS.

UPDATE 1/10/17:
My son did very well with the switch to alternating hydroxy- and methyl- type B12 injections and continues to use them. He injects every other day, alternating types, and can tell when he misses one! He is 23 now and injects himself (and told me it was much better doing it himself than having weenie mom do it!)

My son also told me to stop being a baby and switch to injections! I did and now use the same injection schedule that he does - every other day alternating hydroxy- and methyl- types. I can tell they are much more effective than the sublingual tablets I used to use - like my son, I feel the positive effects immediately. You have to purchase injections from a compounding pharmacy - any doctor can write a prescription. Our dietician calculated dosage for us - we both take the same amount (he is about 150 pounds and I am about 130). We take 3.5 mg in each dose, but we request a highly concentrated solution - 25 mg/ml - so that each injection is tiny, just 0.14 ml. I have heard different recommendations for both subcutaneous (just under the skin) and intramuscular (into the muscle, using a longer needle) type injections. We have always used subcutaneous, on the advice of our dietician, which are tiny needles that you barely even feel, injected into our stomachs, and as I said, they are very effective for us.

ADDENDUM 8/25/15: Our dietician recently advised us that people with ME/CFS should NOT take only cyanocobalamin. The cyano- means it contains cyanide which must be detoxed and coverted to other forms before you can use the B12. The detox pathway is part of the methylation process and uses up LOTS of glutathione which is already in short supply for us - so it does more harm than good if you take too much of it. Cyanocobalamin is, however, a part of the methylation process and can be taken as a small part of a product with multiple types of B12. This is especially important to know because as a manufactured form of B12, it is very common in typical B12 supplements and is the only ingredient in a new B12 prescription pill marketed under the brand name Eligen. It's best to avoid cyanocobalamin (or only use it in small amounts, combined with other types) and stick to one of the other 3 types, especially early on in the process of improving methylation.

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