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The Vitamin B-12 – ME/CFS/FM Connection: A Key to Improved Health for Many?

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What we know as vitamin B-12 is really a collection of four different cobalt-containing molecules, each with distinct and crucial roles to play in the body.

Triggers thought to initiate ME/CFS and Fibromyalgia (FM) are numerous and varied. Because these diseases have consistent symptoms, researchers believe there are biochemical abnormalities common to all sufferers. If shared biochemical aberrations can be found, treatments directed toward these aberrations could hasten improvement for those affected.

In the search for a unifying theory of ME/CFS/FM, two models with much scientific credibility have emerged. Research shows that a connection between ME/CFS/FM, Lyme disease, Multiple Chemical Sensitivities (MCS), and Gulf War Syndrome – and an equally complicated and misunderstood vitamin – may be a key to improved health for many sufferers.

The Vitamin B-12 – ME/CFS/FM Connection

In searching for common biochemical threads among ME/CFS/FM patients, researchers have noted numerous similarities between vitamin B-12 deficiency and symptoms of ME/CFS/FM and other multi-symptom diseases.

In fact, most respected ME/CFS/FM researchers and physicians – including Drs. Paul Cheney, Charles Lapp, Kenny DeMeirleir, Jacob Teitelbaum, and Martin Pall – consider vitamin B-12 a mainstay of treatment.

Symptoms of Vitamin B-12 Deficiency

Vitamin B-12 is required for manufacture of red blood cells, the myelin sheath surrounding nerve cells, and DNA. In its various forms, B-12 is required in numerous other physical functions. Deficiencies can have widespread effects.

  • Energy. Even minor deficiencies of vitamin B-12 can cause anemia, fatigue, shortness of breath and weakness.
  • The Nervous System. Deficiencies of B-12 can cause neurological changes including numbness and tingling in the hands and feet, balance problems, depression, confusion, poor memory and Alzheimer’s-like symptoms.
  • The Gastro-Intestinal System. B-12 deficiency can cause decreased appetite, constipation, diarrhea, and abdominal pain.
  • The Immune System. Vitamin B-12 is necessary for normal functioning of white blood cells, helps regulate Natural-Killer T-cells, and prevents chromosome damage.
  • The Cardiovascular System. Vitamin B-12 participates in the conversion of homocysteine to methionine. Elevated homocysteine levels are a known independent risk factor for heart attack, stroke and thrombosis

Vitamin B-12: Which Form Is Best?

What we know as vitamin B-12 is really a collection of four related but different cobalt-containing molecules. Each form plays a distinct role in the body.

Hydroxocobalamin – a unique form of B-12 that is essential in quenching excess nitric oxide (NO), the precursor to peroxinitrite (ONOO-). Hydroxocobalamin also participates in detoxification, especially cyanide detoxification.

Methylcobalamin – the most active form of vitamin B-12, is a required nutrient in the Methylation Cycle. It protects the nervous system by regulating glutamate-induced neuronal damage and has been shown to improve sleep quality.

Adenosylcobalamin (dibencozide) – another active form of vitamin B-12, is essential for energy metabolism, normal myelin sheath formation, and nucleoprotein synthesis. Deficiencies are associated with nerve and spinal cord degeneration.

Cyanocobalamin – the most common form of B-12 found in nutritional supplements, is a synthetic not found in nature. It has the lowest biological activity and must be converted in the liver to more biologically active forms. However, it is required to balance hydroxocobalamin in performing NO-quenching functions.

Is ME/CFS/FM a Vitamin B-12 Deficiency?

Although B-12 deficiency symptoms share many commonalities with ME/CFS/FM, researchers do not suggest that ’Chronic Fatigue Syndrome’ and related multi-system diseases are simply a vitamin B-12 deficiency.

Instead, two biochemical abnormalities, each heavily involved in ME/CFS/FM and other multi system diseases, are both related to forms of vitamin B-12 deficiency.

The Nitric Oxide/Peroxynitrite (“No, Oh No!”) Model of ME/CFS/FM

ME/CFS/FM is thought to be triggered by many different factors. Viral, bacterial or other infections, physical or psychological trauma, chemical exposure or other stressors often precede disease symptoms. In this regard, ME/CFS shares similarities with Fibromyalgia, Lyme disease, Multiple Chemical Sensitivities, and Gulf War Syndrome.

Noted researcher Dr. Martin Pall observed that virtually every initiator of ME/CFS/FM and other multi-system diseases increases either nitric oxide (NO) or the superoxide radical (O2-) or both. These quickly react to form peroxynitrite (ONOO-), a potent oxidant capable of damaging a wide range of biological molecules.

There is increasing evidence to support this pathway as a primary underlying abnormality in ME/CFS/FM and Lyme disease, Multiple Chemical Sensitivities (MCS), and Gulf War Syndrome. [For more on Dr. Pall’s research, see “Nitric Oxide Cycle Theory: Will It Explain ME/CFS, FM, and Other ‘Unexplained’ Illnesses?”]

KEY to Figure 1: The NO/ONOO- Cycle

Nitric oxide (NO), a naturally occurring “messenger molecule” in the body, is a pro-oxidant and free radical. Depending on amount and where it is released, NO can be either beneficial or toxic.

Superoxide (O2-) is a potent free radical.

OONO- (peroxynitrite) is a powerful oxidant formed when NO and O2- react with each other. Peroxynitrite is known to damage cells through a variety of mechanisms. OONO- acts through multiple mechanisms to regenerate NO and O2-. Hence, a “vicious cycle” of damage creating more damage begins.

This runaway NO/ONOO- cycle is also associated with increased perception of pain.

Hydroxocobalamin Breaks the NO/ONOO- Cycle

Hydroxocobalamin, a unique form of vitamin B-12, is a potent nitric oxide (NO) scavenger and the ONLY form of vitamin B-12 that neutralizes the NO molecule. Hydroxocobalamin is the form of vitamin B-12 needed to break the NO/ONOO- cycle of oxidative damage.

The Methylation Cycle and ME/CFS/FM

The Methylation Cycle is a biochemical pathway in the manufacture of DNA, RNA, phospholipids (myelin sheath of nerves), neurotransmitters, adrenal hormones and over 100 enzymes. The Methylation Cycle is also required for numerous detoxification reactions.

Defects in the Methylation Cycle are a second proposed mechanism in the development of ME/CFS/FM.

Methylation defects reduce detoxification ability and cellular energy production, decrease serotonin, dopamine, melatonin and other neurotransmitter production, decrease adrenal hormone production and increase levels of toxic homocysteine.

The methylcobalamin form of vitamin B-12 is required in the Methylation Cycle. If any one step in the Methylation Cycle fails, the entire cycle fails.

Who is Vitamin B-12 Deficient and Why?

Irritable bowel syndrome (IBS), affecting some 80% of ME/CFS/FM patients, is a major cause of B-12 deficiency.

A much larger segment of the general population is vitamin B-12 deficient than previously thought. Recent studies indicate that up to 78% of seniors are deficient.

Vitamin B-12 deficiencies often appear so slowly as to go unnoticed, and blood tests miss early deficiency states at least 50% of the time.

Vitamin B-12 Is Best Obtained From Supplements

Food is not a significant source of vitamin B-12. Further, absorption is hampered by low stomach acid, IBS, bacterial overgrowth of the small intestine and many other conditions.

The U.S. Institute of Medicine recommends that adults over 50 obtain their vitamin B-12 from supplements.

Oral Vs. Injectable: Which Is Best?

Vitamin B-12, once administered by injection, can now be obtained through oral supplementation. Oral vitamin B-12 is as effective as injection in treating B-12 deficiencies.

Conclusions and Recommendations

Suffering from ME/CFS/FM and related multi-system diseases is widespread. Current research provides new insights into the underlying mechanisms of these complicated illnesses.

The Nitric Oxide/Peroxynitrite (NO/ONOO-) and Methylation Cycles have emerged as two primary mechanisms for ME/CFS/FM, Lyme disease, Multiple Chemical Sensitivities, and Gulf War Syndrome. Deficiencies of hydroxocobalamin and/or methylcobalamin play a significant role in these biochemical processes.

Since vitamin B-12 (especially hydroxocobalamin and methylcobalamin) offers such potential benefits for ME/CFS/FM sufferers, without known risks, it seems prudent for those suffering with ME/CFS/FM or other related multi-system illness to consider taking a supplement containing these two unique forms of vitamin B-12.

(To read an expanded, much more detailed, version of this article including more than 200 footnotes, click here.)

* Dr. Dana Myatt, NMD, is a practicing naturopathic family physician, educator, author, and speaker with a special interest in nutrition. She lectures widely to medical and lay audiences, and hosts a website. Mark Ziemann, RN, Dr. Myatt’s husband and collaborator, is also an educator, author, and speaker specializing in holistic nursing practice and patient education.

Note: This information has not been evaluated by the FDA. It is generic and is not meant to prevent, diagnose, treat or cure any condition, illness, or disease. It is very important that you make no change in your healthcare plan or health support regimen without researching and discussing it in collaboration with your professional healthcare team.

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17 thoughts on “The Vitamin B-12 – ME/CFS/FM Connection: A Key to Improved Health for Many?”

  1. fefonsec says:


  2. chattycathy9 says:

    I find this article very interisting as I have a problem with B-12 deficiency. It seems that I am on a vicious cycle of building up my B-12 level, stopping the shots, then finding out a few months later that I am right back to a deficiency. My doctor then starts the routine over again. This has been going on again and again. Not only that, I have been anemic all of my life. Everyone has always blamed it on “heavy” periods or “iron” deficiency anemia. Lo and behold, I am no 58, have had a hysterectomy with both overies removed and still the problem exists!

    I was diagnosed with “fibrositis” long ago, I have had a gastric bypass and stapling in 1980. I have had three motor vehicle accidents (all of which were not my fault) in which I sustained injuries to my cervical and lumbar spine. X-Rays and MRI’s revealed not only the damage from the accidents but a birth defect which was described as “a whole in your spine”, “degenerative arthritis”, spondylosis, scoliosis, osteoarthritis, bulging discs, etc., all of which are inoperable and of course should not be causing me so much pain.

    The latest insurance “Independent Evaluation” determined that they will no longer continue to pay for treatment by my present physician, who is a DO, because the Independent physician, also a DO, has determined after a 15 minute examination that I have reached the limit of improvement osteopathically. This is quite ironic as anyone reading the history of my doctor’s treatment would be able to determine that I had not even been treated “osteopathically” but had been treated “medically”. My present doctor wants me to consult a lawyer to fight this determination so that I may continue with his treatment plan.

    Now that I have seen this article I am ready to pursue another avenue and ditch all these doctors. I feel that I need to consult with doctors familiar not only with expertise in spinal problems but with the bio-chemical system of the human body and the effect it has on the functioning of other systems in the body.

  3. morningsonshine says:

    “especially hydroxocobalamin and methylcobalamin” Your article says both are safe with no side effect.

    I would like to caution people about Methylcobalmin, it can combine with Mercury in your system, causing methlmercury with can cross the blood brain barriar and cause a reaction.

    This happened to me, and was very unpleasant, when i took my first methylcobalamin shot after a heavy metal test.

    From my experience i believe the hydroxocobalmin is much safer.

    Many of us with FM/CFS have toxic loads of heavy metals in our bodies.

  4. judcypie says:

    I all my life have suffered from a B-12 deficiency or anemia. It wasn’t until my Dr. put me on a cholestral fighting statin,that I suffered the worst B-12 deficiency in my life. I fell into the worst case of fatigue (later diagnosed with CFS ). All of my nerves in my body had a tingling that I could feel my pulse constantly throuhout my body. My doctor after having me go through nerve tests & a complete heart check up put me on massives doses of B-12. That along with other vitamin supplements bought me back to as near normal as can be for me.Statin drugs can delete those important vitamin nutrients that we need to survive. I promptly stopped them & take Niacin,Red Yeast Rice & CoQ10 to keep my cholestal down & it works.

  5. fefonsec says:


    What is the usual dosage of wellbutrin who have CFS ????? And i would like to know who use B12 ( cianocobalamina ) in high dosage and if it is useful ?????

    Fernando Fonseca From Brazil

  6. lestercrombie says:

    I have been using intra-muscular injections of B12. I was injecting 20mg of Cyanocobalamin once a week. This certainly improved my CFS condition. I tried injecting 10mg of methylcobalamin once a week, but strangely found the cyanocobalamin worked better for me. As well as the injection, I took two Berroca B tablets (made by Roche) at the same time. It is a fizzy B complex with 1000mg of Vitamin C. (It is important to take B complex with B12.)

    Since I really needed to find work, I tried injecting 10mg of Cyanocobalamin(ie B12) every day and also took a Berocca B tablet every day. I then went on a training course for five days. I had to get up at 6am, travel from 7am until 8.30pm by bus, then do the course from 9am – 5 pm. It was usually 7 pm by the time I got home. At night I had to study, so I was up till 12 midnight.

    Admittedly, I was completely exhausted by the end of the week and had to sleep on Sat, Sun and Mon, but at least I had seen the effect of daily large doses of Cyanocobalamin via intra-muscular injection. It may be the key to my returning to the workforce.

    Of course, the cost of doing this is significant. 6 vials (each containing 20 mg of Cyanocobalamin) costs $AUD 140.00. By doing the injections myself, I save money. Does anyone know a cheap, quality source of B12 for intra-muscular injection???

    I have tried oral B12, but not found it very effective. (Yes, I have tried the ones under the tongue as well.) Low dosage injctions of 1 mg do not work for me either.

    One doctor I was talking to, who has done research on B12, said that he had done tests by measuring chemicals in urine samples of patients taking B12 and that 10mg of oral B12 was equivalent to approximately 1mg of injected B12.


    1. olsen46 says:

      for the poster who noted use of statins caused adverse efffects–the red yeast rice you are taking IS A STATIN. RYR contains Monacolin K , the same ingredient in Merck’s “mevacor” preparation. although the amount of this “statin” in RYR is unknown (unregulated), it is there.

    2. proo says:

      The article was most informative and timely.

      My mother had polymyalgia rheumatica and her mother received B 12 injections. My rheum. started me on the sub lingual (under tongue) B12. This has to be made up by a compounding pharmacy and is quite expensive and must be kept cold. I saw no improvement but will continue for a little longer. My doctor has suggested a genetics test, $350, not covered by insurance, that would better guide her treatment.

    3. desertblue says:

      Hello. I too have begun to function much better following B12 injections. I get mine by prescription from Walmart (30ml bottles of cyanocobalamin) and am currently taking 3cc 2 times a week. The RX was written for 1000 mcg/cc. I had tried the sublingual methylcobalamin prior to this, but even if I took several, I wasn’t able to get the effect I wanted. I did read in your comment that you are not in the US, so hope this can help you… Good luck.

    4. lestercrombie says:

      Hi DesertBlue

      How much does 30ml of B12 cost?
      How many mg of B12 does a 30 ml bottle contain?



    5. judy2008happy says:

      I have been diagnosed with ME and have multiple issues with my health, being bed-ridden nearly every day. I have taken B supplements in the past, brewers yeast for example, and have found myself intolerant of them: I suffer with awful nausea and Vitamin B supplements make me really sick… what form of B-12 would you recommend for me? I live in the UK and I don’t think my GP would prescribe me injections of B-12. Could I get enough B-12 from non-yeast foods?

    6. desertblue says:

      Assuming my calculations are correct (my CFS seems to unknowingly sabotage my thinking at times), I get 10 injections per bottle (a dose of 3,000 mcgs) for $5 plus change. In general, I have found Walmart to be about the cheapest pharmacy around. I do order the syringes and needles from them in bulk (again, they are pretty cheap, something like $.10 per syringe, and $.16 per needle when I buy a box of 100 of each).


    7. CWB says:

      Dr. Myatt’s article is so helpful, but I want to caution my fellow ME/CFIDS sufferers that jumping into taking a great B12 supplement may lead to a Herxheimer response. We all know what those can be like, and that it’s best to look at your calendar to see if you can manage having one of those along with what else you’re hoping to do. After reading this article, I looked into changing my B12 supplement. First, let me say that I’m super responsive to vitamins, supplements, and pharmaceuticals and always proceed with caution. I used to recieve B12 shots but found them downright “speedy”–so speedy that I couldn’t sleep well the night of the day I had them each week, which lead to worse ME/CFIDS sypmtoms. I switched to a sublingual supplement, taking 1,000 mg most days, 1500 on “big days.” WHile I’ve read that it’s not easily assimilated, I could feel the difference. Most B12 supplements are just cyanocobalamin, but I found a liquid version that contains methyl- and dibenocozide co-enzyme forms as well. (Also, it looks like the shots are usually the Hydroxocobalamin form, not available orally at all.) I know that this B12 supplement is working to boost my immune system because, after two weeks starting at a half dose, I’m completely having a Herxheimer response. This is really bad timing for me (you know that goes; you work really hard to manage the little energy/time you get, so having less at critical times is awful), so I’m going off of it for a few weeks until I can give my body the time it needs to go throuh the painful detox. I look forward to trying again–and will probably start with a 1/4 dose. Plan accordingly, fellow travelers!

    8. cheresherri says:


      The Herxheimer Response is a set of symptoms experienced due to toxin release from bacteria dying from antibiotic treatment. What does that have to do with Vitamin B-12?

      SMiller, RN

  7. FannyFreckles says:

    I’ve been taking B-12 injections and B6 pills for about a year and it has made a significant difference to my energy and pain levels of my fibromyalgia.

    Because of that success I have shared the information with others. However I cannot find or remember the reason why I am taking injections. It just makes sense to me that it gets into your system faster rather than through the digestive system. Could you please elaborate on injection versus tablet?


  8. jayare says:

    I have had Fybromyalgia for a number of years and have tried many different drugs and treatments.I Also had cardiac bypass surgery,and have disc problems in my spine.Iam currently having test to evaluate my B12 levels which i feel is important.I take statins for cholesterol.My GP AND MY Cardiologist are both doing the best they can for me. However, i recently made a decicision to put more effort into dealing with my problems.I am doing pain management,seeing a psychcologist and trying to maintain a positive attitude towards my condition.I do regular exercise in a gym with an instructor who knows about my situation and can guide me correctly with exercise that is helpful and harmful.I,m starting to become more active in the community and most importantly i have an emotionaly good relationship with my condition.I find having a sense of humour,(NOT EASY WHEN YOUR BODY,S SCREAMING PAIN!), does help.Not bad for someone who didn,t think life was worth living six months ago. By the way, i am from Australia and am very fortunate that we have a health system that allows me to access services at a minimal cost.GOOD LUCK EVERYONE AND GOD BLESS. jayare.

  9. CWB says:

    Hi–You can also get the Herxheimer response when you boost your immune system because the same thing happens–only it’s the immune system killing off pathogens rather than the antibiotics. Even the sick feeling we have with the flu is the same thing; we don’t “feel sick” from the virus, we feel sick from the toxic die-off of that results from our immune system killing the critters.

    I meant this as a reply to the person who last wrote–not to delete my original post. That one was a caution for others on the ME/CFIDS path about B12 supplements. After reading this excellent article, I found a liquid of B12 version that contains 3 of the 4 B-12’s: Cyanocobalamin, Mehtylcobalamin, and Dibencozide in co-enzyme form. It boosted my immune system so well that it lead to a prfound Herxheimer. Since we all know how hard it is to manage the relative health that we have, I wanted to let people know to proceed with caution. It’s great to find something that works, but you have to manage the timing of profound side effects with the rest of your life. After two months off of that stuff, I’m starting again at a 1/4 dose and will work up slowly to full dose.

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