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.
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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.