Hydroxocobalamin (hi-DROX-oh-koe-BAHL-a-min) is a natural and uniquely powerful form of vitamin B-12. Clinical studies and practice have shown it can help to improve cognitive functioning, fight fatigue, promote heart health, and more.
Vitamin B-12 is an essential nutrient needed to make red blood cells that carry oxygen throughout the body, the myelin sheath that surrounds nerve cells, and various proteins. It also plays a role in fat and carbohydrate metabolism. Yet, despite its importance to overall health, vitamin B-12 deficiency is relatively common. It is estimated that up to 15% of the general population may be deficient in B-12 - and more among those with chronic illnesses.
Dietary Sources of Vitamin B-12
Vitamin B-12 is produced exclusively in the digestive tracts of animals. Therefore, the richest dietary sources of B-12 are organ meats like liver or kidney. Other good natural sources include meat, fish, eggs and dairy products. Although some food products like cereals and some beverages may be enriched with B-12, they do not contain adequate amounts to be used as the sole dietary sources.
In order for the B-12 obtained from food to be absorbed it must attach to a protein called intrinsic factor, which is secreted in the stomach. Unfortunately, a number of things can inhibit the secretion of intrinsic factor, which in turn blocks the absorption of B-12 and results in a vitamin B-12 deficiency.
Causes of Vitamin B-12 Deficiency
A deficiency of vitamin B-12 is not usually caused by insufficient dietary intake but rather by a lack of intrinsic factor secretion. Without intrinsic factor, vitamin B-12 cannot be absorbed. This situation can occur with:
• Digestive disorders such as celiac disease, Crohn's disease, bacterial overgrowth in the small intestine or a parasite.
• Surgery to remove or bypass part of the stomach or the part of the small intestine called the ileum.
• Certain medications, particularly diabetes medications like metformin, and long-term use of proton pump inhibitors (such as Prilosec, Prevacid, Nexium, etc.) commonly prescribed for heartburn, acid reflux and GERD.
• Vegetarian or vegan diets, since B-12 is found almost exclusively in animal foods.
• Pernicious anemia – a decrease in red blood cells that develops when the body lacks the intrinsic factor necessary to naturally absorb vitamin B-12 from food.
Symptoms of Vitamin B-12 Deficiency
Early symptoms of a B-12 deficiency may be overlooked, diagnosed as another illness, or attributed to “just getting older” because many of them mimic classic signs of aging. Of course, this isn't surprising since low serum levels of vitamin B-12 are fairly common in elderly patients.(1) Some of the symptoms of a vitamin B-12 deficiency may include:
- Memory loss
- Cognitive functioning problems
- Diarrhea or constipation
- Loss of appetite
- Shortness of breath
- Beefy, red, smooth and sore tongue
- Sore mouth and/or bleeding gums
- Numbness and tingling of hands and feet
- Poor sense of balance
- Vision problems
- Loss of hearing and tinnitus
- Pale, possibly yellowish pallor in light-skinned individuals; blotchy pigmentation in dark-skinned individuals.
A B-12 deficiency can be difficult to diagnose because serum blood levels of B-12 may test normal. Having circulating B-12 in blood doesn't mean it is being utilized properly by the body's cells. Some doctors suggest that a test measuring methylmalonyl coenzyme A levels in the urine gives a more accurate reading of B-12’s availability in the body.
Which Vitamin B-12 is Better – Hydroxocobalamin or Cyanocobalamin?
The name vitamin B-12 is used for a group of cobalt-containing enzymes called cobalamins. (It's the cobalt that gives B-12 its red color.) There are several members of the cobalamin family, but cyanocobalamin and hydroxocobalamin are two of the best known.
• Cyanocobalamin is the type of B-12 found in most supplements and in prescribed injectible forms - largely because it is inexpensive and the most stable form of B-12.
• However, studies have found that hydroxocobalamin raises B-12 levels higher and lasts longer than cyanocobalamin.(2)(3)
Another interesting fact – cyanocobalamin contains cyanide. It's actually a cyanide molecule attached to a cobalamin. Although the amount of cyanide is miniscule enough that it is not thought to be harmful to most people, it could be dangerous for those who have cyanide metabolism defects or kidney failure. There is also the possibility that it could be toxic if taken in extremely large doses.
On the other hand, hydroxocobalamin has a high affinity for cyanide. It pulls the cyanide out of the mitochondria of the cell and combines with it to form cyanocobalamin, which is then excreted in the urine. In 2006 hydroxocobalamin was approved by the FDA as an antidote for cyanide poisoning.
Since cyanide is present in cigarette smoke (and essentially reduces the cells' ability to use oxygen), hydroxocobalamin would be a good option for smokers seeking a B-12 supplement.
Hydroxocobalamin's Relationship to Fibromyalgia and Chronic Fatigue Syndrome
Many of the symptoms fibromyalgia and ME/CFS patients report are also symptoms of a B-12 deficiency – cognitive functioning problems, memory loss, and fatigue to name a few. Is that merely a coincidence or is there a connection?
In a 1997 study of 12 patients with fibromyalgia and ME/CFS: Most had little or no detectable B-12 in their cerebrospinal fluid - despite the fact that all had normal B-12 blood levels. Conversely, they had high levels of homocysteine in their cerebrospinal fluid.(4)
Homocysteine is an amino acid, too much of which can be toxic to nerves and blood vessels, and may result in increased pain sensitivity and/or heart disease.
• When there is not enough vitamin B-12, homocysteine levels increase.
• As B-12 levels rise, homocysteine levels decrease.
ME/CFS specialist and researcher Dr. Paul Cheney, MD, PhD, utilizes large doses of hydroxocobalamin as part of his treatment protocol. He believes it is a potent brain detoxifier and says data suggests that megadoses in the range of 10,000 mcg or more per day, given before bedtime, may be effective. He also notes that hydroxocobalamin is superior to cyanocobalamin as a detoxifier of the brain.(5)
Another researcher, Dr. Martin L. Pall, PhD, hypothesizes that elevated levels of nitric oxide and peroxynitrite (affecting brain function and pain sensitivity) may be the common etiology of ME/CFS, fibromyalgia, multiple chemical sensitivity and post-traumatic stress disorder.(6) He believes hydroxocobalamin's ability to “mop up” excess nitric oxide may be why it has proven to be so useful in treating those illnesses.(7)
Hydroxocobalamin's Effect on Other Conditions
Studies have shown hydroxocobalamin to have positive effects on a variety of different diseases and disorders. In these examples, hydroxocobalamin:
• Improved cognitive function in older cobalamin-deficient persons.(8)
• Inhibited HIV-1 infection of normal human blood monocytes and lymphocytes.(9)
• Showed remarkable improvement in asthma wheezing.(10)
There are also individual or small case reports indicating a possible correlation with B-12 deficiency in some cases of infertility, dementia, diabetic neuropathy, neuromyelopathy, multiple sclerosis, autism, motion sickness, and even psychosis to name a few.
Shots or Pills – Is There a Difference?
Most hydroxocobalamin studies have used the intramuscular injection form. However, that requires patients to return to the doctor's office for every dose (unless they learn to do it themselves). Therefore injections are a more time-consuming, expensive and - let's face it - painful way to go. But are they more effective?
Two studies addressing that question concluded that oral supplementation with large doses of B-12 was as effective, if not more effective, than injections.
• A 1997 study showed that oral supplementation with 2,000 mcg per day was three times as effective as injections in increasing B-12 levels in pernicious anemia patients.(11)
• Another study done in 2005 concluded that 2,000 mcg doses of oral B12 was as effective as intramuscular administration in vitamin B-12 deficient patients. (12)
When it comes to oral supplementation of B-12, sublingual tablets are the best option because they are absorbed directly into the mucous membrane and don't have to go through the digestion process, which is often the cause of the deficiency to begin with.
How Much Is Enough? ...Too Much?
There is no set upper dose limit for hydroxocobalamin because there are no known toxic effects, even at extremely high dosages. Many of the studies used 1,000 or 2,000 mcg/day. Dr. Cheney generally prescribes 10,000 mcg/day for ME/CFS patients. Dr. Susan Solomon, MD, recommends at least 5,000 mcg/day sublingual for chronically ill patients. Dr. Sarah Myhill, MD, usually starts with 5,000 mcg/day for ME/CFS and then adjusts the frequency according to the response.
Clinical research and practice strongly supports the use of hydroxocobalamin as a safe and highly effective method for correcting a vitamin B-12 deficiency.
1. Stott DJ, et al. “Prevalence and haemopoietic effects of low serum vitamin B-12 levels in geriatric medical patients.” Br J Nutr. 1997 Jul;78(1):57-63.
2. Hall CA, et al. “The availability of therapeutic hydroxocobalamin to cells.” Blood. 1984 Feb;63(2):335-41.
3. Glass GBJ, et al. “Hydroxocobalamin V. Prolonged Maintenance of High Vitamin B-12 Blood Levels following a Short Course of Hydroxocobalamin Injections.” Blood, 1966, Vol. 27, No. 2, pp. 234-241.
4. Regland B, et al. “Increased concentrations of homocysteine in the cerebrospinal fluid in patients with fibromyalgia and chronic fatigue syndrome.” Scand J Rheumatol. 1997;26(4):301-7.
5. Hoh D. “Treatment at the Cheney Clinic.” The CFIDS Chronicle. July/August, 1998:13-14.
6. Pall ML. “Common etiology of posttraumatic stress disorder, fibromyalgia, chronic fatigue syndrome and multiple chemical sensitivity via elevated nitric oxide/peroxynitrite.” Med Hypotheses. 2001 Aug;57(2):139-45.
7. Pall ML. “New theory on explanations for chronic fatigue syndrome. ProHealth.” February 13, 2001.
8. vanAsselit DZ, et al. “Cobalamin supplementation improves cognitive and cerebral function in older, cobalamin-deficient persons.” J Gerontol A Biol Sci Med Sci. 2001 Dec;56(12):M775-9.
9. Weinberg JB, et al. “Inhibition of productive human immunodeficiency virus-1 infection by cobalamins.” Blood. 1995 Aug 15;86(4):1281-7.
10. Wright, JV. “Treatment of childhood asthma with parenteral vitamin B-12, gastric re-acidification, and attention to food allergy, magnesium and pyridoxine: three case reports with background an integrated hypothesis.” Journal of Nutritional Medicine, 1990; 1:277-282.
11. Journal of the American Geriatrics Society. January, 1997; 45(1):124
12. Butler CC, et al. “Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B-12 deficiency: a systematic review of randomized controlled trials.” Fam Pract. 2006 Jun;23(3):279-85. Epub 2006 Apr 3.
* Karen Lee Richards is Lead Expert specializing in Fibromyalgia and ME/CFS, for HealthCentral's ChronicPainConnection (www.chronicpainconnection.com). Karen is co-founder of the National Fibromyalgia Association (NFA) and was Executive Editor of Fibromyalgia AWARE magazine for four years.
Note: This information has not been reviewed by the FDA. It is general information 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.