Hydroxocobalamin: The Powerful Brain-Boosting Vitamin B-12

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Hydroxocobalamin: The Powerful Brain-Boosting Vitamin B-12

Hydroxocobalamin is a natural and uniquely powerful form of vitamin B-12. Clinical studies and practice have demonstrated its ability to help improve cognitive functioning, fight fatigue, promote heart health, aid in detoxification and more.


Vitamin B-12 is an essential nutrient – one that your body needs but cannot produce itself. It is necessary to make: the red blood cells that carry oxygen throughout the body, the myelin sheath that surrounds nerve cells, and various proteins. B-12 also plays an important 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 and as much as 20% of older adults may be deficient in B-12. Low vitamin B-12 levels can cause altered cellular metabolism, which may result in cognitive decline and other age-related issues like cardiovascular disease and bone health.


Causes of Vitamin B-12 Deficiency

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.


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.
  • Aging – Nearly a third of people over 60 are not able to extract B-12 from the foods they eat.
  • 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.


Vitamin B-12 Deficiency Symptoms

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. Some of the symptoms of a vitamin B-12 deficiency may include:


  • Fatigue

  • Weakness

  • 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

  • Depression

  • Confusion

  • Insomnia

  • Vision problems

  • Loss of hearing and tinnitus

  • Pale, possibly yellowish pallor in light-skinned individuals; blotchy pigmentation in dark-skinned individuals


Vitamin B-12 Tests

A vitamin B-12 deficiency can be difficult to diagnose because serum blood levels of B-12 may test normal. Having circulating B-12 in the 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 blood or urine gives a more accurate reading of B-12’s availability in the body.


Vitamin B-12 in Food

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 beverages, nutritional yeasts and food products like cereals may be enriched with B-12, they generally do not contain adequate amounts to be used as the sole source of this essential nutrient.


Since the only natural source of B-12 is from animals, it is particularly important for vegetarians and vegans to pay special attention to how much vitamin B-12 they are getting. It is strongly recommended that they consider taking a B-12 supplement.


Which Form of Vitamin B-12 Is Better – Hydroxocobalamin or Cynocobalamin?

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.

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 fact hydroxocobalamin is so effective at this process that in 2006 it 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 Research

Studies have shown hydroxocobalamin to have positive effects on a variety of different diseases and disorders.


  • In a 2001 study, hydroxocobalamin improved cognitive function in older cobalamin-deficient persons.

  • A study conducted at a VA Medical Center found that hydroxocobalamin inhibited HIV-1 infection of normal human blood monocytes and lymphocytes in vitro.

  • In three case studies of childhood asthma, the use of hydroxocobalamin resulted in remarkable improvement in asthma wheezing.

There are also individual or small case reports indicating a possible correlation with vitamin B-12 deficiency in some cases of infertility, dementia, diabetic neuropathy, neuromyelopathy, multiple sclerosis, autism, motion sickness, and even psychosis to name a few.


Vitamin B-12 Injections vs. 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 vitamin B-12 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 in the Journal of the American Geriatrics Society showed that oral supplementation with 2,000 mcg per day was three times as effective as vitamin B-12 injections in increasing B-12 levels in pernicious anemia patients.
  • 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.

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 Vitamin B-12 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.


In Summary

Clinical research and practice strongly supports the use of hydroxocobalamin as a safe and highly effective method for correcting a vitamin B-12 deficiency.

Show references
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Hall CA, et al. “The availability of therapeutic hydroxocobalamin to cells.” Blood. 1984 Feb;63(2):335-41. Retrieved from: https://www.ncbi.nlm.nih.gov/pubmed/6692038

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. doi: 10.1182/blood.V27.2.234.234

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. doi: 10.1093/gerona/56.12.m775

Weinberg JB, et al. “Inhibition of productive human immunodeficiency virus-1 infection by cobalamins.” Blood. 1995 Aug 15;86(4):1281-7. Retrieved from: https://www.ncbi.nlm.nih.gov/pubmed/7632933

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.http://www.vitasearch.com/get-clp-summary/5624 Journal of Nutritional Medicine, 1990; 1:277-282. Retrieved from: http://www.vitasearch.com/get-clp-summary/5624

Journal of the American Geriatrics Society. January, 1997; 45(1):124.

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. doi: 10.1093/fampra/cml008

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