@ods.od.nih.gov/factsheets/V...
The above link is to the U.S. nih site relating to dietary supplements. If you scroll down you can find a section called Heslth risks from excessive B12 that confirms that no upper limit is set and quotes two studies on long term high usage of B 12.
Please remove the @ sign from the above URL in order to make the link.
I'm not sure what you're trying to achieve with the @ but if you are trying to fool the forum into thinking that the url isn't a url then it won't work if you just put the @ (or any other random character) at the beginning of the url.
Realised that after posting 😒 but never mind, this is a useful reference anyway. My gp has problems regarding liability etc. and has been very difficult over implementing a 3 month trial recommended by my neuro. The two obstacles are these, 1) that high dosage might be dangerous, and 2) that a sensitivity may develop over time. Would be happy if there was some evidence that discounted the latter, as I have never seen anything that even mentions the possibility, let alone a study.
Very high doses of hydroxocobalamin are given IV for cyanide poisoning, ( Hydroxocobalamin 5 g was administered intravenously )and no harmful side effects, only side effect such as temporarily discolouring of skin and urine, blood presure, allergic effects such as spots etc see:
cmaj.ca/content/180/2/251.full
More detailed info on Human Toxicity here (if you get search expired just put hydroxocobalamin in the search option), see:
toxnet.nlm.nih.gov/cgi-bin/...
toxnet.nlm.nih.gov/cgi-bin/...
Hydroxocobalamin:
Human Health Effects:
Human Toxicity Excerpts:
/HUMAN EXPOSURE STUDIES/ Independent groups of healthy volunteers received single intravenous doses of 2.5, 5, 7.5, or 10 g hydroxocobalamin over 7.5 to 30 minutes. In the pharmacokinetic population (n = 41), hydroxocobalamin caused short-lived mean blood pressure increases. Blood pressure increased shortly after initiation of infusion and returned nearly to baseline by 4 hours post-infusion. The time course of blood pressure changes coincided with that of changes in plasma total and free cobalamins-(III). Change in mean arterial pressure (MAP) was strongly correlated with plasma area-under-the-concentration-time curves (AUCs) of total and free cobalamins-(III) during infusion (r > 0.7) but not through 24 hours post-infusion (r < or = 0.36). The short-lived increase in mean blood pressure during administration of antidotal doses of hydroxocobalamin is closely linked to initial exposure to total and free cobalamins-(III).
[Uhl W et al; Clin Toxicol (Phila) 46 (6): 551-9 (2008)] **PEER REVIEWED** PubMed Abstract
/OTHER TOXICITY INFORMATION/ Hydroxocobalamin is a complexation agent that acts by direct binding of the cyanide ions, resulting in cyanocobalamin which is a highly stable, nontoxic compound that is excreted in the urine. In addition, increased blood pressure observed in some healthy subjects of the phase I clinical study and results of a non-clinical study performed in anesthetized rabbits suggest an interference of hydroxocobalamin with the NO system.
[European Medicines Agency (EMEA), The European Agency for the Evaluation of Medicinal Products, European Public Assessment Report (EPAR) for Authorized Medicinal Products for Human Use; Cyanokit, Scientific Discussion (2007). Available from, as of November 24, 2008: emea.europa.eu/humandocs/Hu... **PEER REVIEWED**
Drug Warnings:
Caution should be exercised when administering other cyanide antidotes simultaneously with Cyanokit, as the safety of coadministration has not been established. If a decision is made to administer another cyanide antidote with Cyanokit, these drugs should not be administered concurrently in the same IV line.
[Thomson Health Care Inc.; Physicians' Desk Reference 62 ed., Montvale, NJ 2008, p. 1033] **PEER REVIEWED**
Use caution in the management of patients with known anaphylactic reactions to hydroxocobalamin or cyanocobalamin. Consideration should be given to use of alternative therapies, if available. Allergic reactions may include: anaphylaxis, chest tightness, edema, urticaria, pruritus, dyspnea, and rash. Allergic reactions including angioneurotic edema have also been reported in postmarketing experience.
[Thomson Health Care Inc.; Physicians' Desk Reference 62 ed., Montvale, NJ 2008, p. 1033] **PEER REVIEWED**
Maternal Medication usually Compatible with Breast-Feeding: B12: Reported Sign or Symptom in Infant or Effect on Lactation: None. /from Table 6/
[Report of the American Academy of Pediatrics Committee on Drugs in Pediatrics 93 (1): 140 (1994)] **PEER REVIEWED**
While determination of blood cyanide concentration is not required for management of cyanide poisoning and should not delay treatment with Cyanokit, collecting a pretreatment blood sample may be useful for documenting cyanide poisoning as sampling post- Cyanokit use may be inaccurate.
[Thomson Health Care Inc.; Physicians' Desk Reference 62 ed., Montvale, NJ 2008, p. 1033] **PEER REVIEWED**
Elevations in blood pressure (> or + 180 mm Hg systolic or > or + 110 mm Hg diastolic) were observed in approximately 18% of healthy subjects (not exposed to cyanide) receiving hydroxocobalamin 5 g and 28% of subjects receiving 10 g. Increases in blood pressure were noted shortly after the infusions were started; the maximal increase in blood pressure was observed toward the end of the infusion. These elevations were generally transient and returned to baseline levels within 4 hours of dosing.
[Thomson Health Care Inc.; Physicians' Desk Reference 62 ed., Montvale, NJ 2008, p. 1033] **PEER REVIEWED**
Hydroxocobalamin absorbs visible light in the UV spectrum. It therefore has potential to cause photosensitivity. While it is not known if the skin redness predisposes to photosensitivity, patients should be advised to avoid direct sun while their skin remains discolored.
[Thomson Health Care Inc.; Physicians' Desk Reference 62 ed., Montvale, NJ 2008, p. 1033] **PEER REVIEWED**
Administration of Cyanokit to cyanide-poisoned patients with the attendant formation of cyanocobalamin resulted in increases in blood pressure and variable changes in heart rate upon initiation of hydroxocobalamin infusions.
[Thomson Health Care Inc.; Physicians' Desk Reference 62 ed., Montvale, NJ 2008, p. 1034] **PEER REVIEWED**
FDA Pregnancy Risk Category: C /RISK CANNOT BE RULED OUT. Adequate, well controlled human studies are lacking, and animal studies have shown risk to the fetus or are lacking as well. There is a chance of fetal harm if the drug is given during pregnancy; but the potential benefits may outweigh the potential risk./
[Thomson Health Care Inc.; Physicians' Desk Reference 62 ed., Montvale, NJ 2008, p. 1034] **PEER REVIEWED**
In some patients, an acneiform rash may appear anywhere from 7 to 28 days following hydroxocobalamin treatment. This rash will usually resolve without treatment within a few weeks.
[Novak, K.M. (ed.). Drug Facts and Comparisons2008 Edition. Wolters Kluwer Health. St. Louis, Missouri 2008., p. 563] **PEER REVIEWED**
Folic acid should be administered with extreme caution to patients with undiagnosed anemia, since folic acid may obscure the diagnosis of pernicious anemia by alleviating hematologic manifestations of the disease while allowing neurologic complications to progress. This may result in severe nervous system damage before the correct diagnosis is made. Vitamin preparations containing folic acid should be avoided by patients with pernicious anemia because folic acid may actually potentiate neurologic complications of vitamin B12 deficiency. Conversely, doses of cyanocobalamin or hydroxocobalamin exceeding 10 mcg daily may improve folate-deficient megaloblastic anemia and obscure the true diagnosis. /Vitamin B12/
[American Society of Health System Pharmacists. AHFS Drug Information 2008. Bethesda, Maryland 2008] **PEER REVIEWED**
Serum potassium concentrations should be monitored during early vitamin B12 therapy and potassium administered if necessary, since fatal hypokalemia could occur upon conversion of megaloblastic anemia to normal erythropoiesis with vitamin B12 as a result of increased erythrocyte potassium requirements. Because vitamin B12 deficiency may suppress the signs of polycythemia vera, treatment with cyanocobalamin or hydroxocobalamin may unmask this condition. The increase in nucleic acid degradation produced by administering vitamin B12 to vitamin B12-deficient patients could result in gout in susceptible individuals. Therapeutic response to vitamin B12 may be impaired by concurrent infection, uremia, folic acid or iron deficiency, or by drugs having bone marrow suppressant effects (e.g., chloramphenicol). /Vitamin B12/
[American Society of Health System Pharmacists. AHFS Drug Information 2008. Bethesda, Maryland 2008] **PEER REVIEWED**
Vitamin B12 is usually nontoxic even in large doses; however, mild transient diarrhea, peripheral vascular thrombosis, itching, transitory exanthema, urticaria, feeling of swelling of the entire body, anaphylaxis, and death have been reported in patients receiving parenteral vitamin B12. Although allergic reactions to vitamin B12 have generally been attributed to impurities in the preparation, a few patients have reacted positively to skin testing with purified cyanocobalamin or hydroxocobalamin. Pulmonary edema and congestive heart failure have been reported during early therapy with parenteral vitamin B12, possibly because of an increase in blood volume induced by the drug. /Vitamine B12/
[American Society of Health System Pharmacists. AHFS Drug Information 2008. Bethesda, Maryland 2008] **PEER REVIEWED**
After antidotal doses, body fluids become pink or red after hydroxocobalamin administration; this subsides within 2-7 days. Nausea, vomiting, hypertension, and mild muscle twitching or spasms have been reported occasionally. Allergic reactions have not been reported with acute intravenous therapy for cyanide poisoning. However, allergic reactions have been reported when it has been used for chronic IM therapy.
[Olson, K.R. (Ed.); Poisoning & Drug Overdose. 5th ed. Lange Medical Books/McGraw-Hill. New York, N.Y. 2007., p. 460] **PEER REVIEWED**
Pustular or papular rash was detected in a small number of subjects treated with 5 g or more of hydroxocobalamin. The rash was most often located on the face and neck, and resolved spontaneously without treatment.
[European Medicines Agency (EMEA), The European Agency for the Evaluation of Medicinal Products, European Public Assessment Report (EPAR) for Authorized Medicinal Products for Human Use; Cyanokit, Scientific Discussion (2007). Available from, as of November 24, 2008: emea.europa.eu/humandocs/Hu... **PEER REVIEWED**
Allergic reactions have been reported infrequently in healthy volunteers as well as in post-marketing experience. Similar reactions have been reported with chronic use of low-dose hydroxocobalamin in the treatment of Vitamin B12 deficiency.
[European Medicines Agency (EMEA), The European Agency for the Evaluation of Medicinal Products, European Public Assessment Report (EPAR) for Authorized Medicinal Products for Human Use; Cyanokit, Scientific Discussion (2007). Available from, as of November 24, 2008: emea.europa.eu/humandocs/Hu... **PEER REVIEWED**
In some smoke inhalation victims, hydroxocobalamin was associated with reversible and transient increases in blood pressure and, more rarely, with tachycardia. The observed alterations in cardiovascular status rarely, if ever, appear to pose a risk to patients. The risk of these potential side effects must be weighed against the very real lethality induced by exposure to cyanide.
[European Medicines Agency (EMEA), The European Agency for the Evaluation of Medicinal Products, European Public Assessment Report (EPAR) for Authorized Medicinal Products for Human Use; Cyanokit, Scientific Discussion (2007). Available from, as of November 24, 2008: emea.europa.eu/humandocs/Hu... **PEER REVIEWED**
Elevated blood pressure was detected in some healthy volunteers treated with 2.5 g or more of hydroxocobalamin. A return to near pre-dose mean blood pressure values was generally observed within 4 to 8 hours post-dose.
[European Medicines Agency (EMEA), The European Agency for the Evaluation of Medicinal Products, European Public Assessment Report (EPAR) for Authorized Medicinal Products for Human Use; Cyanokit, Scientific Discussion (2007). Available from, as of November 24, 2008: emea.europa.eu/humandocs/Hu... **PEER REVIEWED**
Erythema was detected in most subjects treated with 5.0 g or more of hydroxocobalamin. Erythema appeared during the administration of hydroxocobalamin and resolved without treatment or sequelae.
[European Medicines Agency (EMEA), The European Agency for the Evaluation of Medicinal Products, European Public Assessment Report (EPAR) for Authorized Medicinal Products for Human Use; Cyanokit, Scientific Discussion (2007). Available from, as of November 24, 2008: emea.europa.eu/humandocs/Hu... **PEER REVIEWED**
Chromaturia was detected in most subjects treated with hydroxocobalamin. Chromaturia appeared promptly after administration of hydroxocobalamin and resolved without treatment or sequelae.
[European Medicines Agency (EMEA), The European Agency for the Evaluation of Medicinal Products, European Public Assessment Report (EPAR) for Authorized Medicinal Products for Human Use; Cyanokit, Scientific Discussion (2007). Available from, as of November 24, 2008: emea.europa.eu/humandocs/Hu... **PEER REVIEWED**
Oh and found this again:
Expert Group on Vitamins and Minerals 2003
webarchive.nationalarchives...
"Toxicity
Human data
There are a few case reports of adverse effects associated with ingestion of vitamin B12, either as a
supplement, or following the consumption of yeast extract products, which also contain
cyanocobalamin. Five cases of allergic reactions were reported, three of which were recurrences of
symptoms in individuals who had been previously exposed to cobalamin by the parenteral route. One
further case reported the occurrence of a skin eruption that resembled acne rosacea. Vitamin B12
exposures were generally not specified.
No adverse effects were reported in an experiment designed to determine the uptake of single oral
doses of cyanocobalamin (up to 100 mg). However, only three participants were administered the very
high doses.
Oral studies have been conducted to investigate the effects of vitamin B12 on pernicious anaemia.
However, although no adverse effects are apparent, these studies are not relevant to the general
population since absorption of vitamin B12 is reduced in this condition. The effect of high oral-dose
cyanocobalamin on plasma homocysteine levels in healthy females of child-bearing age and the
benefits of cyanocobalamin in patients with seasonal affective disorder have been investigated. No
adverse affects related to treatment were reported in any study including those in which individuals
received up to 4.5 mg/day cyanocobalamin for 14 days, 2.0 mg/day cyanocobalamin for up to one year
or 1.0 mg/day cyanocobalamin for several years. Less information is available following the oral
administration of the hydroxocobalamin form of vitamin B12. However, no adverse effects were reported".
"Carcinogenicity and genotoxicity
There is no evidence suggesting that vitamin B12 is carcinogenic or genotoxic in vitro or in vivo. How ever,
although data are not consistent, there is some limited evidence to suggest that high doses of vitamin
B12 may have tumour promoting activity."
Many thanks, Marre.
Apologies, still not clear. Not PA but referring to 'functional B12 deficiency' only.
B12 serum versus B12 active 
Low b12, gallstones and bilirubin 
help with diagnosis b12 215 vs 211 reference range GP refuses to treat. 
Stomach Acid, B12 and Thyroid
