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Vitamin B12



Vitamin B12 (cobalamin) is the largest and most chemically complex of all the vitamins and typically gets the greatest mention of the B vitamins.  It is unique among the vitamins in that it contains a metal ion, cobalt, from which it derives its name. It is vital to multitudes of cell functions, participates with folate in the production of DNA, which is critical for the production of red blood cells,  and helps reduce homocysteine levels and therefore cardiovascular risk. B12 protects the myelin sheath of nerves, helps maintain the immune system, and is required for proper carbohydrate metabolism. Those with low levels of B12 can suffer from higher lactate levels,  fatigue and weakness, depression, memory loss, diminished immune function, peripheral neuropathy, and can develop megaloblastic anemia similar to that associated with folate deficiency. Symptoms of deficiency can include numbness and tingling in the hands and feet, dementia, disorientation, difficulty walking, lost appetite, tongue soreness and constipation.  


Methylcobalamin is required in the pathway which yields the active folate form 5-tetrahydrofolate.  If there is insufficient B12 present, the folate remains in an unusable form and symptoms of folate deficiency can ensue despite the presence of adequate folate.  This decreases DNA methylation and synthesis necessary for rapid cell division and in the case of red blood cell development, yields large, immature RBCs, low in hemoglobin content and weak in oxygen transport abilities.  When this megaloblastic anemia results from an autoimmune condition that destroys the stomach parietal cells' ability to produce intrinsic factor it is termed pernicious anemia. Megaloblastic anemia can have drastic impacts on athletic performance, can lead to elevated homocysteine levels and associated cardiovascular risks.  It has also been associated with weakened bone integrity and stomach cancer. If this condition is simply treated with a methylated folate supplement, the symptoms should reduce but a hidden B12 deficiency may go unrecognized and untreated. It is therefore advisable to assess for both pathways that lead to the development of megaloblasts or macrocytes, namely folate and/or B12 deficiency to be safe.  


Research has shown that a significant number of endurance athletes don't get enough Vitamin B12.  Studies have found that significant numbers of female and male triathletes and highly trained female cyclists did not consume the recommended daily intake of B12. Vegetarian athletes especially, can struggle to get enough B12 in their diets.  B12 cannot be produced by plants or animals. It is formed from the enzymatic activity of certain bacteria such as some found in the gut.  Plants do not concentrate B12 from the soil and have very little B12 content as a result. Animal products such as meats, liver, shellfish, eggs and dairy are prime sources of B12.  


More often than inadequate intake, malabsorption poses great impediment to the uptake of B12.  Adequate hydrochloric acid (HCL) levels in the stomach are required to break down proteins and free the B12 for absorption.  Many athletes, especially as they age over 40, have more and more difficulty absorbing B12 due to declining HCL production as in hypochlorhydria (low HCL) or achlorhydria (no HCL). (Learn more about HCL's role in micronutrient absorption here)  The prevalence of these issues in the general populous makes B12 supplementation a worthy consideration as athletes get older. Gastrointestinal pathology such as colitis and celiac, leaky gut syndrome, and food sensitivities can make it difficult to adequately absorb B12 and all other micronutrients.  As mentioned, the absorption of B12 also requires adequate production of the protein called intrinsic factor in the stomach. After HCL frees B12 from protein, intrinsic factor binds with B12 in the stomach and is necessary for absorption. An autoimmune condition can cause a lack of intrinsic factor and typically results in a B12 deficiency anemia termed "pernicious anemia".   Athletes suffering from low B12 will have less ability to repair cells and recover from exercise. They typically will tire easily, be more prone to injury, feel weak and unsteady and often find it difficult to concentrate or make decisions.




B12, along with folate, also helps in the production of the critically important S-adenosylmethionine (SAMe) in the liver.  SAMe is vital to neurotransmitter production, nerve health and has positive influences on mood by improving serotonin and dopamine activity.  SAMe is also a phenomenal aid against joint damage and osteoarthritis. Recent research findings looking into its benefits for those with joint problems are very positive.  It increases the number of cartilage producing cells and protects against cartilage loss in joints. It has the capacity to block enzymes that damage cartilage and protects synovial cells from being destroyed by the immune agent, tumor necrosis factor or TNF, relieving pain and inflammation.   SAMe also exhibits powerful liver regenerative effects. It aids in the development of the body's master antioxidant and detoxification agent, glutathione, and can reverse the liver damage caused by cirrhosis. SAMe can be supplemented effectively in an enteric coated form to protect its methyl groups from gastric juices,  and should be researched and considered by athletes with joint pain and degenerative concerns and/or who are generally grumpy or depressed.


Forms of B12:


Vitamin B12 is has two active forms in the body, methylcobalamin and 5-deoxyadenosyl  (adenosyl) cobalamin. The pathway by which B12 works with folate to lower homocysteine levels by converting it to methionine requires methylcobalamin as a cofactor.  The methionine produced can then be used in DNA methylation. Adenosyl cobalamin is vital in the energy production pathways involving proteins and fats and in the production of hemoglobin.  The most common form of supplemental B12 and that most typically used in fortified foods is cyanocobalamin. This is an inferior, synthetic and biologically inactive form of the vitamin. It is widely available and inexpensive.  It is formed with a cyanide group attached to the B12 component. Cyanocobalamin requires breakdown, or methylation to the active form methylcobalamin and the cyanide group itself requires detoxification/methylation to protect the body from it's inherent toxicity, and can put pressure on precious glutathione stores and detoxification pathways.  Less toxic but still inactive and requiring conversion to active B12 is hydroxocobalamin. The RunTheLabs recommenced supplemental form of choice for B12 is methylcobalamin or a combination of methylcobalamin and hydroxycobalamin or adenosylcobalamin. Methylcobalamin is available in a variety of forms of supplementation from suspensions with fish oil to liquid drops, sublinguals and capsules, tablets and transdermal patches.  


Dietary Intake and Supplementation:


The Dietary Reference Intake for vitamin B12 is 1.8 mcg per day for 9-13 year olds, 1.8 mcg per day for 14 and older and  2.4 mcg and 2.6 mcg per day for pregnant and breastfeeding mothers respectively. For those wishing to supplement B12, one consideration would be to use a complete B vitamin complex due to all of the synergism in and amongst this group of vitamins.  A quality B complex will have safe and appropriate levels of each of the B vitamins and will use only the methylated forms of folate and B12, and "P5P" for B6. Avoid products with folic acid as many people have single nucleotide polyorphisms, subtle genetic mutations, that make the breakdown of folic acid in active folate difficult.  B-Complex with Metfolin and Intrinsic Factor by Douglas Labs is our product of choice as it ticks all of those boxes, contains intrinsic factor to help B12 absorption for those lacking the protein, and contains the only form of folate known to cross the blood-brain barrier. Athletes could find significant benefit in taking one to two capsules of this product per day, depending on body mass, general dietary intake of B rich foods and training intensity.  If B12 levels are very low, less than 550 pg/mL, a solo B12 product can be added for an additional 1000mcg per day to a total of 1500-2000mcg per day. This additional B12 would likely only be necessary for a few weeks as the liver will build up a store of it.  Those with very stubborn low levels, or with suspicion of B12 deficiency related nerve damage should seek consultation with their primary care physician who can consider the administration of a schedule of intramuscular injections of B12. Be mindful that this is often administered in cyanocobalamin form.


There is no known toxicity to taking in large quantities of B12 form food or supplemental form.  For reasons listed above, we would not generally suggest high intake of the cyanocobalamin form. High doses of B12 typically administered in the treatment of pernicious anemia have generally been well tolerated without significant side effects.  Part of that may owe to the low absorption of oral supplement forms of the vitamin. No tolerable upper limit (UL) has been established by the USDA owing to the lack of toxicity.


Foods rich in B12:

Foods with the highest natural B12 content include shellfish, liver, beef, milk, cheese, eggs, and  fish such as mackerel.


Drug Interactions:


B12 absorption from foods can be hampered with the use of drugs which lower stomach acid levels.  These include over the counter antacids as well as H2 receptor antagonists and proton pump inhibitors.  Individuals taking these drugs should track their B12 and other micronutrient levels and supplement accordingly.  The diabetes medication metformin, antibiotics neomycin and chloramphenicol, the high cholesterol medicine cholestyramine,  and the gout medicine cholchicine also block B12 absorption from foods. Nitrous oxide, a common anesthetic, inactivates B12 and can potentiate symptoms of deficiency.  

How We Test:

Serum B12 = level of all forms of B12 in the serum                       

RunTheLabs Optimum Range: 825-1100 ng/mL


The low end of standard lab references ranges for vitamin B12 are woefully inadequate for athletes.  Ranges are considered normal by U.S. labs from 260-935 pg/mL for 10-17 year olds and 200-1100 pg/mL for those over 17 years.  In contrast Japan and some European countries have their lower limit set at 500-550 pg/mL. Data from the Framingham Offspring Study (2000) which looked at just under 3,000 individuals showed that 39 percent of people between the ages of 26 and 83 had plasma B12 levels below 350 pg/mL and 17 percent had levels below 251 pg/mL.  9 percent were below 201 pg/mL. Surprisingly, this study showed no major differences between levels in younger or older participants or any correlation of levels to amounts of meat consumption. There were no vegetarians in the study. The findings disprove the notion that adequate animal product intake alone is an effective safeguard against B12 insufficiency and establishes that omnivores are at risk as well.   Estimates are that about 40 percent of people over 60 years of age are B12 deficient. It is plausible to suggest that some of the symptoms normally attributed to the aging process (cognitive decline, memory loss, low energy, decreased physical ability) are at least in part owing to low B12. It has been established that some will experience neuropsychiatric and hematological abnormalities at plasma levels between 200-400 pg/mL. 


Some individuals may test high, even way out of range at times, for B12.  This is most commonly due to supplementation.   For unexplained high levels consistently out of the standard lab reference range, in the absence of supplementation, consultation with a physician should be considered. For dramatically high unexplained numbers, over 1500 ng/uL, without supplementation, we recommend consultation with a physician.

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