Vitamin B12 deficiency, vitamin B2 and hypothyroidism


Symptoms of vitamin B12 deficiency and hypothyroidism

Many of the symptoms of hypothyroidism are similar to the symptoms of vitamin B12 deficiency. Thus, fatigue, weakness, depression, irritability, memory loss, abnormal menstrual cycles, decreased libido and poor mental growth are similar. to both conditions.  Confounding the situation is that  there is a high (approx 40%) prevalence of vitamin B12 deficiency in hypothyroid patients. Traditional symptoms are not a good guide to determining presence of B12 deficiency. Screening for vitamin B12 levels should be undertaken in all hypothyroid patients, irrespective of their thyroid antibody status.

Why hypothyroidism leads to vitamin B12 deficiency.

Normal cycling of folate results in the formation of an irreversible reaction in which 5, 10 methylenetetrahydrofolate is converted to 5-methyltetrahydrydrofolate (5-MTHF) by the enzyme 5,10 methyltetrahydrofolate reductase (MTHFR). Of note in this reaction is that MTHFR uses FAD (derived from riboflavin, vitamin B2) as an essential cofactor. In addition, the reduction that occurs requires input from NADH + H+ (derived from nicotinamide, vitamin B3). In the absence of these two vitamins (B2/B3) the enzyme is not functional. In this situation, folate is not able to recycle via the conversion of 5,10-methenyltetrahydrofolate to 5-methyltetrahydrofolate. This leads to an intracellular deficiency of folate, MeCbl, methionine and SAM.


Role of the Thyroid in FAD synthesis

Synthesis of Flavin Mononucleotide (FMN) from riboflavin requires the addition of phosphate from ATP, via riboflavin kinase, with the input of triiodothryonine (T3) and thyroxine (T4). Both T3 and T4 are produced in the thyroid following stimulation by thyroid stimulating hormone (TSH). The subsequent synthesis of FAD from FMN also involves contribution of thyroxin in the presence of FAD plus AMP. Deficiency in thyroxine, due to hypothyroidism can result in reduced levels of FAD in the body. Similarly dietary deficiency in either iodine and/or riboflavin can result in reduced FAD.

In persons with hypothyroidism, or vitamin B2, or vitamin B3 deficiency, or those who have mutations in the MTHFR gene, the MTHFR enzyme has reduced activity and so the amount of 5MTHF that is synthesized is reduced, and so the 5MTHF + OHCbl <=> THF + MeCbl reaction cannot operate efficiently and hence supplies of MeCbl are rapidly turned into inactive OHCbl. (The extent of reduction is dependent upon the extent of deficiency or how many and which types of mutations occur in the MTHFR gene). As a consequence, the normal addition of the methyl group from the folate cycle is reduced and so must be supplied by MeCbl. As the methyl group cannot be recycled via the normal route, every methyl group used in synthesis must be supplied by MeCbl. This leads to rapid depletion of VB12 stores.