From the Guidelines
Low vitamin B12 and folate deficiencies are primarily caused by inadequate dietary intake, malabsorption conditions, and certain medications, as highlighted in the most recent guideline summary from 2024 1. The causes of low vitamin B12 levels include a diet low in vitamin B12, such as a vegan diet, and health conditions like atrophic gastritis, coeliac disease, and autoimmune conditions.
- A diet that excludes or is low in animal source foods increases the risk of vitamin B12 deficiency
- Certain health conditions, such as atrophic gastritis, coeliac disease, and autoimmune conditions, can lead to malabsorption of vitamin B12
- Medications like metformin, H2 receptor antagonists, and phenobarbital can also reduce vitamin B12 levels Folate deficiency, on the other hand, can occur due to poor dietary intake, malabsorption, and drug interactions, as noted in a study from 2017 1.
- Folate deficiency is often related to vitamin B12 deficiency, as the latter plays a crucial role in folate metabolism
- A diet lacking leafy greens, fruits, and fortified foods can lead to folate deficiency
- Certain medications, such as methotrexate and trimethoprim, can interfere with folate metabolism It is essential to identify and address the underlying cause of the deficiency to provide appropriate treatment and prevent long-term health consequences, such as anemia, neurological symptoms, and other health problems 1.
From the FDA Drug Label
A vegetarian diet which contains no animal products (including milk products or eggs) does not supply any Vitamin B12. Colchicine, para-aminosalicylic acid and heavy alcohol intake for longer than two weeks may produce malabsorption of Vitamin B12. Folate deficiency may result from increased loss of folate, as in renal dialysis and/or interference with metabolism (e. g. folic acid antagonists such as methotrexate); the administration of anticonvulsants, such as diphenylhydantoin, primidone, and barbiturates; alcohol consumption and, especially, alcoholic cirrhosis; and the administration of pyrimethamine and nitrofurantoin The causes of low Vitamin B12 and folate levels include:
- Vegetarian diet without animal products 2
- Malabsorption due to certain medications (colchicine, para-aminosalicylic acid) or heavy alcohol intake 2
- Increased loss of folate due to renal dialysis 3
- Interference with metabolism due to folic acid antagonists (methotrexate) 3
- Administration of certain anticonvulsants (diphenylhydantoin, primidone, barbiturates) 3
- Alcohol consumption and alcoholic cirrhosis 3
- Administration of certain medications (pyrimethamine, nitrofurantoin) 3
From the Research
Causes of Low Vitamin B12 Levels
- Low dietary intake of vitamin B12, particularly in strict vegetarians (vegans) and individuals with low intake of animal-source foods 4, 5, 6
- Malabsorption of vitamin B12, commonly observed as food-bound cobalamin malabsorption due to gastric atrophy in the elderly, and probably as a result of Helicobacter pylori infection 4, 5
- Gene polymorphisms in transcobalamins affecting plasma vitamin B12 concentrations 4
- Defects in cellular delivery and uptake of vitamin B12 5
- Limited dietary intake of vitamin B12, particularly in populations with food insecurity 5
Causes of Low Folate Levels
- Low intake of sources rich in folate, such as legumes and green leafy vegetables 4, 6
- Increased risk of folate deficiency in lactation and alcoholism 4
- Poor folate status in vulnerable women of childbearing age, increasing the risk of neural tube birth defects 6
Interaction between Vitamin B12 and Folate
- High-folate-low-vitamin B12 interaction as a novel cause of vitamin B12 depletion with specific etiology 7
- Excessive intake of folic acid depleting serum holotranscobalamin (holoTC) and decreasing active vitamin B12 in the circulation 7
- Vitamin B12 supplementation decreasing homocysteine and methylmalonic acid but also serum folate in patients with end-stage renal disease 8