Vitamin B12, also called cobalamin, is essential for many body functions. While vitamin B12 deficiency is well-known, having too much B12, hypercobalaminemia, may be associated with certain health conditions. Emerging research indicates that elevated B12 levels may be associated with certain underlying conditions and should be evaluated by a healthcare provider.
This article presents a comprehensive overview of high vitamin B12 levels, focusing on the causes and symptoms, potential long-term risks of high B12, and how to lower the levels.
[signup]
Understanding Vitamin B12 and the Levels
Vitamin B12 is a water-soluble vitamin that helps in the DNA-making process, forms red blood cells, and keeps the central nervous system functioning well. There are two main active forms of vitamin B12: methylcobalamin and 5-deoxyadenosylcobalamin.
Vitamin B12 helps as a co-factor for the enzyme methionine synthase. Methionine synthase helps convert homocysteine to an important amino acid called methionine. Methionine is needed to make S-adenosylmethionine, which is used by the body to make DNA, RNA, proteins, and fats. Thus, having adequate levels of vitamin B12 is necessary for the proper DNA methylation process.
What Does High B12 Mean?
Normal B12 levels range from 160 to 950 picograms per milliliter (pg/mL). Having B12 levels higher than 950 pg/mL can be a sign of various underlying medical conditions or can be due to taking high amounts of B12 supplements.
The recommended daily allowance (RDA) of vitamin B12 is 2.4 mcg for adults. Since B12 is a water-soluble vitamin, the body removes any unused amounts through the urine. Therefore, from a scientific perspective, vitamin B12 overdose is rare.
The Food & Nutrition Board has not established a tolerable upper intake limit for vitamin B12. Even in large amounts, vitamin B12 is generally considered safe.
What Causes High B12 Levels?
High vitamin B12 levels can be caused by eating foods that are high in B12, taking large amounts of B12 supplements due to various medical conditions, or because of certain gene variations.
Dietary Causes
Vitamin B12 is found in dairy products, eggs, poultry, meat and fish. Plant-based foods do not naturally have B12. However, many breakfast cereals are fortified with B12, and nutritional yeast contains vitamin B12 that the body can easily absorb.
Table 1 shows different foods and their vitamin B12 levels per serving.
Table 1. Food Sources of Vitamin B12
While many foods listed in this table are rich in vitamin B12, the body’s ability to absorb vitamin B12 from food can vary depending on many individual factors. High intake from food sources is generally well-regulated by the body and rarely leads to toxicity.
B12 Supplements
While vitamin B12 supplementation is generally safe when taken as recommended, high vitamin B12 levels can often occur from taking high amounts of B12 via supplements like capsules, tablets, or lozenges. A study reported that B12 from dietary supplements is absorbed almost 50% higher than the same amount of B12 from food.
In some studies, the daily intake of free cyanocobalamin at doses of 1.5 - 2.5 mcg for 4 to 6 months has been reported to increase plasma vitamin B12 by 10 pg/mL. Thus, it is important to supplement vitamin B12 under a doctor’s advice and monitor the levels regularly.
Prescription vitamin B12 injections and nasal gel sprays used to treat low levels of B12 should also be monitored closely to prevent levels from rising too high.
Medical Conditions
There can be various causes of high B12 levels in the absence of supplementation or high B12 food intake. Various studies have reported an increase in vitamin B12 levels due to changes in B12 metabolism associated with several underlying health conditions, including -
Liver Disease
Several liver diseases, such as acute hepatitis, cirrhosis, hepatocellular carcinoma, and metastatic liver disease, can lead to high vitamin B12 levels. This happens when damaged liver cells release B12 into the bloodstream or when the liver decreases its B12 metabolism.
Kidney Disease
Various kidney diseases can increase vitamin B12 levels because the kidneys may not work properly to remove the excess B12 from the body.
Hematologic Disorders
Blood disorders such as chronic myelogenous leukemia, polycythemia vera, myeloproliferative neoplasm, myelodysplastic syndrome, and hypereosinophilic syndrome can lead to elevated vitamin B12 levels. This often occurs due to increased production of B12-binding proteins such as haptocorrin.
Solid Neoplasms
An increase in B12 levels has been seen in various solid cancers. Various studies have documented a positive correlation between high levels of B12 and the incidence of lung, pancreatic, and liver cancers.
Immune Complexes
The presence of vitamin B12 bound to immunoglobulins, such as IgG or IgM, can falsely show high B12 serum levels. One study reported at least 8% of the samples with elevated vitamin B12 had an immunoglobulin complexed form of circulating B12. These immune complexes are biologically inactive and interfere with the measurement of vitamin B12 levels. Additionally, a condition called macro-B12, where B12-binding protein forms a complex with serum immunoglobulins can similarly present as falsely elevated B12 levels.
It is important to note that while certain medical conditions are correlated with high B12 levels, a healthcare provider must perform further diagnostic evaluation to determine the cause.
Genetic Causes
Various genetic changes can lead to higher vitamin B12 levels by affecting how the vitamin is absorbed, transported, and used in the body.
- Variants in FUT2, FUT6, TCN1, and TCN2 genes can affect how B12 is transported and used throughout the body, potentially contributing to higher B12 levels.
- Variants in the CUBN gene can increase the absorption efficiency of B12, causing more vitamin B12 to enter the bloodstream.
- Variants in the CD320 gene can reduce the amount of B12 taken up by cells, potentially increasing the circulating B12 serum levels.
- Mutations in the MMACHC and MMAA genes can lead to problems with how vitamin B12 is used at the cellular level. This can cause abnormal accumulation of B12 in the blood while the cells might not be getting enough active form of B12. This can cause metabolic issues and a condition known as methylmalonic aciduria.
- Variants in the MUT gene can affect the enzyme called methylmalonyl-CoA mutase, which helps complete the last step of B12 metabolism and how the body uses vitamin B12. This may cause higher levels of B12 in the blood.
Disclaimer: The information in this section is provided for educational purposes only. Elevated vitamin B12 levels can be influenced by a variety of factors, and only a healthcare professional can determine the underlying cause of high B12 levels.
Symptoms of High B12 Levels
Although rare, high amounts of vitamin B12 may cause the following symptoms:
- Headaches
- Nausea and vomiting
- Diarrhea
- Fatigue or weakness
- Tingling sensations in the hands and feet
Lab Tests for High B12 Levels
High vitamin B12 levels can be evaluated through various laboratory and biomarker tests.
Initial Testing
The initial test done for checking vitamin B12 levels is the serum B12 test. This test measures the total amount of vitamin B12 in the blood.
A holotranscobalamin (holoTC) test can also be done to measure the active form of B12 that is available for the cells to use. For both these tests, a blood sample is drawn from a vein and tested in a laboratory.
Normal serum vitamin B12 values are 160 to 950 pg/mL. However, these ranges may vary slightly among different laboratories. Therefore, it is important to consult individual lab companies regarding specific reference ranges.
Additional Testing
- Testing for related biomarkers: Methylmalonic acid (MMA) and homocysteine are two key metabolic markers. Elevated levels of MMA and homocysteine can indicate functional B12 deficiency despite high serum B12 levels.
- Genetic tests: Genetic tests for high vitamin B12 levels are not commonly used in the clinical setting. These tests are done only when there is a suspicion of a genetic disorder affecting B12 metabolism. Next-generation sequencing based gene panel testing is helpful when other serum and biomarker tests do not provide clear results to determine the cause of high B12 levels.
- Imaging and other diagnostic tools: These may be helpful in diagnosing various underlying conditions that could be causing high B12 levels.
Potential Health Risks of High B12 Levels
The potential short-term risks of high vitamin B12 levels mainly involve the side effects. In the long term, high B12 levels are associated with various chronic conditions.
Short-Term Risks
In the short term, taking high amounts of vitamin B12 can lead to various acute symptoms discussed above. These symptoms often resolve once the patient discontinues or lowers the amount of the B12 supplement.
Long-Term Risks
Consistently high vitamin B12 levels may be associated with certain health concerns, according to research. It is important to work with a healthcare provider to monitor and assess B12 levels, especially when taking supplements or managing underlying health conditions.
General Health Risks:
Some studies suggest a potential link between elevated B12 levels and an increased risk of mortality. A systematic review and meta-analysis indicated that for each 135 pg/mL increase in serum B12 concentration, there was a 4% higher risk of all-cause mortality in the general population and a 6% higher risk in older adults.
Research has also observed that individuals with very high B12 levels (above 1000 pg/mL) who were hospitalized and at nutritional risk had a greater likelihood of in-hospital mortality. However, these findings may be influenced by pre-existing conditions, and further research is needed to confirm these associations.
Cancer Considerations:
Persistently high B12 levels have been studied in relation to the risk of certain cancers. Research indicates that elevated B12 levels may be associated with an increased likelihood of solid cancers, including lung, liver, and pancreatic cancers, as well as myeloid neoplasms.
A systematic review reported a positive correlation between high B12 levels and the incidence of specific cancers. For instance, one cohort study found a higher 1-year cancer risk in patients with plasma B12 levels exceeding 1,355 pg/mL. These findings underscore the importance of investigating potential underlying causes of elevated B12 levels, such as undiagnosed health conditions.
These findings associated with consistently high vitamin B12 levels highlight the importance of closely monitoring B12 levels and using B12 supplements under the doctor’s guidance. It is important to identify and manage the underlying causes of high vitamin B12 levels.
How to Lower B12 Levels
Lowering vitamin B12 levels depends on the underlying cause of the high levels.
Dietary Adjustments
If a patient consumes a high amount of the B12-rich foods listed in Table 1 above, dietary changes can be considered to reduce the B12 levels.
Medical Interventions
There is no specific antidote for cobalamin that can help lower vitamin B12 levels. Discontinuing vitamin B12 supplements can help reduce elevated levels, particularly in patients who are taking high amounts of supplements without a clear medical need.
Additionally, treating the underlying medical conditions that cause elevated B12 may help lower the levels.
Monitoring and Follow-Up
Regular monitoring of serum B12 levels, along with MMA and homocysteine, is recommended. Follow-up tests should include complete blood count, liver function tests, and renal function tests to identify any underlying conditions.
B12 levels should be monitored every 3 to 6 months until they are in the normal range. It is also important to assess and monitor the clinical symptoms and adjust treatment plans as needed to address the underlying cause of high B12.
[signup]
Key Takeaways
- Vitamin B12 is a water-soluble vitamin, which means the body usually gets rid of the extra amounts through urine.
- High B12 levels can be caused by various factors, such as taking large amounts of supplements, eating a diet high in B12-rich foods, certain medical conditions, and some genetic factors.
- High B12 levels are usually diagnosed via blood tests. Additional tests may be needed to identify underlying conditions.
- While B12 toxicity is rare, having high levels for a long time can cause side effects and might lead to some health risks.
- It is important to talk to your doctor when taking B12 supplements. Regular monitoring of the levels can help detect high levels, diagnose the underlying cause, and begin treatment to lower the levels as necessary.
%201.svg){kind=logo}
