by Dr. Miles Nichols and Aaron Mello, CNTP, MNT
Vitamin B12 is an essential nutrient that is involved in many crucial functions in the body, and B12 injections are a great way to increase your levels. Do you know if you have enough B12? Consequences of B12 deficiency range from fatigue, vision loss and constipation to neurological problems, psychiatric problems and certain types of anemia. Vitamin B12 is found almost exclusively in animal foods, so long-term vegans and vegetarians are at an elevated risk of deficiency. In addition, absorption of this nutrient from food is a somewhat complex process and may be impaired in some people.
In this blog we’ll review the most important functions of Vitamin B12 in the body, which foods are good sources, what conditions and medications interfere with absorption, how to test for Vitamin B12 deficiency and the researched benefits of B12 injections. Because B12 absorption can be impaired even if you’re eating enough, you may be deficient even if you’re eating B12-rich foods. If you’re deficient in B12 despite eating good food, B12 injections are the most effective way to raise B12 levels. Keep reading to learn about the benefits of B12 injections!
Also known as cobalamin, vitamin B12 is an essential water-soluble nutrient that is part of the B complex of vitamins. B12 is more complex than the other B vitamins. The name cobalamin comes from the fact that this vitamin contains cobalt. B12 is the only B vitamin which contains this element. Different forms of cobalamin are available in supplement form, including cyanacobalamin, methylcobalamin, and hydroxocobalamin. Different forms of B12 injections are appropriate depending on an individual’s methylation status. Next, we’ll look at the roles B12 plays in the body.
Functions of vitamin B12
Vitamin B12 is required for many functions in the body. People who get B12 injections often cite increased energy as a primary benefit. One main way B12 improves energy levels is its role in the production of erythrocytes (red blood cells), which carry oxygen to the cells, where it is used to fuel energy-producing mitochondria. B12 deficiency leads to a type of anemia called megaloblastic anemia, which is characterized by depressed numbers of erythrocytes that are also immature and large, or macrocytic. Low levels of erythrocytes impair the body’s ability to supply cells with sufficient oxygen, resulting in anemic fatigue.
In addition to helping synthesize erythrocytes, Vitamin B12 is also used for:
- DNA synthesis
- Converting homocysteine to methionine
- Neurotransmitter function
- Synthesis of hormones
- Producing the myelin sheath that coats nerves
- Fetal development during pregnancy (1)
These are just some of the most important known functions of B12 and is certainly not an exhaustive list. Now that we know some of the critical functions of B12 in the body, let’s go on to symptoms of B12 deficiency before getting into the benefits of B12 injections.
Signs and symptoms of B12 deficiency
Because B12 is used for so many processes in the body, there can be many signs and symptoms. Because symptoms can have overlapping causes, these should not be used to diagnose B12 deficiency. With that said, these signs and symptoms may indicate that B12 testing is appropriate.
Here are the main signs and symptoms:
- Pale or jaundiced skin
- Weakness and fatigue
- Peripheral sensation of “pins and needles” in extremities
- Unsteady gait or trouble balancing
- Glossitis – red, smooth and swollen tongue
- Breathlessness or dizziness
- Disturbed vision
- Depression and other mood changes
Next, we’ll look at which foods are high in B12.
Food sources of vitamin B12
Vitamin B12 is primarily found in animal foods, so long-term vegans may be at increased risk for B12 deficiency if they are not supplementing or getting B12 injections. One review of 40 studies found that up to 86% of vegans may be deficient in B12 (2). Vegans with low B12 levels may want to consider whether their diet is still serving them. Omnivores may also be deficient, usually due to impaired ability to absorb B12 known as pernicious anemia, which we’ll discuss shortly. We’ll also get into testing to establish whether your B12 levels are adequate.
These foods are best sources of B12:
- Grass-fed beef liver
As you can see, these are all animal and marine sources. The best sources for vegetarians who eat seafood (pescetarians) are shellfish (especially clam), fish like sardines and salmon, eggs and yogurt. Some mushrooms also contain some B12, although it’s disputed whether the amount is significant (3). The same is true for fermented food like tempeh – the bacteria which ferment soybean into tempeh synthesize some B12, but it may be a form that has low affinity for intrinsic factor and is not well absorbed (4).
Consequently, supplementation is especially important for strict vegans. For most people, B12 injections are the best option to raise their B12 levels, whether they vegan, omnivorous or somewhere in the middle. This form bypasses the digestive tract and any problems that may prevent absorption. We’ll talk about absorption problems in the next section.
Inability to absorb B12
Many factors can result in an impaired ability to absorb B12 from food. In contrast to other B vitamins, B12 is more complex and absorption of this nutrient is more complicated. The parietal cells in the stomach secrete hydrochloric stomach acid (hcl) as well as intrinsic factor, which is required to absorb B12. Intrinsic factor binds to B12 and enables its absorption in the small intestine. B12 absorption relies on both intrinsic factor and adequate hcl. Many of the causes of B12 malabsorption are related to impaired hcl and intrinsic factor production.
Some of the most common causes of impaired B12 absorption are:
- Pernicious anemia – more on this shortly
- Parasitic infections like fish tapeworm and Giardia lamblia
- Small Intestine Bacterial Overgrowth (SIBO)
- Familial factors
- Hypochlorhydria (low stomach acid)
- Aging – stomach acid production declines with age
- Gastrointestinal surgery that removes significant sections of the terminal ileum
- Digestive disorders like Crohn’s disease or celiac disease
- Certain medications like oral contraceptives, Metformin, proton pump inhibitors (PPIs) and others (5)
If a person is consuming a reasonable about of B12-rich foods in the diet but B12 levels are still low, this may indicate an issue with B12 absorption. In these cases, oral B12 supplements are unlikely to make much of an impact, as they too must be absorbed in the small intestine. These cases are especially good candidates for B12 injections, since that route of administration bypasses the digestive tract.
If a person is unable to absorb B12, it’s important to treat the root cause for that malabsorption. B12 shots bring levels of this crucial nutrient back up, but they do not resolve the underlying root cause. A B12 deficiency in an individual who’s eating B12-rich foods provides valuable information to indicate an underlying problem. It’s important to work with a qualified functional medicine practitioner to not just correct B12 levels with B12 injections, but also treat the underlying root cause. We’ll go into B12 malabsorption in the next section.
Pernicious anemia (PA) is also known as B12 deficiency anemia, and occurs when the body is unable to absorb B12. We’ve already talked about the role of B12 in anemia and problems with absorption. Pernicious anemia is a common cause of B12 malabsorption and accounts for 20-50% of B12 deficiency in adults. It usually results from an autoimmune attack against either gastric parietal cells which secrete intrinsic factor and hydrochloric acid, or intrinsic factor itself. PA is diagnosed by testing for antibodies against intrinsic factor and/or gastric parietal cells (GPC) (6).
Pernicious anemia was identified in 1855 by Thomas Addison, the English physician best known in the context of Addison’s disease. At that point, PA was often fatal until science discovered that it was a B12 deficiency, hence the name pernicious, which means highly destructive or fatal. Even once the B12 connection was made it was still difficult to treat, as many people with PA are not able to absorb oral B12 supplements or foods high in B12 like liver (7). Happily, today it is easily treated with B12 injections, which bypass the digestive tract.
PA causes a type of anemia known as megaloblastic anemia, which we mentioned briefly earlier. Megaloblastic anemia is a form of macrocytic anemia characterized by large, oversized and immature erythrocytes paired with low overall levels of erythrocytes. Because B12 is required for proper maturation of erythrocytes, a deficiency of this vitamin results in pernicious anemia. Now that we understand the role B12 plays in PA, let’s go on to testing for B12 deficiency.
Testing for B12 deficiency
We use a blood test to diagnose B12 deficiency. In addition to getting serum B12 levels, we also run methylmalonic acid (MMA), which helps to provide more accurate results. The combination of these two markers provides the most accurate picture of B12 levels. MMA is inversely correlated with B12 levels and high MMA levels indicate a B12 deficiency and a need for B12 injections.
B12 is the only cofactor that metabolizes MMA into succinyl-CoA. Consequently, elevated MMA levels indicate there is not enough B12 to make the conversion to succinyl-CoA. MMA is considered a superior marker to serum B12 because that value can change fairly rapidly if B12 has been ingested recently, so B12 by itself can change quickly and be misleading. We like to run both B12 and MMA levels.
Another marker that is useful but not commonly available from US labs is holotranscobalamin II. This marker can detect even early stages of B12 deficiency (stage I and II). MMA detects middle stages, and serum B12 detects later stages. For a functional range on the most common test, we like to see serum B12 at least at 400 pg/ml (evidenced by research and supported in lab ranges in some countries like Japan). We optimally prefer to see 500 pg/ml or higher.
High homocysteine can be an indirect marker / indicator of B12 deficiency. It is also possible that homocysteine can be elevated with low folate or low B6 also. So it is not a guarantee of just B12 since there are other nutrients that can be depleted causing elevated homocysteine levels.
Benefits of B12 injections
If you are deficient in vitamin B12, injections are the most effective way to bring levels back up and alleviate a lot of symptoms. In this section we’ll explain some of the most common benefits.
- Reduce fatigue:
- Low B12 levels inhibits production of erythrocytes (red blood cells) and leads to fatigue. Bringing B12 levels back up through injection can significantly improve energy levels.
- Improve athletic performance:
- Exercise increases the body’s oxygen needs to fuel the mitochondria. Because B12 deficiency leads to anemia (low erythrocytes) and a reduced ability to carry oxygen to the mitochondria, athletic performance suffers. Bringing B12 levels back up can help improve oxygenation of mitochondria, and as a result, boost athletic performance.
- Protects the heart by lowering homocysteine:
- Prevent cognitive decline associated with dementia:
- High homocysteine is a risk factor for dementia in addition to heart disease and B12 can lower homocysteine. The benefits directly related to dementia may be limited to those with pernicious anemia who are unable to absorb B12 (9).
- Reduce symptoms of depression:
- Depressed patients often have low levels of B12. In addition, B12 and folate are required for S-adenyl methionine (SAMe) production, which donates methyl group that are crucial for proper neurological function (10).
- We recently wrote about pyroluria, a condition that can cause symptoms of depression, as well as how omega-3s can impact pyroluria.
- Improve hair, skin and nails:
- B12 isn’t just used to produce erythrocytes, it’s required for multiple rapidly dividing cell lines including hair, skin and nails. In fact, one common symptoms of B12 deficiency anemia is brittle fingernails (11).
- Increase sperm count and motility:
- Vitamin B12 improves semen quality, increases sperm count and improves sperm motility. These benefits probably result from increased reproductive organ functionality, decreased homocysteine toxicity, reduced nitric oxide and reducing oxidative damage to sperm (12).
- Reduces fetal development problems:
- B12 is required for proper fetal development and deficiency has been linked to cognitive, motor and growth problems in fetal development (13).
- Improve B12 deficiency symptoms:
- We listed symptoms of deficiency earlier, including: Pale or jaundiced skin, weakness and fatigue, peripheral sensation of “pins and needles,” unsteady gait or trouble balancing, glossitis, breathlessness or dizziness and disturbed vision. These all stand to improve after correcting low B12 levels.
Vitamin B12 is a critical nutrient for many processes in the body, and deficiency can have serious consequences. Some effects of B12 deficiency can result in permanent damage, such as irreversible nerve damage. If you suspect that you may be deficient, it’s important to work with a qualified functional medicine practitioner to properly diagnose the deficiency, correct it with B12 injections and identify what underlying root cause is contributing to the deficiency.
When considering the value of increasing B12 levels:
- Functional lab testing for serum B12, MMA, Homocysteine, and if possible Holotranscobalamin II can help identify a deficiency
- Look at dietary sources and for vegans or vegetarians who are willing to have some shellfish, consider a weekly serving or two of clam
- Consider B12 injections and/or supplementation if there is an absorption issue or if there is a medication being used that is depleting levels
- Look for methylcobalamin or hydroxocobalamin for supplements and/or injections and avoid cyanocobalamin because of trace amounts of cyanide present in cyanocobalamin
- Work with a functional medicine practitioner to find underlying root causes for why B12 levels are not sufficient and correct the root causes
- Black MM. Effects of vitamin B12 and folate deficiency on brain development in children. Food and nutrition bulletin. 2008;29(2 Suppl):S126-S131.
- Pawlak, R, et al. “The Prevalence of Cobalamin Deficiency among Vegetarians Assessed by Serum Vitamin B12: a Review of Literature.” European Journal of Clinical Nutrition, vol. 68, no. 5, 2014, pp. 541–548., doi:10.1038/ejcn.2014.46.
- Watanabe F, Yabuta Y, Bito T, Teng F. Vitamin B12-Containing Plant Food Sources for Vegetarians. Nutrients. 2014;6(5):1861-1873. doi:10.3390/nu6051861.
- O’Leary F, Samman S. Vitamin B12 in Health and Disease. Nutrients. 2010;2(3):299-316. doi:10.3390/nu2030299.
- Office of Dietary Supplements. “Vitamin B12.” NIH Office of Dietary Supplements, U.S. Department of Health and Human Services, 24 June 2011, ods.od.nih.gov/factsheets/VitaminB12-Consumer/.
- Andres E, Serraj K. Optimal management of pernicious anemia. Journal of Blood Medicine. 2012;3:97-103. doi:10.2147/JBM.S25620.
- Chanarin, I. (2000), A history of pernicious anaemia. British Journal of Haematology, 111: 407–415. doi:10.1111/j.1365-2141.2000.02238.x
- Verhoef, P., et al. “Homocysteine Metabolism and Risk of Myocardial Infarction: Relation with Vitamins B6, B12, and Folate.” American Journal of Epidemiology, vol. 143, no. 9, Jan. 1996, pp. 845–859., doi:10.1093/oxfordjournals.aje.a008828.
- Werder SF. Cobalamin deficiency, hyperhomocysteinemia, and dementia. Neuropsychiatric Disease and Treatment. 2010;6:159-195.
- Coppen, Alec, and Christina Bolander-Gouaille. “Treatment of Depression: Time to Consider Folic Acid and Vitamin B12.” Journal of Psychopharmacology, vol. 19, no. 1, 2005, pp. 59–65., doi:10.1177/0269881105048899.
- Brescoll, Jennifer, and Steven Daveluy. “A Review of Vitamin B12 in Dermatology.” American Journal of Clinical Dermatology, vol. 16, no. 1, June 2015, pp. 27–33., doi:10.1007/s40257-014-0107-3.
- Banihani SA. Vitamin B12 and Semen Quality. Bähler J, ed. Biomolecules. 2017;7(2):42. doi:10.3390/biom7020042.
- Pepper, M. Reese, and Maureen M. Black. “B12 In Fetal Development.” Seminars in Cell & Developmental Biology, vol. 22, no. 6, 2011, pp. 619–623., doi:10.1016/j.semcdb.2011.05.005.