Vitamin B12, also known as cobalamin, is a water-soluble vitamin, which means it dissolves in water and is not stored in the fat cells. It is derived from animal products such as red meat, dairy, and egg. It plays a significant role in several physiological processes, including normal nervous system functioning, and red blood cell development and maturation.
Parietal cells in the stomach produce a glycoprotein called intrinsic factor, which is necessary to absorb vitamin B12 in the terminal ileum. It has been observed that vitamin B12 also has antioxidant effects when it gets absorbed, and it is used as a cofactor for enzymes that are involved in the synthesis of deoxyribonucleic acid (DNA), fatty acids, and myelin.
Vitamin B12 is also a micronutrient, which means the body requires it in relatively small quantities. However, despite the small amount needed, the effects of a deficiency can be devastating.
As vitamin B12 is not stored in the body, therefore excess amounts are often removed in urine. That is why the human body is prone to vitamin B12 deficiency if ingestion is reduced. Therefore, it is advised to consume an adequate amount of vitamin B12 regularly through diet or supplements.
Mechanism of Action of Vitamin B12 on Neurotransmitters
Vitamin B12 plays several important roles in the nervous system and its deficiency can lead to neurological symptoms and may contribute to the development of neurodegenerative diseases. Cobalamin is also famous for its role in hematopoiesis and it plays an essential role as a coenzyme in many biochemical processes that maintain or restore the health of the nervous system.
Thus, vitamin B12 is especially awarded a function in the DNA synthesis of myelin‐producing oligodendrocytes and the synthesis of myelin. The myelin sheath surrounds the axons of many nerves and serves as an electrical insulation, thereby facilitating fast conduction velocity because of this it was confirmed that Vitamin B12 promotes axon growth of neuronal cells after peripheral nerve injury, and therefore widely used for treatment of peripheral nerve damage in the clinical trials.
There are several functions mentioned below:
- Myelin Synthesis: Vitamin B12 is involved in the synthesis of myelin, which is a fatty substance that surrounds and insulates nerve fibers. It is crucial for neurotransmission, hence deficiency of vitamin B12 can result in demyelination and can stop proper nerve functioning.
- Homocysteine Metabolism: Vitamin B12 is a cofactor for the enzyme methionine synthase, which is involved in the conversion of homocysteine to methionine. Methionine is then used to produce S-adenosylmethionine (SAMe). SAMe is a methyl donor involved in various methylation reactions in the body, including the synthesis of some neurotransmitters, such as dopamine and serotonin. These neurotransmitters play a significant role in mood regulation. When there is low vitamin B12 in the body, there is less production of these neurotransmitters, which causes mood disorders or depression.
- Homocysteine Toxicity: Elevated levels of homocysteine, which can occur in vitamin B12 deficiency, are generally associated with neurotoxicity and it can increase the risk of neurodegenerative diseases. Homocysteine can induce oxidative stress, inflammation, and vascular dysfunction, all of which can contribute to neurological damage.
Natural Sources of Vitamin B12
- Meat
- Fish and Seafood
- Dairy Products
- Eggs
- Fortified foods
- Fermented foods
What is Vitamin B12 Deficiency?
Reduced serum vitamin B12 levels (< 200 ng per mL [148 pmol per L]) are considered vitamin B12 deficiency. Although B12 deficiency in the primary care setting is not typically treated for levels more than 200pg/mL, most psychiatrists and neurologists, first observe psychiatric symptoms such as panic attacks, inattention, and memory problems in levels < 400pg/mL and report levels > 600pg/mL to be ideal.
Vitamin B12 deficiency is widespread. Some population groups such as older people, vegetarians, pregnant women, and patients with renal or intestinal diseases are at more risk of having vitamin B12 deficiency.
Vitamin B12 deficiency can lead to megaloblastic anemia, various neuropsychiatric symptoms, and other clinical manifestations. It has been observed that the liver is used to store Vitamin B12 in excess to decrease the likelihood of deficiency. However, there are certain conditions in which vitamin B12 cannot be absorbed, for example, due to dietary insufficiency, malabsorption, or lack of intrinsic factor, hepatic stores are depleted, and deficiency ensues.
Screening for vitamin B12 deficiency is done for patients with one or more risk factors, such as gastric or small intestine resections, and inflammatory bowel disease. Initial laboratory assessment should include a complete blood count and serum vitamin B12 level. Asymptomatic patients with usually low levels of vitamin B12 are at high risk of vitamin B12 deficiency. To confirm the level of vitamin B12, serum methylmalonic acid is measured.
Why is Vitamin B12 Deficiency Common?
There are many reasons why vitamin B12 deficiency is common. The most prominent reason is the limited dietary sources of vitamin B12, which is primarily found in animal products such as meat, fish, dairy, and eggs. Therefore, it is especially common in vegans.
B12 deficiency can affect individuals of all ages, but most particularly elderly individuals, as older adults are more likely to have decreased stomach acid production, which is necessary for B12 absorption and they easily develop vitamin B12 deficiency.
Vitamin B12 deficiency is believed to be widespread all over the world. It has significant health implications, so it’s essential to understand its prevalence. Approximately 1.5% to 15% of people have vitamin B12 deficiency. Here are the percentages of people who have vitamin B12 deficiency based on their age ranges:
- At least 3% of people aged 20 to 39 years old have vitamin B12 deficiency
- At least 4% of people aged 40 to 59 years old have vitamin B12 deficiency
- At least 6% of people who are 60 years or over have vitamin B12 deficiency
Why is it Important to Screen for Vitamin B12 Deficiency?
It is important to screen for Vitamin B12 deficiency because early detection through screening can prevent the symptoms and their progression. In patients with suspected B12 deficiency, initial lab tests should include a complete blood count (CBC) with a peripheral smear and serum B12 and folate levels. In cases where the diagnosis is still unclear after initial testing, other lab tests, such as MMA and homocysteine levels, are available.
It is observed that in patients who are deficient in Vitamin B12, the CBC would show anemia, which manifests as a decrease in both hemoglobin and hematocrit. In addition, the mean corpuscular volume (MCV), which is responsible for measuring the size of red blood cells, would be increased to a level greater than 100. This is consistent with a diagnosis of macrocytic anemia. A peripheral blood smear would show hypersegmented neutrophils, with a portion of the neutrophils having greater than or equal to five lobes.
Who is at Risk of Vitamin B12 Deficiency?
It is observed that infants, children, adolescents, and women of reproductive age are also at high risk of deficiency; it is mostly found in the population restricted with dietary intake of B12-containing animal-derived foods. Three reasons can cause deficiency, inadequate intake, inadequate bioavailability, or malabsorption.
Some medical conditions like individuals with gastrointestinal disorders such as Crohn’s disease, and celiac disease, or those who have undergone gastric bypass surgery may also be at risk of developing vitamin B12 deficiency due to impaired absorption. Additionally, Pernicious anemia, an autoimmune condition affecting the stomach’s ability to produce intrinsic factor (a protein necessary for B12 absorption), can also lead to deficiency.
Why are Vegetarians at Risk of Developing Vitamin B12 Deficiency?
Vegetarians are indeed at risk of developing vitamin B12 deficiency since vegetarians have a lower intake of vitamin B12 than non-vegetarians. It has been experimented that plants do not contain vitamin B12, so individuals who follow a vegetarian diet, especially strict vegetarians who avoid all animal products, may not get enough B12 unless they consume fortified foods or supplements.
However, even lacto-ovo-vegetarians run the risk of becoming deficient in B12. Therefore, health professionals advise vegetarians to regularly take supplements of B12, and keep a check on their vitamin B12 level.
Why Vegans are at Risk of Vitamin B12 Deficiency?
From the above section, it is clear that the human body is unable to use the plant-based form of vitamin B12, which means that vegetarians and vegans are at high risk of developing a deficiency in this vitamin.
Without adequate intake of B12, vegans can easily develop deficiency over time, leading to symptoms such as fatigue, weakness, constipation, loss of appetite, weight loss, and nerve problems therefore the researchers recommend that vegans and vegetarians should add vitamin B12 to their diet by eating fermented foods, particular types of mushroom that contain the vitamin and B12-enriched vegetables.
Causes of Vitamin B12 Deficiency
- Inadequate dietary intake
- Malabsorption disorders
- Insufficient stomach acid
- Surgical procedures
- Autoimmune conditions
- Medications
- Age-related factors
Inadequate dietary intake
Vitamin B12 is found only in animal products such as eggs, meat, fish, and dairy products, but vegans and vegetarians do not consume animal products, therefore it is easy to develop vitamin B12 deficiency. Health professionals recommend consuming fortified foods or supplements to avoid deficiency.
Malabsorption disorders
In this disorder, it is difficult for the body to absorb useful nutrients including vitamin B12, through the gastrointestinal tract. Malabsorption happens in some conditions also, such as pernicious anemia, celiac disease, and Crohn’s disease. Where if a person consumes an adequate amount of vitamin B12 in their diet, their body may not be able to absorb it effectively, which can lead to deficiency.
Insufficient stomach acid
Stomach acid, aka hydrochloric acid, plays an important role in releasing vitamin B12 from the proteins in food, which is later on absorbed through the intestine. Therefore, insufficient stomach acid can contribute to vitamin B12 deficiency.
Surgical procedures
Sometimes few surgeries that involve the removal or alteration of the stomach or intestines can affect the body’s ability to absorb vitamin B12 as removal reduces the surface area available for absorption. For example, gastric bypass surgery, which is often used to treat obesity, bypasses part of the stomach and small intestine.
Autoimmune conditions
Autoimmune conditions are also responsible for causing vitamin B12 deficiency. The most common example of an autoimmune condition is “Pernicious Anemia”, where the immune system attacks cells present in the stomach, which are responsible for producing intrinsic factors.
Due to this Vitamin B12 does not get absorbed, as the intrinsic factor is responsible for vitamin B12 absorption. Some similar conditions are also there, which develop vitamin B12 deficiency in persons, such as Crohn’s disease or celiac disease.
Medications
Sometimes certain medications can also contribute to vitamin B12 deficiency. For example: Proton pump inhibitors (PPIs) and H2 receptor antagonists, which are mainly used to reduce stomach acid, can affect the release of vitamin B12 from food and its absorption in the stomach.
Another such example is “Metformin”, which is a medication for type 2 diabetes, which can also interfere with B12 absorption in the gut.
Age-related factors
Older people are at more risk because with age the production of stomach acid and intrinsic factor (a protein necessary for B12 absorption) can decrease. Which as a result impairs the absorption of vitamin B12 from food.
What does Alcohol Abuse Cause Vitamin B12 Deficiency?
Several studies have shown that blood vitamin levels used to be low in alcoholic patients. In addition to this, alcohol abuse is considered a chronic disease that promotes the pathogenesis of many fatal diseases, such as cancer and liver cirrhosis (due to decreased hepatic storage vitamin B12 deficiency can develop quickly in chronic liver illness).
Alcohol abuse can lead to vitamin B12 deficiency due to the following reasons:
- Alcohol consumption can reduce B-12 absorption as chronic alcohol consumption can lead to gastritis (inflammation of the stomach lining) and impair the production of intrinsic factor, which is a protein necessary for the absorption of vitamin B12.
- Additionally, alcohol can damage the cells lining the stomach and intestines leading to deficiencies of both vitamin B6 and B12, leading to anemia, neuropathy, and cognitive issues.
- Even moderate alcohol consumption can decrease vitamin B12 absorption by about 5-6%
Symptoms of Vitamin B12 Deficiency
Historical records suggest that Grigori Rasputin suffered from a vitamin B12 deficiency. Rasputin was the brilliant, quick-witted, handsome courtier, and rumored lover of queen Catherine the Great. He was reported to have developed premature dementia by the age of 35.
Later on, it was discovered that he was suffering from pernicious anemia, which is a severe form of B12 deficiency. Nevertheless, his case is sometimes cited as an example of vitamin B12 deficiency and how severe it can get with time, if left untreated, it can lead to serious health issues, including neurological symptoms like dementia.
Physical Symptoms of Vitamin B12 Deficiency
- Fatigue and weakness
- Pale skin
- Shortness of breath
- Nerve problems
- Mouth ulcers
- Digestive issues
- Vision problems
- Mobility difficulties
Cognitive Symptoms of Vitamin B12 Deficiency
- Peripheral Neuropathy
- Cognitive Disturbances
- Memory Problems
- Reversible Dementia
- Confusion
- Decreased Problem Solving
Psychiatric Symptoms of Vitamin B12 Deficiency
- Depression
- Anxiety
- Intrusive Thoughts
- Irritability
- Psychosis
- Inattention
- Insomnia
- Panic attacks
Treatment of Vitamin B12 Deficiency
It has been observed that oral administration of high-dose vitamin B12 (1 to 2 mg daily) is as effective as intramuscular administration for correcting anemia and neurologic symptoms. And for more rapid improvement intramuscular therapy is used, and it must be considered in patients with severe deficiency or severe neurologic symptoms.
Experiments show that absorption rates improve with supplementation; therefore, it is advised that patients older than 50 years and vegans or strict vegetarians should consume foods fortified with vitamin B12 or take vitamin B12 supplements to avoid vitamin B12 deficiency.
- Vitamin B12 Supplementation
- Dietary Changes
- Addressing Underlying Causes
- Monitoring
- Lifestyle Modifications
- Follow-up Care
Vitamin B12 Supplementation
Vitamin B12 supplementation is the most common treatment used to relieve the symptoms of deficiency. It mainly involves taking oral or injectable forms of vitamin B12 to restore normal levels in the body. The choice of supplementation method depends on the severity of the deficiency and the underlying cause.
Oral supplementation is usually sufficient for individuals with mild to moderate deficiency due to dietary insufficiency or malabsorption disorders. Oral supplements are available in various forms in the market, for example: tablets, capsules, and sublingual (under the tongue) formulations.
In addition to this, there are some medical conditions like pernicious anemia or gastrointestinal disorders, where malabsorption is the main problem. Therefore, in these cases, vitamin B12 may be administered via intramuscular injections. This bypasses the need for absorption in the digestive tract, and it ensures that an adequate amount of vitamin B12 reaches the bloodstream.
Dietary Changes
Dietary changes may play a role in the treatment of vitamin B12 deficiency, but only for individuals having mild deficiencies or are at risk of developing a deficiency. Increasing the intake of foods rich in vitamin B12 can help boost levels in the body.
From the above section, we know that animal products are the primary dietary sources of vitamin B12: meat, poultry, fish, eggs, and dairy products. So incorporating these foods into the diet can help in preventing vitamin B12 deficiency. Fortified foods and supplements can work as good sources of vitamin B12 for vegetarians and vegans.
Addressing Underlying Causes
Addressing underlying causes is critical in treating vitamin B12 deficiency to prevent recurrence and improve management. Conditions like pernicious anemia, gastrointestinal disorders, and certain surgeries can impair B12 absorption, requiring specific interventions. For pernicious anemia, lifelong B12 supplementation, often via injections, is standard.
Managing gastrointestinal disorders such as atrophic gastritis or celiac disease can improve B12 absorption. Adjusting medication regimens or dietary changes may be necessary for those on medications that affect B12 absorption.
Monitoring
Monitoring is a crucial aspect of treating vitamin B12 deficiency to ensure that treatment is effective and to prevent complications. Regular monitoring of vitamin B12 levels allows healthcare providers to adjust supplementation dosages as needed to maintain optimal levels in the body.
For individuals with conditions that affect B12 absorption, such as pernicious anemia or gastrointestinal disorders, monitoring helps to track the progression of the disease and the effectiveness of treatment.
Monitoring can also help identify any potential side effects of supplementation, such as allergic reactions or interactions with other medications. Additionally, monitoring symptoms related to vitamin B12 deficiency, such as fatigue, weakness, and neurological changes, can help assess the overall effectiveness of treatment and guide further management strategies.
Lifestyle Modifications
Lifestyle modifications can complement the treatment of vitamin B12 deficiency, especially when addressing factors that may contribute to or exacerbate the condition. For instance, quitting smoking and reducing alcohol consumption can benefit overall health and may improve the body’s ability to absorb and utilize vitamin B12.
A balanced diet rich in vitamin B12 and other nutrients, along with regular physical activity, can support overall health and help maintain adequate B12 levels. Additionally, managing stress and getting enough sleep can promote overall well-being, which may indirectly benefit vitamin B12 status. Overall, incorporating these lifestyle changes can enhance the effectiveness of other treatment approaches and contribute to long-term health.
Follow-up Care
Follow-up care is essential in the treatment of vitamin B12 deficiency to ensure that levels are being adequately maintained and to monitor for any potential complications. Regular follow-up appointments with healthcare providers allow for ongoing assessment of B12 levels and adjustment of supplementation dosages as needed.
Follow-up care also involves monitoring for symptoms related to B12 deficiency, such as fatigue, weakness, and neurological changes, to assess the effectiveness of treatment. For individuals with underlying conditions that contribute to B12 deficiency, such as pernicious anemia or gastrointestinal disorders, follow-up care may involve managing these conditions to optimize B12 absorption.
Overall, regular follow-up care is crucial for the long-term management of vitamin B12 deficiency and to promote overall health and well-being.
Supplements for Vitamin B12 Deficiency
Supplementing vitamin B12 is found to be challenging for individuals with gastric issues, post-gastric surgery, or any type of gut malabsorption syndrome because these conditions can interfere with the body’s ability to absorb the vitamin from the digestive tract. Due to this, different routes for the administration of supplements may be necessary, such as:
- Oral route of vitamin B12 administration: Oral replacement therapy is recommended to patients with asymptomatic, moderate illness who have no concerns about absorption or compliance. In this case, the supplement is directly taken by mouth and then it gets absorbed through the digestive tract. It is usually in the form of tablets & capsules.
- Intramuscular (IM) route of vitamin B12 administration: In the case of vitamin B12 malabsorption, irrespective of the cause of malabsorption, the intramuscular route is preferred. It is widely recommended for individuals with severe insufficiency and malabsorption syndromes. In this, the supplement is directly injected into the muscle, which allows it to be quickly absorbed into the bloodstream. That is why it is also known as B12 shots.
- Sublingual (SL) route of vitamin B12 administration: The sublingual (SL) route of vitamin B12 administration has been evaluated as an alternative route to oral and IM routes, especially in the case of vitamin B12 malabsorption. In this, the supplements are placed under the tongue and are absorbed through the mucous membranes, bypassing the digestive tract.
Injections for Vitamin B12 Deficiency
Vitamin B12 injections are typically recommended for individuals suffering from severe vitamin B12 deficiency. These individuals are unable to absorb B12 adequately through the digestive system. In these cases, injections are often preferred.
Some other medical conditions are there in which vitamin B12 absorption is compromised where injecting supplements directly is the only option, such as pernicious anemia or gastrointestinal disorders that affect B12 absorption.
The frequency of B12 injections can vary depending on the severity of the deficiency and the underlying cause. In general, initial treatment may involve injections several times a week for several weeks, followed by maintenance injections every 1-3 months. Mainly two types of vitamin B12 injections are usually given – hydroxocobalamin and cyanocobalamin.
Points to be considered while taking hydroxocobalamin:
- It provides instant relief but it will take some days or a few weeks to fully recover.
- In the beginning, multiple injections are given to maintain and increase the B12 levels.
- In severe cases, doctors may recommend hydroxocobalamin injections for the rest of the person’s life.
Points to be considered while taking cyanocobalamin:
- Cyanocobalamin injections are generally given every day during the first week of treatment to get better results.
- When the level of red blood cells returns to normal, then the injections are given on alternate days for the next two weeks.
- This is usually followed by injections every three or four days for the next two to three weeks.
- It is important to note that, cyanocobalamin injections are mostly given once a month once B12 deficiency anemia has been treated to prevent a recurrence of symptoms that could lead to nerve damage.
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