Authors: Payal Bhandari, M.D.

Contributors: Tia Ketsan, Hailey Chin, Vivi Chador 

Key Insights

Vitamin B12 is essential for DNA production, cell division, and making red blood cells. It also helps protect nerves. A B12 deficiency can cause fatigue, anemia, memory problems, nerve damage, and organ failure. A B12-rich diet or supplements can help, but some autoimmune diseases, like pernicious anemia and inflammatory bowel disease, can prevent B12 absorption. This can thicken the blood and prevent tissues from getting energy. Over time, this can lead to inflammation, high blood pressure, poor circulation, and diseases like atherosclerosis, autoimmune disorders, infections, and organ failure.

What is Vitamin B12? 

Vitamin B12 (also called cobalamin) is important for making red blood cells, nerve function, and creating DNA and RNA. The body can’t make B12, so it must be taken in through food or supplements.

To check for B12 deficiency, doctors measure serum or plasma B12 levels. They also look at methylmalonic acid (MMA), a substance related to B12, and homocysteine levels, which can indicate low B12. These tests are sensitive markers for deficiency.

Vitamin B12’s Role in the Body

Vitamin B12 is a crucial nutrient for many body functions.

1. Red Blood Cell Production: B12 helps make healthy red blood cells in the bone marrow. A lack of B12 can cause large, immature red blood cells that can’t carry enough oxygen, leading to fatigue and low energy.

2. Nervous System Health: B12 is needed to create myelin, the protective layer around nerves. Without enough B12, nerves can become damaged, causing symptoms like numbness, tingling, memory loss, and mood changes.

3. DNA and RNA Production: B12, along with folate (B9), helps make DNA and RNA, which are necessary for cell growth and division.

4. Energy Production: B12 helps turn carbohydrates into glucose, the body’s main energy source, especially when the body needs extra energy during stress or mental activity.

B12 Absorption and Regulation 

Vitamin B12 absorption is a multi-step process involving proteins and receptors in the digestive tract. Here’s how it works:

1. B12 Released from Food: When you eat, bacteria in your mouth help release B12 from food. The protein in food breaks down with the help of saliva, turning 40% into nitric oxide, which helps keep arteries healthy. The remaining 60% goes to the stomach, where stomach acid and enzymes break it down further to release B12.

2. B12 Travels to the Small Intestine: B12 binds to a protein called haptocorrin, which protects it from stomach acid as it moves to the small intestine.

3. B12 Absorbed in the Small Intestine: In the duodenum, B12 separates from haptocorrin and binds to another protein called intrinsic factor (IF). This complex then moves to the ileum, where receptors absorb it. Inside the ileum cells, B12 binds to another protein, transcobalamin II (TCII), and enters the bloodstream. It is carried to tissues where it supports DNA synthesis and energy production. B12 is stored mainly in the liver for future use.

Figure 1: Vitamin B12 absorption begins in the mouth, where chewing and saliva help release it from food. It then moves down the esophagus into the stomach, where cells release acid, the enzyme pepsin, and a protein called haptocorrin (HC) to protect B12. In the small intestine, intrinsic factor (IF) binds to B12, allowing it to be absorbed in the last part of the intestine. Once in the bloodstream, B12 attaches to transporter proteins, like holotranscobalamin (TC-Cbl), which carry it to cells where it supports functions such as DNA synthesis, cell growth, and energy production.

B12 Regulation in the Body

Vitamin B12 regulation relies on drinking enough water and proper absorption to produce saliva and stomach acid. Healthy gut bacteria also play a key role in breaking down proteins, making digestive enzymes, and helping transport B12 with proteins like intrinsic factor and transcobalamin II. Issues like dehydration, poor gut bacteria (dysbiosis), or damage to the mouth, stomach, or small intestine can affect B12 absorption and how it moves throughout the body.

Figure 2: A healthy gut microbiota helps with protein metabolism, B12 absorption, digestion, nutrient absorption, and waste removal. Dysbiosis, or a lack of healthy bacteria, disrupts metabolism and causes excess heat (ROS). Without proper energy balance, the body can’t function well.

Figure 3:  Vitamin B12 absorption relies on protein digestion. Healthy bacteria, stomach acid, and enzymes break down proteins to release B12. The pancreas also releases bicarbonate to protect the gut from acid. B12 binds to haptocorrin, which helps it reach the small intestine for absorption. Reduced protein digestion lowers the enzymes needed for B12 absorption.

Clinical Significance of Low Vitamin B12 Blood Levels

When there’s not enough B12 in the body, it affects important functions like DNA synthesis, red blood cell (RBC) production, nerve protection, and the breakdown of carbohydrates into energy. RBCs help deliver oxygen, remove waste, and generate energy. Without enough B12, harmful molecules called reactive oxygen species (ROS) are released, which can damage cells and prevent healthy growth and division. This leads to more damaged cells in the bloodstream, which triggers an immune response that can result in conditions like atherosclerosis.

The lack of B12 also causes problems with blood cell production, leading to conditions like pernicious anemia, and creates more abnormal or cancerous cells. As a result, blood flow is restricted, raising blood pressure and causing issues with organs like the gut. This can lead to “leaky gut,” a condition that worsens digestion and nutrient absorption, including B12. The body’s inability to process nutrients can lead to inflammation and further organ dysfunction.

Dormant infections may also become active, adding to the damage and supporting wound repair. These ongoing inflammatory processes can cause premature aging and contribute to diseases like atherosclerosis, autoimmune disorders, infections, cancers, and more.

Eating protein-rich foods like meat, eggs, and fish can increase certain harmful compounds in the body. When combined with low B12 intake or an unhealthy gut, this can damage protective antioxidants and lead to gene mutations that affect important enzymes. This, in turn, can result in a buildup of harmful amino acids and a decrease in key body functions.

Figure 4: Eating too much protein from animal products and nuts, along with a lack of B6, B9, or B12 vitamins, can interfere with the recycling of certain amino acids, like methylmalonic acid (MMA), and cause the release of harmful hydrogen sulfide (H2S). Not getting enough B12 from foods like leafy greens or having an unhealthy gut can also reduce B12 absorption. This buildup of unused amino acids can harm cell and gut health, cause inflammation, and contribute to early aging and chronic diseases.

B12 deficiency can cause a variety of symptoms, such as fatigue, muscle weakness, nerve damage, and cognitive issues. Early detection and B12 supplementation are crucial to prevent more serious health problems.

Figure 5: Low B12 levels in the blood can affect cell and DNA production, mess with energy and hormone balance, and cause proteins to thicken the blood. This leads to early cell damage, less energy, and can harm the body’s ability to function properly. The figure shows that not having enough B12 can lead to nerve problems and other health issues that contribute to disease and aging.

Clinical Significance of High Vitamin B12 Blood Levels

Vitamin B12 toxicity is rarely a concern, as excess B12 is usually removed through urine. In rare cases, side effects like headaches, nausea, or skin rashes can occur due to additives in supplements or injections. However, high B12 levels are more often linked to liver or kidney problems, not B12 toxicity.

• Liver disease: The liver stores B12, and stress on the liver can release large amounts of B12 into the blood. This increases red blood cell production and helps repair tissue damage by bringing white blood cells and platelets to injury sites. Inflammation in the liver also affects how the body uses energy and reduces the breakdown of fats and proteins.

• Kidney disease: High B12 levels can result from damage to cells, which releases substances like hemoglobin and B vitamins into the blood. Increased levels of reactive oxygen species (ROS) can harm the kidneys, reducing their ability to remove waste and raising B12 levels in the blood.

Prevalence & Significance of B12 Deficiency

B12 deficiencies are common, especially among menstruating women, older adults, and those with chronic health issues like gastrointestinal disorders and autoimmune diseases. These groups are more at risk because their bodies need more B12. Studies show that 43% of older adults have a B12 deficiency, which can lead to problems with energy, memory, nerves, and the immune system. Conditions like inflammatory bowel diseases, pernicious anemia, and chronic gastritis damage the digestive system, making 15-25% of people more likely to develop a B12 deficiency. A lack of B12 can also cause memory problems similar to dementia.

Conclusion

Vitamin B12 is important for making DNA, producing red blood cells, and keeping nerves healthy. A B12 deficiency can lead to problems like low red blood cell production (anemia), poor oxygen delivery to tissues (hypoxia), and difficulty removing waste from cells. Hypoxia lowers the body’s ability to produce energy and allows harmful molecules to damage cells. Eating enough B12 through plant-based foods and supplements is crucial for maintaining good health, especially for pregnant or breastfeeding women, older adults, and people with chronic conditions like autoimmune diseases, heart disease, cancer, infections, or organ problems.

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