VEGANALYZE

Vitamin B12 Deficiency - Causes, Symptoms, Treatment

In our body, Vitamin B12 serves extremely important functions. It is involved in the formation of red blood cells, maintenance of cognitive functions, cell growth, and division. If the demand for Vitamin B12 is not met for an extended period (up to three years) and the body's reserves of 2 to 3 mg are depleted, initial symptoms may occur. If a vitamin B12 deficiency is not addressed, it can lead to severe health damage and, in extreme cases, even irreversible neurological damage 1. Therefore, early detection and treatment of a deficiency are crucial.

At-Risk Groups

Vegans can be affected by a vitamin B12 deficiency just like vegetarians and omnivores 2. Furthermore, a lack of vitamin B12 is a global issue 3. As a result, 20% of the adult population in developed countries suffer from a deficiency 4.

Nevertheless, numerous studies indicate that especially vegans and vegan children have a low vitamin B12 status. 5 6 7 8 9 10 11 12 13 14 15. Particularly, vegans who do not take supplements are affected by a deficiency 16.

Other risk groups include 17:

• Pregnant women
• Nursing mothers
• Infants
• Elderly individuals (absorption decreases with age)
• Patients with gastrointestinal conditions (such as Crohn's disease and short bowel syndrome)
• People with stomach and intestinal disorders
• People taking medications (H2 receptor blockers, metformin, proton pump inhibitors)
• Alcoholics

Causes of Vitamin B12 Deficiency

A deficiency primarily occurs when the absorption of vitamin B12 in the small intestine is disrupted due to a disturbance in the intestinal mucosa or the gastrointestinal tract (such as Crohn's disease, gastritis, or celiac disease) 18 19. The absorption of B12 requires a transport protein called intrinsic factor (IF). If the production or release of intrinsic factor is disrupted (pernicious anemia), the body can no longer absorb the vitamin through this route 20. The ability to absorb through IF decreases with age.

In vegans, a deficiency can occur if no foods containing vitamin B12 or vitamin B12 supplements have been consumed for an extended period of time vitamin B12 foods. This is because vitamin B12 is produced by bacteria and is not present in plant-based foods. However, some bioavailable B12 may be found in mushrooms and algae.

Chronic alcohol consumption can impair B12 absorption. Furthermore, the liver is the most important storage organ for vitamin B12. Liver damage can also have a negative impact on vitamin B12 levels.

Vitamin B12 Deficiency Symptoms

The following symptoms can manifest among others 21 22 23 24 25 26:

• Fatigue
• Loss of appetite
• Weakness / lack of energy
• Sluggishness
• Dizziness
• Pallor
• Yellowing of the eyes
• Regression of the oral and tongue mucosa (glossitis)
• Aphthous ulcers
• Mouth corner cracks (angular cheilitis) due to cell growth disorders
• Hyperpigmentation
• Vitiligo
• Atopic dermatitis
• Nail changes
• Decreased performance
• In rare cases, sensory impairments of the hands and feet

When the central nervous system is affected, reduced motor and sensory abilities can occur. A deficiency of vitamin B12 (5'-deoxyadenosylcobalamin) can also lead to demyelination of peripheral nerves, the spinal cord, and the nerves in the brain, resulting in nerve damage and neuropsychiatric abnormalities 27. Motor impairments manifest as muscle weakness (including poor coordination), sensory impairments as numbness/paralysis, tongue burning, loss of smell and taste, as well as tingling in the hands and feet.

In the case of a prolonged vitamin B12 deficiency, damage to the nervous system may occur. 28 29 30 31 32 33:

• Memory disorders
• Apathy
• Hallucinations
• Disorientation
• Migraine
• Depression
• Dementia
• Alzheimer's
• Psychosis

After several years without vitamin B12 intake, irreversible brain damage can occur.

The symptoms may have been caused by a deficiency of red blood cells (Vitamin B12 deficiency anemia / megaloblastic anemia, also known as macrocytic anemia) 34. One significant characteristic of this type of anemia is the presence of very large red blood cells. Additionally, the interior of the blood cells is not fully developed, leading to reduced cell production in the bone marrow 35. This can result in degeneration of the spinal cord and pancytopenia (reduced blood cell formation) 36. Furthermore, less oxygen is transported through the blood.

A deficiency of vitamin B12 and folate (folic acid) can negatively affect muscle functions, especially in older individuals 37 38. This is related to the effects of both vitamins on homocysteine. If the body does not have enough vitamin B12 available, homocysteine cannot be adequately converted into the amino acid methionine, leading to elevated homocysteine levels. Higher levels are associated with cardiovascular diseases. Scientists found in studies from 2015 that the risk of cardiovascular diseases can be reduced by supplementing vitamin B12 39. Further studies from 2015 associate a vitamin B12 deficiency, along with a deficiency in folic acid and higher homocysteine levels, directly with Alzheimer's disease 40 41.

Note: All mentioned symptoms can also have other causes and do not necessarily have to be attributed to a vitamin B12 deficiency.

Vitamin B12 deficiency during pregnancy, in infants, and in childhood

In infants, a vitamin B12 deficiency can have negative effects on growth and neurological development (permanent brain damage), which can lead to increased risk of depression, lethargy, as well as stagnation or regression of developmental abilities later in life 42 43 44 45 46. Consequences in childhood can include cerebral atrophy (loss of brain tissue) and psychomotor developmental impairments 47.

Symptoms can occur in infants within a few months due to limited vitamin B12 liver reserves 48. Visible symptoms of vitamin B12 deficiency in infants may include involuntary motor movements, dystrophy, weakness, muscle atrophy, loss of tendon reflexes, psychomotor regression, hypotonia (low blood pressure), lethargy, hematological abnormalities, as well as growth disorders and delays 49 50 51 52.

The child's vitamin B12 requirement should be met without fail. Vitamin B12 is transferred through breast milk, so it is crucial for the mother to have an adequate supply of B12, even during pregnancy. It is especially important to promptly identify and treat any deficiencies to prevent long-term neurological problems 53. Therefore, scientists advise vegan and vegetarian women to consume vitamin B12 during pregnancy and breastfeeding 54 55 56.

Diagnosis

Vegans should regularly check their vitamin B12 status. Doctors can determine a vitamin B12 deficiency through blood tests. In most cases, serum levels are examined.

A vitamin B12 deficiency is present when the serum level is less than 200 pg/mL (< 150 pmol/L) 57. If investigations suggest a deficiency but the levels are in the low to normal range (200 to 350 pg/mL), other tests can be performed to confirm a deficiency 58. Test results of homocysteine, holotranscobalamin II (HoloTC), or methylmalonic acid (MMA) provide further insights into an existing deficiency. Particularly, HoloTC (earliest laboratory parameter for vitamin B12 deficiency; levels decrease when sufficient available B12 is not present) and MMA (functional B12 marker; levels increase when B12 stores are depleted) tests have higher sensitivity and specificity compared to vitamin B12 serum determination, and are therefore considered as modern biomarkers 59. Nevertheless, HoloTC still has a wide gray zone of uncertainty, and therefore, MMA should be used as a confirmatory test 60.

It is also possible to perform a urine test at home. The urine sample is sent in, and the methylmalonic acid levels are determined. Elevated methylmalonic acid levels are indicative of a B12 deficiency. Nonetheless, especially in the case of neurological symptoms, it is necessary to promptly consult a doctor to potentially initiate therapy and possibly prevent irreversible damage.

The following values indicate a B12 deficiency: 61 62 63:

Vitamin B12 levels greater than 350 pg/mL appear to no longer cause symptoms. 64.

Folic acid can mask a vitamin B12 deficiency in high doses and have serious effects on health 65.

Furthermore, a cobalamin deficiency can hide (mask) an iron deficiency 66. Therefore, the scientists recommend conducting an iron deficiency examination for all patients diagnosed with a B12 deficiency.

Treatment

When treating a vitamin B12 deficiency, it is important to know the underlying cause of the deficiency. Only then can an appropriate therapy be implemented. Otherwise, the initial symptoms may reoccur in the medium to long term.

If there is insufficient supply of vitamin B12 to the body, the following treatment methods can be helpful. Scientists believe that oral intake (tablet or capsule through the digestive tract) is equally effective in correcting a B12 deficiency and reducing homocysteine levels as sublingual intake (sublingual tablet placed under the tongue and absorbed through the oral mucosa) at a dose of 500 µg of vitamin B12. 67 68 69. Daily oral dosages of 1-2 mg of vitamin B12 also appear to be suitable for patients in whom intestinal absorption is impaired due to cobalamin malabsorption or pernicious anemia 70. The preferred formulation for correcting a deficiency should be a combination of the active forms of vitamin B12, adenosylcobalamin (AdCbl) and methylcobalamin (MeCbl), or hydroxo- and cyanocobalamin 71. The scientists further state that approximately 500 to 750 mcg of MeCbl and AdCbl are required daily through oral administration.

Especially in urgent cases such as Vitamin B12 deficiency anemia, B12 is also administered by injection (500 to 1,000 μg once or twice weekly for 6 to 8 weeks, then once per month for life) or alternatively, Vitamin B12 (500 to 1,000 μg daily) is administered orally. 72 73 74. The absorption rates are significantly higher here (150 µg out of 1,000 µg). Nonetheless, oral Vitamin B12 is equally effective as intramuscular administration in achieving hematological and neurological responses. 75 76.

Vitamin B12 is generally poorly absorbed in its unbound form (in dietary supplements) (see Absorption). Of the 500 µg, only about 2% is absorbed, which corresponds to 10 µg. 77. Only about 13 µg (through passive diffusion) is absorbed from 1,000 µg. This way, a mild B12 deficiency can be quickly corrected.

Preventive Measures

The Vitamin B12 requirements need to be met at regular intervals. Vitamin B12 does not need to be consumed every day as it is stored in the body. It is recommended to consume it within a span of 3 days. Studies have shown that dietary supplements and B12-fortified foods increase the Vitamin B12 levels 78. Foods containing Vitamin B12 can be found here. If the requirement cannot be adequately met through a varied vegan diet, it is essential to supplement Vitamin B12 through dietary supplements. A 2015 study from Switzerland shows that with sufficient Vitamin B12 supplementation, the susceptibility to Vitamin B12 deficiency can be significantly reduced 79.

From the age of 50 onwards, an additional intake of Vitamin B12 is recommended as the body may no longer be able to absorb B12 80. In addition, a Vitamin B12 supplementation is associated with potential prevention of arteriosclerosis-related diseases in individuals with low B12 status 81.