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12 Benefits and Side Effects of Vitamin B12

Vitamin B12, also known as cobalamin or vitamin B12, is the most special member of the B group vitamins (containing the metal ion cobalt), and the structure is large and complex.

If this nutrient is deficient, in addition to causing pernicious anemia, it can also cause symptoms such as homocysteinemia (related to cardiovascular disease), peripheral neuropathy, cognitive impairment, loss of appetite, and burnout.

What are the benefits of vitamin B12 in empirical medicine? What are the side effects of vitamin B12? See text analysis for details.

What is Vitamin B12?

Vitamin B12 is an important water-soluble vitamin with various roles such as hematopoiesis, maintenance of nervous system function, energy production, DNA synthesis, maintenance of intact gastrointestinal mucosa and participation in the metabolism of proteins, fats and carbohydrates.

Since humans cannot synthesize it, it needs to be obtained through diet, as it is found almost exclusively in animal foods.

A typical Western diet consumes 3-30 mcg of vitamin B12 per day, of which about 1-5 mcg is absorbed, while the recommended dietary allowance is 1 to 3 mcg per day.

In addition, the relatively high body stores of vitamin B12 (about 2000-5000 mcg) explain why the clinical manifestations of B12 deficiency often appear later.

Is vitamin B12 deficiency common?

Vitamin B12 is mainly found in animal foods such as fish, meat, shrimp, shellfish, milk and eggs, while plants are less common, only seaweed (less biologically active).

Vitamin B12 absorption is mainly related to gastrointestinal function and dietary factors, so groups that are more likely to be deficient in vitamin B12 are: vegetarians (do not eat eggs and milk), the elderly (poor digestive function), gastrointestinal diseases (such as Crohn’s disease, enterogastric resection, celiac disease, Helicobacter pylori infection), eating disorders, AIDS, tropical aphthous, diabetes and congenital dysfunction.

Even if vitamin B12 levels are common, there may still be a deficiency.

One case report mentioned that up to 50% of patients with symptomatic vitamin B12 deficiency may have “normal” vitamin B12 levels (more than 200 pg/mL).

Therefore, clinicians should measure methylmalonic acid and homocysteine levels if B12 levels are normal but vitamin B12 deficiency is still suspected, especially if the level is on the margins of normal, to confirm the direction of treatment. Note 1

What are the benefits of vitamin B12?

1.  Vitamin B12 is beneficial for diabetic neuropathy

Diabetic neuropathy is one of the most common microvascular complications of diabetes.

Its most common forms are Diabetic Peripheral Neuropathy (DPN), Diabetic autonomic neuropathy (DAN), and the most commonly diagnosed form is cardiovascular autonomic neuropathy neuropathy (CAN)) and painful diabetic neuropathy (PDN).

Peripheral/remote symmetric polyneuropathy can occur in up to 50% of patients, causes sensory symptoms, and is associated with foot infection, ulceration, Charcot’s foot, fractures, and amputation. One third of patients develop PDN, which is accompanied by neuropathic pain and burning, pinpricks, shock-like pain, numbness in the feet, and contact pain, which has a significant impact on quality of life.

A meta-analysis (6 randomized controlled trials of 669 people with diabetic neuropathy) suggested that vitamin B12 alone or in combination with other drugs reduced neuropathic symptoms and improved pain compared with placebo. Note 1

The mechanism behind it may be related to vitamin B12 increasing the availability and potency of norepinephrine (noradrenaline) and 5-hydroxytryptamine.

*Conclusion: Vitamin B12 may provide positive help for diabetic neuropathy, but limited by small sample sizes, more research is needed to confirm these data.

2. Vitamin B12 is beneficial for autism spectrum disorder

First defined in 1943 by child psychiatrist Kanne, Autism spectrum disorders are a distinct syndrome, a heterogeneous group of neurological disorders clinically manifested by deficits in social, communication, and stereotyped behavior, with a global prevalence of about 1 percent, with a 4:1 male-to-female ratio.

Non-diagnostic features of children with autism spectrum disorder include gastrointestinal problems, sleep disturbances, immune system abnormalities, neurotrophic factor disorders, mitochondrial dysfunction, and oxidative stress. Oxidative stress can cause damage to lipids, proteins, and DNA in cells, leading to the development of human disease.

A systematic literature review and meta-analysis (including 17 studies of autism spectrum disorder) suggests that vitamin B12, particularly subcutaneous injection of mB12 (methylcobalamin), improves associated clinical symptoms and metabolic abnormalities. Note 1

*Conclusion: Vitamin B12 may be a positive help for autism spectrum disorder, but more large placebo-controlled studies are needed to confirm these data due to the measurement bias of the included studies.

3. Vitamin B12 can treat vitamin B selective absorption disorder syndrome

Vitamin B12 selective absorption disorder syndrome (Imerslund-Grasbeck syndrome/IGS) is a rare autosomal recessive disorder discovered by Imerslund and Gräsbaeck in 1960 with an estimated prevalence of less than 6:1,000,000.

It occurs in children aged 1 to 5 years and presents with megaloblastic anemia, asymptomatic intermittent proteinuria, vitamin B12 deficiency, dysplasia, recurrent gastrointestinal/respiratory infections, and mild neurological symptoms.

Diagnosing IGS is often a time-consuming and uncertain process, based on ruling out other causes of vitamin B12 insufficiency such as malnutrition, parasites, small intestinal bacterial overgrowth, exocrine pancreatic insufficiency, ileitis, birth defects, and medications.

IGS is treated in the same way as pernicious anemia, with lifelong or intravenous vitamin B12. Note 1

4. Vitamin B12 can treat cyanide poisoning (caused by fire smoke inhalation)

Inhalation injury accounts for about 30% of fire-related injuries. Among them, cyanide poisoning is the leading cause of death from inhalation injuries related to fire smoke.

Once internalized, cyanide binds to cytochrome oxidase A3, a process that prevents aerobic metabolism, leading to diffuse clinical symptoms such as dizziness, headache, fatigue, and shortness of breath, and progression to seizures, paralysis, and coma.

Hydroxocobalamin, a precursor to vitamin B12, was approved by the U.S. Food and Drug Administration in 2006 for the treatment of cyanide poisoning

A retrospective study (in patients suspected of cyanide toxicity due to smoke inhalation) noted that routine administration of hydroxycobalamin was associated with lower rates of pneumonia, faster release from the ventilator, and reduced length of stay in intensive care units. Note 1

5. Vitamin B12 is beneficial for gestational diabetes

Gestational diabetes mellitus (GDM) is a common complication of pregnancy that refers to spontaneous hyperglycemia that occurs during pregnancy, with an estimated 14% of pregnant women worldwide suffering from gestational diabetes, or about 18 million newborns per year

Associated risk factors include overweight, obesity, Westernized diets and micronutrient deficiencies, advanced maternal age, and a family history of insulin resistance, or diabetes.

While gestational diabetes usually goes into remission after childbirth, it can have long-term health effects, including an increased risk of obesity, cardiovascular disease, type 2 diabetes or GDM for the mother and offspring.

A systematic literature review and meta-analysis (6 observational studies, 1810 pregnant women, 309 cases of gestational diabetes) noted that pregnant women with vitamin B12 deficiency (defined as concentrations < 200 pg/mL) had a higher risk of gestational diabetes compared with pregnant women with vitamin B12 adequacy. Note 1

*Conclusion: Vitamin B12 deficiency during pregnancy appears to be associated with an increased risk of gestational diabetes, but more studies are needed to validate this due to small sample sizes.

6. Vitamin B12 is beneficial for cardiovascular and cerebrovascular diseases

Cardiovascular and cerebrovascular diseases are among the highest in the world, with a lifetime risk of more than 60 percent, and it is estimated that more than 2,200 Americans die every day (one every 40 seconds).

Decades of research have identified risk factors for cardiovascular and cerebrovascular diseases, the most common of which are hypertension, smoking, obesity (due to poor diet and/or lack of physical activity), hyperlipidemia, and genetic susceptibility.

A meta-analysis (11 RCTs involving 26,395 patients) noted that B vitamin supplementation had no effect on the incidence of cardiovascular events, including myocardial infarction. Note 1

However, subgroup analysis of stroke showed that B vitamin supplementation reduced stroke risk with longer follow-up, and was more significant in subjects with low doses of folic acid, increased B12/B6 doses, and cardiovascular and cerebrovascular history.

*Conclusion: Combined folic acid, vitamin B6, and B12 supplementation may not have a significant effect on cardiovascular and cerebrovascular disease events and the incidence of myocardial infarction, but may reduce stroke risk and homocysteine levels.

7. Vitamin B12 improves herpes neuralgia

Postherpetic neuralgia is a chronic neuropathic pain syndrome that originates from the damage to surrounding and central neurons in the inflammatory response activated by the varicella zoster virus, and is one of the important complications after herpes zoster infection.

It is estimated that 5% to 20% of people with shingles develop postherpetic neuralgia, which increases in frequency and severity with age.

In addition to age, associated risk factors include prodromal symptoms (defined as pain and abnormal sensations before rash onset), severe rash (defined as > 50 papules, vesicles, or crusted vesicles), and severe pain in the acute phase.

A meta-analysis (4 randomized controlled trials with 383 patients with shingles) noted that vitamin B12 (subcutaneously) helped improve postherpetic neuralgia intensity scores (NRS) and quality of life compared with placebo, and reduce painkiller use. Note 2

The mechanism behind it may be related to vitamin B12 improving nerve conduction velocity, promoting nerve regeneration, and inhibiting the spontaneous emission of ectopic neurons.

*Conclusion: Vitamin B12 may help improve herpes-related neuralgia, but more research is needed to support this due to small sample sizes

8. Vitamin B12 reduces the risk of colorectal cancer

Colorectal cancer is the third most common cancer in the world, with nearly 1.4 million cases diagnosed worldwide each year, with an average lifetime risk of about 5%, and if current trends continue, 2.2 million colorectal cancer cases are expected to be diagnosed annually worldwide by 2030.

Colorectal cancer risk can be highly modified through diet and lifestyle, with reports showing that up to 47% of colorectal cancer cases can be prevented by staying physically active, maintaining a healthy weight and eating a healthy diet.

A meta-analysis (17 studies, 10,601 participants) showed that when vitamin B12 intake exceeded a certain threshold (every 4.5 mcg/day increase), vitamin B12 intake was inversely associated with the risk of colorectal cancer. Note 3

In addition, the association between blood vitamin B12 levels and colorectal cancer risk was not significant.

*Conclusion: Higher vitamin B12 intake is associated with a lower risk of colon cancer, but more research is needed to confirm whether supplementation is clinically beneficial.

9. Vitamin B12 is beneficial for osteoporosis

Osteoporosis is a chronic, multifactorial disease characterized by low bone mass and degeneration of bone microstructure, making people more prone to fractures.

The most common osteoporotic fracture sites include the hip, spine, and wrist, and in particular spinal and hip fractures have a poor prognosis and usually require hospitalization and surgery.

Many risk factors are associated with osteoporotic fractures, including low peak bone mass, hormonal factors, drug use (e.g., glucocorticoids), smoking, low physical activity, low calcium and vitamin D intake, race, small size, and personal or family history of fractures.

A systematic review of 17 studies noted that the relationship between vitamin B12 levels, low bone density, and fracture risk has not been fully established due to inconsistent findings, especially for vulnerable groups such as postmenopausal women. Note 4

*Conclusion: As of now, the relationship between vitamin B12 deficiency and bone health remains to be confirmed

10. Vitamin B12 reduces the occurrence of neural tube defects

Neural tube defects are common severe congenital malformations (characterized by failure of the neural tube closure process at the embryonic stage resulting in exposure of the brain or spinal cord nerve tissue to the extraembryonic environment), alongside congenital heart malformations and genitourinary defects

Neural tube defects occur in about 0.5 to 2 out of every 1000 pregnancies worldwide (300,000 newborns are affected globally each year), mainly due to genetic, lifestyle and environmental factors

A meta-analysis (9 studies, 567 cases and 1566 controls) found that maternal vitamin B12 deficiency during pregnancy did increase the incidence of neural tube defects in the fetus (odds ratio up to 2.41). Note 5

*Conclusion: Low vitamin B12 levels in the mother during pregnancy may be an important risk factor for the development of fetal neural tube defects.

11. Vitamin B12 is beneficial for melancholy

Depressive disorder is a widespread and devastating disease that affects about 17% of people’s lives worldwide, causing enormous personal suffering and economic loss.

Depression is not only highly comorbid with anxiety disorders, but also strongly associated with dementia, type 2 diabetes, coronary artery disease, Parkinson’s disease, epilepsy, pain, cancer, aging, osteoporosis, and irritable bowel syndrome.

A systematic literature review and meta-analysis (11 randomized placebo-controlled trials) found that short-term folic acid and vitamin B12 supplementation (days to weeks) did not help improve depressive symptoms in people receiving antidepressants for depression. Note 6

However, longer use (weeks to years) may reduce the risk of recurrence and the occurrence of clinical symptoms in people at risk.

*Conclusion: Treatment with folic acid and vitamin B12 does not reduce the severity of depressive symptoms in a short period of time, but may be beneficial for the long-term management of people at high risk of depression.

12. Vitamin B12 reduces the incidence of preterm birth

Preterm birth and low birth weight are important factors in neonatal mortality and morbidity, causing nearly one million infants and young children to die every year, and may cause neurodevelopmental disorders, gastrointestinal complications, cerebral palsy, sensory impairments, learning disabilities, respiratory diseases, etc

A meta-analysis (18 studies, 11,216 participants) showed that lower maternal blood levels of vitamin B12 increased the risk of preterm birth in the fetus, especially for those with deficiency (21% increase in the chance of preterm birth). Note 11

In addition, during pregnancy, maternal vitamin B12 levels were associated with low birth weight, but deficiency also increased the incidence of low birth weight by 15%.

*Summary: Vitamin B12 deficiency during pregnancy is positively associated with preterm birth and low birth weight

When to eat vitamin B12 (best time)?

Vitamin B12 is a water-soluble vitamin, generally speaking, it is best absorbed on an empty stomach, and the best time to take it is before eating in the morning, or 30 minutes before a meal and 2 hours after a meal.

Are there any side effects of vitamin B12?

For generally healthy individuals and at appropriate dosages, vitamin B12 is considered non-toxic and has no side effects.

While the “Upper Tolerable Intake Level” for vitamin B12 has not been established, there are risks associated with consuming too much B12 in large doses.

Possible side effects or adverse effects when vitamin B12 is used in high doses include: dizziness, headache, anxiety, nausea, vomiting, itching, acne and rosacea.

In addition, there have been cases of severe allergic reactions caused by vitamin B12, although extremely rare, it is still important to be aware that symptoms include swelling of the face, tongue and throat, difficulty swallowing and breathing, if these conditions occur after taking it, seek medical attention immediately.

Safety precautions

1. A placebo-controlled study in older adults showed that daily folic acid (400 mcg) and vitamin B12 (500 mcg) supplementation for 2 to 3 years may increase the risk of colon cancer. Note 7

2. In patients with diabetic nephropathy, the use of high doses of B vitamins (containing 1000 mcg of vitamin B12) may lead to decreased kidney function and increased cardiovascular events. Note 8

3. Sublingual and dissolvable B12 supplements often contain sugar substitutes, which may cause bloating and diarrhea

4. An observational study pointed out that for pregnant women, if the blood concentration of vitamin B12 is greater than 600 pmol/L, the incidence of autism will increase several times (the recommended daily intake of vitamin B12 for pregnant women is 2.6 mcg). Note 9

5. Taking folic acid, vitamin B6 and vitamin B12 after coronary artery stenting may increase the risk of stenosis in the stent. Note 10

6. Megaloblastic anemia is sometimes treated with vitamin B12, but it is best to use it under the close supervision of a medical professional due to possible side effects

7. Do not take with antibiotics: Chloramphenicol may affect the ability of vitamin B12 to participate in the production of new red blood cells

8. The following drugs may inhibit vitamin B12 absorption, such as anti-epileptic drugs (Dilantin, Mysoline), chemotherapy drugs (methotrexate), gout drugs (Colchicine), cholic acid binders, used to lower cholesterol (Questran, Colestid), inhibitor gastric acid inhibitors (Proton pump inhibitors), diabetes drugs (Metformin), Aminosalicylic acid, Colchicine, metformin

9. Long-term use of high doses of folic acid (greater than 800 mcg) may mask vitamin B12 deficiency and seriously lead to nervous system damage, so long-term use of folic acid alone should be paid attention to, or use comprehensive compound to prevent

What are the forms of vitamin B12? Which absorption rate is good?

Vitamin B12 supplements are most commonly available in the form of cyanocobalamin or methylcobalamin

Cyanocobalamin, a synthetic form of vitamin B12 that does not exist in nature, is used more frequently in supplements, and is more stable and cost-effective.

When cyanocobalamin enters the body, it is converted to methylcobalamin or adenosylcobalamin, the active form of vitamin B12 in the body

Unlike cyanocobalamin, methylcobalamin is a naturally occurring form of vitamin B12 (also known as active methyl B12) that can be obtained through supplements as well as foods such as fish, meat, eggs, and milk, but supplementation with methylcobalamin does not increase adenosylcobalamin levels.

Another major difference between methylcobalamin and cyanocobalamin, is the way they are absorbed and retained in the body, with some studies suggesting that methylcobalamin has higher absorption and retention rates.

However, some studies suggest that the difference in bioavailability between the two forms can be negligible, with absorption rates more influenced by factors such as age and genetics.

Therefore, for vitamin B12 deficiency, the use of cyanocobalamin, or a combination of methylcobalamin and adenocobalamin, can help.

If you think you may be deficient in vitamin B12, it’s best to consult a specialist to determine the most beneficial treatment options.