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Methylcobalamin for Depression

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Vitamin B12 is the 3 most important B vitamins (the others are vitamins B6 and B9). It is essential to many biological processes in the body including brain functioning. Available studies indicate that vitamin B12 can both protect the brain from damage and also stimulate its normal functions. Does this essential vitamin has a role in the treatment of depression? If so, how can it help and how is it used? Read on to discover the link between vitamin B12 and depression.

What is Vitamin B12?

Vitamin B12, also known as cobalamin, is one of the B vitamins. It plays a major role in the metabolism of all cells in the body.

Besides supporting cellular metabolism, vitamin B12 also promotes the normal functioning of the brain and nervous system by contributing to the development of nerve cells. One of the other prominent functions of vitamin B12 is to support the production of red blood cells.

Furthermore, a series of biochemical pathways for DNA synthesis is dependent on vitamin B12. In most enzymatic biochemical reactions, the vitamin acts as a cofactor.

Vitamin B12 cannot be synthesized naturally in the human body. In fact, the enzymes needed for the production of this vitamin can only be found in bacteria and algae. Therefore, plant and animal sources rich in vitamin B12 obtain this vitamin through some symbiotic relationships with vitamin B12-producing bacteria.

The principle involved in the bacterial production of vitamin B12 is also applied in the industrial production of the vitamin. Vitamin B12 supplements are generally manufactured by a process known as bacterial fermentation.

Vitamin B12 actually describes a family of structurally similar chemical compounds. These chemically related compounds are referred to as vitamers. The vitamers of vitamin B12 include cyanocobalamin, hydroxocobalamin, methylcobalamin, adenosylcobalamin. 

All the vitamin B12 vitamers contain cobalt, an element rarely found in organisms.

For vitamin B12 to be widely transported around the body, a glycoprotein produced in the stomach is needed. This glycoprotein (also known as an intrinsic factor or gastro-intrinsic factor) is produced in the stomach but it acts in the small intestine where it binds to vitamin B12. As a result, low production of this glycoprotein can lead to a deficiency in vitamin B12.

Recommended Intake, Interactions and Deficiency

The results of the majority of studies involving vitamin B12 show that the vitamin has a very low toxicity potential. Therefore, high doses have been found not to pose any health risk in healthy individuals. This is because vitamin B12 is a water-soluble vitamin and an excess amount of the vitamin is simply excreted with urine.

Consequently, the National Academy of Sciences did not establish any tolerable upper limit for vitamin B12.

However, in rare cases, allergic reactions may be observed, especially when vitamin B12 injection is administered. In addition, due to the cobalt component of vitamin B12, individuals who are allergic to this element should avoid vitamin B12 supplements.

The recommended intake of vitamin B12 depends on age. The recommended daily allowances (RDA) of vitamin B12 as provided by the National Academy of Sciences are listed in the table below.

Recommended Daily Intake of Vitamin B12
  • For infants between 0 and 6 months, 0.4 mcg;
  • For infants between 7 months and 12 months, 0.5 mcg;
  • For children between 1 and 3 years, 0.9 mcg;
  • For children between 4 and 8 years, 1.2 mcg;
  • For children between 9 and 13 years, 1.8 mcg;
  • For adolescents and adults of 14 years and above, 2.4 mcg

Pregnant and breastfeeding women may require a higher daily intake of vitamin B12. Doses of 2.6 and 2.8 mcg are usually advised to be taken daily by pregnant and breastfeeding women respectively.

Furthermore, the absorption of vitamin B12 from food sources may be diminished in some elderly people who are above the age of 51. Therefore, to meet the recommended intake, they are encouraged to adopt vitamin B12-fortified foods in their diet and also take vitamin B12 supplements.

Excellent food sources of vitamin B12 include milk, cheese, eggs, meat, fish, and poultry products. Many processed foods such as breakfast cereals are also fortified with vitamin B12.

Vitamin B12 is usually sold in the form of pills. It can also be found in many multivitamin formulations sold over the counter. When there is a problem with the digestive absorption of vitamin B12, the vitamin can be delivered via injections and patches.

Vitamin B12 is also sold in other dosage forms such as liquid and nasal spray.

A low amount of vitamin B12 which is below the level required by the body will result in vitamin B12 deficiency. This deficiency presents a number of health problems. The major sign of vitamin B12 deficiency is pernicious anemia.

Furthermore, due to the importance of the vitamin in the normal functioning of the brain and nervous system, vitamin B12 deficiency may cause neuronal damage including memory loss, cognitive impairment, and other neurodegenerative disorders.

Therefore, symptoms such as fatigue, depression, and poor memory may be observed in those with vitamin B12 deficiency.

Some members of the B vitamins (vitamin B6 and folic acid) are more closely tied to vitamin B12 than others. For example, some animal studies have shown a strong link between vitamin B6 deficiency and low absorption of vitamin B12 in the body.

When taken in excessive amounts, folic acid may conceal the effects of vitamin B12 deficiency. In this case, megaloblastic anemia which is caused by vitamin B12 deficiency is corrected by folic acid while neurological damage is left uncorrected.

How Vitamin B12 Works for Depression

A number of studies have been done to investigate the link between vitamin B12 deficiency and depression. Most of these studies agree that vitamin B12 deficiency is common among depressed patients.

SAMe and Depression

The link between depression and vitamin B12 has been connected to the metabolism of S-adenosylmethionine (SAMe) and increased homocysteine levels in the body.

While S-adenosylmethionine itself has an important anti-depressive function, vitamin B12 deficiency disrupts the production of this co-substrate and thus increases the risk of depression.

Together with folic acid, vitamin B12 is essential to the complex metabolic pathway that leads to the synthesis of S-adenosylmethionine. S-adenosylmethionine, in turn, is the major donor of methyl groups needed for the production of monoamine neurotransmitters. This process of transferring methyl groups is known as transmethylation.

When the production of monoamine neurotransmitters (serotonin, norepinephrine, and dopamine) is disturbed, the regulation of mood is disrupted. This is often what causes depression.

Lastly, S-adenosylmethionine can also improve the response of receptors to the neurotransmitters essential to the regulation of mood.

Homocysteine and Depression

Besides SAMe, homocysteine is another important factor that may contribute to depression. A number of studies have confirmed that depressed patients who are deficient in vitamin B12 have high levels of homocysteine. In fact, one of the functional markers of vitamin B12 deficiency is the increase in the blood levels of homocysteine.

Homocysteine is an amino acid that is not used to make proteins. It is similar in chemical structure to cysteine, only having an extra methylene group. Homocysteine is toxic and its accumulation can actually cause damage to the heart and brain.

To prevent the buildup of homocysteine in the body, it is converted to methionine or recycled to its precursor amino acid. Vitamin B12 is one of the B vitamins needed for these conversions.

Therefore, vitamin B12 deficiency impairs the conversion of homocysteine to methionine thereby resulting in an accumulation of this toxic substance in the body. This places oxidative stress on nerve cells and, in general, on the central nervous system.

Homocysteine can cause the oxidative destruction of the parts of the brain involved in regulating mood. By preventing the accumulation of homocysteine, vitamin B12 can help prevent and treat depression.

Furthermore, vitamin B12 is useful in the management of depression not only because it prevents neurodegeneration but also because it is important in neuronal regeneration or the development of nerve cells.

Lastly, a membrane that envelops and protects the nerve cells (known as myelin sheath) has been shown to form less efficiently when there is a deficiency in vitamin B12. This can lead to degeneration of the nervous system and thus cause depression.

All of these mechanisms provide support for the use of vitamin B12 in the treatment of depression.

Studies on Vitamin B12 and Depression

A 2003 study published in the journal, BioMedCentral Psychiatry, examined the correlation between vitamin B12 levels and the recovery of depressed patients.

In this study, 100 patients suffering from depression were closely monitored over a six-month check-up period. The levels of vitamin B12 in the blood of the patients were measured and recorded at the start and throughout the entire duration of the study.

After the six-month period, the result of the study showed significantly better improvement in patients who had higher blood levels of vitamin B12 compared to those with lower levels.

Vitamin B12, Folic Acid, Homocysteine, and Depression

A more recent study published in The British Journal of Psychiatry in 2008 investigated the association between folic acid, vitamin B12, homocysteine, and late-life depression.

A total of 732 Korean volunteers aged 65 years and above were recruited for the study. The conditions of the patients were evaluated and blood levels of folic acid, vitamin B12, homocysteine were measured at the beginning and throughout the study.

521 patients from a total of 732 were found not to be depressed and they were observed over a period of 2 to 3 years. During the course of the study, incident depression was determined with the Geriatric Mental State schedule.

The results of the study showed that there was a link between higher risks of incident depression and decreased blood levels of vitamin B12 over the period of the study. An increase in homocysteine levels over the follow-up period was also found to be associated with an increased risk of incident depression.

Another study published in The American Journal of Psychiatry in 2000 investigated whether community-dwelling older women with metabolically significant vitamin B12 or folate deficiency are at risk of depression.

For this study, 700 disabled women aged 65 years and above were recruited. The researchers measured homocysteine, folic acid and vitamin B12 levels in the participants during the course of the study.

The symptoms of depression in the participants were evaluated and scored based on the Geriatric Depression Scale. The participants were divided into three groups:

  • No depression group: 478,
  • Mild depression group: 100,
  • Severe depression group: 122.

The result of the study showed that deficiency of vitamin B12 was found in 14.9% of the non-depressed group, 17.0% of the mildly depressed group, and 27.0% of the severely depressed group.

Even after correcting for other health status factors, it was found that participants deficient of vitamin B12 were twice as likely to develop severe depression as those with normal levels of the vitamin.

In another study published in the same journal in 2002, the association of vitamin B12, folate, and homocysteine with depression were also examined.

278 patients with depressive symptoms, as well as 112 with depressive disorders, and 416 randomly selected reference subjects were examined out of 3,884 participants recruited for the study.

Folate, vitamin B12, and homocysteine blood levels of the participants were measured and compared. There were adjustments based on age, gender, cardiovascular disease, and functional disability.

The result of the study showed different associations between folate, vitamin B12, homocysteine, and depressive disorders. Both folate and vitamin B12 levels were associated with improved mood.

However, after adjustments for functional disability and cardiovascular diseases were made, the link between folic acid and depression was weaker but vitamin B12 deficiency remained a strong cause of depression.





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