Role of Omega 3 Fatty Acids, Vitamin D, Vitamin B12,Vitamin B6 and Folate in Mental Wellbeing- A Short Review of the Literature

(click photo for full article)

Mental well-being is a core component of optimal

health, and is a status that individuals can manage stress

from daily living and make positive achievements pursuing

public interest and contribution to the community.

The World Health Organization (WHO) estimates that

several hundred million people in the world suffer from

a mental or behavioural disorder at the beginning of the

new millennium. In addition, mental illnesses are the

second leading cause of disability worldwide.

Mental disorders, which are the same as psychiatric disorders,

are clusters of syndromes which disturb an individual’s

cognition, emotion regulation or behaviour. Common

mental disorders include bipolar disorders (manic

disorder, depression, and manic-depression), dementia,

schizophrenia, and panic disorder.

Depression, the most common mental disorder, is one of the major

global public health problems and projected to become

the second leading cause of burden of disease by 2030.

Maintaining individual’s mental health is important to

improve personal life values, to reduce medical cost and

other social expenses to deal with mental disorders, and

to enhance national competitiveness. Several factors affecting

the development of mental disorders include genetic factors,

stress, diet, physical inactivity, drugs, and other environmental factors.

Among these factors, dietary factors may aggravate or ameliorate symptoms

and the progression of the disorders although those are

not major etiologies. Nutritional deficiencies, resulting

from insufficient intake or absorption of nutrients

critical to human health, are now a recognized risk factor

for psychiatric disorders.

Nutritional factors having beneficial effect on mental health are

polyunsaturated fatty acids (PUFAs), especially omega-3 FAs, phospholipids, cholesterol, niacin, folate, vitamin B6, vitamin B12, and vitamin D.

Omega 3 Fatty Acids and Mental Health

Omega-3 fatty acids play a critical role in the

development and function of the central nervous system.

Emerging research is establishing an association between

omega-3 fatty acids (alpha-linolenic, eicosapentaenoic,

docosahexaenoic) and major depressive disorder.

Omega-3 PUFAs play fundamental roles in the

development, functioning and aging of the brain.

In humans, dietary deficiencies of omega-3 PUFAs, such

as docosahexaenoic acid and eicosapentaenoic acid,

have been associated with an increased risk of various

mental disorders. Omega-3 fatty acids are long-chain,

polyunsaturated fatty acids (PUFA) of plant and marine

origin. Because these essential fatty acids cannot be

synthesized by the human body, they must be derived

from dietary sources.

Flaxseed, hemp, canola and walnut oils are all generally

rich sources of the parent omega-3, alpha linolenic acid (ALA).

Dietary ALA can be metabolized in the liver to the longer-chain

omega-3 eicosapentaenoic (EPA) and docosahexaenoic acid

(DHA). This conversion is limited in human beings,

it is estimated that only 5–15% of ALA is ultimately

converted to DHA .

Aging, illness and stress, as well as excessive amounts of

omega-6 rich oils (corn, safflower, sunflower, cottonseed) can all

compromise conversion. They have long been investigated for their

cardio protective and anti-inflammatory roles, which has

lead to their increased use as dietary supplements.

A new application for omega-3 fatty acids has emerged

recently, the treatment of certain forms of mental illness.

Such a use is biologically plausible given that omega-3

fatty acids, in particular DHA, are abundant in the brain

and are involved in, or modulate, the mechanism by

which brain neurons communicate .

The Role of Omega

3 fatty acids in improving cognitive functions has been

extensively studied in a variety of populations ranging

from infants to the elderly, and from healthy individuals

to patients with psychiatric, neurodegenerative or

neurodevelopment disorders.

For example, omega 3 fatty acids supplementation has been

shown to improve depressive symptoms and verbal fluency in

elderly with mild cognitive impairments. They have been shown

to alter the functioning of neural systems utilising

dopamine and serotonin, both of which are thought to

play an important role in mental illness and are major

targets of psychoactive medications.

Furthermore, animal models of mental illness have suggested that

omega-3 fatty acids can affect brain processes such as

those that control mood and anxiety.

Vitamin D and Mental Health

Vitamin D deficiency is commonly defined as

levels of 25-hydroxyvitamin D (25OHD) less than

25nmol/L, insufficiency as between 25 and 50nmol/L

and sufficiency as greater than 50nmol/L. Its RDA is

400 IU or 10 mg, it binds to the receptor of target cells

and regulate through gene expression.

Poor diet, lack of sun exposure, decreased synthesis of vitamin D and

decreased renal hydroxylation of 25(OH) D due to old

age are the main cause of Vitamin D deficiency.

Nearly 30 percent to 50 percent of people

are estimated to have deficiency of vitamin

D, and insufficiency and vitamin D deficiency

are recognized as global health issues in the

world.

Scientific findings about the role of vitamin D

in healthy people and patients with numerous diseases

increasingly accumulate in medical literature. The fact

that, taking into account recommended optimal values,

about a third or more of adult population in societies

with higher life standard had a deficiency of vitamin

D, raises additional, widespread concern.

Vitamin D3 (cholecalciferol) is taken in the diet (fortified dairy

products and fish oils) or is synthesized in the skin from

7-dehydrocholesterol by ultraviolet irradiation. It is

transported in the blood by the vitamin D binding protein

(DBP) to the liver. In the liver it is hydroxylated, resulting

in the formation of 25 hydroxyvitamin D3 (25(OH)

D3). This is then transported to the kidney by DBP. In

the proximal renal tubule 25(OH)D3 is hydroxylated,

resulting in the hormonally active form of vitamin D,

1,25-dihydroxyvitamin D3 (1,25(OH)2D3), which is

responsible for most if not all of the biologic actions

of vitamin D.

Vitamin D is crucial for several key physiological processes,

including brain development, DNA repair, and regulation of many

genes. Evidence indicates that prenatal and early postnatal vitamin

D deficiency increases autism risk, probably through

multiple effects, including impaired brain development

and increased de-novo mutations.

Vitamin D receptors (VDR) were found in neurons and glial cells in brain

areas responsible for the development of depression

and suggesting a role of vitamin D for development

of some mental disorders. Vitamin D helps protect

against oxidative stress, which is a key cause of DNA

damage, and also aids in the repair of DNA damage once

it occurs.

Vitamin B12 and Mental Health

Vitamin B12 plays a crucial role in cell reproduction,

normal erythropoiesis, nucleoprotein and myelin

synthesis, normal growth, DNA synthesis, and one

carbon metabolism.

Normal daily requirement is about 1 μg. Vitamin B12 helps in

synthesis of methionine from homocysteine and conversion of

methylmalonylcoA to succinylcoA. Methionine is converted to SAM

which donates its methyl group to myelin, membrane

phospholipids and various neurotransmitters and free

THF is liberated from N5 methyl THF which is used

in synthesis of purine, pyrimidine and nucleic acid.

An elevated level of Hcy as a neurotoxin was also shown to

affect the redox signalling pathways in neurons through

the generation of reactive oxygen species (ROS) and

a decrease in endogenous antioxidants. If patterns of

DNA methylation in redox-related genes can modulate

cognitive impairment caused by vitamin B12 deficiency

and hyperhomocysteinaemia is therefore of interest,

low levels of vitamin B12 can cause serious cognitive

dysfunction.

Psychiatric symptoms attributable to vitamin B12 deficiency have

been described for decades. The earlier studies are for the most part

in accord with more recent ones, despite being diagnostically less

precise in psychological and hematologic terms. These

symptoms tend to fall into many clinically distinct

categories: slow cerebration; confusion; memory

changes; delirium, with or without hallucinations and/or

delusions; depression; acute psychotic states; and more

rarely) reversible manic and schizophreniform states.

Folate and Mental Health

Folate deficiency and insufficiency are common

among patients with mood disorders and correlate with

illness severity.

Folate deficiency may specifically affect central monoamine

metabolism and aggravate depressive disorders. There must be

two reasons of folate deficiency, the biologically active form of folate,

L-methylfolate, may act as a trimonoamine modulator

and enhance the synthesis of three monoamines

including dopamine, norepinephrine, and serotonin, and

this has been reported to be involved in the efficacy of

antidepressant.

Patients with a methylenetetrahydrofolate

reductase (MTHFR) C677T polymorphism produce

a less active form of the enzyme. The TT genotype is

associated with major depression and bipolar disorder.

Dietary folate must be converted to L-methylfolate for

use in the brain. Other potential explanation may be due

to malnutrition or poor nutrition intake.

Vitamin B6 and Mental Health

Vitamin B6 deficiency has been associated with

neuropsychiatric conditions, including seizures,

migraines, chronic pain and depression. In the control

of mental function and mood, vitamin B6, containing

three chemically distinct compounds, pyridoxal,

pyridoxamine, and pyridoxine, is involved.

Vitamin B6 is also an important re-methylation cofactor for

homocysteine, and deficiency is associated with

an increase in levels of homocysteine in the blood.

Homocysteine is a cerebrovascular disease risk factor

and may also have a direct toxic impact on central

nervous system neurons.

Conclusion

Nutrition deficiency leads to serious mental

disorders, as body require adequate amount of nutrition

for its proper functioning. Poor nutrition status in mental

disorders leads to folate deficiency which appears to

predominate in melancholic depression; anorexia and

weight loss are common features of this type. In these

settings, supplementation with folate or its derivative,

methylfolate, may be found to play an important role

in effective antidepressant treatment. Both folate and

vitamin B12 deficiency may cause similar neurological

depression, dementia, and a demyelinating myelopathy.

Deficiency of omega 3 fatty acids, vitamin D, vitamin

B12, folate, vitamin B6 are commonly seen in mental

disorders, so adequate amount of nutrition and

supplements should