Role of vitamins in psychiatry

PRESENTER : DR.VIPIN GEORGE

“If forgiveness is medicine for the soul, then gratitude is vitamins.”  DR.STEEVE MARABOLI

Overview

• Classification.

• Role of vitamins in brain functioning.

• Deficiency and psychiatric manifestations.

• Treatment and supplementation.

• Nutrition plays a key role in maintaining optimal brain

health throughout the lifespan of an individual .

• The studies examining the link between nutrition and

mental health have gained widespread attention in recent

years.

What is a vitamin?

• The term vitamin is from words “vital” and “amine” ,

vitamins are required for life and were originally thought

to be“amines”.

• Vitamins are complex organic substances necessary to our

diet in small amounts to promote and regulate the chemical

reactions and processes In the human body.

• Vitamins are called micro nutrients needed in only very

small quantities.

• They are dietary components other than carbohydrates,

fats, minerals, and proteins that are necessary for life.

Where are they found?

• Most of our vitamins through the food and drink we eat, but

we can also obtain vitamins in supplement form.

• Varied diet to allow for a wide range of nutrients to be

absorbed by the body.

CLASSIFICATION OF VITAMINS

• There are 9 water soluble vitamins.

• These are readily excreted from the body

• 1. Vitamin B1 2. Vitamin B2 3. Vitamin B6 4.

Vitamin B12 ,5. Vitamin C (ascorbic acid) 6.

Folic acid 7. Niacin 8. Biotin 9. Pantothenic

acid.

There are 4 fat soluble vitamins

• 1. Vitamin A 2. Vitamin D 3. Vitamin E 4. Vitamin K.

• They can dissolve in lipids solutions .

• These are absorbed through intestinal track with

the help of lipids.

• Deficiencies may play a causative role in mental

illness .

• Exacerbate symptoms.

• Psychiatric symptoms can result in poor nutrition.

In mental illness

• vitamin insufficiency—defined as subclinical deficiency—

may compromise patient recovery.

• Genetic differences may compromise vitamin and

essential nutrient pathways.

. B vitamins

• Proper functioning of the methylation cycle.

• Monoamine production.

• DNA synthesis.

• Maintenance of phospholipids such as myelin.

Fat-soluble vitamins play important roles in

• Genetic transcription

• Antioxidant recycling

• Inflammatory regulation in the brain.

One carbon metabolism• Crucial biosynthetic pathway for DNA syn&repair and

numerous methylation reactions.

• Amino acid methionine plays central role .

• Dietary source of methionine in insufficient.

• Folate converts methionine to SAM,donor for most of

methylation reactions.

• When folate is low SAM depletion .

• The vitamins folic acid, B12 and B6 and B2 are the source

of coenzymes which participate in one carbon metabolism.

• A carbon unit from serine or glycine is transferred to

tetrahydrofolate (THF) to form methylene-THF.

• This is either used as such for the synthesis of thymidine,

which is incorporated into DNA,

Oxidized to formyl-THF is used for the synthesis of purines,

which are building blocks of RNA and DNA,

or reduced to methyl-THF which used to methylate

homocysteine to form methionine, a reaction which is

catalyzed by a B12-containing methyltransferase.

• Much of the methionine which is formed is converted to S-

adenosylmethionine (SAM), a universal donor of methyl

groups, including DNA, RNA, hormones, neurotransmitters,

membrane lipids & proteins .

Water-soluble vitamins

Vitamin B1 (Thiamine) 

• Essential for glucose metabolism.

• Thiamine is a helper molecule (i.e., a coenzyme) of

carbohydrate metabolism. Intermediate products of

these pathways are needed for the generation of other

essential molecules in the cells (e.g., building blocks

of proteins and DNA as well as brain chemicals)

Thiamine–rich foods include meat and poultry; whole

grain cereals (e.g., brown rice and bran); nuts; and

dried beans, peas, and soybeans

Humans require a minimum of 0.33 milligrams (mg)

thiamine /1,000 (kcal) of energy they consume.

• A daily intake of 1.1 mg thiamine is currently

recommended for adult women and 1.2 mg for adult

men.

• Studies have found that most healthy people

typically consume 0.4 to 2.0 mg thiamine daily.

• The cells of the nervous system and heart seem

particularly sensitive to the effects of thiamine

deficiency.

• In the brain, thiamine is required both by the nerve

cells (i.e., neurons) and by other supporting cells in

the nervous system (i.e., glia cells).

Thiamine deficiency

• Pregnancy, lactation, and fever increase the need

and tea, coffee, and shellfish can impair its

absorption.

• Chronic alcohol consumption can result in thiamine

deficiency by causing inadequate nutritional thiamine

intake, decreased absorption of thiamine from the

gastrointestinal tract,and impaired thiamine utilization.

Deficiency leads to an increase in.

• Reactive oxygen species

• Proinflammatory cytokines

• Blood-brain barrier dysfunction

.

  

In short term deficiency

Neurasthenic picture :fatigue, weakness,emotional

Acute & fulminant deficiency wernicke’s encephalopathy.

WKS typically consists of two components, a short–

lived and severe condition called Wernicke’s

encephalopathy (WE) and a long–lasting and

debilitating condition known as Korsakoff’s psychosis.

WE is an acute life–threatening neurologic disorder

stem from the, brain’s inability to oxidize glucose for

energy.

Many WE patients, however, do not exhibit all three of

these signs and symptoms, WE may be present even if

the patient presents with only one or two of them.

• Approximately 80 to 90 percent of alcoholics with WE develop

Korsakoff’s psychosis, a chronic neuropsychiatric syndrome

characterized by behavioral abnormalities and memory

impairments .

• Although these patients have problems remembering old

information (i.e., retrograde amnesia), it is the disturbance in

acquisition of new information (i.e., anterograde amnesia) that

is most striking Korsakoff’s psychosis also is called alcohol

amnestic disorder

Brain regions affected by thiamine deficiency

Various brain regions differ in their sensitivity to alcohol’s

effects

Cerebellum most sensitive

This heightened susceptibility is consistent with the cognitive

deficits typically associated with alcoholism.

Cerebellar damage or of damage to the frontal lobes, which

are connected to the cerebellum through neural pathways.

Reversal of thiamine deficiency revereses cerebellar damage

&improve some brain functions typically associated with the

frontal lobe

Chronic severe deficiency leads to

Beriberi with

Neuropathy,cardiac failure,or peripheral edema

Treatment

Without neuropsychiatric complications

Oral thiamine min of 300mg /day.

Wernickes encephalopathy

parentral thiamine 500mg 3 times daily for 3-5 days.followed by

500mg once daily for 5days.

Vitamin B2 (riboflavin)• Essential for oxidative pathways.

• Monoamine synthesis.

• Methylation cycle.

B2 is needed to create the essential flavoprotein

coenzymes for synthesis of L-methylfolate—the active

form of folate—and for proper utilization of B6.

Deficiency can occur after 4 months of inadequate

intake.

Marginal B2 levels are more prevalent in depressed

patients, possibly because of B2’s role in the function

of glutathione, an endogenous antioxidant.

symptoms

Lethargy,multiple somatic complaints.

Look for sore throat,glossitis,seborrhoeic dermatitis

Top dietary sources of B2

Dairy products, meat and fish, eggs, mushrooms,

almonds, leafy greens, and legumes.

Riboflavin is destroyed by light. So food should be

stored away from light to protect its riboflavin content.

.

Niacin Vitamin B3.

• Nicotinic acid and nicotinamide are precursors of two

important co-enzymes: nicotinamide adenine dinucleotide

(NAD) and nicotinamide adenine dinucleotide phosphate

(NADP).

• NAD and NADP are crucial to a number of oxidative and

reductive reactions - eg, steroid formation, fatty acid

synthesis, protein metabolism and DNA repair.

Sub acute deficiency

• Pellagra :gi symptoms,dermatitis,psychiatric disturbances

Acute and sudden depletion

• Encephalopathy with or without symptoms /signs in other

systems

• Vitamin B3 is found in many foods including yeast, meat,

fish, milk, eggs, green vegetables, beans, and cereal

grains

Deficiency

• c/c alcoholism.

• Malnourished homeless.

• Carcinoid syndrome.

• Hartnups d/s defective absorption from diet.

• 2-pyridone and 2-methyl nicotinamide in urine .

• Can be measured to assess niacin deficiency (low levels

will be present).

• RBC levels of NAD/NADP can also be useful in the

diagnosis.

Treatment • Oral supplementation with nicotinamide is usually used (eg,

100-200 mg three times a day until symptoms remit.

Vitamin B6 refers to 3 distinct compounds: pyridoxine,

pyridoxal, and pyridoxamine.

B6 is essential to glycolysis, the methylation cycle, and

recharging glutathione, an innate antioxidant in the brain.

Higher levels of vitamin B6 are associated with a lower

prevalence of depression in adolescents.

and low dietary and plasma B6 increases the risk and

severity of depression in geriatric patients. 

• Deficiency is common (24% to 56%) among patients

receiving hemodialysis.

• Women who take oral contraceptives are at increased risk

of vitamin B6 deficiency. 

• It is needed for normal brain development and function

• Role in syn. of hormones serotonin and norepinephrine,

which influence mood

• Melatonin, which helps regulate the circadian rhythm.

• Helps control levels of homocysteine in the blood.

• Need B6 in order to absorb vitamin B12 and to make red

blood cells and cells of the immune system.

• It is rare to have a significant deficiency of B6.

Deficiency

• Convulsions Mental deterioration in infants.

• Premenstrual syndrome and depression in women taking

ocp.

• May have role in depression.

• Doses of vit b6 up to 100mg daily are likely to be of benefit

in treating .

•  Top dietary sources are fish, beef, poultry, potatoes,

legumes, and spinach.

Vitamin B5 [Pantothenic acid ]

• From the Greek root “pantos”, meaning "everywhere,"

because it is available in a wide variety of foods.

Deficiency

• Sensory neuropathy ‘burning feet syndrome’

• Role in psychiatric disorder has not been clearly established.

Biotin vit B7/vit H• Vitamin B7, formerly known as Vitamin H or coenzyme R.

Foods with a relatively high biotin content .

 peanuts and other leafy green vegetables, raw

egg yolk(however, the consumption of avidin-containing egg

whites with egg yolks minimizes the effectiveness of egg

yolk's biotin in one's body), liver

Biotin is also called vitamin H (the H represents Haar und

Haut, German words for "hair and skin") or vitamin B7

Valproate can cause biotin deficiency and may lead to low

serum and liver tissue biotinidase enzyme a major clinical

manifestation of biotin deficiency is alopecia.

Vitamin B9 [Folic acid] • Participates in one carbon metabolism.

• A carbon unit from serine or glycine is transferred to

tetrahydrofolate (THF) to form methylene-THF.

• This is either used as such for the synthesis of thymidine,

which is incorporated into DNA.

• oxidized to formyl-THF which is used for the synthesis of

purines, which are building blocks of RNA and DNA.

or it is reduced to methyl-THF which used to methylate

homocysteine to form methionine, a reaction which is

catalyzed by a B12-containing methyltransferase.

Co factor in the re methylation of homocysteine to methionine hence deficiency leads to increased homocysteine

Neuronal excitotoxicity through NMDA [r]

Increased oxidative stress

Neuronal damage and apoptosis

• Synthesis of serotonin, norepinephrine, dopamine, and

DNA and in phospholipid production.

• Low maternal folate status risk of neural tube defects in

newborns.

• Folate deficiency and insufficiency are common among

patients with mood disorders and correlate with illness

severity.

• Leafy greens and legumes such as lentils are top dietary

sources of folate.

• Dietary folate must be converted to L-methylfolate for use in

the brain. 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.Clinical trials

have shown that several forms of folate can enhance

antidepressant treatment.Augmentation with L-methylfolate,

which bypasses the MTHFR enzyme, can be an effective

strategy for treating depression in these patients.

Deficiency• A diet low in fresh fruits, vegetables, and fortified cereals is

the main cause of folate deficiency.

• Diseases that affect absorption in the gastrointestinal

Crohn’s disease,celiac disease

• Genetic mutation that hinders converting dietary or

supplemental folate to its usable form, methylfolate.

• Medications: phenytoin ,methotrexate

• Excessive alcohol intake interferes with folate absorption

Folic acid deficiency :serum level <5nmol/L

Treatment

Replacement with folic acid 5mg thrice daily

Always screen for vit b12 def.to prevent neurological

disturbances.

Augmentation with L-methylfolate, which bypasses the

MTHFR enzyme, can be an effective strategy for treating

depression .

Vitamin B12 (cobalamin)•  An essential cofactor in one-carbon metabolism, B12 is

needed to produce monoamine neurotransmitters and

maintain myelin.

• Maintenance of equilibrium between neurotrophic and

neurotoxic factors in the central nervous system .

Neurotrophins are growth factors that influence the

proliferation, differentiation,survival and death of neuronal

and non-neuronalcells.

•

Deficiency is found in up to one-third of depressed patients and

compromises antidepressant response

• Pernicious anemia ,Gastrointestinal illness, older adults with

achlorhydria, and vegetarians,

• Proton pump inhibitors interfere with B12 absorption

Elevated methylmalonic acid and total homocysteine

concentrations are considered as sensitive metabolic

markers for vitamin B12 deficiency .

S.Vit b12 assy less sensitive for assessing tissue deficiency .

vitamin B12 deficiency

• Myelopathy and neuropathy are known to be the main

clinical manifestations

• Megaloblastic anaemia,tingling and numbness of the

extremities, gait abnormalities,visual disturbances,

• Memory loss and dementia.

• Psychotic depression .

•  Low B12 levels and elevated homocysteine increase the

risk of cognitive decline and Alzheimer’s disease and are

linked to a 5-fold increase in the rate of brain atrophy.

• Psychiatric symptoms of B12 deficiency may present before

hematologic findings. Folic acid supplementation may mask

a B12 deficiency by delaying anemia but will not delay

psychiatric symptoms. Ten percent of patients with an

insufficiency (low normal levels of 200 to 400 pg/mL) have

elevated homocysteine, which increases the risk of psychiatric

disorders as well as comorbid illnesses such as cardiovascular

disease.

Treatment

Intramuscular hydroxycobalamin at a dosage of 1 mg weekly

for eight weeks, followed by 1 mg monthly for life.

Top dietary sources include fish,meat, and dairy products

..

Vitamin C•   Vital for the synthesis of monoamines such as serotonin

and norepinephrine.

• Vitamin C’s primary role in the brain is as an antioxidant. As

a necessary cofactor, it keeps the copper and iron in

metalloenzymes reduced, and also recycles vitamin E.

• Proper function of the methylation cycle depends on vitamin

C, as does collagen synthesis and metabolism of

xenobiotics by the liver.

• Humans cannot manufacture vitamin C.

• vitamin C (90 mg/d) .

•  Older adults and patients with a poor diet due to drug or

alcohol abuse, eating disorders, or affective symptoms are

at risk.

• Scurvy is caused by vitamin C deficiency and leads to

bleeding gums and petechiae.

Patients with insufficiency report irritability, loss of appetite,

weight loss, and hypochondriasis.

Vitamin C intake is significantly lower in older adults (age ≥60)

Citrus, potatoes, and tomatoes are top dietary sources of

vitamin C.

Fat-soluble vitamins

Vitamin A.•  Although vitamin A activity in the brain is poorly understood,

retinol—the active form of vitamin A—is crucial for formation

of opsins, which are the basis for vision.

• Childhood vitamin A deficiency may lead to blindness.

• . Vitamin A also plays an important role in maintaining bone

growth, reproduction, cell division, and immune system

integrity.

•  

• Animal sources such as beef liver, dairy products, and eggs

provide retinol, and plant sources such as carrots, sweet

potatoes, and leafy greens provide carotenoids that humans

convert into retinol.

vitamin A deficiency

• Deficiency most often seen with excessive alcohol use,

rigorous dietary restrictions, and gastrointestinal diseases

accompanied by poor fat absorption.

Excess vitamin A ingestion may result in bone abnormalities,

liver damage, birth defects, and depression.

Isotretinoin—a form of vitamin A used to treat severe acne—

carries an FDA “black-box” warning for psychiatric adverse

effects, including aggression, depression, psychosis, and

suicide.

Vitamin D• Normally, vitamin D is obtained from dietary intake and ultra

violet exposure through normal skin synthesis. Skin

absorption is influenced by duration of sunlight exposure,

skin pigmentation, age, gender, and innate factors(e.g.,

genetic polymorphism) .

• Vitamin D2 and vitamin D3 are available to human beings

as ergocalciferol and cholecalciferol,respectively

• The most robust metabolite of vitamin D is 1α, 25-

dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), which has potent

regulatory properties.

• It is the primary bioavailable form of vitaminD has a half-life

of about two to three weeks and is the sole vitamin D

metabolite used to establish vitamin D status.

• The optimal threshold of vitamin D is ≥30 ng/ml

Clearly vitamin D status plays a role in overall health

promotion.

• Vitamin D is primarily associated with calcium homeostasis

and is essential in optimal intestinal calcium absorption;

• Serum calcium balance;

• Musculoskeletal health

• Calcium phosphorous metabolism.

vitamin D receptors (VDR) Prefrontal cortex, the amygdala and the hippocampus.• Vitamin D metabolites protect the integrity of

neurons .• Upregulation of neurotrophic factors present in the

hippocampus and neocortex.• vitamin D affects inflammatory pathways

(downregulating autoimmune pathways producing proinflammatory cytokines and promoting anti-inflammatory pathways through VDR-mediated gene transcription that in turn have been linked to depression.

• In depression higher levels of

pro-inflammatory cytokine interleukin(IL-1)beta and lower

levels of anti-inflammatory cytokine IL-10

• Medications used to treat depression& schizophrenia

• serum levels of interleukin-1beta and interferon-gamma

and stabilize the overproduction of inflammatory cytokines.

Aberrations in these mechanisms are associated with an

imbalance betweenserum 1, 25-Dihydroxyvitamin D3 and

prostaglandin cellular signaling processes.

.

Prescribing Vitamin D

Vit D supplementation as a potential anti-inflammatory option

for mild to moderate depression

The clinical challenge is to diagnose vitamin D deficiency and

determine the appropriate dose of vitamin D supplementation.vitamin D deficiency< 20 ng/mL (< 50 nmol/L) Sub optimal status: 20–30 ng/mL (50–75 nmol/L) Target concentrationfor optimal Vitamin D effects: 30–50 ng/mL (75-125nmol/L)

Treatment

How much vitamin D is needed to correct deficiency?

Although not validated by clinical trials, a commonly applied

strategy is to prescribe a “loading dose” (eg, 50,000 IU of vitamin

D orally once weekly for 2-3 months, or 3 times weekly for 1

month.

• Once an optimal concentration of 25(OH)D of 30–50 ng/mL

(75–125 nmol/L) is attained

• Order serum levels several months later and then twice a

year

• Daily doses of 800–2,000 IU/day to sustain 20–50 ng/per

day. • Vitamin D exists in food as either D2 or D3, from plant and

animal sources, respectively. Concentrated sources

include oily fish, sun-dried or “UVB-irradiated” mushrooms,

and milk

Vitamin E • There are 8 isoforms of vitamin E

• 4 tocopherols and 4 tocotrienols

• Function as fat-soluble antioxidants and also promote

innate antioxidant enzymes.

• Protects neuronal membranes from oxidation, low levels

may affect the brain via increased inflammation.

• Alpha-tocopherol is the most common form

•

• Mediate disease by modifying transcription factors in the

brain, such as glutathione reductase, superoxide dismutase,

and nuclear factor-kappa B. 

• Low plasma vitamin E levels are found in depressed

patients,.

• Foods rich in vitamin E include almonds, sunflower seeds,

leafy greens, and wheat germ.

Points to remember• Many pts may neglect to care for themselves or adopt

particular eating patterns.

• Deficiencies are more common among geriatric patients

and those who are medically ill.

• Because dietary patterns are linked to the risk of psychiatric

disorders, nutritional inquiry often identifies multiple

modifiable risk factors, such as folate, vitamin B12, and

vitamin D intake.

• Psychiatrists should assess patients’ dietary patterns and

vitamin status, particularly older adults and those with

• Lower socioeconomic status or food insecurity

• A history of treatment resistance

• Restrictive dietary patterns such as veganism

• Alcohol abuse.

On initial assessment, test your patient’s blood levels of folate

and vitamins D and B12.

Simple assessment of dietary patterns • A typical breakfast, lunch, and dinner, their favorite snacks

and foods, and specific dietary habits or restrictions (eg, not

consuming seafood, dairy, meat, etc.)

• Rudimentary nutritional recommendations can be effective

in changing a patient’s eating habits, particularly when

provided by a physician.

• Encourage patients to eat nutrient-dense foods and a

variety of vegetables and fruits / consult with a clinical

nutritionist.

Conclusion

• Vit B Proper functioning of the methylation cycle,

Monoamine production, DNA synthesis.

• Fat-soluble vitamins play important roles in Genetic

transcription Antioxidant recycling Inflammatory regulation

in the brain.

• Special mention to folic acid,vit B12,vitD.

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4.Y Milaneschi, W Hoogendijk, P Lips, A C Heijboer, R Schoevers, A M van Hemert, A T F Beekman,

J H Smit and B W J H Penninx The association between low vitamin D and depressive disorders

Molecular Psychiatry 19, 444-451 (April 2014) | doi:10.1038/mp.2013.36,

.5. Antai-Otong Vitamin D: an anti-inflammatory treatment option for depression?Issues Ment Health

Nurs. 2014 Mar;35(3):227-34. doi: 10.3109/01612840.2013.875086.

6.Lishmans textbook of organic psychiatry.