Folate deficiency, also known as vitamin B
9 deficiency, is a low level of
folate and derivatives in the body. Signs of folate deficiency are often subtle. A
low number of red blood cells (anemia) is a late finding in folate deficiency and folate deficiency anemia is the term given for this medical condition. It is characterized by the appearance of large-sized, abnormal
red blood cell
Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek ''erythros'' for "red" and ''kytos'' for "holl ...
s (
megaloblasts), which form when there are inadequate stores of folic acid within the body.
Signs and symptoms
Loss of appetite and
weight loss
Weight loss, in the context of medicine, health, or physical fitness, refers to a reduction of the total body mass, by a mean loss of fluid, body fat (adipose tissue), or lean mass (namely bone mineral deposits, muscle, tendon, and other conn ...
can occur. Additional signs are
weakness
Weakness is a symptom of a number of different conditions. The causes are many and can be divided into conditions that have true or perceived muscle weakness. True muscle weakness is a primary symptom of a variety of skeletal muscle diseases, i ...
, sore tongue,
headache
Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches.
Headaches can occur as a result ...
s, heart
palpitation
Palpitations are perceived abnormalities of the heartbeat characterized by awareness of cardiac muscle contractions in the chest, which is further characterized by the hard, fast and/or irregular beatings of the heart.
Symptoms include a rapi ...
s,
irritability, and
behavioral disorder
Emotional and behavioral disorders (EBD; also known as behavioral and emotional disorders) refer to a disability classification used in educational settings that allows educational institutions to provide special education and related services to ...
s.
In adults,
anemia
Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, th ...
(macrocytic,
megaloblastic anemia) can be a sign of advanced folate deficiency.
Women with folate deficiency who become
pregnant
Pregnancy is the time during which one or more offspring develops (gestation, gestates) inside a woman, woman's uterus (womb). A multiple birth, multiple pregnancy involves more than one offspring, such as with twins.
Pregnancy usually occur ...
are more likely to give birth to
low birth weight
Low birth weight (LBW) is defined by the World Health Organization as a birth weight of an
infant of or less, regardless of gestational age. Infants born with LBW have added health risks which require close management, often in a neonatal intensi ...
premature
Premature may refer to:
* ''Premature'' (2014 film), an American comedy film
* ''Premature'' (2019 film), an American romantic drama film
* ''PREMature'', a 2015 British television drama miniseries
See also
* Premature aging, of an organism
* P ...
infants, and infants with
neural tube defects
Neural tube defects (NTDs) are a group of birth defects in which an opening in the Vertebral column, spine or cranium remains from early in human development. In the third week of pregnancy called gastrulation, specialized cells on the dorsal si ...
and even
spina bifida. In infants and children, folate deficiency can lead to
failure to thrive or slow growth rate,
diarrhea
Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin wi ...
,
oral ulcer
A mouth ulcer (aphtha) is an ulcer that occurs on the mucous membrane of the oral cavity. Mouth ulcers are very common, occurring in association with many diseases and by many different mechanisms, but usually there is no serious underlying cause ...
s,
megaloblastic anemia,
neurological deterioration
Cognitive deficit is an inclusive term to describe any characteristic that acts as a barrier to the cognition process.
The term may describe
* deficits in overall intelligence (as with intellectual disabilities),
* specific and restricted defici ...
. An
abnormally small head,
irritability,
developmental delay
Global developmental delay is an umbrella term used when children are significantly delayed in their cognitive and physical development. It can be diagnosed when a child is delayed in one or more milestones, categorised into motor skills, speech, c ...
,
seizures
An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or neural oscillation, synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much o ...
,
blindness
Visual impairment, also known as vision impairment, is a medical definition primarily measured based on an individual's better eye visual acuity; in the absence of treatment such as correctable eyewear, assistive devices, and medical treatment†...
and
cerebellar ataxia
Cerebellar ataxia is a form of ataxia originating in the cerebellum. Non-progressive congenital ataxia (NPCA) is a classical presentation of cerebral ataxias.
Cerebellar ataxia can occur as a result of many diseases and may present with symptoms ...
can also be observed.
Causes
A deficiency of
folate can occur when the body's need for folate is increased, when dietary intake or absorption of folate is inadequate, or when the body excretes (or loses) more folate than usual. Medications that interfere with the body's ability to use folate may also increase the need for this vitamin.
Some research indicates that exposure to
ultraviolet light
Ultraviolet (UV) is a form of electromagnetic radiation with wavelength from 10 nm (with a corresponding frequency around 30 PHz) to 400 nm (750 THz), shorter than that of visible light, but longer than X-rays. UV radiation i ...
, including the use of
tanning bed
Indoor tanning involves using a device that emits ultraviolet radiation to produce a cosmetic tan. Typically found in tanning salons, gyms, spas, hotels, and sporting facilities, and less often in private residences, the most common device is a ho ...
s, can lead to a folate deficiency. The deficiency is more common in pregnant women, infants, children, and adolescents. It may also be due to poor diet or a consequence of
alcoholism
Alcoholism is, broadly, any drinking of alcohol (drug), alcohol that results in significant Mental health, mental or physical health problems. Because there is disagreement on the definition of the word ''alcoholism'', it is not a recognize ...
.
Additionally, a defect in
homocysteine methyltransferase
Methionine synthase also known as MS, MeSe, MTR is responsible for the regeneration of methionine from homocysteine. In humans it is encoded by the ''MTR'' gene (5-methyltetrahydrofolate-homocysteine methyltransferase). Methionine synthase forms ...
or a deficiency of
vitamin B12 may lead to a so-called "methyl-trap" of
tetrahydrofolate (THF), in which THF is converted to a reservoir of methyl-THF which thereafter has no way of being metabolized, and serves as a sink of THF that causes a subsequent deficiency in folate.
Thus, a deficiency in B
12 can generate a large pool of methyl-THF that is unable to undergo reactions and will mimic folate deficiency.
Folate (pteroylmonoglutamate) is absorbed throughout the small intestine, though mainly in the
jejunum. Important steps in the absorption are reduction of the polyglutamate chain by pteroylpolyglutamate hydrolase (
gamma-glutamyl hydrolase) and then transport across the
brush border
A brush border (striated border or brush border membrane) is the microvilli-covered surface of simple cuboidal and simple columnar epithelium found in different parts of the body. Microvilli are approximately 100 nanometers in diameter and the ...
membrane by the
proton-coupled folate transporter (SLC46A1). Diffuse inflammatory or degenerative diseases of the small intestine, such as
Crohn disease
Crohn's disease is a type of inflammatory bowel disease (IBD) that may affect any segment of the gastrointestinal tract. Symptoms often include abdominal pain, diarrhea (which may be bloody if inflammation is severe), fever, abdominal distension ...
,
celiac disease, chronic enteritis or the presence of an entero-enteric fistula may reduce absorption.
Situational
Some situations that increase the need for folate include:
*
bleeding
*
kidney dialysis
Kidney dialysis (from Greek , , 'dissolution'; from , , 'through', and , , 'loosening or splitting') is the process of removing excess water, solutes, and toxins from the blood in people whose kidneys can no longer perform these functions natura ...
*
liver
The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...
disease
*
malabsorption, including
celiac disease and
fructose malabsorption
*
pregnancy
Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins.
Pregnancy usually occurs by sexual intercourse, but ca ...
and
lactation
Lactation describes the secretion of milk from the mammary glands and the period of time that a mother lactates to feed her young. The process naturally occurs with all sexually mature female mammals, although it may predate mammals. The proces ...
(breastfeeding)
*
tobacco smoking
Tobacco smoking is the practice of burning tobacco and ingesting the resulting smoke. The smoke may be inhaled, as is done with cigarettes, or simply released from the mouth, as is generally done with pipes and cigars. The practice is believed ...
* alcohol consumption
Medication
Medications can interfere with folate metabolism, including:
*
anticonvulsant
Anticonvulsants (also known as antiepileptic drugs or recently as antiseizure drugs) are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of b ...
medications (such as
phenytoin
Phenytoin (PHT), sold under the brand name Dilantin among others, is an anti-seizure medication. It is useful for the prevention of tonic-clonic seizures (also known as grand mal seizures) and focal seizures, but not absence seizures. The intr ...
,
primidone
Primidone, sold under various brand names, is a barbiturate medication that is used to treat partial and generalized seizures, as well as essential tremors. It is taken by mouth.
Common side effects include sleepiness, poor coordination, nause ...
,
carbamazepine or
valproate)
*
metformin (sometimes prescribed to control
blood sugar
Glycaemia, also known as blood sugar level, blood sugar concentration, or blood glucose level is the measure of glucose concentrated in the blood of humans or other animals. Approximately 4 grams of glucose, a simple sugar, is present in the blo ...
in
type 2 diabetes
Type 2 diabetes, formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent urination, ...
)
*
methotrexate
Methotrexate (MTX), formerly known as amethopterin, is a chemotherapy agent and immune-system suppressant. It is used to treat cancer, autoimmune diseases, and ectopic pregnancies. Types of cancers it is used for include breast cancer, leuke ...
, an anti-cancer drug also used to control inflammation associated with Crohn disease, ulcerative colitis and rheumatoid arthritis.
*
5-fluorouracil
Fluorouracil (5-FU), sold under the brand name Adrucil among others, is a cytotoxic chemotherapy medication used to treat cancer. By intravenous injection it is used for treatment of colorectal cancer, oesophageal cancer, stomach cancer, pancrea ...
*
hydroxyurea
Hydroxycarbamide, also known as hydroxyurea, is a medication used in sickle-cell disease, essential thrombocythemia, chronic myelogenous leukemia, polycythemia vera, and cervical cancer. In sickle-cell disease it increases fetal hemoglobin and ...
*
trimethoprim
*
sulfasalazine (used to control inflammation associated with
Crohn disease
Crohn's disease is a type of inflammatory bowel disease (IBD) that may affect any segment of the gastrointestinal tract. Symptoms often include abdominal pain, diarrhea (which may be bloody if inflammation is severe), fever, abdominal distension ...
,
ulcerative colitis and
rheumatoid arthritis
Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and hands are involv ...
)
*
triamterene (a
diuretic
A diuretic () is any substance that promotes diuresis, the increased production of urine. This includes forced diuresis. A diuretic tablet is sometimes colloquially called a water tablet. There are several categories of diuretics. All diuretics in ...
)
*
birth control pills Oral contraceptives, abbreviated OCPs, also known as birth control pills, are medications taken by mouth for the purpose of birth control.
Female
Two types of female oral contraceptive pill, taken once per day, are widely available:
* The combin ...
(also related to the duration use of birth control pills) may reduce serum folate levels but without inducing clinically significant folate deficiency.
When
methotrexate
Methotrexate (MTX), formerly known as amethopterin, is a chemotherapy agent and immune-system suppressant. It is used to treat cancer, autoimmune diseases, and ectopic pregnancies. Types of cancers it is used for include breast cancer, leuke ...
is prescribed, folic acid supplements are sometimes given with the methotrexate. The therapeutic effects of
methotrexate
Methotrexate (MTX), formerly known as amethopterin, is a chemotherapy agent and immune-system suppressant. It is used to treat cancer, autoimmune diseases, and ectopic pregnancies. Types of cancers it is used for include breast cancer, leuke ...
are due to its inhibition of
dihydrofolate reductase
Dihydrofolate reductase, or DHFR, is an enzyme that reduces dihydrofolic acid to tetrahydrofolic acid, using NADPH as an electron donor, which can be converted to the kinds of tetrahydrofolate cofactors used in 1-carbon transfer chemistry. In ...
and thereby reduce the rate ''
de novo''
purine
Purine is a heterocyclic compound, heterocyclic aromatic organic compound that consists of two rings (pyrimidine and imidazole) fused together. It is water-soluble. Purine also gives its name to the wider class of molecules, purines, which includ ...
and
pyrimidine
Pyrimidine (; ) is an aromatic, heterocyclic, organic compound similar to pyridine (). One of the three diazines (six-membered heterocyclics with two nitrogen atoms in the ring), it has nitrogen atoms at positions 1 and 3 in the ring. The other ...
synthesis and cell division. Methotrexate inhibits cell division and is particularly toxic to fast dividing cells, such as rapidly dividing cancer cells and the progenitor cells of the immune system. Folate supplementation is beneficial in patients being treated with long-term, low-dose methotrexate for inflammatory conditions, such as rheumatoid arthritis (RA) or
psoriasis
Psoriasis is a long-lasting, noncontagious autoimmune disease characterized by raised areas of abnormal skin. These areas are red, pink, or purple, dry, itchy, and scaly. Psoriasis varies in severity from small, localized patches to complete ...
, to avoid macrocytic anemia caused by folate deficiency. Folate is often also supplemented before some high dose chemotherapy treatments in an effort to protect healthy tissue. However, it may be counterproductive to take a folic acid supplement with methotrexate in cancer treatment.
Cerebral folate deficiency
Cerebral folate deficiency is when levels of 5-methyltetrahydrofolate are low in the brain as measured in the
cerebral spinal fluid
Cerebrospinal fluid (CSF) is a clear, colorless body fluid found within the tissue that surrounds the brain and spinal cord of all vertebrates.
CSF is produced by specialised ependymal cells in the choroid plexus of the ventricles of the bra ...
despite being normal in the blood.
Symptoms typically appear at about five months of age. Without treatment there may be poor muscle tone, trouble with coordination, trouble talking, and
seizures
An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or neural oscillation, synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much o ...
.
[ The causes of cerebral folate deficiency include mutations of ]gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
s responsible for folate metabolism and transport. Mutations of the SLC46A1
The proton-coupled folate transporter is a protein that in humans is encoded by the ''SLC46A1'' gene. The major physiological roles of PCFTs are in mediating the intestinal absorption of folate (Vitamin B9), and its delivery to the central nervous ...
gene that encodes the proton-coupled folate transporter (PCFT) result in CFD syndromes with both systemic folate deficiency and cerebral folate deficiency. Even when the systemic deficiency is corrected by folate, the cerebral deficiency remains and must be treated with folinic acid
Folinic acid, also known as leucovorin, is a medication used to decrease the toxic effects of methotrexate and pyrimethamine. It is also used in combination with 5-fluorouracil to treat colorectal cancer and pancreatic cancer, may be used to tr ...
.
Pregnancy
Folate deficiency can occur during pregnancy
Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins.
Pregnancy usually occurs by sexual intercourse, but ca ...
as a result of the increasing number of cells of the growing fetus
A fetus or foetus (; plural fetuses, feti, foetuses, or foeti) is the unborn offspring that develops from an animal embryo. Following embryonic development the fetal stage of development takes place. In human prenatal development, fetal deve ...
, decreased absorption and intake of folate, maternal hormones that mediate its metabolism, vascular circulation of maternal and fetal blood and an increasing amount of blood resulting in dilution.[ Sickle cell anemia and living in areas of malaria result in even higher folate needs for women who are pregnant.][ When supplemented with 450 micrograms of folic acid per day, the risk of developing birth defects, specifically neural tube defects, is decreased.][ Supplementation to prevent birth defects is most effective one month prior to and during the first twelve weeks of pregnancy.][ Utilization of folic acid supplementation before conception has shown to result in a decrease in neural tube defects by 70%.]
Diagnosis
Folate deficiency is diagnosed with a blood test to measure the serum level of folate, measured as methyltetrahydrofolate
Levomefolic acid (INN, also known as L-5-MTHF, L-methylfolate and L-5-methyltetrahydrofolate and (6''S'')-5-methyltetrahydrofolate, and (6''S'')-5-MTHF) is the primary biologically active form of folate used at the cellular level for DNA reprodu ...
(in practice, "folate" refers to all derivatives of folic acid, but methylhydrofolate is the quasi unique form of "folate" in the blood).
Homocysteine is elevated (5-MTHF
Levomefolic acid (INN, also known as L-5-MTHF, L-methylfolate and L-5-methyltetrahydrofolate and (6''S'')-5-methyltetrahydrofolate, and (6''S'')-5-MTHF) is the primary biologically active form of folate used at the cellular level for DNA reprodu ...
is used to convert homocysteine to methionine
Methionine (symbol Met or M) () is an essential amino acid in humans. As the precursor of other amino acids such as cysteine and taurine, versatile compounds such as SAM-e, and the important antioxidant glutathione, methionine plays a critical ro ...
) as in vitamin B12 deficiency
A vitamin is an organic molecule (or a set of molecules closely related chemically, i.e. vitamers) that is an essential micronutrient that an organism needs in small quantities for the proper functioning of its metabolism. Essential nutrien ...
, whereas methylmalonic acid
Methylmalonic acid (MMA) (conjugate base methylmalonate) is a dicarboxylic acid that is a ''C''-methylated derivative of malonate.
The coenzyme A linked form of methylmalonic acid, methylmalonyl-CoA, is converted into succinyl-CoA by methylmalonyl ...
is normal (elevated in vitamin B12 deficiency).
More specifically, according to a 2014 UK guideline,
* A serum folate level of less than 7 nmol/L (3 μg/L) is indicative of folate deficiency;
* Red blood cell folate testing is not routinely performed, since serum folate is sufficient in most cases, however, if there is a strong suspicion of folate deficiency despite a normal serum folate level, a red cell folate test may be performed.
* Plasma total homocysteine is only measured in special circumstances. A level above 15 μmol/L could be indicative of a folate deficiency, but local reference ranges should be taken into account.
Prevention and treatment
Diet
Folate is acquired in the diet by the consumption of leafy green vegetables, legumes and organ meats. When cooking, use of steaming
Steaming is a method of cooking using steam. This is often done with a food steamer, a kitchen appliance made specifically to cook food with steam, but food can also be steamed in a wok. In the American southwest, steam pits used for cooking ha ...
, a food steamer
A food steamer or steam cooker is a small kitchen appliance used to cook or prepare various foods with steam heat by means of holding the food in a closed vessel reducing steam escape. This manner of cooking is called steaming.
History
F ...
, or a microwave oven
A microwave oven (commonly referred to as a microwave) is an electric oven that heats and cooks food by exposing it to electromagnetic radiation in the microwave frequency range. This induces polar molecules in the food to rotate and produce t ...
can help keep more folate content in the cooked foods.
Supplementation
Folic acid is a synthetic derivative of folate and is acquired by dietary supplementation. Multi-vitamin dietary supplements contain folic acid as well as other B vitamins. Non-prescription folic acid is available as a dietary supplement in some countries, and some countries require the fortification of wheat flour, corn meal or rice with folic acid with the intention of promoting public health through increasing blood folate levels in the population.
Fortification
After the discovery of the link between insufficient folic acid and neural tube defects
Neural tube defects (NTDs) are a group of birth defects in which an opening in the Vertebral column, spine or cranium remains from early in human development. In the third week of pregnancy called gastrulation, specialized cells on the dorsal si ...
, governments and health organizations worldwide made recommendations concerning folic acid supplementation for women intending to become pregnant. Because the neural tube closes in the first four weeks of gestation, often before many women even know they are pregnant, many countries in time decided to implement mandatory food fortification programs. A meta-analysis of global birth prevalence of spina bifida showed that when mandatory fortification was compared to countries with healthcare professionals advising women but no mandatory fortification program, there was a 30% reduction in live births with spina bifida, with some countries reported a greater than 50% reduction.[
Over 80 countries require folic acid fortification in some foods.][ Fortification of ]rice
Rice is the seed of the grass species ''Oryza sativa'' (Asian rice) or less commonly ''Oryza glaberrima
''Oryza glaberrima'', commonly known as African rice, is one of the two domesticated rice species. It was first domesticated and grown i ...
is common. The USDA
The United States Department of Agriculture (USDA) is the federal executive department responsible for developing and executing federal laws related to farming, forestry, rural economic development, and food. It aims to meet the needs of com ...
has required the fortification of flour
Flour is a powder made by grinding raw grains, roots, beans, nuts, or seeds. Flours are used to make many different foods. Cereal flour, particularly wheat flour, is the main ingredient of bread, which is a staple food for many culture ...
since 1998.[ Since then, Hispanics in the United States have seen the greatest reduction of neural tube defects.][ Canada has mandated folic acid fortification of flour since 1998 which has resulted in a 42% decrease in neural tube defects.] Fortification of wheat
Wheat is a grass widely cultivated for its seed, a cereal grain that is a worldwide staple food. The many species of wheat together make up the genus ''Triticum'' ; the most widely grown is common wheat (''T. aestivum''). The archaeologi ...
and corn
Maize ( ; ''Zea mays'' subsp. ''mays'', from es, maÃz after tnq, mahiz), also known as corn (North American and Australian English), is a cereal grain first domesticated by indigenous peoples in southern Mexico about 10,000 years ago. Th ...
flour, milk
Milk is a white liquid food produced by the mammary glands of mammals. It is the primary source of nutrition for young mammals (including breastfed human infants) before they are able to digestion, digest solid food. Immune factors and immune ...
and rice is required in Costa Rica
Costa Rica (, ; ; literally "Rich Coast"), officially the Republic of Costa Rica ( es, República de Costa Rica), is a country in the Central American region of North America, bordered by Nicaragua to the north, the Caribbean Sea to the no ...
which has led to a reduction of neural tube defects of as much as 60%.[
]
Epidemiology
Folate deficiency is very rare in countries with folic acid fortification programs. Overall, the worldwide prevalence of anemia due to folic acid deficiency is very low. However, data on the prevalence of deficiency amongst specific high risk groups is lacking.
Research
Folate deficiency during gestation or infancy due to development by the fetus or infant of autoantibodies
An autoantibody is an antibody (a type of protein) produced by the immune system that is directed against one or more of the individual's own proteins. Many autoimmune diseases (notably lupus erythematosus) are associated with such antibodies.
Pr ...
to the folate receptor
Folate receptors bind folate and reduced folic acid derivatives and mediates delivery of tetrahydrofolate to the interior of cells. It is then converted from monoglutamate to polyglutamate forms - such as 5-methyltetrahydrofolate - as only monog ...
might result in various developmental disorders
Developmental disorders comprise a group of psychiatric conditions originating in childhood that involve serious impairment in different areas. There are several ways of using this term. The most narrow concept is used in the category "Specific Di ...
.
Studies suggest that insufficient folate and vitamin B12 status may contribute to major depressive disorder
Major depressive disorder (MDD), also known as clinical depression, is a mental disorder characterized by at least two weeks of pervasive low mood, low self-esteem, and loss of interest or pleasure in normally enjoyable activities. Introdu ...
and that supplementation might be useful in this condition.
The role of vitamin B12 and folate in depression is due to their role in transmethylation
Transmethylation is a biologically important organic chemical reaction in which a methyl group is transferred from one compound to another.
An example of transmethylation is the recovery of methionine from homocysteine. In order to sustain suffic ...
reactions, which are crucial for the formation of neurotransmitters (e.g. serotonin
Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and vas ...
, epinephrine
Adrenaline, also known as epinephrine, is a hormone and medication which is involved in regulating visceral functions (e.g., respiration). It appears as a white microcrystalline granule. Adrenaline is normally produced by the adrenal glands and ...
, nicotinamide
Niacinamide or Nicotinamide (NAM) is a form of vitamin B3 found in food and used as a dietary supplement and medication. As a supplement, it is used by mouth to prevent and treat pellagra (niacin deficiency). While nicotinic acid (niacin) may ...
s, purines, phospholipids
Phospholipids, are a class of lipids whose molecule has a hydrophilic "head" containing a phosphate group and two hydrophobic "tails" derived from fatty acids, joined by an alcohol residue (usually a glycerol molecule). Marine phospholipids typ ...
). The proposed mechanism, is that low levels of folate or vitamin B12 can disrupt transmethylation reaction, leading to an accumulation of homocysteine (hyperhomocysteinemia) and to impaired metabolism of neurotransmitters (especially the hydroxylation of dopamine
Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic compound, organic chemical of the catecholamine and phenethylamine families. Dopamine const ...
and serotonin
Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and vas ...
from tyrosine
-Tyrosine or tyrosine (symbol Tyr or Y) or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a non-essential amino acid with a polar side group. The word "tyrosine" is from the Gr ...
and tryptophan
Tryptophan (symbol Trp or W)
is an α-amino acid that is used in the biosynthesis of proteins. Tryptophan contains an α-amino group, an α- carboxylic acid group, and a side chain indole, making it a polar molecule with a non-polar aromatic ...
), phospholipids, myelin
Myelin is a lipid-rich material that surrounds nerve cell axons (the nervous system's "wires") to insulate them and increase the rate at which electrical impulses (called action potentials) are passed along the axon. The myelinated axon can be ...
, and receptors. High homocysteine levels in the blood can lead to vascular injuries by oxidative mechanisms which can contribute to cerebral dysfunction. All of these can lead to the development of various disorders, including depression.
References
External links
{{DEFAULTSORT:Folate Deficiency
Vitamin deficiencies
Nutritional anemias