Folate deficiency
Encyclopedia
Folate deficiency is a lack of folic acid
in the diet and the signs are often subtle. Folate deficiency anemia is the medical name given for the condition.
can occur. Additional signs are weakness
, sore tongue, headache
s, heart palpitation
s, irritability
, and behavioral disorders.
Women with folate deficiency who become pregnant are more likely to give birth to low birth weight
and premature
infants, and infants with neural tube defects
. In adults, anemia
(macrocytic, megaloblastic anemia
) can be a sign of advanced folate deficiency. In infants and children, folate deficiency can slow growth rate.
Late studies suggested an involvement in tumorogenesis (especially in colon) through demethylation/hypomethylation of fast replicating tissues.
Some of the symptoms can also result from a variety of medical conditions other than folate deficiency. It is important to have a physician
evaluate these symptoms so that appropriate medical care can be given.
status may play a role in depression.
The role of vitamin B12 and folate in depression is due to their role in transmethylation
reactions, which are crucial for the formation of neurotransmitters (e.g. serotonin
, epinephrine
, nicotinamides, purines, phospholipids).
Low levels of folate or vitamin B12 can disrupt transmethylation reaction, leading to an accumulation of homocysteine
(hyperhomocisteinemia) and to impaired metabolism of neurotransmitters (especially the hydroxylation of dopamine
and serotonin
from tyrosine
and tryptophan
), phospholipids, myelin, and receptors. Hyperhomocysteinemia could also 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.
Low plasma B12 and low plasma folate has been found in studies of depressive patients. Furthermore, some studies have shown that low folate levels are linked to a poor response of antidepressant treatment, and other studies also suggest that a high vitamin B12 status may be associated with better treatment outcomes.
Therefore, not only does adequate consumption of these two vitamins help decrease the risks of developing depression, but they can also help in the treatment of depression when antidepressant drugs are used.
When sulfasalazine is prescribed, folic acid supplements are normally given with the sulfasalazine. The purpose of methotrexate
is to inhibit dihydrofolate reductase
and thereby reduce the rate de novo
purine
and pyrimidine
synthesis and cell division. It may therefore be counter-productive to take a folic acid supplement with methotrexate. Although the folic acid inhibition of sulfasalazine is normally seen as a side effect, it is possible that it is a part of the therapeutic effect of the drug, given that methotrexate, a frank folic acid inhibitor, is often given if sulfasalazine fails. It would therefore be wise to consult with a physician before taking a folic acid supplement along with sulfasalazine or methotrexate.
or of a food steamer
can help keep more folate content in the cooked foods, thus helping to prevent folate deficiency (see USDA reference in the steaming
article).
Folate deficiency during human pregnancy has been associated with an increased risk of infant neural tube defects. Such deficiency during the first four weeks of gestation can result in structural and developmental problems. NIH guidelines recommend oral B vitamin supplements to decrease these risks near the time of conception and during the first month of pregnancy.
Folic acid
Folic acid and folate , as well as pteroyl-L-glutamic acid, pteroyl-L-glutamate, and pteroylmonoglutamic acid are forms of the water-soluble vitamin B9...
in the diet and the signs are often subtle. Folate deficiency anemia is the medical name given for the condition.
Symptoms
Loss of appetite, and weight lossWeight loss
Weight loss, in the context of medicine, health or physical fitness, is a reduction of the total body mass, due to a mean loss of fluid, body fat or adipose tissue and/or lean mass, namely bone mineral deposits, muscle, tendon and other connective tissue...
can occur. Additional signs are weakness
Weakness
Weakness is a symptom represented, medically, by a number of different conditions, including: lack of muscle strength, malaise, dizziness, or fatigue. 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...
, sore tongue, headache
Headache
A headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...
s, heart palpitation
Palpitation
A palpitation is an abnormality of heartbeat that causes a conscious awareness of its beating, whether it is too slow, too fast, irregular, or at its normal frequency. The word may also refer to this sensation itself...
s, irritability
Irritability
Irritability is an excessive response to stimuli. The term is used for both the physiological reaction to stimuli and for the pathological, abnormal or excessive sensitivity to stimuli; It is usually used to refer to anger or frustration....
, and behavioral disorders.
Women with folate deficiency who become pregnant are more likely to give birth to low birth weight
Low birth weight
Low birth weight is defined as a birth weight of a liveborn infant of less than 2,500 g. regardless of gestational age-Causes:LBW is either the result of preterm birth or of the infant being small for gestational age , or a combination of...
and premature
Premature birth
In humans preterm birth refers to the birth of a baby of less than 37 weeks gestational age. The cause for preterm birth is in many situations elusive and unknown; many factors appear to be associated with the development of preterm birth, making the reduction of preterm birth a challenging...
infants, and infants with neural tube defects
Neural tube defects
Neural tube defects are one of the most common birth defects, occurring in approximately one in 1,000 live births in the United States. An NTD is an opening in the spinal cord or brain that occurs very early in human development. In the 2nd week of pregnancy called gastrulation, specialized cells...
. In adults, anemia
Anemia
Anemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...
(macrocytic, megaloblastic anemia
Megaloblastic anemia
Megaloblastic anemia is an anemia that results from inhibition of DNA synthesis in red blood cell production. When DNA synthesis is impaired, the cell cycle cannot progress from the G2 growth stage to the mitosis stage...
) can be a sign of advanced folate deficiency. In infants and children, folate deficiency can slow growth rate.
Late studies suggested an involvement in tumorogenesis (especially in colon) through demethylation/hypomethylation of fast replicating tissues.
Some of the symptoms can also result from a variety of medical conditions other than folate deficiency. It is important to have a physician
Physician
A physician is a health care provider who practices the profession of medicine, which is concerned with promoting, maintaining or restoring human health through the study, diagnosis, and treatment of disease, injury and other physical and mental impairments...
evaluate these symptoms so that appropriate medical care can be given.
Depression
Studies suggest that folate and vitamin B12Vitamin B12
Vitamin B12, vitamin B12 or vitamin B-12, also called cobalamin, is a water-soluble vitamin with a key role in the normal functioning of the brain and nervous system, and for the formation of blood. It is one of the eight B vitamins...
status may play a role in depression.
The role of vitamin B12 and folate in depression is due to their role in transmethylation
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 sufficient reaction rates during metabolic stress, this...
reactions, which are crucial for the formation of neurotransmitters (e.g. serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...
, epinephrine
Epinephrine
Epinephrine is a hormone and a neurotransmitter. It increases heart rate, constricts blood vessels, dilates air passages and participates in the fight-or-flight response of the sympathetic nervous system. In chemical terms, adrenaline is one of a group of monoamines called the catecholamines...
, nicotinamides, purines, phospholipids).
Low levels of folate or vitamin B12 can disrupt transmethylation reaction, leading to an accumulation of homocysteine
Homocysteine
Homocysteine is a non-protein amino acid with the formula HSCH2CH2CHCO2H. It is a homologue of the amino acid cysteine, differing by an additional methylene group. It is biosynthesized from methionine by the removal of its terminal Cε methyl group...
(hyperhomocisteinemia) and to impaired metabolism of neurotransmitters (especially the hydroxylation of dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
and serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...
from tyrosine
Tyrosine
Tyrosine or 4-hydroxyphenylalanine, is one of the 22 amino acids that are used by cells to synthesize proteins. Its codons are UAC and UAU. It is a non-essential amino acid with a polar side group...
and tryptophan
Tryptophan
Tryptophan is one of the 20 standard amino acids, as well as an essential amino acid in the human diet. It is encoded in the standard genetic code as the codon UGG...
), phospholipids, myelin, and receptors. Hyperhomocysteinemia could also 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.
Low plasma B12 and low plasma folate has been found in studies of depressive patients. Furthermore, some studies have shown that low folate levels are linked to a poor response of antidepressant treatment, and other studies also suggest that a high vitamin B12 status may be associated with better treatment outcomes.
Therefore, not only does adequate consumption of these two vitamins help decrease the risks of developing depression, but they can also help in the treatment of depression when antidepressant drugs are used.
Causes
A deficiency of folate can occur when the body's need for folate is increased, when dietary intake 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, including the use of tanning beds, can lead to a folic acid deficiency. http://www.americanpregnancy.org/pregnancyhealth/tanningmethods.htmlSituational
Some situations that increase the need for folate include:- certain anemiaAnemiaAnemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...
s - kidney dialysis
- liverLiverThe liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
disease - malabsorptionMalabsorptionMalabsorption is a state arising from abnormality in absorption of food nutrients across the gastrointestinal tract.Impairment can be of single or multiple nutrients depending on the abnormality...
, including celiac disease - pregnancyPregnancyPregnancy refers to the fertilization and development of one or more offspring, known as a fetus or embryo, in a woman's uterus. In a pregnancy, there can be multiple gestations, as in the case of twins or triplets...
and lactationBreastfeedingBreastfeeding is the feeding of an infant or young child with breast milk directly from female human breasts rather than from a baby bottle or other container. Babies have a sucking reflex that enables them to suck and swallow milk. It is recommended that mothers breastfeed for six months or...
(breastfeeding) - tobacco smokingTobacco smokingTobacco smoking is the practice where tobacco is burned and the resulting smoke is inhaled. The practice may have begun as early as 5000–3000 BCE. Tobacco was introduced to Eurasia in the late 16th century where it followed common trade routes...
Pharmacological
Medications can interfere with folate utilization, including:- anticonvulsantAnticonvulsantThe anticonvulsants are a diverse group of pharmaceuticals used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of bipolar disorder, since many seem to act as mood stabilizers, and in the treatment of neuropathic pain. The goal of an...
medications (such as phenytoinPhenytoinPhenytoin sodium is a commonly used antiepileptic. Phenytoin acts to suppress the abnormal brain activity seen in seizure by reducing electrical conductance among brain cells by stabilizing the inactive state of voltage-gated sodium channels...
, and primidonePrimidonePrimidone is an anticonvulsant of the pyrimidinedione class, the active metabolites of which, phenobarbital and phenylethylmalonamide , are also anticonvulsants...
) - metforminMetforminMetformin is an oral antidiabetic drug in the biguanide class. It is the first-line drug of choice for the treatment of type 2 diabetes, in particular, in overweight and obese people and those with normal kidney function. Its use in gestational diabetes has been limited by safety concerns...
(sometimes prescribed to control blood sugarGlucoseGlucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...
in type 2 diabetes) - methotrexateMethotrexateMethotrexate , abbreviated MTX and formerly known as amethopterin, is an antimetabolite and antifolate drug. It is used in treatment of cancer, autoimmune diseases, ectopic pregnancy, and for the induction of medical abortions. It acts by inhibiting the metabolism of folic acid. Methotrexate...
, an anti-cancer drug also used to control inflammation associated with Crohn's disease, ulcerative colitis and rheumatoid arthritis. - sulfasalazine (used to control inflammation associated with Crohn's diseaseCrohn's diseaseCrohn's disease, also known as regional enteritis, is a type of inflammatory bowel disease that may affect any part of the gastrointestinal tract from mouth to anus, causing a wide variety of symptoms...
, ulcerative colitisUlcerative colitisUlcerative colitis is a form of inflammatory bowel disease . Ulcerative colitis is a form of colitis, a disease of the colon , that includes characteristic ulcers, or open sores. The main symptom of active disease is usually constant diarrhea mixed with blood, of gradual onset...
and rheumatoid arthritisRheumatoid arthritisRheumatoid arthritis is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. The process produces an inflammatory response of the synovium secondary to hyperplasia of synovial cells, excess synovial fluid, and the development...
) - triamterene (a diureticDiureticA diuretic provides a means of forced diuresis which elevates the rate of urination. There are several categories of diuretics. All diuretics increase the excretion of water from bodies, although each class does so in a distinct way.- Medical uses :...
)
When sulfasalazine is prescribed, folic acid supplements are normally given with the sulfasalazine. The purpose of methotrexate
Methotrexate
Methotrexate , abbreviated MTX and formerly known as amethopterin, is an antimetabolite and antifolate drug. It is used in treatment of cancer, autoimmune diseases, ectopic pregnancy, and for the induction of medical abortions. It acts by inhibiting the metabolism of folic acid. Methotrexate...
is to inhibit dihydrofolate reductase
Dihydrofolate reductase
- Function :Dihydrofolate reductase converts dihydrofolate into tetrahydrofolate, a methyl group shuttle required for the de novo synthesis of purines, thymidylic acid, and certain amino acids...
and thereby reduce the rate de novo
De novo synthesis
De novo synthesis refers to the synthesis of complex molecules from simple molecules such as sugars or amino acids, as opposed to their being recycled after partial degradation. For example, nucleotides are not needed in the diet as they can be constructed from small precursor molecules such as...
purine
Purine
A purine is a heterocyclic aromatic organic compound, consisting of a pyrimidine ring fused to an imidazole ring. Purines, including substituted purines and their tautomers, are the most widely distributed kind of nitrogen-containing heterocycle in nature....
and pyrimidine
Pyrimidine
Pyrimidine is a heterocyclic aromatic organic compound similar to benzene and pyridine, containing two nitrogen atoms at positions 1 and 3 of the six-member ring...
synthesis and cell division. It may therefore be counter-productive to take a folic acid supplement with methotrexate. Although the folic acid inhibition of sulfasalazine is normally seen as a side effect, it is possible that it is a part of the therapeutic effect of the drug, given that methotrexate, a frank folic acid inhibitor, is often given if sulfasalazine fails. It would therefore be wise to consult with a physician before taking a folic acid supplement along with sulfasalazine or methotrexate.
Prevention and treatment
When cooking, use of steamingSteaming
Steaming is a method of cooking using steam. Steaming is considered a healthy cooking technique and capable of cooking almost all kinds of food.-Method:...
or of a food steamer
Food steamer
A food steamer or steam cooker is a kitchen appliance used to prepare various foods in a sealed vessel that limits the escape of air or liquids below a preset pressure.-Advantages:...
can help keep more folate content in the cooked foods, thus helping to prevent folate deficiency (see USDA reference in the steaming
Steaming
Steaming is a method of cooking using steam. Steaming is considered a healthy cooking technique and capable of cooking almost all kinds of food.-Method:...
article).
Folate deficiency during human pregnancy has been associated with an increased risk of infant neural tube defects. Such deficiency during the first four weeks of gestation can result in structural and developmental problems. NIH guidelines recommend oral B vitamin supplements to decrease these risks near the time of conception and during the first month of pregnancy.