Folate deficiency symptoms
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Symptoms of Folate Deficiency: A Comprehensive Overview
Hematological Symptoms: Megaloblastic Anemia
Folate deficiency is traditionally associated with megaloblastic macrocytic anemia, a condition characterized by the presence of abnormally large red blood cells due to impaired DNA synthesis in rapidly dividing bone marrow cells2. This condition can also affect other rapidly dividing cells, such as those in the gastrointestinal tract, leading to malabsorption issues2.
Neuropsychiatric Symptoms: Depression and Cognitive Impairment
Recent studies have expanded the understanding of folate deficiency to include significant neuropsychiatric symptoms. Common manifestations include mild depression, fatigue, and abnormal intellectual functioning, which can occur even in the absence of severe hematological changes1. Folate deficiency is frequently observed in patients with depressive disorders, including those with primary endogenous or non-endogenous depression, and in individuals with conditions such as alcoholism and anorexia7. The deficiency may interfere with methylation and hydroxylation processes, potentially aggravating psychiatric disturbances7.
Neurological Symptoms: Neuropathy and Cerebral Folate Deficiency
Folate deficiency can also lead to neuropathy, characterized by slowly progressive polyneuropathy with predominant involvement of the lower extremities. This condition tends to manifest as sensory rather than motor neuropathy, with predominant deep sensory loss3. Additionally, cerebral folate deficiency (CFD) is a specific condition where low levels of 5-methyltetrahydrofolate in the cerebrospinal fluid lead to symptoms such as delayed development, hypotonia, ataxia, and in severe cases, dyskinesias, spasticity, and epilepsy4 5.
Cardiovascular Symptoms: Hyperhomocysteinemia
Folate deficiency is linked to elevated levels of homocysteine, a risk factor for occlusive vascular disease and thrombosis2. This condition, known as hyperhomocysteinemia, increases the predisposition to cardiovascular diseases and is a significant non-hematological manifestation of folate deficiency2.
Immunological and Oncological Symptoms
There is evidence suggesting that folate deficiency may interfere with immunologic status and increase the predisposition to neoplasia2. This highlights the broader implications of folate deficiency beyond its traditional hematological and neurological impacts.
Pregnancy-Related Symptoms: HELLP Syndrome Mimicry
In pregnancy, severe folate deficiency can mimic the syndrome of hemolysis, elevated liver enzymes, and low platelets (HELLP), leading to complications such as hemolytic anemia, thrombocytopenia, and coagulopathy6. Proper diagnosis and treatment of folate deficiency in pregnant women are crucial to avoid unnecessary preterm deliveries and other complications6.
Conclusion
Folate deficiency presents a wide array of symptoms affecting various bodily systems. While traditionally associated with megaloblastic anemia, it is now recognized to cause significant neuropsychiatric, neurological, cardiovascular, immunological, and pregnancy-related symptoms. Early diagnosis and appropriate folate supplementation are essential to mitigate these diverse and potentially severe manifestations.
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Most relevant research papers on this topic
Folate deficiency and decreased brain 5-hydroxytryptamine synthesis in man and rat
Folate deficiency and oversupplementation are associated with decreased brain 5-hydroxytryptamine synthesis, leading to neuropsychiatrie symptoms in both humans and rats.
Non-RCT
Highly CitedFolate deficiency beyond megaloblastic anemia: hyperhomocysteinemia and other manifestations of dysfunctional folate status.
Folate deficiency can lead to increased risk of vascular disease, mood disturbances, and even spinal cord syndromes, as well as disrupting immune function and increasing the risk of neoplasia.
Highly CitedClinicopathologic features of folate-deficiency neuropathy
Folate-deficiency neuropathy is a slowly progressive, sensory-dominant condition with different clinical features than thiamine-deficiency neuropathy.
Rigorous JournalCerebral folate deficiency
Cerebral folate deficiency (CFD) is a rare condition in children, with symptoms onset at around 4 to 6 months of age and affecting delayed development, hypotonia, ataxia, dyskinesias, spasticity, speech difficulties, and epilepsy.
Cerebral folate deficiency
Cerebral folate deficiency (CFD) is a neurological syndrome characterized by low cerebrospinal fluid concentration of 5-methyltetrahydrofolate (5MTHF) in the presence of normal peripheral folate status.
SEVERE FOLATE DEFICIENCY MASQUERADING AS THE SYNDROME OF HEMOLYSIS, ELEVATED LIVER ENZYMES, AND LOW PLATELETS
Folate deficiency in pregnancy can mimic HELLP syndrome, leading to preterm delivery, and supplementation during pregnancy can help prevent complications.
Case ReportThe biology of folate in depression: implications for nutritional hypotheses of the psychoses.
Folate deficiency, along with other nutritional factors like vitamins B6, B12, and C, may predispose to or aggravate psychiatric disturbances, particularly depression.
Highly CitedMetabolic evidence of vitamin B-12 deficiency, including high homocysteine and methylmalonic acid and low holotranscobalamin, is more pronounced in older adults with elevated plasma folate.
Low vitamin B-12 is associated with more pronounced metabolic evidence of vitamin B-12 deficiency in older adults with elevated folate levels.
Observational Study
Very Rigorous JournalHighly CitedVitamin B12-folate interrelationships.
Vitamin B12 deficiency can lead to a functional folate deficiency, which in turn is induced by cobalamin deprivation, through the methyl trap hypothesis.
Literature ReviewHighly CitedFolic acid with or without vitamin B12 for cognition and dementia.
Folic acid supplementation, with or without vitamin B12, may improve cognitive function in elderly individuals at risk of cognitive decline or dementia.
Systematic ReviewHighly Cited