Folate is found in leafy green vegetables. Multi-vitamins also tend to include Folate as well as many other B vitamins. B vitamins, such as Folate, are water-soluble and excess is excreted in the urine.

When cooking, use of steaming, a food steamer, or a microwave oven can help keep more folate content in the cooked foods, thus helping to prevent folate deficiency.

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.

Medications can interfere with folate utilization, including:

- anticonvulsant medications (such as phenytoin, primidone, carbamazepine or valproate )

- metformin (sometimes prescribed to control blood sugar in type 2 diabetes)

- 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 disease, ulcerative colitis and rheumatoid arthritis)

- triamterene (a diuretic)

- birth control pills

When methotrexate is prescribed, folic acid supplements are sometimes given with the methotrexate. The therapeutic effects of methotrexate are due to its inhibition of dihydrofolate reductase and thereby reduce the rate "de novo" purine and pyrimidine 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, 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.

B can be supplemented by pill or injection and appear to be equally effective in those with low levels due to absorption problems.

When large doses are given by mouth its absorption does not rely on the presence of intrinsic factor or an intact ileum. Generally 1 to 2 mg daily is required as a large dose. Even pernicious anemia can be treated entirely by the oral route. These supplements carry such large doses of the vitamin that 1% to 5% of high oral doses of free crystalline B is absorbed along the entire intestine by passive diffusion.

Very high doses of B over many years has been linked to an increase in lung cancer risk in male smokers.

The National Institutes of Health has found that "Large amounts of folic acid can mask the damaging effects of vitamin B deficiency by correcting the megaloblastic anemia caused by vitamin B deficiency without correcting the neurological damage that also occurs", there are also indications that "high serum folate levels might not only mask vitamin B deficiency, but could also exacerbate the anemia and worsen the cognitive symptoms associated with vitamin B deficiency". Due to the fact that in the United States legislation has required enriched flour to contain folic acid to reduce cases of fetal neural-tube defects, consumers may be ingesting more than they realize. To counter the masking effect of B deficiency the NIH recommends "folic acid intake from fortified food and supplements should not exceed 1,000 μg daily in healthy adults." Most importantly, B deficiency needs to be treated with B repletion. Limiting folic acid will not counter the irrevocable neurological damage that is caused by untreated B deficiency.

Treatment involves a diet which includes an adequate amount of riboflavin containing foods. Multi-vitamin and mineral dietary supplements often contain 100% of the Daily Value (1.3 mg) for riboflavin, and can be used by persons concerned about an inadequate diet. Over-the-counter dietary supplements are available in the United States with doses as high as 100 mg, but there is no evidence that these high doses have any additional benefit for healthy people.

As a chemical compound, riboflavin is a yellow-orange solid substance with poor solubility in water compared to other B vitamins. Visually, it imparts color to vitamin supplements (and bright yellow color to the urine of persons taking a lot of it).

In the United States, biotin supplements are readily available without a prescription in amounts ranging from 1,000 to 10,000 micrograms (30 micrograms is identified as Adequate Intake).

Since biotin is in many foods at low concentrations, deficiency is rare except in locations where malnourishment is very common. Pregnancy, however, alters biotin catabolism and despite a regular biotin intake, half of the pregnant women in the U.S. are marginally biotin deficient.

A vitamin deficiency can cause a disease or syndrome known as an avitaminosis or hypovitaminosis. This usually refers to a long-term deficiency of a vitamin. When caused by inadequate nutrition it can be classed as a "primary deficiency", and when due to an underlying disorder such as malabsorption it can be classed as a "secondary deficiency". An underlying disorder may be metabolic as in a defect converting tryptophan to niacin. It can also be the result of lifestyle choices including smoking and alcohol consumption.

Examples are vitamin A deficiency, folate deficiency, scurvy, vitamin D deficiency, vitamin E deficiency, and vitamin K deficiency. In the medical literature, any of these may also be called by names on the pattern of "hypovitaminosis" or "avitaminosis" + "[letter of vitamin]", for example, hypovitaminosis A, hypovitaminosis C, hypovitaminosis D.

Conversely hypervitaminosis is the syndrome of symptoms caused by over-retention of fat-soluble vitamins in the body.

- Vitamin A deficiency can cause keratomalacia.

- Thiamine (vitamin B1) deficiency causes beriberi and Wernicke–Korsakoff syndrome.

- Riboflavin (vitamin B2) deficiency causes ariboflavinosis.

- Niacin (vitamin B3) deficiency causes pellagra.

- Pantothenic acid (vitamin B5) deficiency causes chronic paresthesia.

- Vitamin B6

- Biotin (vitamin B7) deficiency negatively affects fertility and hair/skin growth. Deficiency can be caused by poor diet or genetic factors (such as mutations in the BTD gene, see multiple carboxylase deficiency).

- Folate (vitamin B9) deficiency is associated with numerous health problems. Fortification of certain foods with folate has drastically reduced the incidence of neural tube defects in countries where such fortification takes place. Deficiency can result from poor diet or genetic factors (such as mutations in the MTHFR gene that lead to compromised folate metabolism).

- Vitamin B12 (cobalamin) deficiency can lead to pernicious anemia, megaloblastic anemia, subacute combined degeneration of spinal cord, and methylmalonic acidemia among other conditions.

- Vitamin C (ascorbic acid) short-term deficiency can lead to weakness, weight loss and general aches and pains. Longer-term depletion may affect the connective tissue. Persistent vitamin C deficiency leads to scurvy.

- Vitamin D (cholecalciferol) deficiency is a known cause of rickets, and has been linked to numerous health problems.

- Vitamin E deficiency causes nerve problems due to poor conduction of electrical impulses along nerves due to changes in nerve membrane structure and function.

- Vitamin K (phylloquinone or menaquinone) deficiency causes impaired coagulation and has also been implicated in osteoporosis

Iron deficiency can be avoided by choosing appropriate soil for the growing conditions (e.g., avoid growing acid loving plants on lime soils), or by adding well-rotted manure or compost. If iron deficit chlorosis is suspected then check the pH of the soil with an appropriate test kit or instrument. Take a soil sample at surface and at depth. If the pH is over seven then consider soil remediation that will lower the pH toward the 6.5 - 7 range. Remediation includes: i) adding compost, manure, peat or similar organic matter (warning. Some retail blends of manure and compost have pH in the range 7 - 8 because of added lime. Read the MSDS if available. Beware of herbicide residues in manure. Source manure from a certified organic source.) ii) applying Ammonium Sulphate as a Nitrogen fertilizer (acidifying fertilizer due to decomposition of ammonium ion to nitrate in the soil and root zone) iii) applying elemental Sulphur to the soil (oxidizes over the course of months to produce sulphate/sulphite and lower pH). Note: adding acid directly e.g. sulphuric/hydrochloric/citric acid is dangerous as you may mobilize metal ions in the soil that are toxic and otherwise bound. Iron can be made available immediately to the plant by the use of iron sulphate or iron chelate compounds. Two common iron chelates are Fe EDTA and Fe EDDHA. Iron sulphate (Iron(II)_sulfate) and iron EDTA are only useful in soil up to PH 7.1 but they can be used as a foliar spray (Foliar_feeding). Iron EDDHA is useful up to PH 9 (highly alkaline) but must be applied to the soil and in the evening to avoid photodegradation. EDTA in the soil may mobilize Lead, EDDHA does not appear to.

Treatment of THB deficiencies consists of THB supplementation (2–20 mg/kg per day) or diet to control blood phenylalanine concentration and replacement therapy with neurotransmitters precursors (L-DOPA and 5-HTP) and supplements of folinic acid in DHPR deficiency.

Tetrahydrobiopterin is available as a tablet for oral administration in the form of "tetrahydrobiopterin dihydrochloride" (BH4*2HCL). BH4*2HCL is FDA approved under the trade name Kuvan. The typical cost of treating a patient with Kuvan is $100,000 per year. BioMarin holds the patent for Kuvan until at least 2024, but Par Pharmaceutical has a right to produce a generic version by 2020. BH4*2HCL is indicated at least in tetrahydrobiopterin deficiency caused by GTPCH deficiency or PTPS deficiency.

In common forms of MTHFR deficiency, elevated plasma homocysteine levels have sometimes been treated with Vitamin B12 and low doses of folic acid. Although this treatment significantly decreases the serum levels of homocysteine, this treatment is not thought to improve health outcomes.

Due to the ineffectiveness of these treatments, it is no-longer considered clinically useful to test for MTHFR in most cases of thrombophilia or recurrent pregnancy loss.

Whether MTHFR deficiency has any effect at all on all-cause mortality is unclear. One Dutch study showed that the MTHFR mutation was more prevalent in younger individuals (36% relative to 30%), and found that elderly men with MTHFR had an elevated mortality rate, attributable to cancer. Among women, however, no difference in life expectancy was seen. More recently, however, a meta-analysis has shown that overall cancer rates are barely increased with an odds ratio of 1.07, which suggests that an impact on mortality from cancer is small or zero.

Low-protein food is recommended for this disorder, which requires food products low in particular types of amino acids (e.g., methionine).

Because HFM is a rare disorder, there are no studies that define its optimal treatment. Correction of the systemic folate deficiency, with the normalization of folate blood levels, is easily achieved with high doses of oral folates or much smaller doses of parenteral folate. This will rapidly correct the anemia, immune deficiency and GI signs. The challenge is to achieve adequate treatment of the neurological component of HFM. It is essential that the folate dose is sufficiently high to achieve CSF folate levels as close as possible to the normal range for the age of the child. This requires close monitoring of the CSF folate level. The physiological folate is 5-methyltetrahydrofolate but the oral formulation available is insufficient for treatment of this disorder and a parenteral form is not available. The optimal folate at this time is 5-formyltetrahydrofolate which, after administration, is converted to 5-methyltetrahydrofolate. The racemic mixture of 5-formyltetrahydrofolate (leucovorin) is generally available; the active S-isomer, levoleucovorin, may be obtained as well. Parenteral administration is the optimal treatment if that is possible. Folic acid should not be used for the treatment of HFM. Folic acid is not a physiological folate. It binds tightly to, and may impede, FRα-mediated endocytosis which plays an important role in the transport of folates across the choroid plexus into the CSF (see above). For a further consideration of treatment see GeneReviews.

Symptoms include leaves turning yellow or brown in the margins between the veins which may remain green, while young leaves may appear to be bleached. Fruit would be of poor quality and quantity. Any plant may be affected, but raspberries and pears are particularly susceptible, as well as most acid-loving plants such as azaleas and camellias.

The life expectancy of patients with homocystinuria is reduced only if untreated. It is known that before the age of 30, almost one quarter of patients die as a result of thrombotic complications (e.g., heart attack).

As of June 2014 (the latest update on HFM in GeneReviews) a total of 32 families had been reported with a clinical diagnosis of HFM of which there was genotypic confirmation in 24 families. Since then, another two confirmed cases have been reported and an additional case was reported based on a clinical diagnosis alone. Most cases emerge from consanguineous parents with homozygous mutations. There are three instances of HFM from non-consanguineous parents in which there were heterozygous mutations. HFM cases are worldwide with mostly private mutations. However, a number of families of Puerto Rican ancestry have been reported with a common pathogenic variant at a splice receptor site resulting in the deletion of exon 3 and the absence of transport function. A subsequent population-based study of newborn infants in Puerto Rico identified the presence of the same variant on the island. Most of the pathogenic variants result in a complete loss of the PCFT protein or point mutations that result in the complete loss of function. However, residual function can be detected with some of the point mutants.

Nutritional anemia refers to the low concentration of hemoglobin due to poor diet. According to the World Health Organization, a hemoglobin concentration below 7.5 mmol/L and 8. mmol/L for women and men, respectively, is considered to be anemic. Thus, anemia can be diagnosed with blood tests. Hemoglobin is used to transport and deliver oxygen in the body. Without oxygen, the human body cannot undergo respiration and create ATP, thereby depriving cells of energy.

Nutritional anemia is caused by a lack of iron, protein, B12, and other vitamins and minerals that needed for the formation of hemoglobin. Folic acid deficiency is a common association of nutritional anemia and iron deficiency anemia is the most common nutritional disorder.

Signs of anemia include cyanosis, jaundice, and easy bruising. In addition, anemic patients may experience difficulties with memory and concentration, fatigue, lightheadedness, sensitivity to temperature, low energy levels, shortness of breath, and pale skin. Symptoms of severe or rapid-onset anemia are very dangerous as the body is unable to adjust to the lack of hemoglobin. This may result in shock and death. Mild and moderate anemia have symptoms that develop slowly over time.[5] If patients believe that they are at risk for or experience symptoms of anemia, they should contact their doctor.

Treatments for nutritional anemia includes replacement therapy is used to elevate the low levels of nutrients.[1] Diet improvement is a way to combat nutritional anemia and this can be done by taking dietary supplements such as iron, folate, and Vitamin B12.[2] These supplements are available over-the-counter however, a doctor may prescribe prescription medicine as needed, depending on the patient’s health needs.

Internationally, anemia caused by iron deficiencies is the most common nutritional disorder. It is the only significantly prevalent nutritional deficiency disorder in industrialized countries. In poorer areas, anemia is worsened by infectious diseases such as HIV/AIDS, tuberculosis, hookworm infestation, and Malaria. In developing countries, about 40% of preschool children and 50% of pregnant women are estimated to be anemic. 20% of maternal deaths can be contributed to anemia. Health consequences of anemia include low pregnancy outcome, impaired cognitive and physical development, increased rate of morbidity, and reduced rate of work in adults.

'

Nutritional Anemia has many different causes, each either nutritional or non-nutritional. Nutritional causes are vitamin and mineral deficiencies and non-nutritional causes can be infections. The number one cause of this type of anemia however is iron deficiency.

An insufficient intake of iron, Vitamin B12, and folic acid impairs the bone marrow function.

The lack of iron within a person’s body can also stem from ulcer bacteria. These microbes live in the digestive track and after many years cause ulcer’s in the lining of your stomach or small intestine. Therefore, a high percentage of patients with nutritional anemia may have potential gastrointestinal disorder that causes chronic blood loss. This is common in immunocompromised, elderly, and diabetic people. High blood loss can also come from increases loss of blood during menstruation, childbirth, cancers of the intestines, and a disorder that hinders blood’s ability to coagulate.

Medications can have adverse effects and cause nutritional anemia as well. Medications that stop the absorption of iron in the gut and cause bleeding from the gut (NSAIDs and Aspirin) can be culprits in the development of this condition. Hydrocortisones and valproic acid are also two drugs that cause moderate bleeding from the gut. Amoxicillin and phenytoin are the ability to cause a vitamin B12 deficiency.

Other common causes are thyroid disorders, lead toxcities, infectious diseases (e.g Malaria), Alcoholism, and Vitamin E deficiency.

Symptoms

Symptoms of nutritional anemia can include fatigue and lack of energy. However if symptoms progress, one may experience shortness of breath, rapid pulse, paleness --especially in the hands, eyelids and fingernails---, swelling of ankles, hair loss, lightheadedness, compulsive and atypical cravings, constipation, depression, muscle twitching, numbness, or burning and chest pain.

Those who have nutritional anemia often show little to no symptoms. Often, symptoms can go undetected as mild forms of the anemia have only minor symptoms.

----[1] “Micronutrient deficiencies” World Health Organization. Accessed March 31, 2017. http://www.who.int/nutrition/topics/ida/en/

[2] "Ibid."

[3] "Ibid."

[4] "Ibid"

[5] "Ibid"

[6] "Ibid"

----[1] "Ibid".

[2] “Treatments for Nutritional anemia.” Right Diagnosis. Assessed March 31, 2017. http://www.rightdiagnosis.com/n/nutritional_anemia/treatments.htm

----[1] "Ibid".

[2] “What are the symptoms of anemia?” Health Grades, INC. Accessed March 31, 2017. https://www.healthgrades.com/conditions/anemia--symptoms.

[3] "Ibid."

[4] "Ibid."

[5] "Ibid."

[6] "Ibid"

----[1] "Ibid".

[2] "Ibid".

----[1] "Nutritional Anemia." The Free Dictionary. Accessed March 31, 2017. http://medical-dictionary.thefreedictionary.com/nutritionalanemia.

[2] "Ibid".

[3] "Ibid".

[4] "Ibid".

Nutritional anemia refers to types of anemia that can be directly attributed to nutritional disorders.

Examples include Iron deficiency anemia and pernicious anemia.

It is often discussed in a pediatric context.

Administration of cytidine monophosphate and uridine monophosphate reduces urinary orotic acid and ameliorates the anemia.

Administration of uridine, which is converted to UMP, will bypass the metabolic block and provide the body with a source of pyrimidine.

Uridine triacetate is a drug approved by FDA to be used in the treatment of hereditary orotic aciduria.

This condition is very rare; approximately 600 cases have been reported worldwide. In most parts of the world, only 1% to 2% of all infants with high phenylalanine levels have this disorder. In Taiwan, about 30% of newborns with elevated levels of phenylalanine have a deficiency of THB.

The conversion of tryptophan to serotonin and other metabolites depends on vitamin B. If tryptophan catabolism has any impact on brain glutaric acid and other catabolite levels, vitamin B levels should be routinely assayed and normalized in the course of the treatment of GA1.

Vegetarian diets and, for younger children, breastfeeding are common ways to limit protein intake without endangering tryptophan transport to the brain.

The most important measure is prevention – avoidance of the drugs and foods that cause hemolysis. Vaccination against some common pathogens (e.g. hepatitis A and hepatitis B) may prevent infection-induced attacks.

In the acute phase of hemolysis, blood transfusions might be necessary, or even dialysis in acute kidney failure. Blood transfusion is an important symptomatic measure, as the transfused red cells are generally not G6PD deficient and will live a normal lifespan in the recipient's circulation. Those affected should avoid drugs such as aspirin.

Some patients may benefit from removal of the spleen (splenectomy), as this is an important site of red cell destruction. Folic acid should be used in any disorder featuring a high red cell turnover. Although vitamin E and selenium have antioxidant properties, their use does not decrease the severity of G6PD deficiency.

Megaloblastic anemia (or megaloblastic anaemia) is an anemia (of macrocytic classification) that results from inhibition of DNA synthesis during red blood cell production. When DNA synthesis is impaired, the cell cycle cannot progress from the G2 growth stage to the mitosis (M) stage. This leads to continuing cell growth without division, which presents as macrocytosis.

Megaloblastic anemia has a rather slow onset, especially when compared to that of other anemias.

The defect in red cell DNA synthesis is most often due to hypovitaminosis, specifically a deficiency of vitamin B and/or folic acid. Vitamin B deficiency alone will not cause the syndrome in the presence of sufficient folate, as the mechanism is loss of B dependent folate recycling, followed by folate-deficiency loss of nucleic acid synthesis (specifically thymine), leading to defects in DNA synthesis. Folic acid supplementation in the absence of vitamin B prevents this type of anemia (although other vitamin B-specific pathologies may be present). Loss of micronutrients may also be a cause. Copper deficiency resulting from an excess of zinc from unusually high oral consumption of zinc-containing denture-fixation creams has been found to be a cause.

Megaloblastic anemia not due to hypovitaminosis may be caused by antimetabolites that poison DNA production directly, such as some chemotherapeutic or antimicrobial agents (for example azathioprine or trimethoprim).

The pathological state of megaloblastosis is characterized by many large immature and dysfunctional red blood cells (megaloblasts) in the bone marrow and also by hypersegmented neutrophils (those exhibiting five or more nuclear lobes ("segments"), with up to four lobes being normal). These hypersegmented neutrophils can be detected in the peripheral blood (using a diagnostic smear of a blood sample).