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.

Serum B levels are often low in B deficiency, but if other features of B deficiency are present with normal B then further investigation is warranted. One possible explanation for normal B levels in B deficiency is antibody interference in people with high titres of intrinsic factor antibody.

Some researchers propose that the current standard norms of vitamin B levels are too low.

One Japanese study states the normal limits as 500–1,300 pg/mL. Range of vitamin B12 levels in humans is considered as normal: >300 pg/mL; moderate deficiency: 201–300 pg/mL; and severe deficiency: <201 pg/mL.

Serum vitamin B tests results are in pg/mL (picograms/milliliter) or pmol/L (picomoles/liter). The laboratory reference ranges for these units are similar, since the molecular weight of B is approximately 1000, the difference between mL and L. Thus: 550 pg/mL = 400 pmol/L.

Serum homocysteine and methylmalonic acid levels are considered more reliable indicators of B deficiency than the concentration of B in blood. The levels of these substances are high in B deficiency and can be helpful if the diagnosis is unclear.

Routine monitoring of methylmalonic acid levels in urine is an option for people who may not be getting enough dietary B, as a rise in methylmalonic acid levels may be an early indication of deficiency.

If nervous system damage is suspected, B analysis in cerebrospinal fluid is possible, though such an invasive test should be considered only if blood testing is inconclusive.

The Schilling test has been largely supplanted by tests for antiparietal cell and intrinsic factor antibodies.

The assessment of vitamin B status is essential, as the clinical signs and symptoms in less severe cases are not specific. The three biochemical tests most widely used are the activation coefficient for the erythrocyte enzyme aspartate aminotransferase, plasma PLP concentrations, and the urinary excretion of vitamin B degradation products, specifically urinary PA. Of these, plasma PLP is probably the best single measure, because it reflects tissue stores. Plasma PLP less than 10 nmol/l is indicative of vitamin B deficiency. A PLP concentration greater than 20 nmol/l has been chosen as a level of adequacy for establishing Estimated Average Requirements and Recommended Daily Allowances in the USA. Urinary PA is also an indicator of vitamin B deficiency; levels of less than 3.0 mmol/day is suggestive of vitamin B deficiency.

The classic syndrome for vitamin B deficiency is rare, even in developing countries. A handful of cases were seen between 1952 and 1953, particularly in the United States, and occurred in a small percentage of infants who were fed a formula lacking in pyridoxine.

A deficiency of vitamin B alone is relatively uncommon and often occurs in association with other vitamins of the B complex. The elderly and alcoholics have an increased risk of vitamin B deficiency, as well as other micronutrient deficiencies. Evidence exists for decreased levels of vitamin B in women with type 1 diabetes and in patients with systemic inflammation, liver disease, rheumatoid arthritis, and those infected with HIV. Use of oral contraceptives and treatment with certain anticonvulsants, isoniazid, cycloserine, penicillamine, and hydrocortisone negatively impact vitamin B status. Hemodialysis reduces vitamin B plasma levels.

Because riboflavin is fluorescent under UV light, dilute solutions (0.015-0.025% w/w) are often used to detect leaks or to demonstrate coverage in an industrial system such a chemical blend tank or bioreactor. (See the ASME BPE section on Testing and Inspection for additional details.)

Overt clinical signs are rarely seen among inhabitants of the developed countries. The assessment of Riboflavin status is essential for confirming cases with unspecific symptoms where deficiency is suspected.

- Glutathione reductase is a nicotinamide adenine dinucleotide phosphate (NADPH) and FAD-dependent enzyme, and the major flavoprotein in erythrocyte. The measurement of the activity coefficient of erythrocyte glutathione reductase (EGR) is the preferred method for assessing riboflavin status. It provides a measure of tissue saturation and long-term riboflavin status. In vitro enzyme activity in terms of activity coefficients (AC) is determined both with and without the addition of FAD to the medium. ACs represent a ratio of the enzyme’s activity with FAD to the enzyme’s activity without FAD. An AC of 1.2 to 1.4, riboflavin status is considered low when FAD is added to stimulate enzyme activity. An AC > 1.4 suggests riboflavin deficiency. On the other hand, if FAD is added and AC is < 1.2, then riboflavin status is considered acceptable. Tillotson and Bashor reported that a decrease in the intakes of riboflavin was associated with increase in EGR AC. In the UK study of Norwich elderly, initial EGR AC values for both males and females were significantly correlated with those measured 2 years later, suggesting that EGR AC may be a reliable measure of long-term biochemical riboflavin status of individuals. These findings are consistent with earlier studies.

- Experimental balance studies indicate that urinary riboflavin excretion rates increase slowly with increasing intakes, until intake level approach 1.0 mg/d, when tissue saturation occurs. At higher intakes, the rate of excretion increases dramatically. Once intakes of 2.5 mg/d are reached, excretion becomes approximately equal to the rate of absorption (Horwitt et al., 1950) (18). At such high intake a significant proportion of the riboflavin intake is not absorbed. If urinary riboflavin excretion is <19 µg/g creatinine (without recent riboflavin intake) or < 40 µg per day are indicative of deficiency.

Novel zinc biomarkers, such as the erythrocyte LA:DGLA ratio, have shown promise in pre-clinical and clinical trials and are being developed to more accurately detect dietary zinc deficiency.

The diagnostic workup of a suspected iodine deficiency includes signs and symptoms as well as possible risk factors mentioned above. A 24-hour urine iodine collection is a useful medical test, as approximately 90% of ingested iodine is excreted in the urine. For the standardized 24-hour test, a 50 mg iodine load is given first, and 90% of this load is expected to be recovered in the urine of the following 24 hours. Recovery of less than 90% is taken to mean high retention, that is, iodine deficiency. The recovery may, however, be well less than 90% during pregnancy, and an intake of goitrogens can alter the test results.

If a 24-hour urine collection is not practical, a random urine iodine-to-creatinine ratio can alternatively be used. However, the 24-hour test is found to be more reliable.

A general idea of whether a deficiency exists can be determined through a functional iodine test in the form of an iodine skin test. In this test, the skin is painted with an iodine solution: if the iodine patch disappears quickly, this is taken as a sign of iodine deficiency. However, no accepted norms exist on the expected time interval for the patch to disappear, and in persons with dark skin color the disappeance of the patch may be difficult to assess. If a urine test is taken shortly after, the results may be altered due to the iodine absorbed previously in a skin test.

The prevalence of vitamin K deficiency varies by geographic region. For infants in the United States, vitamin K deficiency without bleeding may occur in as many as 50% of infants younger than 5 days old, with the classic hemorrhagic disease occurring in 0.25-1.7% of infants. Therefore, the Committee on Nutrition of the American Academy of Pediatrics recommends that 0.5 to 1.0 mg Vitamin K be administered to all newborns shortly after birth.

Postmenopausal and elderly women in Thailand have high risk of Vitamin K deficiency, compared with the normal value of young, reproductive females.

Current dosage recommendations for Vitamin K may be too low. The deposition of calcium in soft tissues, including arterial walls, is quite common, especially in those suffering from atherosclerosis, suggesting that Vitamin K deficiency is more common than previously thought.

Because colonic bacteria synthesize a significant portion of the Vitamin K required for human needs, individuals with disruptions to or insufficient amounts of these bacteria can be at risk for Vitamin K deficiency. Newborns, as mentioned above, fit into this category, as their colons are frequently not adequately colonized in the first five to seven days of life. (Consumption of the mother's milk can undo this temporary problem.) Another at-risk population comprises those individuals on any sort of long-term antibiotic therapy, as this can diminish the population of normal gut flora.

Some situations that increase the need for folate include the following:

- hemorrhage

- kidney dialysis

- liver disease

- malabsorption, including celiac disease and fructose malabsorption

- pregnancy and lactation (breastfeeding)

- tobacco smoking

- alcohol consumption

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.

Zinc deficiency can be classified as acute, as may occur during prolonged inappropriate zinc-free total parenteral nutrition; or chronic, as may occur in dietary deficiency or inadequate absorption.

Iodine deficiency is treated by ingestion of iodine salts, such as found in food supplements. Mild cases may be treated by using iodized salt in daily food consumption, or drinking more milk, or eating egg yolks, and saltwater fish. For a salt and/or animal product restricted diet, sea vegetables (kelp, hijiki, dulse, nori (found in sushi)) may be incorporated regularly into a diet as a good source of iodine.

The recommended daily intake of iodine for adult women is 150–300 µg for maintenance of normal thyroid function; for men it is somewhat less at 150 µg.

However, too high iodine intake, for example due to overdosage of iodine supplements, can have toxic side effects. It can lead to hyperthyroidism and consequently high blood levels of thyroid hormones (hyperthyroxinemia). In case of extremely high single-dose iodine intake, typically a short-term suppression of thyroid function (Wolff–Chaikoff effect) occurs. Persons with pre-existing thyroid disease, elderly persons, fetuses and neonates, and patients with other risk factors are at a higher risk of experiencing iodine-induced thyroid abnormalities. In particular, in persons with goiter due to iodine deficiency or with altered thyroid function, a form of hyperthyroidism called Jod-Basedow phenomenon can be triggered even at small or single iodine dosages, for example as a side effect of administration of iodine-containing contrast agents. In some cases, excessive iodine contributes to a risk of autoimmune thyroid diseases (Hashimoto's thyroiditis and Graves' disease).

As always, laboratory values have to be interpreted with the lab's reference values in mind and considering all aspects of the individual clinical situation.

Serum ferritin can be elevated in inflammatory conditions; so a normal serum ferritin may not always exclude iron deficiency, and the utility is improved by taking a concurrent C-reactive protein (CRP). The level of serum ferritin that is viewed as "high" depends on the condition. For example, in inflammatory bowel disease the threshold is 100, where as in chronic heart failure (CHF) the levels are 200.

Biotinidase deficiency can be found by genetic testing. This is often done at birth as part of newborn screening in several states throughout the United States. Results are found through testing a small amount of blood gathered through a heel prick of the infant. As not all states require that this test be done, it is often skipped in those where such testing is not required. Biotinidase deficiency can also be found by sequencing the "BTD" gene, particularly in those with a family history or known familial gene mutation.

Menaquinone (vitamin K), but not phylloquinone (vitamin K), intake is associated with reduced risk of CHD mortality, all-cause mortality and severe aortic calcification.

Iron is needed for bacterial growth making its bioavailability an important factor in controlling infection. Blood plasma as a result carries iron tightly bound to transferrin, which is taken up by cells by endocytosing transferrin, thus preventing its access to bacteria. Between 15 and 20 percent of the protein content in human milk consists of lactoferrin that binds iron. As a comparison, in cow's milk, this is only 2 percent. As a result, breast fed babies have fewer infections. Lactoferrin is also concentrated in tears, saliva and at wounds to bind iron to limit bacterial growth. Egg white contains 12% conalbumin to withhold it from bacteria that get through the egg shell (for this reason, prior to antibiotics, egg white was used to treat infections).

To reduce bacterial growth, plasma concentrations of iron are lowered in a variety of systemic inflammatory states due to increased production of hepcidin which is mainly released by the liver in response to increased production of pro-inflammatory cytokines such as Interleukin-6. This functional iron deficiency will resolve once the source of inflammation is rectified; however, if not resolved, it can progress to Anaemia of Chronic Inflammation. The underlying inflammation can be caused by fever, inflammatory bowel disease, infections, Chronic Heart Failure (CHF), carcinomas, or following surgery.

Reflecting this link between iron bioavailability and bacterial growth, the taking of oral iron supplements in excess of 200 mg/day causes a relative overabundance of iron that can alter the types of bacteria that are present within the gut. There have been concerns regarding parenteral iron being administered whilst bacteremia is present, although this has not been borne out in clinical practice. A moderate iron deficiency, in contrast, can provide protection against acute infection, especially against organisms that reside within hepatocytes and macrophages, such as malaria and tuberculosis. This is mainly beneficial in regions with a high prevalence of these diseases and where standard treatment is unavailable.

Copper deficiency is a very rare disease and is often misdiagnosed several times by physicians before concluding the deficiency of copper through differential diagnosis (copper serum test and bone marrow biopsy are usually conclusive in diagnosing copper deficiency). On average, patients are diagnosed with copper deficiency around 1.1 years after their first symptoms are reported to a physician.

Copper deficiency can be treated with either oral copper supplementation or intravenous copper. If zinc intoxication is present, discontinuation of zinc may be sufficient to restore copper levels back to normal, but this usually is a very slow process. People who suffer from zinc intoxication will usually have to take copper supplements in addition to ceasing zinc consumption. Hematological manifestations are often quickly restored back to normal. The progression of the neurological symptoms will be stopped by appropriate treatment, but often with residual neurological disability.

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

The treatment is some form of Vitamin E supplementation.

Aggressive vitamin E replacement therapy has been shown to either prevent, halt or improve visual abnormalities.

There are two main types of protein C assays, activity and antigen (immunoassays). Commercially available activity assays are based on chromogenic assays that use activation by snake venom in an activating reagent, or clotting and enzyme-linked immunosorbant assays. Repeated testing for protein C functional activity allows differentiation between transient and congenital deficiency of protein C.

Initially, a protein C activity (functional) assay can be performed, and if the result is low, a protein C antigen assay can be considered to determine the deficiency subtype (Type I or Type II). In type I deficiencies, normally functioning protein C molecules are made in reduced quantity. In type II deficiencies normal amounts of dysfunctional protein C are synthesized.

Antigen assays are immunoassays designed to measure the quantity of protein C regardless of its function. Type I deficiencies are therefore characterized by a decrease in both activity and antigen protein C assays whereas type II deficiencies exhibit normal protein C antigen levels with decreased activity levels.

The human protein C gene (PROC) comprises 9 exons, and protein C deficiency has been linked to over 160 mutations to date. Therefore, DNA testing for protein C deficiency is generally not available outside of specialized research laboratories.

Manifestation of purpura fulminans as it is usually associated with reduced protein C plasma concentrations of <5 mg IU/dL. The normal concentration of plasma protein C is 70 nM (4 µg/mL) with a half live of approximately 8 hours. Healthy term neonates, however, have lower (and more variable) physiological levels of protein C (ranging between 15-55 IU/dL) than older children or adults, and these concentrations progressively increase throughout the first 6 months of life. Protein C levels may be <10 IU/dL in preterm or twin neonates or those with respiratory distress without manifesting either purpura fulminans or disseminated intravascular coagulation.

In plants a micronutrient deficiency (or trace mineral deficiency) is a physiological plant disorder which occurs when a micronutrient is deficient in the soil in which a plant grows. Micronutrients are distinguished from macronutrients (nitrogen, phosphorus, sulfur, potassium, calcium and magnesium) by the relatively low quantities needed by the plant.

A number of elements are known to be needed in these small amounts for proper plant growth and development. Nutrient deficiencies in these areas can adversely affect plant growth and development. Some of the best known trace mineral deficiencies include: zinc deficiency, boron deficiency, iron deficiency, and manganese deficiency.

Raw eggs should be avoided in those with biotin deficiency, because egg whites contain high levels of the anti-nutrient avidin. The name avidin literally means that this protein has an "avidity" (Latin: "to eagerly long for") for biotin. Avidin binds irreversibly to biotin and this compound is then excreted in the urine.

Micronutrient deficiencies affect more than two billion people of all ages in both developing and industrialized countries. They are the cause of some diseases, exacerbate others and are recognized as having an important impact on worldwide health. Important micronutrients include iodine, iron, zinc, calcium, selenium, fluorine, and vitamins A, B, B, B, B, B, and C.

Micronutrient deficiencies are associated with 10% of all children's deaths, and are therefore of special concern to those involved with child welfare. Deficiencies of essential vitamins or minerals such as Vitamin A, iron, and zinc may be caused by long-term shortages of nutritious food or by infections such as intestinal worms. They may also be caused or exacerbated when illnesses (such as diarrhoea or malaria) cause rapid loss of nutrients through feces or vomit.

Vitamin E deficiency is rare and is almost never caused by a poor diet. Instead, there are three specific situations when a vitamin E deficiency is likely to occur:

- Premature, very low birth weight infants - birth weights less than 1500 grams, or 3.5 pounds. A neonatologist, a pediatrician specializing in the care of newborns, typically evaluates the nutritional needs of premature infants.

- Rare disorders of fat metabolism - There is a rare genetic condition termed isolated vitamin E deficiency or 'ataxia with isolated with vitamin E deficiency', caused by mutations in the gene for the tocopherol transfer protein. These individuals have an extremely poor capacity to absorb vitamin E and develop neurological complications that are reversed by high doses of vitamin E.

- Fat malabsorption - Some dietary fat is needed for the absorption of vitamin E from the gastrointestinal tract. Anyone diagnosed with cystic fibrosis, individuals who have had part or all of their stomach removed or who have had a gastric bypass, and individuals with malabsorptive problems such as Crohn's disease, liver disease or exocrine pancreatic insufficiency may not absorb fat (people who cannot absorb fat often pass greasy stools or have chronic diarrhea and bloating). Abetalipoproteinemia is a rare inherited disorder of fat metabolism that results in poor absorption of dietary fat and vitamin E. The vitamin E deficiency associated with this disease causes problems such as poor transmission of nerve impulses, muscle weakness, and degeneration of the retina that can cause blindness.