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.

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

Complex regulatory mechanisms control metabolism. Recent epidemiologic evidence suggests that there is a narrow range of vitamin D levels in which vascular function is optimized. Levels above or below this range increased mortality. Animal research suggests that both excess and deficiency of vitamin D appears to cause abnormal functioning and premature aging.

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

In the United States, overdose exposure to all formulations of "vitamins" was reported by 62,562 individuals in 2004 (nearly 80% [~78%, n=48,989] of these exposures were in children under the age of 6), leading to 53 "major" life-threatening outcomes and 3 deaths (2 from vitamins D and E; 1 from polyvitaminic type formula, with iron and no fluoride). This may be compared to the 19,250 people who died of unintentional poisoning of all kinds in the U.S. in the same year (2004). In 2010, 71,000 exposures to various vitamins and multivitamin-mineral formulations were reported to poison control centers, which resulted in 15 major reactions but no deaths.

Before 1998, several deaths per year were associated with pharmaceutical iron-containing supplements, especially brightly colored, sugar-coated, high-potency iron supplements, and most deaths were children. Unit packaging restrictions on supplements with more than 30 mg of iron have since reduced deaths to 0 or 1 per year. These statistics compare with 59 confirmed deaths due to aspirin poisoning in 2003 and 147 deaths known to be associated with acetaminophen-containing products in 2003.

Treatment consists of vitamin K supplementation. This is often given prophylactically to newborns shortly after birth.

Excessive exposure to sunlight poses no risk in vitamin D toxicity through overproduction of vitamin D precursor, cholecalciferol, regulating vitamin D production. During ultraviolet exposure, the concentration of vitamin D precursors produced in the skin reach an equilibrium, and any further vitamin D that is produced is degraded. This process is less efficient with increased melanin pigmentation in the skin. Endogenous production with full body exposure to sunlight is comparable to taking an oral dose between 250 µg and 625 µg (10,000 IU and 25,000 IU) per day.

Vitamin D oral supplementation and skin synthesis have a different effect on the transport form of vitamin D, plasma calcifediol concentrations. Endogenously synthesized vitamin D travels mainly with vitamin D-binding protein (DBP), which slows hepatic delivery of vitamin D and the availability in the plasma. In contrast, orally administered vitamin D produces rapid hepatic delivery of vitamin D and increases plasma calcifediol.

It has been questioned whether to ascribe a state of sub-optimal vitamin D status when the annual variation in ultraviolet will naturally produce a period of falling levels, and such a seasonal decline has been a part of Europeans' adaptive environment for 1000 generations. Still more contentious is recommending supplementation when those supposedly in need of it are labeled healthy and serious doubts exist as to the long-term effect of attaining and maintaining serum 25(OH)D of at least 80nmol/L by supplementation.

Current theories of the mechanism behind vitamin D toxicity propose that:

- Intake of vitamin D raises calcitriol concentrations in the plasma and cell

- Intake of vitamin D raises plasma calcifediol concentrations which exceed the binding capacity of the DBP, and free calcifediol enters the cell

- Intake of vitamin D raises the concentration of vitamin D metabolites which exceed DBP binding capacity and free calcitriol enters the cell

All of which affect gene transcription and overwhelm the vitamin D signal transduction process, leading to vitamin D toxicity.

With few exceptions, like some vitamins from B-complex, hypervitaminosis usually occurs more with fat-soluble vitamins (D, E, K and A or 'DEKA'), which are stored in the liver and fatty tissues of the body. These vitamins build up and remain for a longer time in the body than water-soluble vitamins.

Conditions include:

- Hypervitaminosis A

- Hypervitaminosis D

- Hypervitaminosis E

- Hypervitaminosis K, unique as the true upper limit is less clear as is its bioavailability.

According to Williams' Essentials of Diet and Nutrition Therapy it is difficult to set a DRI for vitamin K because part of the requirement can be met by intestinal bacterial synthesis.

- Reliable information is lacking as to the vitamin K content of many foods or its bioavailability. With this in mind the Expert Committee established an AI rather than an RDA.

- This RDA (AI for men age 19 and older is 120 µg/day, AI for women is 90 µg/day) is adequate to preserve blood clotting, but the correct intake needed for optimum bone health is unknown. Toxicity has not been reported.

High-dosage A; high-dosage, slow-release vitamin B; and very high-dosage vitamin B alone (i.e. without vitamin B complex) hypervitaminoses are sometimes associated with side effects that usually rapidly cease with supplement reduction or cessation.

High doses of mineral supplements can also lead to side effects and toxicity. Mineral-supplement poisoning does occur occasionally, most often due to excessive intake of iron-containing supplements.

If treatment is initiated early in disease the neurologic sequelae may be reversed and further deterioration can be prevented.

Treatment normally consists of rigorous dieting, involving massive amounts of vitamin E. Vitamin E helps the body restore and produce lipoproteins, which people with abetalipoprotenimia usually lack. Vitamin E also helps keep skin and eyes healthy; studies show that many affected males will have vision problems later on in life. Developmental coordination disorder and muscle weakness are usually treated with physiotherapy or occupational therapy. Dietary restriction of triglycerides has also been useful.

Precise diagnosis by measuring proteins induced by vitamin k absence (PIVKA).

But this is usually not required.

Hypervitaminosis E is a state of vitamin E toxicity. Since vitamin E can act as an anticoagulant and may increase the risk of bleeding problems, many agencies have set a tolerable upper intake levels (UL) for vitamin E at 1,000 mg (1,500 IU) per day. This UL was established due to an increased incidence of hemorrhaging with higher doses of supplemental vitamin E. Doses of vitamin E above the UL can also magnify the antiplatelet effects of certain drugs such as anti-coagulant medications and aspirin, which can cause life-threatening symptoms in ill patients. Hypervitaminosis E may also counteract vitamin K, leading to a vitamin K deficiency.

Treatment of LPLD has two different objectives: immediate prevention of pancreatitis attacks and long term reduction of cardiovascular disease risk. Treatment is mainly based on medical nutrition therapy to maintain plasma triglyceride concentration below 11,3 mmol/L (1000 mg/dL). Maintenance of triglyceride levels below 22,6 mmol/L (2000 mg/dL) prevents in general from recurrent abdominal pain.

Strict low fat diet and avoidance of simple carbohydrates

Restriction of dietary fat to not more than 20 g/day or 15% of the total energy intake is usually sufficient to reduce plasma triglyceride concentration, although many patients report that to be symptom free a limit of less than 10g/day is optimal. Simple carbohydrates should be avoided as well. Medium-chain triglycerides can be used for cooking, because they are absorbed into the portal vein without becoming incorporated into chylomicrons. Fat-soluble vitamins A, D, E, and K, and minerals should be supplemented in patients with recurrent pancreatitis since they often have deficiencies as a result of malabsorption of fat. However, the diet approach is difficult to sustain for many of the patients.

Lipid lowering drugs

Lipid-lowering agents such as fibrates and omega-3-fatty acids can be used to lower TG levels in LPLD, however those drugs are very often not effective enough to reach treatment goals in LPLD patients. Statins should be considered to lower elevated non-HDL-Cholesterol.

Additional measures are avoidance of agents known to increase endogenous triglyceride levels, such as alcohol, estrogens, diuretics, isotretinoin, anidepressants (e.g. sertraline) and b-adrenergic blocking agents.

Gene therapy

In 2012, the European Commission approved alipogene tiparvovec (Glybera), a gene therapy for adults diagnosed with familial LPLD (confirmed by genetic testing) and suffering from severe or multiple pancreatitis attacks despite dietary fat restrictions. It was the first gene therapy to receive marketing authorization in Europe; it was priced at about $1 million per treatment, and as of 2016, only one person had been treated with it.

Primary prophylaxis with low-molecular weight heparin, heparin, or warfarin is often considered in known familial cases. Anticoagulant prophylaxis is given to all who develop a venous clot regardless of underlying cause.

Studies have demonstrated an increased risk of recurrent venous thromboembolic events in patients with protein C deficiency. Therefore, long-term anticoagulation therapy with warfarin may be considered in these patients.

Homozygous protein C defect constitutes a potentially life-threatening disease, and warrants the use of supplemental protein C concentrates.

Liver transplant may be considered curative for homozygous protein C deficiency.

While SSADH deficiency has been studied for nearly 30 years, knowledge of the disorder and its pathophysiology remains unclear. However, the progress that has been made with both murine and human models of the disorder have provided a lot of insights into how the disease manifests itself and what more can be done in terms of therapeutic interventions. Much of the current research into SSADH has been led by a dedicated team of physicians and scientists, including Phillip L. Pearl, MD of the Boston Children's Hospital at Harvard Medical School and K. Michael Gibson, PhD of Washington State University College of Pharmacy. Both have contributed significant efforts to finding appropriate therapies for SSADH deficiency and have specifically spent most of their recent efforts into understanding the efficacy of the ketogenic diet for patients with SSADH deficiency. In addition, a lot of the research that was published in 2007 examined the pathogenesis for the disorder by examining the role of oxidative stress on tissues in various cerebral structures of Aldh5a1-/- mice.

Ultimately, the metabolic pathway of SSADH deficiency is known, but how the enzyme deficiency and accumulation of GABA and GHB contribute to the clinical phenotype is not. For the future however, treatment strategies should focus on both decreasing the total production of GHB and increasing the total concentration of GABA and further assessing whether the effects of these changes influences the neurological manifestations seen in patients afflicted with SSADH deficiency.

Response to treatment is variable and the long-term and functional outcome is unknown. To provide a basis for improving the understanding of the epidemiology, genotype/phenotype correlation and outcome of these diseases their impact on the quality of life of patients, and for evaluating diagnostic and therapeutic strategies a patient registry was established by the noncommercial International Working Group on Neurotransmitter Related Disorders (iNTD).

During prolonged periods of fasting, ketone bodies serve as the primary energy source for the brain. In 2006, Henderson et al. showed that there is a therapeutic effect of maintaining a ketogenic diet – a diet consisting of high fat/low carbohydrate meals – in children with epilepsy. Ketogenic diets have also been shown to have some neuroprotective effects in models of Parkinson's disease and hypoxia as well. In a recent study conducted at the Hospital for Sick Children in Canada in 2007, researchers found that a ketogenic diet prolonged the lifespan of Aldh5a1-/- mice by greater than 300%, along with the normalization of ataxia and some improvement in various seizure types seen in SSADH deficient murine models. These effects were in conjunction with "...a significant restoration of GABAergic synaptic activity and region-specific restoration of GABA receptor associated chloride channel binding." Ultimately, the data seen in the study indicated that a ketogenic diet may work in its ability to restore GABAergic inhibition. But further studies on murine models need to be conducted, ultimately leading to the possibility of conducting a controlled study on humans afflicted with the disorder.

There is speculation that a ketogenic diet may be harmful for humans with SSADH deficiency as it may cause elevated levels of GHB in the bloodstream.

Treatment including addressing the cause, such as improving the diet, treating diarrhea, or stopping an offending medication. People without a significant source of potassium loss and who show no symptoms of hypokalemia may not require treatment.

Mild hypokalemia (>3.0 meq/l) may be treated with oral potassium chloride supplements (Klor-Con, Sando-K, Slow-K). As this is often part of a poor nutritional intake, potassium-containing foods may be recommended, such as leafy green vegetables, avocados, tomatoes, coconut water, citrus fruits, oranges, or bananas. Both dietary and pharmaceutical supplements are used for people taking diuretic medications.

Severe hypokalemia (<3.0 meq/l) may require intravenous supplementation. Typically, a saline solution is used, with 20–40 meq/l KCl per liter over 3–4 hours. Giving IV potassium at faster rates (20–25 meq/hr) may predispose to ventricular tachycardias and requires intensive monitoring. A generally safe rate is 10 meq/hr. Even in severe hypokalemia, oral supplementation is preferred given its safety profile. Sustained-release formulations should be avoided in acute settings.

Difficult or resistant cases of hypokalemia may be amenable to a potassium-sparing diuretic, such as amiloride, triamterene, spironolactone, or eplerenone. Concomitant hypomagnesemia will inhibit potassium replacement, as magnesium is a cofactor for potassium uptake.

When replacing potassium intravenously, infusion by a central line is encouraged to avoid the frequent occurrence of a burning sensation at the site of a peripheral infusion, or the rare occurrence of damage to the vein. When peripheral infusions are necessary, the burning can be reduced by diluting the potassium in larger amounts of fluid, or mixing 3 ml of 1% lidocaine to each 10 meq of KCl per 50 ml of fluid. The practice of adding lidocaine, however, raises the likelihood of serious medical errors.

The disorder affects about 1 out of 1,000,000 people, however epidemiological data are limited and there are regional differences due to cofounder effect (e.g. in Canada) or intermarriage.

Causes include:

The newest mnemonic was proposed in "The Lancet" reflecting current causes of anion gap metabolic acidosis:

- G — glycols (ethylene glycol & propylene glycol)

- O — oxoproline, a metabolite of paracetamol

- L — L-lactate, the chemical responsible for lactic acidosis

- D — D-lactate

- M — methanol

- A — aspirin

- R — renal failure

- K — ketoacidosis, ketones generated from starvation, alcohol, and diabetic ketoacidosis

The mnemonic MUDPILES is commonly used to remember the causes of increased anion gap metabolic acidosis.

- M — Methanol

- U — Uremia (chronic kidney failure)

- D — Diabetic ketoacidosis

- P — Paracetamol, Propylene glycol (used as an inactive stabilizer in many medications; historically, the "P" also stood for Paraldehyde, though this substance is not commonly used today)

- I — Infection, Iron, Isoniazid (which can cause lactic acidosis in overdose), Inborn errors of metabolism (an especially important consideration in pediatric patients)

- L — Lactic acidosis

- E — Ethylene glycol (Note: Ethanol is sometimes included in this mnemonic as well, although the acidosis caused by ethanol is actually primarily due to the increased production of lactic acid found in such intoxication.)

- S — Salicylates

Another frequently used mnemonic is KARMEL.

- K — Ketoacidosis

- A — aspirin

- R — Renal failure

- M — Methanol

- E — Ethylene glycol

- L — Lactic acidosis

Another frequently used mnemonic is KULT.

- K — Ketoacidosis (DKA, AKA)

- U — Uremia

- L — Lactic acidosis

- T — Toxins (Ethylene glycol, methanol, as well as drugs, such as aspirin, Metformin)

The preferred mnemonic of D. Robert Dufour, the chief of the Pathology and Laboratory Medicine Service, Veterans Affairs Medical Center, is DUMPSALE, which omits the I of MUDPILES as the proposed values of *I* are exceedingly rare in clinical practice.

- D — Diabetic ketoacidosis

- U — Uremia

- M — Methanol

- P — Paraldehyde

- S — Salicylates

- A — Alcoholic ketoacidosis

- L — Lactic acidosis

- E — Ethylene Glycol

The mnemonic for the [rare, in comparison] toxins is ACE GIFTs: Aspirin, Cyanide, Ethanolic ketosis, Glycols [ ethylene and propylene ], Isoniazid, Ferrous iron, Toluene. Most of these cause a lactic acidosis.

When acidosis is present on blood tests, the first step in determining the cause is determining the anion gap. If the anion gap is high (>12 mEq/L), there are several potential causes.

High anion gap metabolic acidosis is a form of metabolic acidosis characterized by a high anion gap (a medical value based on the concentrations of ions in a patient's serum). An anion gap is usually considered to be high if it is over 12 mEq/L.

High anion gap metabolic acidosis is caused generally by acid produced by the body. More rarely, high anion gap metabolic acidosis may be caused by ingesting methanol or overdosing on aspirin. The Delta Ratio is a formula that can be used to assess elevated anion gap metabolic acidosis and to evaluate whether mixed acid base disorder (metabolic acidosis) is present.

The list of agents that cause high anion gap metabolic acidosis is similar to but broader than the list of agents that cause a serum osmolal gap.

In the United States, hyperkalemia is induced by lethal injection in capital punishment cases. Potassium chloride is the last of the three drugs administered and actually causes death. Injecting potassium chloride into the heart muscle disrupts the signal that causes the heart to beat. This same amount of potassium chloride would do no harm if taken orally and not injected directly into the blood.

Heterozygous protein C deficiency occurs in 0.14–0.50% of the general population. Based on an estimated carrier rate of 0.2%, a homozygous or compound heterozygous protein C deficiency incidence of 1 per 4 million births could be predicted, although far fewer living patients have been identified. This low prevalence of patients with severe genetic protein C deficiency may be explained by excessive fetal demise, early postnatal deaths before diagnosis, heterogeneity in the cause of low concentrations of protein C among healthy individuals and under-reporting.

The incidence of protein C deficiency in individuals who present with clinical symptoms has been reported to be estimated at 1 in 20,000.

The affected animal should be left in the pasture, and not forced to come back to stall because excitation can darken the prognosis, even after adequate treatment.

Intravenous mixed calcium and magnesium injection are used. Subcutaneous injection of magnesium sulfate (200 ml of 50% solution) is also recommended.

Magnesium supplements are used to prevent the disease when ruminants, for obvious economic reasons, must have access to dangerous pastures.

In terms of treatment, acute hypoglycemia is reversed by raising the blood glucose, but in most forms of congenital hyperinsulinism hypoglycemia recurs and the therapeutic effort is directed toward preventing falls and maintaining a certain glucose level. Some of the following measures are often tried:

Corn starch can be used in feeding; unexpected interruptions of continuous feeding regimens can result in sudden, hypoglycemia, gastrostomy tube insertion (requires a minor surgical procedure) is used for such feeding.Prolonged glucocorticoid use incurs the many unpleasant side effects of Cushing's syndrome, while diazoxide can cause fluid retention requiring concomitant use of a diuretic, and prolonged use causes hypertrichosis. Diazoxide works by opening the K channels of the beta cells. Octreotide must be given by injection several times a day or a subcutaneous pump must be inserted every few days, octreotide can cause abdominal discomfort and responsiveness to octreotide often wanes over time. Glucagon requires continuous intravenous infusion, and has a very short "half life".

Nifedipine is effective only in a minority, and dose is often limited by hypotension.

Pancreatectomy (removal of a portion or nearly all of the pancreas) is usually a treatment of last resort when the simpler medical measures fail to provide prolonged normal blood sugar levels. For some time, the most common surgical procedure was removal of almost all of the pancreas, this cured some infants but not all. Insulin-dependent diabetes mellitus commonly develops, though in many cases it occurs many years after the pancreatectomy.Later it was discovered that a sizeable minority of cases of mutations were focal, involving overproduction of insulin by only a portion of the pancreas. These cases can be cured by removing much less of the pancreas, resulting in excellent outcomes with no long-term problems.