| Vitamin deficiency | |
|---|---|
| Other names | Avitaminosis, hypovitaminosis |
| Specialty | Endocrinology |
Vitamin deficiency is the condition of a long-term lack of avitamin. When caused by not enough vitamin intake it is classified as aprimary deficiency, whereas when due to an underlying disorder such asmalabsorption it is called asecondary deficiency. An underlying disorder can have 2 main causes:
Conversely,hypervitaminosis refers to symptoms caused by vitamin intakes in excess of needs, especially for fat-soluble vitamins that can accumulate in body tissues.[3][5][11]
The history of the discovery of vitamin deficiencies progressed over centuries from observations that certain conditions – for example,scurvy – could be prevented or treated with certain foods having high content of a necessary vitamin, to the identification and description of specific molecules essential for life and health. During the 20th century, several scientists were awarded theNobel Prize in Physiology or Medicine or theNobel Prize in Chemistry for their roles in the discovery of vitamins.[12][13][14]
A number of regions have published guidelines defining vitamin deficiencies and advising specific intakes for healthy people, with different recommendations for women, men, infants, the elderly, and during pregnancy and breast feeding including Japan, theEuropean Union, the United States, and Canada.[6][3][5] These documents have been updated as research is published. In the US,Recommended Dietary Allowances (RDAs) were first set in 1941 by the Food and Nutrition Board of theNational Academy of Sciences. There were periodic updates, culminating in theDietary Reference Intakes.[4] Updated in 2016, the USFood and Drug Administration published a set of tables that defineEstimated Average Requirements (EARs) and (RDAs).[3][15] RDAs are higher to cover people with higher than average needs. Together, these are part of Dietary Reference Intakes. For a few vitamins, there is not sufficient information to set EARs and RDAs. For these, an Adequate Intake is shown, based on an assumption that what healthy people consume is sufficient.[3] Countries do not always agree on the amounts of vitamins needed to safeguard against deficiency. For example, for vitamin C, the RDAs for women for Japan, the European Union (called Population Reference Intakes) and the US are 100, 95 and 75 mg/day, respectively.[3][5][16] India sets its recommendation at 40 mg/day.[17]
| Vitamin | Symptoms & Diagnosis | Information |
|---|---|---|
| Thiamine (Vitamin B1) deficiency | Weight loss, emotional disturbances, impaired sensory perception, weakness and pain in the limbs, and periods of irregular heart beat. Deficiency is assessed byred blood cell status andurinary output.[18][19] | Especially common in countries that do not require fortification of wheat and maize flour and rice to replace the naturally occurring thiamine content lost tomilling,bleaching and other processing.[10] Severe deficiency causesberiberi, which became prevalent in Asia as more people adopted a diet primarily of white rice.Wernicke encephalopathy andKorsakoff syndrome are forms of beriberi. Alcoholism can also cause vitamin deficiencies. Long-term deficiencies can be life-threatening.[20] |
| Riboflavin (Vitamin B2) deficiency | Deficiency causes painful red tongue with sore throat, chapped and cracked lips, and inflammation at the corners of the mouth (angular cheilitis). Eyes can be itchy, watery, bloodshot and sensitive to light. Riboflavin deficiency also causesanemia with red blood cells that are normal in size and hemoglobin content, but reduced in number. This is distinct from anemia caused by deficiency of folic acid or vitamin B12.[21][22] | Especially common in countries that do not require fortification of wheat and maize flour and rice to replace the naturally occurring riboflavin lost during processing.[10] |
| Niacin (Vitamin B3) deficiency | Deficiency causespellagra, a reversible nutritional wasting disease characterized by four classic symptoms often referred to as the four Ds:diarrhea,dermatitis,dementia, and death. The dermatitis occurs on areas of skin exposed to sunlight, such as backs of hands and neck. Niacin deficiency is a consequence of a diet low in both niacin and theamino acidtryptophan, a precursor for the vitamin. Low plasma tryptophan is a non-specific indicator, meaning it can have other causes. The signs and symptoms of niacin deficiency start to revert within days of oral supplementation with large amounts of the vitamin.[23][24] | Chronic alcoholism is a contributing risk factor. |
| Pantothenic acid (Vitamin B5) deficiency | Irritability, fatigue, andapathy.[25][26] | Extremely rare. |
| Vitamin B6 deficiency | Microcytic anemia,electroencephalographic abnormalities, dermatitis,seborrhoeic dermatitis-like eruption,atrophic glossitis withulceration,angular cheilitis,conjunctivitis, andintertrigo. Neurologic symptoms of depression,somnolence, confusion, andneuropathy (due to impairedsphingosine synthesis) andmicrocytic anemia[27][28] | Uncommon, although it may be observed in certain conditions, such asend-stage kidney diseases ormalabsorption syndromes, such asceliac disease,Crohn disease orulcerative colitis. |
| Biotin (Vitamin B7) deficiency | Rashes including red, patchy ones near the mouth and fine, brittle hair.Hallucinations,Lethargy, Milddepression, which may progress to profoundfatigue and, eventually, tosomnolence, Generalized muscular pains (myalgia) andParesthesias. Decreased urinary excretion of biotin and increased urinary excretion of3-hydroxyisovaleric acid are better indicators of biotin deficiency than concentration in the blood.[29] | Rare, although biotin status can be compromised in alcoholics and during pregnancy and breastfeeding.Deficiency affects hair growth and skin health.[30][31] |
| Folate (Vitamin B9) deficiency | Symptoms may includefeeling tired, heartpalpitations,shortness of breath, feeling faint, open sores on the tongue, loss of appetite, changes in the color of the skin or hair, irritability, andbehavioral changes.[32] In adults,anemia (macrocytic,megaloblastic anemia) can be a sign of advanced folate deficiency. | Common, and associated with numerous health problems, but primarily withneural tube defects (NTDs) in infants when the mother's plasma concentrations were low during the first third of pregnancies. Government-mandated fortification of foods with folic acid has reduced the incidence of NTDs by 25% to 50% in more than 60 countries using such fortification.[10] Deficiency can also result from raregenetic factors, such asmutations in theMTHFR gene that lead to compromised folate metabolism.[33][34]Cerebral folate deficiency is a rare condition in which concentrations of folate are low in the brain despite being normal in the blood.[35] |
| Vitamin B12 deficiency | Anemia,neurological anddigestive disorders.[36][37] This may result in feeling tired, shortness of breath, lightheadedness, headaches, mouth ulcers,pale skin, rapid heartbeat, loss of appetite, hair loss, low blood pressure, decreased ability to think, joint pain,numbness and tingling to the fingers and toes, and tinnitus.[38] Damage to nerves may result in depression, confusion, memory loss, difficulty walking, sense loss,mania, andpsychosis. | Lead tomegaloblastic anemia,subacute combined degeneration of spinal cord, andmethylmalonic acidemia, among other conditions. Supplementation with folate can mask vitamin B12 deficiency.[39][40] Consuming a vegan diet increases the risk, since Vitamin B12 is mostly found in food and drinks made from animal products, including eggs and dairy products. |
| Vitamin C deficiency | Deficiency leads to weakness, weight loss and general aches and pains. Longer-term depletion affectsconnective tissues, severegum disease, and bleeding from the skin.[41][42] | Rare, consequently, no countries fortify foods as a means of preventing this deficiency.[10] The historic importance of vitamin C deficiency relates to occurrence on long sea-going voyages, when the ship food supplies had no good source of the vitamin. Deficiency results inscurvy when plasma concentrations fall below 0.2 mg/dL, whereas the normal plasma concentration range is 0.4 to 1.5 mg/dL. |
| Vitamin | Symptoms & Diagnosis | Information |
|---|---|---|
| Vitamin A deficiency | Can causenyctalopia (night blindness) andkeratomalacia, the latter leading to permanent blindness if not treated. The normal range is 30 to 65 μg/dL, butplasma concentrations within the range are not a good indicator of a pending deficiency because the normal range is sustained until liver storage is depleted. After that happens, plasmaretinol concentration falls to lower than 20 μg/dL, signifying a state of vitamin A inadequacy.[43][44][45] | It is the leading cause of preventable childhood blindness, afflicting 250,000 to 500,000 malnourished children in the developing world each year, about half of whom die within a year of becoming blind, as vitamin A deficiency also weakens theimmune system. |
| Vitamin D deficiency | Usually asymptomatic, causes reduced bone density (osteomalacia), rickets, myopathy, and is associated with the development ofschizophrenia. It is typically diagnosed by measuring the concentration of the25-hydroxyvitamin D (25(OH)D) in plasma, which is the most accurate measure of stores of vitamin D in the body. Deficiency is defined as less than 10 ng/mL, and insufficiency in the range of 10–30 ng/mL. Serum 25(OH)D concentrations above 30 ng/mL are "not consistently associated with increased benefit." Serum concentrations above 50 ng/mL may be cause for concern. | Common, most foods do not contain vitamin D, indicating that a deficiency will occur unless people get sunlight exposure or eat manufactured foods purposely fortified with vitamin D. Vitamin D deficiency is a known cause ofrickets, and has been linked to numerous other health problems.[46][47] |
| Vitamin E deficiency | Causes poor conduction of electrical impulses along nerves due to changes in nerve membrane structure and function.[48][49] The US Institute of Medicine defines deficiency as a blood concentration of less than 12 μmol/L. | Rare, occurring as a consequence of abnormalities in dietary fat absorption or metabolism, such as a defect in thealpha-tocopheroltransport protein, rather than from a diet low in vitamin E. |
| Vitamin K deficiency | Signs and symptoms can include sensitivity to bruising, bleeding gums, nosebleeds, and heavy menstrual bleeding in women.[50][51] | Rare as consequence of low dietary intake. A deficient state can be a result of fat malabsorption diseases. Newborn infants are a special case. Plasma vitamin K is low at birth, even if the mother is supplemented during pregnancy, because the vitamin is not transported across the placenta. Vitamin K deficiency bleeding (VKDB) due to physiologically low vitamin K plasma concentrations is a serious risk for premature and term newborn and young infants. Untreated, consequences can cause brain damage or death. The prevalence of VKDB is reported at 0.25 to 1.7%, with higher risk in Asian populations. The recommended prevention treatment is anintramuscular injection of 1 mg of vitamin K at birth (called theVitamin K shot.).[52] There are protocols for oral administration, but intramuscular injection is preferred.[53] |
Food fortification is the process of addingmicronutrients (essential trace elements and vitamins) to food as apublic health policy which aims to reduce the number of people with dietary deficiencies within a population.Staple foods of a region can lack particular nutrients due to the soil of the region or from inherent inadequacy of a normal diet. Addition of micronutrients to staples and condiments can prevent large-scaledeficiency diseases in these cases.[7]
As defined by theWorld Health Organization (WHO) and theFood and Agriculture Organization of the United Nations (FAO), fortification refers to "the practice of deliberately increasing the content of an essential micronutrient, i.e., vitamins and minerals in a food irrespective of whether the nutrients were originally in the food before processing or not, so as to improve the nutritional quality of the food supply and to provide a public health benefit with minimal risk to health", whereas enrichment is defined as "synonymous with fortification and refers to the addition of micronutrients to a food which are lost during processing".[8] The Food Fortification Initiative lists all countries in the world that conduct fortification programs,[9] and within each country, what nutrients are added to which foods. Vitamin fortification programs exist in one or more countries for folate, niacin, riboflavin, thiamin, vitamin A, vitamin B6, vitamin B12, vitamin D and vitamin E. As of 21 December 2018, 81 countries required food fortification with one or more vitamins.[10] The most commonly fortified vitamin – as used in 62 countries – is folate; the most commonly fortified food is wheat flour.[10]
Starting in 2000, rice was experimentally genetically engineered to produce higher than normalbeta-carotene content, giving it a yellow/orange color. The product is referred to asgolden rice (Oryza sativa).[54][55] Biofortifiedsweet potato, maize, andcassava were other crops introduced to enhance the content of beta-carotene and certain minerals.[56][57]
When eaten, beta-carotene is aprovitamin, converted to retinol (vitamin A). The concept is that in areas of the world where vitamin A deficiency iscommon, growing and eating this rice would reduce the rates of vitamin A deficiency, particularly its effect on childhood vision problems.[54] As of 2018, fortified golden crops were still in the process of government approvals,[58] and were being assessed for taste and education about their health benefits to improve acceptance and adoption by consumers in impoverished countries.[56]
Some vitamins cause acute or chronictoxicity, a condition calledhypervitaminosis, which occurs mainly forfat-soluble vitamins if over-consumed by excessive supplementation.Hypervitaminosis A[59] andhypervitaminosis D[60] are the most common examples. Vitamin D toxicity does not result from sun exposure or consuming foods rich in vitamin D, but rather from excessive intake of vitamin D supplements, possibly leading tohypercalcemia, nausea, weakness, andkidney stones.[61]
The United States, European Union and Japan, among other countries, have established"tolerable upper intake levels" for those vitamins which have documented toxicity.[3][5][11]
| Year of discovery | Vitamin |
|---|---|
| 1913 | Vitamin A (Retinol) |
| 1910 | Vitamin B1 (Thiamine) |
| 1920 | Vitamin C (Ascorbic acid) |
| 1920 | Vitamin D (Calciferol) |
| 1920 | Vitamin B2 (Riboflavin) |
| 1922 | Vitamin E (Tocopherol) |
| 1929 | Vitamin K1 (Phylloquinone) |
| 1931 | Vitamin B5 (Pantothenic acid) |
| 1931 | Vitamin B7 (Biotin) |
| 1934 | Vitamin B6 (Pyridoxine) |
| 1936 | Vitamin B3 (Niacin) |
| 1941 | Vitamin B9 (Folate) |
| 1948 | Vitamin B12 (Cobalamins) |
In 1747, the Scottish surgeonJames Lind discovered thatcitrus foods helped preventscurvy, a particularly deadly disease in whichcollagen is not properly formed, causing poor wound healing, bleeding of thegums, severe pain, and death.[62] In 1753, Lind published hisTreatise on the Scurvy, which recommended using lemons andlimes to avoidscurvy, which was adopted by the BritishRoyal Navy. This led to the nicknamelimey for British sailors. Lind's discovery, however, was not widely accepted by individuals in the Royal Navy'sArctic expeditions in the 19th century, where it was widely believed that scurvy could be prevented by practicing goodhygiene, regular exercise, and maintaining themorale of the crew while on board, rather than by a diet of fresh food.[62]
During the late 18th and early 19th centuries, the use of deprivation studies allowed scientists to isolate and identify a number of vitamins. Lipid fromfish oil was used to curerickets in rats, and the fat-soluble nutrient was called "antirachitic A". Thus, the first "vitamin" bioactivity ever isolated, which cured rickets, was initially called "vitamin A"; however, the bioactivity of this compound is now calledvitamin D.[63] In 1881,Russian medical doctorNikolai I. Lunin studied the effects of scurvy at theUniversity of Tartu. He fed mice an artificial mixture of all the separate constituents of milk known at that time, namely theproteins, fats,carbohydrates, andsalts. The mice that received only the individual constituents died, while the mice fed by milk itself developed normally. He made a conclusion that substances essential for life must be present in milk other than the known principal ingredients. However, his conclusions were rejected by his advisor,Gustav von Bunge.[64]
In East Asia, where polishedwhite rice was the common staple food of the middle class,beriberi resulting from lack of vitamin B1 wasendemic. In 1884,Takaki Kanehiro, a British-trained medical doctor of theImperial Japanese Navy, observed that beriberi was endemic among low-ranking crew who often ate nothing but rice, but not among officers who consumed a Western-style diet. With the support of the Japanese Navy, he experimented using crews of twobattleships; one crew was fed only white rice, while the other was fed a diet of meat, fish, barley, rice, and beans. The group that ate only white rice documented 161 crew members with beriberi and 25 deaths, while the latter group had only 14 cases of beriberi and no deaths. This convinced Takaki and the Japanese Navy that diet was the cause of beriberi, but they mistakenly believed that sufficient amounts of protein prevented it.[65] That diseases could result from some dietary deficiencies was further investigated byChristiaan Eijkman, who in 1897 discovered that feeding unpolished rice instead of the polished variety to chickens helped to prevent beriberi.[66] The following year,Frederick Hopkins postulated that some foods contained "accessory factors" — in addition to proteins, carbohydrates, fatsetc. — that are necessary for the functions of the human body.[62] Hopkins and Eijkman were awarded theNobel Prize for Physiology or Medicine in 1929 for their discoveries.[12]
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In 1910, the first vitamin complex was isolated by Japanese scientistUmetaro Suzuki, who succeeded in extracting a water-soluble complex of micronutrients from rice bran and named itaberic acid (laterOrizanin). He published this discovery in a Japanese scientific journal.[67] When the article was translated into German, the translation failed to state that it was a newly discovered nutrient, a claim made in the original Japanese article, and hence his discovery failed to gain publicity. In 1912 Polish-born biochemistCasimir Funk, working in London, isolated the same complex of micronutrients and proposed the complex be named "vitamine". It was later to be known as vitamin B3 (niacin), though he described it as "anti-beri-beri-factor" (which would today be called thiamine or vitamin B1). Funk proposed the hypothesis that other diseases, such as rickets,pellagra,coeliac disease, and scurvy could also be cured by vitamins.Max Nierenstein, a friend and reader of Biochemistry at Bristol University, reportedly suggested the "vitamine" name (from "vital amine").[68][69] The name soon became synonymous with Hopkins' "accessory factors", and by the time it was shown that not all vitamins areamines the word was already ubiquitous. In 1920,Jack Cecil Drummond proposed that the final "e" be dropped to deemphasize the "amine" reference, after researchers began to suspect that not all "vitamines" (in particular,vitamin A) have an amine component.[65]
In 1930,Paul Karrer elucidated the correct structure forbeta-carotene, the main precursor of vitamin A, and identified othercarotenoids. Karrer andNorman Haworth confirmed Albert Szent-Györgyi's discovery ofascorbic acid and made significant contributions to the chemistry offlavins, which led to the identification oflactoflavin. For their investigations on carotenoids, flavins and vitamins A and B2, Karrer and Haworth jointly received theNobel Prize in Chemistry in 1937.[13] In 1931,Albert Szent-Györgyi and a fellow researcher Joseph Svirbely suspected that "hexuronic acid" was actuallyvitamin C, and gave a sample toCharles Glen King, who proved its anti-scorbutic activity in his long-establishedguinea pig scorbutic assay. In 1937, Szent-Györgyi was awarded theNobel Prize in Physiology or Medicine for this discovery. In 1938,Richard Kuhn was awarded theNobel Prize in Chemistry for his work on carotenoids and vitamins, specifically B2 and B6.[14] In 1943,Edward Adelbert Doisy andHenrik Dam were awarded the Nobel Prize in Physiology or Medicine for their discovery ofvitamin K and its chemical structure. In 1967,George Wald was awarded the Nobel Prize in Physiology or Medicine (jointly withRagnar Granit andHaldan Keffer Hartline) for the discovery that vitamin A could participate directly in a physiological process.[12]
