vitamin A

Fat soluble vitamin

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This entry is made by Compilation and application of scientific encyclopedia entries of "Science Popularization China" to examine.

Vitamin A is a Fat soluble vitamin , organic compound, chemical formula C twenty H thirty O， It is stable to heat, acid and alkali, and easy to be oxidized. Ultraviolet ray can promote its oxidative damage. Vitamin A includes A1 and A2, A1 is Retinol 。 Vitamin A2 is 3-dehydroretinol, whose physiological activity is 40% of vitamin A1.^[1]

Vitamin A has many physiological functions, such as promoting growth and reproduction, maintaining normal secretion of bone, epithelial tissue, vision and mucosal epithelium. Vitamin A and its analogues can prevent precancerous lesions. In case of deficiency, it is manifested as growth retardation and dark adaptation decline, resulting in night blindness. Because of epidermis and mucosa epithelial cells Dry eye disease occurs due to dryness, desquamation, hyperkeratosis, and decreased secretion of lacrimal glands. In severe cases, corneal softening, perforation, and blindness occur. The epithelial cells of the respiratory tract become keratinized and lose their cilia, which reduces their resistance to infection. The recommended vitamin A intake (RNI) for adults in China is 800 μ g retinol activity equivalent per day for men and 700 μ g retinol activity equivalent per day for women.^[2] Foods rich in vitamin A include liver, egg yolk and milk powder of poultry and livestock, Carotene It can be changed into vitamin A, red yellow and dark green vegetables in the intestinal mucosa, and fruits contain more carotene.^[1]

Chinese name: vitamin A^[6]
Foreign name: Vitamin A^[6-7]
Alias: Retinol^[6]
chemical formula: C twenty H thirty O^[6]
molecular weight: two hundred and eighty-six point four five two^[6]
CAS No: 68-26-8^[6]

Including types: Retinol Retinal 、 Retinoic acid , retinol acetate, retinol palmitate, etc
Nature: Fat soluble vitamin
Whether included in medical insurance: yes
Dosage form: Regular oral dosage form^[8]
Drug type: Vitamins^[8]

catalog

one brief introduction
two Structure and physical and chemical properties
three Synthesis of vitamin A
four Determination of vitamin A
five physiological function
▪ Visual function
▪ Maintain the integrity of skin and mucosa
▪ Nuclear hormone like effect
▪ Maintain and promote immune function

brief introduction

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Vitamin A is extremely important and easily lacking, which is necessary for human body to maintain normal metabolism and function Fat soluble vitamin It was discovered by American scientists Elmer Mc Collum and MargAret Davis between 1912 and 1914. In fact, as early as 1000 years ago, Chinese physicians in the Tang Dynasty Sun Simiao (581~682 AD) In the "Qianjin Prescription", it was recorded that the use of animal liver could treat night blindness, and there were also records about the use of cod liver oil to treat dry eye disease in Brazil, and olive oil to treat dry eye disease in Denmark. Before MargAret DAvis and others extracted a yellow viscous liquid vitamin A from cod liver, people did not know the existence of vitamin A, so he first named it "fat soluble A" (A is the first letter of German dry eye disease "AugendArre"). With the discovery of new fat soluble substances necessary for human body, by 1920, "fat soluble A" was officially named as vitamin A by British scientists.^[3]

Molecular structure of vitamin A

Vitamin A is not a single compound, but a series of Retinol （retinol）、 Retinal （retinene）、 Retinoic acid Retinoic acid, retinyl acetate, retinyl palmitate and other retinol derivatives. Their molecular structures are shown in the figure Molecular Structure of Vitamin A. Vitamin A only exists in animals, and it is very abundant in fish, especially in cod liver oil. Plants do not contain vitamin A, but many vegetables and fruits do Pro vitamin A —— Carotene It can be decomposed into vitamin A in the small intestine. One molecule of β - carotene can be decomposed into two molecules of vitamin A, while one molecule of A-carotene or γ - carotene can only produce one molecule of vitamin A.^[3]

Vitamin A is yellow flake crystal or crystalline powder, insoluble in water and glycerin, but soluble in most organic solvents such as alcohol, ether, hydrocarbon and halohydrocarbon. Its chemical property is relatively stable, but it will be easily damaged when exposed to heat, light or air, so it should be kept away from light. The chemical name of retinol, the main body of vitamin A, is all trans 3,7-dimethyl-9 - (2,6,6-trimethyl-1-cyclohexenyl-1) - 2,4,6,8-nontetraen-1-ol, and there are 4 Conjugated double bond In theory, there are 16 Geometric isomer Due to the steric hindrance effect, the geometric isomers existing in nature are all trans without hindrance, 9-cis, 13-cis, 9,13-bis cis and 11 cis with hindrance biological activity highest. Because vitamin A acetate (retinol acetate) is more stable than vitamin A alcohol (retinol), the products called "vitamin A" in the market are actually vitamin A acetate, which is a yellowish oily liquid that can be solidified after freezing, almost odorless or slightly fishy, but without rancidity, and very soluble in chloroform or ester, It is also soluble in anhydrous ethanol and vegetable oil, but insoluble in glycerol and water. It is unstable in air and light.^[3]

Structure and physical and chemical properties

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Vitamin A refers to all compounds with retinol biological activity. There are two categories of substances that can provide retinol bioactivity. One is retinol, its metabolites and synthetic analogs with similar structures. This kind of substances is also called Retinoids, also known as preformed vitamin A. The main dietary sources are retinol and retinoyl esters contained in animal foods. The other is provitamin A carotenoids, which refer to carotenoids from plant foods that can be converted into retinol in the body. They are the precursors of dietary retinol, mainly including β - carotene, α - carotene and β - cryptoxanthin.^[4]

Vitamin A is a group of 20 carbon structure with a β - ionone ring and four heads and tails connected isoprene The side chain composed of the unit and the molecular set that combines a hydroxyl group (retinol), or aldehyde group (retinol), or carboxylic acid group (retinoic acid), or ester group (retinol ester) at the carbon-15 position. Carotenoids are Polyisoprene Compound or Terpenoid It has been found that there are more than 600 forms of carotenoids in nature, of which only some have provitamin A nutritional activity, but only β - carotene, α - carotene and β - cryptoxanthin have the meaning of dietary vitamin A. All trans isomers are the most common and stable form of every carotene, but there are also many cis isomers. Carotenoids usually contain 40 carbon atoms and have an extensive conjugated double bond system. At the end of its conjugated carbon chain, they have one or two ring structures. The exception is lycopene, which has no ring structure and no vitamin A activity.^[4]

Vitamin A is a fat soluble vitamin, which can be dissolved in most organic solvents to varying degrees, but is insoluble in water. Vitamin A and its derivatives are easy to be oxidized and isomerized, especially when exposed to light (especially ultraviolet light), oxygen, active metals and high temperature environment, which can accelerate this oxidative damage. But the general cooking process will not cause too much damage to vitamin A in food. Under ideal conditions, such as low temperature freezing, serum, tissue or crystalline retinoids can remain stable for a long time. In the absence of oxygen, retinol is relatively stable to base, but unstable in acid, which may lead to dehydrogenation or rearrangement of double bonds. In the process of rancidity, the vitamin A and carotene contained in oil will be seriously damaged. Phospholipids, vitamin E or others in food antioxidant It can improve the stability of vitamin A. Among the derivatives of vitamin A, retinoic acid and retinoyl ester have the best stability.^[4]

Retinol and other retinoids have continuous conjugated double bonds, and they can produce unique ultraviolet or visible absorption spectra. The maximum absorption wavelength in ethanol is 325 nm for all trans retinol, 381 nm for all trans retinol, and 350 nm for all trans retinoic acid. Retinol can produce 470 nm fluorescence under 325 nm UV light. At present, the most common retinoid detection method is to use the above characteristics Reversed phase high performance liquid chromatography , with ultraviolet light/ Fluorescence detector To complete. Vitamin A is mainly stored in the liver in the body, accounting for 90% - 95% of the total amount, and a small amount is found in adipose tissue.^[4]

β - carotene is the most prominent component of carotenoids, because it is the first known carotenoid component; It is almost a carotenoid component with high content in human body; It is the most widely distributed and abundant in our food, especially in vegetables and fruits. Almost all vegetables and fruits have their traces more or less; In addition, it is also a class Carrot Among the components, the activity of provitamin A is the strongest.^[4]

The molecular formula of β - carotene is C forty H fifty-six Its molecular weight is 536.87, and its molecular structure has many conjugated double bonds. These double bonds can absorb some spectra in the visible light, making it show a special color, and at the same time, it has a strong ability to quench reactive oxygen free radicals, which can reduce the antioxidant damage of the body and play a role in disease prevention. Beta carotene molecule is actually a retinol molecule with two tails connected, which can be converted into two or one vitamin A through central or eccentric splitting. β - carotene is divided into all trans and cis isomers. All trans beta carotene can generate two molecules of all trans retinol (vitamin A) through central cleavage, while the yield of cis beta carotene converted to vitamin A is low.^[4]

The molecular structure of α - carotene is similar to that of β - carotene, which is isomer, but the difference is that β - ionone The 5 ', 6' double bond in the ring changes, and this β - ionone ring is an essential structure for vitamin A activity. Therefore, the production of α - carotene converted into vitamin A is only half of that of β - carotene. In addition to vitamin A activity. The properties and efficacy of α - carotene are similar to that of β - carotene.^[4]

β - lutein, also known as β - cryptoflavin and β - carotene-3-ol, is an oxyxanthin carotenoid with the molecular formula C forty H fifty-six O， The molecular weight is 552.87. Compared with beta carotene, The molecular structure of β - cryptoxanthin is that one light radical replaces the original hydrogen atom at position 3, and its molecule has one more oxygen atom than β - carotene, which results in the structural change of β - ionone ring, making it possible for this half of the molecule to lose the activity of vitamin A. Therefore, like α - carotene, β - cryptoxanthin has only half of the output of vitamin A converted into β - carotene. In addition to vitamin A activity, β - cryptoxanthin also has strong antioxidant activity.^[4]

Carotenoids in the diet are relatively stable, less damaged during cooking, and food processing and heat treatment help to improve plant cell The release of internal carotene improves its absorption rate. However, the loss will increase significantly under long-term high temperature, especially under the conditions of oxygen and ultraviolet radiation. The preservation rate of carotene is 70% - 90% in China's cooking methods.^[4]

Synthesis of vitamin A

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Synthesis of vitamin A by BASF method

Although vitamin A can be extracted from animal tissues, the resources are relatively dispersed, the steps are complicated, and the cost is high. Therefore, commercial vitamin A is a chemical synthetic product. Industrial synthesis of vitamin A at home and abroad mainly includes Roche in Switzerland and BASF in Germany. The former uses β - ionone It is the starting material and characterized by Grignard reaction. It is completed through Darzens reaction, Grignard reaction, selective hydrogenation, hydroxyl bromination and dehydrobromination Vitamin A acetate Synthesis of; The typical feature of the latter is Wittng reaction, and its synthesis route is shown in the figure "Synthesis of Vitamin A by BASF Method". It uses β - ionone as the starting material and acetylene to carry out Grignard reaction to generate acetylene - β - ionol, select hydrogenation to obtain ethylene - β - ionol, and then after Wittng reaction, use sodium alkoxide as the catalyst to condense with C5 aldehyde to generate vitamin A acetate.^[3]

Determination of vitamin A

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Common methods for testing vitamin A mainly include colorimetry 、 Ultraviolet spectrophotometry 、 Near infrared spectroscopy and High performance liquid chromatography 。 The principle of colorimetric determination of vitamin A is based on the fact that vitamin A can react with various acids to produce blue purple to pink colored compounds, in which vitamin A and Antimony trichloride - Trichloromethane The blue compound generated by solution (or trifluoroacetic acid chloroform solution) has characteristic absorption at 620nm wavelength, which is an earlier sensitive method. With the development of UV spectrophotometry and high performance liquid chromatography, this method has been rarely used for quantitative detection, only for qualitative detection. The principle of ultraviolet spectrophotometry is based on the maximum absorption of vitamin A at 325 or 328nm wavelength for quantitative detection. near infrared spectroscopy The rule is based on the fact that vitamin A has two relatively stable characteristic absorption peaks at 1721 and 1872 nm wavelength. High performance liquid chromatography is usually based on the characteristic absorption of vitamin A in the ultraviolet region and the natural fluorescence characteristics of vitamin A.^[3]

physiological function

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Vitamin A has extensive and important physiological functions in the human body, which mainly include vision, cell proliferation and differentiation regulation, intercellular information exchange and immune response. Its lack will lead to physiological function abnormalities and pathological changes.^[4]

Visual function

The classic or earliest recognized function of vitamin A is to participate in the maintenance of dark vision photosensitive material circulation in visual cells. The rod cells in the retina contain Rhodopsin , is composed of 11 cis retinol and opsin, which is sensitive to dark light. After rhodopsin is sensitized, 11 cis retinol is converted to all trans retinol and separated from opsin to generate visual electrical signals. The dissociated all trans retinol is reduced to all trans retinol in the rod cells and transported to retinal pigment epithelial cells. Together with all trans retinol from plasma, it starts a complex isomerization process, participates in the supply of 11 cis retinol required for the re synthesis of rhodopsin, and maintains dark light adaptation. Therefore, in order to maintain good dark vision, it is necessary to continuously supply sufficient 11 cis retinol to the rod cells. Vitamin A deficiency The supply of 11 cis retinol decreased and the dark adaptation time prolonged.^[4]

Maintain the integrity of skin and mucosa

Vitamin A is a coenzyme that regulates the synthesis of glycoprotein epithelial cells Its cell membrane plays a stabilizing role in maintaining the morphological integrity and functional integrity of epithelial cells. This effect of vitamin A on tissue function and integrity is achieved by mediating information exchange between adjacent cells. Vitamin A deficiency will cause drying of epithelial tissue, and normal columnar epithelial cells will change into angular layers Squamous cell , leading to cell keratinization. Epithelial cells of all kinds of tissues in the body will be affected, but the earliest affected cells are conjunctiva, cornea and lacrimal gland epithelial cells. Decreased lacrimal gland secretion leads to dry eye, dry conjunctiva or cornea, softening or even perforation. Skin hair follicles, sebaceous glands, sweat glands, tongue taste buds, respiratory and intestinal membranes, urinary and reproductive membranes and other epithelial cells will be affected, resulting in corresponding clinical manifestations and mucosal barrier function damage.^[4]

Nuclear hormone like effect

Vitamin A regulates and controls the expression of retinoid receptors in the nucleus Messenger RNA Activation and expression of. There are retinol like receptors in the nucleus, including three retinoic acid receptors RAR α, β and γ, and three nine cis isomers of retinol x receptors RxR α, β and γ. RARs can bind to and react with retinoic acid and isomers, while RXRs specifically bind to retinoic acid isomers (9-cis retinoic acid). These nuclear receptors form various homodimers or heterodimers by polymerization in pairs and bind to the corresponding retinoic acid reaction elements RARE or RXRE, thus regulating the corresponding regions of target cell genes. The most important function of retinoid receptors is to regulate cell division and differentiation. Reduction of information substances including RXR cell proliferation And promote Programmed cell death (Apoptosis). about cell differentiation The regulatory function of retinoids in cells mainly plays a role through RAR affecting cyclin. The results of this regulation can affect all aspects of the body, including growth and development, reproductive function, immune function, hematopoietic function, etc.^[4]

Maintain and promote immune function

Retinoids are essential for maintaining immune function, which depends on cell differentiation and proliferation induced by immune stimulation. Retinoid can improve cellular immune function and promote Immune cell Producing antibodies and promoting T lymphocytes Generate some Lymphokine 。 The effect of retinoic acid on maintaining adequate levels of circulating blood Natural killer cells Extremely important, the latter has antiviral and anti-tumor activities. It has been proved that retinoic acid can improve rats macrophage The phagocytic activity of IL-1 and other cell factor The latter is the mediating factor of inflammatory reaction and T B lymphocytes Activation factor of production. In addition, retinol is also required for the growth, differentiation and activation of B lymphocytes. When vitamin A is deficient, the expression of retinoic acid receptor in immune cells decreases accordingly, affecting the immune function of the body. Children with vitamin A deficiency and marginal deficiency have increased risk and mortality of infectious diseases.^[4]

Promote growth and development and maintain reproductive function

Reproductive tissue and mammalian Embryogenesis Relying on RAR for gene regulation, vitamin A plays an extremely important role in these tissues through related ways. These effects are also realized through the regulation of cell proliferation and differentiation, especially participating in endochondral osteogenesis. When vitamin A is deficient, the formation of long bones and the development of teeth are hindered; Male testis atrophy, sperm number and vitality decrease.^[4]

Antagonism to vitamin D activity and its effect on bone metabolism

Many research results show that vitamin A is closely related to bone metabolism. Vitamin A deficiency can Osteoclast The number decreases, Osteoblast Its function is out of control, resulting in excessive periosteal bone hyperplasia and smaller bone cavity. The adverse effects of excessive vitamin A on bone mineralization and structural integrity have become a recent concern. Excessive vitamin A can stimulate bone resorption and inhibit bone regeneration. This effect may be related to the Hypercalcemia They share a common mechanism. Considering vitamin A and vitamin D They are widely involved in the regulation of nuclear receptors in many cells. The effects of vitamin A deficiency and excess on bone metabolism may be related to their antagonism to vitamin D activity.^[4]

Anti cell proliferation

In addition to affecting normal health-related evolutionary functions, vitamin A also has a regulatory role in correcting a variety of pathological states. Vitamin A and its isomers can promote terminal differentiation, inhibit proliferation, and promote apoptosis, which plays a role in tumor during tissue malignant transformation. A variety of cancer cell lines in vitro have found that high-dose retinoids have anti-cancer ability.^[4]

Promote hemoglobin production and increase iron intake in food

Early studies found that vitamin A intervention experiment can increase the risk of hemoglobin And blood cell count. Vitamin A and provitamin A may improve iron absorption by blocking the interference of phytic acid. The study found that the effect of vitamin A nutrition on the blood system is not only the direct effect of dietary vitamin A on promoting iron absorption, but also has some regulatory effect on iron nutrition, including stimulating hematopoietic mother cells, promoting anti infection, and mobilizing iron into the red blood cell line. From the yolk sac stage in the early embryo, to the fetal hepatogenesis stage in the uterus, and then to the bone marrow generation stage, there are relevant literature to prove the existence of retinoids regulating hematopoiesis. Vitamin A not only affects the proliferation of bone marrow hematopoietic cell lines, but also affects platelet production and Thrombosis It also has an impact.^[4]

Application and side effects

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Vitamin A is mainly used to prevent and treat night blindness, dry eye disease, and also used for the local skin after burns Suppurative infection 。 Vitamin A intake by human body shall not exceed 3mg/day for adults and 2mg/day for children. If a large dose of vitamin A is taken, acute disease may occur due to low excretion ratio Hypervitamin A The main symptoms are short-term hydrocephalus and vomiting, and some may have headache, lethargy, nausea and other symptoms [9]. After taking large doses of vitamin A for a long time, children will suffer from excessive vitamin A, mainly Hepatosplenomegaly Red blood cells and white blood cells are reduced, bone marrow grows too fast, long bones become brittle, and fracture is easy to occur. A new Swedish study shows that middle-aged men with high concentrations of vitamin A in their blood are much more likely to have fractures in their old age than those with low levels of vitamin A. Therefore, vitamin A is indispensable to the human body and cannot be abused. As long as the diet is rich in vitamin A or carotene, it can effectively prevent vitamin A deficiency without taking additional vitamin A supplements.^[3]

Excessive hazard

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The toxic and side effects of vitamin A mainly depend on the intake of retinol and retinoyl ester, and are related to the physiological and nutritional status of the body. The concentration of vitamin A in liver exceeding 300mg/g is considered to be excessive and will cause corresponding clinical toxicity. The clinical manifestations of acute vitamin A excess include severe rash, headache, pseudotumor coma and rapid death. Chronic overdose is relatively common, and its clinical manifestations include central nervous system disorder symptoms Hepatic fibrosis , ascites and skin damage. Recently, it has been reported that bone marrow depression caused by vitamin A excess in infants and hypercalcemia caused by chronic vitamin A excess in adults. The study found that the toxicity of oil-based vitamin A or liver derived vitamin A was only 1/10 of that of hydrated, emulsified and solid retinol supplements.^[4]

Teratogenic effect

Studies have confirmed that 13 cis retinoic acid has teratogenic effects, so people are worried that high-dose vitamin A supplementation may have teratogenic effects. A large number of animal experiments have confirmed that excessive vitamin A can cause embryonic malformation. Epidemiological data show that excessive intake of preformed vitamin A can lead to birth defect 。 The most sensitive period is embryogenesis (early pregnancy). The birth defects caused by excessive vitamin A mainly occur in the organs evolved from brain nerves, such as craniofacial malformations central nervous system Malformations (excluding neural tube malformations), thyroid and heart malformations, etc. It is estimated that long-term daily intake of preformed vitamin A more than 10000 IU can cause teratogenesis. These birth defects may occur in the treatment of skin diseases with oral retinol analogues. Local use of vitamin A analogues in early pregnancy has little or no risk of growth abnormalities.^[4]

Bone mineral loss and risk of osteoporosis

Animal experiments have found that long-term vitamin A excess can lead to bone mineral loss, which may also have a similar effect in humans. A cross-sectional survey of Swedish women reported in 1998 and Case control study The results showed that when the daily intake was less than 1.5 mg, the BMD increased with the increase of vitamin A intake; However, when the daily intake is more than 1.5mg, increasing vitamin A intake can increase osteoporosis And the risk of medullary fracture.

Due to the limitations of various factors in the epidemiological study, the conclusions obtained have both support and opposition to the evidence that excessive vitamin A affects bone health. At present, great attention has been paid to this, but no clear conclusions have been formed. In particular, it is far from confirmed that the pre formed intake of vitamin A is a risk factor for bone health, and the definition of retinol intake that has a significant impact on bone health cannot be established, but it is certain that excessive intake of vitamin A should not be beneficial to bone health.^[4]

Liver injury

Animal experiment and human experiment data confirm that excessive vitamin A is associated with Abnormal liver function There is a very clear causal relationship between them, because the liver is the main storage organ of vitamin A and the main target organ of vitamin A toxicity. Liver abnormalities caused by vitamin A excess include reversible increase of liver enzyme activity, liver fibrosis, cirrhosis and death.^[4]

Increased risk of cardiovascular disease

yes Cardiovascular disease Of Observational research It was found that excessive vitamin A may increase the risk of cardiovascular disease. Adult in the United States cohort study High serum retinol levels are associated with a high risk of cardiovascular disease, but only in men. The current research data show that the toxicity of carotenoids such as beta carotene is very low. Unlike vitamin A, there are no reports of carotenoid deficiency or toxicity. Excessive intake of beta carotene can lead to carotenemia and temporary skin yellowing. It is reported that carotenemia can occur when subjects take a large amount of carrots and other foods for a long time or supplement 30 mg or more of beta carotene every day. These symptoms can be reversed a few days or weeks after reducing such carotenoid intake.^[4]

Lack of hazards

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Vitamin A deficiency has clinical and functional characteristics. For primary vitamin A deficiency, the tolerance of each person is different, which depends on a series of geographical and epidemiological factors. Vitamin A deficiency The main clinical manifestations of the disease are the symptoms and signs of ocular, visual and other epithelial dysfunction.^[4]

Eye and visual performance

Dry eye is one of the typical clinical features of vitamin A deficiency. According to specific ocular manifestations, dry eye can be divided into several stages. XN stage is the earliest stage, which mainly presents night blindness caused by dark adaptation function damage. Later, it is Phase X1A, Goblet cell Decreased secretion of mucus, resulting in dry conjunctiva; The next stage was X1B, where the terminal Pitt's patches appeared on the frontal surface of the conjunctiva. X2 stage is the disease progression stage, which shows simple corneal dryness. When the cornea is softened or ulcerated, or the liquefaction process of both, it is called X3 stage. At this time, if the liquefied surface is less than 1/3 of the corneal area, it is stage X3A, and if it is greater than 1/3, it is stage X3B. The ocular injury caused by keratomalacia is called dry eye fundus disease, also called XF stage.^[4]

Other manifestations of epithelial dysfunction

Hair follicle thickening（ Keratinization of hair follicle ）It is the skin representation of vitamin A deficiency. The reduction of mucin production in the mucosa and the abnormality of the morphology, structure and function of the mucosa can lead to pain and the decline of mucosal barrier function, which can affect the mucosa of the throat, tonsils, bronchi, lungs and digestive tract. Vitamin A deficiency and marginal deficiency lead to increased risk of infectious diseases and mortality in children.^[4]

Abnormal embryonic growth and development

Vitamin A deficiency can damage embryonic growth. The experimental animals severely deficient in vitamin A are prone to embryo absorption, and the surviving embryos will also have eye, lung, urinary tract and cardiovascular system abnormalities. When the human body is deficient in vitamin A, there is less abnormal morphology, but abnormal lung function can be seen.^[4]

Impaired immune function

Vitamin A deficiency can lead to blood Lymphocyte count Natural killer cells decreased and specific antibody reaction weakened. When vitamin A intake is insufficient, it can be observed that the number of white blood cells decreases, the weight of lymphoid organs decreases, the function of T cells is damaged, and the resistance to immunogenic tumors is reduced. In laboratory animal and human experiments, vitamin A deficiency leads to abnormal humoral and cellular immune functions.^[4]

Increased morbidity and mortality of infectious diseases

Vitamin A deficiency can lead to increased morbidity and mortality of infectious diseases in laboratory animals and humans, especially in developing countries. Children with mild to moderate vitamin A deficiency respiratory tract infection And increased risk of diarrhea; The mortality rate of children with mild xerophthalmia is four times that of children without xerophthalmia. High dose vitamin A supplementation for hospitalized children with measles can significantly reduce the non mortality rate of children and reduce the severity of complications. Research shows that vitamin A supplementation can reduce the severity of diarrhea and malaria in young children.^[4]

Prevention and treatment of deficiency

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Vitamin A deficiency is the main cause of blindness in children in developing countries and is also common among children in developing countries Nutritional deficiency 。 Because of the impact of VAD (vitamin A deficiency) and SVAD (marginal vitamin A deficiency) on children's health, the prevention and control of VAD and SVAD has become one of the public health problems that need to be solved urgently worldwide.^[5]

WHO and United Nations Children's Fund The intervention of vitamin A is carried out in various ways, including increasing the consumption of food containing vitamin A, food fortification of vitamin A, improving breastfeeding, and regular high-dose vitamin A supplementation.^[5]

Assessment of vitamin A nutritional status

Accurate evaluation of vitamin A nutrition level of susceptible individuals and populations is of great significance for the study of VAD, SVAD and the formulation, implementation and evaluation of nutrition intervention strategies. In practical work, the commonly used methods to check the vitamin A nutritional status of a group or individual mainly include: clinical examination of dry eye disease, dietary survey, determination of dark adaptability, inquiry of night blindness history, determination of serum retinol content, relative dose response test Isotope dilution method Determination of vitamin A content in liver and conjunctival imprinting cell method.^[5]

Nutrition education and reasonable dietary measures

Balanced nutrition

Through nutrition education and reasonable diet, the dietary intervention method to improve the intake of existing vitamin A rich foods in the region has long been considered as the most lasting method that can fundamentally improve the status of VAD and SVAD. Nutrition education should focus on promoting breastfeeding and increasing the supply of milk, eggs and dark vegetables.^[5]

Food fortified vitamin A

Food fortified vitamin A is a direct, effective and inexpensive method to prevent VAD and SVAD. Vitamin A, vitamin Bl Vitamin B2 Folic acid, nicotinic acid, iron, iodine, zinc and calcium are the main nutrients for nutritional fortification in China.^[5]

Equivalent content of vitamin A and retinol in food

Regular supplementation of vitamin A preparations

Regular supplementation of vitamin A preparations is a rapid and direct way to improve the nutritional status of vitamin A. It includes clinical dry eye disease, measles innutrition Clinical supplementation for children, targeted delivery by existing health service institutions and preventive supplementation for all high-risk groups.^[5]

At present, WHO puts forward the following suggestions for the prevention and treatment of vitamin A deficiency in different high-risk groups and for future research^[5] ：

① Infants under 5 months old (including newborns): vitamin A supplementation is not recommended. The role of vitamin A supplementation in reducing infant morbidity and mortality remains to be seen in the future randomized controlled trial To further confirm, and to further study the high incidence of VAD in mothers, the relationship between vitamin A and immune function, and to determine the appropriate evaluation indicators of VAD in this age group.^[5]

② Children aged 6-59 months: It is recommended to implement high-dose vitamin A supplementation for children aged 6-59 months whose VAD is a public health problem (that is, the incidence of VAD in this population is ≥ 20% or the incidence of night blindness is ≥ 1%), including 100000 IU supplementation for infants aged 6-11 months (HIV+or -), and 200000 IU supplementation every 4-6 months for children aged 12-59 months. In the future, it is also necessary to further study better vitamin A supplementation methods, improve the understanding of the joint intervention of vitamin A and vaccines, and seek better clinical and biochemical VAD evaluation indicators.

③ Pregnant women: vitamin A supplementation is not recommended as a part of routine prenatal care to prevent the morbidity and mortality of pregnant women and infants. For pregnant women in regions or countries (pregnant women) where VAD is a serious public health problem (i.e., the incidence of night blindness of pregnant women or infants aged 24 to 59 months is ≥ 1%), vitamin A supplementation can prevent night blindness, Supplemental dose: 10000 IU per day or 25000 IU per week for pregnant women over 12, but the duration and frequency of supplementation need further study. In the future, more research should focus on the effect of vitamin A supplementation during pregnancy, especially the combined effect of other interventions on mortality and the comprehensive review of the effect of vitamin A supplementation in the third month of pregnancy on the level of vitamin A in human milk.

④ Nursing mothers: It is not recommended to supplement vitamin A to nursing mothers as an intervention measure to prevent the morbidity and mortality of mothers and infants. The effect of supplementation of 200000 IU of vitamin A to lactating mothers 6 weeks after delivery on the level of retinol in human milk, as well as its metabolism, dose distribution, and excretion, needs further research.

⑤ Maternal and infant HIV infection: Vitamin A supplementation is not recommended for HIV positive mothers.^[5]

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