Vitamin A Toxicity – Nutritional Disorders

By

Larry E. Johnson

, MD, PhD, University of Arkansas for Medical Sciences

Reviewed/Revised Nov 2022

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Vitamin A toxicity can be acute (usually due to accidental ingestion by children) or chronic. Both types usually cause headache and increased intracranial pressure. Acute toxicity causes nausea and vomiting. Chronic toxicity causes changes in skin, hair, and nails; abnormal liver test results; and, in a fetus, birth defects. Diagnosis is usually clinical. Unless birth defects are present, adjusting the dose almost always leads to complete recovery.

Vitamin A is required for the formation of rhodopsin, a photoreceptor pigment in the retina (see table ). Vitamin A helps maintain epithelial tissues and is important for lysosome stability and glycoprotein synthesis.

Dietary sources of preformed vitamin A include fish liver oils, liver, egg yolks, butter, and vitamin A–fortified dairy products. Normally, the liver stores 80 to 90% of the body’s vitamin A. To use vitamin A, the body releases it into the circulation bound to prealbumin (transthyretin) and retinol-binding protein. Beta-carotene and other provitamin carotenoids, contained in green leafy and yellow vegetables, carrots, and deep- or bright-colored fruits, are converted to vitamin A. Carotenoids are absorbed better from vegetables when they are cooked or homogenized and served with some fat (eg, oils).

Retinol activity equivalents (RAE) were developed because provitamin A carotenoids have less vitamin A activity than preformed vitamin A; 1 mcg retinol = 3.33 units.

Synthetic vitamin analogs (retinoids) are being used increasingly in dermatology. The possible protective role of beta-carotene and retinoids against some epithelial cancers is under study.

When taken as a supplement, beta-carotene has been associated with increased cancer and cardiovascular risk; risk does not seem to increase when carotenoids are consumed in fruits and vegetables.

(See also Overview of Vitamins Overview of Vitamins Vitamins may be Fat soluble (vitamins A, D, E, and K) Water soluble (B vitamins and vitamin C) The B vitamins include biotin, folate, niacin, pantothenic acid, riboflavin (B2), thiamin (B1)… read more .)

Acute vitamin A toxicity in children may result from taking large doses (> 300,000 units [> 100,000 RAE]), usually accidentally. In adults, acute toxicity has occurred when arctic explorers ingested polar bear or seal livers, which contain several million units of vitamin A.

Chronic vitamin A toxicity in older children and adults usually develops after doses of > 100,000 units (> 30,000 RAE)/day have been taken for months. Megavitamin therapy is a possible cause, as are massive daily doses (150,000 to 350,000 units [50,000 to 120,000 RAE]) of vitamin A or its metabolites, which are sometimes given for nodular acne or other skin disorders. Adults who consume > 4500 units (> 1500 RAE)/day of vitamin A may develop osteoporosis. Infants who are given excessive doses (18,000 to 60,000 units [6,000 to 20,000 RAE]/day) of water-miscible vitamin A may develop toxicity within a few weeks. Birth defects occur in children of women receiving isotretinoin (which is related to vitamin A) for acne treatment during pregnancy. Megadoses of vitamin A can cause liver toxicity.

Although carotene is converted to vitamin A in the body, excessive ingestion of carotene causes carotenemia, not vitamin A toxicity. Carotenemia is usually asymptomatic but may lead to carotenosis, in which the skin becomes yellow.

Although symptoms of vitamin A toxicity may vary, headache and rash usually develop during acute or chronic toxicity.

Acute toxicity causes increased intracranial pressure. Drowsiness, irritability, abdominal pain, nausea, and vomiting are common. Sometimes the skin subsequently peels.

Early symptoms of chronic toxicity are sparsely distributed, coarse hair; alopecia of the eyebrows; dry, rough skin; dry eyes; and cracked lips. Later, severe headache, idiopathic intracranial hypertension (pseudotumor cerebri), and generalized weakness develop. Cortical hyperostosis of bone and arthralgia may occur, especially in children. Fractures may occur easily, especially in the older people. In children, toxicity can cause pruritus, anorexia, and failure to thrive. Hepatomegaly and splenomegaly may occur.

In carotenosis, the skin (but not the sclera) becomes deep yellow, especially on the palms and soles.

• Clinical evaluation

Diagnosis of vitamin A toxicity is clinical. Blood vitamin levels correlate poorly with toxicity. However, if clinical diagnosis is equivocal, laboratory testing may help. In vitamin A toxicity, fasting serum retinol levels may increase from normal (28 to 86 mcg/dL [1 to 3 mcmol/L]) to > 100 mcg/dL (> 3.49 mcmol/L), sometimes to > 2000 mcg/dL (> 69.8 mcmol/L). Hypercalcemia Hypercalcemia Hypercalcemia is a total serum calcium concentration > 10. 4 mg/dL (> 2.60 mmol/L) or ionized serum calcium > 5.2 mg/dL (> 1.30 mmol/L). Principal causes include hyperparathyroidism… read more is common.

Differentiating vitamin A toxicity from other disorders may be difficult. Carotenosis may also occur in severe hypothyroidism and anorexia nervosa, possibly because carotene is converted to vitamin A more slowly.

Complete recovery usually occurs if vitamin A ingestion stops. Symptoms and signs of chronic toxicity usually disappear within 1 to 4 weeks. However, birth defects in the fetus of a mother who has taken megadoses of vitamin A are not reversible.

Vitamin A is stopped.

• Vitamin A toxicity can be caused by ingesting high doses of vitamin A—acutely (usually accidentally by children) or chronically (eg, as megavitamin therapy or treatment for skin disorders).

• Acute toxicity causes rash, abdominal pain, increased intracranial pressure, and vomiting.

• Chronic toxicity causes rash, increased intracranial pressure, sparse and coarse hair, dry and rough skin, and arthralgia; risk of fractures is increased, especially in the older people.

• Diagnose based on clinical findings.

• When vitamin A is stopped, symptoms (except birth defects) usually resolve within 1 to 4 weeks.

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Vitamin A Toxicity – StatPearls

Continuing Education Activity

Vitamin A toxicity can due to either topical or oral vitamin A administration. Oral vitamin A toxicity can be acute, due to the ingestion of a large amount of vitamin A over a short period of time, or chronic, due to oral ingestion over a longer duration. The most severe adverse effect of systemic retinoids is teratogenicity. The most common adverse effect of topical vitamin A is skin irritation, erythema, and peeling. This activity describes the evaluation and management of vitamin A toxicity and highlights the role of the interprofessional team in improving care for affected patients.

Objectives:

• Describe the pathophysiology of vitamin A toxicity.

• Review the presentation of a patient with vitamin A toxicity.

• Describe the typical laboratory findings of a patient with vitamin A toxicity .

• Describe the importance of coordination among the interprofessional team to ensure safe prescribing practices for vitamin A supplements, in particular in women that are or may become pregnant.

Access free multiple choice questions on this topic.

Introduction

Vitamin A toxicity can occur from either the topical or oral form of Vitamin A. Each has its own set of adverse effects. Oral vitamin A toxicity can be acute or chronic. In acute toxicity, ingestion occurs because of the ingestion of a large amount of vitamin A over a short period of time. In chronic toxicity, intake is over a longer duration. The most common adverse effect of topical retinoids is skin irritation, notably erythema and peeling. The most severe adverse effect of systemic retinoids is teratogenicity. Each year, in the US alone over 60,000 cases of Vitamin toxicity are reported. Unlike the water-soluble vitamins, the fat-soluble vitamins tend to accumulate in the body.

Etiology

As noted above, vitamin A toxicity can occur from either topical or oral use. Oral vitamin A delivery comes in two forms: provitamin A (a prodrug that is metabolized to vitamin A) and preformed vitamin A. Pre-formed vitamin A is obtained from animal food sources, including dairy products and liver, and in most supplements. A list of other foods containing Vitamin A includes milk, cheese, margarine, butter, eggs, chicken, chicken liver, beef, beef liver, processed meats, pizza, fish, and cold breakfast cereals[1]. Provitamin A (beta-carotene and other carotenoids), found in plants such as green leafy vegetables, sweet potatoes, and carrots, must be metabolized to vitamin A. As a result, it is less likely to cause toxicity.

Many people in the United States take either isolated supplemental Vitamin A or other supplements that contain vitamin, A in addition to dietary intake. The current recommended dietary allowance of vitamin A is 800 retinol equivalents or 2700 international units (IU) for women[1].

Excessive intake of preformed vitamin A, but not precursors, has been linked to teratogenicity in both human and animals studies[1]. In women taking over 10,000 IUs of preformed vitamin A per day from supplements, it is estimated that 1 of 57 babies is born with a secondary congenital disability.

Epidemiology

Reported incidences of vitamin A toxicity are quite rare, with fewer than 10 cases per year from 1976 to 1987[2]. Epidermal irritation is the most common side effect of topical retinoids. Teratogenicity is the most severe side effect of oral retinoids, affecting 1 in 57 women ingesting over 10,000 IUs daily of preformed vitamin A [1]. Isotretinoin is estimated to increase the risk of malformation 25-fold[2].

Pathophysiology

Skin irritation in the form of peeling and erythema is the most common adverse effect from topical vitamin A use. The peeling from topical retinoids is secondary to the hyper-proliferation of the epidermis mediated by retinoic acid receptor stimulation [3]. Interestingly, the erythema may be mediated through a different mechanism.

The risk of teratogenicity from the use of topical retinoids is extremely low given that systemic absorption has been inconsequential in animal and human studies [4]. Topical retinoid application has not been proven to cause congenital disorders when used during pregnancy. Other adverse effects include transient hypopigmentation and hyperpigmentation, Koebnerization of psoriasis, allergic contact dermatitis, and ectropion.

With regards to systemic retinoid usage, teratogenicity is the most worrisome adverse effect. Teratogenic findings include craniofacial (cleft lip/palate), cardiac (transposition of the great vessels), thymic, and central nervous system (microcephaly, hydrocephalus) abnormalities [2]. Isotretinoin is estimated to increase the risk of these malformations 25-fold. The mechanism is thought to be through a toxic effect on neural crest cells, possibly affecting the regulation of axial patterning in the embryo via the expression of the homeobox gene Hoxb-1[5].

Acute retinoid toxicity has resulted in mucocutaneous and laboratory abnormalities. Mucocutaneous effects include dry lips, cheilitis, and dry oral, ophthalmic, and nasal mucosa. The putative mechanism is decreased sebum production, reduced epidermal thickness, and altered barrier function. Other cutaneous effects seen include overall skin dryness and pruritus, peeling of palms and soles, and fingertip fissuring. Telogen effluvium may be seen with higher doses.

Chronic retinoid toxicity can affect many organ systems. Bone effects include changes such as bone spurs, calcinosis, and bone resorption with resulting hypercalcemia[6]. Long-term consumption of high levels of dietary vitamin A may stimulate bone resorption and inhibit formation, contributing to osteoporosis and hip fractures[7]. Central nervous system effects include headache, nausea, and vomiting. Pseudotumor cerebri syndrome rarely has been noted secondary to vitamin A toxicity [8]. Hypothyroidism, reversible upon cessation of therapy, was seen in 40% of patients in Cutaneous T-cell lymphoma trials with bexarotene [9]. Additionally, reversible renal dysfunction characterized by elevated creatinine was seen with etretinate but not isotretinoin[10].

Hypertriglyceridemia is the most common systemic effect of retinoids. Both triglyceride and cholesterol levels have been found to be elevated in patients using bexarotene, isotretinoin, etretinate, and acitretin. Total and LDL elevations may occur[11][12]. Accompanying cases of acute hemorrhagic pancreatitis and eruptive xanthomas can also be seen.

Elevated serum transaminases may occur with oral retinoid usage. These elevations more often occur with etretinate or acitretin as compared to isotretinoin and bexarotene. These elevations typically occur 2-8 weeks after initiation of therapy with normalization over another 2-4 weeks. Liver damage leading to fibrosis and hepatic stellate cell activation have both been seen in patients with hypervitaminosis A[13].

No causal association exists between isotretinoin and depression, psychosis, or suicide attempts, although a link had been previously suggested[14].

Toxicokinetics

The dose used in the treatment of degenerative eye diseases is 15,000 IUs daily. This is less than the maximal dose of 25,000 IU/day and is well tolerated after 12 years of treatment[15].

No safe minimum dose of oral retinoids during pregnancy has been established.

LRAT (lecithin retinol acyltransferase) is the enzyme that catalyzes retinoid esterification and storage[16]. CRBPs (cellular retinoid binding proteins) assist LRAT in regulating retinoid uptake and metabolism. These two proteins are essential in the mechanism of retinoids and may also be responsible for their toxicity.

History and Physical

With topical retinoid use, peeling and erythema may be seen at the site of application.

With systemic use, the patient may exhibit overall xerosis of the skin, oral, ophthalmic, and nasal mucosa. Fissuring and redness of the lips (cheilitis) may also be seen, as well as peeling of the palms and soles and fissuring of the fingertips. Diffuse hair shedding may also occur.

Mental status changes are common following Vitamin A intoxication. In addition, there is a risk for seizures, headache, and blurred vision (due to elevated intracranial pressure). Chronic toxicity can lead to alopecia, anorexia, pruritus, dryness of mucous membranes, muscle and bone pain and hyperlipidemia.

Evaluation

Given that elevated triglyceride and cholesterol levels are the most common lab abnormality in patients taking isotretinoin, both of these levels should be checked periodically in a patient taking this medication[17]. Liver enzyme elevations are typically mild and reversible. However, alanine aminotransferase and aspartate aminotransferase monitoring are recommended based upon dosage and patient comorbidities. The patient must also have two negative urine or serum pregnancy tests (beta-hCG) 30 days apart prior to initiation of isotretinoin. Beta-hCG should be checked monthly while on therapy as well as one month after cessation of treatment. A complete blood count may be considered before initiation although abnormalities are rare and idiosyncratic. Skeletal monitoring for hyperostosis is only recommended if the patient is receiving multiple courses of isotretinoin or is on the medication long-term.

In a patient taking a vitamin A-containing medication who is complaining of a persistent headache, evaluation should be undertaken for increased intracranial pressure to rule out pseudotumor cerebri syndrome.

Free T4 should be monitored before and during treatment with bexarotene[18]. Baseline fasting serum lipids should also be monitored at initiation and every 1-2 weeks during therapy until stable.

If a patient on etretinate therapy has a history of kidney disease, monitor their renal function during treatment[10].

Treatment / Management

Management of skin irritation from topical retinoids is accomplished with reduced medication volume of application, reduced frequency, and increased emollient use. Reassurance that this side effect will improve with continued use should also be provided.

For ophthalmologic dryness, artificial tears and lubricating eye drops, such as methylcellulose containing eye drops, can be helpful.

Oral retinoid administration discontinuation, dose reduction, or addition of fish oil or a fibrate medication may be considered with a fasting triglyceride level of 800 mg/dL or higher due to an elevated risk of pancreatitis. Milder elevations may be monitored or similarly treated.

For bexarotene, concomitant use of a statin or fibrate may be considered to treat retinoid-induced hyperlipidemia and reduce pancreatitis risk[19]. Elevations higher than three times the upper limit of normal may necessitate cessation of therapy if the levels remain elevated despite intervention[19].

Acute retinoid toxicity is rare, but in the cases that have been documented, recovery is rapid upon cessation of medication[20].

In patients with pseudotumor cerebri syndrome, discontinuation of the medication containing vitamin A as well as treatment with acetazolamide has been effective in reducing intracranial pressure[8].

Acute cases may require admission with close monitoring. The hypotension needs to be managed with fluids and the hypercalcemia may require calcitonin and/or corticosteroids.

Differential Diagnosis

• Migraine headache

• Munchausen syndrome

Prognosis

For most patients who discontinue the vitamin, the symptoms gradually reverse and complete recovery is the norm. However, if vitamin A ingestion is continued, then the adverse effects on the nerves and brain are not always reversible.

Pearls and Other Issues

Teratogenicity is the most significant adverse effect of vitamin A toxicity. Patients should be advised not to ingest more than the recommended maximum amount of supplemental vitamin A during pregnancy. The majority of other adverse effects, including skin irritation, dryness, and increased intracranial pressure, will resolve once ingestion or application of vitamin A is reduced or discontinued. Effects such as elevated triglycerides, cholesterol, or transaminases typically resolve despite the ongoing continuation of the medication. However, these levels should be monitored, and the medication should be discontinued if elevations persist or worsen.

Enhancing Healthcare Team Outcomes

A significant number of people regularly consume large quantities of vitamins in the belief that they are available over the counter and thus safe. In fact, close to 60,000 vitamin toxicities are reported each year in the US alone. The key is public education and this requires an interprofessional team. In most cases, the pharmacist is in the prime position to educate the public about vitamin safety. Rather than encourage the use of supplements, the pharmacist should educate the public on a healthy diet- not only is this cheaper, but it is safer. Countless cases of counterfeit vitamin products have been reported over the years.

Nurses should also encourage patients to consume a healthy diet and refrain from taking vitamins unless there is a documented deficiency.

Pregnancy is an absolute contraindication to isotretinoin therapy. However, patients may ingest other medications containing vitamin A such as isolated vitamin A, other supplements, and weight loss medications that may also have teratogenic effects. It is the responsibility of the nurses and medical aides entering medications, as well as the obstetrician or physician managing females’ care, acting in concert as a coordinated health care team, to be sure that all medications, including vitamins and supplements, are included in a patient’s medication-list and reviewed with the patient at each visit. The patient should be informed of the risk of vitamin A ingestion during pregnancy and the maximum recommended dosages during pregnancy. [Level I]

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References

1.

Hunt JR. Teratogenicity of high vitamin A intake. N Engl J Med. 1996 May 02;334(18):1197. [PubMed: 8602195]

2.

Lammer EJ, Chen DT, Hoar RM, Agnish ND, Benke PJ, Braun JT, Curry CJ, Fernhoff PM, Grix AW, Lott IT. Retinoic acid embryopathy. N Engl J Med. 1985 Oct 03;313(14):837-41. [PubMed: 3162101]

3.

Kang S, Duell EA, Fisher GJ, Datta SC, Wang ZQ, Reddy AP, Tavakkol A, Yi JY, Griffiths CE, Elder JT. Application of retinol to human skin in vivo induces epidermal hyperplasia and cellular retinoid binding proteins characteristic of retinoic acid but without measurable retinoic acid levels or irritation. J Invest Dermatol. 1995 Oct;105(4):549-56. [PubMed: 7561157]

4.

Jick H. Retinoids and teratogenicity. J Am Acad Dermatol. 1998 Aug;39(2 Pt 3):S118-22. [PubMed: 9703138]

5.

Marshall H, Studer M, Pöpperl H, Aparicio S, Kuroiwa A, Brenner S, Krumlauf R. A conserved retinoic acid response element required for early expression of the homeobox gene Hoxb-1. Nature. 1994 Aug 18;370(6490):567-71. [PubMed: 7914354]

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Scheven BA, Hamilton NJ. Retinoic acid and 1,25-dihydroxyvitamin D3 stimulate osteoclast formation by different mechanisms. Bone. 1990;11(1):53-9. [PubMed: 2331432]

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Genaro Pde S, Martini LA. Vitamin A supplementation and risk of skeletal fracture. Nutr Rev. 2004 Feb;62(2):65-7. [PubMed: 15080368]

8.

Chisholm JT, Abou-Jaoude MM, Hessler AB, Sudhakar P. Pseudotumor Cerebri Syndrome with Resolution After Discontinuing High Vitamin A Containing Dietary Supplement: Case Report and Review. Neuroophthalmology. 2018 Jun;42(3):169-175. [PMC free article: PMC5958954] [PubMed: 29796052]

9.

Sherman SI, Gopal J, Haugen BR, Chiu AC, Whaley K, Nowlakha P, Duvic M. Central hypothyroidism associated with retinoid X receptor-selective ligands. N Engl J Med. 1999 Apr 08;340(14):1075-9. [PubMed: 10194237]

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Cribier B, Welsch M, Heid E. Renal impairment probably induced by etretinate. Dermatology. 1992;185(4):266-8. [PubMed: 1477420]

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Koo J, Nguyen Q, Gambla C. Advances in psoriasis therapy. Adv Dermatol. 1997;12:47-72; discussion 73. [PubMed: 8973735]

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Duvic M, Martin AG, Kim Y, Olsen E, Wood GS, Crowley CA, Yocum RC., Worldwide Bexarotene Study Group. Phase 2 and 3 clinical trial of oral bexarotene (Targretin capsules) for the treatment of refractory or persistent early-stage cutaneous T-cell lymphoma. Arch Dermatol. 2001 May;137(5):581-93. [PubMed: 11346336]

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Nollevaux MC, Guiot Y, Horsmans Y, Leclercq I, Rahier J, Geubel AP, Sempoux C. Hypervitaminosis A-induced liver fibrosis: stellate cell activation and daily dose consumption. Liver Int. 2006 Mar;26(2):182-6. [PubMed: 16448456]

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Bigby M. Does isotretinoin increase the risk of depression? Arch Dermatol. 2008 Sep;144(9):1197-9; discussion 1234-5. [PubMed: 18794466]

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Sibulesky L, Hayes KC, Pronczuk A, Weigel-DiFranco C, Rosner B, Berson EL. Safety of <7500 RE (<25000 IU) vitamin A daily in adults with retinitis pigmentosa. Am J Clin Nutr. 1999 Apr;69(4):656-63. [PubMed: 10197566]

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Moise AR, Noy N, Palczewski K, Blaner WS. Delivery of retinoid-based therapies to target tissues. Biochemistry. 2007 Apr 17;46(15):4449-58. [PMC free article: PMC2562735] [PubMed: 17378589]

17.

Goldsmith LA, Bolognia JL, Callen JP, Chen SC, Feldman SR, Lim HW, Lucky AW, Reed BR, Siegfried EC, Thiboutot DM, Wheeland RG., American Academy of Dermatology. American Academy of Dermatology Consensus Conference on the safe and optimal use of isotretinoin: summary and recommendations. J Am Acad Dermatol. 2004 Jun;50(6):900-6. [PubMed: 15153892]

18.

Gniadecki R, Assaf C, Bagot M, Dummer R, Duvic M, Knobler R, Ranki A, Schwandt P, Whittaker S. The optimal use of bexarotene in cutaneous T-cell lymphoma. Br J Dermatol. 2007 Sep;157(3):433-40. [PubMed: 17553039]

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Wiegand UW, Chou RC. Pharmacokinetics of acitretin and etretinate. J Am Acad Dermatol. 1998 Aug;39(2 Pt 3):S25-33. [PubMed: 9703120]

20.

Nagai K, Hosaka H, Kubo S, Nakabayashi T, Amagasaki Y, Nakamura N. Vitamin A toxicity secondary to excessive intake of yellow-green vegetables, liver and laver. J Hepatol. 1999 Jul;31(1):142-8. [PubMed: 10424294]

Disclosure: Jazmine Olson declares no relevant financial relationships with ineligible companies.

Disclosure: Muhammad Atif Ameer declares no relevant financial relationships with ineligible companies.

Disclosure: Amandeep Goyal declares no relevant financial relationships with ineligible companies.

Insidious vitamin. Why are beta-carotene and retinol dangerous? | Proper nutrition | Health

Vitamin A is very difficult. For example, in its action, this vitamin is in many ways closer to hormones.

There are two forms of vitamin A.

1. Beta-carotene, considered its precursor or, scientifically speaking, a provitamin. Our body cannot produce it, and it must be obtained from plant foods, since it is practically absent in animals. Beta-carotene itself is extremely useful and necessary for our body, it is a powerful antioxidant. Only part of this substance is converted into vitamin A, it is believed that out of 12 beta-carotene molecules, only one goes to the production of the vitamin. The remaining 11 molecules “work” for our benefit in a different way. An overdose of beta-carotene is practically safe, its main manifestation is yellowing of the skin, more like a sunburn than jaundice.

2. Retinol – or vitamin A itself. We can synthesize it from beta-carotene. And we can still get it in its pure form from animal products, poultry and fish, as well as from multivitamin preparations. This is a very important substance necessary for cell differentiation (the transformation of stem cells into specific cells of the liver, kidneys, muscles and other organs), for the growth and development of the body, for vision and immunity. In carrying out these functions, vitamin A often behaves like a hormone: it regulates the activity of genes and thus has a strong influence on the formation of our body. And it is in this form, in the form of retinol, that vitamin A can be very toxic: it is extremely easy to get it in excess, because there are many foods that contain a daily amount of it in one serving. And in some – even 9daily norms, as, for example, in 100 grams of beef liver.

What follows from these paradoxes?

First, don’t try to get all your vitamin A from foods that contain it in the form of retinol. Getting it with vegetables and fruits in the form of provitamin beta-carotene (see table), you can avoid a lack of vitamin A. That is why it is almost never found in vegetarians.

Such a diet – with a lot of vegetables and fruits (at least 450-500 g per day) – is considered very useful. Beta-carotene is found in all yellow and orange fruits and vegetables and is what gives them their color. But there is a lot of it in the green and red gifts of nature. It’s just that in them beta-carotene is “muffled” by other pigments and does not manifest itself so brightly. For example, there is a lot of it in green leaves, and it becomes visible when the green pigment chlorophyll is destroyed in autumn and the leaves turn yellow. Therefore, in people who eat properly and balanced, a lack of vitamin A is unlikely.

Secondly, if starchy foods (bread, potatoes, cereals and pasta) with mainly processed meat (sausages, sausages and cheap minced meat) form the basis of nutrition, the risk of such hypovitaminosis is quite real. And – what to hide – this style of eating is common for many. They do not solve the problem of pickles, sauerkraut and marinades, which many consume in winter instead of fresh vegetables rich in beta-carotene. That is why in the old days, when there were simply no such vegetables from mid-autumn to summer, “night blindness” often developed. This was the name given to the state when a person began to see poorly at dusk and when it took a long time to “adjust” vision when moving from a bright room to a dark one. This is due to the fact that retinol is needed for the visual pigment rhodopsin, which converts sunlight in the retina into electrical impulses that go to the brain. Especially often these vision problems used to occur after a big fast, when dairy products and any animal sources of retinol were generally excluded.

Thirdly, in addition to vitamin A deficiency (it usually occurs in poor countries in Africa and Southeast Asia), its overdose is no less a serious problem. This is especially true for developed countries, where the so-called consumer society has formed. We are approaching this: we have popular preparations with vitamins (many have very decent doses of retinol). Plus, many can afford an excess amount of animal food, expensive liver pates, oily fish, caviar. All of these are rich in retinol and increase the risk of overdose (see table).

Amount of vitamin and beta-carotene in some popular products

Why is an overdose dangerous?

This is especially dangerous for pregnant women. Exceeding a daily dose of 3000 mcg significantly increases the risk of malformations in the fetus. Therefore, they should not abuse liver dishes and eat fatty fish more than once a week. For pregnant women, if they are taking multivitamins, it is very important to know what dose of retinol they contain. There is a lot of it in some preparations. If you look at the dose of retinol in them, you will see that it is often more than 1500 micrograms. Moreover, there are many multivitamins that contain over 3000 micrograms of retinol (and this is already a toxic dose for pregnant women). So, it’s quite easy to “sort out” vitamin A. At the same time, it is also necessary to take into account ordinary food products, in which there is a lot of retinol (see table).

In addition, even a moderate excess of this substance can make bones weaker, increasing the risk of fractures. This has been proven in a serious and long-term study by Swedish scientists. They assessed not just the intake of vitamin A according to surveys, but specifically determined its content in the blood, that is, the study is very accurate and can be completely trusted. The researchers calculated that even taking more than 1,500 mcg of retinol per day poses a risk. What does this mean for the average multivitamin lover? This dose is about one and a half times the recommended daily intake for men and 2 times for women.

Here is a list of other signs that may indicate a retinol overdose:

• Dry skin, cracks, itching, increased sensitivity to sunlight;
• Brittle and brittle nails;
• Increased oily hair, hair loss;
• Inflammation of the gums;
• Irritability, fatigue, drowsiness, anxiety.

How to determine the correct dose of retinol

If you start calculating the doses of vitamin A intake by comparing multivitamin instructions and data from its content in products, you will most likely get confused. The fact is that it can be indicated in different units: micrograms (mcg), international units (IU), International Units (IU) and even in some strange “mcg RE” (this is the so-called “retinol equivalent” – dose calculation vitamin A, one retinol each). And if you add to this the recalculation of beta-carotene into retinol, then you will definitely be mistaken. Even doctors cannot always bring all this to a common denominator, but we will teach you this.

In order to freely convert between all these units of measure, you need to use the following formula that links them all together. Here it is:

1 mcg = 1 mcg RE = 3.33 IU = 3.33 IU = 12 mcg of beta-carotene

Why is vitamin A deficiency dangerous? ) it can cause real blindness. If the degree of deficiency is very high, xerophthalmia occurs: dryness of the cornea of ​​\u200b\u200bthe eye, which eventually turns into a thorn.

Retinol is important for the skin and mucous membranes that cover the entire respiratory tract and digestive tract. Therefore, with its shortage, there are often colds, pneumonia, and intestinal problems. The skin can be dry, rough, rough, and often looks like “goosebumps”: it is formed by nodules in the area of ​​\u200b\u200bthe hair follicles, which are usually found on the elbows, knees, buttocks and outer thighs.

There may also be problems with fertility (infertility), and in children – growth retardation.

Who and how much vitamin A (retinol) needs

Why is it necessary to control the level of vitamin A (retinol) in the body?

Looking through collections of publications on the chemistry of plant and animal compounds, physiology and nutrition for 1870-1907, E. McCollum discovered the work of the Russian student N. Lunin, who, in experiments on mice, showed that a diet limited to a mixture of purified proteins (casein), carbohydrates, fats and inorganic salts, caused an early death of the experimental subjects. This and similar experiments by thirteen other authors inspired E. McCollum to start a new series of experiments to determine vital food components. With the participation of student M. Davis, in a series of experiments on the inclusion of egg yolk in the diet, rats showed the ability to grow and develop safely. This fat-soluble nutrient was called the letter A [McCollum, 1952, 1967].

Vitamin A is now the generic name for a class of compounds with retinoid activity that occur naturally in three main forms: retinol, retinal, and retinoic acid [Weeks, 2003].

In terms of antioxidant protection, vitamins A, E and C are considered as synergists. At the same time, vitamins A and E have the opposite effect on the synthesis of prostaglandins E ₁ and E ₂ . In relation to calcium metabolism, an excess of vitamin A causes bone resorption and decalcification, while calcium absorption and retention are caused by its antagonist – vitamin D. Vitamin C, reducing the copper content in the body, thereby indirectly causing the accumulation of iron in body tissues, promotes the oxidation of vitamin A For the mobilization of vitamin A from the liver through the production of retinol binding protein (RBP), zinc is required, the lack of which prevents the replenishment of vitamin A deficiency, as well as hormones of the adrenal cortex. It is believed that the conversion of beta-carotene to vitamin A is influenced by thyroxine, and hypothyroidism and insufficiency of the adrenal cortex cause vitamin A deficiency. With vitamin A deficiency, the sensitivity of tissues to estrogens increases, it is noted that the concentration of RBP is minimal before the ovulatory peak in women [Watts, 1991].

Vitamin A is required already at the stage of conception: an adequate level of the vitamin is necessary for full spermatogenesis, and the gradient of vitamin A in the tissues of the uterus determines the site of implantation of a fertilized egg. Embryogenesis and cell differentiation proceed normally only in the presence of a sufficient amount of vitamin A, which is necessary for the growth and development of bone tissue [Weeks, 2003].

Kh. Kozakova et al. showed that vitamin A deficiency causes disturbances in enzyme systems in the intestinal epithelial tissue, provoking dysbiosis in rats [Kozakova, 2003]. A number of researchers tend to extrapolate this mechanism to the development of lethal diarrhea in adolescents, and also explain sudden infant death syndrome to them [Weeks, 2003].

Signs of vitamin A deficiency are visual disturbances – dryness, reduced eye adaptation to darkness, any disorders of the mucous tissue, including allergic rhinitis, gastritis, ulcers. Vitamin A is necessary for the normal functioning of the immune system, protects against colds, flu and infections of the respiratory tract, digestive tract, urinary tract [Weeks, 2003].

With this vitamin indispensable for healthy longevity, many manufacturers are fortifying foods and cosmetics with retinoids. Against this background, the abuse of vitamin preparations and overeating of animal foods rich in vitamin A can cause toxic manifestations called hypervitaminosis A. Symptoms of hypervitaminosis include alopecia, erythema, desquamation, myalgia, stomatitis and conjunctivitis. Excess beta-carotene causes yellowing of the skin.

Symptoms of both deficiency and overdose of vitamin A are sufficient grounds for monitoring the concentration of retinol in the blood as their differential diagnosis. However, the isolated determination of the concentration of retinol has limited clinical significance, since for the correct correction of these conditions, it is necessary to take into account the synergism and antagonism of other vitamins and microelements.

1. Early experiences with vitamin A–a retrospect. McCollum EV. Nutr Rev. 19Jun 52;10(6):161-3.
2. The paths to the discovery of vitamins A and D. McCollum EV. J Nutr. 1967 Feb;91(2): Suppl 1:11-6.
3. Vitamin A deficiency leads to severe functional disturbance of the intestinal epithelium enzymes associated with diarrhoea and increased bacterial translocation in gnotobiotic rats.