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Vitamin A

Vitamin A is an essential fat-soluble nutrient for vision, epithelial integrity, immunity, and development.[13][15]

Vitamin A has been used to counter steroid-impaired healing, but this is not a proven routine perioperative intervention. Treat established deficiency and address overall nutrition; do not automatically prescribe high-dose retinol to every patient taking corticosteroids.[13][15]

Biochemistry and Metabolism​

"Vitamin A" encompasses a family of fat-soluble retinoid compounds:[13]

  • Preformed dietary vitamin A (retinol and retinyl esters). Found in animal-source foods, fortified foods, and supplements. Retinyl esters are hydrolyzed to retinol in the intestine, absorbed with dietary fat, and transported to the liver via chylomicrons.
  • Provitamin A carotenoids (β-carotene, α-carotene, β-cryptoxanthin). Plant-derived pigments enzymatically cleaved to retinal in the intestine. Conversion varies with food matrix and absorption. Dietary reference calculations use 12 μg dietary β-carotene or 24 μg dietary α-carotene or β-cryptoxanthin per 1 μg retinol activity equivalent (RAE); adequate intake is possible from a suitably planned diet.[13]

Most body vitamin A is stored in the liver, predominantly as retinyl esters in hepatic stellate cells (HSCs).[2][3] When needed, retinyl esters are hydrolyzed to retinol, which is released bound to retinol-binding protein (RBP) for delivery to target tissues. Sufficient hepatic stores can maintain requirements for months to years.[4]

Three active metabolites mediate vitamin A's biological functions:[13]

  • Retinal (retinaldehyde). Needed for vision; 11-cis-retinal is the chromophore in rhodopsin and cone opsins.
  • Retinoic acid (all-trans and 9-cis). The primary transcriptionally active form; binds RAR/RXR nuclear receptors to regulate cell differentiation, proliferation, apoptosis, and immune function.
  • Retinol. The principal circulating transport form and precursor of retinal and retinoic acid; storage is mainly as retinyl esters.

Dietary Sources and Requirements​

Preformed vitamin A is found in liver, fish oils, dairy products, and eggs, with the contribution varying by diet. Provitamin A carotenoids are found in dark green leafy vegetables, carrots, sweet potatoes, mangoes, and red palm oil.[13]

PopulationRDA (μg RAE/day)UL (μg/day preformed)
Adult men9003,000 (~ 10,000 IU)
Adult women7003,000 (~ 10,000 IU)
Pregnant adults7703,000
Lactating adults1,3003,000
Children 1–3 years300600
Children 4–8 years400900

RAE accounts for differences between preformed vitamin A and carotenoids. The adult UL is 3,000 μg RAE/day of preformed vitamin A, equivalent to 10,000 IU retinol; it is not a recommended intake. Fat malabsorption can impair uptake.[13]

Assessment of Vitamin A Status​

Assessing vitamin A status is challenging because serum retinol is homeostatically regulated across a wide range of liver stores and may remain normal despite depleted stores; inflammation can also lower the measurement without equivalent depletion.[1][4]

  • Serum retinol. Most commonly used biomarker. Common thresholds are <0.70 μmol/L (20 μg/dL) and <0.35 μmol/L (10 μg/dL) for severe biochemical deficiency; these are not stand-alone individual diagnostic rules.[1][13]
  • Confounders. Infection, inflammation, low transport proteins, liver disease, and pregnancy complicate interpretation. Oral contraceptives can increase plasma vitamin A; kidney disease can also distort retinol or RBP interpretation. As with albumin and zinc, inflammation significantly reduces measured levels independent of true stores.[1][10]
  • Retinol-binding protein (RBP). Less expensive alternative to serum retinol; shares homeostatic, inflammatory, hepatic, and renal limitations; it cannot reliably exclude deficiency.[1]
  • Liver biopsy and retinol isotope dilution. Reference tests for total body vitamin A stores, but impractical for routine use.[1][4]
  • Clinical assessment. Night blindness (earliest sign), Bitot's spots, conjunctival xerosis, corneal xerosis and keratomalacia are features warranting clinical assessment for deficiency; corneal involvement requires urgent ophthalmic care.[4]

2025 Cochrane diagnostic review: 40 studies, none designed as diagnostic-accuracy studies. Against retinol isotope dilution at a liver-store cutoff of 0.1 μmol/g, serum retinol <0.70 μmol/L had pooled sensitivity of 10% (95% CI 2–38; 23 studies, 385 reference-positive participants; very low certainty) and specificity of 92% (95% CI 85–96; 23 studies, 1,110 reference-negative participants; low certainty). These estimates vary by reference standard and come mainly from community studies of at-risk people across life stages assessed for subclinical vitamin A deficiency. A normal blood result cannot safely rule out deficiency in a symptomatic high-risk patient, and a low result during inflammation is not proof of depleted stores.[1]

Causes of Deficiency​

CategoryExamples
Dietary insufficiencyInadequate intake of both preformed vitamin A and provitamin A sources; restrictive diets or food insecurity
MalabsorptionCeliac disease, IBD, chronic pancreatitis, cystic fibrosis, short bowel syndrome, bariatric surgery (especially BPD/DS, RYGB)
Liver diseaseCirrhosis, alcoholic liver disease (impaired storage and RBP synthesis)
Increased demandPregnancy (especially third trimester), lactation, rapid growth in infancy
InfectionsMeasles, diarrheal illness, HIV (increased catabolism and urinary losses)

Clinical Manifestations of Deficiency​

Ocular. The hallmark of vitamin A deficiency is xerophthalmia, a spectrum of progressive eye disease:[4]

  1. Night blindness (nyctalopia). Earliest symptom; impaired dark adaptation from insufficient 11-cis-retinal for rhodopsin regeneration.
  2. Conjunctival xerosis. Drying and keratinization of the conjunctiva.
  3. Bitot's spots. Triangular, foamy deposits on bulbar conjunctiva; a characteristic sign requiring assessment in context.
  4. Corneal xerosis. Drying and haziness of the cornea.
  5. Corneal ulceration / keratomalacia. Liquefactive necrosis of the cornea; medical emergency that can lead to permanent blindness.

Corneal injury can progress rapidly. Do not wait for laboratory confirmation before arranging urgent ophthalmic assessment and treatment when xerophthalmia is suspected.

Immune. Deficiency impairs both innate and adaptive immunity, including epithelial barrier integrity, neutrophil function, NK-cell activity and T-cell differentiation. Susceptibility to measles, diarrheal diseases and respiratory infections is increased.[13][5]

Other. Growth retardation, impaired hematopoiesis (anemia), follicular hyperkeratosis, increased childhood mortality.[13]

Clinical Applications​

Childhood Mortality and Measles​

Population prevention and treatment of an ill child use different schedules. Cochrane 2022 included 47 trials (approximately 1.22 million community-dwelling children aged six months to five years). Its mortality meta-analysis included 19 trials and found a 12% relative reduction, RR 0.88 (95% CI 0.83–0.93).[5] The older 24% estimate came from an earlier review.[6] These trials excluded children already hospitalized or ill.[5][6]

Measles: current CDC guidance permits supervised vitamin A for children with measles and recommends it for severe or hospitalized cases. If used, give immediately and repeat the next day: 50,000 IU below six months, 100,000 IU at 6–11 months, or 200,000 IU from 12 months. Vitamin A does not replace vaccination or prevent measles infection.[20]

Retinoids in Dermatology​

Vitamin A derivatives are among the most widely used pharmacologic agents in dermatology:[7][8]

  • Isotretinoin (oral). Disease-modifying treatment for severe nodulocystic acne; suppresses sebum, normalizes keratinization, modulates innate immunity. Teratogenic (see Safety below).
  • Tretinoin, adapalene, tazarotene, trifarotene (topical). Topical retinoids are strongly recommended for acne; some topical retinoids are also used for photoaging and melasma.[24][7]
  • Acitretin (oral). Psoriasis, pityriasis rubra pilaris, Darier disease, ichthyoses. For patients who can become pregnant, the US label requires pregnancy prevention during treatment and for at least three years afterward; they must avoid ethanol during treatment and for two months afterward because it can form longer-lived etretinate.[25]
  • Bexarotene (oral / topical). Cutaneous T-cell lymphoma.

Retinoids in Oncology​

All-trans retinoic acid (ATRA) is a differentiation treatment for acute promyelocytic leukemia within hematology-directed combination regimens.[9]

Treatment of Vitamin A Deficiency​

Suspected xerophthalmia or corneal involvement requires urgent specialist treatment. Dose and route depend on age, pregnancy, absorption, and ocular findings. Scheduled population supplementation every 4–6 months is not treatment for acute eye disease.

ContextVerified regimen and limits
Post-bariatric deficiency without corneal changesASMBS describes 10,000–25,000 IU orally daily until clinical improvement, usually 1–2 weeks; reassess absorption and response.[14]
Post-bariatric deficiency with corneal changesASMBS describes 50,000–100,000 IU IM daily for three days, then 50,000 IU IM daily for two weeks. Urgent ophthalmic/nutrition supervision is required.[14]
Adult deficiency requiring parenteral treatmentAQUASOL A labeling specifies 100,000 IU IM daily for three days, then 50,000 IU IM daily for two weeks. Its two-month oral multivitamin follow-up (10,000–20,000 IU/day) applies when absorption is adequate; the label calls for an equivalent parenteral preparation when malabsorption persists. The product is for intramuscular use; intravenous administration is contraindicated because anaphylactic shock and death have been reported with that route.[10]

These are high-dose deficiency-treatment regimens, not preventive prescriptions, and should not be applied to pregnancy without specialist assessment. ASMBS assigns both post-bariatric vitamin A repletion schedules Grade D, best evidence level 4.[14] The AQUASOL A label states that safety of more than 6,000 IU vitamin A daily in pregnancy has not been established and contraindicates amounts above the recommended dietary allowance in women who are or may become pregnant.[10] Evaluate concurrent deficiencies, especially iron and copper after bariatric surgery.[10][14]

Maintenance after bariatric surgery: ASMBS recommends 5,000 IU/day after banding (Grade C, BEL 3), 5,000–10,000 IU/day after sleeve or RYGB (Grade D, BEL 4), and 10,000 IU/day after duodenal switch (Grade B, BEL 2), individualized to procedure, deficiency history, levels, and pregnancy status. Prevention and repletion are separate; higher doses are not automatically better.[14]

Toxicity (Hypervitaminosis A)​

Excess preformed vitamin A can cause hepatotoxicity, skin changes, alopecia, headache or intracranial hypertension, bone symptoms, and PTH-independent hypercalcemia. Dose, duration, formulation, hepatic or renal disease, and concurrent retinoids affect risk. The dietary UL is not a sharp threshold below which toxicity is impossible or above which everyone develops toxicity.[10][11][13]

β-carotene does not ordinarily cause classic retinol toxicity; excess dietary carotenoids may discolor skin. High-dose β-carotene supplements are not harmless, however. In the randomized ATBC trial, 29,133 Finnish male smokers were assigned to β-carotene 20 mg/day or no β-carotene for five to eight years; supplementation increased lung-cancer incidence by 18% (95% CI 3–36).[18] In CARET (18,314 smokers, former smokers and asbestos-exposed participants), β-carotene plus retinyl palmitate increased lung cancer, RR 1.28 (1.04–1.57), and all-cause mortality, RR 1.17 (1.03–1.33).[19] Do not use these supplements for cancer prevention.[18][19]

Teratogenicity — A Critical Safety Concern​

Excess preformed vitamin A and systemic retinoid medicines can cause fetal harm. Vitamin A at nutritional intake is essential. Check supplements, liver or fish-liver-oil products, and prescriptions together.[12][13]

  • Isotretinoin: follow the current iPLEDGE requirements for patients who can become pregnant, including pregnancy tests and required contraception or program-defined continuous abstinence. Avoid pregnancy during treatment and for one month afterward. Do not extrapolate that interval to every retinoid or vitamin A preparation.
  • 2026 iPLEDGE change: FDA has delayed implementation of the newly approved modifications to November 15, 2026. Pre-treatment tests remain in a medical setting; the FDA describes enforcement discretion for prescriber-supervised home testing during or after treatment. Use the current program requirements rather than a fixed checklist copied here.[16]
  • Topical retinoids: systemic exposure is much lower, but EMA advises avoidance during pregnancy and when planning pregnancy.[17]
  • Nutritional deficiency in pregnancy: requires obstetric and nutrition assessment. WHO population supplementation guidance is restricted to settings of severe vitamin A deficiency to prevent night blindness; it is not a general high-dose pregnancy recommendation.[21]

An inadvertent exposure warrants teratology counseling. Heterogeneous reports do not support presenting fixed fetal-risk percentages as a precise prognosis.

Vitamin A and Liver Disease​

Liver disease can alter retinol storage, transport proteins, and blood levels. A low serum result does not alone establish the size of hepatic stores. Excess supplementation can itself injure the liver; do not infer that every low retinol measurement in cirrhosis needs high-dose replacement. Coordinate suspected deficiency with nutrition and hepatology.[2][3][11]

Reconstructive Relevance​

Corticosteroids and Wound Healing​

Vitamin A has a biologic rationale and historical experimental use for steroid-impaired healing. Ehrlich and Hunt (1968) and Hunt and colleagues (1969, in animals and humans) reported that vitamin A reversed the inhibitory effect of cortisone on wound healing.[22][23] This underlies the surgical teaching of short perioperative vitamin A for patients on chronic corticosteroids. A wound-healing review explicitly describes the human evidence as limited and the supplementation recommendation as expert opinion without rigorous therapeutic trials.[15]

Do not use an automatic oral or compounded topical vitamin A protocol solely because a patient takes steroids. Assess nutrition and the cause of poor healing, correct documented deficiency, and coordinate steroid management with the prescribing clinician. High-dose vitamin A has hepatic and reproductive risks and should not be used to deliberately counter necessary immunosuppression.

Malabsorption and Nonhealing Wounds​

Review the patient's bariatric operation, intake, existing supplementation, visual symptoms, liver or renal disease, and evidence of malabsorption. In a 2026 systematic review, median time to ocular presentation among 19 reported patients was five years after RYGB and 14–27 years after BPD-DS, jejunoileal bypass, or revisional surgery.[26] ASMBS recommends screening for vitamin A deficiency within the first postoperative year, particularly after BPD/DS regardless of symptoms (Grade B, BEL 2), and measuring vitamin A after RYGB or BPD/DS, particularly with protein-calorie malnutrition (Grade B, BEL 2); obtain targeted tests when deficiency is plausible.[14] A vitamin A level is not a mandatory preoperative test for every wound or reconstructive operation.[14]

Medication and Pregnancy Review​

Identify systemic or topical retinoids and high-dose supplements during preoperative medication review. Preserve the drug-specific pregnancy-prevention plan and arrange specialist review of exposures; avoid a generic one-month washout for all vitamin A products.

See Also​

References​

1. Gannon BM, Huey SL, Mehta NH, et al. "Selected Laboratory-Based Biomarkers for Assessing Vitamin A Deficiency in at-Risk Individuals." Cochrane Database of Systematic Reviews. 2025;5:CD013742. doi:10.1002/14651858.CD013742.pub2

2. Haaker MW, Vaandrager AB, Helms JB. "Retinoids in Health and Disease: A Role for Hepatic Stellate Cells in Affecting Retinoid Levels." Biochimica et Biophysica Acta. Molecular and Cell Biology of Lipids. 2020;1865(6):158674. doi:10.1016/j.bbalip.2020.158674

3. Kamm DR, McCommis KS. "Hepatic Stellate Cells in Physiology and Pathology." The Journal of Physiology. 2022;600(8):1825–1837. doi:10.1113/JP281061

4. Tanumihardjo SA. "Vitamin A: Biomarkers of Nutrition for Development." The American Journal of Clinical Nutrition. 2011;94(2):658S–665S. doi:10.3945/ajcn.110.005777

5. Imdad A, Mayo-Wilson E, Haykal MR, et al. "Vitamin A Supplementation for Preventing Morbidity and Mortality in Children From Six Months to Five Years of Age." Cochrane Database of Systematic Reviews. 2022;3:CD008524. doi:10.1002/14651858.CD008524.pub4

6. Mayo-Wilson E, Imdad A, Herzer K, Yakoob MY, Bhutta ZA. "Vitamin A Supplements for Preventing Mortality, Illness, and Blindness in Children Aged Under 5: Systematic Review and Meta-Analysis." BMJ. 2011;343:d5094. doi:10.1136/bmj.d5094

7. Dessinioti C, Katsambas A. "Vitamins and the Skin: Vitamin A and Retinoids in Dermatology." Clinics in Dermatology. 2026;44(2):212–222. doi:10.1016/j.clindermatol.2026.02.005

8. Beckenbach L, Baron JM, Merk HF, Löffler H, Amann PM. "Retinoid Treatment of Skin Diseases." European Journal of Dermatology. 2015;25(5):384–391. doi:10.1684/ejd.2015.2544

9. Orfali N, McKenna SL, Cahill MR, Gudas LJ, Mongan NP. "Retinoid Receptor Signaling and Autophagy in Acute Promyelocytic Leukemia." Experimental Cell Research. 2014;324(1):1–12. doi:10.1016/j.yexcr.2014.03.018

10. AQUASOL A Parenteral (retinyl palmitate), Rising Pharma. Prescribing information, label effective March 2026. Current label.

11. Borgan SM, Khan LZ, Makin V. "Hypercalcemia and Vitamin A: A Vitamin to Keep in Mind." Cleveland Clinic Journal of Medicine. 2022;89(2):99–105. doi:10.3949/ccjm.89a.21056

12. Rothman KJ, Moore LL, Singer MR, et al. "Teratogenicity of High Vitamin A Intake." The New England Journal of Medicine. 1995;333(21):1369–1373. doi:10.1056/NEJM199511233332101

13. NIH Office of Dietary Supplements. Vitamin A and Carotenoids: Health Professional Fact Sheet.

14. Parrott J, Frank L, Rabena R, et al. ASMBS Integrated Health Nutritional Guidelines—2016 Update: Micronutrients. Surg Obes Relat Dis. 2017;13:727–741. doi:10.1016/j.soard.2016.12.018.

15. Zinder R, Cooley R, Vlad LG, Molnar JA. Vitamin A and Wound Healing. Nutr Clin Pract. 2019;34:839–849. doi:10.1002/ncp.10420.

16. FDA. iPLEDGE Risk Evaluation and Mitigation Strategy. June 16, 2026 implementation-delay update.

17. EMA. Updated measures for pregnancy prevention during retinoid use. 2018.

18. Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group. The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. N Engl J Med. 1994;330:1029–1035. doi:10.1056/NEJM199404143301501.

19. Omenn GS, Goodman GE, Thornquist MD, et al. Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease. N Engl J Med. 1996;334:1150–1155. doi:10.1056/NEJM199605023341802.

20. CDC. Clinical Overview of Measles. Current vitamin A treatment guidance.

21. WHO. Vitamin A supplementation during pregnancy. Current recommendation.

22. Ehrlich HP, Hunt TK. Effects of cortisone and vitamin A on wound healing. Ann Surg. 1968;167(3):324–328. doi:10.1097/00000658-196803000-00004

23. Hunt TK, Ehrlich HP, Garcia JA, Dunphy JE. Effect of vitamin A on reversing the inhibitory effect of cortisone on healing of open wounds in animals and man. Ann Surg. 1969;170(4):633–641. doi:10.1097/00000658-196910000-00014

24. Reynolds RV, et al. "Guidelines of care for the management of acne vulgaris." J Am Acad Dermatol. 2024;90(5):1006.e1–1006.e30. doi:10.1016/j.jaad.2023.12.017

25. DailyMed. "Acitretin capsule (Amneal Pharmaceuticals): prescribing information." Updated January 23, 2024. Drug label.

26. Abdel-Sayyed A, Bigam S, Alizada A, Milad D, Al-Ani A. "Prevalence, Ocular Manifestations, and Treatment Response in Post-Bariatric Vitamin A Deficiency: A Systematic Review and Meta-Analysis." Am J Ophthalmol. 2026 Sep 24. Online ahead of print. doi:10.1016/j.ajo.2026.09.026