vitamin A

see also:

• retinoids
• vitamin D

• although known that eating liver can Rx night blindness since ancient times, vitamin A was discovered in the 1920's
• a family of compounds known as retinoic acids
• 2 main forms:
  • pro-vitamin A carotenoids:
    • mainly found in plants and conversion to vitamin A is controlled thus overdosage does not occur
    • beta carotene is the main one converted to vitamin A in mammals
  • pre-formed vitamin A:
    • mainly found in animal livers and most vitamin A supplements
    • these are hydrolyzed into retinol in the lumen of the small intestine by retinyl ester hydrolases
    • there is no feedback regulation of this GIT absorption mechanism thus excessive ingestion may cause toxicity causing hypervitaminosis A
    • retinol, retinal, retinoic acid, and retinyl esters
• 50 to 85% of total body retinol is stored in the liver
• recommended daily intake:
  • adult males is 3000 IU (900 micrograms retinol) daily
  • adult females 2300 IU (700 micrograms retinol) daily.

• in retinal rod cells, it combines with a membrane-bound protein called opsin to make rhodopsin which is critical for night vision
• in retinal cone cells, it forms iodopsin
• it is crucial in the fetal development of tissues, in particular, the eye
• immunologic dendritic cells (DCs) produce retinoic acid via an enzyme, either ALDH1a3, or in certain subtypes of DC, ALDH1a2 ¹⁾
  • it activates a receptor in the cell's nucleus to initiate a molecular signaling cascade that alters gene expression. Its production by DCs is known to induce the generation of immune cells known as regulatory T cells (Tregs) in the gut that restrain potentially dangerous autoimmune reactions.
  • production of retinoic acid can reduce immune action against cancer cells via various mechanisms:
    • favors the development of macrophages that are less efficient than DCs in combating cancer cells
    • ALDH1a3 is overexpressed in diverse cancers to generate retinoic acid, but that cancer cells lose their responsiveness to retinoid receptor signaling, avoiding its potential anti-proliferative or differentiating effects
  • this helps explain the paradox of high intake of vitamin A actually increases the incidence of cancer (and cardiovascular disease) and related mortality

• inadequate diet - usually in the Third World countries only, but also in some patients with very limited diets
• malabsorption of fat from GIT:
  • cystic_fibrosis
  • coeliac disease
  • cholestatic liver disease eg. primary biliary cirrhosis
  • Crohn's disease of small bowel
  • pancreatic insufficiency

• night blindness
• xerophthalmia with Bitot's spots and keratomalacia
• poor bone growth
• replacement of hair follicles with mucus-secreting glands
• hyperkeratosis
• phrynoderma (follicular hyperkeratosis)
• impaired humoral and cell mediated immune system

• serum levels do not correspond with toxicity as it is stored in the liver mainly
• fasting serum retinyl ester concentrations >10 percent of the total vitamin A pool may indicate toxicity

• excessive vitamin A intake:
  • eating food rich in pre-formed vitamin A:
    • livers
    • kidney
    • egg yolk
  • overdose of pre-formed vitamin A supplements, or use with retinoids such as isotretinoin (Roaccutane)
• toxicity may be increased in patients with:
  • liver disease
  • kidney disease
  • alcoholism
  • use of some drugs, such as tetracycline antibiotics
  • children with cystic_fibrosis are at risk of toxicity even with standard doses

• single dose of >660,000 IU (>200,000 micrograms) of vitamin A is ingested in adults
  • nausea, vomiting
  • vertigo
  • blurry vision
  • if very high dose: drowsiness, malaise, and recurrent vomiting
• infants under 6 months may develop toxicity even if given doses > 20,000IU or 6000mcg for a few weeks

• doses > 10x recommended daily dose
• dry skin
• nausea
• headache (benign raised intracranial hypertension)
• ataxia
• alopecia
• hyperlipidaemia
• hepatotoxicity and cirrhosis
• bone and muscle pain
• osteoporosis in post-menopausal women and hip fractures
• visual impairment
• hepatomegaly and elevated ALT, AST
• hypercalcaemia
• increased cancer risk
• increased cardiovascular risks
• many other symptoms

• doses only several times the recommended daily intake in the 1st trimester may cause:
  • spontaneous abortions
  • fetal malformations, including microcephaly and cardiac anomalies