More Related Content
Similar to Vitamin A.pptx
Similar to Vitamin A.pptx (20)
More from JasperOmingo
More from JasperOmingo (10)
Recently uploaded
Recently uploaded (20)
Vitamin A.pptx
- 1. VITAMIN A Mobilization of vitamin A from the liver and serum transport -Retinol is released from the liver bound to RBP.RBP has a molecular weight of 21 000 and one binding site for retinol. -Holo-RBP (the RBP-retinol complex)is released from the liver bound to another protein,transthyretin(TTR).TTR has a molecular weight of 55 000 and was previously known as thyroxine-binding pre-albumin;it also has one binding site,so the whole complex is a 1:1:1 structure. -In plasma ,95% of the retinol is bound in the retinol-RBP-TTR complex. The binding of retinol to RBP confers a number of physiological advantages; *RBP(and all the vitamin A-binding proteins within the cell)facilitate the transport of a lipid-soluble compound through the aqueous environment of the plasma. *There is protection of retinol from oxidative damage during transport *There is regulation of retinol mobilization *There is delivery of retinol to specific sites on the surface of target cells,particularly the eye ,where a lack of RBP results in night blindness *There is formation of a large molecule as a complex,which is not easily lost from plasma during vasodilation -Holo-RBP is taken up by specific cell-surface receptors.Once the retinol is transferred within the cell, the apo-RBP(the free protein)is released from the receptor and can be recycled.Some is excreted by the kidney. Retinol inside the cell is bound to CRBP1. -Some cells can also take up retinol palmitate from circulating chylomicrons via lipoprotein receptors. Within the cell the ester is hydrolysed and retinol is bound to CRBP1 for further metabolism. -Inside the cell,retinol is oxidised to retinal and then to all-trans retinoic acid by local expression of retinoic acid-synthesizing aldehyde dehydrogenase. -Some of the all-trans retinoic acid is converted to 9-cis retinoic acid.The two forms ,all-trans and 9-cis retinoic acid,interact with the nuclear receptors RAR and RXR,respectively. -The cytochrome P450 enzyme CYP26,which has specific retinoic acid 4-hydroxylase activity,may regulate steady state levels of the active retinoids in target tissues. -Plasma carotenes are transported mainly in the low-density lipoproteins,while the more water-soluble xanthophylls are most concentrated in the high-density lipoprotein. -Depletion studies suggests that half lives of beta and alpha-carotene and beta-cryptoxanthin are <2 weeks,of lycopene is 2-4 weeks ,and lutein and zeaxanthin are 4-8 weeks. -The shorter half lives of the pro-vitamin A carotenoids may be evidence of their conversion to vitamin A in the tissues but >80% of retinol synthesis from carotenes takes place in the gut during absorption. Excretion -In a healthy person,no vitamin A is secreted per se. -Oxidised metabolites can be found in the urine and any conjugated vitamin A products that might be formed by vitamin A, excess would be secreted into the bile and then lost in the faeces . -During illness,particularly in persons with fever ,retinol is lost through urine,together with RBP,and the amounts can be as high as 500micro grams retinol/day. Deficiency of vitamin A -Vitamin A deficiency can result from inadequate intake,fat malabsorption or liver disorders. -Deficiency impairs immunity and hematopoiesis and causes rashes and typical ocular effects(e.g xerophthalmia,night blindness) -Diagnosis based on typical ocular findings and low vitamin A level. -Treatment consists of vitamin A given orally or if symptoms are severe or malabsorption is the cause parentally. -Vitamin A is required for the formation of rhodopsin,a photoreceptor pigment in the retina. -Vitamin A helps maintain epithelial tissues and is important for lysosome stability and glycoprotein synthesis.
- 2. *Vitamin A and its precursors are ingested in the food matrix. *Proteolysis may release some of Vitamin A and carotenoids from foods. *However to release pro-vitamin A carotenoids from vegetables,they should be thoroughly cooked and masticated,otherwise the carotenoids will remain within cellulose structures and unavailable for absorption. *Released vitamin A and carotenoids aggregate with lipids into globules and pass into the upper part of the small intestine. *Here pancreatic lipase and other esterases hydrolyse lipids (triglycerides e.t.c),retinyl esters and any esters of carotenoids. *Bile salts assist in emulsifying the contents of the gut lumen and lipid micelles are formed. Absorption -Retinol->lipid micelles are taken up by the cells lining the intestine and as much as 90% of retinol in foods is absorbed and utilized. -The high efficiency of this process may be due to the existence of a specific binding protein(CRBPII)in the mucosal cell that carries the retinol to the enzyme lecithin:retinol acyltransferase(LRAT)and this is the main intestinal enzyme that esterifies retinol and delivers it to the chylomicrons. -Very little retinyl rester is absorbed,but hydrolysis of the vitamin A esters in the gut is fairly efficient so more than 50%of the vitamin A in large(pharmaceutical doses)is also absorbed. -Within the enterocyte, absorbed retinol is re-esterified to retinol palmitate and,together with triglycerides and other fat-soluble nutrients,is packaged into chylomicrons for transport to the liver. Carotenoids -Are also fairly efficiently absorbed at low doses(<5mg) but the amount absorbed falls off steeply as the dose rises. There are three potential fates for the carotenes absorbed : *some is metabolised by beta-carotene 15,15’-dioxygenase to form first retinal,then retinol,finally retinol pamitate. *Some carotene is taken up by the chylomicrons unchanged,while the epithelial cell retains the remainder,which if not converted to retinol is lost through cell turnover in the faeces. Transport from gut to Liver -Retinol esters and carotenoids are transported from the gut,via lymphatic vessels,that drain into the jugular vein,with triglyceride in the core of chylomicrons. -The chylomicrons circulate around the body on their way to the liver. -Most triglycerides are transferred to extrahepatic tissues and most vitamin A is removed from the circulation by the livet’s parenchymal cells when the chylomicron remnants(cholesterol esters,retinol palmitate,carotenoids,and other fat soluble vitamins)reach the liver. -The retinyl esters are hydrolysed in the parenchymal cells and,after meeting any physiological needs,the retinol is transferred to the stellate cells in a process involving retinol-binding protein(RBP). -Stellate cells are modified macrophages which comprise 7% of liver cells numbers but only 2% of the volume. -Within the stellate cells,the retinol is mainly stored as palmitate(<90%). -More than 80% of the total body vitamin A is stored in the liver and some in the kidney. -Generally vitamin A in the liver increases with age.On average, a 70kg man with a liver weighing 1.8kg would have 150-300mg of stored vitaminA,enough to last for a year or more of no intake. 350-500 1-6yrs 400 7-12yrs 500 Adolescents 600 Men 600-900 Women 600-900 Pregnant 700-800 Lactating 850,1100,1300 Classification of vitamin A *All-trans retinol(vitamin A1,Alcohol form) *All-trans retinal(aldehyde form)
- 3. *Vitamin A and its precursors are ingested in the food matrix. *Proteolysis may release some of Vitamin A and carotenoids from foods. *However to release pro-vitamin A carotenoids from vegetables,they should be thoroughly cooked and masticated,otherwise the carotenoids will remain within cellulose structures and unavailable for absorption. *Released vitamin A and carotenoids aggregate with lipids into globules and pass into the upper part of the small intestine. *Here pancreatic lipase and other esterases hydrolyse lipids (triglycerides e.t.c),retinyl esters and any esters of carotenoids. *Bile salts assist in emulsifying the contents of the gut lumen and lipid micelles are formed. Absorption -Retinol->lipid micelles are taken up by the cells lining the intestine and as much as 90% of retinol in foods is absorbed and utilized. -The high efficiency of this process may be due to the existence of a specific binding protein(CRBPII)in the mucosal cell that carries the retinol to the enzyme lecithin:retinol acyltransferase(LRAT)and this is the main intestinal enzyme that esterifies retinol and delivers it to the chylomicrons. -Very little retinyl rester is absorbed,but hydrolysis of the vitamin A esters in the gut is fairly efficient so more than 50%of the vitamin A in large(pharmaceutical doses)is also absorbed. -Within the enterocyte, absorbed retinol is re-esterified to retinol palmitate and,together with triglycerides and other fat-soluble nutrients,is packaged into chylomicrons for transport to the liver. Carotenoids -Are also fairly efficiently absorbed at low doses(<5mg) but the amount absorbed falls off steeply as the dose rises. There are three potential fates for the carotenes absorbed : *some is metabolised by beta-carotene 15,15’-dioxygenase to form first retinal,then retinol,finally retinol pamitate. *Some carotene is taken up by the chylomicrons unchanged,while the epithelial cell retains the remainder,which if not converted to retinol is lost through cell turnover in the faeces. Transport from gut to Liver -Retinol esters and carotenoids are transported from the gut,via lymphatic vessels,that drain into the jugular vein,with triglyceride in the core of chylomicrons. -The chylomicrons circulate around the body on their way to the liver. -Most triglycerides are transferred to extrahepatic tissues and most vitamin A is removed from the circulation by the livet’s parenchymal cells when the chylomicron remnants(cholesterol esters,retinol palmitate,carotenoids,and other fat soluble vitamins)reach the liver. -The retinyl esters are hydrolysed in the parenchymal cells and,after meeting any physiological needs,the retinol is transferred to the stellate cells in a process involving retinol-binding protein(RBP). -Stellate cells are modified macrophages which comprise 7% of liver cells numbers but only 2% of the volume. -Within the stellate cells,the retinol is mainly stored as palmitate(<90%). -More than 80% of the total body vitamin A is stored in the liver and some in the kidney. -Generally vitamin A in the liver increases with age.On average, a 70kg man with a liver weighing 1.8kg would have 150-300mg of stored vitaminA,enough to last for a year or more of no intake.
- 5. *Vitamin A and its precursors are ingested in the food matrix. *Proteolysis may release some of Vitamin A and carotenoids from foods. *However to release pro-vitamin A carotenoids from vegetables,they should be thoroughly cooked and masticated,otherwise the carotenoids will remain within cellulose structures and unavailable for absorption. *Released vitamin A and carotenoids aggregate with lipids into globules and pass into the upper part of the small intestine. *Here pancreatic lipase and other esterases hydrolyse lipids (triglycerides e.t.c),retinyl esters and any esters of carotenoids. *Bile salts assist in emulsifying the contents of the gut lumen and lipid micelles are formed. Absorption -Retinol->lipid micelles are taken up by the cells lining the intestine and as much as 90% of retinol in foods is absorbed and utilized. -The high efficiency of this process may be due to the existence of a specific binding protein(CRBPII)in the mucosal cell that carries the retinol to the enzyme lecithin:retinol acyltransferase(LRAT)and this is the main intestinal enzyme that esterifies retinol and delivers it to the chylomicrons. -Very little retinyl rester is absorbed,but hydrolysis of the vitamin A esters in the gut is fairly efficient so more than 50%of the vitamin A in large(pharmaceutical doses)is also absorbed. -Within the enterocyte, absorbed retinol is re-esterified to retinol palmitate and,together with triglycerides and other fat-soluble nutrients,is packaged into chylomicrons for transport to the liver. Carotenoids -Are also fairly efficiently absorbed at low doses(<5mg) but the amount absorbed falls off steeply as the dose rises. There are three potential fates for the carotenes absorbed : *some is metabolised by beta-carotene 15,15’-dioxygenase to form first retinal,then retinol,finally retinol pamitate. *Some carotene is taken up by the chylomicrons unchanged,while the epithelial cell retains the remainder,which if not converted to retinol is lost through cell turnover in the faeces. Transport from gut to Liver -Retinol esters and carotenoids are transported from the gut,via lymphatic vessels,that drain into the jugular vein,with triglyceride in the core of chylomicrons. -The chylomicrons circulate around the body on their way to the liver. -Most triglycerides are transferred to extrahepatic tissues and most vitamin A is removed from the circulation by the livet’s parenchymal cells when the chylomicron remnants(cholesterol esters,retinol palmitate,carotenoids,and other fat soluble vitamins)reach the liver. -The retinyl esters are hydrolysed in the parenchymal cells and,after meeting any physiological needs,the retinol is transferred to the stellate cells in a process involving retinol-binding protein(RBP). -Stellate cells are modified macrophages which comprise 7% of liver cells numbers but only 2% of the volume. -Within the stellate cells,the retinol is mainly stored as palmitate(<90%). -More than 80% of the total body vitamin A is stored in the liver and some in the kidney. -Generally vitamin A in the liver increases with age.On average, a 70kg man with a liver weighing 1.8kg would have 150-300mg of stored vitaminA,enough to last for a year or more of no intake.
- 6. T
Editor's Notes
- Mobilization of vitamin A from the liver and serum transport -Retinol is released from the liver bound to RBP.RBP has a molecular weight of 21 000 and one binding site for retinol. -Holo-RBP (the RBP-retinol complex)is released from the liver bound to another protein,transthyretin(TTR).TTR has a molecular weight of 55 000 and was previously known as thyroxine-binding pre-albumin;it also has one binding site,so the whole complex is a 1:1:1 structure. -In plasma ,95% of the retinol is bound in the retinol-RBP-TTR complex. The binding of retinol to RBP confers a number of physiological advantages; *RBP(and all the vitamin A-binding proteins within the cell)facilitate the transport of a lipid-soluble compound through the aqueous environment of the plasma. *There is protection of retinol from oxidative damage during transport *There is regulation of retinol mobilization *There is delivery of retinol to specific sites on the surface of target cells,particularly the eye ,where a lack of RBP results in night blindness *There is formation of a large molecule as a complex,which is not easily lost from plasma during vasodilation -Holo-RBP is taken up by specific cell-surface receptors.Once the retinol is transferred within the cell, the apo-RBP(the free protein)is released from the receptor and can be recycled.Some is excreted by the kidney. Retinol inside the cell is bound to CRBP1. -Some cells can also take up retinol palmitate from circulating chylomicrons via lipoprotein receptors. Within the cell the ester is hydrolysed and retinol is bound to CRBP1 for further metabolism. -Inside the cell,retinol is oxidised to retinal and then to all-trans retinoic acid by local expression of retinoic acid-synthesizing aldehyde dehydrogenase. -Some of the all-trans retinoic acid is converted to 9-cis retinoic acid.The two forms ,all-trans and 9-cis retinoic acid,interact with the nuclear receptors RAR and RXR,respectively. -The cytochrome P450 enzyme CYP26,which has specific retinoic acid 4-hydroxylase activity,may regulate steady state levels of the active retinoids in target tissues. -Plasma carotenes are transported mainly in the low-density lipoproteins,while the more water-soluble xanthophylls are most concentrated in the high-density lipoprotein. -Depletion studies suggests that half lives of beta and alpha-carotene and beta-cryptoxanthin are <2 weeks,of lycopene is 2-4 weeks ,and lutein and zeaxanthin are 4-8 weeks. -The shorter half lives of the pro-vitamin A carotenoids may be evidence of their conversion to vitamin A in the tissues but >80% of retinol synthesis from carotenes takes place in the gut during absorption. Excretion -In a healthy person,no vitamin A is secreted per se. -Oxidised metabolites can be found in the urine and any conjugated vitamin A products that might be formed by vitamin A, excess would be secreted into the bile and then lost in the faeces . -During illness,particularly in persons with fever ,retinol is lost through urine,together with RBP,and the amounts can be as high as 500micro grams retinol/day. Deficiency of vitamin A -Vitamin A deficiency can result from inadequate intake,fat malabsorption or liver disorders. -Deficiency impairs immunity and hematopoiesis and causes rashes and typical ocular effects(e.g xerophthalmia,night blindness) -Diagnosis based on typical ocular findings and low vitamin A level. -Treatment consists of vitamin A given orally or if symptoms are severe or malabsorption is the cause parentally. -Vitamin A is required for the formation of rhodopsin,a photoreceptor pigment in the retina. -Vitamin A helps maintain epithelial tissues and is important for lysosome stability and glycoprotein synthesis.
- Daily Requirements Microgram retinol equivalents per day Infants 350-500 1-6yrs 400 7-12yrs 500 Adolescents 600 Men 600-900 Women 600-900 Pregnant 700-800 Lactating 850,1100,1300 Classification of vitamin A *All-trans retinol(vitamin A1,Alcohol form) *All-trans retinal(aldehyde form) *3-dehydroretinol(vitamin A2) Vitamin A2 is found in freshwater fish.
- Metabolism of Vitamin A *Vitamin A and its precursors are ingested in the food matrix. *Proteolysis may release some of Vitamin A and carotenoids from foods. *However to release pro-vitamin A carotenoids from vegetables,they should be thoroughly cooked and masticated,otherwise the carotenoids will remain within cellulose structures and unavailable for absorption. *Released vitamin A and carotenoids aggregate with lipids into globules and pass into the upper part of the small intestine. *Here pancreatic lipase and other esterases hydrolyse lipids (triglycerides e.t.c),retinyl esters and any esters of carotenoids. *Bile salts assist in emulsifying the contents of the gut lumen and lipid micelles are formed. Absorption -Retinol->lipid micelles are taken up by the cells lining the intestine and as much as 90% of retinol in foods is absorbed and utilized. -The high efficiency of this process may be due to the existence of a specific binding protein(CRBPII)in the mucosal cell that carries the retinol to the enzyme lecithin:retinol acyltransferase(LRAT)and this is the main intestinal enzyme that esterifies retinol and delivers it to the chylomicrons. -Very little retinyl rester is absorbed,but hydrolysis of the vitamin A esters in the gut is fairly efficient so more than 50%of the vitamin A in large(pharmaceutical doses)is also absorbed. -Within the enterocyte, absorbed retinol is re-esterified to retinol palmitate and,together with triglycerides and other fat-soluble nutrients,is packaged into chylomicrons for transport to the liver. Carotenoids -Are also fairly efficiently absorbed at low doses(<5mg) but the amount absorbed falls off steeply as the dose rises. There are three potential fates for the carotenes absorbed : *some is metabolised by beta-carotene 15,15’-dioxygenase to form first retinal,then retinol,finally retinol pamitate. *Some carotene is taken up by the chylomicrons unchanged,while the epithelial cell retains the remainder,which if not converted to retinol is lost through cell turnover in the faeces. Transport from gut to Liver -Retinol esters and carotenoids are transported from the gut,via lymphatic vessels,that drain into the jugular vein,with triglyceride in the core of chylomicrons. -The chylomicrons circulate around the body on their way to the liver. -Most triglycerides are transferred to extrahepatic tissues and most vitamin A is removed from the circulation by the livet’s parenchymal cells when the chylomicron remnants(cholesterol esters,retinol palmitate,carotenoids,and other fat soluble vitamins)reach the liver. -The retinyl esters are hydrolysed in the parenchymal cells and,after meeting any physiological needs,the retinol is transferred to the stellate cells in a process involving retinol-binding protein(RBP). -Stellate cells are modified macrophages which comprise 7% of liver cells numbers but only 2% of the volume. -Within the stellate cells,the retinol is mainly stored as palmitate(<90%). -More than 80% of the total body vitamin A is stored in the liver and some in the kidney. -Generally vitamin A in the liver increases with age.On average, a 70kg man with a liver weighing 1.8kg would have 150-300mg of stored vitaminA,enough to last for a year or more of no intake.
- Vitamin A(retinol,retinoic acid) is a nutrient important for vision,growth,cell division,reproduction and immunity.Vitamin A also has antioxidant properties.Antioxidants are substances that might protect your cells against the effect of free radicals.Molecules produced when your body breaks down food or is exposed to tobacco smoke and radiation. Major sources of Vitamin A *Spinach *Dairy products like milk&yoghurt *liver *other sources are;green leafy vegetables,carrots,cheese,egg yolk,butter and fish
- VITAMIN A DEFICIENCY Vitamin A deficiency can result result from inadequate intake, fat malabsorption or liver disorders. Deficiency impairs immunity and hematopoesis and causes rashes and typical ocular effects. Treatment consists of vitamin a given orally or if symptoms persist malabsorption is the cause parentally. Vitamin A is required for the formation of rhodopsin, a photoreceptor pigment in the retina. Vitamin A helps in maintaining epithelial tissues and is important for lysosome stability and glycoprotein synthesis.
- Etiology of Vitamin A deficiency 1)Primary vitamin A deficiency is caused prolonged dietary despiration. 2)Secondary vitamin A deficiency may be due to : *Decreased bioavailability of provitamin A carotenoids. *Interference with absorption stage or transport of vitamin A. Sign and symptom of vitamin A deficiency is impaired dark adaptation of the eyes which can lead to night blindness, respiratory infections, changes in gastro intestinal tract resulting into diarrhoea,failure in teeth enamel as a result of deprivation in vitamin A, lost of some of smell and taste, dry skin, poor wound healing. Prevention of vitamin A deficiency -Using available foods. -Breastfeeding. -Fortification and enrichment. *Fortification is the addition of vitamin A to a widely used food that would not normally contain the vitamin. *Enrichment is the addition of vitamin A to a food to replace the lost vitamin during processing. Functions of vitamin A *Vision- the most recognizable function of vitamin Ais its involment with the eye and normal vision. After all trans retinol binds with specific receptors on retinol pigment epithelial cells of the eye, retinol enters the cells and becomes bound to CRBP. It is isomerised to 11-cis retinol. 11 cis retinol undergoes oxidative conversion to 11-cis retinal. It is then transferred to the photoreceptors and associates with specific lysin residue in the membrane protein, opsin, forming rhodopsin .
- FUNCTIONS OF VITAMIN A Growth-vitamin A deficiency causes loss of apetite. Slow bone growth. Affects CNS. Reproduction- Retinal and retinol are essential for normal reproduction. Maintenance of epithelial cells- essential for the normal differentiation of epithelial tissues and mucus secretion. It causes stabilization of cellular and intracellular membrane. It helps in the synthesis of glycoproteins. It enhance imunity to infecton .
- SYMPTOMS OF VITAMIN A DEFICIENCY Night blindness. Causes trouble in seeing in low light, which may damage the cornea and retina. Infections- the person with vitamin A deficiency can experience more health concerns as they will not be able to fight infections. Bitot spot- this condition is a build up of keratin in the eyes causing hazy vision. Skin irritation-the victims experience problems with their skin such as dryness, itching and scaling. Stunded growth-slow bone growth in children. Infertility. Keratomalacia- eye disorder involving dryng and clouding of the cornea. Keratinisation- process by which cells become filled with keratin protein, die and form tough, resistant structures in urinary, gastointestinal and respiratory tracts.
- vitamin a toxicity; Toxic effects of vitamin A The most serious toxic effects of vitamin A are teratogenic as a result of overdose during the first trimester of pregnancy. Such effects include spontaneous abortions or foetal abnormalities, including those of the cranium (microcephaly), face (hairlip), heart, kidney, thymus, and central nervous system (deafness and lowered learning ability). Since embryogenesis is under the control of retinoic acid isomers, short-term increases in these compounds are probably responsible. Normal concentrations of plasma retinoic acid are 1–2 nmol/L. In one experiment, large doses of vitamin A (>300 000 IU, >100 mg) given to 10 women caused 10–100-fold increases in plasma retinoic acid concentrations at 4 hours. The same amount of vitamin A given as liver-only increased plasma retinoic acid concentrations 10-fold at 4 hours. Thus, women who are pregnant or who could become pregnant should not be exposed to retinoid therapy either for skin conditions or as supplements. Daily intakes should not exceed 10 000 IU (3 mg RE). Acute and chronic toxic effects of vitamin A overdose can also occur in all individuals. Very high single doses can cause transient symptoms that may include bulging fontanelles in infants, headaches in older children and adults, and vomiting, diarrhoea, and loss of appetite in all age groups. It is rare for toxicity to occur from ingestion of food sources of vitamin A. When it does, it is usually due to the consumption of a large amount of liver as, for example, in arctic and antarctic explorers who consumed polar bear, seal, or dog liver. In these extreme circumstances additional symptoms included blurred or double vision, vertigo, uncoordinated movements, elevated cerebrospinal pressure, and skin exfoliation. Deaths have also occurred. Single large doses of vitamin A in infancy and childhood have been reported to cause transient toxic eff ects, but these are usually avoided if the dose is not more than 50 000 IU for infants below 6 months, 100 000 IU between 6 and 12 months, and 200 000 IU for children over 1 year. Doses are not given more frequently than once every 3 months. Chronic toxicity is induced by consuming for a month or more at least 10 times the recommended daily allowance (e.g. 10 mg RE per day or 33 300 IU). A wide range of symptoms have been reported including headache, bone and muscle pain, ataxia, visual impairment, skin disorders, alopecia, liver toxicity, and hyperlipidaemia. It is usual to fi nd high concentrations of retinol palmitate in the blood (3–8 μmol/L). Normally, retinol palmitate is only found in the blood for 3–4 hours after a meal, in the chylomicron fraction. High intakes of carotenoids, e.g. from tomato or carrot juice or red palm oil, can lead to hypercarotenaemia and yellow coloration of the skin, especially the palms of the hands or the soles of the feet and the nasolabial folds (not the eyes), but this is not associated with toxic eff ects. High doses of β-carotene (180 mg/day) are used in the treatment of erythropoietic protoporphyria and have never been found to cause harm. The only worrying effects with carotenoids are prolonged use of high-dose β-carotene in smokers.