Vitamin A (Retinol, Retinal) and Beta-Carotene

1. RETINOIDS: RETINOL, RETINAL (PREFORMED VITAMIN A)

Preformed vitamin A (retinol) naturally occurs only in animal foods. In your body, retinol is made into the active forms of vitamin A–retinal and retinoic acid–which are collectively called retinoids ^[4].

The name retinoids originates from the Latin retina–the inner layer of the eye–which is part of the visual system.

Recommended Daily Intake

According to Institute Of Medicine in the US, the Recommended Dietary Allowance (RDA) for retinol for adults is 900 mcg RAE (3,000 IU) for men, 700 mcg RAE (2,333 IU) for women, 770 mcg RAE (2,567 IU) during pregnancy and 1,300 mcg RAE (4,333 IU) during breastfeeding ^[4].

Human breast milk of healthy mothers contains about 600 mcg RAE retinol per liter, which is enough to meet the needs of infants 0-12 months old ^[1,3].

Picture 2. Vitamin A sources

Foods High in Retinol

Foods rich in retinol include liver, fish oil, oily fish, cheese, milk, egg yolk, orange fruits, yellow, orange and green leafy vegetables and fortified foods and beverages ^[3].

Drying can reduce the retinol and beta-carotene content of foods by up to 50% and cooking by 25%, so usually retinol and beta-carotene are considered thermostable ^[5,6].

Chart 1. Foods High in Retinol
ANIMAL FOODS	Retinol (mcg RAE)
Beef or veal liver (3 oz, 85 g)	6,300-18,000
Turkey liver (3 oz, 85 g)	9,140
Pork liver (3 oz, 85 g)	4,600
Chicken liver (3 oz, 85)	3,780
Fish oil, cod liver (1 tsp, 4.5 g)	1,350
Fish: eel, tuna (bluefin) (3 oz, 85 g)	650
Cheese: goat (hard) (2 oz, 57 g)	280
Fish: cuttlefish, mackerel (king), sturgeon (3 oz, 85 g)	175-220
Cheese: brick, caraway, cheddar, colby, fontina, gjetost, goat (soft), gruyere, limburger, muenster, roquefort (2 oz, 57 g)	150-200
Veal, kidney (3 oz, 85 g)	120-170
Eggnog (1 cup, 237 mL)	150
Cheese: American-pasteurized, blue, brie, camembert, edam, gouda, monterey, mozzarella, provolone, queso fresco, Swiss, tilsit	100-150
Clams (3 oz, 85 g)	145
Milk, buffalo, goat (1 cup, 237 mL)	130
Goose liver pate (1 tbsp, 13 g)	130
Bluefish, wolffish, salmon (chinook) (3 oz, 85 g)	120-130
Milk, cow, sheep, whole (1 cup, 237 mL)	110
Cheese: feta, muenster, ricotta, romano	50-100
Butter (1 tbsp, 14 g)	100
Beef, kidney (3 oz, 85 g)	90
Sablefish, trout (3 oz, 85 g)	90
Mussels, oysters, shrimps (3 oz, 85 g)	80
Egg (50 g); all retinol is in the yolk	75
Chicken, duck, turkey (3 oz, 85 g)	20-70
Milk, 1-2% fat (1 cup, 237 mL)	30-70
Yogurt, plain (6 oz, 177 mL)	50
PLANT FOODS	Beta-carotene (mcg RAE)
Carrot juice (1 cup, 237 mL)	2,250
Sweet potato (1 cup, 237 mL)	1,900
Squash, winter, butternut (1 cup, 237 mL)	1,150
Collards, dandelion greens, kale, pokeberry shoots, pumpkin, spinach, turnip greens (1/2 cup, 120 mL)	350-500
Melon, cantaloupe (1 cup, 237 mL)	300
Beet greens, mustard greens, Swiss chard (1/2 cup, 120 mL)	270
Chinese cabbage, lettuce (cos, romaine) (172 cup, 120 mL)	180-200
Garden cress (1/2 cup, 120 mL)	150
Apricot, grapefruit, loquats, passion fruit, persimmon, pitanga, tangerines (1 cup, 237 mL)	110-150
Passion-fruit (1 cup, 237 mL)	150
Grapefruit (1 cup, 237 mL)	140
Lettuce, green leaf, tomato (orange) (1 cup, 237 mL)	130
Buttermilk (1 cup, 237 mL)	115
Peppers, red (1/2 cup)	60-100
Mango, papaya, tomato (red) (1 cup, 237 mL)	70-90
Cherries, sour, red (1/2 cup, 120 mL)	50
RETINOL FORTIFIED FOODS
Various nutritional beverages (1 cup, 237 mL)	100-1,000
Cereals (30 g dry, yields 1 cup prepared)	100-560
Formulated bars (50-80 g)	100-500
Peanut butter (2 tbsp, 30 g)	375
Orange juice (1 cup, 237 mL)	285
Margarine and margarine-like spread (1 tbsp, 14 g)	100-200
Milk and soy milk (1 cup, 237 mL)	130-150

Absorption and Body Stores

Retinol, which is present in foods and supplements mainly as retinyl palmitate, is absorbed in the first part of the small intestine (duodenum) ^[1,11]. Retinol can be absorbed only in the presence of fats from foods and when sufficient amount of bile and pancreatic enzymes–which enable the absorption of fat–is available. Retinol is stored mainly in the liver and fat tissue in the form of retinyl palmitate ^[1]. The body stores of vitamin A in adults are sufficient for 1-2 years but in children only for several weeks ^[11,16].

Bioavailability, Retinol Activity Equivalents (RAE) and International Units (IU)

Retinol in your body can come from retinol and beta-carotene from foods and supplements, and from alpha-carotene and beta-cryptoxanthin from foods. Different retinol sources have different activities. The Retinol Activity Equivalent (RAE) is the amount of different vitamin forms that has the same activity as 1 microgram of retinol.

• 1 mcg of retinol = 1 RAE
• 2 mcg of beta-carotene from supplements = 1 RAE, which means 2 mcg of beta-carotene are needed to have the same activity (effect) than 1 mcg of retinol (see Chart 2 below) ^[1].

Another unit for the amount of vitamin A are International Units (IU):

• 1 IU retinol = 0.3 mcg RAE
• 1 IU beta-carotene from dietary supplements = 0.15 mcg RAE
• 1 IU beta-carotene from food = 0.05 mcg RAE
• 1 IU alpha-carotene or beta-cryptoxanthin = 0.025 mcg RAE

Chart 2. RAE and IU
Vitamin A Form	1 RAE* (mcg)	IU*
Retinol from animal foods, fortified foods and supplements	1 mcg	3.3
Beta-carotene from supplements	2 mcg	6.7
Beta-carotene from plant foods	12 mcg	20
Alpha-carotene from plant foods	24 mcg	40
Beta-cryptoxanthin from plant foods	24 mcg	40

Reference [1] * RAE = Retinol Activity Equivalents; IU = International Units ^[1].

Normal Blood Levels

Normal blood plasma retinol levels are higher than 1.05 micromoles/L (30 micrograms (mcg)/dL) ^[1]. Levels lower than 0.7 micromoles/L (20 mcg/dL) indicate vitamin A deficiency ^[1].

The blood retinol levels are not a very good indicator of the vitamin A status in the body, because they fall only when the liver retinol stores are severely decreased ^[1].

Retinol Supplements

Without prescription (over-the-counter):

• Retinyl acetate and retinyl palmitate as standalone supplements, or in combination with beta-carotene or as part of multivitamins. Available forms include tablets, capsules and liquid (drops).

By prescription:

• Retinyl palmitate intramuscular injection (when poor absorption from the intestine is expected)

Possible Benefits of Retinol Supplements

Retinol is EFFECTIVE in:

• Prevention and treatment of vitamin A deficiency ^[2]

Retinol is POSSIBLY EFFECTIVE in:

• Reduction of complications of malaria, measles and diarrhea in children with low vitamin A levels ^[1,2,4,11]
• Slowing down the progress of retinitis pigmentosa, a genetic disorder with a progressive vision loss ^[1,4,17]
• Correction of iron deficiency anemia (along with iron supplements), mainly in children with both vitamin A and iron deficiency ^[4,14,15,17]

Retinol is POSSIBLY INEFFECTIVE in prevention or treatment of arthritis, cancer (breast, gastric), HIV transmission during pregnancy, delivery and breast-feeding, side effects of chemotherapy in children, head and neck tumors or pneumonia, inflammatory bowel disease (Crohn’s disease), miscarriage, osteoarthritis, pneumonia or tuberculosis ^[1,2].

There is INSUFFICIENT EVIDENCE about the retinol effectiveness in prevention or treatment of age-related macular degeneration (AMD), alcohol-related liver disease, asthma, cancer (colorectal, esophageal, lung, melanoma, ovarian, pancreatic, prostate, chronic myelogenous leukemia), cataract, diabetes, glaucoma, headaches, HIV/AIDS, infections, kidney stones, miscarriage, parasite infestation, precancerous mouth sores (leukoplakia), premenstrual syndrome (PMS), psoriasis, ringing in the ears (tinnitus), skin conditions other than acne, improving vision, wound healing or immunity or relieving hay fever symptoms, raising sperm count in men, slowing aging or promoting weight loss ^[2,4].

Retinol Side Effects and Toxicity

Retinol supplements are likely safe for adults and children when taken in recommended doses by mouth or as intramuscular injections ^[26]. According to Institute Of Medicine (IOM) in the US, the Tolerable Upper Intake Level (UI) for retinol–the amount that should not cause side effects–for adults is 3,000 mcg (10,000 IU)/day ^[1]. Before taking higher doses of retinol, speak with your doctor. In poor areas, doses up to 50,000-200,000 IU can be used to treat severe vitamin A deficiency ^[16].

During Pregnancy

Retinol supplements are pregnancy category X, which means they may cause birth defects in children ^[16]. Pregnant women should limit their retinol intake from foods (especially liver) and supplements combined to 3,000 mcg (3,000 RAE or 10,000 IU) per day; these or lower amounts taken during pregnancy have not been associated with increased risk of birth defects in babies ^[4]. Retinol can be stored in the human body for prolonged periods, so taking retinol supplements in high doses even before pregnancy may increase the risk of birth defects in babies; this means that women who plan to be pregnant at any time should avoid high doses of retinol ^[1,4].

Side Effects

Side effects may include blurry vision, bone pain, breathing difficulty, chronic inflammation of the liver, cirrhosis, cracked fingernails, cracked lips, depression, diarrhea, fever, hair loss, high cholesterol, hypothyroidism, increased pressure in the brain, indigestion, inflammation of the conjunctiva (conjunctivitis), joint pain, mouth ulcers, muscle pain, psoriasis flare-ups and seizures ^[18].

Complications. Prolonged intake of retinol supplements in doses exceeding 1,500 mcg (5,000 IU)/day may increase the risk of osteoporosis in old people ^[4,26].

Overdose (Hypervitaminosis A)

Acute hypervitaminosis A can occur after intake of high doses (100-200 mg) of retinol supplements or consuming large amounts of animal liver ^[1]. Symptoms include nausea, vomiting, headache, dizziness, fatigue, blurred vision, loss of appetite, skin scaling, excessive sweating, muscular incoordination and, in severe cases, brain edema, coma or death ^[1].

Chronic hypervitaminosis A may develop after months of excessive (>8-10 mg or > 25,000-33,000 IU/day) intake of retinol supplements or consuming large amounts of animal liver and may present with fatigue, irritability, depression, loss of appetite, nausea, vomiting, mild fever, excessive sweating, dry, scaly and itchy skin, headache, bone and joint pain or, in severe cases, coma and death ^[1,26]. Chronic hypervitaminosis A may result in liver and neurological disorders and birth defects ^[26].

Long-term high doses of vitamin A can increase the risk of death ^[26].

Retinol Interactions With Nutrients and Drugs

• Chronic alcohol consumption lowers the activity of retinol in the body, but high doses of vitamin A may be toxic for liver that was previously affected by alcohol.
• Retinoid drugs, such as retinoic acid, bexarotene, etretinate and isotretinoin, should not be used in combination with retinol supplements, because they may increase the risk of vitamin A toxicity ^[4].
• Zinc deficiency might decrease the activity of vitamin A in the body ^[4].
• Iron deficiency can prevent effectiveness of vitamin A supplements to correct vitamin A deficiency ^[11]. Vitamin A deficiency can cause iron-deficiency anemia ^[4].

Retinoids as Prescribed Medications or Anti-Wrinkle Creams

Retinoids as prescribed vitamin A-like medications (acitretin, all-trans-retinoic acid, bexarotene, etretinate and isotretinoin) may be used to treat retinitis pigmentosa, acute promyelocytic leukemia, severe acne, psoriasis and other skin disorders. Certain over-the-counter (OTC) anti-wrinkle or anti-aging creams contain retinol or other retinoids. These medications and creams may cause birth defects even months after stopping the treatment, so pregnant women and those who plan pregnancy should avoid them ^[4].

2. CAROTENOIDS (PROVITAMIN A)

Provitamins A–beta-carotene, alpha-carotene and beta-cryptoxanthin–can be converted to retinol in the human body ^[13].

2.a. BETA CAROTENE

Beta-carotene is composed of two molecules of vitamin A (retinol) ^[13,21,22].

Foods High in Beta-Carotene

Beta-carotene is found mainly in plant foods, for example in carrots, sweet potatoes and winter squash, and in cheese and milk (it can give yellow color to cheese and even milk ^[22]. For more foods high in beta-carotene, see Chart 1 above.

Chopping or mashing foods releases some beta-carotene from other food components and thus makes it easier to absorb ^[21].

Beta-Carotene Supplements

Beta-carotene supplements are either extracted from algae or palm oil, or artificially produced ^[4]. They are available as tablets or capsules as a separate supplement or as part of multivitamins. In average, beta-carotene from supplements is 6 times as absorbable as beta-carotene from foods ^[1].

Possible Beta-Carotene Supplements Benefits

Beta-carotene is POSSIBLY EFFECTIVE in prevention or treatment of vitamin A deficiency ^[13].

Beta-carotene is POSSIBLY INEFFECTIVE in prevention or treatment of Alzheimer’s disease, actinic keratosis (scaly skin due to sun damage), cancer (bladder, brain, cervical, colorectal, esophageal, gastric, lung, pancreatic, skin, thyroid), cataracts, diabetes type 2, heart disease, moles or stroke ^[19].

There is INSUFFICIENT EVIDENCE about effectiveness of beta-carotene in prevention or treatment of age-related macular degeneration (AMD), chronic fatigue syndrome (CFS), depression, epilepsy, erythropoietic protoporphyria, exercise-induced asthma, headaches, heartburn, high blood pressure, HIV/AIDS, infertility, leukemia, liver disease, Parkinson’s disease, rheumatoid arthritis, schizophrenia, sunburn, tuberculosis, viral infections, as an antioxidant, in improving human immunity, night vision, physical performance or wound healing or promoting weight loss ^[12,13]. A combination of beta-carotene, vitamin C, vitamin E, selenium and zinc might lower cancer rates in men, but not women ^[12,19].

Beta-Carotene Supplements Safety: Side Effects, Toxicity

Carotenemia

High doses of beta-carotene supplements (>30 mg/day) or consumption of large amounts of sweet potatoes, carrots or squash, may result in a harmless increase of beta-carotene blood levels (carotenemia) and accumulation of beta-carotene in the skin (carotenodermia or xanthoderma), with transient yellow discoloration of the skin, mainly on the palms, soles and around the nose, but not the eye whites ^[13,21]. Hypothyroidism, diabetes mellitus, liver and kidney disorders and anorexia nervosa may also cause carotenemia ^[21].

Other side effects of beta-carotene supplements may include burping, constipation, diarrhea, dizziness, headache, joint pain, muscle pain, vision problems and worsening cholesterol levels ^[19] and yellow discoloration of urine ^[23]. Beta-carotene in high doses does not likely result in hypervitaminosis A, since the conversion of beta-carotene to vitamin A (retinol) stops when the body stores of retinol are saturated ^[13,21].

Complications

• In some, but not all, studies, beta-carotene supplements in high doses (20 mg/day for 5-8 years) were associated with increased risk of lung cancer in smokers, former asbestos workers and heavy alcohol drinkers ^[1,13,25,27].
• Beta-carotene supplements may increase the risk of bladder, stomach and prostate cancer, colds, coronary heart disease or bleeding ^[20].

During Pregnancy

Beta-carotene supplements, even in high doses, have not been associated with birth defects, but their safety during pregnancy has not been well established, so Linus Pauling Institute in the US recommends limiting the dose to 3,000 mcg (5,000 IU) per day during pregnancy and breastfeeding unless prescribed otherwise by a doctor ^[13,20]. There is no need to limit foods high in beta-carotene during pregnancy or breastfeeding, though.

2.b. ALPHA-CAROTENE

24 micrograms of alpha-carotene has the same effect as 1 microgram of retinol ^[1]. Examples of foods high in alpha-carotene are pumpkin and carrots ^[13].

2.c. BETA-CRYPTOXANTHIN

24 micrograms of beta-cryptoxanthin has the same effect as one microgram of retinol ^[1]. Examples of foods high in beta-cryptoxanthin are pumpkins and papayas ^[13].

Retinol and Beta-Carotene as Antioxidants

Retinol and beta-carotene can act as antioxidants in the human body, which means, they can block the action of the substances that act as oxidants (free radicals), but there is insufficient evidence about their effect in the prevention or treatment of diseases caused by oxidants, such as atherosclerosis or cancer ^[24,25].