Vitamin A was the first fat-soluble vitamin to be recognized. Although identified as a necessary growth factor as early as 1913, it was not chemically characterized until 1930. Two groups of researchers, McCollum and Davis of the University of Wisconsin and Osborne and Mendel of Yale University, made the initial discovery of the vitamin. A almost simultaneously. They observed that young animals, fed a diet low in natural fat, had health problems, as evidenced by their slowed growth and weak immune responses. These researchers also noted that, following a similar diet, the eyes of the animals underwent severe inflammation and infection: a state from which they emerged quickly following the ' adding butterfat or cod liver oil to their diet. Formerly known as the 'anti-infective vitamin', vitamin A has recently been recognized as a critical component of the immune system. Carotenes, some of which can be converted to vitamin A, are also getting a great deal of attention for their ability to boost the immune system. Due to the vitamin A-like activity of some carotenes, both vitamin A and carotenes are examined in this chapter. they are getting a great deal of attention for their ability to strengthen the immune system. Due to the vitamin A-like activity of some carotenes, both vitamin A and carotenes are examined in this chapter. they are getting a great deal of attention for their ability to strengthen the immune system. Due to the vitamin A-like activity of some carotenes, both vitamin A and carotenes are examined in this chapter.(1) .
Carotenes
Carotenes represent the most widespread group of pigments found in nature. They are a group of fat-soluble compounds, of an intense color (red and yellow). All organisms that transform sunlight into chemical energy through the process of photosynthesis do so with the help of carorene.These compounds not only play a role in photosynthesis, but are also essential in protecting the organism or plant against the huge amount of free radicals produced during this process.
Scientists have characterized over 600 carotenoids, of which only 30-50 appear to have activity similar to that of vitamin A. Per years it has been assumed that the biological activity of carotene coincides with its activity as vitamin A. Recent research, however, suggest that this function of carotene has been over-emphasized and carotenoids have been shown to have many other activities. Researchers have described beta-carotene as the most active of the carotenoids due to its high pro-vitamin A activity, although several other carotenes exert greater antioxidant effects.
Retinolo
Isolated in its pure form, Vitamin A is a fat-soluble yellow crystal. It is called retinol because it is an alcohol involved in the functioning of the retina. In nature, retinol mostly has the structure of a long chain. The aldehyde form is commonly called retinaldehyde or retinal, the acid form is called retinoic acid. Some scientists suggest that retinol serves only as a precursor of these last two active forms of vitamin A: the retinal, in fact, acts above all on sight and reproduction, while retinoic acid is important in other functions of the organism, such as growth. and differentiation.
Synthetic derivatives of retinoic acid have been developed for the treatment of many skin diseases and. more recently, including some forms of cancer. Isotretinoin (13-cis retinoic acid) is used in the treatment of severe forms of cystic acne and for disorders of keratinization, such as Darier's disease and lamellar ichthyosis. Etretinate, an aromatic derivative of retinoic acid, has no appreciable effect against acne, while it is considered by some to be more potent than isotretinoin in the treatment of psoriasis. These substances, however, are not without side effects, such as liver damage, nausea, vomiting, and muscle pain (1,2) .
Food sources
The most concentrated sources of preformed vitamin A are liver, kidney, butter, whole and semi-skimmed milk: while the main sources of provitamin A carotene are green leafy vegetables such as kale and yellow-orange vegetables, such as carrot, sweet potato and melon (see table 3.1).
Green leafy vegetable carotene is found in chloroplasts along with chlorophyll, usually in the form of a complex with a protein or fat. Beta-carotene is the predominant form in most green leaves and, in general, the more intense the color, the higher the concentration of beta-carotene. The fruits and vegetables of orange color; such as carrot, bicocca, mango, sweet potato, melon etc., usually have a higher concentration of provitamin A carotenoids and, again, the amounts of provitamin A is directly related to the intensity of the color. Yellow plants have a higher concentration of xanthophylls, therefore a lower pro-vitamin A activity. In yellow-orange fruits and vegetables, beta-carotene concentrations are high, however other provitamin A carotenoids usually prevail. Purple-red fruits and vegetables, such as tomatoes, red cabbage, berries and plums, contain high amounts of active non-vitamin A pigments, including flavonoids. Other important sources of carotenoids are legumes, cereals and seeds.
Carotenoids are also found in foods of animal origin, such as salmon and other fish, egg yolk, shellfish, milk and poultry. Carotenoids are frequently added to foods for their coloring Energy (see tables 3.2 and 3.3).
Absorption
The extent of vitamin A and carotene absorption is influenced by a number of factors. Unlike retinol, carotene requires the presence of bile acids that facilitate its absorption. Other factors affecting the absorption of vitamin A and carotene include: presence of fat, Protein and antioxidants in food; presence of bile and a normal complement of pancreatic enzymes in the intestinal lumen; integrity of mucosal cells. The absorption efficiency of dietary vitamin A is usually very high (80 to 90%),
| Table 3.1 CONTENTS OF VITAMIN A |
|||||||
| Ox liver | 43900 | ||||||
| Veal liver | 22500 | ||||||
| Cayenne pepper | 21600 | ||||||
| Dandelion root | 14000 | ||||||
| Chicken liver | 12100 | ||||||
| Carrots | 11000 | ||||||
| Dried apricots | 10900 | ||||||
| Version | 9300 | ||||||
| Kale | 8900 | ||||||
| Sweet potatoes | 8800 | ||||||
| Parsley | 8500 | ||||||
| Spinach | 8100 | ||||||
| Mustard | 7000 | ||||||
| Mango | 4800 | ||||||
| Melon | 3400 | ||||||
| Apricots | 2700 | ||||||
| Broccoli | 2500 | ||||||
| The values are expressed in International Units per 100g of food | |||||||
| Table 3.2 FOOD SOURCES OF PROVITAMIN A CAROTENOIDS |
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| Carotenoid | Activity (percentage) | Food sources | ||||||
| Alpha-carotene | 50-54 | Green vegetables, carrots, corn, watermelons, green pepper, potatoes, apples, peaches | ||||||
| Beta-apo-8'-carotenal | 72 | Citrus fruits, green vegetables | ||||||
| Beta-apo-12'-carotenal | 120 | Alfalfa | ||||||
| Beta-carotene | 100 | Green vegetables, carrots, sweet potatoes, spinach, apricots, green pepper | ||||||
| Beta-zeacarotene | 20-40 | Corn, tomatoes, yeast, cherries | ||||||
| Cryptoxanthin | 50-60 | Corn, green pepper, khaki, papaya, lemons, oranges, apples, apricots, paprika, poultry | ||||||
| Gamma-carotene | 42-50 | Carrots, sweet potatoes, corn, tomatoes, watermelons, apricots | ||||||
| Table 3.3 FOOD SOURCES OF NON-PROVITAMIN A CAROTENOIDS |
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| Carotenoid | Food sources | ||||||
| Cantaxantina | Mushrooms, trout, shellfish | ||||||
| Capsantina | Cayenne pepper, paprika | ||||||
| Crocetina | Saffron | ||||||
| Lycopene | Tomatoes, carrots, green pepper, apricots, pink grapefruit | ||||||
| Lutein | Green vegetables, corn, potatoes, spinach, carrots, tomatoes, fruit | ||||||
| Zeaxantina | Spinach, paprika, corn, fruit | ||||||
with a slight reduction in case of high doses. On the contrary, the absorption efficiency of beta-carotene is much lower (from 40 to 60%) and rapidly decreases with increasing dose (1,2) . Carotene supplements are better absorbed than carotene extracted from cybo (3) .
Transformation in the intesatinal mucosa
Most of the absorbed retinol forms a complex with palmitic acid or another free fatty acid within the intestinal mucosal cells. The retinol-fatty acid complex is then incorporated, together with other fatty substances (such as triglycerides, phospholipids and cholesterol), in a large sphere of fatty substance, the chylomicron, which is transported along the lymphatic channels until it reaches the circulatory system and is eventually removed from the liver. Unless it is converted into vitamin A, carotene is absorbed without alteration and is transported by the chilomicrons (4,5) .
Conversion of carotene into vitamin A
The conversion of provitamin A carotene into vitamin A depends on several factors, including protein status, thyroid hormones, zinc and vitamin C 6 . Conversion decreases as carotene intake increases and when serum retinol levels are adequate (7) . Scientists originally believed that beta-carotene and other provitamin A carotenes were broken down by an enzyme (carotene dioxygenase) to form two retinal molecules. Today, however, it is common to believe that the enzyme attacks any double bond of beta-carotene in a non-specific way. Sometimes, therefore, two retinal molecules may result, although in most cases this does not happen. The retinal is then converted into retinol.
Transport, storage and expulsion
After reaching the liver, vitamin A is stored mainly within particular cells, the Ito cells. Although small amounts of vitamin A can be found in most tissues ( see table 3.4), the liver stores more than 90% of the total content of this vitamin in the body. This is stored as a complex consisting of 96% retinyl esters (retinol plus acid
| Table 3.4 DISTRIBUTION OF VITAMIN A AND CAROTENE IN SOME HUMAN TISSUES |
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| Fabric | Vitamin A | Carotene | Beta-carotene | ||||||
| Adrenal glands | 10.4 | 20.1 | 10.8 | ||||||
| Liver | 149 | 8.3 | Not determined | ||||||
| Testicles | 1.14 | 5.0 | 4.7 | ||||||
| Fat | 1.46 | 3.9 | 1.3 | ||||||
| Pancreas | 0.52 | 2.3 | 1.1 | ||||||
| Spleen | 0.89 | 1.6 | 1.2 | ||||||
| Lungs | 0.91 | 0.6 | Not determined | ||||||
| Thyroid | 0.43 | 0.6 | Not determined | ||||||
| The values are expressed in mcg per kg of fabric | |||||||||
fat) and 4% from non-esterified retinol. When the body needs more vitamin A, an enzyme, which transfers the released retinol to the retinol binding protein, breaks down the retinyl esters. The bound retinol is then processed and secreted into the blood, where it forms a 1: 1 complex with a protein (prealbumin) (1,2) .
An adequate protein diet and zinc are necessary for proper retinal mobilization. The half-life of RBP ( Retinol-Binding Protein ) and prealbumin is less than 12 hours, which makes them particularly susceptible to deficiencies during protein-calorie malnutrition or other situations in which protein metabolism is abnormal . Deficiency of zinc or vitamin E severely impairs the metabolism of vitamin A, as these two nutrients work synergistically in many physiological processes of vitamin A metabolism (in particular, absorption, transport and mobilization) (2) .
Retinol is transferred into the cell after RBP has bound to the receptor on the cell surface. The retinol is then rapidly bound by CRBP ( Cellular Retinol-Binding Protein , protein
retinol-binding cell) and brought inside the cell.
The body metabolizes retinoic acid differently than retinol. Retinoic acid is absorbed and transported in the blood, being bound to a different protein (albumin). It does not accumulate inside the liver or other tissues in significant quantities. It is metabolized rather rapidly into more polar oxygen compounds. Inside cells, it is linked to CRBP (1) .
The metabolites of vitamin A are mainly eliminated in the faeces (via the bile) and urine. In periods of deficiency there is an adaptation in use, as demonstrated by the reduction in the rate of catabolism of vitamin A (1,2) .
Per carotene there is no protein in the blood that acts as a specific vector. These compounds are usually transported in plasma in association with lipoproteins, primarily low-density lipoprotein (LDL, Low Density Lipoprotein ). As a consequence, patients with high serum cholesterol or low density lipoprotein levels tend to have high serum carotene values. Concentrations present in plasma usually reflect concentrations in the diet, with beta-carotene typically being between 20 and 25% of the total serum carotene level (8) .
Carotene can be stored in adipose tissue, in the liver, in other organs (adrenal glands, testes and ovaries have the highest concentrations) and in the skin ( see table 3.4). Deposition in the skin causes a yellowing known as carotenoderma, a benign (and probably very beneficial) condition. Carotenoderma, while not directly attributable to dietary intake or supplements, may indicate a deficiency in a necessary conversion factor, such as zinc, thyroid hormone, vitamin C, or protein (2,5) .
Signs and symptoms of deficiency
Vitamin A deficiency can be caused by an inadequate diet (primary deficiency) or by some secondary factor that interferes with the absorption, storage or transport of the vitamin. Some factors known to induce this deficiency are: malabsorption due to pancreatic or biliary insufficiency, protein deficiency malnutrition, liver disease, zinc deficiency and abetalipoproteinemia (1) .
Immune system abnormalities associated with vitamin A deficiency include: inability to produce an effective antibody response, decreased T- helper lymphocytes , changes in the respiratory tract and digestive tract mucosa. Individuals with vitamin A deficiencies are more prone to infectious-type diseases and have a higher mortality rate. Furthermore, in the course of an infection, the vitamin A stores are quickly depleted and a vicious circle is therefore set in motion.
Among the infectious diseases associated with vitamin A deficiency are measles, chicken pox, virus infections, respiratory syncytial, AIDS and pneumonia.
Prolonged vitamin A deficiencies cause the characteristic signs of follicular hyperkeratosis (accumulation of cellular debris in the hair follicles, resulting in a sort of goosebumps; occurs most frequently in the back of the arms), night blindness and increased incidence of infections. As conditions worsen, the deficiency also affects the mucous membranes of the respiratory, gastrointestinal, and genitourinary tracts. In a short time, the typical eye disease, characteristic of vitamin A deficiency, known as xerophthalmia, occurs. Even moderate deficiency of vitamin A is associated with a significant increase in mortality. This data is very noteworthy, since this hypovitaminosis is particularly widespread in developing countries, especially in Asia,(1,2) .
Recommended daily dose
Originally, the activity of Vitamin A was measured in International Units (IU). One IU is equivalent to 0.3 mcg of crystalline retinol or 0.6 mcg of beta-carotene. In 1967 an FAO / WHO expert committee recommended measuring vitamin A activity in terms of retinol equivalents rather than IU, where 1 microgram of retinol equals 1 retinol equivalent (RE). The amount of beta-carotene required for 1 RE is 6 mcg, while the amount required for the other provitamin A carotenes is 12 mcg. In 1980 the Food and Nutrition Board of the NRC / NAS (National Research Council / National Academy of Sciences) adopted this indication: since then the recommended daily intake for vitamin A is measured in mcg and retinol equivalents.
| Table 3.5 RECOMMENDED DAILY DOSE FOR VITAMIN A |
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| Retinol equivalents | International units UI | |||
| Infants up to 1 year | 375 | 1875 | ||
| Children 1-3 years 4-6 years 7-10 years |
400 500 700 |
2000 2500 3500 |
||
| Adolescents and adults Males over 11 years Females over 11 years Pregnant women Breastfeeding women |
1000 800 800 800 |
5000 4000 4000 4000 |
||
Beneficial effects
Science understands the role of vitamin A especially in relation to its effects on the visual apparatus. The human retina has four types of photo pigments containing vitamin A: rhodopsin, present in rods (the cells of the retina responsible for night vision), and three iodopsins, present in each of the different cones responsible for day vision (blue, yellow and red. ). The form of vitamin A found in these pigments is the 11-cis isomer of vitamin A ( retinal ) aldehyde . When a photon of light hits the rod, the retinal 11-cis separates from the rhodopsin molecule, resulting in opsin and all-trans retinol . This reaction causes a change in the membrane potential and a consequent transmission of the.
When there is a flash of bright light (such as car headlights), a temporary discoloration of the rhodopsin occurs. It may take a few seconds for the retina to regenerate and sight to return. If vitamin A levels are low, more adaptation time is required (1,2) . Poor adaptation to changes in brightness and poor night vision are some of the initial symptoms of vitamin A deficiency (1) .
Forms available
Natural vitamin A is available in the form of retinol or as retinyl palmitate. Micellization and emulsification improve absorption. Micellization is the process in which the fat-soluble vitamin A is reduced into very small droplets (micelles), so that the material is dispersed in water. Emulsification is the process in which vitamin A is emulsified with another chemical (such as lecithin) so that it can be mixed with water. Despite the claims of the manufacturers, regular vitamin A is absorbed at a rate of 80-90%. I am particularly fascinated by the claims of a manufacturer that its micellised vitamin A would be absorbed up to 520% more than other forms of vitamin A.
There are three primary sources of carotene on the market: synthetic all-trans beta-carotene , beta- and alpha-carotene from Dunaliella seaweed , and a blend of carotene made from palm oil. Of these three, palm oil carotene is the best form. I will first analyze the antioxidant effects (see table 3.7).
Palm oil carotene appears to provide the best antioxidant protection. The complex contained in palm oil faithfully reproduces the structure found in foods with a high content of carotene. In particular, unlike the synthetic version, which only provides the trans configuration of beta-carotene, natural carotene sources provide beta-carotene in both the trans and cis configurations :
60% beta-carotene (both trans and cis isomers);
34% alpha-carotene;
3% gamma-carotene;
3% lycopene.
Palm oil carotene is absorbed four to ten times better than synthetic all-trans beta-carotene (9-11) , but carotene from Dunaliella is also absorbed well.
Widespread health concerns about the use of "tropical oil" such as palm and coconut oils do not apply to carotene extracts from palm oil, as the fat content is minimal. Also, the real problems with palm oil are when it is treated. or partially hydrogenated.
| Table 3.7 ANTIOXIDANT POTENTIAL OF CAROTENE PRODUCTS |
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| Extinction rate | Percentage in the source | mg contained in 25 000 IU | Antioxidant potential |
|||
| Synthetic beta-carotene analysis | ||||||
| Beta-carotene | 1.4 | 100 | 14.97 | 3.90 | ||
| Total | 3.90 | |||||
| Carotene analysis of algae | ||||||
| Alpha-carotene | 1.9 | 4 | 0.61 | 0.22 | ||
| Beta-carotene | 1.4 | 96 | 14.69 | 3.83 | ||
| Total | 4.05 | |||||
| Palm oil analysis | ||||||
| Alpha-carotene | 1.9 | 33.0 | 7.36 | 2.60 | ||
| Beta-carotene | 1.4 | 63.0 | 14.04 | 3.66 | ||
| Gamma-carotene | 2.5 | 2.5 | 0.56 | 0.26 | ||
| Lycopene | 3.1 | 0.1 | 0.02 | 0.01 | ||
| Total | 6.54 | |||||
Interactions
Vitamin E and zinc are very important for the adequate action of vitamin A. Deficiencies in zinc, vitamin C, protein or thyroid hormone interfere with the conversion of provitamin A into vitamin A.
NOTE
1. Olson R, ed., Nutrition Reviews' Present Knowledge in Nutrition, 6th Edition. Nutrition Foundation, Washington, DC, 1989, pp. 96-107.
2. Underwood B, Vitamin A in animal and human nutrition. The Retinoids. Vol 1, Sporn M, Roberts A. and Goodman S (eds.), Academic press, Orlando. FL, 1984, Chapter 6, pp. 282-392.
3. Brown ED, et al., Plasma carotenoids in normal men after a single ingestion of vegetables or purified beta-carotene. Am J Clin Nutr 49, 1258-1265, 1989.
4. Simpson KL and Chichester CO, Metabolism and significance of carotenoids. Ann Rev Nutr 1, 351·374, 1981.
5. Krause MV and Mahan LK, Food, Nutrition and Diet Therapy, 5th Edition. WB Saunders, Philadelphia, PA, 1984, pp. 103-107, 224.
6. Brubacher GB and Weiser H, The vitamin A activity of beta-carotene. Int J Vir Nutr Res 55, 5-15, 1984.
7. Ganguly J and Sastry PS, Mechanism of conversion of beta-carotene into Vitamin A-Central cleavage versus random-cleavage. Wld Rev Nutr Diet 45, 198-220, 1985.
8. Olson JA, Serum levels of vitamin A and carotenoids as reflectors of nutritional status. JNCI73, 1439-1444. 1984.
9. Ben-Amotz A. et al., Bioavailability of a natural isomer mixture as compared with synthetic all-trans beta-carotene in rats and chicks. J Nutr 119, 1013-1019, 1989.
10. Mokady S, Avron M, and Ben-Amotz A, Accumulation in chick livers of 9-cis versus all-trans beta-carotene. J Nutr 120, 889-892, 1990.
11. Carughi A and Hooper FG, Plasma carotenoid concentrations before and after supplementation with a carotenoid mixtute. Am J Clin Nutr 59, 896-899, 1994.
