CC BY
9UDC 613.261:577 https://doi.org/10.29296/25877313-2021-03-06
VITAMIN A AND ITS STATUS IN VEGETARIANS AND VEGANS
© Galchenko A.V., Ranjit R., 2021 A.V. Galchenko
Assistant at the Department of Medical Elementology, Peoples' Friendship University of Russia (Moscow, Russia) ORCID: 0000-0001-7286-5044 E-mail: [email protected] R. Ranjit
Resident at the Department of Oncology and Radiology, Peoples' Friendship University of Russia (Moscow, Russia) ORCID: 0000-0002-4255-4197 E-mail: [email protected]
Vitamin A is an essential fat-soluble micronutrient. It is necessary for the normal functioning of epithelial tissues, replication of genetic materials, perception of light or for smoothly running the immune system. Provitamins A (carotenoids) are powerful antioxidants. They can also be precursors for not only retinol but also for the most active forms of vitamin A - retinal and retinoic acid. However, the reverse transformation doesn't take place, it is impossible to endogenously obtain carotenoids from retinol or its oxidized forms. The efficiency of converting carotenoids to retinol depends mainly on two factors. The first one is the type of carotenoid. p-carotene is converted to vitamin A twice as efficiently as other carotenoids, and the second factor is the bioavailability of the provitamin A. As fat-soluble substances, carotenoids are better absorbed in the presence of enough fats.
Vitamin A deficiency is associated with the malfunction of visual system as a result of xerophthalmia or night blindness. In addition, the lack of vitamin A can cause deterioration of the skin and mucous membranes and may lead to a high infant mortality rate. At the same time, hypervitaminosis A is a serious teratogenic factor.
An insufficient supply of carotenoids impairs the antioxidant defence mechanism of the body, which increases the risks of oxidative damage of cellular structures, and probably leads to cancerous diseases.
Vitamin A is not synthesized by plants. Herbivorous and fruit-eating animals synthesize it from carotenoids obtained from plant foods but carnivores have almost lost this ability. Thus, only animal tissues are sources of vitamin A for them.
As a result, vegetarians consume substantially less vitamin A than omnivores, and vegans don't consume vitamin A at all. However, they get much more carotenoids from their diet, and as a result, the total intake of retinol equivalent does not differ much among the groups. Serum p-carotene concentrations are generally higher in vegans. However, there is a disparity regarding the level of retinol. Thus, there is little evidence to date to conclude that any of the three groups has an increased risk of vitamin A deficiency compared to the others.
Key words: retinol, retinal, retinoic acid, carotenoids, p-carotene, vegetarianism, veganism.
For citation: Galchenko A.V., Ranjit R. Vitamin A and its status in vegetarians and vegans. Problems of biological, medical and pharmaceutical chemistry. 2021;24(3):40-48. https://doi.org/10.29296/25877313-2021-03-06
INTRODUCTION
Vitamin A is an essential fat-soluble vitamin with a pivotal role in various metabolic and physiological processes within the body. Chemically, it is a group of compounds that includes retinol, retinal, retinoic acid, and several provitamin A carotenoids (most notably P-carotene) [1]. The different structures of vitamin A are presented in table 1.
Mostly, vitamin A is found in two principal forms in foods:
1. Preformed vitamin A (retinol and retinyl ester) is derived from animal sources such as meat, dairy products or fish.
2. Provitamin A (carotenoids) is obtained mostly from colourful fruits and vegetables.
Both ingested forms of vitamin A must be converted to retinal and retinoic acid after absorption to
support biologic processes [2]. But, interestingly, most carnivores (entirely meat-eating animals) are poor converters of beta-carotene, and they cannot create any vitamin A from beta-carotene [3].
PHYSIOLOGICAL ROLE
Vitamin A is necessary for a multitude of physiological processes such as maintaining the integrity and function of all surface tissues i.e. epithelia: for instance, the lining of the respiratory tract, gut, skin, bladder, inner ear, eye and so on. Besides that, vitamin A also supports the daily replacement of skin cells and ensures that tissue such as the conjunctiva is able to produce mucous to create a barrier to infection. It also takes part in vision under poor lighting conditions, maintains a healthy immune system, and involves in growth and development related to the reproductive system [4, 5].
Table 1. Structures of some common forms of vitamin A
Figure 1.1: a-Carotene
Figure 1.2: [3-Carotene
Figure 1.3: Lycopene
Figure 1.5: Zeaxanthin
Figure 1.7: retinoic acid
Furthermore, the involvement of vitamin A in cell morphogenesis, differentiation and proliferation is paramount to gene regulation. Additionally, it functions as an antioxidant and decreases free radical damage to DNA [6].
Antioxidants protect cells from the damaging effects of free radicals, which are molecules that contain an unshared electron. Free radicals damage cells and might contribute to the development of cardiovascular diseases or cancer [7]. Unshared electrons are by nature highly energetic and react rapidly with oxygen to form reactive oxygen species (ROS). The body also forms ROS endogenously during metabolism, and antioxidants can be helpful to protect cells from the damaging effects of ROS. Unfortunately, our body is also continuously exposed to free radicals from environmental exposures, such as air pollution, cigarette smoke, or ultraviolet radiation from the sun [8]. ROS are also part of signalling mechanisms among cells [9]. Carotenoids are effective physical and chemical quenchers of oxygen and ROS. Moreover, they are also considered to have protective actions against ROSmediated disorders [10].
B-carotene, due to its unique structure and cleavage efficiency, is the most efficient vitamin A precursor. It not only scavenges reactive oxygen species and singlet oxygens but also possesses a potential role in controlling thermogenesis and in regulating the size of adipose tissue deposit [11].
Finally, vitamin A in the form of retinoic acid functions as an immune regulator especially for the humoral defence of viral or gastrointestinal infections [12], and retinal is an important photoreactive chromo-phore in rhodopsin which absorbs photons and converts it into potential energy for the brain to interpret the signal [13]. Similarly, retinoic acid is useful for treating different dermatological pathologies like acne or psoriasis, and even promyelocytic leukemia [14].
HYPOVITAMINOSIS,
VITAMIN A DEFICIENCY DISORDERS
Deprivation of vitamin A replaces normal epithelium with stratified, leading to keratinization of the epithelium in the eyes, periocular glands, respiratory, alimentary or genitourinary tracts [15]. One of the prominent disorders due to the lack of vitamin A is xerophthalmia, which is the major cause of blindness in children worldwide [16]. Night blindness is another clinical sign of vitamin A deficiency because rod cells that are responsible for night vision have a photopig-
ment - rhodopsin, which utilizes the protein scotopsin and the retinol [17].
Another issue linked with vitamin A deficiency is child death. Indeed, the connection between them is highly correlated and the mortality rates in children under 5 years are now taken to be a 'surrogate' indicator of vitamin A deficiency. Vitamin A deficiency is considered to be a public health issue in countries with mortality rates in children under 5 years more than 50 deaths per 1000 live births. In sub-Saharan Africa, 40 countries have child mortality rates under 5 years old above this level (50 deaths per 1000 live births); of these, 37 countries have twice the mortality rate (over 100 deaths per 1000) [18].
In addition to it, a deficiency in vitamin A is believed to play a role in neoplastic transformation and carcinogenesis [6]. It has been purposed that the mechanism underlying the carcinogenic effects of vitamin A deficiency is due to the fact that retinoids exposure has been found to inhibit growth by blocking the cell cycle or by inducing apoptosis in in-vitro studies [19].
HYPERVITAMINOSIS A
Excess vitamin A results in acute and chronic deleterious effects on health. However, vitamin A toxicity is far rarer than vitamin A deficiency. The tolerable upper intake levels of vitamin A for different age groups are given in table 2.
Table 2. Tolerable Upper Intake Levels (UILs)
of vitamin >4 [20, 21]
Age UILs (in (ig)
0-3 years 600
4-8 years 900
9-13 years 1700
14-18 years 2800
>19 years 3000
The WHO estimates that 3 million children develop clinical vitamin A deficiency annually compared to 200 registered cases of hypervitaminosis per year [20]. It is more commonly associated with abuse of vitamin A supplements than with health intervention programs. Toxicity may also be inflicted by consuming liver products, which are rich in vitamin A or by administrating excess of vitamin A supplements.
Age and hepatic functions are the key factors to determine the amount of vitamin A to cause toxicity. However, it is to be noted that a single ingestion of 25,000 IU/kg or more can lead to acute vitamin A toxicity. Nausea, vomiting, dizziness, lethargy, diarrhoea, drowsiness, increased intracranial pressure, or skin changes such as erythema, pruritus, or desquamation are the manifestations of its toxic effects.
Excessive ingestion of 4000 IU/kg or more daily for 6-15 months may lead to chronic vitamin A toxicity. Its signs and symptoms include low-grade fever, headache, fatigue, anorexia, intestinal disturbances, hepatosplenomegaly, anaemia, hypercalcemia, subcutaneous swelling, nocturia, joint and bone pain, and skin changes such as yellowing, dryness, alopecia, or photosensitivity [20].
Pregnancy is another situation where a higher intake of vitamin A can have a detrimental effect, as it is highly teratogenic. It was found that high concentrations of certain metabolites of retinoic acid such as trans-retinoic acid and 13-cis-retinoic acid adversely affect on the functioning of genes in critical periods of organogenesis and embryogenesis [22, 23]. For example, the expression of homeobox gene Hoxb-1 is influenced by retinoids, which regulates axial patterning of the embryo. Birth abnormalities include cardiac, craniofacial, and central nervous system malformations. Therefore, it is better to avoid treatment with vitamin A in pregnant patients except for the conditions where vitamin A deficiency is highly prevalent. In such circumstances, the upper limit of supplementation should be 10,000 IU daily [20].
SOURCES OF VITAMIN A AND CAROTENOIDS, AND THEIR DAILY REQUIREMENT
The recommended daily allowances for vitamin A for different age groups are present in table 3.
There exist two main sources of vitamin A: animal sources and plant sources (Table 4). All the sources of vitamin A need some fats in the diet to aid absorption.
In animal sources, vitamin A is found as retinol, the 'active' form of vitamin A. Liver, especially fish liver, is a rich source. Other animal sources are egg yolk (not the white) and dairy products such as milk (including human breast milk), cheese or butter. Meat, from the animal's muscles, is not a good source of vitamin A.
Plant sources contain vitamin A in the form of carotenoids, which can be converted into retinol. Ca-
rotenoids are the pigments, that in combination with chlorophyll, give plants their green colour; and some fruits and vegetables their red or orange colour. [3-carotene is usually found in vegetables like carrots, sweet potatoes, squash or peppers, with carrot being the richest source among them [11]. Yellow fruits such as Papaya, orange or tomato are the major source of [3 cryptoxanthin [24]. Similarly, good sources of a-carotene are pumpkin, carrot, tomato or pea [25]. Although carotenoids such as [3-carotene are abundant in colourful and leafy vegetables and certain fruits, because it takes 12 |ig of dietary [3-carotene to provide 1 retinol activity equivalent (RAE) [20] (as compared to previous recommendations where 1 |ig of retinol was thought to be provided by 6 |ig of [3-carotene [11]), a greater amount of fruits and vegetables than previously recommended are required to meet the daily carotenoid requirements for vegetarians and those whose primary source of vitamin A is colourful and leafy vegetables [20].
It is important not to overcook sources of vitamin A, as this can reduce the vitamin A content. Ultraviolet light can also reduce the vitamin A content of the food, so the practice of drying fruits, like in mangos, should not be done in direct sunlight [4].
Diets that rely heavily on local carbohydrates, such as rice, millet or sorghum are very low in vitamin A unless fortified with it [26]. In order to solve the problem, the United States has a plethora of vitamin A-fortified foods, including milk, cereals or infant formulae. Furthermore, certain food products, such as sugar, are being fortified with vitamin A in some developing countries [12].
Table 3. Recommended Dietary Allowances (RDAs) for vitamin A [20]
Age RDA in |ig as RAE*
0-6 months 400
7 months - 1 year 500
1-3 years 300
4-8 years 400
9-13 years 600
>14 years 900
* Retinol Activity Equivalent.
Table 4. Some food sources of vitamin A [27, 28]
Types of food Food, 100 gm RAE*, ng Percent DV**
Dairy products and eggs Cheese 270 30
Milk 64 7
Butter 465 51
Egg yolk 381 42
Meat Beef liver 7679 853
Chicken breast 53 5
Fish Salmon 70 11
Tuna 23 2
Fish liver 30000 3333
Vegetables Sweet potato 764 84
Spinach 469 52
Pumpkin 426 47
Raw carrot 835 93
Broccoli 31 3
Canned tomato juice 23 2
Winter Squash 426 47
Pepper 157 17
Pea 38 4
Tomato 42 4
Fruits Mango 54 6
Dried apricot 180 2
Papaya 47 5
Orange 11 1
* Retinol Activity Equivalent
** Daily Value. The concept of DV has been developed by FDA for helping consumers to compare the nutrient contents of foods within the context of a total diet. The DV for vitamin A is 900 \ig RAE for adults and children age 4 years and older, where 1 \ig RAE = = 1 \ig retinol, 12 \ig P-carotene and 24 \ig of other carotenoids. However if the carotenoids are consumed with fats, the values decrease by a factor of 6 [29].
VITAMIN A INTAKE IN VEGETARIANS AND VEGANS
Even if (3-carotene is consumed without fats (taking RAE of 12 |ig for dietary (3-carotene), it has been found that RDA for vitamin A can be met by those following a vegetarian or a vegan diet. But it is to be noted that the consumed food should contain deeply coloured fruits and vegetables, which are rich sources of (3-carotene [20].
A plethora of studies have shed a light on the consumption of different forms of vitamin A by vegetarians and non-vegetarians (Table 5), but their findings are contradictory. The RAE consumption in vegans found by Elorinne et al. [30] and Janelle et Barr
[31] was two folds greater than the amount found by Larsson et al. [32]. Intake of RAE by omnivorous was also significantly greater in the research done by Janelle et al. [31] in comparison to Larsson et Johansson [32]. Another significant difference is that intake of RAE by males was consistently lower than in females as suggested by Larsson et al. [32], whereas it was the other way around in the study of Elorinne et al. [30] and Janelle et Barr [31]. Similarly, in Larsson et Johansson [32] and Elorinne et al. [30] studies, vegans were found to consume less RAE in comparison with non-vegetarians, whereas Janelle et Barr [31] study found a substantial increased intake of the RAE by vegans.
Table 5. Intake of vitamin A in vegans, vegetarians, and omnivores
Number Intake
References Types of diet of Retinol [3-carotene RAE
participants (Hg/day) (Hg/day) ( |ig/day)
Larsson et Johansson [32] Vegans M=15 N/A N/A 1045
F=15 966
Omnivores M=15 1226
F=15 1169
Davey et al. [34] Vegans M=770 74 N/A N/A
F=1342 76.6
Vegetarians M=3748 306
F=12347 227
Pescatarian M=1500 337
F=6931 308
Omnivores M=6951 740
F=22962 654
Elorinne et al. [30] Vegans 22 N/A 5807 1100
Omnivores 15 7609 1744
Li et al. [33] Vegans 18 218 12590 N/A
Vegetarians 43 438 6559
Omnivores (< 285 gm of meat per day) 60 761 4599
Omnivores (> 285 gm of meat in a day) 18 1640 7262
Gorbachev et al. [35] Vegetarians 46 N/A N/A 803
Janelle et Barr [31] Vegans 8 N/A N/A 2687
Vegetarians 15 1268
Vegans + Vegetarians 23 1763
Omnivores 22 1638
As far as (3-carotene is concerned, Li et al. [33] found that vegans consumed it two times greater than any other group. Vegetarians consumed a slightly higher amount of [3-carotene than omnivores.
The findings from different authors in case of retinol are in line with each other. All the studies show that the omnivorous diet provides that greatest amount of retinol which is followed by vegetarians and then by vegans [33, 34].
VITAMIN A SUPPLY IN VEGETARIANS AND VEGANS
The serum concentrations of [3-carotene revealed in Krajcovicova-Kudlackova et al. studies [36-38] are pretty close to each other and show that vegetarians are approximately twice as rich as non-vegetarians (Table 6). The only exception was found in the study of Schiipbach et al. [39], which disclosed that vegetarians and omnivores were almost equally supplied with [3-carotene.
Table 6. Serum concentrations of vitamin A in vegans, vegetarians, and omnivores
References Types of diet Number of participants Serum concentration
Retinol (|шю1/Ь) Percentage of subjects below cutoff for deficiency [3-carotene (|imol/L) Percentage of subjects below cutoff for deficiency
Schiipbach et al. [39] Vegans 53 1.562 3.8 4.137 0
Vegetarians 53 1.599 0 3.839 0
Omnivores 100 1.869 1.0 3.617 1
Elorinne et al. [30] Vegans 21 N/A N/A 0.75 N/A
Omnivores 18 N/A 1.8 N/A
Krajcovicovâ-Kudlâckovâ et al. [36] Vegetarians M=42 N/A N/A 0.50 N/A
F=39 N/A 0.57 N/A
Non-vegetarians M=29 N/A 0.34 N/A
F=33 N/A 0.36 N/A
Krajcovicovâ-Kudlâckovâ et al. [37] Vegetarians M=29 2.24 Within threshold 0.46 Within threshold
F=38 2.20 0.53 N/A
Non-vegetarians M=38 1.77 0.23 Not within threshold
F=37 1.63 0.24
Gorbachev et al. [35] Vegetarians 46 1.325 0 0.559 10
Kazimirova et al. [38] Vegetarians 24 N/A N/A 0.41 N/A
Omnivores 24 N/A 0.26 N/A
Millet et al. [40] Vegetarians M=ll 3.4 6 1.1 N/A
F=26 3.14 3 1.4 N/A
Non-vegetarians M=33 3.91 0 0.47 N/A
F=36 3.21 0 1.03 N/A
Furthermore, results of Schiipbach et al. [39] showed a disparity in serum concentrations of [3-carotene. Their results showed that serum [3-carotene concentration was greater than the findings of the other authors by the factor of 6.
There was no such huge disparity in the case of retinol status among the authors [35, 37, 39]. However, the findings are not totally consistent with each other. According to Schiipbach et al. [39], omnivores had the greatest concentrations of retinol which were followed by vegetarians and then by vegans. On the other hand, results of Krajcovicova-Kudlackova et al. [37] showed that vegetarians had higher retinol concentrations than non-vegetarians.
CONCLUSION
Vegans almost do not consume vitamin A. However, high carotenoids consumption provides them with enough RAE, comparable with omnivores. Clinical studies to date have still not provided a clear answer about vitamin A status in vegetarians and vegans. It is necessary to conduct large population studies, and assess the consumption of carotenoids (including (3-carotene), retinol and RAE by different groups. Similarly, a correlation analysis should be performed between the consumed vitamin and provitamin A forms and the retinol serum levels.
Conflict of interest
Authors declare no conflicts of interest.
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Поступила 3 января 202 г.
ВИТАМИН А И ЕГО СТАТУС СРЕДИ ВЕГЕТАРИАНЦЕВ И ВЕГАНОВ
A.B. Гальченко
ассистент кафедры медицинской элементологии, Медицинский институт, Российский университет дружбы народов (Москва) 0RCID: 0000-0001-7286-5044 E-mail: [email protected] Р. Ранджит
ординатор кафедры онкологии и рентгенорадиологии, Медицинский институт, Российский университет дружбы народов (Москва) 0RCID: 0000-0002-4255-4197 E-mail: [email protected]
Витамин А является важнейшим жирорастворимым микронутриентом. Он необходим для нормального функционирования эпителиальных тканей, иммунной системы, участвует в репликации генетического материала и восприятии света. Провитамины А -каротиноиды - являются мощными антиоксидантами. Они также могут быть предшественниками ретинола и наиболее активных форм витамина А - ретиналя и ретиноевой кислоты. Однако обратная трансформация невозможна: из ретинола или его окисленных форм эндогенно получить каротиноиды нельзя.
Эффективность конвертации каротиноидов в ретинол зависит от типа каротиноида - ß-каротин превращается в витамин А вдвое более эффективно, чем остальные каротиноиды - и биодоступности этого провитамина А. Будучи жирорастворимыми веществами, каротиноиды лучше всасываются в присутствии достаточного количества жиров. Дефицит витамина А сопряжен с поражением зрительного аппарата в результате развития ксерофтальмии и никталопии, ухудшением состояния кожи и слизистых, а также критическим повышением риска детской смертности. В то же время, гипервитаминоз А является серьезным фактором тератогенеза. Недостаточная обеспеченность каротиноидами снижает антиоксидантную защиту организма, что повышает риски окислительного повреждения клеточных структур, и, вероятно, канцерогенеза.
Витамин А не синтезируется растениями. Траво- и плодоядные животные синтезируют его из каротиноидов, получаемых из растительной пищи. Хищники в основном утратили эту способность. Таким образом, источниками витамина А для них являются только животные продукты.
В результате этого, вегетарианцы потребляют существенно меньше витамина А, чем люди на смешанном рационе, веганы практически не потребляют его вовсе. Однако они получают с пищей гораздо больше каротиноидов, и в итоге общее потребление ретинолового эквивалента не так сильно различается между группами.
Сывороточные концентрации ß-каротина обычно выше у веганов. Полученные результаты различий в содержании в крови ретинола несколько расходятся. Таким образом, на сегодняшний день нет достаточно оснований, чтобы заключить, что какая-либо из трех рассматриваемых пищевых групп имеет повышенный риск дефицита витамина А в сравнении с остальными.
Ключевые слова: ретинол, ретиналь, ретиноевая кислота, каротиноиды, ß-каротин, вегетарианство, веганство.
Для цитирования: Гальченко A.B., Ранджит Р. Витамин А и его статус среди вегетарианцев и веганов. Вопросы биологической, медицинской и фармацевтической химии. 2021;24(3):40-48. https://doi.org/10.29296/25877313-2021-03-06
