Doctor’s Article

Facts about Vitamin A

● Vitamin A Physiology 
● Vitamin A and provitamin A

          The term vitamin A should be used as the generic descriptor for retinoids exhibiting the qualitative biological activity of retinol.  The main molecular structure contains a cyclic part and a non-cyclic chain with 5 double bonds in the all-trans position.  A functional group is found at the end of the non-cyclic part which can be an alcohol (retinol), an aldehyde (reninaldehyde), a palmitate (retinolpalmitate), etc. The term provitamin A carotenoid should be used as the generic descriptor for all carotenoids exhibiting qualitatively the biological activity of beta-carotene. In order to have some indicator of activity we now speak of retinol equivalents. 
  1mcg retinol equivalent = 1 mcg retinol       = 6 mcg beta carotene       = 12 mcg other carotenoids 
  1 IU (international unit)  = 0.3 mcg retinol 
  1mcg retinol = 3.3 IU 

          Vitamin A is, after ingestion, absorbed in the gut in the chylomicron fraction and then transported via the lymphatics, to the liver.  The availability of fats in the intestine will influence the fraction of the available vitamin that will be absorbed. Once stored in the liver as retinolpalmitate it will be transported to the target organs bound to a protein, the retinol binding protein (RBP).  Zinc and an adequate intake of protein are required for normal production of RBP.  

          Vitamin A activities 

1. Function in rhodopsin for night vision.
2. Role in the differentiation process of epithelial tissues. 
3. Necessary for normal ciliary function. 
4. Role in the synthesis of glycoproteins. 
5. Stabiliser of lysosomal membranes. 
6. Function in the cell mediated immunity. 
7. Reproduction. 
As a result of this wide spectrum of activities, a deficit of vitamin A will have several effects. 

1. It causes night blindness. 
2. It causes xerophthalmia. 
3. Increases the overall mortality.  Some authors state by as much as 16%. 
4. Increases morbidity.  A higher frequency of diarrhoea, ARTI (acute respiratory tract infection) and otitis media have been noted. 
5. Is an attributing factor in the causality of stunting. 

         Importance of the problem 

1. Vitamin A deficiency is the most important cause of blindness in children in the world today.  More important than gonorrhoea, trachoma, cataract, onchocerciasis, trauma or glaucoma. 
2. It is an important factor in the cause of stunting which is more prevalent than malnutrition. 
3. It is an important contributing factor in mortality which is still very high in the majority of the third world countries.  This can for a large extend be explained by the role vitamin A has in maintaining the immunological response and the differentiation and maintenance of epithelial surfaces, like the skin, bronchi, gut and genito-urinal tract, which are more prone to invasion by bacteria in a vitamin deficiency states.  These effects are present well before there are overt clinical signs at the level of the eye. 

       Diagnosis of vitamin A deficiency 
Before going into further details it is necessary to revise some important definitions: 
      Xerophthalmia Although it literally means (xeros= dry ; ophthalmos = eye) dryness of the eye and is used as such by the ophthalmologists, it is used in a broader sense in the public health context of vitamin A deficiency.  Here it means all lesions, internal and external, attributable to the deficit of vit A:  dryness of conjunctiva and cornea, Bitot spots, keratomalacia and night blindness. 
      Keratomalacia Is a liquefaction necrosis of the cornea varying from small ulcerations to softening and rupture of the cornea, with resulting loss of anterior chamber fluid and collapse of the eye. In young children keratomalacia can occur without preceding stages such as dryness of the conjunctiva or Bitot spots. 
      Xerosis Is a dryness.  The clinical dryness of the conjunctivae in vitamin A deficiency is due to squamous metaplasia and keratinization. 
      Bitot spots Greyish – whitish spot, foamy aspect to be found on the conjunctiva.  It can have different forms, round, oval, small spots dispersed.  The triangular form is the most frequent.  The basis is against the rim of the cornea “the limbus cornea” and the top points to the outside of the eye.  Can be uni- or bilateral.  This lesion does not hurt. 
      The diagnosis can be made:  Clinically  By measuring hepatic reserves.  By measuring plasma levels of retinol.  Impression cytology 
       The natural course of the disease progresses from night blindness to dryness of the cornea, sometimes with Bitot spots, to keratomalacia.  Night blindness is not always perceived because it is a subjective sign on the one hand and because it’s perception is very much influenced by the availability of electricity on the other hand. 
         Night blindness Is the inability to see in poor lighting conditions like those which prevail at the end of the day when the evening is setting, and a longer adaptation of vision to the dark, like when one is getting from a light to a darker environment.  People will complain of stumbling over objects in the house in the evening or that their children can’t find the parents anymore in the house in the evening. Quantifiable: dark adaptation test, but difficult to evaluate objectively in children. 
          Conjunctival xerosis Dry appearance of the cornea, looses it lustre.  Some undulation can be seen. 
          Bitot spots A triangular whitish, pearly coloured spot, which is usually found on the lateral side of the conjunctiva.  Has a foamy appearance.  Note that the progression of the clinical picture does not always pass through this stage. 
          Corneal dryness The light reflex of the cornea looses its well-defined appearance and becomes mottled and hazy.  The cornea becomes less translucent and more opaque. 
           Keratomalacia Small lesions like ulcerations can develop.  The cornea looses its spherical appearance, softens and bulges. Eventually it ruptures and the anterior chamber liquid runs out and the eye collapses. 
           Fundus examination  Small white spots can be found on the retina. Moderate forms  (loss of night vision, conjunctival dryness) will disappear after 2-4 days of treatment without leaving any lesions or sequelae.  

            Hepatic reserves Are only measured on an experimental and research basis.  Are measured as a rapid dose response (RDR).  After administration of a small dose of retinol (1.800 IU) the plasma retinol levels are measured again and compared with the retinol concentrations before the administration.  If the concentration increases with more than 20 % we say that the reserves are low. 
             Plasma levels The problem with measuring plasma retinol levels is that they only change after a prolonged period of vitamin deficit, due to the buffering action of the liver. Their use is limited to research evaluations of vitamin A deficiency and of very little practical use in real life situations. 
              Plasma retinol   >= 30 mcg/100 ml 30-20 mcg/100 ml  20- 10 mcg/100 ml  <  10 mcg/100 ml 
Normal  Mild deficiency Associated with night blindness, Bitot spots Moderate deficiency Definitely low, severe deficiency 

               A technique to detect the degree of metaplasia of the conjunctiva.  The lack of differentiation and the decrease or absence of goblet cells is looked for.  Not a routine diagnostic test. 
              Vital staining   Detecting the degree of conjunctival metaplasia by putting dye (Lissamon green or Bengal rose) on the conjunctiva.  This method lacks specificity. 
6.4 Vitamin A deficiency as a Public Health problem 
Since vitamin A deficiency gives a multitude of signs and symptoms reflecting different degrees of progress a classification has been proposed by the WHO.  Minimum prevalence rates for the clinical stages of Xerophthalmia and low plasma retinol levels have been published by the WHO to assist in defining the public health significance of vitamin A in the community. 

              Criteria for assessing the Public Health Significance of  Xerophthalmia and vitamin A deficiency, based on the prevalence  among children aged 6 months – 6 years. 

              Causes of vitamin A deficiency 
Both an insufficient input and an increased need can result in the deficiency. 
            1. Insufficient intake 

              Aanimal sources of vit A:  milk – butter – fish oils – liver – meat – egg yolk vegetables: green leaf vegetables – carrots fruits: mango – papaya oils : palm oil   Infections of the gut, malabsorption, worm infestations and particularly giardiasis decrease vitamin A absorption. 
          2 Increased needs 
               Infections can increase vitamin A demands dramatically.  Some investigators even calculated the increase during infections in the order of 3000 IU per day.  Particularly children with measles are very likely to develop a very fast progressing Keratomalacia. 
          3 PEM 
               There is a very strong association of vitamin A deficiency with malnutrition.  Both are diseases of the poorer layers of the population and of the deprived. They will have an over all lower food intake but particularly of meats and milk products, sources rich in vitamin A, and of oils and fats, which are necessary for the vitamin A absorption. These children will also have more frequent infections, increasing their demands and interfering with the absorption at the level of the gut. Once their serum protein levels decrease like in severe malnutrition the necessary enzymes for absorption and transportation to the target organs will diminish, aggravating further the deficiency. 
6.6 Recommended daily intakes 
Adult:   750 mcg Pregnancy:  750 mcg Breastfeeding: 1200 mcg Children:  < 1 yr: 300 mcg  1-4 yr:  250 mcg  4-6 yr:  300 mcg  7-9 yr:  400 mcg  10-12 yr: 575 mcg  13-15 yr: 725 mcg 
6.7 Treatment  
              The presence of clinical signs of vitamin a deficiency should be considered and emergency.  Large and repeated doses are therefore given.  Associated illnesses should always be treated. 
             Who should be treated? All children with signs of Xerophthalmia.  The most urgent are those infants with corneal signs. 


              All suspected cases. In an endemic zone, all children with PEM and measles.   
  Children < 1 yr 
  Children 1 yr and above and adults except pregnant women 
  100.000 IU  immediately 100.000 IU  after 24 hrs 100.000 IU  after 14 days * 
  200.000 IU  immediately 200.000 IU  after 24 hrs 200.000 IU  after 14 days 
  * the last dose is mainly to replenish liver stores 
      Below one year of below 8 kg the dose is half of what is found in the vitamin a high dosage capsules.  These contain 6 drops.  Throw away tree drops and give the remainder.   
      Pregnant women  Should not receive large doses of vitamin A due to the possible teratogenic effect.  Smaller doses up to 10.000 IU per day are safe.  A total dose of 200.000 IU should be aimed at. 
      Lactating women Should receive 200.000 IU in the first month postpartum.  One month after delivery again smaller doses up to 10.000 IU per day are preferred.  This because one month after delivery there is the possibility of renewed pregnancy.  


       “Appropriateness” is a basic premise for vitamin A intervention.  Two conditions dictate whether a program, designed to prevent vitamin A deficiency, is appropriate: 
1.A substantial segment of the population is “at risk” of developing clinical or biochemical vitamin A deficiency of sufficient severity to be considered of Public Health importance. 
2.The problem is serious enough to warrant the diversion of scarce resources toward a program to control vitamin A deficiency versus other preventable diseases or community projects within the country. 
                                                   VITAMIN DEFICIENCIES 
    Currently vitamin A prophylaxis is approached through one of the three major intervention strategies: 
1.A change in diet directed toward achieving a continuous intake of vitamin A rich foods, 
2.Fortification of an appropriate dietary vehicle with vitamin Aor administration of a single, large dose of vitamin A administered on a periodic basis. 
    2 Change in dietary intake 
          Different strategies have been applied to increase dietary intake:  Promotion of breastfeeding.  Children entirely breastfed, provided the mother has adequate daily intakes of vitamin A, do not develop vitamin A deficiency in the first six months of life and have a lower prevalence of mild and severe Xerophthalmia during early childhood.  Nutritional education.  Income generating programs  Kitchen gardening programs.  Larger scale agricultural programs. 
   3 Vitamin A fortification 
        Fortification of Mono-sodium Glutamate in the Philippines and of sugar in Guatemala have been highly successful. The success of this type of program depends on the identification of a suitable vehicle, which has to be consumed by all and particularly the population at risk, and in a continuous and constant fashion.  Fluctuations between people and in time should be as small as possible.  The cost of the program on a national scale is usually high enough to raise the question as to who is going to bear it ; the government, the industry or the consumer.  Disagreement over this last point have led to the discontinuation of the fortification programs. 
   4 Distribution of large dose vitamin A capsules 
         Large doses of 200.000 IU are distributed at regular intervals, most frequently every six months.  The seasonal distributions, to protect children in the higher prevalence seasons, reduces cost while maintaining the same impact. 
       Three delivery strategies are possible: 1.The ‘medical’ or ‘therapeutic’ approach, which offers treatment to children who present to a health facility with an illness episode.  They will be given a dose of vitamin A according to a set of preset criteria of high risk of developing vitamin A deficiency. 
       2.The ‘targeted’ distribution which covers groups within the larger general target population; e.g., residents of a high prevalence neighbourhood, those attending mother and child health clinics, etc. 
       3.The ‘universal’ distribution in which all pre-school children and not pregnant lactating mothers in a prescribed region are dosed at prescribed intervals by single or multipurpose workers in the community. 
           The logistics, supervision, personnel demand and cost of this type of program are usually very high compared with the money available for general health care in the country.  This type of programme costs 4 BF in India and 8 BF in Indonesia per administered dose.  Although effective, large dose distribution has been discontinued in a number of countries for these reasons. 

        Acute hypervitaminosis 
            Ingestion of large dose can give rise to transient signs and symptoms of toxicity, which are self limiting and completely reversible.  No deaths have been reported after the ingestion of the doses used in treatment and prevention. 
             Common complaints include headaches and bulging fontanel in young children.  Nausea, vomiting, dizziness, headaches have been described in adults.  Desquamation of the skin, bone pains and hair loss can occur in the following days. 
           2 Chronic hypervitaminosis 
                Is due to ingestion of large doses on a daily basis. This can lead to hepatitis, cirrhosis, hair loss, dry scaling skin, hyperpigmentation, hyperostosis and bone pains, hepato-splenomegaly and anaemia.  It is therefore recommended not to exceed a daily intake of 3000 mcg in children and 7500 mcg in adults. 
            3 Teratogenicity 
                  Although teratogenic in animals, a clear correlation between ingestion of large doses of vitamin A and congenital malformations has not been established.  However it is recommended during pregnancy not to give large doses of vitamin A and not to exceed 10.000 IU per day as treatment dose. 

Food which are rich in vitamin – A :

1.Beef liver

2.Cod liver oil

3.sweet potato



5.Sweet red pepper

 Top  5 Friuts Containing lots of vitamin:

1.Mango –20% DV per Serving

2.Cantalupe — 19% DV per serving

3. Red grapefruit — 16% DV per serving

4.Watermelon — 9% DV per serving

5.Papaya — 8% DV per serving

Limit to take Vitamin-A

level of up to  10,000 IU have been considered safe. Beyond that, though ,vitamin A can build up to cause liver damage and brain swelling ;pregnant women who ingest too much run risk of fetal damage.

symptoms of Vitamin Defiviency 

Too little vitamin A can lead to inflames skin, night blindness , infertility ,delayed growth

and respiratory infections .People with wounds and acne mey have lower blood levels of vitamin A and benifit from treatment with higher doses of vitamin.