Vitamin A deficiency and control programme

Vitamin A is a fat soluble vitamin.
Deficiency lead to many ocular and extra ocular manifestations.

1. Vitamin A deficiency and Control Programme Dr Soni Rani PGT Department Of Community medicine Katihar medical College, Katihar

2. Introduction Vitamin A is a fat soluble vitamin Required for vision, repair, reproduction, growth and tissue differentiation This occurs in two forms, as retinol in animal foods and as b-carotene in plant food. Carotene is converted into retinol in the intestine, which is then absorbed and stored in the liver as retinol- Palmitate .

3. Different Units of Vitamin A The international unit of vitamin A declared in 1954, which is equivalent to 0.3 microgram of Retinol. 1 mcg of Retinaol = 1 RE ( Retinol Equivalent) 1 mcg of β carotene= 0.167 mcg of RE 1 mcg of other carotinoids =0.084 mcg of RE 1RE= 3.333 IU of Vitamin A.

4. Sources Of Vitamin A Animal Foods (as Retinol): These are meat, liver, fish, egg-yolk, milk, cheese, butter, ghee . Richest source is fish liver oil (Cod liver oil and shark liver oil).

5. Sources Of Vitamin A B. Vegetable Sources (as b -carotene ) Cheapest source is green leafy vegetables, e.g. spinach, amaranth. Darker the green color of the vegetables, higher the carotene content. Richest source is red palm oil. Other sources are yellow fruits like mango and papaya. Some roots like carrots are also rich in b-carotene.

6. Sources Of Vitamin A Fortified Foods: Food fortified with Vitamin A ( e.g V anaspati , margarine, milk) can be an important source. The human liver has enormous capacity to store vitamin A in the form of retinol- P almitate . Therefore , under normal conditions , a well-fed person has sufficient reserve of vitamin A to meet his needs for 6 to 9 months. But a newborn child is not having any reserve and it depends upon vitamin A everyday. Thus, an young child is always at a risk of deficiency.

7. Retinol Content Of Selected Foods

8. Digestion, Absorption and Transportation

9. Functions Of Vitamin A Vitamin A helps in the synthesis of a pigment called ‘Rhodopsin ’ in the retina of the eye, which is necessary for the normal vision, especially in the dim-light for dark adoptation . Thus vitamin A is indispensable for normal vision . It maintains the integrity of the skin and mucous membrane of the conjunctiva, cornea, respiratory, alimentary and urinary system.

10. Functions Of Vitamin A It promotes skeletal growth. It increases the immune response. Thus it is anti-infective. It may protect some epithelial cancers such as carcinoma of bronchus.

11. Vitamin A is essential for vision (especially dark adaptation), Immune response, Bone growth, Reproduction, Maintenance of the surface linings of the eyes, epithelial cell growth and repair, and the epithelial integrity of the respiratory, urinary, and intestinal tracts. Vitamin A is also important for embryonic development and the regulation of adult genes. Functions Of Vitamin A

12. Role In Vision In the retina, retinaldehyde functions as the prosthetic group of the light-sensitive opsin proteins, forming Rhodopsin (in rods) and iodopsin (in cones). Any one cone cell contains only one type of opsin , and is sensitive to only one color.

13. Role In Vision The absorption of light by Rhodopsin causes isomerization of the retinaldehyde from 11- cis to all- trans , and a conformational change in opsin . This results in the release of retinaldehyde from the protein, and the initiation of a nerve impulse.

14. Wald’s visual cycle The formation of the initial excited form of Rhodopsin, bathorhodopsin , occurs within picoseconds of illumination. There are then a series of conformational changes leading to the formation of metarhodopsin II, which initiates a guanine nucleotide amplification cascade and then a nerve impulse.

15. Wald’s visual cycle The final step is hydrolysis to release all- trans - retinaldehyde and opsin . The key to initiation of the visual cycle is the availability of 11- cis -retinaldehyde, and hence vitamin A. In deficiency, both the time taken to adapt to darkness and the ability to see in poor light are impaired.

16. Wald’s visual cycle

17. Role in the Regulation of Gene Expression and Tissue Differentiation Retinoic acid is a ligand for certain nuclear receptors that act as transcription factors. The retinoid receptors play an important role in controlling cell proliferation and differentiation. Like vitamin D, retinoic acid interacts with nuclear receptors that bind to control elements which are specific regions on the DNA to regulate the expression of specific genes.

18. Role in the Regulation of Gene Expression and Tissue Differentiation Two families of receptors (RAR and RXR receptors) are active in retinoid-mediated gene transcription. RAR binds all- trans retinoic acid and 9- cis retinoic acid, whereas RXR binds only 9- cis retinoic acid.

19. Role in the Regulation of Gene Expression and Tissue Differentiation All- trans -RA and 9- cis -RA are transported to the nucleus of the cell bound to cytoplasmic retinoic acid-binding proteins. Within the nucleus, all- trans -RA binds to retinoic acid receptors (RAR) and 9- cis -RA binds to retinoid receptors (RXR). RAR and RXR form RAR/RXR heterodimer, which bind to regulatory regions of the chromosome called retinoic acid response elements (RARE).

20. Role in the Regulation of Gene Expression and Tissue Differentiation Binding of all- trans -RA and 9- cis -RA to RAR and RXR respectively allows the complex to regulate the rate of gene transcription. Nuclear Receptors in the Gonads increase gene expression and maintain reproductive tissues while nuclear receptors in epithelial cells regulate cell differentiation.

21. Role of vitamin A in Immunity 1) Vitamin A and retinoic acid (RA) play a central role in the development and differentiation of white blood cells, such as lymphocytes, which play critical role in the immune response. 2) The skin and mucosal cells (function as a barrier and form the body's first line of defense against infections. Retinol and its metabolites are required to maintain the integrity and functioning of these cells. Keratinization of mucous membranes in vitamin A deficiency add up to the risk to infections. 3)Retinol binding protein (RBP) is a negative ‘ Acute phase protein’ , that results in decreased circulatory concentration of the vitamin with further deterioration of the immune system.

22. Role of vitamin A in growth Vitamin A is required for- General body growth Bone and Brain development

23. Vitamin A deficiency- Overview Vitamin A deficiency can result from inadequate intake, fat malabsorption, or liver disorders. Deficiency impairs immunity and hematopoiesis and causes skin rashes and typical ocular effects (e.g., xerophthalmia, night blindness). Diagnosis is based on typical ocular findings and low vitamin A levels. Treatment consists of vitamin A given orally or, if symptoms are severe or malabsorption is the cause, parente rally.

24. Etiology of Vitamin A deficiency Primary vitamin A deficiency Prolonged dietary deprivation Vegetarians, Refugees, and Chronic alcoholics, Toddlers and Preschool children

25. Etiology of Vitamin A deficiency Secondary vitamin A deficiency Sprue , Cystic fibrosis, Pancreatic insufficiency, Duodenal bypass, Chronic diarrhea, Bile duct obstruction, Giardiasis, and cirrhosis .

26. Symptoms of vitamin A deficiency The signs and symptoms are grouped into ocular and extraocular manifestations.

27. Ocular manifestations All the ocular manifestations are due to decreased synthesis of rhodopsin in the retina and due to dryness of conjunctiva and its consequences. All the ophthalmic manifestations due to vitamin A deficiency are included under the term ‘ Xerophthalmia ’ ( Xerosis = dryness; dry eye).

28. Stages Of Ocular manifestation Night blindness ( Nyctalopia ): That means inability to seen the dim light by an young child as the evening sets in . This is because of failure in the dark adoptation because of decreased synthesis of rhodopsin in the retina. The classical complaint by the mother is that her child cannot find her or dashes against the wall as the dark sets in. Nyctalopia is the earliest clinical feature. If not managed at this stage, it passes on to the next stage.

29. Stages Of Ocular manifestation Conjunctival xerosis : The normal, smooth, shiny conjunctiva over the sclera becomes dry, dull and wrinkled giving a smoky appearance. Often this occurs following chronic exposure to dust and smoke also, but among adults.

30. Stages Of Ocular manifestation Bitot’s spots: These are triangular, foamy, pearly-white or yellowish spots on the bulbar conjunctiva, usually lateral to cornea and often bilateral. It is characteristic of vitamin A deficiency.

31. Stages Of Ocular manifestation Corneal xerosis : The smooth, shiny, transparent cornea looks dull and dry, eventually it becomes opaque. If not managed at this stage, it leads on to corneal ulceration. Thus the involvement of cornea constitutes medical emergency.

32. Stages Of Ocular manifestation Corneal ulcer: The ulcer may be big or small, which after healing leaves behind a permanent scar, which affects vision.

33. Stages Of Ocular manifestation Keratomalacia : As the deficiency of vitamin A continues, the entire cornea or a part of it becomes soft and later it is liquefied. This constitutes a grave medical emergency, because the soft cornea may burst open, leading on to prolapse of iris. If the eye collapses, vision is lost.

34. Extraocular Manifestations Retardation of growth Follicular hyperkeratosis ( Phrynoderma ) Anorexia Increased incidence of respiratory and alimentary infections Development of urinary calculi.

35. Assessment of Vitamin A Deficiency Since the ophthalmic manifestations are many due to deficiency of vitamin A, WHO has recommended to consider any one of the following criteria as an evidence of xerophthalmia problem in the community, as per the surveys done among preschool children , aged 6 months to 6 years.

36. Prevalence criteria for determining the Xerophthalmia problem

37. Prevalence Of Vitamin A deficiency in SEAR Country Children <6 years No. of deaths perceived Subclinical VAD (%) Clinical VAD (%) Afghanistan 50,000 53 - Bangladesh 28,000 28 0.7 Bhutan 600 32 0.7 India 3,30,000 57 0.7 Nepal 6,900 33 1 Pakistan 56,000 35 - South Asia region 4,71,500 - - World total 11,50,000 - - Source- UNICEF 2003 UNICEF and MI 2004 : WHO 2000

38. Prevalence of Vitamin A deficiency( India)

39. Prevalence of Vitamin A deficiency( India)

40. Treatment Of Vitamin A deficiency Vitamin A deficiency should be treated urgently. Nearly all of the early stages of xerophthalmia can be reversed by administration of a massive dose (200,00Q IU or 110 mg of retinol palmitate ) orally on two successive days (30 ). All children with corneal ulcers should receive vitamin A whether or not a deficiency is suspected.

41. Prevention Prevention and/or control takes two forms improvement of people's diet so as to ensure a regular and adequate intake of foods rich in vitamin A, and reducing the frequency and severity of contributory factors, e.g., PEM, respiratory tract infections, diarrhoea and measles. Both are long term measures involving intensive nutrition education of the public and community participation.

42. Prevention Since vitamin A can be stored in the body for 6 to 9 months and liberated slowly, a short term, simple technology had been evolved by the National Institute of Nutrition at Hyderabad (India) for community- based intervention against nutritional blindness, which has subsequently been adopted by other countries . The strategy is to administer a single massive dose of 200,000 IU of vitamin A in oil (retinol palmitate ) orally every 6 months to preschool children (1 year to 6 years), and half that dose (100,000 IU) to children between 6 months and one year of age.

43. Prevention In this way, the child would be, as it were "immunized" against xerophthalmia . The protection afforded by six-monthly dosing seems very adequate as measured by clinical signs of deficiency .

44. Recommended Daily Allowances

45. Hypervitaminoses A (Toxicity) An excess intake of retinol causes anorexia, vomiting followed by sleep disorders and skin desquamation. Other features are hepatomegaly , papilledema, bony exostoses (swelling over the long bones), brittleness of the bones and often fractures. The teratogenic effects of massive doses of vitamin A is the most recent focus of interest.

46. Vitamin A supplementation (VAS) programme in India The National Prophylaxis Programme against Nutritional Blindness due to Vitamin A Deficiency ( NPPNB) was initiated in 1970 with the specific aim of preventing nutritional blindness due to keratomalacia . The Programme was started as a 100 per cent centrally sponsored programme . It was launched as an urgent remedial measure to combat the unacceptably high magnitude of xerophthalmic blindness in the country reported in the 1950s and 1960s.

47. To begin with, this Programme was initiated in 11 States of the country. Evaluation studies conducted by the National Institute of Nutrition (NIN), Hyderabad in 1976 in two States revealed positive results of the Programme . In subsequent years, the Programme was extended to all States in the country. Vitamin A supplementation (VAS) programme in India

48. In 1994, under the National Child Survival and Safe Motherhood (CSSM) Programme , the NPPNB due to VAD was modified keeping in view of the vulnerability of VA deficiency in young children. The age group of eligible children for coverage was restricted to 9 to 36 months of age. Vitamin A supplementation (VAS) programme in India

49. Accordingly, each child was to receive five doses of VA before her/his 3rd birthday (children age 6-11 months, 1 dose of 100,000 IU of VA and in age 12- 36 months of age one dose of 200,000 IU of VA every six months ). In view of operational feasibility, the administration of first dose of VA was linked to measles immunization. Vitamin A supplementation (VAS) programme in India

50. In 2006, the age group of eligible children was revised as 6-59 months. This was done after reconsidering the recommendations of WHO, UNICEF and Ministry of Women and Child Development. This was despite the evidence that clinical VAD was limited to a few isolated geographical pockets in the country. Vitamin A supplementation (VAS) programme in India

51. Presently, vitamin A supplementation (VAS) is implemented through the existing network of primary health centres and sub- centres . The female multipurpose worker and other paramedics at the village level sub-health centres are responsible for administering vitamin A solution. Vitamin A supplementation (VAS) programme in India

52. The services of Integrated Child Development Services (ICDS) functionaries are also utilized for the implementation of the Programme . Monthly intensive drives are undertaken every six months to achieve universal coverage of those children who could not be covered during the routine visits of health functionaries. Vitamin A supplementation (VAS) programme in India

53. However, with disappearance of Bitot’s spot, now the subclinical deficiency of VA, as assessed by serum retinol (SR) levels is being advocated and utilized as a marker of VAD. Serum retinol may not be an operationally feasible indicator to be utilized in communities to establish the prevalence of VAD. Estimation of SR requires collection of blood samples of children and sophisticated laboratory equipment. Vitamin A supplementation (VAS) programme in India

54. Reasons for decline in VAD in India The prevalence of severe undernutrition has come down significantly. Immunization coverage for measles and other vaccine preventable diseases has improved from 5-7 per cent in early seventies to currently 60-90 per cent, in different States. T here has been a significant improvement in the overall dietary intake of young children.

55. The ICDS which covers 80 per cent of rural India provides nutritional supplements to children less than six years of age, nutrition education to mothers and also facilitates the distribution of vitamin A supplements. Improvements in infrastructure have led to better access to health care facilities. Food availability in India has improved in the last 30 years Reasons for decline in VAD in India

56. Problem with current Policy Unjustified claims of benefit. Indiscriminate Mega Dosing. Possible Adverse Effects ( Bulging fontanel, Vitamin D Antagonism, Potential Zinc deficiency, Risk Of Acute respiratory Infections) Cost Of Vitamin A Coverage.

57. Need for targeting VAS ..! According to WHO guidelines , vitamin A supplementation in children 6-59 months of age is recommended in settings where vitamin A deficiency is a public health problem. In the Indian context, it would, therefore, be prudent to restrict massive dose prophylaxis in isolated geographical pockets or areas where clinical vitamin A deficiency is a significant public health problem rather than continuing universal prophylaxis.

58. Approach for VA supplementation At this stage, we should focus our efforts on sustainable food based approaches to combat vitamin A deficiency. The solution is to increase local production and consumption of green leafy vegetables and other plant foods that are rich sources of carotenoids. Green leafy vegetables, many fruits and other plant foods are also good sources of folate , vitamin C, Fe, Ca and many other micronutrients and bioactive compounds.

59. A food-based approach to combat VAD in non-clinically deficient areas would be a sustainable and cost effective solution. States of Bihar, Uttar Pradesh and Madhya Pradesh with poor intake of food providing all micronutrients, may have targeted approach of VAS in areas endemic for clinical VAD. Approach for VA supplementation

60. In India, for cost-effective utilization of limited resources available to the health sector, the `Triple A’ (Assessment, Analysis and Action) strategy should be adopted; first, assess the problem of VAD, then undertake the detailed analysis of causes of VAD, and then decide the combination of approaches to be adopted for prevention and control in the community . Countries with limited financial resources and competing health priorities cannot afford the luxury of initiating interventions to raise serum biochemistry alone. Approach for VA supplementation

61. References Government of India, Ministry of Health and Family Welfare, Department of Family Welfare, Child Health Division, Order no. Z.28020/30/2003-CH dated 2 November 2006 Available from: http://www.poshan.nic.in/jspui/bitstream/DL/389/1/mcn-vitamin-a-ifa-supplementation.pdf , accessed on September 12, 2013 . National Nutrition Monitoring Bureau (NNMB). 9. Prevalence of vitamin A deficiency among rural preschool children . Report No 23. Hyderabad, India: National Institute of Nutrition, Indian Council of Medical Research; 2006 . World Health Organization (WHO). 1. Human vitamin and mineral requirements , World Health Organization, Food and Agriculture Organization of the United Nations, Rome. Geneva: WHO Press; 2002. p. 22-8 . M aternal and child health scheme for prophylaxis against nutritional blindness in children caused by vitamin A deficiency . Family Planning Programme , Fourth Five-Year Plan Technical Information: MCH Vitamin A prophylaxis. In: National child survival and safe motherhood programme , MCH Division, Department of Family Welfare, Ministry of Health and Family Welfare, Government of India. New Delhi: Government Press; 1994. p. 88-93 USAID . Cost analysis of the national vitamin A supplementation 40. programs in Ghana, Nepal, and Zambia: a synthesis of three studies. Arlington, VA, USAID, 2004. Available from: httpf /www.mostproject.org/IVACG/GhanaNepalZambiaSythesis.pdf , accessed on May 20, 2011 World Health Organization. Guidelines for Vitamin A 41. supplementation in Infants and Children 6-59 months of age. Geneva: WHO; 2011. Available from: www.who.int/entity/nutrition/ , accessed on January 20, 2011.