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Disease Informatics: Phytates driving from the back-end to Influenza, Encephalitis, Hepatitis, Anemia at the front-end By RP

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Presentation on theme: "Disease Informatics: Phytates driving from the back-end to Influenza, Encephalitis, Hepatitis, Anemia at the front-end By RP"— Presentation transcript:

1 Disease Informatics: Phytates driving from the back-end to Influenza, Encephalitis, Hepatitis, Anemia at the front-end By RP "What is food to one man may be fierce poison to others" –Lucretius (1st century BC) Prerequisite:

2 What is Disease Informatics? …Brush up The application of Information Science in defining the diseases with least error Identifying most of the targets to combat a cluster of diseases and Designing a holistic solution to the problem Be a problem-solver like Dr. Abhay Bang

3 Principles of defining the diseases Purpose: to understand exactly what those are so that those are prevented or reversed Disease Causal Chain (DiCC) consists of many component causes “Many component causes” connotes lot of information The universally shared features as against spatiality are generally considered for diseases definition. However, the most optimum solutions are spatiality dependent, shared by local people than universal.

4 Identifying the targets DiCC could vary from patient to patient, made up of “events” and “risk factors that drive the disease process from backend event to the frontend event”. Event statistics could help in planning public health measures Event has scope to branch out to give rise to frontend events Event may happen as a result of more than one backend events working together The software should be derived to set aside the combination terms (anatomical + physiopathological) from MeSH database of NCBI to build event database DiCC: Disease Causal Chain

5 Designing a holistic solution Frontend event measures are like clipping the apical buds or pruning the branches of disease tree Backend event measures uproot the tree The DiCC’s should be studied as a spatial epidemiological problem for all the diseases together present in the locality. DiCC displays several targets and not just the one DiCC justifies role of nutraceutical and functional foods DiCC: Disease Causal Chain

6 An exemplary case in favor of nutraceutical Failure of ‘herbals described in ancient medicine’ or ‘new chemical entities’ to show antiviral activity in manual or HTS assays does not nullify the traditionally established utility of a principle under investigation in preventing viral disease. Therefore the ability of remedy to alter DiCC should be investigated. Not having done this, patients are deprived of several nutraceuticals and functional foods or lifestyle modalities capable of preventing or reversing the disease. They would be subjected to consuming drugs having tremendous side effects. DiCC: Disease Causal Chain Dr. V. Prakash

7 An exemplary case of multiple morbidity Probiotics reversing viral diarrhoea or hormones reversing viral encephalitis are examples of missing targets to combat complex viral diseases. Dysbiosis and endocrine anomaly are backend events of viral diarrhoea and encephalitis respectively. Intervention to amend the DiCC so that the events leading to viral diseases are bypassed or does not occur (even after exposure to the viruses) are the solutions to the diseases. DiCC: Disease Causal Chain Prof. Linda Fried Boyd CM, Darer J, Boult C, Fried LP, Boult L, Wu AW. Clinical practice guidelines and quality of care for older patients with multiple comorbid diseases: implications for pay for performance. JAMA Aug 10;294(6):

8 Phytic acid (Widely present in plants ) … Here we begin Inositol hexa-phosphate (IP6) Can have several isometric forms Can form crosslinks between phosphate groups Mechanism for Ca and Mg binding remains uncertain Ability to bind other ions depends on how much Ca is present Accompanied with other inositol phosphates (IP4 and IP5)

9 Phytic acid contents of different foods About 0.9 to 1.0% in dry whole grains About % in dry legume seeds 3.7% in dry seeds of linseed (Flax) 4.7% in dry seeds of sesame Spinelli J (1980). Unconventional Feed Ingredients for Fish Feed. In: Fish Feed Technology, FAO Corporate Documentary Repository (ADCP/REP/80/11) Charlotte Eklund-Jonsson (Sweden) Young Scientist working on phytates

10 Phytates (or Phytins) Phytates: Salt forms of phytic acid Store of inositol, phosphate and metals for use by the seedling Mostly concentrated in bran portion Assemble into spheres called globoids Shridhar K. Sathe Editor of a book on Phytates

11 Metal ions bonding with phytic acid Potassium Magnesium Calcium Manganese Iron and Zinc Six phosphate moieties of IP6 can bind to six calcium ions or 5 calcium 1 magnesium etc. John N.A. Lott, Irene Ockenden, Victor Raboy and Graeme D. Batten. Phytic acid and phosphorus in crop seeds and fruits: a global estimate. Seed Science Research (2000) 10, 11–33

12 Phytic Acid Chelation A powerful chelator Bonds with free metal ions from solutions Excretion of free metal ions from intestinal lumen Front-end events of metal chelation must be known The chelating potentially initiates Disease Causal Chains (DiCC) How that could be?

13 Iron deficiency at the front-end event due to Chelation (I) Exemplary reference: Hurrell RF, Reddy MB, Juillerat MA, Cook JD. Degradation of phytic acid in cereal porridges improves iron absorption by human subjects. Am J Clin Nutr May; 77(5): Front end event Factor driving from backend Backend event Deficiency due to the Reduced Availability of iron High phytic acid consumption Marginal iron status

14 Calcium deficiency at the front-end event due to Chelation (II) Bhatia A, Khetarpaul N. Development, acceptability and nutritional evaluation of 'Doli Ki Roti'—an indigenously fermented bread. Nutr Health. 2001;15(2): Front-end event Factor driving from backend Backend event Deficiency due to the Reduced availability of calcium High phytic acid consumption Marginal calcium status

15 Magnesium deficiency at the Front end events due to Chelation (III) Lopez HW, Leenhardt F, Remesy C. New data on the bioavailability of bread magnesium. Magnes Res Dec;17(4): Front-end eventFactor driving from backend Backend event Deficiency due to the Reduced availability of magnesium High phytic acid consumption Marginal magnesium status

16 Zinc deficiency at the Front end events due to Chelation (IV) Chiplonkar SA, Agte VV. Predicting bioavailable zinc from lower phytate forms, folic Acid and their interactions with zinc in vegetarian meals. J Am Coll Nutr Feb;25(1): (IP3 and IP5 were significant influencing factors for bioavailable zinc) Saito A, Nakayama K, Hara H. Mild zinc deficiency and dietary phytic acid accelerates the development of fulminant hepatitis in LEC rats. J Gastroenterol Hepatol Front-end eventFactor driving from backend Backend event Deficiency due to the Reduced availability of zinc High phytic acid consumption Marginal zinc status

17 Manganese deficiency at the Front end events due to Chelation (V) Agte V, Jahagirdar M, Chiplonkar S. Apparent absorption of eight micronutrients and phytic acid from vegetarian meals in ileostomized human volunteers. Nutrition Jun;21(6): Front-end eventFactor driving from backend Backend event Deficiency due to the Reduced availability of manganese High phytic acid consumption Marginal manganese status

18 Front end events of Reduced availability of Iron Front end events Factor driving from backend event Backend event Iron deficiency anemia in subjects taking iron deficient diet Reduced availability of iron due to high phytate consumption Marginal iron status No iron deficiency anemia in subjects taking iron sufficient diet Prevention of colorectal cancer in subjects taking iron excess diet

19 Factors (I and II, expanded) driving from Backend event (Marginal iron status) to iron deficiency anemia at frontend Front-end eventFactor driving from backend event I Factor driving from backend event II Iron deficiency anemia (Severity depends on how far factors responsible for backend events work together) Reduced availability of iron High phytic acid consumption Low supply of ironIron deficient foods Loss of bloodInjury Ulcer Heavy Menstrual blood loss Intestinal parasites etc

20 Back-ends factors working together Front end eventFactors driving from backend event Iron deficiency anemia Reduced availability of Iron + Low supply of iron + Loss of blood + Interactions

21 Front end events of Reduced availability of Calcium Front end eventsBackend event No deficiency in subjects taking calcium sufficient diet Calcium deficiency (reduced availability of Calcium due to IP6) Sub-clinical deficiency in subjects taking calcium deficient diets Rickets in children where component cause is calcium deficiency Osteomalacia / osteoporosis in elderly where component cause is calcium deficiency Degradation of vitamin D in the liver due to calcium deficiency John M Pettifor. Nutritional rickets: deficiency of vitamin D, calcium, or both? Am J Clin Nutr 2004; 80(suppl): 1725S–9S.

22 Front end events of Degradation of vitamin D in the liver Front-end eventsBack-end event No vitamin D deficiency if storage is enough Degradation of vitamin D in the liver Marginal vitamin D deficiency if storage is low Vitamin D deficiency if storage and intakes are low

23 Dr.Narayana Kochupillai Founder faculty member of the Department of Endocrinology, Metabolism & Diabetes at the AIIMS, INDIA "Based on our clinical experience and limited studies, we believe vitamin D deficiency is widespread in northern India,"

24 Front end events of Vitamin D deficiency (Avitaminosis D syndrome, I) D: Finally, a vitamin makes the grade. Several new studies suggest that the so-called sunshine vitamin (because it’s produced in skin exposed to sunlight) may protect against cancer. One study showed that as blood levels of vitamin D go up, women’s breast cancer risk goes down. Another found that fairly large amounts of vitamin D lowered the risk for pancreatic cancer by about 40%. The Top 10 health stories of 2006, from the Harvard Health Letter

25 Front end events of Vitamin D deficiency (Avitaminosis D syndrome, II) Front end eventsBackend event Autoimmune diseases Vitamin D deficiency Type 1 diabetes Heart Disease Osteoporosis

26 The UV Advantage: The Medical Breakthrough That Shows How to Harness the Power of the Sun for Your Health by Michael F. Holick. I Books /Marvel, New York Dr. Michael Holick

27 Front-end events of Vitamin D deficiency (Avitaminosis D syndrome, III) Front-end eventBack-end event Epidemic Influenza (Driving factors to be investigated) Vitamin D deficiency Cannell JJ, Vieth R, Umhau JC, Holick MF, Grant WB, Madronich S, Garland CF, Giovannucci E. Epidemic influenza and vitamin D. Epidemiol Infect Dec;134(6):

28 Epidemic influenza and vitamin D. Epidemiol Infect Dec;134(6): Cannell JJ 2. Vieth R 3. Umhau JC 4. Holick MF 5. Grant WB 6. Madronich S 7. Garland CF 8. Giovannucci E. All authors are from different institutes

29 Disease definition challenged Author’s remark in the conclusion section: Is influenza infection a sign of vitamin D deficiency as much as Pneumocystis carinii pneumonia is a sign of AIDS? J. J. Cannell

30 Motivation for writing review All of the patients on my ward had been taking 2,000 units of vitamin D every day for several months or longer. Could that be the reason none of my patients caught the flu? First, the ward below mine was infected, and then the ward on my right, left, and across the hall - but no patients on my ward became ill. My patients had intermingled with patients from infected wards before the quarantines. The nurses on my unit cross-covered on infected wards. Surely, my patients were exposed to the influenza A virus. How did my patients escape infection from what some think is the most infectious of all the respiratory viruses? My patients were no younger, no healthier, and in no obvious way different from patients on other wards. J. J. Cannell

31 Front-end events of Vitamin D deficiency (Avitaminosis D syndrome, III continued) INDAPUR (INDIA) STUDY Wayse V, Yousafzai A, Mogale K, Filteau S. Association of subclinical vitamin D deficiency with severe acute lower respiratory infection in Indian children under 5 y. Eur J Clin Nutr Apr;58(4): By: Prof. Suzanne Filteau London School of hygiene and Tropical medicine

32 Front-end events of Vitamin D deficiency (Avitaminosis D syndrome, IV) Front-end eventBack-end event Encephalitis (Driving factor: Failure of regulation of cytokine expression?) Vitamin D deficiency Cantorna MT, Woodward B, Hayes CE, DeLuca HF. 1,25- dihydroxyvitamin D3 is a positive regulator for the two antiencephalitogenic cytokines TGF-ß1 and IL-4. J Immunol 160:5314–5319, 1998.

33 Front-end events of Vitamin D deficiency (Avitaminosis D syndrome, V) Front-end eventBack-end event Inflammatory bowel disease (IBD) Vitamin D deficiency Froicu M, Cantorna MT. Vitamin D and the vitamin D receptor are critical for control of the innate immune response to colonic injury. BMC Immunol Mar 30;8:5.

34 Back end events (expanded) of vitamin D deficiency Front-end eventBack-end events Vitamin D deficiency Vegetarian diets and low consumption of animal foods Low exposure to Sun due to shyness Low exposure to solar UVB due to heavy air pollution Dark skin Malfunctioning of Liver or kidney due to toxicities Malfunctioning of Liver or kidney due to Xenobiotic medicines Malfunctioning of VDR (Vitamin D receptor) Fluorosis, lead toxicity leading to calcium deficiency Calcium deficiency

35 Hypothesis drawn on the basis of Disease Causal Chains (DiCC) Optimization of Phytic Acid in the Diets of Indians consuming excessive grains at the back end reduces some burden of various diseases at the front end.

36 Phytates as nutraceutical Phytates are antioxidants Phytates also chelate several minerals in the lumen of intestine Reducing the availability of iron to pathogenic flora (Free iron is required by pathogenic flora of the gut) Could help in prevention of lead toxicity

37 Everything I eat has been proved by some doctor or other to be a deadly poison, and everything I don't eat has been proved to be indispensable for life. But I go marching on. ~George Bernard Shaw

38 Consumption of dry legumes (dicotyledonous seeds) 1. De-hulling (Preparation of Dal) 2. Sprouting of seeds 3. Soaking and pressure cooking 4. Cooking dal flour These common practices remove most of the phytic acid

39 Grains are rich in phytates Chemical fertilizers: N, P and K are majors Phytate content shoots up in chemically fertilized crops Phosphorus is stored as phytic acid / phytates in plants and grains Bran portion of grain is rich in several nutrients as well as phytates People consuming whole grains consume lot of phytates also

40 Phytates in diet of affluent people Phytates reduce enteric toxins The toxins function as: The backend event of several diseases Backend event of colorectal cancers and mammary cancers Hence, affluent people could consider phytates as useful entities if consumed in limited amounts.

41 Grains are cheapest food but… Green revolution has rendered grains as cheapest food in India Further yield enhancement due to chemical fertilization Abundant, hence cheap than animal foods or fruits and vegetables People of low socio-economic status consume grains from fertilized crops excessively ‘Food help’ during famine or floods is mostly grains

42 Phytates in poor man’s diet Poor people in India eat excessive grains Do not eat foods from other groups in enough quantities Face problems of mineral deficiencies Iron, Calcium, Magnesium and Manganese IP6 present in mature seeds effectively inhibit Ca and Zn uptake Inositol phosphates (IP4, IP3 etc) in immature seeds are less effective in this regard

43 Women of India Iron deficiencies are realized in young women due to their high iron requirements Outcome of iron deficiency anemia is: Problematic pregnancy and childbirth Poor reproductive health and Susceptibility to several diseases Reduced working capacity

44 Children and old people Calcium deficiencies are realized in growing children and old age people Vitamin D is degraded very fast in individuals having calcium deficiency This could be the reason why vitamin D deficiency is common in sunny country like India Magnesium is also required for proper metabolism of Vitamin D Avitaminosis D is a component cause of several Diseases

45 How to curtail phytates? The best solution or at least the first solution is to curtail level of phytate intakes. Secondary solutions like fortification of foods should only be implemented till the tackling of the basic problem of anti-nutritional phytates is difficult. Could phytase be activated by making dough for roti on previous day?

46 Primary solution: Education: Replacing part of high phytate foods with low phytate foods (e.g. using protein foods and supplements) Processing foods to allow action of enzyme phytase on foods (Dephytinization): Malting: Germination (sprouting) of grains Use of leavening agent like yeast in preparation of cereal dough Destroying phytates by solar roasting / steaming of grains: Encouraging consumption of thalipeeth prepared from baked grains in place of Roti or Bhakri Intervention: Sukdi type of special preparation (baked/ autoclaved bran laddooes supplemented with minerals)

47 Secondary solutions: Fortification of foods with critical minerals Salt fortification (?) Using iron vessels for cooking Use of multi mineral multi vitamin capsule Implementing lead detoxification Deworming Report of an FAO technical meeting Rome, Italy, November 1995

48 Tertiary solution Research Breed low phytate grain varieties Breed High Phytase grain varieties Bouis HE. Plant breeding: a new tool for fighting micronutrient malnutrition. J Nutr Mar;132(3):491S-494S Dr. Howarth Bouis

49 Quaternary solution Find separate solutions for all front-end problematic events (!)

50


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