disease informatics: phytates driving from the back-end to influenza, encephalitis, hepatitis,...

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

By RP Deolankar [email protected]

"What is food to one man may be fierce poison to others" –Lucretius (1st century BC)

Prerequisite:http://www.publichealth.pitt.edu/supercourse/SupercoursePPT/25011-26001/25371.ppthttp://www.publichealth.pitt.edu/supercourse/SupercoursePPT/25011-26001/25381.ppthttp://www.publichealth.pitt.edu/supercourse/SupercoursePPT/28011-29001/28921.ppt

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

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.

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 eventsEvent 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

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


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.


Dr. V. Prakash

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.


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. 2005 Aug 10;294(6):716-24.

Phytic acid (Widely present in plants) …Here we begin

Inositol hexa-phosphate (IP6)Can have several isometric formsCan form crosslinks between phosphate groupsMechanism for Ca and Mg binding remains uncertainAbility to bind other ions depends on how much Ca is presentAccompanied with other inositol phosphates (IP4 and IP5)

Phytic acid contents of different foodsAbout 0.9 to 1.0% in dry whole grainsAbout 0.6-1.6% in dry legume seeds3.7% 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

Phytates (or Phytins)Phytates: Salt forms of phytic acidStore of inositol, phosphate and metals for use by the seedlingMostly concentrated in bran portionAssemble into spheres called globoids

Shridhar K. SatheEditor of a book onPhytates

Metal ions bonding with phytic acidPotassiumMagnesiumCalciumManganeseIron andZincSix 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

Phytic Acid Chelation

A powerful chelatorBonds with free metal ions from solutionsExcretion of free metal ions from intestinal lumenFront-end events of metal chelation must be knownThe chelating potentially initiates Disease Causal Chains (DiCC)How that could be?

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. 2003 May; 77(5): 1213-9.

Front end event

Factor driving from backend

Backend

event

Deficiency due to the Reduced Availability of iron

High phytic acid consumption

Marginal iron status

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):113-20

Front-end event

Factor driving from backend

Backend event

Deficiency due to the Reduced availability of calcium


Marginal calcium status

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. 2004 Dec;17(4):335-40.

Front-end event Factor driving from backend

Backend event

Deficiency due to the Reduced availability of magnesium


Marginal magnesium status

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. 2006 Feb;25(1):26-33. (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. 2007


Backend event

Deficiency due to the Reduced availability of zinc


Marginal zinc status

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. 2005 Jun;21(6):678-85.


Backend event

Deficiency due to the Reduced availability of manganese


Marginal manganese status

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

Factors (I and II, expanded) driving from Backend event (Marginal iron status) to iron deficiency anemia at frontend

Front-end event Factor 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


Low supply of iron Iron deficient foods

Loss of blood Injury

Ulcer

Heavy Menstrual blood loss

Intestinal parasites etc

Back-ends factors working together

Front end event Factors driving from backend event

Iron deficiency anemia

Reduced availability of Iron + Low supply of iron + Loss of blood + Interactions

Front end events of Reduced availability of Calcium

Front end events Backend 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.

Front end events of Degradation of vitamin D in the liver

Front-end events Back-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

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," http://www.bmj.com/cgi/content/full/326/7379/12/b?etoc

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

Front end events of Vitamin D deficiency (Avitaminosis D syndrome, II)

Front end events Backend event

Autoimmune diseases

Vitamin D deficiency

Type 1 diabetes

Heart Disease

Osteoporosis

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

Front-end events of Vitamin D deficiency (Avitaminosis D syndrome, III)

Front-end event Back-end event

Epidemic Influenza (Driving factors to be investigated)


Cannell JJ, Vieth R, Umhau JC, Holick MF, Grant WB, Madronich S, Garland CF, Giovannucci E. Epidemic influenza and vitamin D. Epidemiol Infect. 2006 Dec;134(6):1129-40

Epidemic influenza and vitamin D. Epidemiol Infect. 2006 Dec;134(6):1129-40

1. Cannell JJ2. Vieth R3. Umhau JC4. Holick MF5. Grant WB6. Madronich S7. Garland CF8. Giovannucci E.

All authors are from different institutes

Disease definition challengedAuthor’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

Motivation for writing reviewAll 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

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 lowerrespiratory infection in Indian children under 5 y. Eur J Clin Nutr. 2004 Apr;58(4):563-7.

By: Prof. Suzanne FilteauLondon School of hygiene and Tropical medicine

Front-end events of Vitamin D deficiency (Avitaminosis D syndrome, IV)


Encephalitis

(Driving factor: Failure of regulation of cytokine expression?)


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.

Front-end events of Vitamin D deficiency (Avitaminosis D syndrome, V)


Inflammatory bowel disease (IBD)


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. 2007 Mar 30;8:5.

Back end events (expanded) of vitamin D deficiency

Front-end event Back-end events


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

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.

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

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

Consumption of dry legumes (dicotyledonous seeds)1. De-hulling (Preparation of Dal)2. Sprouting of seeds3. Soaking and pressure cooking4. Cooking dal flourThese common practices remove most of the phytic acid

Grains are rich in phytatesChemical fertilizers: N, P and K are majorsPhytate content shoots up in chemically fertilized cropsPhosphorus is stored as phytic acid / phytates in plants and grainsBran portion of grain is rich in several nutrients as well as phytatesPeople consuming whole grains consume lot of phytates also

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.

Grains are cheapest food but…

Green revolution has rendered grains as cheapest food in IndiaFurther yield enhancement due to chemical fertilizationAbundant, hence cheap than animal foods or fruits and vegetablesPeople of low socio-economic status consume grains from fertilized crops excessively‘Food help’ during famine or floods is mostly grains

Phytates in poor man’s dietPoor people in India eat excessive grainsDo not eat foods from other groups in enough quantitiesFace problems of mineral deficienciesIron, Calcium, Magnesium and ManganeseIP6 present in mature seeds effectively inhibit Ca and Zn uptakeInositol phosphates (IP4, IP3 etc) in immature seeds are less effective in this regard

Women of IndiaIron deficiencies are realized in young women due to their high iron requirementsOutcome of iron deficiency anemia is:Problematic pregnancy and childbirthPoor reproductive health andSusceptibility to several diseasesReduced working capacity

Children and old peopleCalcium deficiencies are realized in growing children and old age peopleVitamin D is degraded very fast in individuals having calcium deficiencyThis could be the reason why vitamin D deficiency is common in sunny country like IndiaMagnesium is also required for proper metabolism of Vitamin DAvitaminosis D is a component cause of several Diseases

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?

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)

Secondary solutions:Fortification of foods with critical minerals

Salt fortification (?)Using iron vessels for cooking Use of multi mineral multi vitamin capsuleImplementing lead detoxificationDeworming

Report of an FAO technical meeting Rome, Italy, 20-23 November 1995

Tertiary solutionResearchBreed low phytate grain varietiesBreed High Phytase grain varieties

Bouis HE. Plant breeding: a new tool for fighting micronutrient malnutrition. J Nutr. 2002 Mar;132(3):491S-494S

Dr. Howarth Bouis

Quaternary solutionFind separate solutions for all front-end problematic events (!)

disease informatics: phytates driving from the back-end to influenza, encephalitis, hepatitis,...

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