Transcript Front-end events of Vitamin D deficiency

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.ppt
http://www.publichealth.pitt.edu/supercourse/SupercoursePPT/25011-26001/25381.ppt
http://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 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
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
An exemplary case in favor of nutraceutical
Dr. V. Prakash
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
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.
An exemplary case of multiple morbidity
Prof. Linda Fried
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
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)
Phytic acid contents of different foods
About 0.9 to 1.0% in dry whole grains
About 0.6-1.6% 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
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
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
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?
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
Backend
driving from event
backend
Deficiency
due to the
Reduced
Availability
of iron
High phytic Marginal
acid
iron status
consumption
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
Backend
driving from event
backend
Deficiency
due to the
Reduced
availability
of calcium
High phytic Marginal
acid
calcium
consumption 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
Deficiency due
to the Reduced
availability of
magnesium
Factor driving
Backend event
from backend
High phytic acid Marginal
consumption
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
Front-end event
Deficiency due
to the Reduced
availability of
zinc
Factor driving
Backend event
from backend
High phytic acid Marginal zinc
consumption
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.
Front-end event
Deficiency due
to the Reduced
availability of
manganese
Factor driving
Backend event
from backend
High phytic acid Marginal
consumption
manganese status
Front end events of Reduced availability of Iron
Front end
events
Iron deficiency
anemia in subjects
taking iron deficient
diet
No iron deficiency
anemia in subjects
taking iron sufficient
diet
Prevention of
colorectal cancer in
subjects taking iron
excess diet
Factor
driving from
backend
event
Reduced
availability of
iron due to
high phytate
consumption
Backend
event
Marginal iron
status
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
High phytic acid
consumption
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
Iron deficiency
anemia
Factors driving
from backend event
Reduced
availability of Iron
+ Low supply of
iron + Loss of
blood +
Interactions
Front end events of Reduced availability of Calcium
Front end events
No deficiency in subjects taking
calcium sufficient diet
Sub-clinical deficiency in
subjects taking calcium
deficient diets
Rickets in children where
component cause is calcium
deficiency
Backend event
Calcium deficiency
(reduced
availability of
Calcium due to
IP6)
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
No vitamin D deficiency if
storage is enough
Marginal vitamin D
deficiency if storage is low
Vitamin D deficiency if
storage and intakes are low
Back-end event
Degradation of
vitamin D in the
liver
Founder faculty member
of the Department of
Endocrinology,
Metabolism & Diabetes
at the AIIMS, INDIA
Dr.Narayana Kochupillai
"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
Vitamin D
Autoimmune
deficiency
diseases
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 Vitamin D
(Driving factors to deficiency
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.
2.
3.
4.
5.
6.
7.
8.
Cannell JJ
Vieth R
Umhau JC
Holick MF
Grant WB
Madronich S
Garland CF
Giovannucci E.
All authors are from different institutes
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
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
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. 2004 Apr;58(4):563-7.
By: Prof. Suzanne Filteau
London School of hygiene and Tropical medicine
Front-end events of Vitamin D deficiency
(Avitaminosis D syndrome, IV)
Front-end event
Back-end event
Encephalitis
(Driving factor:
Failure of
regulation of
cytokine
expression?)
Vitamin D
deficiency
Cantorna MT, Woodward B, Hayes CE, DeLuca HF. 1,25dihydroxyvitamin 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)
Front-end event
Back-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. 2007 Mar 30;8:5.
Back end events (expanded) of vitamin D deficiency
Front-end event
Vitamin D
deficiency
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 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
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 seeds
3.
Soaking and pressure cooking
4.
Cooking dal flour
These common practices remove most of the phytic acid
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
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
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
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
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
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
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 capsule
Implementing lead detoxification
Deworming
Report of an FAO technical
meeting Rome, Italy, 20-23
November 1995
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. 2002
Mar;132(3):491S-494S
Dr. Howarth Bouis
Quaternary solution
Find separate solutions for all front-end
problematic events (!)