MACRO & MICRO NUTRIENTS TOXICITY

Submitted to: Submitted By:

Dr. B. G. PATEL NEETU GOUDA

PROFESSOR 04-HOMMA-01289-2014

FOOD & NUTRITION DEPARTMENT. Msc. (2nd yr)

CONTENTS:

DEFINITIONS

TOLERABLE UPPER INTAKE LEVEL OF MACRO AND

MICRO NUTRIENTS

MACRONUTRIENTS AND TOXICITY

MICRONUTRIENTS TOXICITY

MINERAL TOXICITY

CONCLUSION2

DEFINITIONS:• Nutrients: A substance that provides nourishment essential for

growth and the maintenance of life.

• TOXICITY: The degree to which a substance (a toxin or poison)can harm humans or animals.

• Acute toxicity involves harmful effects in an organismthrough a single or short-term exposure.

• Sub chronic toxicity is the ability of a toxic substance to causeeffects for more than one year but less than the lifetime of theexposed organism.

• Chronic toxicity is the ability of a substance or mixture ofsubstances to cause harmful effects over an extended period,usually upon repeated or continuous exposure, sometimes lastingfor the entire life of the exposed organism.

• NUTRIENTS TOXICITY: When there is increased amount of anynutrients in the body then its required value, its leads to toxicity inthe body.

3

TOLERABLE UPPER INTAKE LEVEL:

• In 1997 the U.S. Institute of Medicine established a

reference value called the Tolerable Upper Intake Level

(UL). The maximum level of daily nutrient intakes that

is unlikely to pose health risks to almost all of the

individuals in the group for whom they designed.

Consumption of a nutrient in amounts higher than the

UL could be harmful.

4

Substance Amount (males) Amount (females)

Water 3.7 L/day 2.7 L/day

Carbohydrates 130 g/day 130 g/day

Protein 56 g/day 46 g/day

Fiber 38 g/day 25 g/day

Fat 20–35% of calories

Source: https://en.wikipedia.org/wiki/Dietary_Reference_Intake5

MACRONUTRIENTS AND ITS TOXICITY

• There are three macronutrients required by humans:

carbohydrates (sugar), lipids (fats), and proteins. Each of

these macronutrients provides energy in the form of

calories. For example:

• In carbohydrates, there are 4 calories per gram

• In proteins, there are 4 calories per gram

• And in lipids, there are 9 calories per gram

6

BODY COMPOSITION

7

CARBOHYDRATES

• Carbohydrates are primarily found in starchy foods, like grain and

potatoes, as well as fruits, milk, and yogurt.

• Carbohydrates can be simple or complex, which refers to their

chemical structure. Simple carbohydrates taste very sweet (like fruit

sugar), while complex carbohydrates taste savory (like starch in

potatoes).

• Fiber is an indigestible form of carbohydrate.

• Humans need carbohydrates in the largest amounts i.e. 45-65% daily

value for CHO consumption is 300 g/day. Carbohydrates are

incredibly important to the diet.

• Minimum amount of carbohydrate required to avoid ketosis is

considered to be about 50 g/day

8

HARMFUL EFFECTS DUE TO EXCESS CONSUMPTION OF CARBS

Type 2 Diabetes

Type 2 diabetes has been linked to

the overconsumption of refined

carbohydrates, which include white

breads, pasta and many packaged

snack foods. These types of carbs

digest quickly and cause a rush of

glucose into the blood. This

increases the body's need for

insulin and it's theorized that this

higher demand wears out the

insulin-producing cells of the

pancreas leading to the onset of the

disease. 9

Cont…..

Dental Caries

• Dental caries are cavities formedby the destruction of the hardtissues of the teeth.

• They occur when bacteria onyour teeth metabolizecarbohydrates. This leaves behindan acid, slowly destroying thehard enamel covering andunderlying structures of the tooth.Dental carries are commonlyassociated with theoverconsumption of refined carbsand added sugar because theseare the easiest carbs for thebacteria to break down into acids. 10

Cont….

OBESITY

Taking in more than the recommendedamount of carbohydrates also meanstaking in more calories. Extra caloriesthat are not burned are stored in thebody as fat. This may lead to obesity.

CVD

Excess carbohydrate intake also causevascular diseases like CVD as excessglucose which are stored in the liver asglycogen are overloaded so it isdistributed in the blood vessels whichare mostly high triglycerides and verylow density lipoproteins and reducedHDL which directly linked with CVD. 11

Too Much Fiber: Side Effects

• Abdominal bloating and excessive gas (flatulence) may be caused

by soluble fiber.

• Gastroesophageal reflux disease (GERD) may be worsened by

consuming foods high in fructo-oligosaccharides (wheat, onions,

leeks).

• Loose stools or diarrhea may be caused by cellulose supplements.

• A clump of undigested food–a bezoars–in the stomach or intestine

may, rarely, develop in people who eat large amounts of oranges,

persimmons, berries, figs, apples, coconuts, green beans, sauerkraut,

Brussel’s sprouts, potatoes with peels or sunflower seeds with shells.

• Allergic reactions, including anaphylactic reactions, after taking

chitin or chitosan (in people allergic to shellfish), psyllium husk,

insulin or other fiber are possible.12

13

REVIEWS

Carbohydrates India has the second largest

diabetic population in the

world which is projected to rise

to 109 million by 2035. An

estimated 65 million affected

people consume high amount

of carbohydrates, according to

a recent study .In the diabetes

group, the mean percentage of

total energy intake from

carbohydrates was 64.1 per

cent, which is much higher

than the upper limit of 60 per

cent as recommended by the.

According to the International

Diabetes Federation in

collaboration with National

Institute of Nutrition ,

November 19,2014.

14

Carbohydrates

( Simple sugar)

A cross-sectional study carried out

among 420 workers (210 in soft-drinks

factory and 210 in other factories), in

the age group of 20-45 years of Udupi

district, Karnataka, India. The caries

experience was higher in workers

working in soft-drinks factory and this

study also showed that specific caries

index can be used as a valid index for

assessing dental caries experience.

Kumar S, Acharya S,

Vasthare R, Singh SK,

Gupta A, Debnath N.

;Dental caries

experience in high risk

soft drinks factory

workers of South

India: A comparative

study. Indian J Dent

Res 2014;25:174-7

15

PROTEIN

• Proteins are substances consisting of up to 20 different

building blocks, the so-called amino acids

• 10% - 35% of calories in the human diet come from

protein.

• There are 500 known amino acids, 21 of which are needed

by humans. Of the 21 necessary for life, nine are

considered essential since they cannot be produced by the

body and must be eaten. Proteins that contain all nine

essential amino acids are considered 'high quality' proteins.

These high quality proteins tend to come from animal

sources. Proteins that do not contain all nine essential

amino acids are considered 'low quality' proteins, and tend

to come from plant sources.16

PROTEIN RICH FOODS

17

HARMFUL EFFECTS DUE TO EXCESS CONSUMPTION OF PROTEIN

Weight Gain

• .If you take in too much protein, you

may gain weight. If you take in 100

grams of protein, your body can only

use 50 grams of it, your body will store

the extra 200 calories' worth of protein

as fat.

High Cholesterol

• High-protein foods, particularly from

animal sources, contain an abundance

of cholesterol, which contributes to the

development of hardened arteries that

can lead to serious medical conditions,

such as heart attack and stroke. 18

Cont….

Reduced Liver and Brain Function

• An excessive protein intake can be

harmful to your liver, brain and

nervous system. When you eat

protein, your body produces

ammonia, a toxin that your liver

makes harmless. Eating too much

protein over a long period of time

can cause your liver to become

overworked, allowing ammonia and

other toxic substances to build up in

your bloodstream. This can lead to

hepatic encephalopathy. 19

Excess protein is responsible for reactions in the

body:Your blood will turn acidic: When blood

becomes very acidic, the body must correct

itself by making your blood more basic.

The most basic available element in your

body is calcium. Your bones will release

calcium into your blood, which will then

bond to the acidic byproducts of the protein,

turning your blood back to a neutral level.

You could develop kidney stones: Protein

toxicity with proteinuria can result in those

with preexisting , kidney disease or those

who have lost kidney function due to age.

Azotemia :It is an elevation of blood urea

nitrogen (reference range, 8-20 mg/dl) and

serum creatinine (normal value, 0.7-1.4

mg/dl) levels. 20

FATS:

• The basic units of fats are fatty acids and glycerol. There are over

forty different types of fatty acids. Fatty acids can be divided into

three groups:

1. Saturated fatty acids

2. Monounsaturated fatty acids

3. Polyunsaturated fatty acids

• Fatty acids serve several important functions in our body. Fats,

like carbohydrates, provide us with energy, and they are essential

for absorption of vitamins A, D, E, and K.

21

TYPES OF FATTY FOODS:

22

HARMFUL EFFECTS DUE TO EXCESS CONSUMPTION OF FATS

Atherosclerosis

• Eating foods rich in fats increases

your risk of developing

atherosclerosis, which is a condition

that causes the walls of the arteries to

thicken. This constricts the flow of

blood to the tissues, increasing the

risk of heart attack or stroke.

Increased Cancer Risk

• Excessive consumption of dietary fats

from dairy products and red meat

increases the risk of pancreatic cancer23

Cont…..

Risk of Obesity

• Obesity occurs when you consume morecalories than you need. Excessive intake ofboth fats and carbohydrates hastensobesity.

Brain Injury

• Eating foods high in saturated fats maydamage your hypothalamus -- which is thearea of your brain that regulates energybalance.

Constipation

• Diets that are high in fat can affect yourdigestive organs, including the stomachand colon.If your diet is high in saturatedfat to the detriment of your fiber intake,you may become constipated frequently 24

REVIEWS

Fat A study found that the

presence of “bad”

cholesterol or low-

density lipoprotein in the

blood contributed to the

development of

atherosclerosis. Low

density lipoprotein is a

compound made up of

protein and lipid

molecules.

A study published in

August 2002 in the

“Journal of Clinical

Epidemiology”

25

Fats The study involved tracking

the dietary intake of over

500,000 participants

between 1995 and 1996.

Researchers found that men

and women who ate foods

rich in total fats --

specifically animal fats --

had a higher incidence of

pancreatic cancer than

those with low fat

consumption. However

they also noted that further

studies are needed to

determine whether meat, or

lifestyle and dietary

preferences associated with

meat consumption, is the

real culprit.

(According to a study

published in June

2009 in the “Journal

of the National

Cancer Institute.” )

26

Fats A study led by

researchers at

McMaster University

has found that that

trans fats are

associated with greater

risk of death and

coronary heart disease,

but saturated fats are

not associated with an

increased risk of death,

heart disease, stroke,

or Type 2 diabetes.

McMaster University.

"Trans fats, but not

saturated fats like

butter, linked to greater

risk of early death and

heart disease."Science

Daily, 11 August 2015.

27

Micronutrients AND ITS TOXICITY

• A chemical element or substance required in trace amounts for the normal growth and development of living organisms. The micronutrients include all the vitamins and minerals:

Nutrient EAR RDA/AI UL Unit

Vitamin A 625 900 3000 µg

Vitamin C 75 90 2000 mg

Vitamin D 10 15 100 µg

Source: https://en.wikipedia.org/wiki/Dietary_Reference_Intake28

Nutrient EAR RDA/AI UL Unit

Vitamin K NE 120 ND µg

Vitamin B6 1.1 1.3 100 mg

α-tocopherol

(Vitamin E)12 15 1000 mg

Biotin (B7) NE 30 ND µg

Calcium 800 1000 2500 mg

Chloride NE 2300 3600 mg

Chromium NE 35 ND µg

Choline NE 550 3500 mg

Copper 700 900 10000 µg 29

Nutrient EAR RDA/AI UL Unit

Cyanocobalami

n (B12)2.0 2.4 ND µg

Fluoride NE 4 10 mg

Folate (B9) 320 400 1000 µg

Iodine 95 150 1100 µg

Iron 6 8 45 mg

Magnesium 330 400 350 mg

Manganese NE 2.3 11 mg

Molybdenum 34 45 2000 µg

Niacin (B3) 12 16 35 mg 30

Nutrient EAR RDA/AI UL Unit

Pantothenic acid

(B5)NE 5 ND mg

Phosphorus 580 700 4000 mg

Potassium NE 4700 ND mg

Riboflavin (B2) 1.1 1.3 ND mg

Selenium 45 55 400 µg

Sodium NE 1500 2300 mg

Thiamin (B1) 1.0 1.2 ND mg

Zinc 9.4 11 40 mg 31

Vitamin B complex

Vitamin B1- Thiamine

• Thiamine overdose can cause

restlessness, fluid retention, nausea,

weakness and sweating. In severe cases,

a thiamine overdose can cause dizziness,

difficulty breathing, and tightness in the

chest, swelling of the tongue or face, or

discoloration of the skin.

Vitamin B2- Riboflavin

• Riboflavin supplement will frequently

cause the urine to turn a yellow-orange

color. Severe reactions can cause

difficulty breathing, swelling of the face,

lips, throat or tongue, or hives on the

skin.32

Cont….

Vitamin B3- Niacin

• Niacin will frequently cause

flushing, which may include

burning, sweating, tingling, redness

or chills.In severe cases, taking

niacin can result in persistent

headache, irregular heartbeat,

swelling of the arms or legs, joint

pain, or blurred vision.

Vitamin B5- Pantothenic Acid

• Patients who take pantothenic acid

are very prone to overdose. This

can result in severe diarrhea.33

REVIEWS

Vitamin B3Researchers from The

Children's Hospital of

Philadelphia and The

University of Pennsylvania

reported on two adults and two

adolescents who suffered toxic

side effects from taking large

amounts of niacin, also known

as vitamin B3, in mistaken

attempts to foil urine drug

tests.

Both adult patients suffered

skin irritation, while both

adolescents had potentially

life-threatening reactions,

including liver toxicity and

hypoglycemia (low blood

sugar), as well as nausea,

vomiting and dizziness. One of

the teens also had disrupted

heart rhythms.

Children's Hospital of

Philadelphia."Misusing

Vitamin To Foil Drug Test

May Be Toxic; Plus, It Doesn't

Work."Science Daily, 11 April

2007.

34

Cont….

Vitamin B6- Pyridoxine

• Harmless effects of pyridoxine includestomach pain, drowsiness, tingling, andloss of appetite, nausea, or vomiting.

• In rare cases, this can lead to a numbingsensation in various parts of the body,most notably in the hands and feet, poorcoordination or extreme fatigue

Vitamin B7- Biotin

• There is no indication that biotin is toxic,even when took much is taken. However,in pregnant women it has been shown toshrink the placenta, which could lead toproblems for the fetus, or evenmiscarriage

35

Cont….

Vitamin B9- Folic Acid

• Taking excessive amounts of folic acid

can increase the risk of heart attack,

particularly in those who already suffer

from heart trouble. Overusing folic acid

may also increase your risk of developing

lung or prostate cancer

Vitamin B10- Para benzoic acid

• Hypothyroid, liver disease, jaundice,

nausea, vomiting, increased Vitamin C

requirements ,increased Vitamin B6

requirements, decreased estrogen

breakdown by the liver 36

Cont….

Vitamin B12- Cyanocobalamin

• Patients using cyanocobalamin may

experience diarrhea, itching or an

increased risk of blood clots, chest

pain, swelling of the face, tongue, or

lips, swelling of the body, muscle

weakness, fever, chills, bruising or

bleeding.

Choline

• Consuming too much choline can

lead dizziness or lightheadedness in

some cases. Choline overdose can

cause excessive sweating and

salivation as well as a fishy body

odor caused by byproducts of choline

metabolism in your body.37

Vitamin A (Retinol)

• Hypervitaminosis A-This conditionmay be acute or chronic.

• Symptoms vary based on whethertoxicity is acute or chronic; howeverheadaches and rash are common toboth types.

Other potential complications include:

• liver damage

• osteoporosis (a condition causingbones to become brittle, weak, andprone to breaks)

• excessive calcium build-up in thebody

• kidney damage due to excesscalcium 38

REVIEWS

Vitamin AHypervitaminosis A may be

acute or chronic. The acute

form of the condition occurs as

a result of ingesting large

amount of vitamin A over a

short period, such as few hours

or days, whereas the chronic

form results when the

vitamin accumulates in the

body gradually over a long

period. The excess vitamin A

may have been ingested via the

diet, vitamin supplementation

or the use of prescribed

medicines.

Dr Ananya Mandal, MD

http://www.news

medical.net/health/Vitamin-A-

Toxicity.aspx

39

Vitamin- AOsteoporosis is a major cause

of morbidity and mortality

among postmenopausal

women and is the most

common metabolic bone

disorder in the United States.

Furthermore, recent research

has implicated excess vitamin

A as a risk factor for

osteoporosis. Even though

implications suggest that

excess levels of vitamin A

may be a forerunner for

osteoporosis, it is a necessary

vitamin for sustaining a

healthy life.

Carly, James .;

Hypervitaminosis A: An unrecognized

potential risk factor for osteoporosis.

Medicine;

Epidemiology, MAI 49/04, Aug 2011

40

Vitamin C (Ascorbic acid)

Vitamin C toxicity can cause:

• Diarrhea

• Nausea

• Stomach cramps

• Vitamin C toxicity is usually not serious

and is treated by stopping vitamin C

supplements

• For people with a condition called

hemochromatosis, vitamin C toxicity

may be serious. Hemochromatosis

causes the body to store too much iron.

High doses of vitamin C could worsen

iron overload and cause damage to body

tissues.41

Vitamin D

• Vitamin D toxicity, also called

hypervitaminosis D

• The main consequence of vitamin D

toxicity is a buildup of calcium in

your blood (hypercalcemia), which

can cause poor appetite, nausea and

vomiting. Weakness, frequent

urination and kidney problems also

may occur.

• Vitamin D toxicity is usually caused

by megadoses of vitamin D

supplements — not by diet or sun

exposure. 42

REVIEWS

Vitamin D Pregnant women should

avoid taking vitamin D

supplements, new research

suggests. Substitution

appears to raise the risk of

children developing a food

allergy after birth.

A recent study by

Rebsamen and colleagues

found that vitamin D

induced a dose-dependent

increase in vascular smooth

muscle cell migration in rat

aorta, suggesting a possible

mechanism

of vitamin D in

atherosclerosis and vascular

remodeling.

K. Weisse, S. et al.;

Maternal and newborn

vitamin D status and its

impact on food allergy

development in the German

LINA cohort study. Allergy,

2013; 68 (2): 220.

Rebsamen M. C, Sun J.,

Norman AW, Liao JK. 1 ,25-

dihydroxyvitamin D3 induces

vascular smooth muscle cell

migration via activation of

phosphatidylinositol 3-kinase.

Circ Res.

2002;91:17-24.

43

Vitamin E

Vitamin E reduces the blood’s

ability to form clots after a cut or

injury. High doses of vitamin E

from supplements may also cause

serious bleeding in the brain.

This is known as a hemorrhagic

stroke. High doses of vitamin E

may also increase the risk of

death in some adults with serious

health conditions.

Vitamin E toxicity is not usually

caused by getting too much

vitamin E from food44

REVIEWS

Vitamin E and

Selenium

High-dose supplementation

with both the trace element

selenium and vitamin E

increase the risk of high-

grade prostate cancer. But

importantly, this risk

depends upon a man’s

selenium status before

taking the supplements.

"Men using these

supplements should stop,

period. Neither selenium

nor vitamin E

supplementation confers

any known benefits -- only

risks

Alan R. Kristal et al .Baseline

Selenium Status and Effects of

Selenium and Vitamin E

Supplementation on Prostate

Cancer Risk. .; Journal of the

National Cancer Institute, 10;

February 2014 .

45

Vitamin K

Although allergic reaction is

possible, there is no known

toxicity associated with high

doses (dietary or supplemental)

of the phylloquinone (vitamin

K1) or menaquinone (vitamin

K2) forms of vitamin K. The

same is not true for synthetic

menadione (vitamin K3) and its

derivatives. Menadione can

interfere with the function of

glutathione, one of the body's

natural antioxidants, resulting in

oxidative damage to cell

membranes.46

Minerals:

The minerals that are relevant to human

nutrition are water, sodium, potassium,

chloride, calcium, iron, zinc, iodine, and

selenium.

1. Water: Water intoxication, also known as

dilutional hyponatremia, is a potentially

fatal disturbance in brain functions. Water

intoxication provokes disturbances in

electrolyte balance, resulting in a rapid

decrease in serum sodium concentration

and eventual death.

47

Cont….

2. Sodium: Hypernatremia

is an elevated sodium

level in the blood.

Other potential problems

are:

• High Blood Pressure

• Fluid Retention

• Hypernatremia

48

REVIEWS

Sodium A study by scientists

found that using excess

salt to induce vomiting in

intoxicated persons may

lead to death due to fatal

hypernatremia.

University of Hamburg

published in the

January 2005 issue

of “Legal Medicine”

49

Cont…..

3. Potassium:

• Hyperkalemia- If you take morepotassium than your kidneys caneliminate, the concentration ofpotassium in your blood can elevateto a point where you develop acondition called hyperkalemia.

• Side Effects

• Some people who take potassiumsupplements experience side effects,mostly of a gastrointestinal nature.Abdominal pain, nausea, vomiting,and diarrhea are commonlyreported, but people taking enteric-coated potassium chloride tabletsmay develop intestinal ulcers, aswell. 50

REVIEWS

Potassium Taking more than 18 grams of

potassium per day can cause

this mineral to accumulate, as

can kidney failure or diuretic

use, . People with

hyperkalemia may experience

tingling of their extremities,

weakness or cardiac

arrhythmia, or abnormal heart

rhythm that can be deadly,

according to researchers of

(According to the Linus

Pauling Institute a study

published in a 2006 issue of

"Texas Heart Institute

Journal.“)

51

Cont….

4. Zinc: If you overdose on zinc, you

might notice a number of symptoms

caused by the toxic effects of the

mineral.

• Short-Term Effects

• Consuming too much zinc can cause

digestive upset, including diarrhea and

abdominal pain. Very large doses of

zinc -- 225 milligrams in a single dose

-- can also cause you to vomit. Smaller

doses, as little as 50 milligrams in a

single dose, can cause milder digestive

upset. 52

53

Cont…..

5. Calcium: Hypercalcemia is anelevated calcium (Ca2+) level in theblood. Calcium toxicity is usuallycaused by taking too manysupplements. Calcium toxicity is notusually caused by getting too muchcalcium from food sources. Gettingtoo much calcium can causeconstipation. It might also interferewith the body's ability to absorb ironand zinc.

In adults, too much calcium fromdietary supplements might increasethe risk of kidney stones. Too muchcalcium from food sources does notincrease that risk.

54

Cont….

6. Chloride: A higher-than-normal

level of chloride in blood is

known as hyperchloremia.

• Hyperchloremia may be due to :

• excessively high intake of

sodium chloride (table salt) or

potassium chloride

• reduced urinary excretion in

certain cases of cancer, gastritis,

and kidney disease

• dehydration

• intake of certain drugs 55

Cont….

7. Iodine: Moderate toxicity is typically

marked by elevated levels of thyroid

stimulating hormone, or TSH, in the

bloodstream.

Consumption of more than 1,700

micrograms of iodine per day may cause

goiter, or enlargement of the thyroid

gland.

Acute iodine toxicity may cause

symptoms such as diarrhea, nausea and

vomiting, as well as a burning sensation

in the stomach, throat and mouth. Weak

pulse and coma are also potential

complications of acute toxicity. 56

Cont….

8. Selenium: Neurological Effects

Selenium toxicity negatively

affects your nervous system.

Selenosis also causes peripheral

neuropathy -- damage to the

nerves found throughout your

body. This nerve damage prevents

the nerve endings in your tissues

from communicating properly

with your spinal cord and brain.

57

Cont….

9. Iron: Iron overload is known

as hemochromatosis andusually is caused by a gene thatenhances iron absorption.

Other common symptoms ofiron overload include enlargedliver, skin pigmentation,lethargy, joint diseases, loss ofbody hair, amenorrhea andimpotence.

58

REVIEWS

IronResearchers at Wake Forest

Baptist Medical Center have

found that dietary iron intake,

equivalent to heavy red meat

consumption, suppresses

leptin, a hormone that

regulates appetite.

Iron is the one mineral that

humans can't excrete, so the

more iron that is consumed the

greater the likelihood that

leptin levels will drop,

resulting in increased appetite

and the potential to overeat

which will lead to obesity.

Yan Gao, Zhonggang Li, J.

Scott Gabrielsen, Judith A.

Simcox, Soh-hyun Lee,

Deborah Jones, Bob Cooksey,

Gregory Stoddard, William T.

Cefalu, Donald A. McClain.

Adipocyte iron regulates leptin

and food intake. Journal of

Clinical Investigation, 2015;

10.

59

REFERENCES

https://en.wikipedia.org/wiki/Dietary_Reference_Intake

Kumar S, Acharya S, Vasthare R, Singh SK, Gupta A, Debnath N. ;Dental caries

experience in high risk soft drinks factory workers of South India: A comparative study.

Indian J Dent Res 2014;25:174-7.

Children's Hospital of Philadelphia."Misusing Vitamin To Foil Drug Test May Be

Toxic; Plus, It Doesn't Work."Science Daily, 11 April 2007.

Mandal Ananya, MD, Website:http://www.news medical.net/health/Vitamin-A

Toxicity.aspx.

Carly, James .;Hypervitaminosis A: An unrecognized potential risk factor for

osteoporosis.Medicine Epidemiology, MAI 49/04, Aug 201160

K. Weisse, S. et al.; Maternal and newborn vitamin D status and its impact on

food allergy development in the German LINA cohort study. Allergy, 2013; 68

(2): 220.

Rebsamen M. C, Sun J., Norman AW, Liao JK. 1 ,25-dihydroxyvitamin D3

induces vascular smooth muscle cell migration via activation of

phosphatidylinositol 3-kinase. Circ Res.2002;91:17-24.

Alan R. Kristal et al .Baseline Selenium Status and Effects of Selenium and Vitamin E

Supplementation on Prostate Cancer Risk. .; Journal of the National Cancer Institute,

10; February 2014 .

Pauling Linus, Institute a study published in a 2006 issue of "Texas Heart Institute

Journal.“)61

Yan Gao, Zhonggang Li, J. Scott Gabrielsen, Judith A. Simcox, Soh-hyun Lee, Deborah

Jones, Bob Cooksey, Gregory Stoddard, William T. Cefalu, Donald A. McClain.

Adipocyte iron regulates leptin and food intake. Journal of Clinical Investigation, 2015;

10.

62