Dr. Sukhinder K. Cheema, Ph.D.Professor & Deputy Head

Department of Biochemistry & Faculty of MedicineMemorial University, Canada

30 October, 2015

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Key Nutrients to Prevent Metabolic and Nervous System Disorders

Biochemistry and Nutrition

• Biochemistry: the study of chemical processes associated with living organisms.

• Nutrition: the science that studies the means by which we intake and utilize food, and how foods and nutrients regulate biochemical pathways.

• Food Science: the study of the physical, biological, and chemical makeup of food; and the concepts underlying food processing.

Medical Oath

• I will practise my profession with conscience and dignity.

• The health of my patient will be my first consideration.

• …………

http://www.ima-india.org/

Leading Causes of Death: The Role of Diet

India and Heart Disease Issues

WHO 2014WHO, 2014

India May Have the Most Suicides

The Wall Street Journal, India, Sep 2014

The U.N.’s health agency found that India accounted for more than 258,000 of the 804,000 suicide deaths worldwide in 2012. That’s more than in any other country.

Learning Objectives

• Dietary fats in health• Vitamin D in health• Dietary protein and health• Folic acid and health• Maternal nutrition and health of

the next generation

Nutritional Status in India

• Under nourished 380million

• Overnourished 80 million

• Calorie sufficient• /nutrient deficient 570 million

– 342 million consume higher than normal calories with high fat intake

FICCI Ernest & Young Wellness Report 2009

Saturated Fatty Acids

(SFA)

Monounsaturated Fatty Acids

(MUFA)

Types of Dietary Fats

Polyunsaturated Fatty Acids

(PUFA)

ESSENTIAL PUFA

n-6 PUFA

(Linoleic Acid)

n-3 PUFA

(α-Linolenic acid)

FLAX SEEDS

Trans Fats!

• Trans fatty acids are made through hydrogenation to solidify liquid oils to increase the shelf life

• Heating omega-6 oils, such as corn oil, to high temperatures creates trans fats

• Trans fats are found in fried foods

• The intake of trans fatty acids raises the risk of CVD

Synthesis of Longer Chain PUFA

Prostate GlandNobel prize 1982

20:4 n-6

Prostaglandins Actions?• Constriction or dilation in vascular smooth

muscle cells• Aggregation or disaggregation of platelets• Sensitize spinal neurons to pain• Induce labor and regulate hormones• Regulate inflammation• Control cell growth

Prostaglandins Actions?

• Acts on thermoregulatory center of hypothalamus to produce fever

• Acts in the glomerulus of the kidney to increase glomerular filtration rate

• Acts on parietal cells in the stomach wall to inhibit acid secretion

Donald B. Jump, Ann. Rev. Nutr. 1999. 19:63-90

Synthesis of Longer Chain PUFA

Prostate GlandNobel prize 1982

20:4 n-6

N-3 PUFA X

Balance of N-6 and N-3 PUFA

Current ratio of n-6 to n-3 fatty acids is 20-30:1 as opposed to 1-2:1 in earlier times of human evolution

20:1(n-3 PUFA)

(n-6 PUFA)

The American Heart Association recommends two servings of fish

per week to prevent heart disease.

Dietary Fat Intake

Brain function

Heart function

Brain Growth Is Rapid in the First Two Years

DHA Accumulation

Dobbing & Sands, 1973, Archives of Disease in Childhood, 48: 757

Neurological disorders are linked to lower n-3 PUFA content

DHA is supplied by the mother during fetal development

Breast Milk provides DHA after birth

The amount of DHA in Breast Milk is related to

maternal status Maternal DHAM

ilk D

HA

Biological Activities of DHA

• Lipids make more than 50% of newborn’s brain mass

• Brain grey matter contains high levels of DHA, deficiency can result in learning deficits

• Changes in neuronal cell membrane DHA content alters the availability of neurotransmitters

• Very high amounts of DHA in the membranes of retina (50% of total fatty acids)

• DHA is essential for the normal development and function of the retina– Better visual acuity, retinal response to light

Biological Activities of DHA

DHA and N-3 Intake is Too Low

How can one increase the intake of n-3 PUFA?

Sources of N-3 PUFA

• Salmon Walnuts• Tuna Flax• Atlantic Pollock Chia• Sole Soy• Cod Canola Oil• Shrimp Hemp

Marine Vegetarian

Dietary Fat: Recommendations• No more than 30% calories from fat (total

caloric intake)

• No more than 10% of total caloric intake from saturated fat + trans fat

• 1 gram fat=9 calories

• 1 teaspoon=4 grams of fat

• Limit is 65 grams per day

It is suggested that more than 10% of the Indian population is essential fatty acid deficient

Things to find out from your patient….

• Is your patient consuming essential fatty acids?

• Is your patient’s diet sufficient in n-6 fatty acids?

• Is your patient’s diet sufficient in n-3 fatty acids?

Fat soluble vitamins: Vitamin D

Vitamin D: Issues & Importance

Vitamin D Status In India • 70-100% of the Indian population is vitamin D

deficient• Deficiency is defined as 25(OH)D <20ng/ml,

insufficient = 20-29ng/ml and sufficient >= 30 ng/ml

• Deficiency highly prevalent in 50+ years old, pregnant and lactating women, and their breastfed infants– mother’s vit D status reflected in breastmilk

• Cooking habits destroy vitamin D, heating above 200C

Vitamin D: Functions• Promotes absorption of calcium and

phosphorous• Helps deposit calcium and phosphorous in

bones and teeth• Regulates cell growth• Important in immunity

– Prevents heart disease, diabetes, obesity and cancer

Vitamin D: Sources• Sunlight exposure (at least 45 minutes per day

to bare skin vs. 10-15 minutes twice a week for Caucasians)– Darker skin has high melanin, a natural sunscreen

• Salmon with bones• Milk (fortified otherwise very low in vit. D)• Fortified foods

• High salt and high grain (phytates) foods interfere in calcium absorption

Vitamin D Supplements: India• D3 supplements of 60,000 IU is the highest

selling, once per week• Most physicians recommend 60,000 IU per

day for 10 days, followed by 60,000 IU per week for 5-6 weeks

ISSUES: • Vitamin D- fat soluble, body stores, not

excreted• Vitamin D toxicity- brittle bones

Vitamin D:RDA

• Recommended Dietary Allowance (RDA) for vitamin D - 600 IU a day (1 to 70 years of age), and 800 IU a day for 70+.

• For children under 1 year, adequate intake (AI) is 400 IU a day.

Protein Malnourishment?

“In-utero Programming Barker’s Hypothesis”

• Low Birth Weight= Cardiovascular disease

• Placental Insufficiency

• Maternal Under-nutrition

• Dutch hunger famine

The Barker Hypothesis

Maternal Undernutrition

Fetal Growth Retardation

Structural Change within Organs

Disease In Later Life

Poor Childhood Growth

Metabolic and Endocrine

Dysfunction

Death Rates (standardized mortality ratio) From CHD According to B. Wt. in 10141 Men and 5585

Women Hertfordshire, UK

Godfrey & Robinson (1998) Proc. Nutr. Soc. 57:105

Odds Ratio of Type 2 Diabetes at Different Birth Weights

JAMA. 2008;300(24):2886-2897

Birth Wight and Insulin Resistance Syndrome

Barker et al. Diabetologia 1993; 36:62-67

Protein Recommendations

• 10 to 35% of energy intake• OR 0.8g/kg B.wt/day• Approximately 40-60 grams (approximately 4

tablespoons)

• Animal protein provides all essential amino acids (high quality), while plant based proteins are of low quality – need to eat a variety of foods to get all the essential amino acids

Things to ask your patient….

• Is your patient’s diet sufficient in protein, especially that of pregnant women

Mechanisms of Programming?

Nutritional Influence

Reorganisation of organ structureAbnormal early cell-cell interactions?

Altered Cell Number orintracellular organization

Metabolic Differentiation DNA Control?

(altered cell specific gene regulation)

DNA Environment?(altered DNA binding proteins)

Altered DNA methylation?

Mitochondrial DNA?

Defining Epigenetics:

“Epigenetics refers to chromatin and DNA modifications that are heritable through cell division, but do not involve changes in the underlying DNA sequence”

or:

“Gene expression effects mediated by chromatin structure and DNA METHYLATION, but not DNA sequence”

Sedivy et al. 2007 Cell 314:1909-2007

Folic Acid

Folate• Folate plays an important role in cell

division and in the synthesis of amino acids and nucleic acids like DNA

• Essential to the normal development of the spine, brain and skull of the fetus, especially during the first four weeks of pregnancy.

• Supports maternal and fetal tissues growth

Neural Tube Defect

http://simplifiedmed.weebly.com/

Neural Tube Defects: India• A recent meta-analysis concluded: “The

overall prevalence of neural tube defects from India is high compared to other regions of the world, while that of orofacial clefts is similar to other countries. The majority of studies included in the review were hospital based”.

Allagh et al, PLoS One. 2015; 10(3): e0118961.

CVD

X

Vegetarians and B12?

Other Factors Influencing Folate Metabolism

Efficient folate metabolism requires other B vitamins

• vitamin B12

• vitamin B6

• riboflavin

Folate metabolism is affected by• alcohol – inhibits folate absorption• smoking – may impair folate utilisation

Health Canada: Folic Acid

What is India Doing?• Weekly iron folic acid supplementation (WIFS) to

reduce the prevalence and severity of anaemia in adolescent population (10-19 years).

• School going adolescent girls and boys in 6th to 12th class enrolled in government/government aided/municipal schools. Out of school adolescent girls.

• Administration of supervised weekly iron-folic acid supplements of 100mg elemental iron and 500ug folic acid using a fixed day approach.

• Screening of target groups for moderate/severe anaemia and referring these cases to an appropriate health facility. http://nrhm.gov.in/

Oct19, 2015Hindustan Times

Sources of Folate

Health Canada

Things to ask your patient….

• Is your patient’s diet sufficient in folic acid, especially that of pregnant women

Nutritional Status in India

• Under nourished 380million

• Overnourished 80 million

• Calorie sufficient• /nutrient deficient 570 million

– 342 million consume higher than normal calories with high fat intake

– Sugar is another major issue

FICCI Ernest & Young Wellness Report 2009

WESTERNIZATION

A process whereby societies adopt Western culture in areas such as

industry, technology, politics, economics, lifestyle, diet, clothing, language, philosophy and values.

http://www.slate.com/

“If we could give every individual the right amount of nourishment and exercise, not too little and not too much, we would have found the safest way to health."

 

"Let food be thy medicine and medicine be thy food."

-Hippocrates c. 460 - 377 B.C.

“Pregnant women and nurturing mothers need to remember that they are eating not only for themselves but for the next generation”

3As to Improve Health Awareness:

Children/Parents/schools/communityDieticians and doctorsFitness centersMedia

Attitude: Disease prevention Availability and cost

Cheema S

Nutrition Research in India

• Recommendations are generally based on the North American/European population

• Recommendations need to be established for the Indian population – Genetic make up, environment and lifestyle is different

• Solid scientific data needs to be generated in India• Evidence based research is important to establish

proper guidelines and recommendations• The scientific body must be comprised of

scientists from nutrition, food science, medical practitioners, economists and policy makers

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Graduate Students PostDocs: Dr. John McGuire (MUN) Abeer Ahmed Dr. Y. K. Yamori (Japan)Koyode Balogun Alka Mawal Dr. Ramesh Goyal (India)Kanta Chechi Anura JayasureyaRaniru Randunu Hitesh VaidyaBrad Feltham Surendiran GangadharanAnthony Akerele

Technical Staff Sophie GagnonSuresh BelkhodeAdam ByrneDanielle Gardiner

Several Honours and NSERC Summer Students

Acknowledgements

Sources of DHA • 3 oz salmon (Atlantic, farmed), cooked -

1238 mg • 3 oz salmon (sockeye, canned) - 750mg• 3 oz white tuna, canned in water - 535mg• 3 oz cod (Atlantic), cooked – 131mg• 6 large shrimp, steamed – 48mg• 1 omega-3 shell egg – 125mg

Disproportionate Size at Birth Is Implicated in Programming

Folate-mediated one-carbon metabolism is a conduit between the cellular nutrient environment and genome

synthesis and methylation________________________________________

Malnourishment In India• “120 million malnourished children across India who

depend on a government-run program serving lunch five days a week. Still, the modest menus are clearly not enough to make up for the calories and nutrition that poverty has denied…………..More than half the children in Madhya Pradesh state, with a population of nearly 77 million, are underweight and malnourished…………So last month, it was suggested that eggs — a key source of protein — be added to the lunch program. But that idea was rejected………….."

http://bigstory.ap.org/

© Sukhinder Cheema, St. John’s, NL

Icebergs Around St. John’s

Vitamin D Synthesis & Activation

Vitamin D2Vegetable sourcesSun-exposed mushroomsand yeast

UVB

Things to find out from your patient….

• What is the vitamin D status of your patient, especially pregnant and lactating women, and 50+ population?