PRINCIPLES OF DISEASE

Lecture 13: Nutritional Diseases

Thomas J. Thekkumkara, Ph.D.

Reading Assignment

Robbins: Pathologic Basis of Disease, Saunders, Sixth Edition, 1999, Chapter 10, pp. 436-457.

Learning Objectives

At the end of this lecture, candidates should be able to:

• Understand the role of nutritional factors associated with human health and diseases
• Describe the difference between micro and macro nutrients
• Define Energy expenditure
• Know the Balance of nutritional components in the daily diet
• Describe the characteristics of Protein-Energy Malnutrition (PEM)

LECTURE OUTLINE

1. Food and Nutrition

Food - Necessary for life

Nutrition - Why do we care?

• Diet - Most Americans food intake and diet is not optimal
• Pharmacies - Sell an incredible array of vitamins, minerals and supplements
• Disease - There are many nutritional diseases and disorders Deficiencies, Obesity,
• Dieting disorders - Anorexia nervosa and bulimia

i) Macronutrients

• Carbohydrate/sugars - Energy and membrane constituents - Dietary carbohydrate is digested in the mouth and intestine and absorbed from the small intestine
• Amino acids - Energy, Building blocks of proteins - The synthesis of new proteins requires amino acids. The primary sources of amino acids is dietary protein. Breaking down of tissue proteins also provides amino acids.
• Fatty acids and Lipids - Energy and critical components of membranes and signaling pathways - Fat or triacylglycerol, major fuel store of the body. Padding to protect delicate tissues (eye, kidney) against trauma. Insulation against heat loss. Phospholipds are key components of biological membranes and of the lipoproteins that transport lipids in blood. Cholesterol key component of membrane

ii) Micronutrients

· Vitamins - (Fat-soluble and water soluble) Required cofactors in enzymatic pathways that we cannot form on our own

· Minerals - Na, K, Cl, K, Ca, Mg, Fe, Cu, Mn, etc.... - Fluid volume regulation and membrane excitability, Bone formation and remodeling, Key components of enzymes (hemoglobin)

· Water

Some nutrients are considered "dietary essential" - i.e., they are required in certain amounts for normal health and development, but we cannot form them on our own, so they must be provided in the diet.

• Essential amino acids - Examples: Phenylalanine, Leucine, Isoleucine, Methionine, Valine, Tryptophan, Threonine, Lysine, about half of the primary amino acids
• Essential fatty acids - Example: Long chain, polyunsaturated fatty acids

Components that we can synthesize or form on our own in adequate amounts are termed "dietary nonessential."

Both sets are necessary for life.

iii) Energy expenditure: (three components),

• The basal energy expenditure (resting energy expenditure), is the energy used for metabolic processes while at rest. It represents more than 69% of the total energy expenditure.
• The thermic effect of food, the energy required for digesting and absorbing food. It represents more than 10% of the total energy expenditure.
• The activity related expenditure, which varies with the level of physical activity. It represents more than 20-30% of the daily energy expenditure.

The critical components and building blocks of our body are constantly turning over and being renewed

· Endogenous synthesis

· Intake and incorporation from diet

· Turnover rates vary for different proteins and lipids and by function

o Structural components and many "housekeeping" enzymes –

§ Slower (Hours - days)

o Regulatory, responsive or signaling components –

§ More rapid (Minutes - hours)

· The same time other components, which are frequently harmful, are also present:

o Carcinogens

Safrole in nutmeg and parsley

Estragole - in basil and fennel

o Natural Pesticides – plants

o Microorganisms and their toxic products

o Toxicants formed by cooking or preservation

Oxidized fats

Pyrolysis products of amino acids

Polycyclic aromatic hydrocarbons

Nitrosamines

o Toxic metals - Lead, mercury, cadmium

o Food additives (Regulated by FDA)

v Direct - Added purposely to food (like chemical sweeteners, preservatives, food colors)

v Indirect - Get into food indirectly through packaging, contaminants, residues (pesticides) or from feeding to animals (hormones)

You are what you eat!

iv) Balance of components

Total intake of food "calories" - Normally 1000-2000 calories/day

v Carbohydrate (50-60% of the caloric intake)

v Fat (no more than 30% of the caloric intake)

v Protein - (10-20% of the caloric intake) Normally 0.8 g/day/kg

We (humans) do regulate total calorie intake and protein intake. However we do not regulate the fractional contribution of fats vs carbohydrates.

Food choice - Contributions of core components (protein, carbohydrate) and amounts (calories, protein) is highly regulated. We often choose our foods to meet these needs. We will avoid foods with imbalances of amino acids or that do not meet our core needs. Unfortunately, we do not regulate lipids!

Try to do it right. The long term consequences of what and how much you consume are significant. Habit is key.

2. Nutritional Deficiencies

There are very significant nutritional deficiencies in the United States and in the World.

v Primary deficiencies - Dietary intake of one or all of the critical components is inadequate.

v Secondary deficiencies or Conditional Malnutrition - The supply (intake) is adequate, but for one reason or another, they do not meet the needs of the person due to:

o Poor absorption

o Impaired utilization

o Excess loss

o Increased need

Reasons for Nutritional Deficiencies

v Poverty leads to poor dietary intake and hunger.

v Ignorance of basic nutrition and dietary needs also leads to problems even in affluent and financially impoverished groups.

v Alcoholism, both by consuming financial resources and creating dietary imbalances (deficiencies of vitamins - like thiamine) which can lead to permanent brain damage.

v Self imposed restrictions (dieting) and disease can create their own problems. For example, disease can impair physically food intake (vomiting, diarrhea), create anorexia (lack of desire to eat), and strong boost energy needs.

The National Research Council recommends daily allowances for protein, vitamins, and minerals for healthy adults, with separate categories for men and women.

3. Protein-Energy Malnutrition (PEM)

Characterized by low body weight, low fat stores, reduced plasma proteins.

There are two protein compartments of the body which are regulated differently

• Somatic - like brain, skeletal muscle
• Visceral - primarily visceral organs (GI tract and liver)

PEM - primarily seen in children. Loss of skeletal muscle and subcutaneous fat.

• Malnourished - Body weight less than 80% of normal
• Marasmus - Body weight less than 60% of normal is caused by starvation with insufficient intake of food, including both calories and protein.
• Kwashiorkor - Primarily protein malnutrition or protein deficiency greater than that of calorie deficiency. Severe loss of protein from the visceral compartment. Body weight loss can be masked by edema.
• Self imposed starvation - anorexia nervosa

4. Vitamin and Mineral Deficiencies

Thirteen vitamins are necessary for health.

• Four are fat soluble
• The remaining are water soluble.

Fat Soluble

• Vitamin A - Critical component of visual pigments
• Vitamin D - Facilitates intestinal calcium and phosphorous absorption and bone mineralization.
• Vitamin E - Major antioxidant and radical scavenger.
• Vitamin K - Cofactor in hepatic carboxylation of procoagulants. Deficiency causes bleeding disorders

Water Soluble

• Vitamin B1 (thiamine) - Required for pyrophosphate- a coenzyme for decaboxylation reactions
• Vitamin B2 (riboflavin) - Required for flavin nucleotides, cofactor for intermediary metabolism
• Niacin - Required for nicotinamide adenine nucleotides (e.g., NAD), cofactor in redox reactions
• Vitamin B6 (pyridoxine) - Required to form cofactor in reactions
• Vitamin B12 - Required for folate metabolism and DNA synthesis
• Vitamin C - Serves in many oxidation-reduction reactions
• Folic acid - Essential cofactor for nucleic acid synthesis
• Pantothenic acid - Incorporated into Coenzyme A