Nutraceuticals’ Role in Metabolic and Cardiovascular Disease Prevention and Treatment

#1 - Niacin: Re-emergence of an Old Player and Gatekeeper of Emerging Metabolic Pathways and Therapeutic Interventions.

I. Background

1. What are nutraceuticals?

a. Brief historical perspective of the use of nutraceuticals
b. Nutraceutical/Functional Foods vs. pharmaceuticals: Current definitions
c. Table to demonstrate a list of nutraceuticals and show cumulative % effects on triglycerides (as example)

2. Vitamin vs. pharmacological properties of niacin

a. Vitamin – Pellagra
b. Pharmacological

i. First agent used to treat cholesterol in humans (1955)

3. Forms of Niacin

a. Over-the-counter

i. Immediate release
ii. Sustained release
iii. Extended release

b. Prescription formulations

4. Adverse effects

a. Flushing – Niacin receptor activation
b. GI
c. Fatigue

II. Basic Science

1. Signaling events that regulate the breakdown of lipids within fat cells
2. Target tissues

a. Adipose tissue

i. Lipolytic response to niacin

b. Liver

i. Emerging evidence

3. Effects of niacin on blood lipid metabolism

a. Primary effects on HDL-C and triglycerides
b. Effects on LDL-C

4. Emerging effects of niacin beyond lipid metabolism

III. Clinical Research/Applications

1. Clinical Trials

a. Classic and emerging evidence for niacin
b. Effects on morbidity and mortality

i. Decrease non-fatal MI and cardiac death

2. Other nutraceutical and pharmacologicals being developed

a. Adiopose tissue receptor agonists
b. Combination nutraceutical/pharmaceutical therapies
c. Combination with aerobic exercise

Behavioral/Learning Objectives:

1. Describe the various formulations of niacin and describe adverse effects associated with niacin.
2. Describe the proposed mechanisms by which niacin works in its target tissues.
3. Explain the non-lipid lowering effects of niacin and the potential contribution to cardiovascular disease risk reduction.
   

#2 - Omega-3 Fatty Acids (n-3 FA)

I. Background

1. Brief historical perspective on the use of omega-3-fatty acids (n-3 FA)

a. Basic structural and functional differences of n-3 FAs and other unsaturated and saturated fatty acids
b. Sources

i. Coldwater fish

1. Best sources
2. Concerns of cadmium and mercury poisoning

ii. Botanicals: flaxseed, pecans, walnuts, kiwifruit
iii. Formulations

1. Over-the-counter
2. Prescription formulations

2. Ideal “Dosages”

II. Basic Research

1. Role in lipid metabolism

a. Inhibition of key lipogenic enzymes
b. Activation of key fatty acid oxidation enzymes

2. Role in glucose metabolism

a. Insulin sensitivity using clamps or more basic measures support improved insulin action

III. Clinical Research/Applications

1. Longitudinal studies in humans

a. What do we know?

2. Effects on blood lipids and adipokines
3. Combination with other nutraceutical/pharmaceutical compounds
4. Combination with exercise and other compounds

Behavioral/Learning Objectives:

1. Explain the differences in effects of saturated and polyunsaturated fats on lipid synthesis and metabolism.
2. Describe the potential mechanisms by which n-3 fatty acids reduce lipid synthesis in the liver and adipose tissue.
3. Explain the fasting and postprandial effects of n-3 fatty acids on blood lipids and examine the development of new formulations.
   

#3 - Plant Stanol/Sterol Esters

I. Background

1. Brief historical perspective of plant stanol/sterol ester use

a. Sources: Primarily from pine bark, rapeseed oil and soya oil
b. Purchased commercially in products such as margarine and yogurt

2. Structural differences between stanols and sterols and comparison to cholesterol

a. Structure
b. Absorption
c. Competition for absorption
d. Efficacy of stanols and sterols

3. Dosage

a. Feasibility
b. Future product directions

4. Adverse Effects

II. Basic Sciences

a. Effects related to the exclusion of animal cholesterol from intestinal absorption
b. Sterols possible effects on feeding behavior

III. Clinical Research/Applications

a. Clinical Studies involving LDL-C levels
b. No effects on Bile acid markers

Behavioral/Learning Objectives:

1. Identify the structural differences between stanol and sterol esters.
2. Describe the functional differences between stanol/sterol esters and provide the rationale for their use as part of a cholesterol-lowering strategy.
3. Explain the future of plant stanol esters and their role in the modulation of food intake.
   

#4 - Resveratrol

I. Background

1. Mediterranean diets
2. Plant sources
3. Formulations

a. Over-the counter and prescription capsules
b. Amounts found in other sources

4. Dosage
5. Adverse effects

II. Basic Science

1. Model of longevity

i. Structure of resveratrol
ii. Effects in rodents and human studies
iii. Effects on blood glucose, fatty acid oxidation, insulin sensitivity and longevity

III. Clinical Research/Applications

1. Ongoing clinical trials from cancer prevention to Alzheimer’s prevention
2. Improvements in LDL-C, insulin sensitivity, and possbile tumor suppression make for exciting possibilities.

Behavioral/Learning Objectives:

1. Identify the optimal sources of resveratrol and the confluence of other antioxidant compounds in red wine and other sources.
2. Provide support for a dose-dependent effect of resveratrol on oxidative metabolism and free-radical production.
3. Describe the role of resveratrol as an effector of sirtuans (genes that effect ageing) and its impact on quality of life and lifespan.
   

#5 - Soy Isoflavones

I. Background

1. Most prominent producers
2. Brief description of the different varieties of soy
3. Nutrient components of the soybean
4. Dosage and formulations – dietary intake and supplements
5. Structure and function of isoflavones

II. Basic Science

1. Studies on Isolfavones effect on adipogenesis and lipogenesis
2. Other studies indicating increased insulin stimulated glucose uptake and increased glucose and lipid oxidation.

III. Clinical Research/Applications

1. Benefits versus adverse effects: what we know
2. What we can learn from the vegan diet
3. Smaller clinical trials are inconclusive regarding safety (large trials underway)

Behavioral/Learning Objectives:

1. Describe the evidence for benefits and potential risks of soy isoflavones – Are they beneficial or risky?
2. Describe the impact of phytoestrogens in infant formula and other soy products – Are there future beneficial and potentially dangerous consequences?
3. Identify the mechanisms by which isoflavones regulate energy balance and metabolism and how these benefits may outweigh some of the reported adverse effects of soy isoflavones.

#6 - Cinnamon

I. Background

1. Brief history of cinnamon use

a. Primarily found in Vietnam and Sri Lanka
b. Differences between Cassia and Ceylon varieties of cinnamon and the therapeutic efficacy of both varieties

2. Methods of consumption

a. Traditional methods
b. Supplements

3. Dosages
4. Adverse Effects

II. Basic Science

a. Mechanisms of action
b. Effects on insulin receptors
c. Inhibit advanced glycation end products
d. Decreases blood pressure, free fatty acids, LDL-C, triglycerides, anti-oxidant effects.

III. Clinical Reseach/Applications

a. Cinnamon effectiveness in individuals with diabetes
b. Directions for future product development and use

Behavioral/Learning Objectives:

1. Characterize the different varieties of cinnamon and the detection of health-related benefits in regions where cinnamon is grown.
2. Describe the role of cinnamon-derived polyphenolic compounds and their role in diabetes prevention.
3. Describe the possible effects of polyphenols on glucose metabolism and provide insight into the future directions for “packaging” cinnamon to increase awareness and delivery.
   

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