Agenda

1. Agenda • Calendar • Research project presentation • Finish up Lipids • Lecture 9: Vitamins • Lecture outline • Vitamin Background • Fat soluble vitamins

2. Lipid Wrap up • Last time • Lipid Digestion and three main types of lipids • Lipoproteins – Vehicles for fat • Chylomicrons – carry exogenous fat • VLDL – Carry endogenous fat • LDL – transport cholesterol made by liver • HDL – pick up fat and cholesterol and take it back to liver for recyleing • Functions for the various types of lipids • Discussed Cardiovascular disease • Finish up with how to minimize CV disease risk

3. Risk Factors for Heart Disease • Total blood cholesterol >200mg/dL of blood • Especially high when over 240 mg/dL and LDL exceeds 130 mg/dL • Smoking • Increases risk of CV event by 20% • Hypertension – Systolic pressure over 139 ml of mercury and diastolic pressure over 89. • Diabetes – pretty much guarantees a CV event • Remember insulin ↑ cholesterol synthesis in the liver, thus elevating LDL

4. How to mitigate risk • QUIT SMOKING • Overhaul diet and lifestyle • Switch to low-fat diet • Increase exercise • Medications for more aggressive treatment • Statins – reduce liver production of cholesterol • ~$1600 annual • Bile binders/inhibitors – block the emulsifying effects of bile reducing the cholesterol consumed • Triglyceride production inhibitors – aim to reduce triglyceride production in the liver • Overall goal of therapy is to get blood LDL < 70mg/dL

5. Lecture 9 - Vitamins Will Brown 2/7/2012

6. Vitamins Background • Name derived from the words “Vital Amines” • Later shortened to vitamins • Two categories • Fat soluble – A, D, E, and K • Water Soluble – B vitamins and C • Considered “essential” because we are unable or have limited ability to synthesize them • Named as they were found: A, B, C, D, etc • Some turned out to be a collection of compounds • The B vitamins • Others found to not be “essential” and were dropped

7. Vitamins Background • All have disease associated with them when not enough in diet • Scurvy – vitamin C • Both plant and animal sources of vitamins • Supplements • If you are eating a well balanced diet, there is no need for supplements • There are toxic levels of vitamins; “little is good so more is better” mentality does not apply • Synthetic varieties have varying degrees of petency • Natural Vitamin E more potent • Synthetic folic acid (vitamin B9) more potent

8. Vitamins Background • Generally believed all essential vitamins are known • Vitamin storage – most do not stick around to long; they are used fairly quickly • Most fat soluble vitamins are longer lived in the body; not excreted in urine • Exception is vitamin K • Most water soluble vitamins are lost rapidly • Exceptions vitamins b-6 and B-12

9. Vitamins Background • Toxicity • All vitamins have toxic levels although very hard to achieve toxic levels with some • For a 160 lb man, need to eat ~2 kg of vitamin C • Fat soluble vitamins have lower toxic limits • Vitamin A begins at 2X RDA values • Preservation • Because they are organic compounds, vitamins breakdown • Heat, light, air, time from harvest • The fresher the better • Store in cool dry places • Freezing also protects and preserves vitamins

10. Fat soluble Vitamins • There are 4 fat soluble vitamins – A, D, E, and K • Absorbed in dietary fat • Pharmaceuticals that intervene in fat absorption also inhibit uptake of these vitamins • Carried in the bloodstream along with the fat • Stored in liver and to some degree in adipose tissue

11. Vitamin A • Narrow therapeutic range for vitamin A • Too little and you develop blindness • 1 in 3 children in developing countries • Too much you get liver damage • Especially with high levels of alcohol consumption • Comes in multiple forms • Retinoids – preformed vitamin A found in fish and organ meat • Carotenoids – provitamins that are converted to vitamin A • Only 3 (of the over 600) carotenoids can be used by people • Beta-carotene • Lutein • Zeaxanthin • Mainly found in dark green or yellow-orange fruits and veggies

12. REA=Retinal activity equivalents, takes into account preformed and provitamin forms.

13. Functions of Vitamin A • Vision • Critical for component of rhodopsin in eye-retinal • Night blindness is first sign of vitamin A deficiency • Also helps with mucus layer that protects the eye • Second leading cause of blindness world wide • Epithelium requires vitamin A for mucous production • Lower levels of protective mucous in lungs and intestines increases risk of infection

14. Functions of Vitamin A • Retinoic acid form is critical in gene transcription • Specialized nuclear receptors specifically for retinoic acid • Act as antioxidants • May help prevent cardiovascular disease • Lycopene (vitamin A form found in tomatoes) shown to reduce prostate cancer risk • Used in acne medication • Retin-A is topical form • Accutane is oral form but has restricted use because it is teratogenic

15. Vitamin D • Made of a cholesterol based substance 7-dehydrocholesterol • Unique in that it can be produced in the skin due to sun exposure (UVB) • Most common vitamin deficiency in northern climates during winter • Only need about 10 minutes of exposure for fair skinned individuals; the higher the melanin the more exposure is needed • Acts as a prohormone which is converted to active form in kidneys and liver • Toxicity of vitamin D only associated with supplements because the body regulates amount made in skin • Same symptoms as calcium toxicity: weakness, loss of appetite, diarrhea, vomiting, confusion, increased urine output, Ca+ deposits in kidney

16. Functions of Vitamin D • Primary function is to help regulate calcium • Nuclear receptor (VDR) activation leads to increased gene expression of calcium transport molecules in the intestine • VDR activation increases bone remodeling • Indicates why calcium supplements are not enough in osteoporosis patients • Rickets and osteomalacia caused/cured by vitamin D • Vitamin D production decreases with age • VDR activation also plays a role in neurons and in immune cells

17. Vitamin D Recommendations • RDA • 1–70 years of age: 600 IU/day (15 μg/day) • 71+ years of age: 800 IU/day (20 μg/day) • Pregnant/lactating: 600 IU/day (15 μg/day) • Upper intake levels • 0–6 months of age: 1,000 IU • 6–12 months of age: 1,500 IU • 1–3 years of age: 2,500 IU • 4–8 years of age: 3,000 IU • 9-71+ years of age: 4,000 IU • Pregnant/lactating: 4,000 IU

18. Vitamin E • Acts as a fat-soluble antioxidant • Helps to protect cell membranes from breaking down due to oxidization of the fatty acid chains in the phopholipids • One example is hemolysis of red blood cells is reduced with vitamin E • Despite many trials, no known benefit in supplementing vitamin E • Family of 8 molecules; 4 tocopherols and 4 tocotrienols • The book only mentions the tocopherols – they are a, b, g, d

19. Sources and Recommendations for Vitamin E • Primarily come from plant oils – gamma is the most common in plants • Other sources include nuts, seeds and eggs • RDA: 15 mg/day of a-tocopherol; the most common form in human body • Upper limit is 1000 mg/day due to the ability to interfere with vitamin K which leads to hemorrhage

20. Vitamin K • Consists of two primary forms K1 and K2 • No known toxicity for natural forms however synthetic form K3 does have toxicity • K1 is primary form from plant sources • K2 is produced by bacteria in the gut; ~10% of total vitamin K • The K comes from the Danish spelling of coagulation • Discovered by a Danish guy named Henrik Dam

21. Functions of Vitamin K • Involved in the carboxylation of glutamate residues which then can bind Ca+ ions • Found in 3 biological roles • Blood coagulation – all of the major clotting factors contain the glutamate residues • Bone metabolism – many of the proteins involved in calcium binding have the glutamate residues • Vascular biology – certain growth arrest proteins contain the glutamate residues

22. Water Soluble Vitamins • Soluble in water • Consist of the B family (and a related nutrient choline) and vitamin C • Rapidly excreted if taken in excess • Most are lost during food processing • Most B vitamins occur together so a lack of one indicates a lack of the others • B vitamins act as coemzymes– that is the act so that enzymes can function • Play key roles in metabolism of carbs, fats and amino acids • Needs increase as energy needs increase