Agenda

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

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

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

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

Lecture 9 - Vitamins

Will Brown2/7/2012

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

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

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

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

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

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

RAELife stage group

Adequate intakes (AI*)μg/day

Upper limitμg/day

Infants 0–6 months7–12 months 400*

500*600600

Children 1–3 years4–8 years 300

400600900

Males 9–13 years14–18 years19 – >70 years

600900900

170028003000

Females 9–13 years14–18 years19 – >70 years

600700700

170028003000

Pregnancy <19 years19 – >50 years 750

77028003000

Lactation <19 years19 – >50 years 1200

130028003000

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

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

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

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

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

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

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 gd

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

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

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

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