The Fat-Soluble Vitamins: A, D, E, and K Chapter 11.

The Fat-Soluble The Fat-Soluble Vitamins: A, D, E, and Vitamins: A, D, E, and

KKChapter 11

IntroductionIntroduction

How fat-soluble vitamins differ from water-soluble vitamins Require bile for digestion and absorption Travel through lymphatic system Many require transport proteins in

bloodstream Excesses are stored in liver and adipose Risk of toxicity is greater RDA over time is what matters

Vitamin A and Beta-CaroteneVitamin A and Beta-Carotene

Vitamin A, 1st fat-soluble vitamin studied Precursor – beta-carotene, also a

pigment Absorption and conversion

Beta-caroteneThree main active forms (retinoids) retinol, retinal, and retinoic acid

Conversion to other active forms

Retinol, the alcohol form Retinal, the aldehyde form Retinoic acid, the acid form

Cleavage at this point can yield two molecules of vitamin A*

*Sometimes cleavage occurs at other points as well, so that one molecule of beta-carotene may yield only one molecule of vitamin A. Furthermore, not all beta-carotene is converted to vitamin A, and absorption of beta-carotene is not as efficient as that of vitamin A. For these reasons, 12 μg of beta-carotene are equivalent to 1 μg of vitamin A. Conversion of other carotenoids to vitamin A is even less efficient.

Beta-carotene, a precursor

Conversion of Conversion of ββ-carotene-caroteneto Vitamin Ato Vitamin A

Vitamin A and Vitamin A and ββ-Carotene-Carotene Digestion and absorption of vitamin A

SI to lymphatic system Lymphatic system to liver Storage in liver Retinol-binding protein (RBP)

for transport in serum Cells that use vitamin A have receptors

that dictate its job in that cell

Vitamin A and Vitamin A and ββ-Carotene -Carotene Roles in the BodyRoles in the Body

Regulation of gene expression Major roles

VisionProtein synthesis and cell

differentiationReproduction and growth


Retinol Supports reproduction Major transport and storage form

Retinal Active in vision

Retinoic acid Regulates cell differentiation, growth, and

embryonic development

Retinyl esters (in animal foods)

Beta–carotene (in plant foods)IN FOODS:

Retinol (supports reproduction)

Retinal (participates in vision)

Retinoic acid (regulates growth)

IN THE BODY:

Conversion of Vitamin A CompoundsConversion of Vitamin A Compounds


Vision Cornea maintenance Retina

Photosensitive cellsRhodopsin (remember opsin?)

Repeated small losses of retinalNeed for replenishment due to oxidation from visual activity

Vitamin A’s Role in VisionVitamin A’s Role in Vision

As light enters the eye, rhodopsin within the cells of the retina absorbs the light.

Retina cells (rods and cones)Light energy

Cornea

Eye Nerve impulses to the brain

The cells of the retina contain rhodopsin, a molecule composed of opsin (a protein) and cis-retinal (vitamin A).

cis-Retinal trans-Retinal

As rhodopsin absorbs light, retinal changes from cis to trans, which triggers a nerve impulse that carries visual information to the brain.


Protein synthesis & cell differentiation Epithelial cells on all body surfaces

SkinMucous membranes (Linings)

–Ex: GI lumen lining

–Ex: Respiratory tract liningsGoblet cells (secrete mucous)

Mucous Membrane IntegrityMucous Membrane Integrity

Vitamin A maintains healthy cells in the mucous membranes.

Without vitamin A, the normal structure and function of the cells in the mucous membranes are impaired.

Mucus Goblet cells

Vitamin A (retinol) and Vitamin A (retinol) and ββ--Carotene Carotene

Roles in the BodyRoles in the Body Reproduction and growth

Sperm development Normal fetal development Growth of children

Weight and HeightBone remodeling

Antioxidant, cancer protection Beta-carotene, not Vitamin A

Vitamin A DeficiencyVitamin A Deficiency

Def. symptoms can take 1-2 yrs to appear for adult, much sooner for growing child

Vitamin A status depends onAdequacy of stores, 90% in liverProtein status for RBP mfg.

Consequences of deficiency Risk of infectious diseases Blindness Death

Vitamin A DeficiencyVitamin A Deficiency

Infectious diseases Measles, pneumonia, diarrhea Malaria, lung diseases/infections, HIV- AIDS

Night blindness Inadequate supply of retinal to retina

Blindness (xerophthalmia) Lack of vitamin A at the cornea Develops in stages

Vitamin A DeficiencyVitamin A Deficiency Keratin- hard, insoluble hair & nail protein Keratinization Change in shape & size of epithelial cells due

to accumulation of keratinSkin becomes dry, rough, and scalyFewer and less active goblet cells, so normal

digestion and absorption of nutrients from GI tract falters

Weakened defenses in epithelial cells of respiratory tract, vagina, inner ear, and urinary tract

Vitamin AVitamin A Toxicity Toxicity

Develops when binding proteins are swamped Free vitamin A damages cells

Toxicity is a real possibility Preformed vitamin A from animal sources Fortified foods Supplements

Children are most vulnerable

ββ-Carotene Overload-Carotene Overload

β-carotene Found in many excellent fruits and vegetables Excess cannot evolve to Vitamin A toxicity Overconsumption from food harmless

β-carotene storage in fat under skin Overconsumption from supplements risky

Antioxidant becomes prooxidant, promotes cell division, destroys Vitamin A

Most adverse effects for those with heavy EtOH and tobacco use

Vitamin A Toxicity Vitamin A Toxicity (Hypervitaminosis A)(Hypervitaminosis A)

Bone defects May weaken bones

OsteoporosisOverstimulation of osteoclasts

Interferes with vitamin D and serum calcium Birth defects

Cell death in the spinal cord with >10,000 IU/d before 7th week

Vitamin A relatives prescribed for Acne Accutane, topical Retin-A

Accutane Side EffectsAccutane Side Effects Ulcerative colitis Crohn’s Disease, Inflammatory Bowel Disease Severe depression, suicidal thoughts Birth defects Liver damage, with nausea, loss of appetite,

weight loss, and jaundice Allergic reaction to isotretinoin, resulting in

liver disease and other health complications

Vitamin A and Beta-Vitamin A and Beta-Carotene Carotene

Recommendations Expressed as retinol activity equivalents

(RAE) 1 RAE =

1 µg. retinol12 µg. β-carotene3.33 international units (IU’s)

Supplements often measured in International Units (IU)

Vitamin A and Vitamin A and ββ-Carotene -Carotene

Food sources Animal sources for Vitamin A

Liver (1 oz = 3x RDA), dairy fat, eggs Plant sources for β-Carotene

Vitamin A precursorsBioavailability with fat in the same mealDark green and bright orange fruits and

vegetables

ββ-rich Fruits & Vegetables-rich Fruits & Vegetables FRUITS

Apricots, Cantaloupe, Peaches, Persimmon, Mango, Papaya, Purple(on the inside) plums, Watermelon

VEGETABLES Beet greens, Bok Choi, Broccoli, Carrots

Collards, Dandelion Greens, Kale, Mustard Greens, Pumpkin, Spinach, Sweet Potatoes, Yams, Winter Squash

Bold italics mean also C-rich

Vitamin A / Vitamin A / ββ-carotene in -carotene in FoodsFoods

Vitamin D- calciferolVitamin D- calciferol Not an essential nutrient

Body synthesizes SunlightPrecursor from cholesterol

Activation of vitamin D Two hydroxylation reactions

Liver adds OH-

Kidneys add OH-

Vitamin D Synthesis and Vitamin D Synthesis and ActivationActivation

1,25-dihydroxy vitamin D3 (active form) Stepped Art

In the liver:

Ultraviolet light from the sun

In the kidneys:

Vitamin D3 (an inactive form)

Hydroxylation

Foods(ergocalciferol from plants and cholecalciferol from animals)

In the skin: 7-dehydrocholesterol

(a precursor made in the liver from cholesterol)

Previtamin D3

25-hydroxy vitamin D3

Hydroxylation

Vitamin D Roles in the BodyVitamin D Roles in the Body

Active form of vitamin D is a hormone Binding protein carries it to target organs

Ca / P absorption to maintain serum levels Bone growth Ca, Mg, P, Fl absorption preferably from GI Bones resorbed to maintain serum levels

Parathyroid hormone, calcitonin, calbindin

Other roles Enhances or suppresses gene activity

Vitamin D DeficiencyVitamin D Deficiency

Overt deficiency signs are relatively rare Insufficiency is quite common

Contributory factors Dark skin, breastfeeding without

supplementation, lack of sunlight, not using fortified milk

D deficiency → less calbindin transp. prot.→ low calcium absorption → calcium deficiency→ rob the bones for calcium

Vitamin D DeficiencyVitamin D Deficiency

Rickets in children Prevalence >50% Mongolia, Tibet, Netherlands

Bones fail to calcify normally, bend when supporting weight

Beaded ribs Osteomalacia (adult rickets)

Poor mineralization of bones Bones are soft, flexible, brittle, and deformed

Fontanel A fontanel is an open space in the top of a baby’s skull before the bones have grown together. In rickets, closing of the fontanel is delayed.

Anterior fontanel normally closes by the end of the second year.

Posterior fontanel normally closes by the end of the first year.

Vitamin D DeficiencyVitamin D Deficiency Osteoporosis

Loss of calcium from bonesReduced density results in fractures

Elderly Vitamin D deficiency is especially likely

Skin, liver, kidneys lose ability to make and activate vitamin D

Drink less milkToo much time indoors, sunscreen outdoorsDrugs that deplete Vitamin D

http://www.umm.edu/altmed/articles/vitamin-d-000724.htm

Vitamin D Deficiency Vitamin D Deficiency Contributes to OsteoporosisContributes to Osteoporosis

Bone metabolism is influenced by many factors, including vitamin D levels, hormones, genetics, your body weight and your activity levels. Osteoporosis, meaning "porous bones," results from a relative lack of osteoblast activity in comparison to osteoclast activity. Over time, this imbalance leads to a decrease in bone density with a concurrent rise in fracture risk. In adults, vitamin D deficiency leads to a reduction in osteoblast activity, thereby decreasing the rate of bone construction.

National Academy of Science National Academy of Science Vitamin D RecommendationsVitamin D Recommendations

In response to concerns that Americans are consuming too little vitamin D, the National Academy of Sciences reviewed its recommendations and offered new guidelines in November 2010. According to the NAS, adults up to age 70 need no more than 600 IU of vitamin D daily to maintain health, and those over 70 need no more than 800 IU. However, many experts, including those at the University of Miami Miller School of Medicine and the University of Toronto, believe that even these recommendations are too low for most age groups and that all elderly adults should receive at least 2,000 IU of vitamin D daily.

Considerations and Considerations and RecommendationsRecommendations

Many of vitamin D's functions, including its influences on immune function and glucose and lipid metabolism, are just beginning to come to light. As new discoveries unfold -- including advances in osteoporosis research – National Academy of Science dietary guidelines for vitamin D may change. Current guidelines reflect an upward adjustment from those devised in 1997, but some researchers still feel these recommendations are inadequate.

Considerations and Considerations and RecommendationsRecommendations

If you are an adult under age 70 who wishes to prevent osteoporosis, your daily vitamin D-3 intake should be at least 600 IU, and if you are older than 70, 800 IU. Consult your physician about the vitamin D-3 dosage that is best for you.

Vitamin D ToxicityVitamin D Toxicity

Most likely of vitamins to have toxic effects Toxicity raises blood calcium concentrations

Forms stones in soft tissues, esp. kidneys May harden blood vessels

Skin Exposure is Skin Exposure is what it takes what it takes to make Vitamin Dto make Vitamin D

What’s the point?

↑

Vitamin D SourcesVitamin D Sources

Few food sources Oily (fishy-tasting) fish and egg yolks Fortified milk

Sun exposure for 10-20 min (not 2 hrs) per day Dark skin or SPF >8 reduces D synthesis No risk of D toxicity from too much sun Latitude, season, time of day, Overcast, smog, fog

Vitamin D Synthesis and Vitamin D Synthesis and LatitudeLatitude

Free RadicalsFree Radicals

Free Radicals and DiseaseFree Radicals and Disease

Free radical damage Contribute to cell damage, disease

progression, and agingPolyunsaturated fatty acids in lipoproteins

and membranesAlter DNA, RNA, and proteins Illicit inflammatory response

Free RadicalsFree Radicals

Free radical

Free radical

Free radical

Polyunsaturated fatty acids

DNA and RNA Proteins

Lipid radicalsAltered DNA

and RNAAltered proteins

Absence of specific proteins Excess of specific proteins

Impaired cell function Inflammatory response

Cell damage Diseases

Aging

Free Radical Chain ReactionFree Radical Chain Reaction


Free radical Compound with one or more unpaired

electronsLook to steal electron from vulnerable

compoundElectron-snatching chain reaction

Free radical production Degrades or detours normal bodily functions Environmental factors

Vitamin E as Antioxidant

BHA and BHT are synthetic analogues of vitamin E and operate by reducing oxygen radicals and interrupting the propagation

of oxidation processes.

PreservativPreservativeses


Body has natural defenses and repair systems Vit. C, β-carotene,

Zn, Se, Mn, Cu Not 100 percent

effective Less effective with

age

Oxidative stress Cognition Cancer Heart disease Arthritis and cataracts Diabetes Skin Lungs Accelerates aging

Vitamin EVitamin E Four different tocopherol compounds

Alpha, beta, gamma, and delta Only alpha-tocopherol has vitamin E activity

in the body Antioxidant

Stop chain reaction of free radicalsProtect cells and their membranesHeart disease and cancer

Defending Against Free Defending Against Free Radicals Radicals

System of enzymes against oxidants Copper, selenium, manganese, and zinc

Antioxidant vitamins Vitamin E

Defends body lipids Beta-carotene

Defends lipid membranes Vitamin C

Protects other tissues

How Antioxidants defend the How Antioxidants defend the body against cancer and CHDbody against cancer and CHD

Limit free radical formation Neutralize(destroy) free radicals or

their precursors Stimulate antioxidant enzyme activity Repair oxidative damage Stimulate repair enzyme activity Support healthy immune system

Defending Against Heart Defending Against Heart DiseaseDisease

Oxidized LDL fills “foam cells” Accelerate formation of artery-clogging

plaques Additional changes in arterial walls

Vitamin E protection Supplements

Risk of supplement use by those who already have heart disease

Defending Against Defending Against CancerCancer

Damage to cellular DNA Antioxidants may protect DNA from this

damage Inverse relationship with vegetable intake Positive relationship with beef and pork

intake Vitamin C as a prooxidant

Destruction of cancer cells Vitamin E

Vitamin E Deficiency Vitamin E Deficiency

Primary deficiency is rare Secondary deficiency

Fat malabsorption, totally fat-free diet Effects of deficiency

Red blood cells break openErythrocyte hemolysis

Neuromuscular dysfunction Other conditions and vitamin E treatment

Vitamin E Toxicity Vitamin E Toxicity

Liver regulates vitamin E concentrations despite intake

Toxicity is rare UL is 65 times greater than recommended

intake for adults Extremely high doses of vitamin E

May interfere with vitamin K activityThin the blood, increase hemorrhage risk

Vitamin E Vitamin E Recommendations & FoodsRecommendations & Foods

RDA is based on alpha-tocopherol only U.S. intakes tend to fall short of

recommendations Higher requirements for smokers

Widespread in foods Destroyed by heat processing and oxidation

Vitamin E in FoodsVitamin E in Foods

Foods, Supplements, or Both?Foods, Supplements, or Both?

Must replenish dietary antioxidants regularly Foods

Antioxidants and other valuable nutrientsAntioxidant actions of fruits and vegetables are

greater than their nutrients alone Supplements

Contents, bioavailabilityProcessing

Physiological levels vs. pharmacological dose

The Bottom Line on Antioxidants The Bottom Line on Antioxidants and Disease Prevention (HSPH)and Disease Prevention (HSPH)

Free radicals contribute to chronic diseases from cancer to heart disease and Alzheimer's disease to vision loss. This doesn't automatically mean that substances with antioxidant properties will fix the problem, especially not when they are taken out of their natural context. The studies so far are inconclusive, but generally don't provide strong evidence that antioxidant supplements have a substantial impact on disease. But keep in mind that most of the trials conducted up to now have had fundamental limitations due to their relatively short duration and having been conducted in persons with existing disease.

The Bottom Line on Antioxidants The Bottom Line on Antioxidants and Disease Prevention (HSPH)and Disease Prevention (HSPH)

That a benefit of beta-carotene on cognitive function was seen in the Physicians' Health Follow-up Study only after 18 years of follow-up is sobering, since no other trial has continued for so long. At the same time, abundant evidence suggests that eating whole fruits, vegetables, and whole grains—all rich in networks of antioxidants and their helper molecules—provides protection against many of these scourges of aging.

Vitamin KVitamin K

Can be obtained from non-food source Bacteria in the GI tract synthesize K

Acts primarily in blood clotting K is essential for activating prothrombin

Metabolism of bone proteins Osteocalcin binds to bone minerals

Low bone density w/out Vit. K and osteocalcin

Misc. proteins needing vitamin K in the body

Calcium and thromboplastin (a phospholipid) from blood platelets

Fibrinogen (a soluble protein)

Vitamin K

Several precursors earlier in the series depend on vitamin K

Prothrombin (an inactive protein)

Thrombin (an active enzyme)

Fibrin (a solid clot)

Blood-Clotting ProcessBlood-Clotting Process

Vitamin K DeficiencyVitamin K Deficiency

Primary deficiency is rare Secondary deficiency

Fat absorption falters Antibx drugs disrupt vitamin K’s synthesis Anticoagulants have opposite action

Newborn infants Sterile intestinal tract

Single dose of vitamin K given at birth

Vitamin K Toxicity Vitamin K Toxicity

Not common No adverse effects with high intakes

No UL Irregular High doses can reduce

effectiveness of anticoagulant drugs, ie. Coumadin

"Vitamin K" by Elson M. Haas "Vitamin K" by Elson M. Haas M.D.M.D.

"It is important for the production of many nutrients that we keep our "friendly" colon bacteria active and doing their job; to aid this process we should minimize our use of oral antibiotics, avoid excess sugars and processed foods, and occasionally evaluate and treat any abnormal organisms interfering in our colon, such as yeasts or parasites."

"Yogurt, kefir, and acidophilus milk may help to increase the functioning of the intestinal bacterial flora and therefore contribute to vitamin K production."

How much vitamin K can I How much vitamin K can I have each day while on have each day while on

coumadin?coumadin? Rather than focus on how much vitamin K you should eat, experts say it is more important to keep your vitamin K intake consistent from day to day and not to have drastic changes in amounts of vitamin K-rich foods. For example, if you eat 3 cups of a high-vitamin K food like spinach one day and none the next, this can affect the way your Coumadin works. American Dietetic Association Nutrition Care Manual

Vitamin K – Sources Vitamin K – Sources

GI tract Half of person’s need Stored in liver

Food sources Green vegetables Vegetable oils

Vitamin K

Foods

The Fat-Soluble Vitamins The Fat-Soluble Vitamins – In Summary– In Summary

Toxicities are possible Function of fat-soluble vitamins together

Vitamins E and AOxidation, absorption, and storage

Vitamins A, D, and KBone growth and remodeling

Vitamins E and KBlood clotting

The Fat-Soluble Vitamins: A, D, E, and K Chapter 11.

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Transcript of The Fat-Soluble Vitamins: A, D, E, and K Chapter 11.