Fat Soluble Vitamins (A, D, E, and K) - Lecture Notes

Chapter 1 Lecture 11: Fat Soluble Vitamins (A, D, E, and K)

Instructors

• Dr. Kanita Kunaratnam
  • Available by appointment at Building 31, Level 4 (JO)
  • Email: k.kunaratnam@ecu.edu.au
• Sarah Goodwin
  • Available by appointment at Building 5.103 (South West Campus)
  • Email: s.goodwin@ecu.edu.au

Recap of Previous Knowledge

• Deficiency diseases:
  • Riboflavin: Ariboflavinosis
  • Niacin: Pellagra
  • Thiamin: Beriberi
• Vitamin B12 is needed to activate folate.
• Both folate and vitamin B12 are water-soluble vitamins, and their coenzymes are essential for DNA synthesis.

Folate Activation

• Folate naturally occurs as polyglutamate in foods but as monoglutamate in fortified foods and supplements.
• In the intestine, digestion breaks glutamates off and adds a methyl group. Folate is absorbed and delivered to cells.
• In cells, folate is trapped in its inactive form.
• Vitamin B12 removes and keeps the methyl group to activate folate, which in turn activates vitamin B12.
• Both folate and vitamin B12 coenzymes are then active and available for DNA synthesis.

Learning Outcomes

1. Describe the functions of fat-soluble vitamins in the body and relate recommended intakes to food sources, bioavailability, and toxicity levels.
2. Identify requirements and upper levels of intake for fat-soluble vitamins.
3. Identify deficiency symptoms and diseases associated with fat-soluble vitamins.

Table Overview

The table will contain the following information:

• Vitamin/Alternate Name(s)
• RDI (Recommended Daily Intake) or AI (Adequate Intake) & UL (Upper Limit)
• Function
• Interaction
• Food Sources/Fortification/Supplementation
• Food Preparation for Vitamin Retention
• Deficiency Symptoms/Disease
• Toxicity Symptoms/Disease

Water-Soluble vs. Fat-Soluble Vitamins

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

• The function of fat-soluble vitamins depends on the presence of other fat-soluble vitamins.
• There are many interactions of fat-soluble vitamins with minerals.
• Can be stored in the liver and adipose tissue.
• Greater risk of toxicity.
• A generally healthy diet provides adequate intake.

Vitamin A

• Names: Retinol, retinal, retinoic acid.
• Precursor: Beta(β)-Carotene (provitamin).

β-Carotene to Vitamin A Conversion

• β-Carotene conversion to Vitamin A may only yield one molecule of Vitamin A.
• Not all β-Carotene is converted to Vitamin A.
• Absorption of β-Carotene is less efficient than that of Vitamin A.
• $6 \mu g$ β-Carotene is equivalent to $1 \mu g$ of Vitamin A.

Vitamin A - Functional Roles

• Vision, healthy epithelial cells, growth.
  • RDI:
    • Men: $900 \mu g$ RE/day
    • Women: $700 \mu g$ RE/day
  • Vitamin A deficiency is a major health problem worldwide.
  • Upper level for adults: $3000 \mu g$ RE/day.
  • Status depends on liver stores (90% in the liver) and protein status (Retinol Binding Protein transports Vit A in the blood).

Vitamin A - Vision

Two chief roles:

• Helps maintain a crystal-clear cornea.
• Participates in the conversion of light energy into nerve impulses in the retina.

Process of Vision

• As light enters the eye, rhodopsin within the cells of the retina absorbs the light.
• The cells of the retina contain rhodopsin, a molecule composed of opsin (a protein) and cis-retinal (vitamin A).
• As rhodopsin absorbs light, retinal changes from cis to trans, which triggers a nerve impulse that carries visual information to the brain.

Vitamin A - Protein Synthesis & Cell Division

• In cells lining the body’s surface, Vitamin A participates in protein synthesis and cell differentiation.
  • Epithelial tissue (skin & mucous membranes):
    • Skin: Vitamin A helps protect it against damage from sunlight.
    • Mucous membrane integrity: It helps differentiate epithelial cells and goblet cells (which secrete mucous). Otherwise, mucous membranes become impaired.
    • Mucus membranes include the lining of the lungs, GIT, uterus and vagina, bladder and urethra, eyelids, sinuses, etc.

Vitamin A - Reproduction and Growth

• Men: Retinol participates in sperm development.
• Women: Vitamin A supports normal fetal development during pregnancy.
• Children lacking vitamin A fail to grow, impacting bone development.

Vitamin A Deficiency

• Deficiency disease = Hypovitaminosis A
  • Impaired immunity and susceptibility to infectious diseases.
  • Night blindness.
  • Blindness (Xerophthalmia).
  • Keratinization: changes in epithelial cells result in keratinization, rough, dry, and scaly skin.

Vitamin A Toxicity

• Toxicity disease = Hypervitaminosis A.
  • Chronic toxicity symptoms: liver abnormalities, weakened bones contributing to osteoporosis, cause birth defects.
  • Acute toxicity symptoms: blurred vision, nausea, vomiting, vertigo, headaches, and pressure in the skull.
  • Vitamin A toxicity can occur with concentrated amounts of preformed vitamin A (not Beta-carotene) from animal foods, fortified foods, or supplements.

Vitamin A - Food Sources

• Excellent sources: Beef liver, sweet potatoes, mango
• Dark green and deep orange vegetables and fruits, and fortified foods such as milk contribute large quantities of vitamin A
• Some foods are rich enough in vitamin A to provide the RDA and more in a single serving

Vitamin D (Calciferol)

• The body can synthesize it with help from the sun from a precursor that the body makes from cholesterol.
  • Adequate Intake (AI):
    • $5 \mu g$/day for adults 19–50 years old.
    • $10 \mu g$/day for adults 51–70 years old.
    • $15 \mu g$/day for adults older than 70 years of age.
  • Upper Level of Intake for Adults: $80 \mu g$/day

Vitamin D: Synthesis & Activation

• Acts like a hormone.
• Plant version - vitamin D2 or ergocalciferol.
• Animal version - vitamin D3 or cholecalciferol.
• With UV rays, the precursor in the skin is also converted to D3.
• Activation occurs through the action of the liver and the kidneys.
  • $1,25$-dihydroxycholecalciferol (or calcitriol).

Vitamin D in the Body - Bone

• Member of the bone-making team:
  • Vitamin A, C, K, hormones (parathyroid & calcitonin), collagen (protein), and minerals Ca, P, Mg.
• Vitamin D’s main role: maintain blood levels of Ca and P.
  • How?
    • Enhancing GIT absorption.
    • Enhances reabsorption from kidneys.
    • Enhances mobilization from bones into the blood.
• Bones can grow denser and stronger as they absorb & deposit these minerals from the blood

Vitamin D in the Body – Other

• Other Vitamin D target tissues:
  • Immune system
  • Brain and nervous system
  • Pancreas
  • Skin
  • Muscles
  • Cartilage
  • Reproductive organs
• May protect against Tuberculosis, gum inflammation, multiple sclerosis, and even insulin resistance.

Vitamin D Deficiency

• Factors that contribute to deficiency:
  • Dark skin
  • Breastfeeding infants by Vitamin D deficient mothers
  • Lack of sunlight
  • Poor diet
• Deficiency disorders:
  • Rickets in children.
  • Osteomalacia and Osteoporosis in adults.

Elderly and Vitamin D

Elderly are a Higher Risk Group. Why?

1. Skin, liver, and kidneys lose capacity to make & activate Vitamin D.
2. Older people typically drink little or no milk.
3. Spend more time indoors and often wear protective clothing.
   • Deficiency affects balance.
   • In care facilities, vitamin D supplementation is effective in reducing the rate of falls.

Other At-Risk Groups for Vitamin D Deficiency

• Dark-skinned people of either sex, particularly migrants & those wearing modest dress.
• People with a disability or chronic disease (E.g., MS).
• Fair-skinned people and those at risk of skin cancer who avoid sun exposure.
• People working in a closed environment, such as office workers, factory or warehouse workers, taxi drivers, night shift workers.

Potential Health Benefits of Vitamin D

Growing list of health benefits; vitamin D may protect against:

• Diabetes.
• Cardiovascular disease.
• Multiple sclerosis.
• Obesity.
• Autoimmune diseases.
• Cancer and respiratory diseases.

However, mostly observational research.

Vitamin D Toxicity

• Toxicity disease = Hypervitaminosis D
  • Vitamin D from sunlight and food is not likely to cause toxicity.
  • High-dose supplements may cause toxicity.
• Toxicity symptoms:
  • Elevated blood calcium
  • Calcification of soft tissues (blood vessels, kidneys, heart, lungs, and tissues around joints).
  • Frequent urination.

Vitamin D - Recommendations

• Sources
  • Obtained from the sun and from foods
  • Very few foods contain Vitamin D
  • Fortified milk, butter, and margarine.
  • Egg yolks and liver.
  • Fatty fish (e.g., Salmon, herring, mackerel) and their oils.
• Vitamin D supplementation is mandated in margarines and voluntary for low-fat milk, powdered milk, yoghurt, and soy milk.
• Without adequate sunshine, fortification, or supplements, vegans may not meet Vitamin D needs.

Vitamins E and K

Vitamin E

• Name: Alpha-tocopherol
  • There are different tocopherol compounds; α has the highest activity; others aren’t readily converted to α.
• Role: A fat-soluble antioxidant; the main action is to stop the chain of free radicals/producing more free radicals.
  • AI (α-tocopherol Equiv.):
    • Men: $10 mg/d$
    • Women: $7 mg/d$
  • Upper Level: $300 mg/day$
  • Stability: Sensitive to heat and oxygen, therefore fresh-food sources preferred.

Vitamin E and Heart Disease

• Vitamin E may decrease heart disease risk by protecting LDL against oxidation & reducing inflammation.
• Epidemiological studies suggest people who eat food rich in vitamin E have decreased atherosclerotic plaques.
• For people with pre-existing heart disease, supplements may be dangerous.
• The National Heart Foundation (2012) guidelines suggest: “There is no evidence that antioxidant supplements help prevent CVD. There is concern that high doses (> 800 IU/day) of vitamin E supplements may increase the risk of CVD”.

Vitamin E Deficiency

• Primary deficiency due to inadequate intake is rare.
• Erythrocyte hemolysis (Hemolytic anemia):
  • Occurs in premature infants.
  • Can be treated with vitamin E.
• Symptoms:
  • Loss of muscle coordination and reflexes.
  • Impaired vision and speech, nerve damage.

Vitamin E Toxicity

• Rare and the least toxic of the fat-soluble vitamins.
• Extremely high doses may augment the effects of anticlotting medication & cause hemorrhage.

Vitamin E - Food Sources

Widespread in foods:

• Polyunsaturated plant oils such as margarine, salad dressings, and shortenings.
• Leafy green vegetables.
• Wheat germ.
• Wholegrain foods.
• Liver and egg yolks.
• Nuts and seeds.

Vitamin K

• Names: phylloquinone, menaquinone, and menadione.
• Vitamin K is unique in that half of human needs are met through the action of intestinal bacteria.
• Role: Synthesis of blood clotting and bone proteins.
  • Adequate Intake:
    • Men: $70 \mu g/d$
    • Women: $60 \mu g/d$
  • No Upper Level of Intake Set

Vitamin K - Roles in the Body

• Synthesis of blood-clotting proteins.
• Without vitamin K, a hemorrhagic disease may develop.
• Hemophilia is a hereditary disorder and is not cured with vitamin K.
• Vitamin K also participates in the metabolism of bone protein (osteocalcin). Without Vitamin K, osteocalcin cannot bind to minerals that form bones = low bone density.

Vitamin K - Blood Clotting

• Vitamin K is essential for the synthesis of blood-clotting proteins.
• Prothrombin (an inactive protein) requires vitamin K to be converted into thrombin (an active enzyme).
• Thrombin then converts fibrinogen (a soluble protein) into fibrin (a solid clot).

Vitamin K - Sources

• Bacterial synthesis in the digestive tract.
• Liver.
• Leafy green vegetables (e.g., Spinach, lettuce, brussels sprouts, and cabbage).
• Milk.

Vitamin K - Deficiency & Toxicity

• Deficiencies (Hemorrhagic Disease):
  • Primary deficiencies are rare.
  • Secondary deficiencies are possible if poor fat absorption or due to some drugs (e.g., Antibiotics, anticoagulants).
• Newborns are unique:
  • They are given a single dose at birth (injected dose or orally).
• Deficiency can cause hemorrhaging.
• Toxicities: None known; however, high doses can decrease the effectiveness of anticlotting medications (e.g., Warfarin).

Fat-Soluble Vitamins - Summary

• The 4 fat-soluble vitamins play specific roles in the growth & maintenance of the body.
• Toxicities are possible, especially when people use supplements.
• The function of 1 fat-soluble vitamin often depends on the presence of another (i.e., they often interact with each other).
• To attain them, we need to eat a wide variety of foods.

Summary Table of Fat-Soluble Vitamins

Review Questions:

1. Fat-soluble vitamins:

   • c. Require bile for absorption

2. The form of vitamin A active in vision is:

   • a. Retinal

3. Vitamin A deficiency symptoms include:

   • c. Night blindness & keratomalacia

4. Calcification of the soft tissues is a symptom of:

   • b. Vit D excess

5. To keep minerals available in the blood, Vit D targets:

   • c. The intestines, kidneys, and bones

6. Vit D can be synthesized from a precursor that the body makes from:

   • c. Cholesterol

7. Vitamin E’s most notable role is to:

   • a. Protect lipids from oxidation

8. The most common nutrient-dense source of Vit E:

   • d. Vegetable oils

9. A significant source of vitamin K comes from:

   • c. Bacterial synthesis