Fat Soluble Vitamins

What are the fat-soluble vitamins?

Vitamins A, D, E, and K

Water-Soluble Vitamins

• Soluble in in the watery compartments of foods and are distributed into the water-filled compartments of the body

• absorbed primarily via the portal system

• Except for B9 and B12, not stored in the body

Fat-Soluble Vitamins

• typically occur together in the fats and oils consumed in a balanced diet

• absorbed via the same process that we absorb lipids

  • incorporated into chylomicrons that are formed when fat is being digested and together they get absorbed into the lymphatics → stored in the liver and adipose tissue

• from storage point, they are transported throughout the blood to where they are needed

What do fat-soluble vitamins since they are not soluble in aqueous solutions like blood?

• carrier proteins → stop them from precipitating out of the blood

  • retinol-binding protein

    • binds retinol (one of 3 forms of vitamin A) from the liver and transports it throughout the blood

Intake of Fat-Soluble Vitamins

• Stored in the body means that there is a certain amount of the vitamin in reserve within the body

• don’t need to eat the daily recommended amount of a fat-soluble vitamin every day → maintain that daily requirement as an average intake over time

Primary Deficiency

• occurs when an individual does not consume enough of the vitamin in their diet

Secondary Deficiency

• Occurs as a consequence of another pathological process

What can cause a secondary deficiency of fat-soluble vitamins?

• Any pathology that causes a problem with the absorption of lipids from the digestive system

Sources of Vitamin A

• Cantaloupe

• Carrots

• Dairy products

• Eggs

• Fortified cereals

• Green leafy vegetables (eg, spinach, broccoli)

• Pumpkin

• Red peppers

• Sweet potatoes

Sources of Vitamin D

• Eggs

• Fish (herring, mackerel, salmon, trout, tuna)

• Fish liver oil

• Fortified cereals

• Fortified dairy products

• Fortified margarine

• Fortified orange juice

• Fortified soy beverages (soymilk)

Sources of Vitamin E

• Fortified cereals and juices

• Green vegetables (eg, broccoli, spinach)

• Nuts and seeds

• Peanuts, peanut butter

• Vegetable oils

Sources of Vitamin K

• Green vegetables (eg, broccoli, kale, spinach, turnip greens, collards, Swiss chard, mustard greens)

Function of Vitamin A

• Associated with gene expression, vision, cell differentiation via the regulation of transcription factors (thereby maintaining the health of body linings and skin), immunity, reproduction and growth

Vitamin A in Eye

• Part of rhodopsin and iodopsin

Vitamin A in Skin

• Epithelial cell renewal, mucus membrane maintenance

Vitamin A in Fetus

• Cellular differentiation of epithelial cells (into pancreatic cells, lungs),

  bone development

Retinol

• major transport and storage form of vitamin A

Retinal

• component of rhodopsin, the light-sensing biological pigment in the rods of the retina. On exposure to light, rhodopsin triggers a G-protein cascade that allows the human eye to sense the amount of light in the environment.

Retinoic Acid

• acts as a hormone, regulating cell differentiation, growth, and

  embryonic development

Primary Vitamin A Deficiency

• occurs because of insufficient intake

Secondary Vitamin A Deficiency

• Results from any pathology that disrupts lipid absorption b/c fat-soluble vitamins are absorbed w/ fats from diet

Symptoms of Vitamin A Deficiency

• Cell differentiation and maturation are impaired

  • epithelial cells flatten and begin to produce keratin

    • leads to drying and hardening of the cornea (xerosis) and may progress to permanent blindness (xeropthalmia)

  • drying and scaling of skin

  • negatively affects various mucosal lining of the body, such as the gastrointestinal and respiratory tracts → decreased structural integrity → increased susceptibility to infections (pneumonia and diarrhea)

Indicator of Vitamin A Deficiency

• Impaired eye adaptation at night (night blindness) → nyctaopia

• Drying and scaling of skin

Major cause of preventable blindness in children worldwide?

Vitamin A deficiency

Vitamin A Deficiency in Eye

• Reduction in goblet cells and reduction in production of mucin leads to dry eyes

• Bitot spots

• Keratomalacia

Vitamin A Deficiency in Skin

• Keratinization (Hyperkeratosis)

  • change in shape & size of epithelial cells

  • skin becomes dry, rough, and scaly

  • normal digestion and absorption of nutrients from GI tracts falters

  • weakened defenses in respiratory tract, vagina, inner ear, and urinary tract

Vitamin A Toxicity

• occurs when a person consumes large amounts of vitamin A from concentrated sources in foods derived from animals, fortified foods, or supplements

• poisoning can be acute or chronic

  • acute: occurs quickly when a person takes several hundred thousand international units (IU) of vitamin A

  • chronic: occurs in a person consuming >30,000 μg/d for months

  • > than the daily recommended amount of 900 μg for men and 700 μg for women.

  • children are more susceptible to toxicity at lower levels

Why doesn’t vitamin A toxicity occur from vitamin A intake from plants

• Vitamin A in plants is in its inactive precursor form, beta-carotene

• precursor doesn’t convert to the active form of vitamin A fast enough to cause toxicity

Symptoms of Vitamin A Toxicity

• rash and headache → develop in both acute and chronic toxicities

• pregnancy

  • poses a teratogenic risk due to its modulation of transcription factors, affecting the development of the fetus

  • injure the spinal cord and other tissues of developing fetus → increases risk of birth defects

Symptoms of Acute Vitamin A Toxicity

• nausea

• vomiting

• vertigo

• blurry vision

Symptoms of Chronic Vitamin A Toxicity

• High levels over years may weaken the bones and contribute to fractures and osteoporosis

• can lead to hair loss, dry skin, hepatoxicity, and intracranial hypertension

Accutane

• the vitamin A derivative known as isotretinoin

• requires patients to use two forms of birth control for at least 1 month prior to starting the medication, as well as have a negative pregnancy test result at the time of prescription.

Vitamin D

Calciferol

Vitamin D2

• primarily comes from plant foods in a normal balanced diet

Vitamin D3

• comes from animal foods in the diet and is also synthesized in the skin from cholesterol

Vitamin D Activation

• The initial activation step occurs in the liver, forming 25-hydroxyvitamin D3 (25-OH D3)

• The second activating step occurs in the kidney, forming 1,25-dihydroxyvitamin D3 (1,25-[OH]2 D3).

Function of Vitamin D

• main role: maintaining bone health

• assists in the absorption of calcium and phosphorus to maintain blood concentrations of these minerals

• plays a role in muscle cells and encourages normal muscle function in children and deserves function in adults

• supports and modulates both adaptive and innate immune functions, aiding the body in its ability to defend against infectious diseases

Rickets

• caused by Vitamin D Deficiency

• the softening and weakening of bones in children

• delayed growth and bowing of the legs

Treatment of Rickets

• Adding vitamin D and calcium

Osteomalacia

• vitamin D deficiency in adults

• poor mineralization of bone

• early stages → may not present with any symptoms

• as disease progresses → bone pain and muscle weakness may develop

• same process as rickets, but adults have already grown enough that there are no longer growth plates, so the process manifests as severe bone dain rather than grossly apparent skeletal deformities

• failure to synthesize adequate vitamin D or obtain enough from foods → loss of calcium from the bones → fractures secondary to

  osteoporosis

Vitamin D Toxicity

• most likely to have toxic effects when consumed in excess → over-supplementation rather than from excess vitamin D in the diet or via sunlight

  • body regulates the amount of vitamin D produced by sunlight and foods don’t contain enough to cause toxicity

• excess intake raises the concentration of blood calcium which precipitates in the soft tissues and forms stones, especially in the kidneys, where calcium is concentrated → symptoms of pain on the side and back that comes in waves

• Calcification → harden blood vessels through deposition of calcium phosphate, mostly in the form of apatite crystals → arteriosclerosis

  • dangerous in major arteries of brain, heart, and lungs, where it can cause death

Vitamin E Deficiency

• contributing factor to retinopathy of prematurity → retrolental fibroplasia, as well as some cases of intraventricular and subependymal hemorrhage in neonates

Symptoms of Vitamin E Deficiency

• loss of muscle coordination and reflexes with impaired movement, vision, speech

Cause of Vitamin E Deficiency

• developed countries → associated with diseases that cause malabsorption of fat

  • diseases of the intestine, liver, gallbladder, and pancreas

  • various hereditary diseases involving digestion and absorption of nutrients

• developing countries → inadequate intake

Vitamin E Toxicity

• muscle weakness, fatigue, nausea, diarrhea

• interferes with the blood-clotting action of vitamin K and enhance the action of anticoagulant medications, leading to hemorrhage

• occurs if taken in excess of 1000 mg/d or a patient currently taking warfarin

Function of Vitamin K

• role in hemostasis in human body

• acts as a coenzyme for vitamin K-dependent carboxylase

  • required for the synthesis of γ-carboxyglutamate from glutamate in various proteins that are directly involved in the clotting cascade

• vitamin K-dependent clotting factors : II, VII, IX, X, protein C, and protein S

  • required to bind calcium for optimal function

    • γ-Carboxyglutamate: with its side chain containing two negatively charged COO- groups, can bind Ca2+

    • Glutamate: contains only a single negatively charged COO-, cannot

Symptoms of Vitamin K Deficiency

• problems w/ hemostasis: increased risk of potentially fatal hemorrhage

  • increased PT (prothrombin time) and PTT (partial thromboplastin time) values

    • PT and PTT values indicate proper function of the extrinsic and intrinsic clotting pathways, respectively

Cause of Vitamin K Deficiency

• can occur due to diseases that cause fat malabsorption or ingestion of drugs that interfere with the vitamin’s metabolism

  • cystic fibrosis, pancreatic insufficiency, small

    bowel disease

• antibiotics (cephalosporin class) → kill bad bacteria but can also kill the good vitamin K- producing bacteria that normally live in a person’s gut

• newborns lack colonization by vitamin K-producing bacteria