Fat Soluble Vitamins and Their Functions

Fat Soluble Vitamins

• Fat soluble vitamins require dietary fat and bile salts for absorption.
• Vitamins ADEK are collectively important for vision, calcium homoeostasis, antioxidant activity, and blood clotting.

Vitamin A

• A group of compounds (retinoids) including retinol, retinaldehyde, and retinoic acid
• Animal sources: liver, dairy, eggs, fish oil
• Plant sources: beta-carotene (pro-vitamin A)
• Functions:
  • Retinaldehyde participates in vision as part of rhodopsin
  • Retinoic acid regulates gene expression
• Carried by retinol binding protein (RBP) which is bound to transthyretin in blood
• Deficiency:
  • Night blindness: inability to see in low light conditions
  • Xerophthalmia: dryness of the eyes, leads to corneal ulceration and blindness
  • Reproductive issues: impaired spermatogenesis and increased risk of fetal resorption
• Deficiency can be caused by protein malnutrition due to lack of RBP.
• Excess:
  • Teratogenic (causes birth defects)
  • Chronic ingestion of large amounts can lead to liver and bone damage, hair loss, headaches
• RDA: 600-900 RAE/day (RAE - retinol activity equivalent), where 1 µg retinol = 12 µg β-carotene

Vitamin D

• Hormone-like functions: regulates calcium absorption and homoeostasis
• Functions in immune system
• Sources: oily fish, eggs, liver, fortified foods and sunlight
• Synthesised in the skin under the action of sunlight, leading to potential deficiency in winter/northern latitudes
• Deficiency:
  • Rickets: in children, failure of bone mineralization
  • Osteomalacia: in adults, demineralization of bone
• Converted in the liver and kidney (stimulated by parathyroid hormone or PTH) to the active form called calcitriol
• Excess:
  • Elevated plasma calcium, leading to blood vessel constriction and calcification of soft tissues
• Adequate intake: 5-15 μg/day for elderly

Vitamin E

• Group of 8 tocopherols, with alpha-tocopherol being the most active
• Functions primarily as an antioxidant in cell membranes to protect from radical damage.
• Protects polyunsaturated fatty acids (PUFAs)
• Deficiency:
  • Rare, but can occur in fat malabsorption syndromes
  • Premature infants (not easily transported across the placenta)
  • Haemolytic anaemia: fragility of RBC membrane
  • In experimental animals: testicular atrophy, skeletal and cardiac muscle damage, nervous system problems
• Sources: nuts, soybeans, vegetable oil, spinach.
• Least toxic of the vitamins: 300 mg/day has no reported ill effects

Vitamin K

• Cofactor for enzymes that carboxylate glutamate to γ-carboxyglutamate
• Important for blood clotting: synthesis of prothrombin and factors II, VII, IX, X
• Other proteins containing γ-carboxyglutamate: osteocalcin in bone
• Sources: green leafy vegetables and gut bacteria
• Deficiency:
  • Coagulation defects: increased prothrombin time
  • Osteoporosis: higher vitamin K intake correlates with greater bone density
  • Supplements may improve bone health, especially post-menopause
• Deficiency usually caused by poor absorption in the gut, not dietary inadequacy

Water Soluble Vitamins

• Vitamins B complex and Vitamin C are water soluble, and have a variety of functions including energy metabolism, cell growth and repair, and immunity.

Thiamine (B1)

• Coenzyme for:
  • Pyruvate dehydrogenase: links glycolysis and Krebs cycle
  • α-ketoglutarate dehydrogenase: in Krebs cycle
  • Transketolase: in pentose phosphate pathway
• Important for energy metabolism, NAD reduction, and glucose metabolism
• Deficiency:
  • Beriberi: classified as 'wet' or 'dry'
    • Wet: cardiovascular disease, signs of cardiac involvement
    • Dry: peripheral and central neuropathy
  • Wernicke-Korsakoff syndrome: confusion, ataxia, paralysis of eye movement (Wernicke encephalopathy), amnesia, confabulation (Korsakoff psychosis). Common in alcoholics
• Sources: brown rice, whole grains, legumes, nuts, seeds, meat, fish
• Requirements: 0.5 mg/1000kcal for adults consuming more than 2000kcal; 0.8-1.0mg for low energy intake
• RDA: 0.9 - 1.2 mg/day

Riboflavin (B2)

• Electron carriers in many redox reactions
• Forms part of flavoenzymes
• Involved in energy metabolism (NADH and FADH2 production) and glutathione reductase (important for red blood cell health)
• Deficiency:
  • Angular stomatitis: cracks at the corners of the mouth
  • Glossitis: inflammation of the tongue
  • Dermatitis: skin inflammation
  • Conjunctivitis: inflammation of the conjunctiva (eye lining)
  • Opacity of the lens: clouding of the lens of the eye
• Sources: milk, dairy products, eggs, meat, fish
• RDA: 0.9 - 1.3 mg/day

Niacin (B3)

• Precursor for NAD and NADP, which are crucial for energy metabolism
• Can be synthesised from tryptophan, but this process is inefficient
• Inhibits lipolysis in adipose tissue, reducing LDL and VLDL cholesterol
• High doses (100x RDA) are used to treat type IIb hyperlipoproteinemia
• Sources: grains, milk, liver
• RDA: 12-16 mg/day (7 mg/1000kcal)
• Deficiency:
  • Pellagra: deficiency of niacin and tryptophan, characterized by 'the 3 D's': Dermatitis, Diarrhea, Dementia
  • Dermatitis is photosensitive
  • Dementia may be caused by tryptophan deficiency due to reduced serotonin synthesis
  • Maize is poor in niacin and tryptophan, contributes to pellagra

Pantothenate (B5)

• Forms the functional moiety of coenzyme A, essential for energy metabolism and fatty acid synthesis
• Widespread in the diet, making deficiency very rare.
• RDA: not established, adequate intake: 4-5 mg/day

Pyridoxine (B6)

• Group of molecules including pyridoxine, pyridoxamine, and pyridoxal. Essential for various metabolic pathways.
• Pyridoxal phosphate: coenzyme for many enzymes, especially those involved in amino acid metabolism (e.g. aminotransferases)
• Deficiency leading to clinical signs is rare.
• Experimental animals show increased sensitivity to steroid hormones.
• Some evidence links poor B6 intake to poor breast cancer prognosis
• Sources: raw foods, especially those rich in protein, as heating can cause reactions with lysine
• RDA: 1-1.7 mg/day

Biotin (B7)

• Coenzyme in carboxylation reactions:
  • Acetyl-CoA carboxylase: in fatty acid synthesis
  • Pyruvate carboxylase: in glucose metabolism
• Deficiency is rare because it's widely available in the diet and synthesized by gut bacteria.
• Deficiency Symptoms:
  • Dermatitis, hair loss, glossitis, nausea, loss of appetite
  • Raw egg white contains avidin which binds biotin tightly and can lead to deficiency when consumed in large amounts (>20 eggs/day)
• RDA: not established but adequate intake is estimated to be 20-30mg/day

Folate (B9)

• Functions as 1-carbon carrier in the synthesis of amino acids, purines, and thymine
• Important for DNA synthesis, cell division, and growth
• Sources: fruits, vegetables, supplements
• RDA: 300-400 μg/day
• Increase intake to 200-400 μg/day before conception
• Deficiency:
  • Macrocytic (megaloblastic) anaemia: abnormal development of blood cells due to purine deficiency affecting DNA synthesis
  • In pregnancy:
    • Foetal neural tube defects (spina bifida)
    • Low birth weight

Vitamin B12 (Cobalamin)

• Only produced by bacteria/yeast. Animals obtain it from their flora or other animals
• Sources: liver, meat, milk, eggs
• Absorption:
  • Requires intrinsic factor: glycoprotein produced by the stomach
  • Intrinsic factor complexes with B12 for absorption in the lower ileum
• Large stores in the body (4-5 mg) - a few years supply
• Coenzyme for:
  • Leucine aminopeptidase
  • Methylmalonyl-CoA mutase
  • Methionine synthase (connection to folate metabolism): involved in methyl group transfer
• Deficiency:
  • Pernicious anaemia: megaloblastic anaemia and subacute combined degeneration of the spinal cord (neurological effects)
  • Other neurological effects: demyelination, nerve cell death, numbness, subacute combined degeneration of the spinal cord
• Deficiency can be due to:
  • Dietary deficiency (rare, except in strict vegans)
  • Intestinal disease: impaired absorption in the lower ileum
  • Bacterial overgrowth: some bacteria require B12, overgrowth can interfere with absorption
  • Gastric malfunction: autoimmune diseases, malignancy, gastrectomy (leading to lack of intrinsic factor)
• RDA: 1.4-2.4 μg/day

Fat Soluble Vitamins

• Dietary Sources
  • Vitamin A: Animal sources include liver, dairy, egg yolk, fish oils; Plant sources include beta carotene (pro-vitamin A).
  • Vitamin D: Oily fish, eggs, liver, fortified foods. Can be synthesised in the skin through sunlight exposure.
  • Vitamin E: Nuts, soy beans, vegetable oil, spinach.
  • Vitamin K: Green leafy vegetables, synthesized by gut bacteria.
• Absorption
  • Requires normal pancreatic function, intestinal cells, and bile salts for lipid emulsification.
• Functions
  • Vitamin A: Retinaldehyde acts as light-sensitive pigment in vision, retinoic acid is a gene regulator.
  • Vitamin D: Hormone-like functions, regulates calcium absorption and homeostasis, some immune functions.
  • Vitamin E: Antioxidant in cell membranes, limits radical damage from oxidation of polyunsaturated fatty acids.
  • Vitamin K: Cofactor for enzymes involved in carboxylation of glutamate to γ-carboxyglutamate. Necessary for formation of prothrombin and other clotting factors.
• Deficiencies
  • Vitamin A: Night blindness, xeropthalmia, infertility, can result from protein malnutrition.
  • Vitamin D: Rickets in children, osteomalacia in adults.
  • Vitamin E: Rare, but can occur in fat malabsorption syndromes, can lead to anaemia due to fragile RBC membrane.
  • Vitamin K: Coagulation defects, osteoporosis.
• Toxicity
  • Vitamin A: Teratogenic, chronic excessive intake can cause liver and bone damage, alopecia, headaches.
  • Vitamin D: Elevated plasma calcium, calcification of soft tissues.

Water Soluble Vitamins

• Dietary Sources
  • Vitamin C: Blackcurrants, guava, citrus fruits.
  • Vitamin B Complex: Found in a variety of foods, including grains, meat, poultry, fish, eggs, dairy products, legumes.
• Absorption
  • Specific transporters in the intestines.
• Functions
  • Vitamin C: Important in hydroxylation reactions, especially in collagen synthesis. Also involved in carnitine synthesis and iron absorption.
  • Thiamine (B1): Coenzyme for pyruvate dehydrogenase, α-ketoglutarate dehydrogenase, and transketolase. Essential for energy metabolism.
  • Riboflavin (B2): Electron carrier in redox reactions.
  • Niacin (B3): Precursor for NAD and NADP, essential for energy metabolism. Can be synthesized from tryptophan.
  • Pantothenate (B5): Functional moiety of Coenzyme A, involved in energy metabolism and fatty acid synthesis.
  • Pyridoxine (B6): Coenzyme for many enzymes involved in amino acid metabolism.
  • Biotin (B7): Coenzyme in carboxylation reactions, involved in fatty acid synthesis.
  • Folic acid (B9): 1-carbon carrier in the synthesis of amino acids, purines, and thymine.
  • Cobalamin (B12): Required for the synthesis of myelin and DNA, essential for the development of red blood cells.
• Deficiencies
  • Vitamin C: Scurvy, characterized by sore gums, loose teeth, fragile blood vessels, anaemia, fatigue.
  • Thiamine (B1): Beriberi, can be wet or dry, characterized by cardiovascular involvement, peripheral and central neuropathies. Wernicke-Korsakoff Syndrome, a neurological disorder associated with alcoholism.
  • Riboflavin (B2): Angular stomatitis, glossitis, dermatitis, conjunctivitis and opacity of the lens.
  • Niacin (B3): Pellagra, characterized by the three D's: dermatitis, diarrhea, dementia.
  • Folate (B9): Macrocytic (megaloblastic) anaemia, neural tube defects during pregnancy.
  • Cobalamin (B12): Megaloblastic anaemia, neurological disorders.
• Toxicity
  • Vitamin C: High doses can cause gastrointestinal upset, diarrhoea, and kidney stones.

Fat Soluble Vitamins

• Vitamin A
  • Functions:
    • Retinaldehyde functions as a light-sensitive pigment in vision, in Rhodopsin.
    • Retinoic acid functions as a gene regulator.
  • Deficiency can result from protein malnutrition due to a lack of RBP (Retinol Binding Protein).
  • Excess can cause teratogenicity, liver damage, bone damage, alopecia and headaches.
• RDA: 600 - 900 RAE/day - RAE = 1 μg retinol, 12 μg β-carotene.
• Vitamin D
  • Functions:
    • Hormone-like functions, including regulation of calcium absorption and homeostasis.
    • Some immune functions.
  • Deficiency:
    • Rickets in children, failure of bones to mineralize properly.
    • Osteomalacia in adults, demineralization of bone.
  • Sources are few and natural: oily fish, eggs, liver; Fortified foods also contribute to Vitamin D intake.
  • Converted in the liver and kidney by PTH (Parathyroid Hormone) to its active form, Calcitriol.
  • Toxicity: elevated plasma calcium can lead to contraction of blood vessels and calcification of soft tissues.
  • RDA: Adequate intake for the elderly is 5 - 15 μg/day
• Vitamin E
  • Functions:
    • Antioxidant in cell membranes.
    • Limits radical damage from oxidation of PUFA (polyunsaturated fatty acids)
  • Deficiency is rare, may be seen in fat malabsorption syndromes.
    • Premature infants: not easily transported across the placenta.
  • Sources: nuts, soy beans, vegetable oil, spinach.
  • Least toxic vitamin, with no ill effects up to 300 mg/day.
• Vitamin K
  • Functions:
    • Cofactor for enzymes involved in carboxylation of glutamate to γ-carboxyglutamate.
    • Necessary for formation of prothrombin, factors II, VII, IX, X.
    • γ-carboxyglutamate is also found in other proteins, e.g. osteocalcin in bone.
  • Warfarin is a vitamin K "antagonist", used as an anticoagulant.
  • Sources: green leafy vegetables. Also synthesized by gut bacteria.
  • Deficiency can cause coagulation defects, increased prothrombin time, osteoporosis, and potential heart disease.
  • Newborns should receive a single prophylactic injection of Vitamin K to compensate for a lack of gut bacteria, milk, and possible poor placental transfer.
  • Though an RDA has not been established, adequate intake is 60 - 120 μg/day.

Water Soluble Vitamins

• Function:
  • Thiamine (B1): Co-enzyme for pyruvate dehydrogenase, α-ketoglutarate dehydrogenase, and transketolase, all of which have important roles in energy metabolism.
  • Riboflavin (B2): Electron carriers in many redox reactions.
  • Niacin (B3): Precursor for NAD and NADP, coenzymes in redox reactions and central roles in energy metabolism.
  • Pantothenic acid (B5): Important in the formation of coenzyme A (CoA), which functions as a vital component of carbohydrate, fat, and protein metabolism.
  • Pyridoxine (B6): Involved in amino acid metabolism, synthesis of neurotransmitters and hemoglobin, and the conversion of glycogen to glucose.
  • Biotin (B7): Functions as a coenzyme in carboxylation reactions, essential for fatty acid and glucose metabolism.
  • Folic acid (B9): Essential for synthesis of DNA and RNA, cell division and growth, formation of red blood cells.
  • Cobalamin (B12): Necessary for the formation of myelin, a vital component of the central nervous system, and the metabolism of fatty acids and proteins. It also works with folate to produce red blood cells.
  • Vitamin C (Ascorbic Acid): Main function is as a reducing agent, co-enzyme in hydroxylation reactions, hydroxylation of proline and lysine in collagen, synthesis of carnitine.
• Absorption of water soluble vitamins depends on a balance of transporter proteins, passive and active transport mechanisms.

Deficiency Effects

• Thiamine (B1): Deficiency can cause beriberi, characterized by wet or dry symptoms.
  • Wet: Signs of cardiac involvement.
  • Dry: Peripheral and central neuropathies.
    • Wernicke-Korsakoff Syndrome: Confusion, ataxia, paralysis of eye movement, amnesia and confabulation.
• Riboflavin (B2): Deficiency can cause angular stomatitis, glossitis, dermatitis, conjunctivitis, and opacity of the lens.
• Niacin (B3): Deficiency can cause Pellagra, characterised by dermatitis, dementia, diarrhea.
• Vitamin B6 (Pyridoxine): Deficiency can cause seizures, anemia, and neurotoxicity.
• Vitamin B12 (Cobalamin): Deficiency can cause megaloblastic anemia due to folate deficiency and neurological effects, including demyelination and nerve cell death. This can lead to numbness, muscle weakness, and subacute combined degeneration of the spinal cord.
• Vitamin C (Ascorbic Acid): Deficiency can cause scurvy, characterized by sore spongy gums, loose teeth, fragile blood vessels, anemia, and fatigue. It can disrupt collagen synthesis as well.
• Vitamin K: Deficiency is most often due to poor absorption in the gut rather than dietary inadequacy (e.g., Celiac disease, Crohn's disease, fat malabsorption syndromes), resulting in problems with blood clotting.