Tuesday, February 26, 2019

Vitamins




Summary

Vitamins are a group of chemically diverse organic compounds that an organism requires for normal metabolism. Apart from a few exceptions (e.g., vitamin D), the human body cannot synthesize vitamins on its own in sufficient amounts and must, therefore, ensure a steady supply through the diet. Vitamins are micronutrients that do not provide energy (like macronutrients) but instead have very specific biochemical roles: They are coenzymes in various reactions (B vitamins, vitamins A and K) and antioxidants that protect the cell and its membranes from free radicals (vitamins C and E), enable cell signaling (vitamin A) and gene transcription (vitamins A and E), and serve hormone-like functions (e.g., vitamin D). Vitamins are classified as fat-soluble vitamins, which the body can store, and water-soluble vitamins, which, with the exception of vitamins B9 (folate) and B12, cannot be stored in the body over significant lengths of time and therefore require continuous intake. A balanced diet typically supplies the body with all the vitamins it requires, and deficiencies occur mainly due to malnutrition, malabsorption disorders, or restrictive diets (e.g., vitamin B12 in a vegan diet).

Overview of vitamins

Fat-soluble vitamins

Fat-soluble vitamins are nonpolar molecules that require lipids for resorption. Since the body can store them for long periods of time, mainly in the liver and adipose tissue, excess accumulation is possible and may cause toxicity. While toxicity occurs mainly in industrialized countries due to oversupplementation, most deficiencies are a health concern mainly in developing countries (vitamin D being the notable exception). Treatment of deficiency involves oral supplementation, dietary adjustment (e.g., if due to restricted diet), or causal treatment of the underlying disease (esp. malabsorption disorders). For further information on etiology, diagnostics, and differential diagnoses, see the learning card on “Malabsorption.”
  • Resorption and transport of fat-soluble vitamins
    1. Bile salts combine with lipids and fat-soluble vitamins in aqueous environments to form micelles.
    2. Micelles are resorbed in the intestinal tract (esp. in the duodenum) and packed to form chylomicrons.
    3. Chylomicrons are released into the lymphatic system and transported into circulation via the thoracic duct.
    4. Transport to liver
    5. Transport from liver to target cell with the aid of specialized transport proteins
The fat cat is in the ADEK (pronounced “attic”).




Vitamin A

Chemistry

Physiology

  • Sources
    • Plant sources: as inactive provitamin in yellow and leafy vegetables (e.g., spinach, kale, carrots)
    • Animal sources: in storage form, e.g., in liver, fish, eggs, butter
  • Activation: The carotinoid is cleaved into two retinal molecules. Retinal can be reversibly reduced to retinol and reversibly oxidized to retinoic acid.
  • Transport:
  • Storage: in hepatic stellate cells 
    • Storage form: retinyl ester (e.g., retinyl palmitate)
  • Excretion: via bile and urine

Functions

Retinal plays a major role in vision, while retinoic acid and retinol are involved mainly in gene transcriptionand tissue maintenance!

Deficiency [1]

Excess

  • Causes: Oversupplementation
  • Symptoms
    • Acute
      • Nausea
      • Vertigo
      • Fatigue
      • Headache
      • Blurry vision
    • Chronic
    • Teratogenic (e.g., microcephaly, cleft palate, skeletal, neurologic, and cardiac abnormalities, fetal death)

Therapeutic uses

Isotretinoin is a strong teratogenic agent. A negative pregnancy test and two forms of contraception are required before prescription in women.
Vitamin A should be given to patients with measles to boost their immune system, especially in countries where vitamin A deficiency is endemic.
References:[3][4][5]

Vitamin D

Chemistry

Physiology

Vitamin D is the only vitamin that the human body can produce entirely on its own!





Functions

  • Calcium and phosphate metabolism (see also calcium homeostasis)
    • Increases resorption of calcium and phosphate in the intestine
    • Increases reabsorption of calcium in the kidney 
  • Stimulation of bone mineralization and remodeling
    • Indirectly: through maintenance of serum calcium and phosphate levels
    • Directly: through activation of osteoblasts and promotion of osteoclast differentiation

Vitamin D deficiency [6]

Excess

Vitamin E

Chemistry

Physiology

Functions

  • Antioxidant: protects sensitive substances, esp. erythrocytes and cell membranes, from free radicals
    • Tocopherol interrupts free radical chains caused by oxidative damage and becomes oxidized itself in the process. 
  • Other functions

Deficiency

Excess

  • Toxicity is very rare.
  • Causes: Oversupplementation
  • Symptoms
    • In children: increased risk of enterocolitis
    • Can alter the metabolism of warfarin → enhanced anticoagulant effect → increased risk of bleeding
    • Studies have linked long-term high-dose supplementation to increased incidence of heart failure and increased risk of fatal subarachnoid hemorrhage and mortality.
References:[9]

Vitamin K

Chemistry

  • Fat-soluble vitamin
  • Synonyms: phytomenadione, phylloquinone, phytonadione
  • Substance class: naphthoquinones
  • Inactive precursors (provitamins): none
  • Active form: vitamin K hydroquinone

Physiology

  • Sources: leafy green vegetables ; synthesized in small amounts by intestinal flora
  • Transport: via lipoproteins; no specific protein
  • Storage: liver
  • Excretion: bile and urine
  • Activated by the enzyme epoxide reductase → cofactor for γ-carboxylation of glutamic acid residues on clotting factors → adequate hemostasis

Functions

In 1972 vitamin K Killed CSf

Deficiency[10]

Excess




Water-soluble vitamins

Water-soluble vitamins are polar molecules that function primarily as coenzymes in various chemical reactions. They are not stored in the body except vitamins B9 and B12, which are stored in the liver. Accumulation and consequent toxicity are exceedingly rare, even with vitamins B9 and B12. Treatment of deficiency involves oral supplementation, dietary adjustment (e.g., if due to restricted diet), and causal treatment of underlying disease (esp. malabsorption disorders). For more information on etiology, diagnostics, and differential diagnoses, see the learning card on “Malabsorption.” Deficiency of B-complex often causes glossitis, dermatitis, and diarrhea.
  • Resorption and transport
    1. Resorption in the intestine: active transport and passive diffusion
    2. Transport in the blood: active, via various transport proteins








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