• Clinical science

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 can be coenzymes in various reactions (B vitamins, vitamins A and K) and/or antioxidants that protect the cell and its membrane from free radicals (vitamins C and E). They can also enable cell signaling (vitamin A) and gene transcription (vitamins A and E) or function as hormones (e.g., vitamin D). Vitamins are classified into fat-soluble vitamins, which the body can store, and water-soluble vitamins, which, with the exception of vitamins B9 (folate) and B12 (cobalamin), the body cannot store over significant periods of time and, therefore, require continuous intake. A balanced diet typically supplies the body with all vitamins it requires. Deficiencies occur mainly due to malnutrition, malabsorption disorders, or restrictive diets (e.g., vitamin B12 deficiency in a vegan diet).

Overview of vitamins

Fat-soluble vitamins Water-soluble vitamins
Vitamins
Sources
  • Mainly diet
  • Intestinal flora: small amounts of vitamin K are synthesized by intestinal bacteria
  • Vitamin D is predominantly synthesized in the body
  • Mainly diet
  • Intestinal flora: small amounts of vitamin B7, B9, and B12 are synthesized by intestinal bacteria
Absorption
  • Absorption depends on intestinal and pancreatic function
  • Require lipids for absorption
  • Absorption in the intestine via specific luminal transporters
Storage
  • Not stored in the body, except vitamins B9 and B12, which are stored in the liver
    • Hepatic stores of B9 last for approx. 3-4 months, whereas hepatic stores of B12 last for approx. 3-4 years.
Functions
  • Function primarily as
    • Coenzymes and precursors to organic cofactors in various chemical reactions (e.g., B vitamins)
    • Antioxidants (vitamin C)
Deficiency
  • Causes include
    • Restricted diet (e.g., vegan diet)
    • Malabsorption disorder (e.g., gastritis, following gastric resection)
    • Congenital disorders (e.g., Hartnup disease)
  • Deficiency of B-complex often causes glossitis, dermatitis, and diarrhea
Excess
  • Excess accumulation is possible (due to oversupplementation) → toxicity
  • Accumulation and subsequent toxicity are exceedingly rare
  • No toxicity has been described for vitamins B1, B2, B5, B7, B9, and B12.

Accumulation and toxicity occur almost exclusively with fat-soluble vitamins.

Fat-soluble vitamins

Name

Active forms Sources Functions Deficiency Toxicity
Vitamin A (retinol)
  • Liver, kidney, butter, egg yolks, leafy vegetables
  • Acute toxicity: nausea, vomiting, blurred vision, dizziness
  • Chronic toxicity
  • Teratogenicity
Vitamin D (calciferol)
  • Cholecalciferol (provitamin D3): fish, milk, plants, exposure to sunlight
  • Ergocalciferol (provitamin D2): plants, fungi, yeast, fortified foods (e.g., milk, cereals, formula)
  • Calcium and phosphate homeostasis
  • ↑ Absorption of Ca2+ and PO43- in the intestine
  • ↑ Bone resorption at high levels
  • ↑ Bone mineralization at low levels
  • Rickets (in children)
  • Osteomalacia (in adults)
  • Hypocalcemic tetany
Vitamin E (tocopherol)
  • Meat, eggs, oils, leafy vegetables
  • Antioxidant
Vitamin K (phytomenadione)
  • Green vegetables, broccoli, spinach
  • Synthesized by intestinal flora

To remember the fat-soluble vitamins, think: “The fat cat is in the ADEK” (pronounced “attic”).

Vitamin A (retinol)

Characteristics

  • Synonyms: retinol
  • Substance class: retinoids
  • Chemical structure: isoprenoid
  • Inactive precursors (provitamins): carotenoids (esp., alpha-carotene, beta-carotene, gamma-carotene)
  • Activation: carotinoid is cleaved into two retinal molecules; it can be reversibly reduced to retinol and reversibly oxidized to retinoic acid
  • Active forms: retinal (protein for transport, not involved in chemical reactions), retinoic acid
  • Sources
    • Plant sources; : as inactive provitamin (esp. beta-carotene) in yellow and leafy vegetables, e.g., spinach, kale, carrots
    • Animal sources: in storage form; (esp. retinyl ester), e.g., in liver, kidney, fish, eggs, butter
  • Transport: via transport proteins (in the form of retinol)
    • Cellular retinoic acid-binding (CRAB) protein: selectively binds retinoic acid
    • Retinol-binding protein: retinol transport vehicle in serum
  • Storage: : in hepatic cells; (Ito cells) within the perisinusoidal space (of Disse)
    • Storage form: retinyl ester (e.g., retinyl palmitate)
  • Excretion: via bile and urine

Functions

Retinal is a major component of the retinal pigment rhodopsin in rods, which is necessary for vision, while retinoic acid and retinol are involved mainly in gene transcription and tissue maintenance!

Retinol (vitamin A) for your retinA.

Vitamin A deficiency [1]

Vitamin A toxicity

  • Causes: oversupplementation
  • Clinical features

Isotretinoin is highly teratogenic. A negative pregnancy test and two forms of contraception are required before prescribing to women.

Therapeutic uses

Vitamin A should be given to patients with measles to boost their immune system and reduce the risk of complications and mortality, especially in countries where vitamin A deficiency is endemic.

References:[3][4][5]

Vitamin D (calciferol)

Characteristics

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

Functions

  • Calcium and phosphate metabolism (see calcium homeostasis)
    • ↑ Absorption of calcium and phosphate in the intestine
    • ↑ Reabsorption of calcium in the kidneys
  • 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
  • Excess vitamin D stimulates bone resorption at high vitamin D levels

Vitamin D deficiency [6]

Vitamin D toxicity

Therapeutic uses

Vitamin E (tocopherol)

Characteristics

  • Synonyms: tocopherol; , tocotrienols
  • Substance class: tocopherols
  • Chemical structure: chromane with isoprenoid side chain
  • Inactive precursors (provitamins): none
  • Active form: tocopherol
  • Sources: meat, eggs, vegetable oils, leafy vegetables[7]
  • Transport: alpha-tocopherol transfer protein (α-TTP)
  • Storage: adipose tissue, parenchymal cells of the liver
  • Excretion: via bile

Functions

Vitamin E deficiency

Vitamin E toxicity

Therapeutic uses

Vitamin K (phytomenadione)

Characteristics

  • Synonyms
  • Substance class: naphthoquinones
  • Chemical structure:
    • Vitamin K1
    • Vitamin K2
  • Inactive precursors (provitamins): none
  • Active form: vitamin K hydroquinone; activation occurs via enzyme epoxide reductase
  • Sources
    • Leafy green vegetables (vitamin K1)
    • Eggs, dairy, and meat (vitamin K2)
    • Synthesized in small amounts by intestinal flora
  • Transport: via lipoproteins; no specific protein
  • Storage: liver
  • Excretion: bile and urine

Functions

Warfarin inhibits the vitamin K-dependent synthesis of clotting factors and proteins!

Koagulation isn't the same without Vitamin K!

Vitamin K deficiency [10]

Vitamin K toxicity

Therapeutic uses

Water-soluble vitamins

Name Active forms Sources Functions Deficiency Toxicity
Vitamin B1 (thiamine)
  • Whole grain cereals (e.g., whole wheat, brown rice), yeast, pork, legumes
  • No toxicity has been described
Vitamin B2 (riboflavin)
  • Meat, fish, eggs, milk, green vegetables, yeast
  • Coenzyme in redox reactions
  • No toxicity has been described
Vitamin B3 (niacin)
  • Meat (liver), cereals, seeds, legumes
  • Coenzyme in redox reactions
Vitamin B5 (pantothenic acid)
  • Liver, kidney, egg yolks, broccoli, milk
  • No toxicity has been described
Vitamin B6 (pyridoxine)
  • Meat, nuts, whole grains, vegetables
  • Dizziness
  • Nausea
  • Peripheral neuropathy
  • Dermatosis, photosensitivity [11]

Vitamin B7 (biotin)

  • Eggs, meat, fish, seeds, nuts
  • Cofactor for carboxylases, transcarboxylases, and decarboxylases
  • No toxicity has been described
Vitamin B9 (folate)
  • Green leafy vegetables, dried legumes
  • Coenzyme for 1-carbon transfer methylation reactions
  • Synthesis of nitrogen-containing bases for DNA and RNA
  • No toxicity has been described

Vitamin B12 (cobalamin)

  • Cobamamide
  • Methylcobalamin
  • Meat and dairy products
  • Macrocytic, megaloblastic anemia
  • Neurologic symptoms (e.g., paresthesias)
  • Hypersegmented polymorphonuclear cells
  • No toxicity has been described
Vitamin C (ascorbic acid)
  • Citrus fruits, strawberries, tomatoes, potatoes, cabbage, spinach
  • Scurvy
  • Weakened immune response

Vitamin B₁ (thiamine)

Characteristics

  • Synonyms: thiamine
  • Inactive precursor (provitamin): none
  • Active form: thiamine pyrophosphate (TPP); activation via intracellular phosphorylation of thiamine
  • Sources: whole grain cereals (e.g., whole wheat, brown rice), yeast, pork, legumes[12]
  • Resorption: via thiamine transporter-2 (ThTR2)
  • Transport in blood: mainly via blood cells; only ∼10% is free or bound to albumin

Functions

To remember the enzymes that thiamine is a cofactor for, think: “Thiamine PATs your Back!” (Pyruvate dehydrogenase, Alpha-ketoglutaric acid dehydrogenase, Transketolase, Branched-chain ketoacid dehydrogenase).

Vitamin B1 deficiency [13]

In malnourished or alcohol-dependent patients, always administer thiamine before giving dextrose to decrease the risk of precipitating or exacerbating Wernicke encephalopathy.

Vitamin B1 deficiency causes Ber1Ber1.

References: [15]

Vitamin B₂ (riboflavin)

Characteristics

Functions

Vitamin B2 deficiency [16]

  • Causes
    • Malnutrition
    • Restricted diet (e.g., vegan, lactose-free)
    • ↑ Demand: pregnancy, lactation
  • Clinical features
  • Diagnosis
    • Erythrocyte glutathione reductase assay: identifies subtle deficiencies
    • Erythrocyte glutathione reductase activity coefficient: the activity coefficient (AC) of glutathione reductase is measured in the presence and absence of FAD

The 2 C's of Vitamin B2 deficiency are Corneal vascularization and Cheilitis!

References: [17]

Vitamin B₃ (niacin)

Characteristics

Functions

Vitamin B3 deficiency [12]

  • Causes
  • Clinical features
    • Glossitis
    • Pellagra (caused by severe deficiency)
      • Characteristic dermatitis
        • Broad collar rash on the neck (Casal necklace); affects dermatomes C3 and C4
        • Symmetric rash with hyperpigmented skin lesions in sun-exposed areas
      • Diarrhea and vomiting
      • Neurologic symptoms (e.g, dementia, hallucinations, anxiety, insomnia, encephalopathy)

The four D's of Pellagra: Dermatitis, Diarrhea, Dementia, Death

Vitamin B3 toxicity

Therapeutic use

Vitamin B₅ (pantothenic acid)

Characteristics

Functions

Vitamin B5 deficiency [12]

Vitamin B5 is pento-thenic acid!

Vitamin B₆ (pyridoxine)

Characteristics

  • Synonyms: pyridoxine
  • Substance class: pyridoxine
  • Inactive precursor (provitamin): none
  • Active form: pyridoxal phosphate (PLP)
  • Sources: nuts, whole grains, vegetables, yeast, meat (esp. liver and poultry) [12]
  • Resorption: cleavage by phosphorylases and subsequent resorption by the intestine
  • Transport in blood: partially free, partially bound to albumin

Functions

Vitamin B6 deficiency [19]

Vitamin B6 toxicity

  • Causes: oversupplementation
  • Clinical features
    • Dizziness
    • Nausea
    • Peripheral neuropathy
    • Dermatosis, photosensitivity [11]

Therapeutic use

Vitamin B₇ (biotin)

Characteristics

  • Synonyms: biotin
  • Inactive precursor (provitamin): none
  • Active form: biotin
  • Sources
    • Plants (e.g., soy products, nuts), animal products (e.g., liver, egg yolk, dairy products)
    • Small amounts are synthesized by intestinal flora
  • Resorption: pancreatic enzyme biotinidase cleaves protein-bound biotin into free biotin active intestinal resorption
  • Transport in blood: mainly free

Functions

Biotin is a coenzyme in all carboxylase enzyme complexes that are not vitamin K-dependent!

Vitamin B7 deficiency

  • Causes
    • Malnutrition
    • Prolonged use of antibiotics (destruction of intestinal flora)
    • Excessive consumption of raw egg white: contains avidin binds biotin in the intestinal lumen → inhibition of biotin resorption
  • Clinical features

Eating raw eggs (contain avidin) impairs the resorption of biotin. Biotin loves avidin!

Vitamin B₉ (folate)

Characteristics

  • Synonyms: folic acid, folate
  • Substance class: pteridines
  • Inactive precursor (provitamin): none
  • Active form: tetrahydrofolic acid (THF)
  • Sources
    • Leafy green vegetables, fortified foods (e.g., bread, flour, and cereal)
    • Small amounts are synthesized in intestinal flora
  • Resorption: jejunum via specific transporters
  • Transport in blood: via folate-binding transport proteins
  • Storage: small reserve in the liver (enough for approx. 3–4 months)

Foliage (leafy green vegetables) contains Folate!

Function

  • THF: coenzyme for 1-carbon transfer and methylation reactions
  • Involved in the synthesis of purine bases

Vitamin B9 deficiency [20]