The absorption of ascorbic acid occurs actively as well as passively (see Chapter 16 ‘How do drugs get into cells?’ p. 123). When the concentrations of ascorbic acid are low, active transport predominates, whereas at high concentration the active transport system becomes saturated leaving only passive diffusion. Therefore, slowing down the rate of stomach emptying (see Chapter 15 ‘Methods of administration’, p. 117) or providing a slow-release form of ascorbic acid should increase its absorption.

• Dietary Sources

• Fruits: particularly citrus fruits and juices.

• Vegetables: potatoes are a common source.

• Green and red peppers.

• Deficiency

Scurvy: a group of symptoms including tiredness, muscle weakness, joint and muscle aches, bleeding gums and skin rash.

• High Doses

• High doses of vitamin C will cause diarrhoea due to the increased concentration of vitamin C in the gut pulling water into the gut by osmosis.

• Very high doses of vitamin C can precipitate an acute sickle-cell crisis in patients with sickle-cell disease.

• If a patient has iron-overload (as is the case with porphyria; see Chapter 28 ‘Blood disorders’, p. 211) vitamin C should be avoided. This might be due to the ability of the ascorbate to stimulate iron-dependent peroxidation of membrane lipids under certain conditions (see Figure 7.4, p. 45).

B-complex Vitamins

These are divided into those associated with:

• Energy production: thiamin (vitamin B₁), riboflavin (vitamin B₂), pantothenic acid (vitamin B₅), niacin (nicotinic acid), pyridoxine (vitamin B₆) and biotin.

• Haematopoietic (blood cell formation) vitamins: cobalamin (vitamin B₁₂) and folic acid.

• B Vitamins Involved with Energy Production

Vitamin B₃ (Niacin or Nicotinic Acid)

Forms part of the nicotinamide adenine dinucleotide (NAD) structure (see Figure 12.3, p. 91 and Chapter 19 ‘Pharmacodynamics: how drugs elicit a physiological effect’, p. 139).

Dietary Sources

Note: Although vitamin B3 is found in maize, it is largely in a bound form and therefore not available as a nutrient. This is worth bearing in mind in patients consuming large quantities of maize in the diet and very little meat.

Signs and Symptoms of Deficiency

• Pellagra: leads to a triad of dermatitis, diarrhoea and dementia.

• Oral lesions and a red tongue: might be the only noticeable symptoms.

Large doses of nicotinic acid have been found to lower both cholesterol and triglyceride levels in the bloodstream, as it is responsible for inhibiting their synthesis.

Note: nicotinamide is usually preferred to nicotinic acid as a supplement because there is less chance of gastric irritation.

Vitamin B₅ (Pantothenic Acid)

Involved in synthesis and oxidation of fatty acids and other important energy- producing reactions (see Chapter 19 ‘Pharmacodynamics: how drugs elicit a physiological effect’, p. 139).

Dietary Sources

Signs and Symptoms of Deficiency

Very rare because it is so easily obtained from food.

Vitamin B₆ (Pyridoxine, Pyridoxal and Pyridoxamine)

• Necessary for normal cell membrane function and stability: assists in the balancing of sodium and potassium, hence neurological problems with a deficiency (see Figure 31.1, p. 236).

• Promotes red blood cell production.

• Prevents the formation of homocysteine (see Chapter 36 ‘Metabolic disorders’, p. 296).

Dietary Sources

This vitamin is easily destroyed by food processing:

• Meats are the best source.

• Fruits.

• Vegetables.

• Whole grains.

Signs and Symptoms of Deficiency

• Tissue changes: including glossitis (inflammation of the tongue), stomatitis.

• Neurological: depression, headaches, nausea, weakness, tingling and pain in the extremities.

• Microcytic hypochromic anaemia: see Chapter 28 ‘Blood disorders’, p. 209).

• Elevated homocysteine levels: see Chapter 37 ‘Metabolic disorders’, p. 296).

Vitamin H (Biotin)

• Involved in fatty acid and amino acid metabolism.

• Contains sulphur.

• Synthesized in the lower gastrointestinal tract by commensals.

Dietary Sources

• Liver.

• Egg yolk: egg white contains a biotin-binding glycoprotein (see Chapter 9 ‘Carbohydrates’, p. 71), so excessive consumption can potentially create a biotin deficiency.

• Grains.

• Soy.

• Yeast.

Signs and Symptoms of Deficiency

• Rare.

• Haemopoietic B Vitamins

Vitamin B₁₂

Vitamin B₁₂ is bound to a protein that is removed in the stomach. Intrinsic factor, a protein produced by the parietal cells in the stomach wall, then combines with the vitamin B₁₂ complex. This protects the complex against bacteria and degradation by digestive enzymes, and improves its absorption through the small intestine wall. Vitamin B₁₂ can be absorbed without intrinsic factor but not as easily. Once absorbed, the intrinsic factor is cleaved off.

Its structure is similar to that of chlorophyll (see Figure 9.1, p. 64) and the haem structure found in red blood cells, but with cobalt instead of magnesium or iron.

Dietary Sources

• Meats.

• Seafood and fish.

• Dairy products (but not to such a great extent as the above).

Given the right environment, the bacteria of the colon can synthesize vitamin B₁₂.

Deficiency

• Pernicious anaemia: vitamin B₁₂ deficiency leads to large red blood cells (macrocytic, megaloblastic anaemia; see Chapter 28 ‘Blood disorders’, p. 210). Although apparently having a normal structure, they are far more fragile than normal blood cells and therefore easily prone to rapidly breaking down.

• Overt vitamin B₁₂ deficiency can take quite a few years to become evident.

• Neurological: paraesthesia, peripheral neuropathy.

Reasons for Vitamin B₁₂ Deficiency

Autoimmune inflammation of the stomach creates a progressive destruction of the cells in the stomach wall, which leads to decreased secretion of the enzymes and acid required to release the vitamin B₁₂ complex from its dietary protein. Antibodies bind to intrinsic factor, inhibiting its attachment to vitamin B₁₂ and therefore its absorption. There is also a neurological element involved.

As vitamin B₁₂ is found only in animal food sources, it might be necessary for vegans to use vitamin B₁₂ supplementation.

Drug Interactions Specific to Vitamin B₁₂

• Proton pump inhibitors (e.g. omeprazole; see Figure 35.3, p. 277): decrease the stomach acid secretions necessary for the efficient absorption of vitamin B₁₂. This does not appear to affect supplements. The H2-receptor antagonists (Tagamet, Zantac, etc.) have also been found to reduce vitamin B₁₂ absorption, but the inhibition of secretions is not as prolonged as with the proton pump inhibitors. For this reason, H₂ receptor antagonists (see Figure 35.2, p. 276) are less of a problem as regards to vitamin B₁₂ deficiency.

• Neomycin (antibiotic).

• Colchicine (antigout).

• Metformin (type 2 diabetes).

Supplementation of vitamin B₁₂ is possible because the vitamin B₁₂ is not bound to protein and enters the body through an alternative pathway to that required for vitamin B₁₂ ingested in the normal diet.

Importance of Vitamin B₁₂ and Folic Acid

• Vitamin B₁₂ and folic acid are required for the synthesis of DNA: the erythroblasts, the precursor to the red blood cells, are unable to form normal red blood cells if these vitamins are deficient.

• Vitamin B₁₂ is responsible for activating folic acid to its active form.

Fat-Soluble Vitamins

• Vitamins A, D, E and K.

• Are absorbed from the gut along with dietary fats, so in any condition in which the fat is substantially reduced in the diet (e.g. a low-fat diet) or in cases where the patient is consuming very little fat absorption, this can be impaired.

• Can be stored in the fat and therefore possibly reach a level of toxicity if they are not utilized.

• Require at least 10g per day of fat in the diet to be absorbed efficiently.

Vitamin D

Two types:

• D₂ (cholecalciferol): of plant origin.

• D₃ (ergocalciferol): manufactured in the skin. Sunlight starts the conversion of a cholesterol-related vitamin D precursor in the skin to an active form.

Needed for:

• Bone formation: in calcium metabolism, works in conjunction with parathyroid hormone (see Figure 37.1, p. 290).

• Regulating blood pressure.

• Tumour suppressant.

• Dietary Sources

• Eggs.

• Butter.

• Fortified food products such as milk or margarine.

Phytates can interfere with vitamin D absorption (see Chapter 15 ‘Methods of administration’, p. 120). Storage, cooking and processing do not appear to degrade vitamin D.