The Fat Soluble Vitamins

The Fat Soluble Vitamins


Vitamin A consists of a family of inter-related preformed vitamers, retinol, retinal and retinoic acid. Retinol and retinal are inter-convertible, whereas retinoic acid is formed by irreversible retinal oxidisation. Vitamin A is stored in the body as retinyl esters that can be hydrolysed to produce retinol, which can then be converted into retinal as required.

Several provitamin compounds called carotenoids are also included in the vitamin A family, as these carotenes, particularly beta-carotene, can be converted by the body into retinal by the enzyme carotene dioxygenase within the  intestinal mucosa.

Vitamin A has multiple functions within the body: it is essential to growth and development, maintenance of good immune system function and retinal is vital to good vision, combining in the eye with the protein opsin to form rhodopsin, which initiates nerve impulses on light exposure. Retinoic acid does not function in the visual cycle but is essential for embryonic growth and cellular differentiation.

Vitamin A deficiency:
Vitamin A deficiency is not uncommon in developing countries and the lower socioeconomic strata of developed countries and may manifest clinically with the following symptoms and signs:

Impaired night-vision, aching and tired and burning eyes, inflamed eyelids, painful eyes, xeropthalmia,
headaches, sinus congestion, recurrent URTI and flu-like illness, dry and flaky skin, lumpy skin(toad skin), acne-type skin lesions, dull and lustreless hair, ridged nails, peeling nails, impaired libido, breast soreness.

Mental changes: Insomnia, fatigue, depression, neuralgia in limbs.

Vitamin A toxicity:
Vitamin A is potentially toxic at daily doses above 10,000 IU/day and even 5000 IU/day over a long time period is thought to contribute to osteoporosis, whilst when  taken during pregnancy is reportedly associated with foetal growth defects.

Supplemental dosage:
Require up to 2000 – 3000 IU/day.  Supplements of 5,000 IU daily in fish liver oil are usually well-tolerated by adults.

Rich Natural Sources:
Animal forms: Cod-liver oil, liver, kidney, egg yolk, butter milk, cheese.
Plant forms (beta-carotene): Leafy green and red vegetables, carrots, sweet-potato, squash and yellow fruits.

Therapeutic dosage:
10,000 to 25,000 IU /day for short periods of time only :
NOTE – this is a potentially toxic dose range. Liver toxicity indices must be closely monitored.

Signs of Toxicity:
Cerebral symptoms: Irritability, insomnia, fatigue, depression, headache, intra-cranial pressure feeling.  Gastro-intestinal symptoms: Anorexia, nausea, abdominal pains, tender liver, enlarged liver, jaundice, weight-loss, oedema.

Skin symptoms:
Dry skin, cracked and flaky skin, cracked lips, hair loss, yellowed skin.

Bone symptoms:
Irregular bone thickening, tender and aching bones, osteopenia, spontaneous fractures.

Muscle and joint aches and pains, sore eyes, eye haemorrhage, night sweats, irregular periods.

NOTE: Excessive Vitamin A is a potent teratogen (causes foetal damage).


Vitamin D is not actually a vitamin, as it is synthesised in the body and comprises several fat-soluble steroid molecules that enhance intestinal absorption of calcium, iron, magnesium, phosphate and zinc. In humans and other animals, sunlight exposure results in the production of Vit D3 (cholecalciferol) from cholesterol, whilst Vit D2 (ergocalciferol) is produced by phytoplankton, yeasts and fungi. Both cholecalciferol and ergocalciferol are readily absorbed from dietary sources and supplements. Vit D3 is initially hydroxylated by the liver into hydroxy-calciferol and binds to the Vit D-Binding Protein for storage and distribution to the rest of the body. When required for active calcium metabolism, calcitriol is further activated into the active metabolites, calcitriol (1’25-dihydroxycalciferol). Ergocalciferol undergoes a similar 2-step activation into calcitriol but is far less active than the Vit D3 form.

Although vitamin D is not an essential dietary vitamin, it was nevertheless identified in studies seeking to find the dietary substance lacking in rickets, the childhood form of osteomalacia.

The active vitamin D metabolite calcitriol mediates its biological effects by binding to the vitamin D receptor (VDR), which is principally located in the nuclei of target cells. Calcitriol binding to the VDR allows the VDR to act as a transcription factor that stimulates the gene expression of transport proteins, which are involved in calcium absorption in the intestine.

One of the most important roles of vitamin D is to maintain skeletal calcium balance by promoting calcium absorption in the intestines and promoting bone resorption thereby regulating calcium and phosphate levels for bone formation, and allowing proper functioning of parathyroid hormone to maintain serum calcium levels.

Vit D deficiency:
Vitamin D deficiency reduces bone mineral density (osteomalacia & rickets) and increases the risk of bone deformity and fracture, due to altered calcium metabolism. As the Vitamin D receptor is involved in cell proliferation and differentiation, Vit D deficiency may affect immune system and white blood cell activity and reportedly impairs anti-cancer and anti-aging processes in the body.

Vit D deficiency may manifest with the following clinical symptoms and signs:
Burning mouth and throat, scalp sweating (esp. at night), insomnia myopia, aching and sore eyes, muscle pain, muscle cramps, bone pain, deformed bone growth, easy fractures, nervousness anxiety, restlessness, hypothyroidism(underactive thyroid).

Supplemental dosage:
Require approximately 400 I.U. /day.  In winter: 1 tspn of cod liver oil is beneficial.

NOTE: Vitamin D may be toxic in high dosage.

Rich Natural Sources:
Cod liver oil, dairy food, skin synthesis with sun exposure.

Therapeutic dosage:
1500 to 2500 IU/day from fish liver oil.
NOTE: Calcium and phosphorus must also be supplied AND patient monitored for toxicity symptoms.

Signs of Toxicity:
Headache, frequent urination, kidney damage,anorexia, nausea, vomiting, diarrhoea, muscular weakness, muscle pain, calcification of soft tissues.


Vitamin E comprises a group of eight fat-soluble compounds, 4 tocopherols (alpha, beta, gamma & delta) and 4 corresponding tocotrienols that constitute the naturally occurring Vit E complex. These compounds are essential components of the human diet and are synthesized exclusively by plants and algae. They exhibit strong antioxidant activity that purportedly protects cell membranes and mitochondria from oxidative damage.

Alpha-tocopherol is the most common and most studied member of the Vitamin E family and current studies suggest that it actually exhibits little antioxidant activity in the body but instead exhibits significant biological activity via regulation of specific enzymes involved in production of inflammatory chemicals, blood platelet aggregation, gene expression involved in cell proliferation and neurological function.

Gamma-Tocopherol is the most common dietary form of vitamin E in the diet in the USA, though not in Europe and it is now clear that, along with other tocopherols & tocotrienols, it exhibit functions that are not shared by alpha-tocopherol. The biological activities of these other Vitamin E forms are not apparently connected to their chemical antioxidant properties but rather reflect anti-inflammatory, anti-neoplastic, and natriuretic (salt excretion) functions. Emerging evidence suggests that γ-tocopherol is a better preventive factor for certain types of cancer and myocardial infarction than is α-tocopherol, whilst the tocotrienols reportedly exhibit significant neuroprotective, antioxidant, anti-cancer and cholesterol lowering properties that differ from the properties of tocopherols.

Because the vast majority (99%) of past studies on Vit E health benefits has been focused almost exclusively on alpha-tocopherol, the more significant preventive health benefits of the other members of the Vit E complex family have been overlooked and provide a highly skewed perspective on the utility of Vit E therapy.

Vit E deficiency:
Vitamin E deficiency may manifest clinically with the following signs and symptoms:
Impaired circulation, cold and pale peripheries, disturbed nail growth, hyperkeratosis of heels, muscle soreness with exercise, tender calf muscles, muscle weakness, muscle wasting, fatigue, restless sleep, insomnia, dizziness, impaired balance, gait disturbance (ataxia), premenstrual syndrome (PMT), breast soreness, menopause symptoms, loss of libido, impotence, signs of premature ageing, cataracts, retinal degeneration, haemolytic anaemia, thrombocytosis, increased risk of arteriosclerosis, heart disease and stroke, liver damage (cirrhosis), and senile dementia.

Supplemental dosage:
RDA is nominally 15 IU/day.  For optimum tissue protection, at least 200 – 800 IU/day of the Vitamin E complex is recommended for adults.

Rich Natural Sources:
Wheat germ, vegetable oils (only if cold-pressed), green-leafy vegetables, whole-grain cereals, nuts and seeds, egg-yolk, meats (especially organ meats such as liver).  NOTE: the requirement for Vitamin E increases with oil intake.

Therapeutic dosage:
500 to 2000 IU for adults.

Symptoms of Toxicity:
Dizziness, headache, muscle weakness, raised blood pressure, immune system suppression at very high intake.


Vitamin K comprises two naturally-occurring fat-soluble vitamers, Vitamin K1 & K2, that are required in the production of specific proteins essential for blood clotting. Vitamin K1 is synthesised by plants and is active in the blood coagulation process. It is converted into Vit K2 by animals, intestinal bacteria and by food fermentation. Vit K2 but not K1 exhibits significant biological activity (in conjunction with Vitamin D) in bone synthesis and metabolic pathways involved in preventing coronary artery calcification, immune system function, cancer prevention and protection against brain cell degeneration.

Vitamin K deficiency:

Vitamin K deficiency may present clinically with an increased bleeding tendency, with easy bruising and haemorrhage, that can be life-threatening.

Whereas, prolonged sub-clinical vitamin insufficiency is associated with increased risk for the development of age-related diseases, such as osteoporosis, cardiovascular disease, accelerated brain cell aging and cancer. Recent research also suggests impaired blood sugar control may occur with inadequate Vitamin K intake.

Supplemental dosage:
Theoretically Vit K supplementation is unnecessary, as Vitamin K is produced in intestine by the friendly flora. However, there is now doubt that intestinal bacterial Vit K2 production is biologically available in humans, and moreover, may be impaired if the bowel flora is heavily disturbed (dysbiosis) or if alcohol intake is high.
In view of the increasing incidence in cardiovascular disease, dementia, diabetes and osteoporosis, specialists in vitamin  K research suggest that greater dietary intake and/or supplements of about 45 – 200 ugm/day be encouraged.

Rich Natural Sources:
Fermented foods (particularly natto), normal intestinal bacterial flora, leafy-green vegetables, tomatoes, pork liver, lean meat, peas, carrots, soybeans, potatoes.

Therapeutic dosage:
200 to 1600 micrograms.

Symptoms of Toxicity:
Natural Vit K1 & K2 are non-toxic, but synthetis Vitamin K3 is toxic and moverdosage may cause haemolytic anaemia and jaundice.

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