Nutrition Facts

There are two natural forms of vitamin K and they are vitamin K₁ and vitamin K₂. Vitamin K₁ is also known as phylloquinone and vitamin K₂ is also known as menaquinone. Phylloquinone can be converted to menaquinone in some organs in humans.

Sources of vitamin K₁:

Vitamin K₁ is found mainly in the dark green leafy vegetables like kale and spinach. Vitamin K is present in vegetable oils also and it is particularly rich in olive, canola, and soybean oils. Margarine and liver also contain good quantity of vitamin K₁. Cow’s milk (60 mcg/liter) is a richer source of Vitamin K than human milk (15 mcg/liter).

Vitamin K₂ is synthesized in the intestines by intestinal flora (bacteria), which can usually supply adequate quantity of vitamin K in humans. Vitamin K is stored in liver and adipose tissues (fat store) in humans. If antibiotics are taken for long term (usually more than a week), it can suppress the normal intestinal flora that are sources of vitamin K₂ and can cause deficiency of vitamin K.

Vitamin K is required to stimulate the production and release of certain blood coagulation factors. Vitamin K is required for the posttranslational carboxylation of glutamic acid, which is must for calcium binding to alpha-carboxylated proteins such as prothrombin (blood coagulation factor II), factors VII, IX, and X. in vitamin K deficiency the prothrombin content of blood is reduced and the blood coagulation time is prolonged considerably.

Recommended daily allowance (RDA) of vitamin K: The recommended daily allowance of vitamin K in humans is approximately 100 mcg (micro gram) per day. This RDA is generally met in humans by combination of dietary sources and microbial synthesis in intestine by intestinal flora.

Infants usually have lower level of vitamin K, due to non establishment of intestinal flora, low breast milk (15 mcg/liter) levels of vitamin K, liver immaturity, poor placental transport and also due to low fat content where vitamin K is stored.

There is no clearly known deficiency disorder of vitamin E. But there is also no doubt that humans need tocopherol or vitamin E in his diet. The deficiency of vitamin E is seen only after resection of small intestine and in prolonged malabsorptive diseases, like celiac disease. There is also a very rare familial form of vitamin E deficiency disease, which is due to defect in  alpha tocopherol transport protein.

Children may develop vitamin E deficiency due to prolonged cholestasis (stasis of bile) or cystic fibrosis of long duration and this is characterized by hemolytic anemia and areflexia. If children suffer from abetalipoproteinemia, they develop vitamin E deficiency very rapidly as they can not absorb or transport vitamin E.

Symptoms of Vitamin E Deficiency:

Vitamin E deficiency causes degeneration of large myelinated axons. Peripheral neuropathy is also a major sign which is characterized by at first areflexia that progresses to ataxic gait and decrease in position and vibration sensation. Pigmented retinopathy, ophthalmoplegia and skeletal myopathy are some other symptoms of vitamin E deficiency. Deficiency of vitamin E increases virulence of viral infection due to increase in viral mutation.

Diagnosis of Vitamin E Deficiency:

Laboratory diagnosis of vitamin E deficiency is done by measuring the blood levels of alpha tocopherols. Vitamin E deficiency is if the level of alpha tocopherol is less than 5µgm/ml or alpha tocopherol is less than 0.8 mg per gram of total lipids.

Vitamin E Toxicity:

High dose of vitamin E (more than 800 mg per day) daily can cause vitamin E toxicity. All forms of vitamin E can cause toxicity. High dose of vitamin E can interfere with vitamin K metabolism and high dose is contraindicated if a patient is taking anticoagulant like warfarin. The symptoms of vitamin E toxicity are diarrhea, nausea, flatulence etc. if the daily intake is more than 1 gram.

Treatment of Vitamin E Deficiency:

Treatment of vitamin E deficiency depends on the severity and type of deficiency. Moderate deficiency with symptoms can be treated with 800-1200 mg of alpha tocopherol per day (RDA is about 15 mg per day). If deficiency is due to abetalipoproteinemia, than as much as 5000-7000 mg per day may be required. Children with symptomatic vitamin E deficiency can be treated with 400 mg/day of water-miscible (which can be mixed with water by adding an emulsifying agent) esters.

Vitamin E is the name of a group of closely related compounds that occurs in nature as fat soluble compounds called “tocopherols” and “tocotrienols”. Out of all the tocopherols, the alpha tocopherol is the most active and potent.

Sources of Vitamin E:

Vitamin E is widely distributed in nature, both in plant sources as well as animal sources. The rich plant sources of vitamin E are vegetable oils (tocopherols are present in sunflower oil, cotton seed oil, safflower oil, wheat germ oil etc. and gamma tocotrienols are present in corn oil and Soya bean oil etc.), nuts, cereals and foods that are rich in polyunsaturated fatty acids. Fruits and vegetables contain small amount of vitamin E. Rich animal source of vitamin D includes meat, egg (mainly egg yolk), butter, milk etc.

Daily Requirement of Vitamin E:

Daily recommended dose of vitamin E or RDA (recommended daily allowance) is dependent on the amount of essential fatty acids we consume. The more essential fatty acid consumption the more is the requirement of vitamin E. But the requirement is about 0.8mg/gram of essential fatty acid consumption. RDA is 15 mg/ day and the requirement is higher if more polyunsaturated fat is consumed.

Functions of vitamin E:

Vitamin E acts as a chain breaking antioxidant and is efficient in removing the chemicals that protects low density lipoproteins (LDLs) and polyunsaturated fats in membranes from oxidation. Other antioxidants like vitamin C helps to keep vitamin E in remaining reduced state. Vitamin E also inhibits synthesis of prostaglandins.

Other Advantages of Vitamin E:

There are many other advantages of vitamin E, but these advantages can not be proved strongly. Vitamin E at high dose may prevent retrolental fibroplasia (opacity of cornea in premature infants due to administration of pure 100% oxygen after delivery or birth), bronchopulmonary dysplasia and intraventricular hemorrhage of premature infants. Vitamin E is supposed to have aphrodisiac effect and also increase sexual performance. Vitamin E is also used in treatment of slowing aging process and intermittent claudication. High doses (60–800 mg/d) of vitamin E have been shown to improve immune function and to reduce colds in nursing home residents. When vitamin E is combined with other antioxidants, it can prevent macular degeneration of eye.

Vitamin D deficiency mainly causes two health problems namely rickets and osteomalacia. Other disorders due to vitamin D deficiency include bowed legs, skeletal deformation and rachitic rosary. Though vitamin D can be synthesized from sun light, the mounting evidence of skin cancer due to exposure to sunlight is forcing the general population and scientists alike to switch to dietary source of vitamin D.

Vitamin D deficiency is present even in developed countries including USA. The third National Health and Nutrition Examination Survey (NHANES III) has shown that in United States the vitamin D deficiency is prevalent throughout the nation.

The clinical manifestations of vitamin D may be due to deficient production of vitamin D in the skin, diets with low vitamin D content, increase loss of vitamin D, impairment in activation of vitamin D or resistance to effects of 1,25(OH)₂D (1,25dihydroxycholecalciferol). The causes of impaired vitamin D action may be due to (a) vitamin D deficiency (diet with poor vitamin D content, mal absorption or less production of vitamin D in skin) (b) increase loss of vitamin D (impaired enterohepatic circulation, increased metabolism due to drugs like rifampin, barbiturates and phenytoin) (c) target organ resistance (mutation of vitamin D receptors or drugs like phenytoin) (d) impaired 1? hydroxylation (renal failure, hypoparathyroidism, 1? hydroxylase mutation,  X-linked hypophosphatemic rickets, osteomalacia and antifungal drugs like ketokonazole) (e) impaired 25, hydroxylation (liver disease and drug like isoniazid).

Vitamin D, in strict sense is not a vitamin (as per definition of vitamin) and unique because it is derived both from dietary sources and sunlight.

1. Sunlight: Vitamin D is synthesized in the human body by the action of UV rays (ultra violet) on 7-dehydrocholesterol. The skin is store of large quantity of 7-dehydrocholesterol. Exposure to good quality of sunlight is very important as air pollution can filter large percentage of UV rays. Skin color if it is dark can be disadvantageous in this regard and black skin can filter up to 95 % of UV ray and hamper the formation of vitamin D from 7-dehydrocholesterol in the skin. So theoretically blacks of Africa and America can be at disadvantageous (there is advantage of black skin that black skin people rarely get skin cancer as their skin filters 95% of the harmful UV rays which are responsible for skin cancer) position as far as production of vitamin D in skin is concerned.
2. Food Sources of Vitamin D: Vitamin D is found only in the foods of animal origin. Liver, egg yolk, butter, cheese etc. are rich source of dietary vitamin D. fish liver oil is the richest source (though not consumed as food) of vitamin D. Foods that are artificially fortified with vitamin like milk, infant foods, cooking oils, ghee etc. are also rich source of vitamin D. Recently it has been found that human milk contain water soluble form of vitamin D (vitamin D sulfate) in good quantity.

Our daily requirement of vitamin D is 2.5 mcg or 100 international units (IU). 1 mcg (microgram) of vitamin D or calciferol is equal to 40 IU or 1 IU = 0.025 mcg. Some of the dietary sources of vitamin D and the content of vitamin D in that food are shown below:

1. • Halibut liver oil = 500-10,000 mcg per 100 grams
   • Cod liver oil = 200-750 mcg per 100 grams
   • Shark liver oil = 30-100 mcg per 100 grams
   • Fish fats = 5-30 mcg per 100 grams
   • Eggs = 1.25-1.5 mcg per 100 grams
   • Butter = 0.5-1.5 mcg per 100 grams
   • Milk = 0.1 mcg per 100 grams

There are two nutritionally important forms of vitamin D in men and they are calciferol or vitamin D3 and cholecalciferol or vitamin D3. Calciferol is derived by irradiation of plant sterol, ergosterol. Cholecalciferol is naturally occurring vitamin D and is found in fish liver oil and animal fats. Cholecalciferol is also derived from exposure to sunlight or ultra violet rays of sun light which can convert 7-dehydrocholesterol in skin to vitamin D. Vitamin D is a fat soluble vitamin and is stored in fat depots.

Vitamin D: The Kidney Hormone

Vitamin D is proposed to be named as kidney hormone as it does not meet the criteria to be defined as vitamin i.e. a substance that has to be obtained by dietary means because of lack of capacity of human body to synthesize it. But vitamin D3 is not a dietary requirement in presence of adequate sunlight. Human body can synthesize adequate amount of vitamin D in the skin by exposure of as little as 5 minutes per day. No more than 5 minutes exposure to sunlight is required to synthesize enough quantity of vitamin D for one day.

Vitamin D itself is metabolically inactive unless it undergoes endogenous transformations to several active metabolites like 25, hydroxy cholecalciferol and 1, 25, dihydroxy cholecalciferol, at first in liver and than in kidney. 25, hydroxy cholecalciferol and 1, 25, dihydroxy cholecalciferol are bound to transport proteins and delivered to target tissues, bone and intestines.

Functions of Vitamin D and its Metabolites:

1. In bone: Vitamin D stimulates normal mineralization of bone. It also increases normal resorption of bone. Vitamin D improves collagen maturation.

2. In Intestine: In the intestine vitamin increase absorption of calcium and phosphorus.

3. In the Kidney: Vitamin D increase re absorption of phosphates in the kidney. The re absorption of calcium in the kidney is variable.

4. Other Functions: Among the other functions of vitamin D, other than the functions mentioned above is its role in the normal growth of human body.

Excess intake of vitamin A (more than recommended daily allowance or RDA for long time, the RDA of vitamin A for normal healthy adult is 600 mcg of retinol) for long duration can lead to vitamin A toxicity, unlike water soluble vitamins, which do not have toxicity due to removal of excess water soluble vitamins through urine as they are water soluble.

Vitamin A toxicity was first reported among Arctic explorers who ate liver of polar bear and vitamin A toxicity is also seen if it is given at very high dose of more than 150 mgs in adults and 100 mgs in children. The vitamin A toxicity is seen more commonly is Eskimos, because they eat polar bear liver and seal livers, both are very rich in vitamin A. the staple diet of Eskimo is made up of rich source of vitamin A.

Excess intake of vitamin A in the form of retinol or any other form can lead to nausea, vomiting, anorexia and sleep disturbances. These are followed by desquamation of skin, enlargement of the liver and papillar edema. Increased intracranial pressure, vertigo, diplopia, bulging fontanels in children, seizures, and exfoliative dermatitis are the common symptoms of vitamin A toxicity and in severe cases it may cause death. Other common symptoms include dry skin, cheilosis, glossitis, vomiting, alopecia, bone demineralization and pain, hypercalcemia, lymph node enlargement, hyperlipidemia, amenorrhea etc. The toxicity of vitamin A mainly occurs if excess amount of vitamin A is consumed for long time from animal sources. Excess plant vitamin A usually does not lead to severe toxicity. Excess beta carotene as found in carrots and other yellow vegetables can lead to yellow coloration of plasma and skin (called carotenemia), but this do not appear to be harmful or dangerous. But excess plant carotinoids should be avoided as it can increase chance of lung cancer in smokers. Hypothyroid patients are more susceptible to the development of carotenemia due to impaired breakdown of carotene to vitamin A. Reduction of carotenes from the diet results in the disappearance of skin yellowing and carotenemia over a period of 30–60 days in these patients.

Most recently the teratogenic (abnormality of fetus due to some compounds) effect of vitamin A is the focus of research. If excess vitamin A is given to pregnant women spontaneous abortions, craniofacial abnormalities, and valvular heart disease has been reported. So in pregnancy daily dose should not be more than 3 mgs. 13-cis-retinoic acid which is commercially available can cause birth defects and should not be given during pregnancy and pregnancy should be avoided by contraception at least for 1 year after giving 13-cis-retinoic acid.

Treatment of Vitamin A Deficiency:

Vitamin A deficiency should be treated urgently as early as possible. Treatment should be very prompt and vigorous. Massive dose of vitamin A should be given, which usually reverses all the eye manifestations of vitamin A deficiency. The massive dose is about 200,000 international units (IU) or 110,000 micro grams (mcg) of retinol orally on two successive days. At this very high dose recovery occurs very fast and sequel of vitamin A deficiency can be avoided.

Prevention of Vitamin A Deficiency:

Prevention of vitamin A deficiency is generally done in two forms. First is to improve people’s diet to ensure a regular and sufficient supply of vitamin A in the regular diet. Secondly to reduce the factors that contribute to vitamin A deficiency like protein energy malnutrition (PEM) diarrhea (reduces absorption of vitamin A), respiratory tract infections measles (increases the demand of vitamin A due to increased requirement of vitamin A in maintaining the normal epithelial lining of respiratory tract, urinary tract etc.) and infectious diseases like. Both the forms of prevention and control of vitamin A deficiency are of long term and require community participation and nutrition education of the community.

The good news is that vitamin A can be stored in the body that last up to 9 months which is liberated slowly over time and can take important role in prevention of vitamin A deficiency. The vitamin A store which can last up to 9 months helps in planning cheap and effective strategy to prevent vitamin A deficiency. In developing countries like India where vitamin A deficiency is highly prevalent has developed simple technologies (National Institute of Nutrition, Hyderabad, India developed simple technology) for effective control of vitamin A deficiency. The technique is base on giving large dose of 110,000 micrograms of vitamin A as retinol palmitate orally to children of 1 to 6 years of age every 6 months. This strategy is giving excellent result in India and many other countries and it is also very cheap. This way it can be said that the children are “immunized” for 6 months against xerophthalmia.

The protection that is afforded by this large single dose of retinol or vitamin A is adequate as seen in the improvement of clinical signs of vitamin A deficiency in the community as a whole. In one of the longitudinal study in Hyderabad, India where the technique is developed, showed that the reduction of keratomalacia is about 80% in the area.

The vitamin A deficiency disorders involve mainly the eye. The vitamin A deficiency disorders include night blindness, conjunctival xerosis, corneal xerosis, Bitot’s spots and keratomalacia. There are also extra ocular manifestations. Xerophthalmia or dry eye is the term, which comprises all the ocular manifestations of the vitamin A deficiency including night blindness to keratomalacia.

1. Night blindness: The vitamin A deficiency first causes night blindness or inability to see in dim light. This is common in poor under developed countries and seen mainly in children. The mother first detects the condition when she observes that the child can not see in dark or in the evening. This is due to impairment in dark adaptation, which requires vitamin A. Night blindness increases unless the vitamin A consumption is increased and gets worsened if the child has diarrhea or other infection.
2. Conjunctival Xerosis: This is the first clinical sign of vitamin A deficiency where the conjunctiva becomes dry and non wettable. The conjunctiva appears muddy and wrinkled instead of shiny and smooth. This is described as “emerging like sand bank at receding tide”.
3. Bitot’s spot: these are ‘triangular, pearly white or yellowish, foamy” spots on the either side of cornea. In children Bitot’s spots indicate vitamin A deficiency, but in adults it indicates the sequel of earlier deficiency in childhood. Bitot’s spots are frequently bilateral (present on both eyes).
4. Corneal Xerosis: This is the stage of serious vitamin deficiency and can lead to corneal opacity and blindness. At first the cornea appears dull and dry (non wettable) and if not treated promptly can lead to corneal opacity. If deficiency is severe there may be corneal ulceration and if the cornea heals also there may be scar and opacity which affect vision.
5. Keratomalacia: This is the most serious form of vitamin A deficiency and there is liquefaction of cornea. It is a grave medical emergency. The whole cornea or part of it may become soft and burst open, which can happen very rapidly. If the eye collapses the vision is lost permanently. In poor and under developed countries keratomalacia is one of the commonest causes of blindness.

Extra ocular manifestations of vitamin A deficiency include anorexia, growth retardation, follicular hyper keratosis etc. But they are non specific. Recent studies suggest there is significant increase in morbidity and mortality even if there is mild vitamin A deficiency.

Vitamin A is widely distributed among animal and plant sources of our food. In animal foods vitamin A is present as preformed vitamin A (retinol) and in plant foods vitamin A is present as provitamin (carotenes).

The vitamin A value of food is expressed as retinol activity equivalent (RAE). 1 RAE is equivalent of 1 mcg (microgram) of retinol, 12 mcg of beta carotene, and 24 mcg of other provitamin A carotenoids.

Animal Sources of Vitamin A: Liver, egg and fish are excellent source of vitamin A (preformed vitamin A). Other rich sources of vitamin A of animal origin include butter, cheese, meat etc. The richest natural source of vitamin A is fish liver oil (cod liver oil, halibut liver oil etc.), but fish liver oil is used as dietary supplement for vitamin A deficiency, rather than as diet or food source of vitamin A. Presence of fat in the diet aid absorption of vitamin A as it is fat soluble vitamin.

Plant Sources of Vitamin A: Very cheap and rich plant source of vitamin A is green leafy vegetable like spinach, amaranth etc. Other rich plant sources of vitamin A include colored vegetables (tomato, pumpkin, carrots, beet root etc.) and fruits like papaya, orange, mango, pineapple, brown grapes etc. The darker the vegetable the better is the vitamin A content of the vegetable. Moderate cooking of vegetables enhances carotenoid release for uptake in the gut and help in absorption of vitamin from gut due to higher availability.

Fortified Foods for Vitamin A: Foods fortified with vitamin A are also very important source of vitamin A. Food fortifications are done for milk, cooking oils, ghee, butter etc.

Some foods with vitamin A content in mcg/100 gram:

• Halibut liver oil- 900,000 mcg/100 grams
• Cod liver oil- 18,000 mcg/100 grams
• Liver (beef) - 16,500 mcg/100 grams
• Egg- 140 mcg/100 grams
• Butter- 825 mcg/100 grams
• Cheese- 350 mcg/100 grams
• Milk (cow) - 38 mcg/100 grams
• Fish- 40 mcg/100 grams
• Carrot- 1167 mcg/100 grams
• Spinach- 607 mcg/100 grams
• Green leaves- 300 mcg/100 grams
• Amaranth- 515 mcg/100 grams
• Tomato- 84 mcg/100 grams
• Mango- 313 mcg/100 grams
• Orange- 25 mcg/100 grams

The liver is the store house for vitamin A in humans and other animals, so liver is a rich source of vitamin A. Vitamin A is stored in liver in the form of retinol palmitate. In normal person the store in liver can supply vitamin A requirement for 6-9 months or more. So in general vitamin deficiency means, it is long term deficiency.