Continuing education.

Fat-soluble vitamins

This quiz has been prepared by Dr Samir Samman, The University of Sydney and Dr Philippa Lyons Wall, Queensland University of Technology. Correspondence should be directed to Samir Samman, Human Nutrition Unit, G08, The University of Sydney, NSW 2006. Email: [e-mail]

Introduction

Vitamins A, D, E and K comprise the fat-soluble vitamins. These vitamins are not single substances. Rather, each represents a family of structurally-related substances or vitamers, which exhibit vitamin activity. Their individual potencies can vary.

Vitamin A occurs in two basic forms: retinol and related compounds, found only in animal sources; and provitamin A carotenoids, that occur mainly in plant sources and can be cleaved to form retinol. Vitamin D as vitamin D3 or cholecalciferol, occurs in animal sources and is also derived from the action of ultraviolet light on 7-dehydrocholesterol present in skin. After absorption cholecalciferol can be hydroxylated to the more active forms, 25 hydroxy- and 1,25 dihydroxy-vitamin D3. Vitamin D2 or ergocalciferol is a synthetic form derived from ultraviolet irradiation of ergosterol (a plant sterol); and is the pharmaceutical form. Vitamin E consists of eight vitamers that exhibit differing biological activities. There are four tocopherols and four tocotrienols, each designated by the prefix [alpha], [beta], [gamma] or [delta]. Vitamin K comprises three main forms: vitamin K1 or phylloquinone which is found in green plants; vitamin K2 or the menaquinone family which is synthesised by bacteria in the large intes tine; and vitamin K3 or menadione which is a synthetic, water-soluble form that has been utilised in animal feeds.

1. Which foods are rich sources of vitamin E?

a. liver, eggs, butter

b. fatty fish, egg yolk, margarine

c. wheat germ oil, almonds, vegetable oils

d. broccoli, cabbage, spinach

2. Rank the following carotenoids in descending order of vitamin A activity.

a. [alpha]-carotene > [beta]-carotene > cryptoxanthin

b. cryptoxanthin > [alpha]-carotene > [beta]-carotene

c. [beta]-carotene > [alpha]-carotene = cryptoxanthin

d. [beta]-carotene = [alpha]-carotene = cryptoxanthin

3. Which of the options below best describes the absorption of fat-soluble vitamins?

a. requires emulsification by bile and micelle formation for maximal absorption

b. requires the action of amylase 

c. requires the action of proteolytic enzymes

d. all of the above

4. The main function attributed to vitamin K is

a. the visual cycle

b. blood clotting

c. antioxidant activity

d. maintenance of bone integrity

5. Which factors contribute to haemorrhagic disease of the newborn?

a. low capacity for synthesis of prothrombin in neonatal liver

b. poor placental transfer of lipids and low content of vitamin K in breast milk

c. absence of bacteria in neonatal intestine

d. all of the above

6. Which of the following groups are at risk of vitamin D deficiency?

a. elderly confined to nursing homes with no access to sunlight

b. children and women who inadvertently avoid sunlight for cultural or religious reasons

c. people with chronic renal failure 

d. all of the above

7. Why is [alpha]-tocopherol the predominant form of vitamin E in (fasting) plasma, while a diversity of forms of vitamin E is available from the diet?

a. [alpha]-tocopherol is the only dietary form of vitamin E which is absorbed

b. [alpha]-tocopherol is preferentially bound to a specific [alpha]-tocopherol binding protein in plasma

c. [alpha]-tocopherol binding protein in liver selectively sequesters or traps [alpha]-tocopherol while other forms are excreted in bile

d. [alpha]-tocopherol is resistant to degradation

8. Which of the following statements about supplementation with fat-soluble vitamins is correct?

a. supplementation with any fat-soluble vitamin at doses greater than the recommended dietary intake poses a health risk because they are not readily excreted in urine

b. vitamin E supplements equivalent to ten times the recommended dietary intake have no demonstrated toxic effect

c. vitamin A supplements have no side effects and can be recommended to any age group

d. fat-soluble vitamins are readily metabolised by the liver and excreted in the faeces

Answers

1. c

Fat-soluble vitamins are obtained mainly (but not always) from foods which are high in fat. Wheat germ oil, almonds and oils from other plant sources such as safflower and sunflower seeds are excellent sources of vitamin E (1). Liver, egg yolk and fortified margarines are rich sources of preformed vitamin A (retinol), with exceptionally high levels found in liver. Liver, eggs and butter provide moderate amounts of vitamin D although in countries such as Australia most of the requirements are obtained from non-dietary sources (action of ultraviolet sunlight on precursors in the skin). Vitamin K is the exception, where good sources include low-fat foods such as broccoli, spinach, cabbage and other green leafy vegetables. Vitamin K is a component of chloroplasts, the green pigments in plants, which explains the high content in these items.

2. c

Carotenoids are a large family of chemicals that provide the red and yellow pigments in plants but only a few have vitamin A activity. [beta]-Carotene is the most potent carotenoid precursor for vitamin A, although dietary factors, such as the cooking process and co-presence of fat, can influence its absorption and bioavailability. [alpha]-Carotene and cryptoxanthin have about half the potency of [beta]-carotene. In the Australian Food Composition Tables (2), carotenes are expressed as:

[beta]-carotene equivalents

= [micro]g [beta]-carotene + [micro]g [alpha]-carotene/2 + [micro]g cryptoxanthin/2

[beta]-carotene has one-sixth the activity of preformed vitamin A (retinol). Therefore the value for retinol equivalents (RE) = [micro]g retinol + [micro]g [beta]-carotene equivalents/6

3. a

Fat-soluble vitamins are absorbed with dietary fats. After ingestion, they are emulsified by bile acids, solubilised into micelles and taken up into the intestinal cells. Once inside the intestinal cells, they are incorporated into chylomicrons, which enter the lymphatic circulation and blood stream and finally deliver the fat-soluble vitamins to the liver. Malabsorption of fat-soluble vitamins may occur with very low-fat diets or with chronic biliary diseases.

The action of amylase and proteolytic enzymes is not required although these enzymes are needed in the process of digestion when other macronutrients are ingested.

4. b

The name vitamin K was coined in 1935 from the German word 'koagulation'. This vitamin is an integral part of the vitamin K cycle which results in the production of gamma-carboxyglutamate (Gla) from the precursor glutamic acid. The special feature of Gla is its ability to bind calcium ions which in turn allows the activation of clotting factors and the formation of the fibrin clot. The best elucidated function of vitamin A is in the visual cycle where it is essential for the formation of the light-sensitive pigment rhodopsin; this pigment is particularly important for vision at night. Vitamin E is a powerful antioxidant that protects cell membranes from oxidative damage by free radicals that are generated by normal metabolism as well as exogenous sources. Vitamin D acts to maintain bone integrity by promoting synthesis of calcium-binding proteins (calbindins) required for the active transport of calcium across the intestinal wall; low vitamin D status is associated with increased risk of osteoporosis.

5. d

Haemorrhagic Disease of the Newborn (HDN) is a bleeding disorder in otherwise healthy infants. HDN results from reduced formation of vitamin K-dependent clotting factors, secondary to low vitamin K status. Infants are at a high risk of HDN because their supply of vitamin K is limited as outlined in options a, b and c. Additional risk factors include the use of antibiotics which inhibit the establishment of the gastrointestinal flora. The flora is able to synthesise forms of vitamin K (vitamin 1(2 or menoquinones) which are readily absorbable. The National Health and Medical Research Council has released a statement regarding the importance of ensuring adequate vitamin K status in neonates (3). The strategy is to give vitamin K by mouth (as three doses) or by intramuscular injection (1 mg).

6. d

Vitamin D status is generally adequate in tropical or semi-tropical environments such as Australia. Although there is no recommended dietary intake (RDI) for this vitamin, it is explained in the background paper that vitamin D supplements may be required for elderly people who are immobile or infirmed and confined indoors; and in patients with chronic renal failure who are unable to hydroxylate the precursor (25 hydroxyvitamin D3) to the active form (1,25 dihydroxyvitamin D3), a process which normally occurs in the kidneys. An emerging issue is the presence of vitamin D deficiency in mainly Moslem or African women who shelter from the sun (and its ultraviolet action) due to cultural or religious reasons (4).

7. c

All forms of vitamin E (tocopherols and tocotrienols) are absorbed. These isomers are transported, by chylomicrons, in post-absorptive plasma to the liver. The liver contains a specific binding protein [alpha]-tocopherol binding protein) which binds [alpha]-tocopherol while other forms remain unbound and are excreted in bile.

8. b

Unlike most water-soluble vitamins, fat-soluble vitamins are retained in various organs which act as metabolic stores. Vitamin A is well stored in the liver and stores can be sufficient for a year or more. Toxicity as a result of consuming preformed vitamin A or retinol (ten to 100 times RDI) has been reported and vitamin A supplements during pregnancy can result in foetal abnormalities. Some complementary medicines may contain toxic quantities of vitamin A (5). Long term vitamin E supplements have no demonstrated adverse effects and some epidemiological data suggest that intake beyond the RDI may lower the risk of heart disease (6). Notably, vitamin D has a low margin of safety and toxicity has been reported in children at levels only five times greater than physiological intakes. There is no reported toxicity associated with supplements of vitamin K1 (phylloquinone) although the water-soluble synthetic form (menadione) has caused severe jaundice and haemolytic anaemia when given in high doses to infants.

References

(1.) Mann JI, Truswell AS. Essentials of human nutrition. 2nd ed. Oxford: Oxford University Press; 2002.

(2.) English R, Lewis J. Nutritional value of Australian foods. Canberra: Australian Government Publishing Service; 1991.

(3.) Available from: <URL: http://www.health.gov.au/nhmrc/publications/synopses/ch39syn.htm>. Accessed 7 May 2002.

(4.) Mason RS, Diamond TH. Vitamin D deficiency in multicultural Australia. Med J Aust 2001;175:236-7.

(5.) Coghlan D, Cranswick NE. Complementary medicine and vitamin A toxicity in children. Med J Aust 2001;175:223-4.

(6.) Rimm EB, Stampfer MJ, Ascherio A, Giovannucci E, Colditz GA, Willett WC. Vitamin E consumption and the risk of coronary heart disease in men. N Engl J Med 1993;328:1450-6.

Continuing education and the APD program

This quiz is an ideal activity for APD members to include in your CPD log, where it relates to personal learning goals. Record the time taken, to the nearest hour, to complete the quiz and any associated research.