Calcium, iron and zinc--essential minerals.

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.

Introduction

There are over 15 minerals which are essential for life. Although comprising only about 4% of total body weight, they are widely required and inadequate intake will result in suboptimal function or a deficiency disease that is preventable by physiological amounts of the mineral. This nutritional science quiz is designed to enhance your understanding of three important minerals--calcium, iron and zinc.

The average body content of calcium is 1000 to 1200 g, primarily localised in the skeleton (99%) where it provides structural rigidity to bones and teeth. The remainder (1%) is distributed in the intra- and extracellular fluids with varied roles including muscle contraction, blood clotting, enzyme activation and other cellular processes. Strict hormonal regulation ensures that optimal concentration of ionised calcium in plasma, a quantitatively small but vital metabolic pool, is maintained (1,2). In contrast, the body contains much smaller amounts of iron and zinc. Although normally between 2 and 4 g, the total amount of iron is not only related to body weight but also to physiological conditions including age, gender, pregnancy and growth. The majority of functional iron (about 65%) is localised in haemoglobin and myoglobin for transport of oxygen to tissues, with a variable proportion (about 25%) in ferritin stores. A small but important fraction is present in the iron-containing enzymes, including the cytochromes, which are involved in oxidative phosphorylation and production of cellular energy (1,2). The normal body content of zinc is between 1.5 and 2.5 g, found in all organs and tissues, mainly intracellularly, and in body fluids. Zinc is an integral component of over 200 different metalloenzymes which contribute to its remarkable diversity of function, including protein digestion, protein synthesis, collagen formation, detoxification of alcohol, elimination of carbon dioxide, sexual maturation, night vision and taste acuity (1,2).

1. Rich food sources of calcium, other than dairy products include:

a. almonds, spinach, broccoli

b. rump steak, wheat bran, oysters

c. sardines, dried figs and tofu

d. wholemeal bread, fortified breakfast cereals and vegemite

2. Absorption of non-haem iron in mixed meals can be maximised by which of the following:

a. 75 g of meat (a moderate serve)

b. 75 mg of vitamin C (equivalent to a glass of fruit juice)

c. 30 g of meat plus 25 nag vitamin C (a small serve of meat plus a small glass of fruit juice, respectively)

d. any of the above

3. Which of the following proteins is integral to the process of calcium absorption?

a. calcitriol

b. calmodulin 

c. calbindin

d. calcitonin 

4. Which of the following factors promotes the bio-availability of calcium from foods?

a. oxalate, fibre and phytic acid

b. lactose

c. ageing

d. surgical resection of the colon

5. A large proportion of Australian women consume zinc at levels lower than the recommended dietary intake yet diagnosed deficiency is rare. Possible reasons are that:

a. the recommended dietary intake is too high

b. biochemical markers of zinc are ineffective

c. symptoms of mild zinc deficiency are unclear

d. all of the above

6. A symptom of mild zinc deficiency is:

a. delayed growth

b. garlic odour to breath

c. rickets 

d. tetany 

7. The prevalence of haemochromatosis is approximately:

a. 1:8

b. 1:200

c. 1:1 000

d. 1:10 000

8. Which is the most sensitive marker of iron deficiency?

a. plasma iron

b. transferrin saturation

c. serum ferritin

d. serum haemoglobin

9. Which of the following statements is true? Zinc supplements:

a. prevent diarrhoeal infections in children

b. reduce symptoms of the common cold

c. are effective in healing arterial or venous ulcers

d. increase lean body mass

Answers

1. c

Calcium is found widely in plant and animal foods. The richest sources of bioavailable calcium are dairy products. Rich non-dairy sources are canned fish with bones (e.g. sardines, salmon), dried fruits (e.g. figs) and tofu, especially when calcium is used to precipitate the curd (3). Other rich but less well absorbed sources are selected nuts (e.g. almonds) and green leafy vegetables (spinach but not broccoli). Meats are notably poor sources of calcium.

Rump steak and other red meats, and wheat bran or germ, are rich sources of iron and zinc. Breakfast cereals can be fortified with these minerals and Vegemite is also a good source. Oysters are a strikingly rich source of zinc although, interestingly, concentrations are fourfold lower in smoked compared to fresh oysters (4).

2. d

Iron in food occurs most commonly as ferric iron which is sparingly soluble and cannot be absorbed without modification to a soluble form. The copresence of animal protein from meat, fish or poultry (the 'MFP' factor) enhances absorption due to the presence of peptides that arise from digestion of the contractile proteins, actin and myosin. Vitamin C can also increase absorption by reducing ferric iron to the more soluble ferrous form; other enhancing factors found in fruit juices include citric acid and sugars, fructose and sorbitol.

Absorption of nonhaem iron can be estimated, using the Monsen equation (cited in 1), from the content of meat, fish or poultry and / or ascorbic acid consumed with the nonhaem iron source. Maximal absorption of 6-8% is achieved with 75 units of ascorbic acid or meat, fish, poultry, or 25 units of meat plus 25 units of ascorbic acid (where one unit is equivalent to 1 mg ascorbic acid or 1 g cooked meat, fish or poultry). The effect is dose-dependent although quantities in excess of 75 units have no added effect. In the absence of enhancing factors, absorption is minimal. In addition to the enhancing effects on nonhaem iron, meat itself is a rich source of iron contained within the haem ring, which is soluble and readily absorbed. Haem iron absorption is inversely related to iron stores, and ranges from 15-35%. Of all foods, meat makes the greatest contribution to iron status.

3. c

Calcitriol or 1,25-dihydroxyvitamin D is the active form of vitamin D. Calcitriol together with parathyroid hormone (PTH) regulates plasma calcium concentrations by interacting at three major sites: the small intestine, bone and kidneys. Hypocalcaemia triggers secretion of PTH which in turn stimulates synthesis of calcitriol in the kidney. Calcitriol interacts with receptors in the enterocyte and upregulates the synthesis of calcium-binding protein, calbindin, which facilitates absorption of calcium. PTH and calcitriol also act on bone to mobilise calcium, and in the distal renal tubule, to stimulate calcium reabsorption.

When calcium concentrations begin to rise above normal, calcitonin is released from the thyroid gland and acts rapidly to promote deposition of calcium in bone, thereby restoring calcium levels. The concentration of plasma calcium is therefore tightly regulated, reflecting the critical role of ionised calcium in muscle contraction. Hypocalcaemia results in tetany due to increased neuromuscular excitability, while hypercalcaemia results in depressed neuromuscular excitability with cardiac arrhythmias and muscular weakness. Calmodulin is a calcium-binding protein that regulates many calcium dependent enzymes (1).

4. b

True enhancers of calcium absorption have not been identified however, carbohydrates such as lactose appear to improve the absorption of calcium by facilitating its passive diffusion across the villi (2,5). In contrast, the most potent inhibitor of calcium absorption is oxalate which is found in spinach, rhubarb and to a lesser extent in sweet potatoes and beans. Oxalate along with dietary fibre and phytic acid are able to bind calcium and reduce its bioavailability. Phytate and tannins are found in many plant foods, especially cereals, nuts and legumes, although concentrations vary widely within food groups. The magnitude of inhibition by these dietary factors is determined largely by the extent of bacterial degradation which frees calcium for absorption in the colon. Surgical resection of the colon can impair absorption and in the elderly, absorption diminishes because of the reduced response to calcitriol (2).

5. d

According to the National Nutrition Survey (NNS), the major source of zinc in the Australian diet is meat and poultry, which provide 39% and 32% of intake for men and women respectively (6). The NNS also shows a large proportion of Australians, especially women and girls, are consuming zinc in amounts well below the recommended dietary intake (RDI). This scenario is also observed in other industrialised countries. The significance of reduced intake relative to the RDI is dependent on the identification of a reliable indicator of zinc status. Current approaches have not been entirely successful. Emerging knowledge about zinc, especially zinc fingers, may lead to a new biomarker of zinc status.

6. a

Zinc has been recognised as an essential nutrient for humans for nearly half a century 12). It is essential because of the large number of metabolic functions in which it participates, mainly via enzymatic action. A more fundamental role of zinc has emerged in recent years, namely its ability to regulate gene expression. Zinc regulates gene expression via the action of 'zinc fingers' which bind to the promoter region of genes and allow their expression. An example of the significance of zinc fingers is in the assimilation of some vitamins and nutrients via the superfamily of nuclear hormone receptors which includes receptors for thyroid hormone, retinoic acid, vitamin D, cholesterol, fatty acids and related metabolites. The physiological actions of a number of nutrients (e.g. vitamin A) and hormones (e.g. thyroid hormone) can be realised only following the interaction between the zinc finger region of the receptor and DNA. The number of physiological functions which is attributed to zinc is growing, since it has been estimated that zinc finger domains are coded by up to 3% of the human genome.

Zinc deficiency results in a reduction in zinc-related metabolic functions which culminate in growth retardation and possibly dwarfism, as reported in the first case of extreme zinc deficiency (2).

7. b

Haemochromatosis is a relatively common genetic disorder with a homozygous frequency in Caucasians of one in 200; a further one in eight individuals are carriers of the gene (7). The disorder is characterised by increased iron absorption, at least two times the normal rate. Since physiological mechanisms for iron excretion are limited, the excess iron slowly accumulates and is deposited in soft tissues. Content can reach as high as 50 g compared to normal levels of 2.5 g (women) or 3.5 g (men). Due to the slow onset and non-specific nature of early symptoms (e.g. fatigue, generalised aches) haemochromatosis is often not diagnosed until middle age, after significant tissue damage. The normal age of diagnosis is 20 to 40 years in men and later, after menopause, in women because iron losses during menstruation and pregnancy provide some protection. Clinical features include cirrhosis, cardiomyopathy and diabetes with bronze pigmentation of skin (or bronze diabetes). Heterozygotes show abnormal iron status but do not usually develop organ abnormalities (1).

Haemochromatosis can be exacerbated by dietary factors that enhance iron absorption. Strategies to minimise iron overload include ingesting less haem (meat and associated MFP factor) compared to nonhaem sources (nuts, fruits, vegetables, grains, eggs) and avoiding vitamin C supplements, which enhance absorption of nonhaem iron 18). In view of the high prevalence and underdiagnosis of haemochromatosis, the relatively high intake of vitamin C in Australia (124 mg/d in adults) (6) could exacerbate the condition in predisposed individuals. The major treatment remains regular phlebotomy.

8. c

The major physiological compartments of iron are hepatic ferritin stores (in equilibrium with serum ferritin), circulating iron (bound to protein transferrin, normally about 30% saturated) and erythrocyte iron (haemoglobin). Iron deficiency occurs in three stages with sequential changes in each compartment.

In the initial stages, iron stores become depleted and serum ferritin concentration is low although iron transport and synthesis of haemoglobin can be normal. As iron deficiency proceeds, circulating iron is lowered and therefore tranferrin saturation decreases. In the final stages, synthesis of red blood cells is reduced and anaemia develops, indicated by a low blood haemoglobin. The red blood cells are pale (hypochromic) and small (microcytic). Iron deficiency is difficult to diagnose from symptoms alone, as symptoms such as tiredness are nonspecific. Therefore in practice, numerous measurements are used to assess iron status but serum ferritin is the more sensitive marker since it indicates early iron deficiency. Serum transferrin receptors on cell surfaces also increase in the initial stages of deficiency, due to upregulation that enables the cells to better compete for iron that is bound to transferrin; although not widely used, they are a potential tool for the future It,5).

9. a

The immune system turns over at a rapid rate and in doing so requires the synthesis of proteins and cells. In order to function optimally, the immune system must also have the ability to react quickly to antigens. Due to its role in zinc fingers and as a component of numerous enzymes, zinc plays a central role in the immune system. In zinc deficiency in humans and in experimental models, there is a suppressive effect on thymic function, T-lymphocyte development, lymphocyte proliferation, T-cell dependent B-cell functions, leading to a decrease in the resistance to infections. Zinc stimulates the production of interleukin-1 (IL-1) and appears to interact with other nutrients in this response.

Recent studies have shown that zinc supplementation reduces the duration of acute, severe diarrhoea in children, especially in those with lower initial zinc status. This effect may be mediated by improving immune status (5). In contrast, the evaluation of a number of clinical trials through the Cochrane Database indicates that the effectiveness of zinc lozenges in the treatment of the common cold is inconclusive (9). Similarly, zinc supplements do not appear to aid in the healing of leg ulcers although there is weak evidence of benefit in people with low serum zinc concentrations (10).

References

(1.) Groff JL, Gropper SS. Advanced nutrition and human metabolism. 3rd ed. Australia: Wadsworth Thomson Learning; 2000.

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

(3.) Holland B, Welch AA, Unwin ID, Buss DH, Paul AA, Southgate DAT. McCance and Widdowson's The composition of foods. 5th ed. Hertfordshire, UK: The Royal Society of Chemistry; 1992.

(4.) English R, Lewis J. Nutritional values of Australian foods. Canberra: Department of Community Services and Health; 1991.

(5.) Shils ME, Olsen JA, Shike M, Ross AC. Modern nutrition in health and disease. 9th ed. Sydney: Williams & Wilkins; 1999.

(6.) McLennan W, Podger A. Australian Bureau of Statistics. National Nutrition Survey: Nutrient intakes and physical measurements, Australia 1995. Canberra: Commonwealth Department of Health and Aged Care; 1998.

(7.) Beers MH, Berkow R, editors. The Merck manual of diagnosis and therapy. 17th ed. Whitehouse Station, NJ: Merck Research Laboratories; 1999.

(8.) Mahan LK, Escort-Stump S, editors. Krause's Food, nutrition & diet therapy. 10th ed. Sydney: WB Saunders; 2000.

(9.) Marshall I. Zinc and the common cold. Cochrane Database of Systematic Reviews, 3, 2003.

(10.) Wilkinson EA, Hawke C. Oral zinc for arterial and venous leg ulcers. Cochrane Database of Systematic Reviews, 3, 2003.

This quiz has been prepared by Dr Philippa Lyons-Wall, School of Public Health, Queensland University of Technology and Associate Professor Samir Samman, Human Nutrition Unit, The University of Sydney. Correspondence should be directed to Philippa Lyons-Wall, School of Public Health, email: [e-mail]