Article pp.375-413 du Vol.21 n°4 (2001)

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CHAPTER 2

Micronutrients

1 - MINERALS AND TRACE ELEMENTS

1.1 Introduction

The essential mineral elements are usually divided into two categories: on the one hand, the major minerals or macro elements, which include sodium (Na), potassium (K) and chlorine (Cl), these first three elements often being described as “electrolytes”, plus calcium (Ca), phosphorus (P) and magnesium (Mg), and, on the other hand, the trace elements, including iron (Fe), zinc (Zn), copper (Cu), manganese (Mn), iodine (I), selenium (Se), chromium (Cr), molybdenum (Mo), fluorine (F), cobalt (Co), silicium (Si), vanadium (V), nickel (Ni), boron (B) and arsenic (As). The last five elements have only very recently been shown to be “essential” in animal species, and in some cases this has not been confirmed in Man; the practical importance of their dietary intake is still rather minor.

Some of these elements can be toxic at relatively low doses (As, Ni, F, Cr…).

Other trace elements can be detected in living tissues, but have not been shown to be essential. Their presence may result from contamination from the air or food.

When enough is known about the metabolism of mineral elements, their nutritional requirements have been assessed, using the factorial method, on the basis of the sum of the net requirements and the coefficient of intestinal absorption.

This has been possible for calcium, phosphorus, magnesium, iron, zinc and copper. For all the other elements, the adequate intakes have been set on the basis of the observed deficiency thresholds, from the state of the reserves and sometimes from the quantities usually consumed with no apparent impact on health.

The values published in the previous edition in 1992 have been updated and in some cases adjusted to take the most recent studies into account. The most

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recent and best documented assessments from other countries have formed the basis of comparison, and in the case of calcium, phosphorus and magnesium, we have drawn on the bulky file that has been published by the Food and Nutrition Board (Institute of Medicine, 1999) in the United States. Any discre- pancies between these values are discussed in detail, particularly those for calcium and phosphorus.

For most trace elements, the basis of comparison is older, and the values given in the previous edition were mainly based on the 1989 American data (FNB, 1989). The 1996 WHO publication, produced jointly with the FAO and the IAEA (FAO/WHO/IAEA, 1996), updates the studies of trace elements, but its conclu- sions and guidelines sometimes differ from those in many western countries.

Some assessments of recommended intakes have led to lively internal debate, and if these have not been resolved, they emerge from the corresponding texts.

This is the case, in particular, of sodium, i.e. common salt, and iron in pregnant women, about which neither side can be said to have won the argument!

Despite improvements in assay methods and research methods there is still room for progress in our understanding of the functions, bioavailability, metabolism and interactions of the minerals, and notably of some of the “new” trace elements. As FAILLA(1999) has shown for copper, zinc, manganese and molybdenum, the discovery and application of more sensitive and specific biological indicators should make it possible to get a more accurate idea of the ideal dietary intake. However, enough data has already been acquired to ensure a good mineral supply in the human diet, particularly because we should not lose sight of the fact that an excessive desire for accuracy is not necessary when we are defining ANCs (Apports nutritionnels conseillés, or recommended dietary intake), which are simply benchmarks towards which we should tend in order to minimize the risk of deficiency in a population.

1.2 Sodium (Na)

NaCl homeostasis requires a minimum daily intake of about 1 to 2 g. Howe- ver, this does not mean that we should recommend such a low salt intake. In fact, there is no prospective and randomized intervention study, which will allow us to define the ANCs of NaCl on a solid basis, particularly with regard to cardiovascular morbidity and mortality.

Recommended intakes are always the subject of debate, due to the link between NaCl consumption and blood pressure, which remains controversial.

Some scientists maintain that the role of high salt intakes in the onset of hypertension is far from having been established (ALDERMAN et al., 1997;

WEINBERGER, 1997; MCCARRON, 1998; TAUBES, 1998), whereas many others consider that it has been established (STAMLER, 1997; MÉNETONet al., 1998;

MACGREGORand DE WARDENER, 1999; SWALES, 1999). In the normotensive individual who is apparently in good health, blood pressure shows little or no relationship to the amount of salt consumed, at least in the short term (MIDGLEY et al., 1996; GRAUDALet al., 1998). In contrast, in some salt-sensitive hypertensive subjects, blood pressure may rise when sodium intake rises (MUNTZEL and DRÜEKE, 1992; CAMPESE, 1994). Most of the studies done up to now (for example, INTERSALT, 1988) concern only the effect of sodium intake upon blood pressure.

376 Sci. Aliments 21(4), 2001 Nutritional Recommendations for the French Population

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In the absence of consensus about ANCs, we can simply say that in general, healthy people should avoid either extreme, which in practice comes down to avoiding a sodium chloride intake of more than 12 g·d^–1or less than 5 g·d^–1. For the population as a whole, this leads to recommending reducing the actual consumption to an average of 6 to 8 g per day.

In hypertensive patients, who will often present an abnormal distribution of Na⁺ and Cl^– between the internal and external media, sodium-containing food which would be appropriate for a healthy individual may exacerbate this imbalance, which may in turn lead to a rise in blood pressure. However, all hypertensive subjects are not sensitive to salt and it is not therefore legitimate to prescribe a “salt-free” diet for all cases of hypertension. Numerous recent studies have shown that only 30 to 40% of hypertensive individuals are “sensitive”

to salt.

High sodium intake has also been incriminated in the onset of some diseases, such as myocardial hypertrophy, osteoporosis, asthma and gastric cancer. However, these hypotheses have not been confirmed for NaCl intakes of between 5 and 12 g·d^–1.

In a context of intense physical exertion, leading to heavy sweating, salt intake should be increased in the form of drinks, in order to compensate for these losses (MELIN, 1996). Massive salt intakes (salt tablets) during exercise are strictly prohibited.

The quantity of NaCl ingested is usually assessed from urinary excretion.

Estimations based on indirect methods such as food surveys are less reliable. In France, the salt present in the actual food itself is estimated to be 1-2 g·d^–1, but intake also includes the remanent salt resulting from additions by the agro-food industry (3-4 g·d^–1) and that added at table in the home (2-3 g·d^–1) or from other sources — mineral water, medicines — (1 g·d^–1) (MOINIER, 1997). The mean apparent salt intake is 7.9 g·d^–1but it is over 10 g for 10% of the population and may be as high as 25 g in a few individuals (VOLATIERet al., 2000). Nevertheless, the actual mean intake is probably higher. The ways to achieve a reduction to 6-8 g per day and to assess it are currently being devised in France.

1.3 Potassium (K)

The usual consumption of potassium in our Western societies is between 60 and 150 mmoles (2340 and 5850 mg) per 24 h; this contrasts with the diet of more primitive populations, which contained much more potassium (BURGESSet al., 1999). These intakes are more than adequate to meet the minimum require- ment, which is estimated to be 10-15 mmoles (390-585 mg) per 24 h. Healthy individuals can withstand very considerable changes in intake without developing either an overload or a deficiency. In contrast, elderly people must have regular and adequate intakes in order to avoid imbalance.

Dietary potassium also has an effect on blood pressure. This effect is the opposite to that of sodium and much more marked, since increased potassium intake results in a fall in blood pressure in many normotensive subjects and most hypertensive subjects, whereas potassium depletion is accompanied by an increase in blood pressure. It is interesting to note that the beneficial effect of potassium is more consistently observed than the harmful effect of sodium.

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There seems to be no need, even in a context of heavy sweating, to recommended routine K intake in drinks during intense physical exertion.

1.4 Calcium (Ca)

Virtually all (99%) the calcium in the body (1.0 to 1.2 kg) is found in the skeleton, and blood calcium is kept constant by drawing on the exchangeable calcium in the bone; therefore, the calcium needs of the body can be reduced to those of the bone. They must be sufficient to produce the complete mineralization of the bone before adulthood and then to maintain this bone calcium for as long as possible, in order to prevent osteoporosis.

As in the previous edition (DUPIN et al., 1992), the mean nutritional require- ments (MNRs) have been assessed using the factorial method. It has been assumed that there is enough data available to make it possible to use this method successfully and that the values obtained are no more inaccurate than those obtained using a more empirical method based on a maximum asympto- tic threshold of calcium retention (MATKOVICand HEANEY, 1992; JACKMANet al., 1997; Institute of Medicine, 1999).

The net maintenance requirement corresponds to the inevitable minimum losses in urine, feces (endogenous part) and sweat. The minimum values found when intake is low, but not zero, have been taken into account. Thus, in an adult man, the minimum maintenance requirement is estimated to be 260 mg of Ca per day, divided between the urine (130 mg), feces (110 mg) and sweat (20 mg) (SPENCERet al, 1986; CHARLESet al., 1991; HEANEYand RECKER, 1994; LEMANN, 1993). The endogenous fecal loss corresponds to the calcium which is not reabsorbed from the intestinal secretions (the calcium cost of digestion), whereas, the inevitable urinary loss results from the constant level of the calcemia and the abundant presence of dietary factors which increase the calciuria, such as protein (KERSTETTER and ALLEN, 1994; MASSEY, 1998) and sodium (SHORTTand FLYNN, 1990; NORDINet al., 1993). The maintenance requirement depends on bodyweight and is low in children (50 to 140 mg per day) (ABRAMSet al., 1991; MATKOVICand ILICH, 1993). It decreases as bone demand rises: 170 mg per day for adolescents between 10 and 14 years of age, who are in the peak period of bone growth, 200 mg per day for breast-feeding women, which is due largely to the reduction in urinary excretion, and in the case of pregnant women, to the improved intestinal absorption of endogenous calcium.

The amount of calcium retained in the skeleton is variable and may reach 400 mg per day during the puberty period. Mean values have been adopted on the basis of many results published about children and adolescents (WIDDOW- SONand DICKERSON, 1964; PEACOCK, 1991; FOMONand NELSON, 1993; CHANet al., 1995; RUIZet al., 1995; BONJOURet al., 1997): 80 to 140 mg per day from 1 to 9 years, 250 mg per day from 10 to 14 years and 100 mg per day from 15 to 19 years. It is accepted that the greatest mineralization of the bone genetically possible is achieved by 18 years, even though some consolidation, notably of cortical bone, may continue up to the age of 30 years (RECKERet al., 1992; MAT- KOVICet al., 1994; SABATIERet al., 1996).

The fetus retains about 20 g of calcium during the last trimester of pregnancy, or on average 220 mg per day. For a Ca content of 320 mg per liter of milk, and a daily volume of 800 mL, the mean need for lactation is 250 mg of Ca per day (LÖNNERDAL, 1997).

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The Coefficient d’Absorption Réelle or CAR (coefficient of true absorption) corresponds to a dietary intake that is slightly greater than the net requirement, for instance for diets containing almost no dairy products and providing about 500 mg of Ca per day. Under these conditions, unless absorption is severely limited by inhibiting factors, the mean potential CAR is of the order of 35 to 40% in adults (mean value of 38%). The problem of the bioavailability of die- tary calcium has been recently reviewed (HEANEY, 1996; GUÉGUEN and POIN- TILLART, 2000).

The CAR values adopted have been increased by 45% for adolescents between 10 and 14 years of age, and by 55% for pregnant women (KENT et al., 1991). Lactation does not seem to produce any definite increase in the efficiency of calcium uptake (KENTet al., 1991; KALKWARFet al., 1996) and a value of 45% has been set. In contrast, the mean CAR value has been lowered to 30% in post-menopausal women and in elderly people to allow for the reduction in calcitriol production, and therefore the lower active absorption of calcium (WEAVER, 1994).

These theoretical bases have been used to calculate the mean nutritional requirements (MNRs), and the recommended dietary intakes (ANCs) have been assessed by increasing the MNRs by 30%, to allow for an assumed coefficient of variation of 15%.

The values thus calculated (table 1) differ little from those in the previous edi- tion, apart from the increase in the intake in women from the age of 55 years, considering that a high calcium intake is effective on bone only about 5 years after the menopause (DAWSON-HUGHES, 1996; MEUNIER, 1999). Compared to the latest values from the USA (Institute of Medicine, 1999), these values are about 100 mg per day lower for adolescents and adults under 50, but match closely for the other population groups. The American values were not obtained by the factorial method, but are “adequate intakes”, based on what is thought to be necessary to obtain maximum calcium retention or, in adults between 30 and 50 years of age, to achieve calcium balance. However, since the mean intake required to achieve a positive or stable balance in 50% of cases is less than 650 mg·d^–1 (including losses in sweat) (MARSHALLet al., 1976), and the MNRs calculated here is 690 mg·d^–1, there is no obvious reason to increase the 900 mg·d^–1intake recommended in the previous edition to 1000 mg·d^–1.

It is well known that in children and adolescents, calcium intake is particularly effective in the prepubertal period, but that this effect is much more difficult to demonstrate after 15-18 years (RUIZet al., 1995; SABATIERet al., 1996). This has been confirmed by a recent multi-center European study (KARDINAALet al., 1999).

In postmenopausal women and the elderly, the calcium ingested acts mainly by reducing the resorption of bone induced by an increase in serum PTH (KANIS, 1999; MEUNIER, 1999). However, calcium appears to act as a “threshold-effect nutrient”, with an effect on PTH and various markers of bone renewal that is greater the lower the dietary intake and that does not have such a significant effect above a threshold of the order of 800 mg per day (FARDELLONE et al., 1998), which does not support any major increase in the recommended intakes.

This 800 mg per day threshold has also been demonstrated by STORM et al.

(1998) who have shown that the maximum winter changes in the loss of bone mass and plasma levels of 25-OH vitamin D and of various bone markers, are only seen below this threshold intake in elderly women.

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Pregnancy and lactation do not produce any additional calcium requirement, due partly to increased absorption during pregnancy, and partly to the inevitabi- lity of a loss of bone mass during breast feeding, which will be compensated by a subsequent increase in retention by the bone (DRINKWATER and CHESNUT, 1991; SPECKERet al., 1991; SOWERSet al., 1993; PRENTICE, 1994; LASKEYet al., 1998; RITCHIE et al., 1998). The value of 1000 mg·d^–1 adopted for pregnant women takes into account the normal “elasticity” of the bone reserves during the pregnancy-breast-feeding cycle (KOETTING and WARDLAW, 1988; PRENTICE, 1997).

The reference nutritional intakes published in the United Kingdom in 1991 (COMA, 1991) are lower, which is accounted for by the fact that obligatory urinary losses are not taken into account in children and adolescents, and by the fact that a rather high (apparent) net absorption coefficient is assumed in adults.

The new American “adequate intakes”, which aim to achieve maximum calcium retention, are higher than the ANCs as defined here. However, they are actually lower than the 1500 mg per day recommended by some authors for subjects over the age of 50 and by a consensus conference on osteoporosis, with an intention to slow bone resorption, notably by limiting secondary hyperparathyroidism in the elderly. Intakes above the ANCs can be legitimately pres- cribed on an individual basis, but this is therapeutic rather than nutritional.

Numerous studies (reviewed in MEUNIER, 1999) have shown the efficiency of much higher intakes of calcium (1500-1700 mg per day) in decreasing bone loss and bone fracture rate in elderly women. However, it is probable that such favo- rable effects could be obtained with more moderate calcium levels.

Finally, since calcium intake is only one of the prophylactic factors against osteoporosis, it is appropriate to stress the other means that are known to have preventative efficacy: vitamin D, hormone replacement treatment for the menopause, physical activity, etc.

Very high calcium intakes (up to 2 g·d^–1) do not seem to have any harmful effect on healthy individuals (WHITING and WOOD, 1997). However, for various reasons, it is prudent to stick to a safety limit of 2 g of Ca per day.

According to many studies, both earlier (reviewed in POTIER DE COURCY et al., 1999) and recent (VOLATIERet al., 2000), the mean values for calcium intake in France seem to be as follows (in mg per day): from 10 to 18 years, 1040 for boys and 820 for girls; for adult men under 65 years of age 850 and 790 for those over 65; for adult women under 50 years of age 770 and 690 for those over 50. Mean intakes of less than 600 mg per day have been found amongst institutionalized elderly people. The percentage of the population consuming less than two thirds of the ANCs (the intake taken to be the critical threshold in identifying high-risk groups) is approximately 20% for men between 18 and 65 years, 30% for adolescent boys and women between 18 and 50 years, 50%

for adolescent girls and men over 65 years, and 75% for women over 50 years.

Nearly two thirds of the calcium ingested comes from milk and dairy products. Otherwise, only a few green leaf vegetables, dried fruits and some chalky mineral waters contain high levels of calcium. A high intake of milk and dairy products during childhood, and above all during adolescence, is necessary to obtain the peak bone mass and is associated with higher bone density in young adults and a lower risk of subsequently developing osteoporosis.

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1.5 Phosphorus (P)

In adults, the plasma phosphorus level is a good indicator of nutritional status. The lower limit of normal is 27 mg·L^–1; an immediate risk of cell dysfunction and bone disorders only develops below 15 mg·L^–1. However, although in adults maintaining normal plasma phosphorus level may be a good indicator that needs are being met, this does not suffice in children or adolescents (Insti- tute of Medicine, 1999).

As in the previous edition, the MNR values have been assessed using the factorial method. This is also the approach taken in children and adolescents in the latest edition of American Dietary Reference Intake figures (Institute of Medi- cine, 1999), in which adult requirements are assessed on the basis of maintaining normal blood phosphorus levels.

As in the case of calcium, the net maintenance requirement corresponds to the minimum inevitable losses in urine, endogenous fecal loss and sweat. In the case of phosphorus, the urinary route predominates strongly. According to the relationship established by NORDIN(1989) between plasma phosphorus levels and the daily intake of P, the lower limit for “normal” plasma phosphorus cannot be ensured without a minimum absorption of 360 mg of P per day, that is by ingesting 550 mg·d^–1if the true absorption coefficient is 65%. The equation derived by LEMANN(1996), which expresses urinary excretion (U) as a function of the quantity ingested (I), U = 54 + 0.51 I, can be used to calculate the corresponding urinary loss. This gives a minimum inevitable loss of phosphorus of 300 mg·d^–1.

In order to obtain the net maintenance requirement, the inevitable endogenous fecal losses must also be added; these are of the order of 0.8 mg of P per kg bodyweight. These losses correspond to the non-absorbed fraction of P in the digestive secretions, which are estimated to amount to a mean value of 3.5 mg of P per kg bodyweight (WILKINSON, 1976).

Using a similar but non-factorial approach, the American Food and Nutrition Board (Institute of Medicine, 1999) has directly set a mean dietary intake of 600 mg·d^–1of P per day to ensure the “minimum normal” value of plasma phosphorus. However, the values taken by the Food and Nutrition Board for the urinary losses of P in children and adolescents are too high, since they correspond to arbitrarily high daily intakes (1000 mg·d^–1) for adolescents, and it is assumed that the Lemann equation established for adults holds good.

The amount of P required for growth can be derived from the values taken for calcium. The Ca/P ratio for weight gain is about 1.7 up to the age of 18 years and, therefore, the net requirements of phosphorus for growth range from 50 to 150 mg·d^–1.

A full-term fetus contains about 17 g of P (FOMONet al., 1982), which indi- cates that the mean retention during the last trimester of pregnancy is 150 mg·d^–1. Given a mean P content in human milk of 150 mg·L^–1and a daily volume of 800 mL, the net requirement for lactation is 120 mg of P per day.

Unlike calcium, the bioavailable phosphorus is very well absorbed and its absorption changes little with physiological factors or the intake level.

The mean values adopted are therefore 70 to 75% in children, adolescents and pregnant women, and 65% in adults and elderly people (WILKINSON, 1976;

GUÉGUEN, 1982).

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The ANCs values calculated in this manner closely match those recently set in the United Stated (Institute of Medicine, 1999) for adults, but are definitely lower for adolescents; this arises from the overestimation of minimum urinary losses by the American Commission as we have already described. Actually it does not seem physiologically logical to suggest ANCs values for P that are as high as those for Ca, since for all species of mammals, a Ca/P ratio of more than 1 is recommended. The recommended intake of phosphorus, like that of calcium, for breast-feeding women has been restricted to 800 mg·d^–1 to take into account the normal “elasticity” of the bone reserves.

The intake of dietary phosphorus is always higher than the ANCs, since the Ca/P ratio of usual diets is between 0.5 and 0.6. The problem that arises is therefore the risk of an absolute or relative excess of phosphorus.

Under normal conditions of diet, there is virtually no risk of acute or chronic toxicity. However, the possible side effects of a slight excess of P on calcium metabolism and bone mineralization should not be overlooked. The simulta- neous intake of P promotes the retention of Ca in the bone by reducing its urinary excretion, however, in the long term, and particularly if this is combined with an inadequate intake of Ca, it can have a detrimental effect on bone turno- ver in response to secondary hyperparathyroidism induced by a slight fall in the serum concentration of ionized calcium. The need to excrete the excess P intake in the urine could also be the primary cause of the activation of the para- thyroids. The negative impact on the bone of a phosphorus-calcium imbalance (due to an excess of P or insufficient Ca) has been demonstrated in various animal species and has long been known to exist (reviews: DRAPER and BELL, 1979; GUÉGUEN, 1982; POINTILLART and GUÉGUEN, 1985; CALVO, 1994). It has been demonstrated beyond doubt that an excess of P, combined with a Ca/P ratio of less than 1, does lead to a loss of bone mass.

The Food and Nutrition Board (Institute of Medicine, 1999) uses the paucity of human data, due to the difficulty of human experimentation, to draw a veil over the possibility that an excess P could have a side effect on bone.

It is indeed difficult to use the data obtained in Man using balance assessments, which are known to be very inaccurate when the balance is close to zero. Thus, a difference of 20 to 30 mg per day in the calcium balance cannot be statistically significant in a trial involving too small a number of adult subjects, even though its long-term impact on bone is very considerable. Further- more, the effect of an overload of P on parathyroid activity or on bone mineralization has been confirmed in several studies in Man (GOLDSMITHet al., 1976; BELL et al., 1977; ZEMEL and LINKSWILER, 1981; SILVERBERG et al., 1986;

CALVO and HEATH, 1988; CALVO et al., 1988, 1990; CALVO and PARK, 1996;

KÄRKÄINENand LAMBERG-ALLARDT, 1996).

It is true that hyperparathyroidism can have an anabolic effect on bone. This has been thoroughly discussed in the review by DEMPSTERet al. (1993). Howe- ver, this anabolic effect may only occur in trabecular bone (DEMPSTER et al., 1993) and only in response to intermittent single administrations of PTH by injection and not to continuous infusions (HOCKand GERA, 1992; HODSMAN et al., 1993).

The mechanisms by which calcium homeostasis is regulated and adjusted to low intakes may therefore be impaired in the most susceptible subjects, notably postmenopausal women and the elderly (CALVOand PARK, 1996).

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The safety limits set by the United States (Institute of Medicine, 1999) are 4 g·d^–1 P for adults and adolescents, and 3 g·d^–1 for children and the elderly.

Such high values are not acceptable, both because they do not take into account the possible side effects on bone of this relative excess of P, and because the way they have been calculated is open to question (see French edition). Consequently, we think that it is logical and prudent to stick to a safely limit of 2.5 g of P per day, which cannot be attained with current normal diets without ill-considered supplementation or the inappropriate use of foods treated with polyphosphates. However, it is universally accepted that an excess of P is better tolerated when the calcium intake is adequate, particularly when the excess P is due to the consumption of dairy products which also simulta- neously provide calcium (ANDERSON, 1991; BIZIKet al., 1996).

All the main foods contain high levels of phosphorus, and the average intake in France is of the order of 1500 to 1600 mg per day (GUÉGUEN, 1982; COUSINet al., 1997; LE FRANÇOIS et al., 1999). The mean contribution of the polyphos- phates, which are used as additives for technological purposes during the processing of some foods and cooked dishes, now no longer exceeds 100 mg per day (GUÉGUEN, 1982), in view of the stringent French legislation.

There is therefore no problem of P deficiency, except in some adolescents on a restricted diet or in adults abusing aluminum-hydroxide based antiacids.

On the contrary, we may worry about the potential risks associated with excessive consumption of phosphorus, particularly if the calcium intake is inadequate. As it is virtually never possible to reduce the phosphorus intake, it is important to monitor calcium intake particularly carefully.

1.6 Magnesium (Mg)

In the absence of data needed to establish the exact ANCs for infants, the adequate intake (AI) is based on the Mg content of human milk and the pro- gressive introduction of solid foods, which have a known impact on the global bioavailability of Mg in the diet (LÖNNERDAL, 1995). The AI for the first week of life is taken to be 30 mg·d^–1 and that during the second six months to be 75 mg·d^–1. According to recent studies carried out using stable isotopes (ABRAMS et al., 1997), the mean requirement in children is estimated to be 5 mg·kg^–1·d^–1. This value must be increased during periods of rapid growth.

The data for adolescents between 14 and 18 years of age based on balance and isotope studies are fairly consistent and lead us to set the required intake at 5.3 mg·kg^–1·d^–1.

In adults of either sex, balance studies, particularly those of LAKSHMANAN and KELSAY(1984), suggest that the magnesium intake required to maintain the balance between the intake and loss of magnesium is about 330 mg·d^–1. Intakes of less than 350 mg·d^–1 are fairly often accompanied by a negative balance, whereas an intake of 380 mg·d^–1 makes it possible to maintain the balance (SPENCERet al., 1994). In the light of the data available, the value taken to be the average requirement is 350 mg·d^–1. The same value is used for elderly people as well.

Pregnancy is accompanied by a higher requirement for Mg, mainly because large amounts of this element are transferred to the fetus during the 3^rdtrimes- ter. This increased demand is not compensated for (as it is in the case of cal-

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cium) by the activation of sparing mechanisms affecting the intestinal uptake or urinary excretion of Mg. The increased expenditure is estimated to be 35 mg·d^–1. The usual net requirement for lactation is calculated to be 25 mg·d^–1. The mean requirement for Mg can therefore be taken to be 5 mg·kg^–1·d^–1for both sexes. The ANCs that allow for a coefficient of variation estimated to be 10% of the mean requirement are therefore generally taken to be 6 mg of Mg per kg and per day. This value matches the recommended daily allowances (RDAs) in the United States, which have recently been increased (Institute of Medicine, 1999). In the past, we have drawn attention to the fact that the values adopted for the RDAs were under-estimated (DURLACHet al., 1992), and there is now a consensus about this. The intake must be increased from this baseline value of 6 mg·kg^–1·d^–1, by 25 mg·d^–1 in adolescents during a period of rapid growth, and by 40 mg·d^–1 during pregnancy and 30 mg·d^–1 during breast-feeding. Our ANCs values are therefore expressed in terms of the bodyweight.

Some data suggest that a high intake of Mg in the diet may have a beneficial effect in some chronic disorders. However, given the difficulty of interpreting these data, it is not possible to use them to suggest an optimum intake above the ANCs. There could be such a specific optimum intake during pregnancy (DURLACHet al., 1998). Since the needs are calculated entirely in terms of the increase in lean body weight, the consequences for the mother and fetus could require an additional intake of 30 mg above the ANCs. Intense physical activity could also call for a magnesium intake slightly greater than the ANCs values (RAYSSIGUIERet al., 1990), which is proportional to the energy expenditure and sweat output. For therapeutic purposes, supplements in the form of Mg salts at a dose of 5 mg·kg^–1·d^–1 are generally administered in magnesium therapy for frank magnesium deficiency. Since acceleration of intestinal transit only occurs in predisposed individuals, renal failure is the only contraindication for this type of supplementation (DURLACH, 1988). More intense oral supplementation is used if a pharmacological effect is sought, but this can lead to adverse effects at excessive dose levels. In practice, the maximum intake can be taken to be 350 mg·d^–1above the ANCs, even though higher pharmacological intakes may produce no harmful effects as a result of renal homeostasis.

Dietary intakes evaluated recently in more than 5000 subjects included in the SU·VI·MAX cohort, were 369 mg·d^–1in men and 280 mg·d^–1in women. Although these are slightly higher than those reported from other industrialized countries, in particular those in the United States and Japan, 18% of the men and 23% of the women in this same cohort had intakes of less than 2/3 of the ANCs (GALAN et al., 1997). In France, as in other developed countries, the inadequate Mg intake in a part of the population is linked to the reduced energy intake and changes in eating habits. In practice, it is better to eat a varied, traditional diet, rather than modern “snacks”, and to eat more cereals and vegetable products, which can considerably increase the magnesium intake (HUNT et al., 1998).

Some mineral waters can also be a useful source of magnesium.

1.7 Iron (Fe)

The human iron requirement is linked to physiological losses. Basal daily iron losses in adults range from 0.9 to 1 mg of iron per day, which is equivalent to about 14 mg·kg^–1. Nearly 0.6 mg are lost in stools, 0.2 to 0.3 mg in sweat and 0.1 mg in urine.

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During the first year of life, a full-term infant will triple its birth weight and almost double its body iron content. In view of the requirements linked to growth, a young child has a high iron requirement (INACG, 1979; FAO/WHO, 1989): at one year, the amount required, expressed per kg bodyweight, is 8 to 10 times higher than that of adult males. The acceleration of growth, particularly during the years of sexual maturation, is also accompanied by an increase in the iron requirement. In adolescent girls, there is also the additional specific iron requirement arising from the onset of menstruation.

For women between puberty and the menopause, it is necessary to add the losses arising from menstrual bleeding to the basal losses (INACG, 1981;

FAO/WHO, 1989). According to studies carried out in various countries, the median loss is between 25 and 30 mL per month, which corresponds to an iron loss of between 12.5 and 15 mg per month, or 0.4 to 0.5 mg·d^–1, in addition to the usual basal losses. Overall, 50% of women have a total iron loss of more than 1.3 mg·d^–1and 10% have a loss of more than 2.1 mg·d^–1. Oral contracep- tion can reduce the volume of menstrual flow by 50%, whereas increases of over 100% may be observed in women fitted with an intra-uterine device.

Iron requirements increase considerably during pregnancy (FAO/WHO, 1989), due to a physiological increase in the erythrocyte mass (requiring about 500 mg of iron), the constitution of the fetal tissues (about 290 mg of iron) and of the placenta (about 25 mg of iron). Therefore a pregnant woman requires 1000 mg of iron to balance her intake and losses of iron during pregnancy, which corresponds to a daily requirement of 2.5 to 5.2 mg, depending on the iron reserves at the beginning of pregnancy. Various studies have demonstrated a clear increase in the intestinal uptake of iron as pregnancy progresses (BAR- RETTet al., 1994; WHITAKERet al., 1991).

The bioavailability of iron varies considerably depending on whether the dietary source is heminic or non heminic (HALLBERGet al., 1972; COOKet al., 1991).

Heminic iron is particularly bioavailable (about 25%), whereas the uptake of non-heminic iron is very variable (often much less than 10%) and depends on the nature of the food eaten (COOKet al., 1991). Some factors may either pro- mote or hinder the bioavailability of non-heminic iron. Depending on the effects of these factors, the uptake of iron from a meal may range from 1 to 20% in individuals with similar iron status. To evaluate dietary requirements, the mean uptake coefficient of iron from normal French meals is taken to be 10% (GALAN et al., 1985; LYNCHand BAYNES, 1996; LYNCH, 1997).

The ANCs values have been estimated not only in order to cater for the needs described above, but also to maintain adequate iron reserves. Intakes below those indicated (table 1) may be sufficient to prevent the onset of iron- deficiency anemia. However, to ensure high reserves of iron, it is necessary to set higher intakes.

Since iron requirements are theoretically so high in pregnant women, it seems to be difficult to meet them from the diet, and early medicinal supplementation is highly desirable (from the end of the 1^sttrimester of the pregnancy).

The advisability of routine supplementation for all pregnant women or targeted supplementation after screening for iron deficiency has not yet been clearly established and remains the subject of debate with regard to the best strategy in terms of public health and safety.

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Even though it does seem to be desirable to constitute and maintain proper iron reserves, it cannot yet be claimed with certainty that maximum iron reserves have any beneficial impact on the individual’s health. Some genetic predispositions lead to the build up of iron in the reserves. The most frequent cause is hemochromatosis (BRISSOT and DEUGNIER, 1993). Furthermore, an excess of iron, particularly in the presence of vitamin C, can increase oxidative stress due to the reactivity of iron in the production and propagation of free radicals (SALONENet al., 1992; LUNDet al., 1999; REHEMAet al., 1998).

The safety limit adopted in France is 28 mg·d^–1(twice the mean ANCs).

In a Western-type diet, the main sources of iron are meat products (20 to 30% of total iron), cereals (20 to 30%), followed by fruit and vegetables, and finally roots and starchy tubers (HERCBERGet al., 1991b; LAMANDet al. 1996). In France, according to various studies (HERCBERG et al., 1991b; ARNAUD et al., 1994; GALAN et al., 1998), mean iron intakes are 12 to 16 mg·d^–1in adult men and 10 to 12 mg·d^–1in women.

Various studies carried out in France (GALANet al., 1985; SOUSTRE et al., 1986; DHUR and HERCBERG, 1989; MEKKI et al., 1989; PREZIOSIet al., 1994), using biochemical markers of iron status, and carried out in “random” population samples, have shown that sizeable fractions of the population have no iron reserves, notably women of child-bearing potential and young children. Iron deficiency appears to affect 29% of children under 2 years of age, 14% of those between 2 and 6 years, 15% of adolescent girls and, depending on the study, 10 to 23% of women of childbearing potential. Iron deficiency has been identi- fied in 60 to 75% of pregnant women at the end of pregnancy (BENAZÉ et al., 1989; HERCBERG and GALAN, 1990; HERCBERG et al., 2000). This deficiency in iron is sufficiently severe to induce anemia in 10 to 30% of these women.

In view of the high incidence of individuals presenting with biochemical signs of moderate iron deficiency in France (as in all industrialized countries), it is essential to continue and develop research in this field in order to identify the functional consequences of this deficiency. It is only once we know this that it will be possible to know if preventive measures are called for, and if so, what form they should take.

1.8 Zinc (Zn)

The intakes recommended in 1992 (DUPIN et al., 1992) were similar to the 1989 American Guidelines (FNB, 1989) (12 mg·d^–1for women and 15 mg·d^–1for adult men). These seem to meet the requirements of the population, but do not take into account either the metabolic changes (increased absorption, reduced loss) in a context of depletion, or the functional consequences of depletion. An intake of 5.5 mg·d^–1is sufficient to maintain the zinc balance in adult men, but leads to the reduction of several functional markers. The ANCs values must be assessed by selecting the most pertinent functional markers and by carrying out epidemiological studies using the largest populations possible (KING, 1996).

They must also take into account the make up of the diet and probably some life style factors (SANDSTEADand SMITH, 1996). For instance, intakes of 2.5 and 3.6 mg·d^–1in adult women and men respectively can be sufficient if the diet is predominantly animal-derived. With a varied diet, intakes of 6.5 mg·d^–1in adult women and of 9.4 mg·d^–1in adult men will suffice, whereas if the diet is predo-

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minantly of vegetable origin, it will be necessary to increase the intake to 13.1 mg·d^–1 in adult women and 18.7 mg·d^–1 in adult men (SANDSTRÖM, 1995;

PARR, 1996).

In view of the definition of the ANCs and the eating habits of French people, two types of nutritional intake can be recommended, depending on whether the diet contains relatively high or low amounts of products of animal origin.

The administration of zinc has not been shown to serve any purpose except in a situation of confirmed deficiency. Intervention studies in pregnant women have shown that the administration of zinc at doses ranging from 15 to 90 mg·d^–1 could reduce the risk of complications during childbirth and of pre- maturity, and also increase the birth weight (BOUGLÉ et al., 1995). Similarly, doses of between 10 and 50 mg·d^–1have a beneficial clinical effect on immune function and growth if blood zinc levels are low. Their efficacy is debatable when blood zinc is normal.

The benefits of long-term multiple supplementations for antioxidant purposes in preventing cardiovascular disease and cancer remains to be demonstrated.

Doses of over 50 mg·d^–1of zinc lead to reductions in plasma levels of ferri- tin, copper, copper-zinc dependent dismutase superoxide, HDL-cholesterol and an increase in the lipoperoxides, and hence an increased risk of oxidative disorders. Pharmacological doses have a negative impact on immunity (SANDSTRÖM, 1995). However, lower intakes of between 15 (MARTIN, 1996a) and 40 (HATH- COCK, 1996) mg·d^–1are proposed as the safety limit. Long-term single-element supplementation (for more than 30 days) at doses of over 20 mg·d^–1should be administered under medical supervision.

The refining and conservation of food leads to the loss of zinc, but may also increase its bioavailability. For instance, wholemeal bread contains more zinc than white bread, but zinc is more readily utilized from white bread, which contains less phytate. Products of animal origin, and in particular beef meat, are good sources of zinc, whereas fresh fruit supplies only small amounts of zinc (about 0.1 mg per 100 g), as do some green vegetables (LAMANDet al., 1996).

1.9 Copper (Cu)

Some balance studies have suggested that the adult requirement for copper is between 2 and 2.6 mg·d^–1, whereas others suggest that it is less than 2 mg·d^–1 or even close to 1 mg·d^–1(KLEVAY et al., 1980). In adults, the loss of copper from the body surface is about 50 to 100 µg·d^–1, and to this must be added the urinary loss (25 to 50 µg·d^–1) and the biliary secretion, most of which is excreted in the feces (300 to 400 µg·d^–1). The unavoidable loss of copper is estimated to be 400 to 500 µg·d^–1and the MNR to compensate for these losses is between 1.35 and 1.65 mg·d^–1, or 20 to 25 µg·kg^–1·d^–1 in adult men, if the absorption coefficient is 30% (SANDSTEAD, 1982). The ANCs values are generally set 1.3 times higher than the requirements and so are between 1.77 and 2.15 mg·d^–1(or on average 2 mg·d^–1).

In infants and young children, the copper requirement is very high, and may reach 40 to 80 µg of Cu·kg^–1·d^–1. The copper stored in the liver plays an important part in meeting this requirement. Premature infants face a risk of copper deficiency. The mother provides the fetus with most of the copper during the last

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trimester of pregnancy (200 µg·d^–1). This means that it is appropriate to increase the daily intake of copper by about 0.5 mg·d^–1in pregnant women. Finally, the daily intake of copper in nursing mothers must be increased by about 0.5 mg·d^–1, since human breast milk provides between 0.1 and 0.3 mg per day.

The true intestinal absorption of copper is 20 to 40% in Man (SANDSTEAD, 1982; WAPNIR, 1998). Various dietary factors can affect it (LÖNNERDAL, 1996). A high intake of zinc can affect the uptake and retention of copper as a result of competition. An excess of inorganic iron can reduce the copper status and induce clinical signs of copper deficiency.

Because the metabolism of copper is less well established than that of iron or zinc, the ANCs cannot be set accurately (TURNLUND, 1994; KLEVAY, 1998).

They are slightly different from those proposed in 1989 by the American Food and Nutrition Board.

An excess of copper can induce hepatitis and serious hemolytic jaundice.

The toxic effects of copper, such as lipid peroxidation or DNA damage, are directly linked to its role in oxygen free-radical production (BREMNER, 1998), even though superoxide dismutase is involved in their destruction. A recent study has shown that ingestion of 3 or 6 mg of Cu·d^–1for a period of 6 weeks does not lead to adverse events in Man (FOODCUE, 1998). Uncontrolled trace- element supplementation can also carry a risk of copper poisoning.

In France, the average daily intake of copper is 1.8 mg·d^–1 in men and 1.47 mg·d^–1in women (HERCBERGet al., 1991b), although other studies (ARNAUD et al., 1994) indicate only 1.05 mg·d^–1 for men. Foods that contain large amounts of copper are starchy foods, dried legumes and above all liver and products derived from it (LAMAND et al., 1996). Fruit, vegetables and red wine are all important sources of copper. The copper content of water may be considerable and varies widely (FITZGERALD, 1998). At present the upper limit for copper in water is 1 mg of Cu per liter.

1.10 Iodine (I)

Metabolic studies carried out in the USA (FNB, 1989) and in Europe have led to setting the same ANCs values for older children, adolescents and adults, but different values for neonates and infants. Compared to the USA, the average iodine content of the environment in Europe is low, which explains why the ANCs for children are higher (30 mg·kg^–1·d^–1 in premature babies and 15 mg·kg^–1·d^–1at full term) (DELANGE, 1993).

The ANCs for pregnant women take into account both the higher renal clea- rance of iodine during pregnancy and the specific needs of the fetus. In breast- feeding women, the ANCs compensate for the average daily loss of 30 to 50 µg of iodine in the breast milk.

France is one of the European countries liable to iodine deficiency (MORNEX, 1987; VALEIXand HERCBERG, 1992; JAFFIOLet al., 1995). The main residual clus- ters are reported in the Pyrénées, the Landes, the Massif Central, the Franche- Comté and Alsace districts (VALEIXet al., 1999). In these regions, urinary levels of iodine are about 60-70 µg·L^–1 and 10 to 20% of women develop a mild stage-I goiter during pregnancy. After childbirth, their babies often suffer from transient neonatal hypothyroidism.

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Sea foods (fish, crustaceans, shell fish, seaweed) are a major and stable source of iodine, containing of the order of 80 to 150 µg per 100 g of the edible product. The agro-food industry is making increasing use of iodinated disinfec- tants, preservatives and coloring agents in the processing of dairy products and cooked meals or frozen foods particularly for the disinfection of milking equip- ment (iodophores). Milk products, cereal products and eggs provide a large part of the iodine intake in children and young adolescents (BROUSSOLLE and ORGIAZZI, 1990; LAMANDet al., 1994).

The limited success of the prophylactic use of iodinated salt in France is related to the inadequate amount added (10 to 15 mg·kg^–1) and to its limited distribution within the domestic market (46% of sales). The recommended added amount (in the chemical form of iodide only) is now 15 to 20 mg·kg^–1. One alternative is to give an annual oral dose of iodinated oil, which, because of the high degree of sequestration within the adipocytes (INGENBLEEK et al., 1997), can also provide low-cost prolonged protection against nuclear risks.

Thyrotoxicosis is an occasional complication of iodine overload. It is rare and can be cured, and so does not cast doubt on the validity or benefits of campaigns to eradicate iodine deficiency.

1.11 Selenium (Se)

The dietary allowances recommended in 1989 in USA (FNB, 1989) for selenium (70 µg·d^–1in men and 55 mg·d^–1in women) and adopted in France (DUPIN et al., 1992) were intended to saturate the activity of selenium-dependent plasma glutathione peroxidase. However, it is not certain that it is necessary for the activity of this enzyme to be at its maximum in order to meet the selenium requirement, because other selenoproteins produce their peak activity at lower Se intakes. In 1996, a committee of FAO/WHO/IAEA experts proposed daily intakes of 40 and 30 µg for men and women respectively (LEVANDER, 1997).

Other countries have set dietary reference intakes for selenium: Great Britain in 1991 (75 µg·d^–1in men, 60 µg·d^–1in women), Germany in 2000 (30-70 µg·d^–1), the Nordic countries in 1996 (50 µg·d^–1 in men and 40 µg·d^–1 in women). It seems that 20 µg·d^–1 is too low, because it is close to the intake found in the Keshan region! The European Scientific Committee for Human Nutrition (SCF, 1993) proposed 40 µg·d^–1 as the average requirement and as the reference value for labeling purposes, which gives derived ANCs of the order of 50 µg·d^–1. Dietary intakes of between 50 and 80 µg per day can be recommended for adolescents and adults, so that even though it is difficult to define the optimum intake, we can accept that a dose of 1 µg·kg^–1bodyweight per day is an adequate dose.

Protein foods contain the most selenium, but their bioavailability is variable:

20 to 50% for seafood, compared to 80% for cereals and brewers’ yeast. The main foods containing high levels of selenium are fish (30-40 µg·100 g^–1), eggs (20 µg·100 g^–1), meat (6-10 µg·100 g^–1), and cheese (5 µg·100 g^–1). Dietary intake in France has been assessed as being 40-50 µg per day (SIMONOFFand SIMONOFF, 1991).

Se supplementation must not be routinely provided. The vitamin E/selenium combination is beneficial because vitamin E, a liposoluble antioxidant, complements the action of selenium, although it cannot replace it (NÈVE, 1995).

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The dietary intakes that can cause toxicity are even less well defined. Up to 1000 µg per day, selenium intake does not induce any clinical sign of toxicity.

The LD50 by oral route is estimated to be between 0.5 and 1 g of inorganic selenium (NÈVE, 1995). A maximum value of 5 µg·kg^–1·d^–1 has been defined as the dose that does not induce any risk of a harmful effect over a lifetime (LEVAN- DERand WHANGER, 1996). A safety limit dose of 150 µg·d^–1has, however, been proposed in France, based on a safety factor of 10 (MARTIN, 1996b). This limit is low, when we realize that the daily intake of some Europeans (Finland) is 100- 200 µg·d^–1.

1.12 Chromium (Cr)

Chromium is an essential trace element, required for carbohydrate and lipid metabolism, of which intake is below optimum in the industrialized countries (ANDERSON, 1997). The determination of requirements and the benefits of supplementation in healthy individuals remain controversial and should lead to the clarification of the claims made for chromium (MARTIN, 1998).

The preceding ANCs (DUPINet al., 1992) were 50 to 200 µg·d^–1from 7 years of age. This rough estimate is open to question given the absence of any valida- ted markers of the chromium status. Furthermore, these values defined in 1980 in the United States and subsequently adopted, were set at a time when assays were probably over-estimated for technical reasons related to the analysis. In the absence of data and studies involving the French population, the margin or uncertainly remains. ANCs are based on the absence of clinical signs of deficiency for an intake of 50 µg·d^–1 and the lack of toxicity below 200 µg·d^–1. However, a downward revision of the recommended intake for healthy subjects, in the light of the analytical problems mentioned, leads us to suggest ANCs of 50 to 70 µg·d^–1.

On the basis of these ANCs values, the optimum intake of chromium cannot be reached for a calorie intake of 10.5 MJ·d^–1(2500 kcal·d^–1). Dietary intake in France seems to be similar to that in the United States (about 40 mg·d^–1) (ANDERSON, 1993).

The foods that contain the most chromium are yeast, liver, egg yolk and spices. Most other foods contain less than 10 µg·100 g^–1. The bioavailability of chromium is very low in meat, milk and green vegetables, but higher in cereals.

In complements, picolinate is better absorbed, as is the biological GTF form in yeast, of the order of 10%.

The efficacy of high doses of chromium picolinate (1000 µg·d^–1) has recently been demonstrated in type-2 diabetes (ANDERSONet al., 1997), but the benefits of supplementation in healthy people are only seen if the chromium status is low;

supplements supplied on the basis of false claims should thus be denounced.

The toxicity of chromium III is generally accepted to be virtually zero. In contrast chromium VI is highly toxic; chronic poisoning induces dermatitis, nephritis and hepatitis.

1.13 Fluorine (F)

Fluorine does not play an essential role: it forms fluoroapatite in the teeth and bones and has a high affinity for calcium. An intake of 0.5 mg·d^–1seems to

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be sufficient in children to prevent caries and the most suitable food for mass supplementation seems to be table salt (ILSI, 1990), even though fluorination of drinking water (which is not permitted in France) to a level of 0.6 to 1.2 mg·L^–1is widely used throughout the world. However, the beneficial effect of fluorine on dental caries is produced by contact and does not necessarily have to involve systemic passage (DIESENDORF et al., 1997). Furthermore, dental fluorosis can occur in children who drink water containing more than 1.6 mg·L^–1. The safety limits range in adults from 4 (SHAPIRO, 1996) to 10 mg·j^–1 (YATESet al., 1998).

Fluorosis of the bones occurs if doses of 10 mg·d^–1are administered for more than 10 years (Institute of Medicine, 1999). Acute toxicity occurs at doses over 500 mg·d^–1. Large quantities of fluorine are found in tea and in sea fish (HUNT and STOECKER, 1996). In contrast, milk contains only a little fluorine. The amount in water is very variable. Some mineral waters contain high levels of fluorine (Vichy springs) and if they are drunk exclusively for several years, they can induce fluorosis of the teeth and bones. Fluorine intakes range from 0.3 to 1.9 mg·d^–1, depending on the country and the policies followed about fluorination of tap water and table salt.

Table 1

Summary of ANCs for minerals and trace elements

Population group Ca P Mg Fe Zn Cu F I Se Cr

mg mg mg mg mg mg mg µg µg µg

Children 1-3 y 500 360 80 7 6 0.8 0.5 80 20 25

Children 4-6 y 700 450 130 7 7 1.0 0.8 90 30 35

Children 7-9 y 900 600 200 8 9 1.2 1.2 120 40 40

Children 10-12 y 1200 830 280 10 12 1.5 1.5 150 45 45

Boys 13-19 y 1200 830 410 13 13 1.5 2.0 150 50 50

Girls 13-19 y 1200 800 370 16 10 1.5 2.0 150 50 50

Adult men 900 750 420 9 12 2.0 2.5 150 60 65

Adult women 900 750 360 16 10 1.5 2.0 150 50 55

Men > 65 y 1200 750 420 9 11 1.5 2.5 150 70 70

Women > 55 y 1200 800 360 9 11 1.5 2.0 150 60 60

Pregnant women 1000 800 400 30 14 2.0 2.0 200 60 60

3rd trim.

Lactating women 1000 850 390 10 19 2.0 2.0 200 60 55

Elderly people ≥75 y 1200 800 400 10 12 1.5 2.0 150 80 –

– Precise ANCs cannot be proposed for sodium, potassium and chloride, whose consumption is generally largely above requirements (see text). Moderate sodium intakes are recommended (6-8 g·d^–1).

– It seems to be too early to propose ANCs for molybdenum and manganese. They would be around 2-3 mg per day for Mn and 30-50mg per day for Mo.

– Iron ANCs for pregnant women are very high and are still controversial. Usual diets do not allow to reach such levels so that supplemental iron is necessary under medical control.

– Values for zinc and iron are rounded means, varying with bioavailability of diet constituents: they are 20-30% lower for diets rich in animal products, especially meat, and 20-30% higher for diets rich in vegetal products.

– For chromium in elderly people, high values, around 125µg·d^–1, have been proposed (CYNOBERet al., 2000), though data from literature do not allow to propose such a precise value.

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1.14 Other trace elements

Some minerals are also essential for Man (Mn, Mo) but do not call for defined ANCs, since the requirements are readily covered by the food.

Other trace elements are thought to be potentially indispensable, because there is evidence that they are indispensable in animal species (As, B, Li, Ni, Si, V) even if this has never really been demonstrated in Man. Knowledge of these elements is too sketchy to make it possible to define ANCs. Three of them (Li, Si, V) are used therapeutically. Finally, some trace elements have not been clearly shown to be indispensable (Al, Br, Cd, Ge, Pb, Rb, Sn).

There is nothing original about the ANCs for any of these elements, compared to the values suggested in other recent publications (FREELAND-GRAVESand TURNLUND, 1996; GREGER, 1998; NIELSEN, 1996a, b; ZAWISLAK, 1991; TURNLUND et al., 1995; UTHUS and NIELSEN, 1993; UTHUS and SEABORN, 1996; DOMINGO, 1996). ANCs for trace elements for sportsmen are given in table 5.

No deficiency in any of these “new” trace-elements has been demonstrated in Man, perhaps because of the lack of sufficiently reliable indicators. We can take it that the dietary intakes do meet the body’s requirements.

2 - VITAMINS

Regarding adult men and women, vitamin ANCs were assessed, when possible, from new data issued from epidemiological studies such as SU·VI·MAX (HERCBERGet al., 1998); this is the case for folates, vitamins B6, B12 and C. When survey data were lacking, ANCs were calculated on the basis of energy requirements, which have decreased since 1992 with the mean trend of the population to a sedentary way of life; this is the case of vitamins B1, B2, B3, B5, B8 et A.

As for growing people, i.e. children and adolescents, data on vitamin requirements are scarce, or even absent, after the first weeks of life. Therefore, the reference values used were primarily vitamin concentrations in maternal milk and, secondly, adult ANCs. For each vitamin, these values were extrapolated taking into account different index of metabolic growth: energy requirements, height, BMI, square height, body surface area… Among all scales of values thus obtained for ages 1 to 20, two were regarded as adequate, due to the regular form of the curve, especially regarding gender, and its conformity to the two initial points:

energy, imaging metabolic rate (selected for vitamins B2, C, A, E) and square height, imaging lean mass (BRAMBILLA et al., 1999) (chosen for vitamins B1, B3, B5, B6, B9, B12). An example of this extrapolation is given in figure 1 for folic acid.

2.1 Vitamins B

2.1.1 Thiamin (vitamin B-1)

Thiamin in its coenzymatic form, thiamin pyrophosphate (TPP) is involved in two main types of metabolic reactions: decarboxylation of α-ketoacids such as pyruvate, α-ketoglutarate and branched-chain keto acids and transketolation in

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the pentose phosphate pathway. Many studies have been made on human thiamin requirements, by both nutrition surveys and experimental deficiency. On the basis of data obtained in a carefully controlled thiamin depletion-repletion expe- riment conducted with seven healthy young men in a metabolic unit, minimum requirement appeared to be 0.20-0.30 mg per 1,000 kcal (SAUBERLICH et al., 1979). In order to allow a factor of safety, the value of 0.50 mg per 1,000 kcal has been recommended as adequate for most persons. In the absence of additional information about thiamin requirement, the 2001 ANCs for this vitamin were extrapolated from the French 1992 values according to the decrease in average energy expenditure from 1992 to 2001. In 1992, the ANCs for thiamin was set at 1.5 mg (e.g. 0.56 mg per 1,000 kcal) for adult men. Therefore, the 2001 ANCs for thiamin were estimated as 1.3 mg for men and 1.0 mg for women aged 20 through 75 years.

2.1.2 Riboflavin (vitamin B-2)

Riboflavin functions primarily as a component of two flavin coenzymes — flavin mononucleotide (FMN) and flavin dinucleotide (FAD) — that catalyze many oxidation-reduction reactions. Currently, one of the most commonly used methods for assessing riboflavin status involves the determination of erythro-

Figure 1

Determination of ANCs for folic acid in children

ANCs/T2, ANCs/E: extrapolation of values for children starting from ANCs of adults (H: men; F:

women) and using either square height (T2) or energy (E); lm/E: extrapolation of values for children starting from mother’s milk and using energy. Only the median curves (ANC/T2) yields a good extrapolation between values for maternal milk and adult requirements.

Age (years)