MINERAL ELEMENTS ESSENTIAL FOR HUMANS E SSENTIAL T RACE E LEMENTS

Trace elements essential for life are ones that generally occur in the body in micrograms per gram of tissue and are usually required by humans in milligrams per day amounts; these elements are copper, iron, manganese, and zinc. The evidence for essentiality for humans is substantial and not controversial for these elements. Specifi c biochemical functions have been found for each of these minerals. Because magnesium has many characteristics of a trace element, it also will be included in this group of elements. Another element that will be included is boron, because it is required to complete the life cycle of zebrafi sh⁵ and frogs,⁶ which suggests that it is essential for higher animals and humans.

Boron

Although it has not been defi nitively established that boron defi ciency interrupts the life cycle of mammals, or has an essential biochemical function in humans, substantial evidence exists for boron being a bioactive food component that is benefi cial, if not required, for optimal bone, neurological and immune function in higher animals and humans. Boron deprivation apparently has numerous physiological effects, because it infl uences the concentration and activity of numerous biochemical substances in tissues and fl uids (see Table 8.1). These numerous responses to boron deprivation occur, because boron apparently acts at

TABLE 8.1

Biochemical, Clinical and Nutritional Aspects of Boron

Biological Function

Established None

Hypothesized A metabolic regulator affecting cell membrane function that infl uences the responses to hormone action, transmembrane signaling, or transmembrane movement of regulatory cations or anions

A metabolic regulator, through complexing with a variety of substrate or reactant compounds which contain hydroxyl and amine groups in favorable positions. Regulation is mainly through an inhibitory effect on enzymes

Signs of Defi ciency

Biochemical Because boron apparently has a regulatory role, low dietary boron induces a variety, most likely indirect, of biochemical changes in humans. These include:

Calcium metabolism: decreased serum 25-hydroxycholecalciferol; increased serum calcitonin Energy metabolism: increased serum glucose; decreased serum triglycerides

Nitrogen metabolism: increased blood urea; increased serum creatinine; decreased urinary hydroxyproline excretion Reactive oxygen metabolism: decreased erythrocyte superoxide dismutase; decreased ceruloplasmin

Response to estrogen: decreased serum 17B-estradiol; decreased plasma copper

Physiological Because boron can cause a variety of biochemical responses, it is not surprising that boron deprivation also has a variety of physiological effects. These include:

Altered electroencephalograms that suggest impaired behavior activation (e.g., more drowsiness) and decreased mental alertness Impaired psychomotor skills

Impaired cognitive processes (e.g., attention and memory)

Increased platelet and erythrocyte numbers; decreased white blood cells

A number of physiological signs of defi ciency have been found in animals that may have some counterparts in humans.

Reported signs include:

Impaired bone development and decreased bone strength Impaired infl ammatory and immune responses Pathological Consequences of Defi ciency

Established None

Suggested Increased susceptibility to osteoporosis and arthritis Impaired cognitive and psychomotor function Predisposing Factors for

Defi ciency

Stressors that affect hormone action or signal transduction at the cell membrane level including vitamin D defi ciency and magnesium defi ciency

Dietary changes that can increase oxidative stress at the cell membrane level such as high intakes of polyunsaturated fatty acids (e.g., omega-6 fatty acid-rich saffl ower oil)

Recommended Intakes

Prevention of defi ciency 1.0 mg/day has been suggested¹⁴

Therapeutic or benefi cial Luxuriant intakes (e.g., ≥3 mg/day) may be benefi cial when stressors are present that lead to osteoporotic or arthritic changes Food Sources Food and drink of plant origin, especially noncitrus fruits, leafy vegetables, nuts, pulses, wine, cider

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the membrane level to affect the response to hormones, transmembrane signaling, and the movement of regulatory cations and anions. Thus, the numerous reported signs of boron deprivation, shown in Table 8.1, may be mostly secondary responses to an unidentifi ed primary defi cient or changed biochemical function at the cell membrane level. Indicators of boron status are still being established. However, plasma boron concentrations lower than 25 ng/ml may be indicative of a low boron status. Most of the information in Table 8.1 can be found in reviews by Nielsen,^7–10 Hunt,^11,12 and Penland.¹³

Copper

Although copper is well established as an essential trace element, its practical nutritional importance for healthy humans, and thus its dietary requirement, still is debated. Well-established consequences of copper deprivation in humans have come mainly from fi ndings from special populations receiving nutrition from limited sources (e.g., parenteral nutrition solutions, milk, or formulas with no supplemental copper), consuming drugs (e.g., penicillamine) or undergoing dialysis resulting in excessive loss of copper, or having a genetic disorder (e.g., Menkes’ disease) that results in defective copper metabolism. Other consequences of inadequate copper intakes for humans have been projected or hypothesized from epidemiological, animal, and short-term human copper deprivation studies. Most of the information found in Table 8.2 has been obtained from reviews by Harris,¹⁵ Klevay and Medeiros,¹⁶ Milne,¹⁷ Cordano,¹⁸ Uauy et al.,¹⁹ and Failla et al.²⁰

TABLE 8.2

Biochemical, Clinical and Nutritional Aspects of Copper

Biological Function Copper is a cofactor for several oxidoreductase enzymes that are involved in the generation of oxidative energy, oxidation of ferrous iron, synthesis of neurotransmitters, bestowment of pigment to hair and skin, provision of strength to bones and arteries, assurance of competence of the immune system, and stabilization of the matrices of connective tissues. These enzymes include: amine oxidase, lysyl oxidase, ferroxidase (ceruloplasmin), dopamine B-monooxygenase, tyrosinase, alpha-amidating monooxygenase, cytochrome c oxidase, and superoxide dismutase. Thus, copper is essential for several fundamental processes, including angiogenesis, neuropeptide and neurohormone signaling, iron metabolism, oxygen transport, energy production and the regulation of genetic expression

Signs of Defi ciency

Biochemical Decreased plasma copper

Short-term human copper depletion studies have inconsistently resulted in several biochemical changes, including decreased erythrocyte superoxide dismutase

Decreased enzymatic and immunoreactive ceruloplasmin and ratio

Decreased platelet and mononuclear white cell cytochrome c oxidase

Increased plasma cholesterol; and decreased interleukin-2

Physiological Copper defi ciency in premature and malnourished infants and infants with Menkes’ disease has established numerous physiological defi ciency signs including:

hematologic changes characterized by hypochromic, normocytic, or macrocytic anemia accompanied by reduced reticulocyte count, neutropenia and thrombocytopenia

bone abnormalities that mimic scurvy, for example, osteoporosis, fractures of the long bones and ribs, epiphyseal separation, fraying and cupping of the metaphyses with spur formation, and subperiostal new bone formation

hypopigmentation of hair

impaired growth

impaired immunity

impaired neurological function Pathological Consequences of Defi ciency

Established Premature and malnourished infants: anemia, osteoporosis, bone fractures, poor growth, and increased incidence of infections

Menkes’ disease: “Kinky-type” steely hair, progressive neurological disorder, death Suggested Fetus and children: impaired brain development²¹

Adults: Osteoporosis,²² ischemic heart disease,^23–25 increased susceptibility to infections,²⁶ and accelerated aging²⁷ Predisposing Factors for Defi ciency

Impaired absorption High intakes of zinc, celiac disease, short bowel syndrome, cystic fi brosis, diarrhea, and jejunoileal bypass surgery Excessive loss Peritoneal dialysis, burn trauma, penicilliamine therapy, dexamethasone treatment, and excessive use of antacids Increased oxidative stress High iron intake or iron overload and marginal zinc deprivation

Continued

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Iron

Among the mineral nutrients, iron has the longest and best-documented history. Despite long and effective intervention activi-ties, iron defi ciency is the most prevalent mineral defi ciency in the United States and the world. Recently, it has been suggested that high intakes of iron also may be a health concern. Table 8.3 only briefl y outlines some of the important aspects of iron nutrition which has been obtained from reviews by Beard and Dawson²⁸ and Baynes and Stipanuk.²⁹

Magnesium

Magnesium is the fourth most abundant cation in the human body, and is second only to potassium in intracellular concen-tration. This concentration refl ects that magnesium is critical for a great number of cellular functions including oxidative phosphorylation, glycolysis, DNA transcription, fatty acid degradation, and protein synthesis. Although it is such a critically important element, surprisingly, reported signs and symptoms of magnesium defi ciency in humans through dietary restriction alone are very limited. Described cases of clinical magnesium defi ciency have generally been conditioned defi ciencies where TABLE 8.3

Biochemical, Clinical and Nutritional Aspects of Iron

Biological Function Iron is involved in oxygen transport and storage, electron transport, and in numerous enzymatic reactions involving substrate oxidation and reduction. The classes of enzymes dependent on iron for activity include the oxidoreductases (e.g., xanthine oxidase/dehydrogenase), monooxygenases (e.g., cytochrome P450), dioxygenases (e.g., amino acid or amine dioxygenases), lipoxygenases, peroxidases, fatty acid desaturases, nitric oxide synthases, and miscellaneous enzymes such as aconitase

Signs and Symptoms of Defi ciency

Biochemical Decreased tissue and blood iron enzymes, myoglobin, hemoglobin, ferritin, transferrin saturation, and iron, and increased erythrocyte protoporphyrin

Physiological Anemia, glossitis, angular stomatitis, spoon nails (koiloncychia), blue sclera, lethargy, apathy, listlessness, and fatigue Pathological Consequences of Defi ciency

Established Impaired thermoregulation, immune function, mental function and physical performance; complications in pregnancy including increased risk of premature delivery, low birth weight, and infant morbidity Suggested Osteoporosis,^30–32 and impaired brain development³³

Predisposing Factors for Defi ciency Blood loss (e.g., menstruation) and vegetarian diets Recommended Intakes

Prevention of defi ciency RDAs (and AIs) set by the Food and Nutrition Board³ for iron (mg/day) are: infants age 0–0.5 year, (0.27) and age 0.5–1 year, 11; children age 1–3 years, 7, and age 4–8 years, 10; adolescents age 9–13 years, 8,

males age 14–18 years, 11, and females age 14–18 years, 15; males age ≥19 years, 8; females age 19–50 years, 18, age >50 years, 8, pregnant, 27, lactating age ≤18 years, 10, and age >19 years, 9

Therapeutic or benefi cial Higher doses than the above can be given to more quickly overcome iron defi ciency, usually caused by blood loss;

doses used include 50 to 60 mg/day or 120 mg/week.^34,35 However, caution is in order because high intakes of iron have been associated with cardiovascular disease and cancer^3,36

Food Sources Red meat, organ meats (e.g., liver), seafood (e.g., oysters, shrimp), fortifi ed cereals, potatoes with skin, tofu; some whole grains and vegetables (e.g., spinach) are high in iron but the bioavailability of this iron may be low

TABLE 8.2 (Continued)

Recommended Intakes

Prevention of defi ciency RDAs (and AIs) set by the Food and Nutrition Board³ (mg/day) are: infants age 0–0.5 year, (0.20) and age 0.5–1 year, (0.22); children age 1–3 years, 0.34 and age 4–8 years, 0.44; adolescents age 9–13 years, 0.70 and age 14–18 years, 0.89; adults, 0.90; pregnancy, 1.0; lactation, 1.3

Therapeutic or benefi cial Increased intakes of copper (e.g., 3 mg/day for adults) may be benefi cial for preventing osteoporosis, overcoming the adverse effects of high zinc intake, and more quickly overcoming the consequences of copper defi ciency

Food Sources Legumes, whole grains, nuts, organ meats (e.g., liver), seafood (e.g., oysters, crab), peanut butter, chocolate, mushrooms, and ready-to-eat cereals

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164 Handbook of Nutrition and Food

factors interfering with absorption or promoting excretion were present (see Table 8.4). However, short-term human magne-sium depletion experiments suggest that low magnemagne-sium intakes similar to those consumed by a signifi cant number of people may induce heart arrhythmias and soft tissue calcium retention that may exacerbate disorders induced by oxidative stress.^37–39 Table 8.4 briefl y outlines some of the important aspects of magnesium defi ciency, most of which were obtained from reviews by Rude⁴⁰ and Shils.⁴¹

Manganese

The essentiality of manganese for animals has been known for over 50 years. Defi ciency causes testicular degeneration (rats), slipped tendons (chicks), osteodystrophy, severe glucose intolerance (guinea pigs), ataxia (mice, mink), depigmentation of hair, and seizures. However, descriptions of signs of manganese defi ciency in humans are very limited. The most convincing case of manganese defi ciency is that of a child with a postoperative short bowel on long-term parenteral nutrition with low manganese content. The child developed short stature and diffuse bone demineralization resulting in brittle bones.⁵⁶ Because manganese defi ciency has been so diffi cult to identify in humans, it is generally not considered to be of great nutritional concern. Most of the information in Table 8.5 has been obtained from reviews by Leach and Harris,⁵⁷ Nielsen,⁵⁸ and Freeland-Graves and Llanes.⁵⁹ Zinc

Signs of zinc defi ciency in humans were fi rst described in the 1960s. However, the prevalence of zinc defi ciency is still unknown because of the lack of satisfactory indicators of zinc status. Zinc supplementation studies indicate that a mild zinc defi ciency

TABLE 8.4

Biochemical, Clinical and Nutritional Aspects of Magnesium

Biological Function Magnesium is a cofactor for more than 300 enzymes in the body. This cofactor role is either as a direct allosteric activator of enzymes or as a part of enzyme substrates for some enzyme reactions (e.g., MgATP and MgGTP).

Magnesium also has functions that affect membrane properties and thus infl uences potassium and calcium channels and nerve conduction

Signs and Symptoms of Defi ciency

Biochemical Low blood potassium, calcium and magnesium

Decreased intracellular potassium

Excessive renal potassium excretion

Impaired parathyroid hormone secretion and vitamin D metabolism

Renal and skeletal resistance to parathyroid hormone

Physiological Neuromuscular signs (e.g., positive Trousseau’s signs, tremors, fasiculations, gross muscle spasms, muscle cramps and weakness, seizures, dizziness, disequilibrium)

Electrocardiographic abnormalities

Cardiac arrhythmias (e.g., rapid heart rate, ventricular premature discharges, atrial and ventricular fi brillation) Pathological Consequences of Defi ciency

Established Conditioned defi ciencies result in cardiac arrhythmias, seizures, cramps, depression, and psychosis

Suggested Based on numerous epidemiological studies and magnesium supplementation trials, low magnesium status is associated with numerous disorders including coronary heart disease,^42,43 hypertension,^44–46 diabetes,^46,47 various types of headaches,^48–50 pain sensitivity,⁵¹ some cancers,⁵² nephrolithiasis,⁵³ and osteoporosis⁵⁴

Predisposing Factors for Defi ciency Factors interfering with absorption and utilization or promoting excretion including alcoholism, kidney failure, malabsorption syndromes, extensive bowel resection, gastroileal bypass, severe or prolonged diarrhea, protein-calorie malnutrition, acute pancreatitis, hyperaldosteronism, diabetes mellitus, thyroid gland disease, parathyroid gland disease, vitamin D resistance or defi ciency, burns, and diuretic therapy

Recommended Intakes

Prevention of defi ciency RDAs (and AIs) set by the Food and Nutrition Board¹ for magnesium (mg/day) are: infants age 0–0.5 year, (30) and age 0.5–1 year, 75; children age 1–3 years, 80, age 4–8 years, 130 and age 9–13 years, 240; males

age 14–18 years, 410, age 19–30 years, 400, and age 31+ years, 420; females age 14–18 years, 360, age 19–30 years, 310, age 31+ years, 320, pregnant, +40

Therapeutic or benefi cial Infusion of magnesium has been indicated as a means to quickly overcome a magnesium defi ciency. An effective treatment⁵⁵ has been found to be intravenous administration of 24 mmol of magnesium as a 50% solution over 24 h for 3 to 7 days. Patients who are hypomagnesemic and have seizures or an acute dysrhythmia may be given 4 to 8 mmol of magnesium over 5 to 10 min followed by the same regimen

Food Sources Whole grains, nuts, legumes, green leafy vegetables

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that results in growth retardation or impaired immune function may be quite prevalent. Unquestionable zinc defi ciency has been induced by providing zinc defi cient total parenteral nutrition, and by feeding cow’s milk to infants who have a genetic inability to absorb zinc from such a source. The information in Table 8.6 primarily comes from reviews by Chesters,⁶³ Prasad,⁶⁴ and Dibley.⁶⁵ ESSENTIAL ULTRA TRACE ELEMENTS

In 1980, the term ultra trace elements began to appear in the nutritional literature; the term was defi ned as an element required by animals in amounts of 50 ng or less per gram of diet. For humans, the term has been used recently to indicate elements with established or estimated requirements quantifi ed by micrograms per day.⁵⁸ There are four essential ultra trace elements. The evidence of essentiality for humans is substantial and not controversial for cobalt, iodine, molybdenum, and selenium; specifi c biochemical functions have been identifi ed for each. Another element, chromium, in the past has been considered an essential ultra trace element, and thus is included in this section. However, it should be noted that a critical review of the fi ndings suggest-ing essentiality reveal that chromium is unable to meet any defi nition of essentiality^75–77 and probably belongs in the possibly essential ultra trace element category.

Chromium

Flaws in the early studies of chromium nutrition inhibited the acceptance of chromium as an essential nutrient until 1977.

In that year, it was reported that signs of chromium defi ciency were found in a patient receiving long-term total parenteral nutri-tion thought to be low in chromium. This patient developed impaired glucose tolerance and a resistance to insulin, which were reversed by an infusion of chromium.⁷⁸ However, skepticism about the nutritional essentiality of chromium began in 1980 when it was found that chromium analyses before then were not valid, and repeated efforts to defi nitively characterize a chromium-containing glucose tolerance factor were unsuccessful. At present, a clearly defi ned biochemical function has not been estab-lished for chromium. Neither has a chromium defi ciency been induced in any animal species that causes death or interrupts the life cycle. Chromium is also unable to meet the older criteria of essentiality, because a consistent reduction in a biological function from optimal that is prevented by physiological amounts of chromium has not been conclusively demonstrated. This inability to fulfi ll the requirements to be classifi ed as essential does not preclude the possibility that chromium may be found essential in the future. There is no question, however, about chromium being a bioactive benefi cial element; supranutritional TABLE 8.5

Biochemical, Clinical and Nutritional Aspects of Manganese

Biological Function Manganese is a cofactor for enzymes involved in protein and energy metabolism, antioxidant action, and mucopolysaccharide synthesis. These enzymes include the metalloenzymes manganese-dependent superoxide dismutase, pyruvate carboxylase and arginase, and the manganese-activated enzymes phosphoenolpyruvate carboxykinase, glycosyl transferases, glutamine synthetase and farnesyl pyrophosphate synthetase. Manganese also can activate numerous other enzymes including oxidorectases, lyases, ligases, hydrolases, kinases, decarboxylases, and transferases; these enzymes are activated by other metals, especially magnesium

Signs of Defi ciency

Biochemical None fi rmly established

Physiological Impaired growth and brittle bones (found in one child); another possible sign is a fl eeting dermatitis Pathological Consequences of Defi ciency

Established Osteoporosis (one case report in a child)⁵⁶

Suggested Low dietary manganese or low blood and tissue manganese has been associated with osteoporosis, diabetes, epilepsy, atherosclerosis, cataracts, and impaired wound healing⁶⁰

Predisposing Factors for Defi ciency High dietary intakes of calcium, phosphorus, iron, fi ber, phytate, and polyphenolic compounds. (Based on human absorption experiments and animal studies)

Recommended Intakes

Prevention of defi ciency AIs set by the Food and Nutrition Board³ for manganese (mg/day) are: infants age 0–0.5 year, 0.003, and age 0.5–1 year, 0.6; children age 1–3 years, 1.2, and age 4–8 years, 1.5; males age 9–13 years, 1.9, age 14–18 years, 2.2, and age ≥19 years, 2.3; females age 9–18 years, 1.6, age ≥ 19 years, 1.8, pregnant, 2.0, and lactating, 2.6

Therapeutic or benefi cial Caution is indicated against high intakes of manganese because of potential neurotoxicological effects,^61,62 especially in people with compromised homeostatic mechanisms, or infants whose homeostatic control of manganese is not fully developed

Food Sources Unrefi ned grains, nuts, green leafy vegetables, and tea

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166 Handbook of Nutrition and Food

amounts of chromium enhance insulin sensitivity or action. The information in Table 8.7 comes primarily from reviews by Offenbacher et al.⁷⁹ Nielsen,⁸⁰ Vincent,⁸¹ and Cefalu and Hu.⁸²

Cobalt

Ionic cobalt is not an essential nutrient for humans; however, vitamin B₁₂, in which cobalt is an integral component, is an essen-tial nutrient for humans. In the nineteenth century, a megaloblastic anemia was described that was called pernicious anemia, because it was invariably fatal. The fi rst effective treatment for this disease was 1 lb of raw liver daily. In 1948, the antiperni-cious anemia factor in liver was isolated and named vitamin B₁₂, and was found to contain 4% cobalt. Vitamin B₁₂ defi ciency is rarely caused by a dietary insuffi ciency and most commonly arises from a defect in vitamin B₁₂ absorption. People with low vitamin B₁₂ status (e.g., vegetarians) can also display signs of defi ciency if stressed with a substance such as nitrous oxide (used

Ionic cobalt is not an essential nutrient for humans; however, vitamin B₁₂, in which cobalt is an integral component, is an essen-tial nutrient for humans. In the nineteenth century, a megaloblastic anemia was described that was called pernicious anemia, because it was invariably fatal. The fi rst effective treatment for this disease was 1 lb of raw liver daily. In 1948, the antiperni-cious anemia factor in liver was isolated and named vitamin B₁₂, and was found to contain 4% cobalt. Vitamin B₁₂ defi ciency is rarely caused by a dietary insuffi ciency and most commonly arises from a defect in vitamin B₁₂ absorption. People with low vitamin B₁₂ status (e.g., vegetarians) can also display signs of defi ciency if stressed with a substance such as nitrous oxide (used

In document Handbook of Nutrition and Food (Page 180-187)