Metabolic Role OF Minerals
Analytical and Clinical Considerations

George M. Tamari, Ph.D.^*
Original published in: Med Organica 1987;16:36-40

Summary

Introduction

T

he presence of minerals and trace elements at optimum levels is essential for the production and maintenance of many enzymes involved in the anabolic and catabolic processes. Deficiency in one or more of these elements may lead to the appearance of degenerative conditions from "unknown" etiology. It seems to be important to measure and monitor the presence of these minerals, possibly at the tissue(cell) level where most metabolic activities take place. By comparing the different alternatives, many well-known scientists agree that hair tissue mineral analysis is the method of choice(1-4). It offers a number of advantages(5)':

1. Hair analysis provides a better assessment of normal trace element concentrations because short-term variations are averaged out. By taking a length of hair equivalent to a few week's growth and measuring the bulk concentration, an average concentration over that period may be found.

2. Hair analysis offers a good way of discerning long-term variations in trace element concentrations. This may be done by measuring the variation along the length of long hair equivalent to several months, or by taking samples periodically. These approaches have been used successfully to demonstrate cases as diverse as abnormal zinc metabolism in pregnant women(6) and the alleged poisoning of Napoleon Bonaparte by periodic doses of arsenic(7).

3. Unlike blood, hair is an inert and a chemically homogeneous substance. It consists of a fibrous protein, a-keratin, set in a matrix of another protein of amorphous structure, which is chemically very similar. The structure of hair is permanent and once a trace element is incorporated into it, it is fixed there.

4. The concentration of most trace elements is relatively high in hair compared to the rest of the body, especially blood. The average concentration of chromium, for example, is about 50 times greater in hair than in blood, while that of cobalt is over 100 times greater(8).

5. Hair provides a record of past as well as present trace element levels. Samples may be taken retrospectively. After a woman has been diagnosed pregnant, for instance, a sample can be taken to discover her condition prior to conception.

6. Specimens can be collected more quickly and easily than specimens of blood, urine, or any other tissue. Taking a sample requires no special training and can be done without pain or embarrassment to the patient. Specimens do not deteriorate and may be kept indefinitely without the need for special storage conditions(9)

7. The detection of heavy metals by blood analysis may not be the best choice. Petering et al(10) concluded that "blood is not a suitable material for an analysis of cadmium since the metal remains in the blood only very briefly and, in consequence, the levels are always extremely low". Blood can be used only for immediate measurement of exposure to lead and cadmium as it gives no indication of the cumulative levels of these elements. Similar arguments apply to testing for arsenic and mercury. When a factory released some arsenic compounds into residential area, it was some time before residents were examined and blood levels had declined to normal(11), but hair was successfully used to determine those contaminated by the release.

In the following sections, data are collected about the implications of deficiency in a single or a group of elements causing certain pathological conditions. Also, there is discussion of elements pre- viously considered to be non-essential: boron, silicon and strontium.

Compromised Carbohydrate Metabolism

Low levels of MAGNESIUM, MANGANESE, CHROMIUM and ZINC may cause difficulties in glucose metabolism and can lead to nutritionally induced adult- onset diabetes. These four elements play an important role in the process of breaking down glucose and converting it into energy. Magnesium also plays a very important role as a catalyst in several hundreds of biological reactions, mostly in the glycolytic enzymes(12). Zinc makes a very specific contribution in the break down of carbohydrate and is involved in the granulation and storage of insulin in the beta cells of the pancreas (13). It has been shown that the defect of dysinsulinemia, a prediabetic state, is caused by the inability of the beta cells to store and granulate insulin(14). For this reason, zinc deficiency may signal an early stage of dysinsulinemia and adult onset diabetes.

CHROMIUM's presence facilitates the entry of glucose into the cell. Studies with experimental animals indicate that supplementing chromium is ineffective without the presence of insulin, and the effectiveness of a given dose of insulin can be enhanced 50-100 percent by the addition of chromium to the system(15). Chromium is believed to bridge the sulfhydryls of the membrane of the target tissue, the disulfite group of the A-chain of the insulin and the glucose molecule.

MANGANESE seems to play a major role in glucose metabolism, and in general in energy production. It activates a key enzyme, isocitric dehydrogenase, in the Krebs cycle and many phosphotransferase enzymes(16). Guinea pigs on a manganese- deficient diet displayed a typical diabetic glucose tolerance curve which reverted with the inclusion of manganese in the diet(17).

Since the presence of MAGNESIUM is essential in converting ADP to ATP and is an activator of many enzymes in the glycolytic pathway (oxidative phosphorylation), a deficiency of it will cause impairment in glucose metabolism(18,19).

Hypothyroidism

Thyroxine is the hormone produced by a properly functioning thyroid gland. In the metabolic process leading to the biosynthesis of thyroxine, the following "row materials" are required: phenylalanine, manganese, copper and iodine. The amino acid phenylalanine is converted via tyrosine into thyroxine and triiodotyrosine(19), which is the active intracellular thyroid hormone. MANGANESE plays an active part in this conversion(20), which is supported by COPPER and ZINC containing enzymes. Copper is essential in converting iodide to elemental iodine in the thyroid acinar cell.

Deficiency of copper, zinc, manganese and iodine in itself is a good reason for an impaired thyroid function. In the population at large, the availability of these minerals is limited, mainly because they are removed at different stages of food-processing. Many patients share a low basal temperature indicating the presence of subclinical hypothyroidism(21). It may be that the deficiency in mineraIs essential in the biosynthesis of thyroxine is the cause of this syndrome, rather than frank hypothyroidism as a result of low production of thyroxine by the thyroid gland.

Cardiovascular Pathology

The role of hypertension in cardiovascular disease is well established. It was shown by Schroeder (22) that the presence of low levels of CADMIUM in the tissues has a very potent hypertensive effect. In experimental animals, cadmium doubled the systolic blood pressure(23). McKenzie and Kay have shown that hypertensive subjects excrete 5 to 10 times more cadmium than their normotensive counter- parts, while no difference was indicated in the excretion of any other minerals(24).

The association of adult onset diabetes mellitus with vascular pathology is well established in the medical literature(25). There is a strong indication of CHROMIUM deficiency as a causative factor in atherosclerosis and coronary heart disease. Dr. A. Abraham of Jerusalem found a significant regression of atherosclerotic plaques after chromium supplementation(26).

The role of COPPER in cardiovascular disease is related to its association with the activation of the enzyme lysil oxidase. Inhibition of this enzyme leads to diminished stability and strength of bone collagen and aortic elastin as a result of impaired cross-linkage of their polypeptide chains(27). According to Klevay, copper deficiency in our diet is a major contributor leading to ischemic heart disease (IHD). In this paper(28), there is a convincing comparative list of symptoms in people suffering from IHD and symptoms of animal deficient in copper (Table 1).

The calcium/magnesium ratio in hair mineral analysis is a valuable indicator to consider. When this ratio approaches 16:1 instead of the normal 8: 1, it indicated that calcium is elevated compared to magnesium. In this case the subject is predisposed to deposit calcium in the tissues, a conditions which may lead to nephrolithiasis and arteriosclerosis. Magnesium supplementation may be of therapeutic value in this case(29).

Learning and Behavior Disorders

A great number of studies indicate a strong correlation between the presence of toxic elements and learning disabilities and also emotional disturbances in children. Children exposed to toxic amounts of LEAD and other metal pollutants are subject to several behavioral disorders resulting from damage to the central nervous system(31,32).

Subtoxic lead levels previously thought harmless are associated with hyperactivity, impulsiveness, and short attention span(33,34,35). Previous investigations have also linked subtoxic CADMIUM, MERCURY and ALUMINUM levels to measures of non-adaptive classroom behaviour (36,37,38). Capel correlates the elevated levels of cadmium and its neuro- toxicity as a causative factor in dyslexia. Lead, cadmium, aluminum and mercury are chemically able to replace essential nutritional elements, calcium, magnesium, copper, iron and zinc, which play an important role in many of our essential enzyme systems. Furthermore, a deficiency in many of the nutritional minerals - being a fact of life in any industrialized country(39) - facilitates absorption into our cells of toxic elements present in the environment. The interaction and antagonism among the different minerals and toxic elements can be used to "replace" the body- burden of the toxic element by nutritional minerals which were deficient in the first place(40)

C.Pfeifer et al.,(41) have postulated that excessive copper may be the primary factor in chemically-induced schizophrenia, or histapenia. Histaminase, a copper-containing enzyme, can destroy histamine. Patients with elevated levels of ceruloplasmin, another copper-rich protein, have a low level of blood histamine.

In gasoline, manganese carbonyl compounds are now used to supplement or replace lead antiknock compounds. These compounds are easily absorbed through the lung and can cause fatigue, weakness, headaches and mental disturbances (manganese madness(42,43).

Bone Formation - Osteoporosis

Osteoporosis is a major epidemic in North America and responsible for over a million fractures per year. More than one- third of women are affected by this degenerative process, mostly after reaching menopause.

Today's management of osteoporosis is centered around estrogen therapy and supplementation of CALCIUM. Although it has been shown that estrogen retards bone loss, it does not prevent it completely. further, the use of estrogen therapy should be weighed against risk of causing endometrial and other cancers(44).

Osteoporosis is an expression of a negative balance between bone formation and bone loss. These processes depend on a multifactorial system in which elements other than calcium and estrogen interact.

In bone formation, collagen acts as a framework upon which the mineral phase is deposited. Collagen is characterized chemically by large amounts of glycine, proline, hydroxyproline and hydroxylysine. The presence of hydroxy- amino acids make collagen unique, since these amino acids are absent in other proteins.

Hydroxyproline is not synthetized in the absence of ascorbic acid. Since the integrity of collagen is affected by ascorbic acid deficiency, it becomes more vulnerable to the effects of minor trauma.

Sixty percent of the body's MAGNESIUM is contained in bone, where it takes part in a number of biochemical reactions. Alkaline phosphatase, a ZINC-dependenant enzyme, is involved in forming new calcium crystals and is activated by MAGNESIUM(61,62). Vitamin D is required for intestinal absorption of CALCIUM. The conversion of vitamin D to its biologically active for, 1,25-dihydroxyvitamin D"requires MAGNESIUM(45).

MANGANESE is required for bone mineralization(45) and for the biosythesis of connective tissue in cartilage and bone(63). Tissue mineral analysis indicated a manganese deficiency in nearly 75 percent of one thousand subjects investigated(46). This finding may be result of food processing in which whole grains are replaced by refined flour(47).

Boron, Strontium and Silicon

An element is considered to be essential if dietary deficiency of that element clearly results in a suboptimal biological function, which is preventable and reversible by physiological amounts of the element.

These criteria of essentiality have been fulfilled by boron, silicon and strontium. Since they are important in many biological functions, they will be discussed in more detail.

BORON was previously thought to be essential only for plants. As indicated by recent studies however, boron is known to be essential in human nutrition, particularly in relation to bone integrity. In one study, postmenopausal women were kept on a conventional diet supplying about 0.23 mg boron per day for 119 days. Boron supplementation of this diet (3mg/ day) markedly reduced the urinary excretion of calcium (44 percent) and almost doubled the serum concentration of 17beta-estradiol, the biologically most active form of estrogen to the same level as in women receiving estrogen therapy(48,49).

Boron supplementation does not pose the same risk as estrogen therapy, which is dose-related. The boron-induced increase in serum 17beta-estradiol is five percent of the oral dose(50).

The nutritional doses of 1-3 mg/day are safe as shown in toxicological studies(51). Consumption of 41 mg boron per day was shown to have no adverse effects(52).

STRONTIUM is deposited in relative large concentration in bones and teeth, replacing part of calcium in hydroxapatite crystals. The importance of strontium in treating bone-loss was indicated by a study involving 32 patients. 22 were treated with strontium lactate alone, and 10 were treated with a combination of strontium lactate, estrogen and testosterone(53)'. Among the group of 22 treated by strontium alone, 18 improved markedly (82%) and 4 improved moderately (18%). Among the group of ten with both strontium and hormones, nine experienced marked subjective improvement. (90%). Although direct toxicological studies were not conducted, strontium appears to be virtually non-toxic(54).

The role played by SILICON in different biological functions came to light only recently. Its abundance in the earth's crust may hint of its potential significance in normal life processes.

Animal studies lead to the conclusion that silicon appeared to be an essential element(55,57). It is involved in the early stages of bone calcification and is present in the active growth areas at a higher ratio of silicon/calcium. In "mature" bone, however, this ratio is reversed. In addition to its role in bone formation, silicon deficiency is manifested by abnormalities involving cartilage and connective tissue. Silicon has been shown to be involved in both collagen and glycosaminoglycan formation. Its primary effect in bone and cartilage appears to be in the formation of the matrix and also in the mineralization process itself.

Silicon supplementation in an organ culture caused a one hundred percent increase of collagen content, compared with a non-supplemented cultures.

In aging, there are recognized changes in the connective tissue, since silicon is an essential part of this tissue, a decline in its concentration can be observed. This decline is particularly dramatic in the aorta, and commences at an early age(58). Fourteen times as much silicon was found in disease free arteries then in atherosclerotic arteries (56).

A study was conducted over many years on a large number of elderly patients suffering from recalcitrant and painful musculoskeletal disorders, including rheumatoid and osteoarthritis, Paget's disease and intractable sciatica of undetermined origin. After silicon supplementation over a three to six month period, a dramatic increase in articular mobility and marked lessening of pain was achieved in the majority of cases. Furthermore, it was found that with supplementation of silicon, sclerotic areas tended to disappear while decalcified areas showed recalcification(59).

Deficiency of silicon affects.the aorta, among other tissues. It is no wonder, therefore, that death from heart disease is lowest in the regions of England and Finland where silicon concentration in drinking water is the highest(60).

In conclusion, the important role of minerals in maintaining homeostasis in the human body is recognized. It seems to be equally important to monitor periodically the tissue levels of minerals and trace elements at intervals. Periodic trace mineral monitoring, using hair analysis, provides an opportunity to promptly identify and correct these subtle imbalances.

George M. Tamari, Ph.D. Clinical Biochemist

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