Toxic & Essential Elements (Whole Blood)

Exposure to arsenic-laden drinking water can induce symptoms of gastroenteritis and lead to cancer, diabetes, and neurological and vascular dysfunction. Long-term arsenic exposure in drinking water shows a dose-response relationship to carotid atherosclerosis. The mechanism involves the induction of expression of genes coding inflammatory mediators. Arsenic has also been linked to dermatosis and cancers of the skin, bladder, and lung. Dietary arsenic is contributed by various foods including cereals and breads, 18.1%; starchy vegetables, 14.9%; and meats and fish, 32.1% of total average daily intake. Arsenic exposure is associated with the following clinical symptoms: → Neurological: Central depression with visual effects, headache and high fever → Hematological: Abnormal RBC counts, increased megalocytes and microcytes → GI tract: Increased peristalsis with “rice water” stools → Skin: “Milk and roses” complexion from vasodilation, darkening and degeneration Laboratory values of arsenic represent both the toxic form of arsenic and the non-toxic form of arsenic. Because seafood is rich in the non-toxic form of arsenic, the clinician should rule out ingestion of seafood in cases of borderline or moderate arsenic elevation before implementing aggressive therapy. Urinary arsenic is most commonly measured to screen for arsenic exposure. Urine reflects arsenic exposure in the few days prior to specimen collection. To eliminate the contribution of seafood to total arsenic levels, avoid seafood 72 hours before test. Hair, nail and urinary arsenic levels have been shown to be comparable. Hair or nail arsenic represents several months of exposure prior to taking the specimen. Hair arsenic greater than 1 μg/g dry weight has been taken to indicate excessive exposure. Since elevated arsenic in the serum drops within 6 to 10 hours, serum is not the best specimen for determining chronic arsenic exposure. Whole blood is suitable for identifying acute exposure to arsenic, and high levels should be addressed immediately. When arsenic toxicity is suspected, arsenic levels in drinking water should be measured. Support clearance of arsenic with B vitamins, especially folate. Give sulfur amino acids, antioxidants, as well as essential elements. Emblica officinalis, a medicinal plant, has shown promising results in animal studies. Associated Symptoms and Diseases: Peripheral arteriosclerosis (“blackfoot disease”) “ricewater” stools, proteinuria, hyperkeratosis, “milk and roses” hyperpigmentation, garlic breath odor, stomatitis Sources: Metal foundry, drinking water, seafood, glues, industrial exposure, contaminated wine, contaminated herbal supplements, cigarette smoke, arsenic-treated wood Protective Measures: Selenium, Emblica officinalis, sulfur amino acids, glutathione Chelating Agents: DMSA, DMPS, DMPA

Barium is used in X-ray contrast media and in some salts for enemas. Many foods contain small concentrations of barium, and it responds somewhat like calcium, magnesium, and strontium to physiological controls. Symptoms of high barium include gastrointestinal complaints, muscle weakness, facial numbness, and hypotension. Treatments for high barium include oral sodium sulfate. Serum potassium levels should also be checked and treat hypokalemia, if present. Sources: X-ray contrast media, enema salts, foods Symptoms: Gastrointestinal complaints, muscle weakness, facial numbness, and hypotension Treatment: Oral sodium sulfate, treat hypokalemia if present

The principal organs most vulnerable to cadmium toxicity are kidney and lung. Environmental cadmium exposure is associated with renal tubular damage and high blood pressure. Cadmium toxicity impacts the kidney, where damage to proximal tubules has been described. Also, cadmium compounds are classified as carcinogenic to humans. Associated conditions include: → Renal: hypertension, kidney failure → Neurological: loss of coordination, numbness of limbs, loss of hearing Whole blood cadmium is indicative of recent exposure, and is therefore not reflective of total-body burden. Normal concentration of whole blood cadmium is up to 1 μg/L for nonsmokers, and up to 4 μg/L for smokers. Whole blood levels of 10 μg/L have been associated with renal dysfunction. Associated Symptoms and Diseases: Femoral pain, lumbago, osteopenia, renal dysfunction, hypertension, vascular disease Sources: Industry, spray paint, tobacco smoke, car emissions, plants grown in cadmium-rich soil Protective Measures: Zinc, iron, antioxidants Chelating Agents: EDTA; DMSA and NAC (experimental)

Calcium is essential for bones and teeth, heart, nerves, muscles, and blood clotting. Calcium’s actions are as wide ranging as neuronal excitation, neurotransmitter release, innate immunity, hormonal secretion, and tone of smooth muscle cells in the vasculature, airways, uterus, gastrointestinal (GI) tract, and urinary bladder. Calcium deficiency can lead to osteoporosis. Other symptoms include musculoskeletal pain, muscle cramps, and tetany. Optimum calcium status can help prevent lead toxicity. Because calcium is high outside of the cell, calcium levels in erythrocytes are not a measurement of total body calcium status, but instead are a measure of cell membrane permeability. Erythrocyte calcium is a useful marker in the management of patients with hypertension and arrhythmias, renal failure, and even pre-menstrual syndrome. Treatment for high intracellular calcium includes magnesium, antioxidants, and fatty acids (to improve the integrity of the cell membrane).

Chromium, when measured in whole blood as part of a Toxic and Essential Elements panel, provides valuable insights into the body's chromium status, which is pivotal for various physiological functions. Chromium is a trace element essential for human health, primarily recognized for its role in enhancing the action of insulin, a hormone critical to the metabolism and storage of carbohydrate, fat, and protein. Its presence in whole blood reflects both recent dietary intake and the body's stores of the mineral. Chromium exists in several forms, but the trivalent chromium (Cr3+) is the biologically active form, considered safe and necessary for human health, while hexavalent chromium (Cr6+) is toxic and carcinogenic. The measurement of chromium in whole blood can be crucial for evaluating nutritional status, particularly in populations at risk of chromium deficiency, such as those with unbalanced diets, the elderly, and individuals with impaired glucose tolerance. Elevated levels of chromium, on the other hand, might indicate excessive exposure, potentially due to occupational hazards or environmental contamination, and can lead to toxic effects including skin rashes, gastrointestinal issues, or more severe organ damage. Given its dual potential as both an essential nutrient and a toxicant at high concentrations, monitoring chromium levels through such panels is vital for both clinical and occupational health assessments, guiding dietary recommendations and exposure prevention strategies.

Cobalt (Co) is an essential trace element due to its well-known role in vitamin B12, important in hematopoiesis and thyroid function. The consequences of B12 deficiency are well known, including central nervous system complaints, pernicious anemia, and potentially fatal macrocytic anemia. Ingested cobalt is largely excreted in urine. Whole-blood cobalt was detected at approximately 0.17 μg/L in patients awaiting surgery. Toxicity may occur at cobalt intakes above 300 mg/d, although even therapeutic doses at 29.5 mg/d have been associated with toxicity, including goiter, hypothyroidism, and heart failure.

Copper, a trace element, is a crucial component on a Toxic and Essential Elements panel when assessed in whole blood. It plays a vital role in numerous physiological processes, acting as a key cofactor in various enzymatic reactions. Copper is integral in the formation of red blood cells, the maintenance of healthy nerves and bones, and the absorption and utilization of iron. It also contributes to the synthesis of ATP, the body's primary energy currency, and is involved in the formation of connective tissue and the functioning of the immune system. However, the balance of copper in the body is delicate; both deficiency and excess can lead to significant health issues. Deficiency might lead to anemia, osteoporosis, and neurological problems, while an excess, often due to genetic disorders like Wilson's disease or overexposure, can cause toxic effects, including liver and kidney damage, and neurological disturbances. Monitoring copper levels in whole blood is thus critical for diagnosing and managing these conditions. The assessment of copper in whole blood provides a more comprehensive understanding than serum copper levels alone, as it reflects both the free and protein-bound forms of copper. Management of abnormal copper levels depends on the underlying cause and may include dietary adjustments, supplementation, or chelation therapy in cases of toxicity. This makes the measurement of copper in whole blood an essential aspect of a Toxic and Essential Elements panel, offering valuable insights into a person's metabolic and nutritional status.

Lead toxicity causes paralysis and pain in the extremities due to effects on demyelinization, axonal degeneration, and presynaptic block. Lead toxicity commonly affects sensory, visual, auditory, and cerebellar (coordination) functions, reflecting its impact on the nervous system. Normocytic, sideroblastic anemia is the consequence of lead’s inhibiting effects on enzymes in the heme biosynthesis pathway. Other clinical signs associated with lead toxicity are kidney damage, epigastric pain and nausea, and male and female reproductive failure. Hyperactivity, anorexia, decreased play activity, low intelligence quotient and poor school performance have been observed in children with high lead levels. Sources of lead include lead pipes, painted toys, some red lipsticks, lead paint or its dust, soil around old cars, old homes, or highways (past leaded gasoline contamination). Whole blood is concentrated about 75-fold greater than that of serum or plasma and it has the highest correlation with toxicity. For this reason, whole blood lead is defined by the CDC as the preferred test for detecting lead exposure. The World Health Organization has defined high whole-blood lead levels as > 20 μg/dL in adults and > 10 μg/dL in children. As of 2007, the CDC acceptable level of whole blood lead was 10 μg/dL. Some have proposed to lower reference values for whole blood lead. Associated Symptoms and Diseases: Microcytic hypochromic anemia, renal dysfunction, hypertension, anorexia, muscle discomfort, constipation, metallic taste, low IQ (children) Sources: Certain supplements, paint, contaminated soils (and plants grown in them), plumbing Protective Measures: Alpha lipoic acidprotection against toxicity, iron (reduces intestinal absorption Chelating Agents: Ca –EDTA

Lithium, a chemical element represented by the symbol Li, is both a therapeutic agent and a potential toxicant, prominently featured in Toxic and Essential Elements panels for whole blood testing. Medically, lithium is primarily used in the treatment of bipolar disorder, effectively stabilizing mood and reducing the extremes of mania and depression. In such therapeutic use, monitoring lithium levels in whole blood is crucial, as the therapeutic range is relatively narrow and closely borders on toxicity. Symptoms of lithium toxicity include nausea, tremors, confusion, and in severe cases, renal impairment and neurotoxicity. In a Toxic and Essential Elements panel, the concentration of lithium in the blood is measured to ensure it remains within a safe and effective range for patients undergoing lithium therapy. This testing is also significant in occupational and environmental health, as lithium exposure can occur through various sources, including batteries and certain industrial processes. By assessing lithium levels in whole blood, healthcare providers can manage appropriate dosing in therapeutic contexts, monitor potential occupational or environmental exposure, and prevent the adverse effects associated with lithium toxicity.

Magnesium, when measured in whole blood, is an essential element of the Toxic and Essential Elements panel, offering significant insights into a person's metabolic and physiological status. As an essential mineral, magnesium plays a pivotal role in over 300 enzymatic reactions within the human body, crucial for processes such as protein synthesis, muscle and nerve function, blood glucose control, and blood pressure regulation. It also contributes to the structural development of bone and is required for the synthesis of DNA, RNA, and the antioxidant glutathione. The measurement of magnesium in whole blood provides a more comprehensive understanding of the body's magnesium status compared to serum magnesium levels, as it includes both intracellular and extracellular magnesium. This is vital because the majority of magnesium in the body is located inside cells or in the bone. Abnormal levels of magnesium in whole blood can indicate various medical conditions: low levels (hypomagnesemia) may result from conditions like malabsorption, alcoholism, or chronic kidney disease, leading to symptoms like muscle cramps, seizures, and arrhythmias; high levels (hypermagnesemia), though less common, can occur due to excessive supplementation or in individuals with impaired kidney function, potentially causing muscle weakness, hypotension, and cardiac arrest. Monitoring whole blood magnesium levels is therefore crucial in clinical settings for both diagnostic and therapeutic purposes, particularly in the management of chronic diseases and critical care situations.

Manganese, a trace element found in whole blood, plays a pivotal role in human health and is measured in a Toxic and Essential Elements panel. As an essential nutrient, manganese is crucial for several biological processes, including bone formation, blood clotting, and immune response. It acts as a cofactor for various enzymes, notably those involved in metabolism and antioxidant defenses, such as superoxide dismutase, which protects cells from damage caused by free radicals. Despite its essentiality, manganese levels must be tightly regulated, as both deficiency and excess can lead to health issues. Deficiency, although rare, may result in impaired growth, skeletal abnormalities, and disrupted carbohydrate and lipid metabolism. Conversely, excess manganese, usually due to environmental exposure or dietary overconsumption, can be toxic, particularly affecting neurological health. It can lead to a condition known as manganism, characterized by symptoms resembling Parkinson's disease, such as tremors and motor skill impairments. The measurement of manganese levels in whole blood provides crucial information for assessing both deficiency and toxicity. This is particularly important in occupational settings where exposure to manganese dust or fumes might be high. In clinical practice, monitoring whole blood manganese levels can help guide dietary recommendations and assess the need for interventions to address imbalances, contributing to the maintenance of optimal health and prevention of manganese-related disorders.

Mercury intoxication is associated with a triad of symptoms: (1) mental changes, (2) spontaneous tremor and deficits in psychomotor performance, and (3) stomatitis and gingivitis. The toxic effects of mercury have been associated with neurological dysfunction, dementia, and autoimmune diseases. Although research suggests that the etiology of autism is multifactorial, numerous reports demonstrate that aspects of mercury toxicity appear similar to autism symptomatology. According to the CDC, mercury released from amalgams may comprise up to 75% of an individual’s mercury exposure. Methylmercury from seafood is considered to be the most important source of non-occupational human mercury exposure. Blood mercury has revealed low level chronic and acute exposure from work environments. Significant exposure is evident when whole blood alkyl mercury is greater than 50 μg/L, or when inorganic mercury (Hg2+) exposure is greater than 200 μg/L. Children’s reference values for whole blood mercury from 1.5 to 1.0 μg/L have been proposed. Risk of Attention Deficit Hyperactivity Disorder (ADHD) was found to be nearly 10 times higher when blood mercury was above 29 nmol/L. The quantity of mercury assayed in blood and hair, but not urine, correlates with the severity of toxicity symptoms. Associated Symptoms and Diseases: Mental symptoms (erethism, insomnia, fatigue, poor short- term memory), tremor, stomatitis, gingivitis, GI and renal disturbances, decreased immunity Sources: Dental amalgams, fish consumption, preservatives (esp. thimerosal), industrial release effects) Protective Measures: Selenium (protects against cellular toxicity) Chelating Agents: DMSA, DMPS References: Suzuki T. et al eds, Advances in Mercury Toxicology, Plenum Press, New York, NY, 1991. World Health Organization: ”Methylmercury”, Environ. Health Criteria 101

Mo is an essential nutrient that functions as an obligatory cofactor for the iron- and flavin-containing enzymes aldehyde oxidase, xanthine oxidase, and sulfite oxidase. Aldehyde oxidase oxidizes and detoxifies the pyrimadines, purines, and pteridines. Xanthine oxidase/ dehydrogenase catalyzes the formation of uric acid from hypoxanthine and sulfite oxidase catalyzes the transformation of sulfite to sulfate. Insufficient sulfite oxidase activity can result in deranged cystiene metabolism. References: - Nielsen, F.H. Ultratrace Minerals, chapter 15 in Modern Nutrition in Health and Disease, 8th ed., vol. 1, Lea & Febiger, 1994. - Falchuk, K.H. Disturbances in Trace Elements, in Fauci, A.S. et. al., eds, Harrison’s Principles of Internal medicine, 14th edition, Mc Graw Hill, 1998.

Deficiency of nickel is associated with poor growth and reproductive dysfunction. Nickel has been shown to work in a cooperative way with calcium, iron, and zinc. Chronic exposure to some forms of nickel via inhalation is carcinogenic. Mucosal tissue irritation associated with nickel can manifest as asthma, rhinitis and sinusitis. Pulmonary inflammation may arise after breathing in nickel in the form of dust or smoke. Nickel toxicity may result in liver necrosis or carcinoma. Hypersensitivity reactions may occur with chronic nickel exposure. Dermatitis is also associated with nickel worn as jewelry. Other sources of nickel include stainless steel, tobacco smoke, industrial exhaust fumes, batteries, as well as electronic and plating and mining industries. Urine and plasma have been used for assessing nickel exposure, although only acute exposure is revealed because nickel is rapidly cleared from blood. Associated Symptoms and Diseases: Carcinogenic, dermatitis, asthma, rhinitis, sinusitis Treatment: Reduce stainless steel cookware and nickel jewelry

Platinum and platinum alloys are used in surgical tools, laboratory utensils, dentistry, jewelry, silicone breast implants, electrical resistance wires, automobile catalytic converters, optical fibers, and liquid crystal display glass, especially for laptops. It is believed that automotive catalytic converters release platinum to the roadside environment. Platinum is used in some chemotherapy drugs, such as cisplatin, which is used to treat ovarian cancer. Workers in the following areas show the highest platinum levels: roadside maintenance, refineries, oncology wards, electronics plants, chemical plants, and jewelry production. Women with silicone breast implants have platinum exposure. One study showed a significant uptake of platinum from platinum-containing dental alloy restorations. The general population is at increasing risk of exposure to platinum because of the widespread use of catalytic converters and growing applications for platinum in various sectors of the economy. Symptoms of platinum salt hypersensitivity are urticaria, contact dermatitis, respiratory disorders including sneezing, shortness of breath, cyanosis, and/or severe asthma. Symptoms usually abate when exposure is removed. A history of atopy, respiratory disease, or smoking may predispose an individual to developing platinum salt hypersensitivity. Platinum as a pure metal is thought to be non-allergenic. Blood levels of platinum in the general population have been recorded at 0.1-2.8 μg/L while occupational exposure resulted in serum platinum levels of 150-440 μg/L. It is thought that little platinum is absorbed in the lungs and GI tract. When ingested or inhaled by experimental animals, platinum is cleared via the lungs, feces, and a small portion is cleared in the urine. Platinum is concentrated in the kidneys, liver, spleen, and adrenals in animal studies. Sources: Jewelry, Surgical tools, Laboratory utensils, Electrical resistance wires, Automobile catalytic converters, Liquid crystal display glass, Dental restorations, Chemotherapy drugs, Silicone breast implants. Symptoms: Contact dermatitis, urticaria Respiratory symptoms Treatment: Avoidance and treat for symptoms and conditions

Selenium, a trace element found in the whole blood, is a significant component of the Toxic and Essential Elements panel, offering vital insights into an individual's nutritional status and potential toxic exposure. As an essential micronutrient, selenium is crucial for various bodily functions, most notably its role in the synthesis of selenoproteins, which includes important antioxidant enzymes like glutathione peroxidases and thioredoxin reductases. These enzymes play a critical role in protecting cells from oxidative damage caused by free radicals, thereby contributing to immune system function and thyroid hormone metabolism. Selenium's optimal range in the body is narrow: both deficiency and excess can lead to health issues. Deficiency of selenium can lead to impaired immune function, hypothyroidism, and in severe cases, Keshan disease—a potentially fatal form of cardiomyopathy. Conversely, excessive selenium intake can result in selenosis, characterized by symptoms such as gastrointestinal upset, hair loss, and neurological abnormalities. The measurement of selenium levels in whole blood provides a more accurate reflection of both short-term dietary intake and long-term body stores compared to serum or plasma testing. This makes it an essential tool for assessing not just nutritional status, but also for evaluating potential toxic exposure, particularly in environments with high selenium soil content, which can lead to elevated dietary selenium. Clinically, monitoring whole blood selenium levels is critical in the context of nutritional supplementation, ensuring that selenium intake remains within a safe and therapeutic range. Erythrocytes can be useful to establish selenium status, as selenium is present in high concentrations in erythrocyte glutathione peroxidase. However, of all the selenoproteins, GPx has the lowest threshold for selenium saturation. Therefore, a patient may have high or normal RBC Se levels (due to GPx), while other tissues are still low in Se. In clinical settings, whole-blood selenium is widely used to assess selenium status. Also, large studies evaluating selenium in cancer and other diseases have relied on plasma and serum levels. → Whole blood selenium may be more reflective of long term selenium status than plasma selenium.

Strontium incorporates into hydroxyl crystal lattice of bone, stimulates new cortical and cancellous bone formation, and decreases bone resorption by inhibiting osteoclastic activity. There are a number of stable isotopes of strontium, including 84Sr, 86Sr, 87Sr, and 88Sr. Radioactive strontium, 90Sr, is a nuclear waste product and a human carcinogen. Serum strontium levels have been evaluated during therapy to establish GI absorption. Strontium has been shown to concentrate in hair with increased environmental exposure. Like calcium and magnesium, strontium is deposited in bone. Conversely, it is mobilized from bone when blood calcium levels fall.

Severe, painful neurological and gastrointestinal symptoms occur from thallium poisoning; alopecia is the most characteristic sign, as it is coupled with a black pigment at the hair root. Nausea, vomiting, and diarrhea have been reported. Thallium exposure may occur due to soil contamination with thallium-containing pesticides although they have been banned since 1972. Specimens used for thallium detection include urine, which is the main route of excretion, and hair. Blood levels have been measured, but thallium is rapidly cleared, so exposure must be acute to achieve accurate results. Treatment for high thallium levels include Prussian blue, DMSA, or activated charcoal for ingested thallium. BAL, D-penicillamine and EDTA are contraindicated.

Tungsten is found in electric lamps, television tubes, car distributors, electrical furnaces, and x-ray targets. It is used in metal evaporation work. Inhaled tungsten has been associated with pulmonary fibrosis, lung cancer, and neurosensory and cognitive deficits. Oral exposure is suspected to cause reproductive, neurological, and developmental effects. Sources: - Filaments for electric lamps, electron and television tubes, and for metal evaporation work. - Electrical contact points for car distributors - X-ray targets - Windings and heating elements for electrical furnaces - Missile and high-temperature applications Symptoms: - Pulmonary fibrosis, lung cancer and neurosensory and cognitive deficits - Reproductive, neurological and developmental effects Treatment: Avoidance and treat for symptoms and conditions

Uranium (U) is an abundant element on earth. Its widespread use in military and industry, including nuclear power, has increased human exposure. Uranium can be ingested or inhaled and is cleared in urine rapidly, although some will pool in bone and kidney tissues. Uranium toxicity in humans leads to renal damage. Lung cancer is commonly associated with inhaled uranium. Urine can be a sensitive specimen for uranium exposure, but assessment should be undertaken promptly. Intravenous sodium bicarbonate 1.4% has been used to treat uranium toxicity and inositol hexaphosphate has been used in animal studies.

Some studies suggest vanadium has a role in glucose and lipid metabolism, red blood cell formation, and thyroid function. Vanadium assessment and treatment may be indicated in cases of metabolic syndrome or non-insulindependent diabetes mellitus due to vanadium’s role in insulin sensitization. Symptoms that appear to be associated with excessive vanadium are hypertension, decreased coenzymes A and Q10, bipolar disorder, and disruption of energy metabolism. Exposure to vanadium in air or water is of concern for those exposed to vanadium industrial plants. Symptoms may include respiratory disorders, green tongue, high urinary excretion of vanadium, and reduced neurobehavioral abilities. Urine vanadium is traditionally used to assess occupational exposure. Whole blood vanadium has been shown to significantly differentiate children with vanadium exposure from non-exposed children but authors stated that hair levels of vanadium did not significantly correlate with vanadium exposure. This may have to do with distinction of acute versus chronic exposure.

Monitor whole-blood zinc levels to assess immune function, growth, wound healing, and metabolic health. Learn what low or high zinc means, symptoms to watch for, and how to support balanced zinc status.