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Vitamins and Supplements Research | See downloads for: Adobe Files |
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This
article is intended to increase awareness among pharmacists regarding
adverse effects of drugs on nutritional status, with emphasis on
vitamin and mineral deficiencies. Several ways in which the pharmacist
can help overcome these to benefit patient outcomes are also
discussed. Learning objectives Upon completing this lesson, successful participants should be able to: 1. Identify some common nutritional deficiencies induced by drugs. 2. Review the clinical significance of some drug-induced nutritional deficiencies. 3. Identify the various drug classes that are likely to induce specific nutrient deficiencies. 4. Demonstrate this knowledge in disease management and patient care. 5. Advocate ways in which patients can actively participate to take charge of their own health care. Introduction Modern medicine has been an effective tool in preventing and treating many diseases. Often these treatments have focused only on the disease and its symptoms, without an appropriate emphasis on the patient's overall health. Accordingly, the only measure of the effectiveness of a medication is its desired action on target tissue(s). However, the same medication can interfere with other biochemical and/or metabolic processes, which sometimes is manifested in the form of side effects or other adverse drug events. Often drugs can alter the ability of the body to digest, absorb, synthesize, transport, store, metabolize or eliminate nutrients. This situation potentially can cause nutrient depletion. Quite often, a patient then is placed on additional medications to combat a new set of symptoms. The cascading effect of such an approach to disease management often leads to a reduction in the patient's quality of life. At this time, few scientific studies specifically address nutritional deficiencies arising from medications. However, there is enough information available to create an awareness regarding this issue and warrant the attention of the medical community. This article discusses some common vitamin and mineral deficiencies associated with drug use, the clinical significance of such deficiencies and the interventions available to the pharmacist to provide benefit to patients. Vitamins and minerals Intake of vitamins and minerals is essential for a diverse range of metabolic functions of the body. These nutrients cannot be synthesized in the body and, therefore, must be supplied from natural food sources or as supplements. Vitamins are non-caloric organic compounds that are absorbed either in the active form or as precursors to be transformed later into active entities. Some vitamins, such as vitamin K, biotin and vitamin B12, are produced by microorganisms in the intestinal tract, whereas others such as folacin, may need to be activated by intestinal enzymes. Vitamin D is synthesized from a precursor in the skin in the presence of sunlight. Based on their solubility characteristics, vitamins are broadly classified as either fat- or water-soluble. The fat-soluble vitamins include vitamins A, D, E and K. Like fats, these are absorbed into lymph and circulate with lipoproteins in the plasma before reaching target tissues. Excess amounts of these vitamins can be stored by the body in the adipose tissue and utilized in the future when systemic levels are depleted. Because of this, the body can compensate for any short-term deficiencies of fat-soluble vitamins in the diet. However, intake of these vitamins will become necessary after fat stores are depleted. On the other hand, because of potential accumulation of these vitamins in fat depots, gross overconsumption of these vitamins can lead to toxicity. The B vitamins and vitamin C are water-soluble and are absorbed directly into the blood stream, then distributed to target tissues. They are stored only in limited amounts, with any excess normally being quickly eliminated. While this prevents any significant risk of toxicity, except in cases of extremely high doses, frequent consumption of these vitamins is necessary to maintain required tissue levels. Minerals are another important class of nutrients that constitute approximately 4 percent to 5 percent of total body weight. Some minerals, such as calcium, magnesium, sulfur and phosphorus, are important as building blocks of tissues and ubiquitous molecules. They are required in relatively large quantities by the body. In contrast, others, such as iron, zinc, copper, iodine, chromium, selenium, manganese, molybdenum and iodine, are required in trace quantities and have limited but essential functions. Potassium and sodium also are important for various important physiological functions. These are categorized mainly as electrolytes rather than minerals because these cations mainly are responsible for the correct balance of intra- and extracellular fluid levels in various tissues and organs of the body. Physiological and clinical significance of vitamins and minerals Some vitamins act as coenzymes for essential biochemical reactions whereas others have hormonal effects. An example would be vitamin A (retinol). Aside from its well-known role in facilitating vision, it is now recognized as an essential hormone for maintaining the structural and functional integrity of epithelial membranes, such as the cornea. It also has a role in inducing epithelial cell differentiation in mucus-secreting cells. Besides night blindness, severe deficiency of this vitamin can cause keratinization of the corneal layer leading to permanent blindness (xerophthalmia). Other organ systems that would be susceptible to vitamin A deficiency include the respiratory (impaired breathing), gastrointestinal (indigestion and diarrhea) and genitourinary systems (calculi formation, impaired spermatogenesis and abortion). Deficiencies of this vitamin also result in increased susceptibility to carcinogenesis of epithelial tissues. Vitamin D (calciferol) also acts like a hormone in that it ensures adequate absorption of calcium and phosphate in the body, and that its deficiency causes rickets in children and osteomalacia in adults. While calcium and phosphorus are important constituents of bones and teeth, both have additional biological significance. Phosphorus is an integral constituent of nucleic acids (DNA and RNA), energy molecules (adenosine triphosphate and ATP) and secondary messengers (cAMP and various kinases). Calcium is an important regulator of intracellular functions in soft tissues including activation of cellular enzymes and cellular transport. It is also required for regulation of heartbeat and for neurotransmitter release at synaptic junctions. In conjunction with sodium, potassium and magnesium, calcium helps to maintain muscle tone and control nerve function. More recently, calcium has been suggested to have protective effects against hypercholesteremia, non-insulin dependent diabetes and colorectal cancers. Calcium and vitamin K are essential factors for the clotting of blood. Because vitamin K is normally synthesized by the intestinal microflora, its deficiency is rare except in association with lipid malabsorption, destruction of intestinal flora or liver disease. The main clinical manifestation of vitamin K deficiency is an increased tendency to bleed, whereas oversupplementation with synthetic forms of this vitamin can possibly lead to toxicities, such as hemolytic anemia and brain damage. Vitamins E (tocopherol) and vitamin C (ascorbic acid) serve as defenders against oxidative damage due to generation of free radicals from cellular metabolic processes. The antioxidant effects of both vitamins are especially important for pulmonary and cardiovascular tissues that are exposed to high oxygen concentrations. While both vitamins have similar biochemical functions, they differ in their sites of action. Because it is water-soluble, vitamin C is distributed mainly in the intra- and extracellular fluids. Vitamin E, being more lipophilic, locates within the lipid bilayers of cell membranes and helps to preserve their integrity by preventing lipid peroxidation. Both vitamins are considered to promote resistance to infection by enhancing the immunologic activities of white blood cells, production of interferon, assisting the inflammatory reaction and maintaining integrity of mucus membranes. Vitamin E deficiency is rare in adults, as it is found in several foods and can be stored by the body. However, long-term intestinal malabsorption due to disease or iatrogenic causes can deplete the levels of this vitamin and induce pathological changes in various tissues including those of the neuromuscular, reproductive and cardiovascular systems. Vitamin C enhances iron absorption by reducing iron from the ferric to ferrous state and by preventing degradation of ferritin, the body's iron-transporter. It is required for synthesis and maintenance of collagen, a major component of connective tissue. Severe vitamin C deficiency causes the disease scurvy, with symptoms of follicular hyperkeratosis, inflamed gums, loose teeth, dry and itchy mucus membranes, delayed wound healing and increased susceptibility to infections. In addition to vitamins C and E, the immune system requires vitamin A and selenium to function effectively. Deficiency of vitamin A has been associated with increased susceptibility to bacterial, parasitic and viral infections. Selenium is associated with glutathione peroxidase, an enzyme that has an important role in antioxidant activities in cells. Selenium deficiency, although rare, has been associated with cardiomyopathy and osteoarthritis. The family of B vitamins is comprised of coenzymes and precursors of coenzymes that are essential for a large number of metabolic reactions. There is a close interrelationship between the various members of this family. Therefore, inadequate intake of one often impairs utilization of others. For example, thiamine (vitamin B1), riboflavin (vitamin B2), niacin (vitamin B3), biotin and pantothenic acid are involved with energy-release mechanisms, including glycolysis and the tricarboxylic acid cycle. Thiamine pyrophosphate is primarily involved in the oxidative decarboxylation of pyruvate to acetyl coenzyme A for the Krebs cycle and of other ( (infinity) keto acids derived from various amino acids. Riboflavin, in the form of flavin adenine mono- or dinucleotide (FMN or FAD), and niacin, as nicotinamide adenine dinucelotide (NAD and NADH) or nicotinamide dinucleotide phosphate (NADP and NADPH), participate in various redox reactions associated with the release of energy from carbohydrate, protein or fat metabolism. This includes both aerobic reactions, such as the mitochondrial respiratory chain, and anabolic pathways such as glycogen synthesis. Pantothenic acid and biotin are particularly important in fatty acid synthesis, post-translational modification of proteins and related processes. Severe thiamine deficiency affects the nervous and cardiovascular systems, causing peripheral neuritis, partial or complete paralysis, dyspnea, tachycardia and palpation upon exertion, and, in rare cases, heart failure. Riboflavin deficiency can cause sore throat, angular stomatitis, glossitis, cheilosis, dermatitis, and in some cases, photophobia, corneal vascularization and cataract formation. Niacin deficiency causes pellagra, a condition characterized by dermatitis, dementia and diarrhea. Pantothenic acid deficiencies can cause neuromuscular degeneration and adrenocortical insufficiency resulting in fatigue, headache, nausea and abdominal and muscle cramps. Vitamin B6 or pyridoxine is a coenzyme for reactions of protein metabolism, glycogen release from liver and muscles, and synthesis of bioentities such as heme, arachadonic acid, sphingolipids and the neurotransmitter, gamma-aminobutyric acid (GABA). Deficiency of this vitamin can cause peripheral neuritis, and in severe cases, CNS abnormalities, such as dementia and convulsions. Folic acid and vitamin B12 (cyanocobalamine) are associated with single carbon transfer reactions during nucleic acid synthesis and amino acid metabolism. These vitamins are important for the normal development and function of cells of the gastrointestinal tract, bone marrow and nervous tissue. Megaloblastic anemia, gastrointestinal disturbances and neuronal demyelination are some clinical manifestations of deficiency of these vitamins. Folate deficiency also causes elevated levels of homocysteine, which has been associated with increased risk of coronary heart disease. Whereas megaloblastic anemia is associated with folate or vitamin B12 deficiency, women and children around the world suffer from the more common hypochromic, microcytic anemia caused by iron deficiency. This essential mineral plays an important role in oxygen and carbon dioxide transport because of its ability to exist in the ferrous and ferric state. Aside from acting as an intracellular cofactor for cellular respiration, iron serves as oxygen carrier in hemoglobin and myoglobin. The metabolic activity of the liver enzymes including the cytochrome P450 system also depends significantly on the electron transport capacity of iron. It is also necessary for normal functioning of the immune system, as well as the nervous system. Magnesium is another essential mineral required in large quantities by the body. Besides its involvement in bone and neuromuscular development and function, magnesium stabilizes the energy-producing biomolecule ATP and acts as a co-factor for the various ATP-dependent metabolic reactions. Magnesium deficiency can cause anorexia, tremors and muscle spasm in mild cases and convulsions and coma in extreme ones. Decreased magnesium levels also are suggested to contribute to hypertension, disrhythmias and myocardial infarction. Sulfur, zinc, copper and other trace elements are also necessary for normal metabolic reactions and organ functions as they regulate activities of several critical enzymes and hormones, or form important constituents of biomolecular entities. Table 1 summarizes common symptoms and clinical manifestations of selected vitamins and minerals. A more complete description of the physiological roles and clinical significance of these vitamins and minerals can be found in biochemistry and clinical nutrition review literature. Drugs as inducers of nutrient deficiencies Most medicines, by the very action of modulating receptor functions or enzymatic reactions, can disrupt one or more metabolic pathways that affect nutrient levels in the body. Others cause inhibited nutrient absorption and disrupt metabolism due to their pharmacologic properties. Drugs can cause nutrient depletion either by preventing nutrient absorption, enhancing nutrient elimination, or both. Nutrients are normally absorbed at different sites of the gastrointestinal tract. Nutrient malabsorption can occur because of intra-luminal events, such as an altered microenvironment of cells of the gastrointestinal tract. For example, tetracycline chelates with calcium to form an insoluble complex. Therefore, patients taking tetracycline typically are advised to avoid concurrent consumption of dairy products. Laxatives can cause malabsorption by increasing gut motility and thereby reducing the time of food at sites of absorption. In addition, some laxatives such as bisacodyl and senna are known to induce mucosal changes. Others, such as mineral oil, solubilize oil-soluble vitamins which prevents their absorption. Bile acid sequestrants, such as cholestyramine, cause malabsorption of fat and of fat-soluble vitamins which require bile salts for optimal absorption. Chronic use of aluminum and magnesium-containing antacids may cause secondary osteomalacia due to phosphate depletion resulting from the formation of insoluble products. In addition, antacid-induced alterations in pH can retard nutrient absorption by influencing the extent of ionization. Water-soluble vitamins are especially susceptible in this scenario. Slow-release preparations of potassium chloride have been shown to reduce absorption of vitamin B12 due to reduced pH in the GI lumen. B12 absorption also is reduced by medications such as cimetidine due to reduced gastric acid secretion and pepsin release, which results in a decrease of the essential gastric intrinsic factor. Other therapeutic agents, such as neomycin, colchicine and methyldopa, cause direct gastric and intestinal mucosal damage resulting in nutrient malabsorption. Some agents may severely damage gastrointestinal integrity and function, even when administered parenterally. Examples include most antineoplastic agents such as methotrexate, anthracyclines and others that inhibit the normal growth and function of intestinal microvilli. Agents such as these can cause a wide range of nutrient deficiencies. This is also true for seemingly harmless medications, such as antibiotics, which tend to destroy the normal intestinal microorganisms that are essential for digestion and biosynthesis of various nutrients. Some drugs directly compete with nutrient entities. Doxorubicin, for example, shares structural similarities with riboflavin and competes with it for enzyme binding sites. Displacement of this vitamin from its binding sites shifts its intracellular equilibrium, resulting in enhanced elimination. Methotrexate also contributes to folate deficiency by binding to the enzyme dihydrofolate reductase and inhibiting the conversion of folic acid to tetrahydrofolate. This results in an acute deficiency of the folate enzyme with concurrent intracellular accumulation of toxic substances. While this is the mechanism by which the drug destroys tumor cells, it also generates significant adverse drug effects and host toxicity. Vitamins and minerals also can be displaced by drugs from non-specific binding sites on carrier proteins in the plasma such as lipoproteins and albumin. The resulting increase in free fraction of the vitamin may also cause nutrient depletion due to increased elimination. Drugs that disrupt the activity of hepatic microsomal enzymes also may indirectly cause nutrient deficiencies since these enzymes regulate the metabolism of various fat-soluble vitamins as well as carrier proteins for the vitamins and minerals. Nutrient deficiencies are more common in elderly patients. One reason for this is that they often receive multiple drugs for a variety of chronic ailments. Some common agents used by this patient population include cardiovascular agents, antidiabetic agents, antilipemic agents, antihypertensives, non-steroidal antiinflammatory agents (NSAIDs), sedatives, hypnotics and antibiotics. As discussed earlier, antilipemic agents such as cholestyramine can inhibit absorption of the fat-soluble vitamins A, D, E and K. Folate deficiency can also develop because bile sequestrants also adsorb folate. Additionally, the elderly sometimes attempt to control obesity and postprandial hyperglycemia in diabetes by consuming bulk agents such as psyllium gum. These gums have been shown to inhibit absorption of vitamins A, C, B12 and riboflavin. Sulfonylureas commonly are used for the treatment of non-insulin-dependent diabetes mellitus and have been associated with thiamine deficiency. Thiamine pyrophosphate is an essential coenzyme in glucose metabolism. Sulfonylureas and other antidiabetic drugs that lead to an improvement of glucose uptake and metabolism by muscles may also increase the need for thiamine and precipitate deficiency. Newer agents, such as metformin, also seem to cause pancreatic damage and thereby indirectly affect nutrient absorption. Iron deficiency is also common in elderly people who use NSAIDs due to mucosal irritation and resulting blood loss. In many patients, diuretics, corticosteroids and amphotericin B will cause significant potassium excretion, thus depleting the levels of this electrolyte. Overly aggressive diuretic therapy can also cause sodium and magnesium depletion. Hypomagnesemia also has been associated with cisplatin and cyclosporine. Glucocorticoids inhibit intestinal absorption of calcium and also increase urinary excretion of phosphorus, depleting the body of these minerals. Infants and children also are more likely to suffer from drug-induced nutrient deficiencies. In addition to the fact that infants and children have a greater need for nutrients due to accelerated growth and development, it must also be remembered that their metabolic systems are not yet fully developed. Recent studies in children undergoing long-term anticonvulsant therapy with phenobarbital, primidone and phenytoin revealed that these children were at risk for development of megaloblastic anemia, due to folate deficiency, and rickets, due to calcium and vitamin D deficiencies. In separate studies, adult patients on anticonvulsant therapy were also shown to have tendencies for development of osteomalacia due to calcium and vitamin D deficiencies. Although the mechanisms are not yet clear, these deficiencies are believed to be linked to the inducing effects of these agents on the microsomal enzymes in the liver. It should be noted that though the focus of the article primarily involves vitamins and minerals, a deficiency of other nutrients such as electrolytes and co-factors can also produce diseases. Table 2 includes a summary of some common nutrient deficiencies reported in literature. It is important to keep in mind that the list is by no means complete as studies of this sort are limited, and that nutrient deficiencies often are identified as serendipitous discoveries during clinical studies. The list is likely to grow as more work is completed in this area. The pharmacist's role As the most trusted healthcare professional, the pharmacist is in a unique position to provide counseling to patients undergoing drug therapy and make suggestions to empower those individuals to better care for themselves. Depending upon his or her expertise, the pharmacist can potentially address several of the issues discussed below. 1. Nutritional supplements Once a patient's nutrient deficiency is identified, an opportunity arises for the pharmacist to help improve therapy by recommending appropriate products to replenish depleted stores. There is evidence to believe that, in many cases, the optimum dose of nutrients is greater than the recommended daily allowance. The RDA for a specific nutrient is determined by the Food and Nutrition Board of the Food and Drug Administration. By definition, they are adequate to meet the known nutritional needs of a healthy person. Obviously, they are only general guidelines since optimum and therapeutic ranges of nutrients needed will vary for individuals based, among other things, on their own health status. Many supplements are available from grocery stores, health food stores, multi-level marketing and professional formulations available only to healthcare providers with special training. These supplements are available in a wide variety of formulations including individual vitamins, minerals, electrolytes, amino acids, fats, carbohydrates, enzymes and herbal products. Combination products are also available. The supplements generally should be high potency, natural vitamins and minerals, and have no additives or artificial fillers that might interfere with the utilization of nutrients by the body. Multivitamins and minerals are important as part of a general approach to a healthy lifestyle; however, higher doses of specific nutrients maybe needed to counteract drug-induced nutritional depletion, especially when the medication is used on a chronic basis. These patients may be better served by products specifically tailored to their needs. Some nutritional manufacturers have recognized this and have produced formulations of nutrients for specific drug classes. These supplements are labeled based upon the medication(s) with which they are designed to be used. Examples would include anti-inflammation, cholesterol, asthma, diabetes, blood pressure and gastrointestinal supplements. It is important to have an understanding of which nutrients are affected by medications in order to be able to choose the appropriate supplement for the patient. For example, the use of most oral antibiotics interferes with the natural bacterial flora in the gastrointestinal tract. Synthesis of pantothenic acid, biotin, folate, vitamin B12 and vitamin K are aided by bacterial flora. These vitamins produce food-absorbing enzymes, inhibit candida growth, lower cholesterol, metabolize calcium and enhance immune function. Acidophilus, one of the natural bacterial flora, forms acidophilin, a strong protective antibiotic which helps to control harmful bacteria such as E. coli, enterococcus and salmonella. Unbalanced intestinal flora has been linked to several conditions, such as increased coagulation times due to vitamin K deficiency. Reduced gastrointestinal flora has also been associated with the increased risk of yeast infections due to fungal overgrowth. Susceptibility to bacterial superinfection is also increased by an imbalance of healthy vs. harmful bacteria. Therefore, gastrointestinal floral changes due to medications also bring with them changes to the dynamics of the intestines with respect to digestion, absorption, metabolism, and elimination of nutrients and toxins. This is especially significant when one considers the number of patients taking antibiotics that the typical pharmacist has counseled with respect to diarrhea and bloating. Probiotics (life-friendly bacteria) are found in supplement form in some pharmacies and health food stores. These would be more than the acidophilus products, rather a broader spectrum of friendly bacteria that are found in clinically based formulas that are of higher potencies and quality than the average ones found in pharmacies and health food stores. The recommendation of clinical dosages of these probiotics from a refrigerated source that is active at a guaranteed potency at time of administration (not guaranteed at time of production) given on an empty stomach with a full glass of water and separated from the antibiotic dose by several hours or given to the patient at the end of the antibiotic therapy, would greatly enhance the amounts of natural flora and restore the gastrointestinal function to its balanced state. 2. Food products Dietary regimens, such as the Standard American Diet (SAD), with its emphasis on processed fast foods, low fiber, high fat, high simple carbohydrates and excessive intake of animal flesh, are not conducive to a balanced nutritional diet. A diet such as this does not contribute to, and in many cases hinders, optimum health. One USDA Food Consumption Survey evaluated the food intake of 21,500 people over three days and found that not a single person consumed 100 percent of the RDA for all of the surveyed nutrients. This is strong evidence that Americans should be reconsidering their dietary habits. In view of the fact that so many Americans are not receiving the nutrition a healthy individual needs, individuals whose clinical picture is complicated by synthetic medications should receive all the more attention from their healthcare providers. This is made all the more significant by a 1988 surgeon general's report which stated that approximately two-thirds of all deaths are associated with dietary and nutritional imbalances. Patients should be counseled to consider a live food diet in exchange for the processed foods that are generally promoted as the norm of today's society. Basic rules include: Eat a balanced diet of whole vegetables, proteins, whole grains, healthy fats (unsaturated or mono-saturated oils), whole fruits, raw nuts and seeds. Avoid foods that aggravate symptoms of fatigue, sinus congestion, skin rash or bloating. Drink at least eight full glasses of water daily. Our bodies are composed mostly of water, and it is the medium in which most bio-chemical and metabolic functions occur. Drink the majority of the water and other fluids away from meals to reduce the dilution of digestive acids and enzymes. Reverse osmosis water is considered best by some. Rotate the foods that are eaten; many people associate healthy diets with boredom. Recommend variety and attempt to challenge the patient to expand his/her taste for new foods. Remind them that variety provides more sources of nutrients. There is a plethora of healthy cookbooks on the market as more companies become aware of the current interest in lifestyle changes. When possible, avoid pre-packed foods that tend to provide additives, preservatives, low quality fats and are void of important enzymes. Buy organic and hormone-free products when possible. Avoid high carbohydrate, high fat, refined sugar snacks in favor of fresh fruit. Take time to enjoy the meal and chew well. Pleasure helps to reduce stress and relax, which aids in digestion. Chewing also improves the extraction of nutrients from the food. Always properly wash fresh produce to remove unwanted chemicals and pesticides. An important consideration is the proper washing of fruits, vegetables and other produce to remove unwanted chemicals, pesticides and biologicals that may be harmful to the body. The recommendation of whole foods and unadulterated animal products that are organic helps improve the chances of better nutrients. However, this by itself does not ensure that patients will receive adequate amounts of all their required nutrients. A random study conducted at Rutgers University by Dr. Firman Bear found nutritional values vary substantially in individual samples of the same vegetable. The iron content varied from 1938ppm (parts per million) to as low as 1ppm in tomatoes, while in lettuce the iron ranged from 518ppm to 9ppm. 3. Complementary/integrated therapy Homeopathies, herbs, nutritionals, enzyme therapy, aromatherapy and other complementary choices add to the services a pharmacist can potentially provide. Continuing education in the area of alternative therapies is available. Certification by private companies, pharmacy associations and nutritional associations is available to aid pharmacists who desire to improve their knowledge base beyond what currently is taught in pharmacy schools or mainstay medical journals. 4. Laboratory tests Laboratory testing also is available. The results may enhance the pharmacist's ability to determine a patient's nutritional status. Medical laboratories provide diagnostic test kits that can be offered to patients through orders from healthcare practitioners in most states. However, review the regulations with your state agencies regarding who can provide such orders and if these kits can be distributed from a pharmacy. Test kits are generally categorized as either gastrointestinal, immunology, nutritional, endocrinology or metabolic in nature. Some laboratories also provide interpretive guidelines with recommendations of which nutrients and protocols to follow. These tests often are able to use hair, saliva, urine, blood, plasma or stool as samples for analysis. Blood samples are utilized to determine the status of 12 to 17 vitamins and a 24-hour urine analysis can be used to determine functional metabolic imbalances which can interfere with enzyme function and bio-chemical pathways. The vitamins commonly measured are B1, B2, niacin, pantothenate, B6, B12, folic acid, biotin, total and free choline, inositol, biopterin, carnitine, the fat-soluble vitamins and beta-carotene. Other forms of laboratory tests include amino acids, organic fatty acids, hormones, allergy profiles, microbiology, digestive functions, adrenal functions, bone resorption, glucose tolerance and blood indices. For mineral analysis, samples of blood, urine or hair are often used. A comprehensive mineral analysis can also be done to determine a detailed mineral status, including heavy metal toxicity. Some of the minerals tested for are calcium, magnesium, zinc, chromium, manganese, copper and selenium. Toxic minerals include zinc, lead, mercury, cadmium and aluminum. Current research is uncovering connections between trace element deficiency and many common health problems. Recent surveys by the Centers for Disease Control and Prevention indicates that significant numbers of people in the United States are not getting enough essential minerals such as magnesium, calcium, iron and zinc. Magnesium, a necessary element in more than 300 different enzyme reactions in the body, has been demonstrated to be low in half of the hospitalized patients for which it was measured. Only 10 percent to 13 percent of patients with insufficient levels of this mineral were even recognized as being clinically deficient. This is significant, given new evidence linking magnesium deficiency to heart attacks and high blood pressure. Magnesium supplementation is proving to be a significant therapy in patients who suffer heart attacks and can significantly lower blood pressure. Zinc is critically important to tissue repair and proper immune function. Low selenium levels have been associated with increased risk for cancer. Chromium and magnesium are effectively used to treat adult-onset diabetes. Subtle iron deficiency has been linked to learning disabilities in the young. 5. Lifestyle modifications Patients should be counseled regarding lifestyle issues, such as appropriate exercise, positive attitudes and relaxation techniques. A mind, body and spirit approach to a balanced life empowers people to the fact that options exist which are within their control. Educating patients to recognize that choices they make can affect their health helps the patient understand that their relationship with healthcare providers is a partnership. The patient should be encouraged to consider themselves to be part of a multidisciplinary team which may include health fitness trainers and nutritional advisors, as well as traditional healthcare providers. The goal is to empower patients to modify their lifestyles as much as possible in a way which will allow them to gain control over their lives. Conclusion Recognizing drug-induced vitamin and mineral deficiencies is an opportunity to the pharmacist to offer expanded services to patients using both traditional and complementary medicine. Use of pharmacological products is important to achieve positive medical outcomes. However, the pharmacist also should have the goal of minimizing adverse drug events through appropriate counseling. Counseling should include both conventional and complementary medicine. Numerous professional articles, publications and continuing education programs now are available to help the pharmacist incorporate a more integrative approach to the practice of pharmacy. Conscientious self-development through educational courses and certification places the pharmacist in a unique position to offer either of these services through patient counseling, traditional consultations or collaboration with alternative healthcare providers. Those who take the time to develop themselves in this field will find themselves to be an integral part of the growing field in health care. Table 1 Nutrient depleted Significance of depletion Vitamins Vitamin A Increased susceptibility to cancer, acne, night blindness and other eye problems; impaired protein utilization by tissues for maintenance, repair and healing; impaired bone and teeth formation; acceleration of aging process.
Niacin Pellagra-like symptoms of dermatitis, dementia and diarrhea;
circulatory problems; heart disease. Pyridoxine Fatigue; carpal tunnel syndrome; water retention;
irritability; increased premenstrual stress; allergies; asthma;
weakened immune system; heart disease. Folic acid Fatigue, anemia, weakness and low energy; problems with
clotting and bruising; birth defects; cervical dysplasia; elevated
homocysteine level (major risk factor in heart disease). Vitamin B12 Anemia; improper digestion and metabolism of foods;
nerve damage; fatigue; uneven gait; infertility; memory loss;
cataracts. Vitamin C Weakened immune system; increased susceptibility to
cancer; impaired wound healing; gum disease; damage to nerves, eyes
and vascular system. Minerals Calcium Osteoporosis; muscle cramps; joint aches; increased
cholesterol levels; nervousness; heart rhythm irregularities; skin
disorders; brittle nails; rheumatoid arthritis; tooth decay; sleep
disturbances; numbness in arms and/or legs; rickets. Magnesium Muscle weakness and twitching; depression; dizziness;
high blood pressure; heart disease. Phosphorus Mineral imbalance, especially calcium and magnesium;
impaired bone and teeth formation, kidney function and heart muscle
contraction. Copper Fatigue; impaired wound healing; osteoporosis; altered sense
of taste. Zinc Impaired wound healing; weakened immune system; impaired sense
of smell and taste. Sodium Fluid and electrolyte imbalance. Potassium Heart irregularities; increased blood pressure; muscle
twitches; fluid imbalances. Coenzyme Q-10 Increased free radical-mediated cell damage; weakened
immune system; accelerated aging process; increased fatigue; asthma;
allergies; respiratory diseases; decreased brain and heart function;
obesity; yeast infections; multiple sclerosis; gum disease and
diabetes. Probiotics/enterobiotics Weakened immune system; impaired
digestion; development of allergic responses. Drug class Subcategory Nutrients depleted Aminoglycosides Other antibacterial agents Sulfa folic acid Antiretroviral agents e.g., Azidothymidine,Retrovir, AZT,
Ribavirin, Zidovudine copper, zinc Diuretics/antihypertensives Thiazides magnesium, zinc,potassium*,
sodium* Potassium-sparing diuretics folic acid, coenzyme Q-10*,calcium Loop diuretics vitamin B1, vitamin B6, magnesium,zinc, potassium*
Hydralazines vitamin B6, coenzyme Q-10*,magnesium Cardiovascular agents Cardiac glycosides calcium, magnesium Beta blockers coenzyme Q-10* Potassium supplements vitamin B12 Lipid-lowering agents HMG-CoA reductases coenzyme Q-10* Bile sequestrants folic acid, vitamin B12, vitamin A,vitamin D,
vitamin E, iron, fat* Antidiabetic agents Sulfonylureas vitamin B1, coenzyme Q-10* Biguanides vitamin B12 Tranquilizers vitamin B2, coenzyme Q-10* Anticonvulsants Barbiturates, Phenytoin, Dilantin folic acid,
vitamin B12, vitamin D,calcium Carbamazepine, Tegretol folic acid Female hormones Oral contraceptives vitamin B2, vitamin B6, vitamin
B12, folic acid, vitamin C, magnesium, zinc ERT agents vitamin B6, magnesium Anti-ulcer agents H-2 receptor antagonists folic acid, vitamin B12,
vitamin D,calcium, iron, zinc Proton pump inhibitors vitamin B12 Antacids Agents with magnesium and aluminum calcium, magnesium,
copper,iron, phosphate, zinc, potassium* Agents with sodium bicarbonate folic acid, magnesium,
potassium*,amino acids*/protein* Laxatives Mineral oil vitamin A, vitamin D, vitamin E, vitamin K
Phenolphthalein vitamin D, calcium, potassium* Bisacodyl potassium* Anti-inflammatory agents Corticosteroids vitamin D, calcium,
selenium, zinc,potassium* Gout medications vitamin B12, vitamin A, potassium*, sodium* Sulfasalazine folic acid Aspirin folic acid, vitamin C, iron,amino acids*/protein* NSAIDs folic acid |
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