The purpose of this module is to provide an overview of the various dietary supplements with a focus on minerals including the potential benefits, risks, and impacts for patients utilizing these products.
By the completion of this module, the APRN should be able to:
- Discuss current recommendations for dietary intake of various minerals.
- Explore the most common dietary supplemental minerals.
- Consider the implications of the use of dietary supplemental minerals.
Dietary supplements are vitamins, minerals, herbs, and other products that can play an important role in health by replacing dietary intake through supplements; they can be in the form of powder, pills, capsules, drinks, or energy bars (The National Library of Medicine [NLM], 2018).
Macronutrients are essential nutrients that have a large minimum daily requirement, including proteins, carbohydrates, fats, and water (Youdim, 2019).
Micronutrients are essential nutrients that are needed in minute amounts, such as vitamins and minerals (Youdim, 2019).
Adequate nutrition is dependent on both vitamins and minerals. The body uses minerals to keep the bones, muscles, brain, and heart properly functioning. Minerals are also necessary for making hormones and enzymes. There are two types of minerals, macrominerals and trace minerals. The body needs a larger amount of macrominerals than trace minerals. These macrominerals include calcium, potassium, sodium, phosphorus, magnesium, chloride, and sulfur. Trace minerals are only needed in small amounts and include iron, copper, iodine, manganese, zinc, fluoride, cobalt, and selenium. Generally, minerals are obtained through dietary intake, but for those who do not eat a wide variety of foods, healthcare providers may recommend a mineral supplement. Individuals with certain health conditions, such as chronic kidney disease, need to limit certain minerals such as potassium (National Library of Medicine [NLM], 2020c).
Calcium is one of the body's electrolytes or a mineral that carries an electric charge when dissolved in fluids, including blood. However, most of the body's calcium is not charged. Approximately 99% of a body's calcium is stored in bones and the remaining calcium stored in cells and blood. Calcium is necessary for the formation of teeth and bones, muscle contractions, blood clotting, and rhythmic heart contractions. Through body processes, calcium is moved from the bones and transported into the blood as needed to maintain a steady level of serum (blood) calcium. Osteoporosis develops when there is not enough calcium in the bones. Calcium deficiency can also cause rickets, though it is more closely related to a vitamin D deficiency. Hypocalcemia or low serum calcium results from medical conditions such as renal failure, surgical removal of the stomach, or certain medications such as diuretics. Transversely, hypercalcemia can cause renal insufficiency, vascular and soft tissue calcification, hypercalciuria (abnormally high levels of calcium in the urine), and kidney stones. While research varies on the exact dose of calcium to impact disease processes, those linked to hypercalcemia include cardiovascular disease (CVD); blood pressure dysregulation; cancers of the breast, colon, rectum, and prostate along with stage 4 lung cancer and Is a life-threatening medical emergency when it occurs; kidney stones; and weight management. Interestingly, a women's health study in Iowa determined that higher calcium intake from diet or supplements was associated with reduced ischemic heart disease mortality in postmenopausal women; however, a Swedish study of older women showed that intake greater than 1400 mg/d were associated with higher rates of death from CVD than the cohort taking between 600 and 1000 mg/d. Significant clinical trials in the US have shown a relationship between increased calcium intake and decreases in blood pressure, but a systematic review found the link to be weak and largely due to the variations in the methodology of the research (National Institutes of Health [NIH], 2020a).
Preeclampsia is a serious medical condition in pregnancy that includes hypertension and proteinuria after 20 weeks’ gestation. There have been studies that indicated calcium supplementation during pregnancy can decrease the risk of preeclampsia. In a randomized trial in India, over 500 healthy women with baseline calcium intakes of 314 mg per day were supplemented with 2,000 mg/d of calcium between weeks 12 and 25 of their pregnancy. Both preeclampsia and premature birth were decreased among this group. A second study in the US with over 4,500 healthy women with similar calcium supplementation found no significant reduction of preeclampsia or premature birth. This group had a baseline of over 1100 mg calcium per day, higher than the Indian study with just over 300 mg/d as their baseline. Thus, the American College of Obstetrics and Gynecology recommends that 1,500-2,000 mg/d of calcium can reduce the severity of preeclampsia in pregnant women who have dietary intakes of less than 600 mg/d (NIH, 2020a).
For normal maintenance of calcium without weakening the bones, an adult should consume 1,000 to 1,500 mg of calcium per day. The primary dietary sources of calcium are dairy products, including milk, yogurt, and cheese. Non-dairy sources include vegetables such as kale, Chinese cabbage, and broccoli. Many foods are fortified with calcium, such as fruit juices, cereals, or tofu (NIH, 2020a).
Calcium has the potential to interact with medications including bisphosphonates such as etidronate (Didronel), fluoroquinolone antibiotics such as ciprofloxacin (Cipro), tetracycline (Tetracon), levothyroxine (Synthroid), phenytoin (Dilantin), tiludronate disodium (Skelid), or thiazide-type diuretics such as hydrochlorothiazide (Microzide). Further, aluminum and magnesium-containing antacids increase urinary calcium excretion, and mineral oil or stimulant laxatives decrease calcium absorption. Glucocorticoids such as prednisone (Deltasone) causes calcium depletion and can lead to osteoporosis with extended use (NIH, 2020a).
Chloride is one of the macronutrients that the human body requires large amounts of for proper functioning. It is typically found in the body in combination with sodium and water. Sodium and chloride combined become salt, which is required to maintain extracellular volume and proper osmotic pressure of body fluids. Further, chloride is a critical partner to hydrogen in forming hydrochloric acid, which is a key digestive component. Chloride is retained or excreted through the kidneys to maintain the appropriate levels. There is no recommended daily allowance (RDA) for chloride, but the adequate intake (AI) for young adults is 2.3 g/day. Older adults (men and women 50 to 70 years of age) require only 2.0 g/d and those over 71 require only 1.8 g/d. The major adverse effect of increased sodium chloride intake is elevated blood pressure. Food sources include table salt or sea salt as sodium chloride, seaweed, rye, celery, olives, or lettuce. Loss of chloride occurs with sweating, vomiting, or diarrhea, and some diuretics can cause low chloride levels. There are no drug interactions with chloride; however, loop diuretics prevent the reabsorption of sodium and chloride and levels should be monitored (National Academies of Sciences, Engineering, and Medicine [NASEM], 2005; NLM, 2020a).
Chromium is required in trace amounts for multiple body functions, including digestion of food. The presence of chromium helps to slow the loss of calcium and is a benefit to those at risk for osteoporosis. In the 1960s, chromium was found to correct glucose intolerance and insulin resistance in animals. Human deficiencies of chromium are very rare, but hospitalized patients who were being tube-fed showed signs of diabetes, including weight loss, impaired glucose tolerance, and neuropathy until chromium was added to their solution. After adding 150 to 250 mcg/d for two weeks, their diabetes was corrected; thus, chromium is added to most total parental nutrition (TPN). There have been studies regarding the link between chromium and a decreased risk of glaucoma and diabetes, without solid evidence at this time. There is a large amount of promotion within the body-builder community for chromium as an aid in building muscle and burning fat, but studies have failed to provide significant evidence of its efficacy. Current controversies or issues with chromium include type 2 diabetes and glucose intolerance. While randomized controlled clinical trials have been done, there is no clear scientific evidence that vitamin and mineral supplementation benefits people with diabetes without underlying nutritional deficiencies in controlling their blood sugar. There is speculation regarding lipid metabolism and chromium, but there is no clear research regarding the mineral’s impact on cholesterol and triglyceride levels. Chromium supplements hype an ability to lower body fat and increase lean muscle, yet in 24 studies examining an intake of 200 to 1,000 mcg/day of chromium picolinate compared to placebo, there was no significant change to body mass or composition (NIH, 2020b).
Foods high in chromium include meat, whole grain products, broccoli, potatoes, garlic, basil, apples, and bananas. Some fruits or fruit juices, such as grape or orange juice, are considered good sources of chromium. There exists insufficient evidence to determine an RDA with chromium; however, the AI for chromium is 35 mcg/d for males, 24 to 25 mcg/d for females, 29 to 30 mcg/d during pregnancy, and 44 to 45 mcg/d while breastfeeding (NIH, 2020b).
Noted medication interactions with chromium include prednisone (Deltasone), H2 blockers such as cimetidine (Tagamet) or famotidine (Pepcid), or proton-pump inhibitors such as omeprazole (Prilosec) or pantoprazole (Protonix). These medications alter the stomach’s acidity which can impair chromium’s absorption or increase its excretion. Other drugs may have an increased effect if taken with chromium or may increase chromium absorption including beta-blockers such as atenolol (Tenormin) or propranolol (Inderal), insulin, nicotinic acid, or non-steroidal anti-inflammatory drugs (NSAIDs) such as ketorolac (Toradol), ibuprofen (Motrin, Advil), or aspirin (Ecotrin) (NIH, 2020b).
Copper is an essential mineral and is present in food from both animal and vegetable sources, as well as being available as a dietary supplement. Copper is not routinely measured or monitored in clinical practice, but a deficiency is associated with anemia, hypopigmentation, hypercholesterolemia, osteoporosis and other bone defects, connective tissue disorders, ataxia, an increased risk of infection, and abnormal lipid metabolism. Groups that are at risk for copper deficiency include people with celiac disease, Menkes disease (a rare, X-linked, recessive disorder), and individuals taking high doses of zinc, as zinc interferes with copper absorption and the excessive amounts can lead to a copper deficiency (NIH, 2020c).
Foods with the highest copper content include organ meats such as beef liver, shellfish, seeds and nuts, wheat-bran cereals, chocolate, and whole-grain products. Beef liver has over 12,000 mcg per serving. Copper absorption is influenced by the amount of copper in the diet. Tap water and other beverages can be good sources of copper. Copper is available in dietary supplements as a singular ingredient or as a component in mixed vitamins such as a daily multivitamin (NIH, 2020c).
Copper has been noted as in the prevention of CVD and AD. Since copper deficiency leads to changes in lipid levels, there is an increased risk of atherosclerotic CVD. Furthermore, copper deficiency has been associated with cardiac abnormalities, possibly due to decreased activity of several cardiac cuproenzymes (enzymes that use copper as a cofactor in their catalysis). Small studies have assessed the impact of copper on CVD with little evidence of impact on cholesterol or triglyceride levels. The evidence is insufficient to date supporting an association between increased copper intake and CVD outcomes. There are experts that believe a copper deficiency could have a role in the etiology and pathophysiology of AD. Studies have shown low copper levels and low activity of copper-dependent enzymes in the brains of people with AD. However, there have also been high levels of copper found in the brains of people with AD, indicating that an excess of copper may also be involved in the development of the disease. In clinical studies, AD patients had no significant improvement with copper supplementation as compared to placebo. Experts agree that individuals at risk for AD should use a multivitamin without copper or iron because excessive intake may contribute to cognitive issues. Health risks associated with excessive copper ingestion include liver damage and GI symptoms. Copper toxicity is rare but has been reported in houses with copper-containing pipes that allow copper to leak into the water supply. People with Wilson's disease, a rare, autosomal recessive disease, have a high risk of copper toxicity due to difficulty with copper clearance. These patients require lifelong copper chelation therapy (medications used to remove copper) or high doses of zinc to prevent organ damage. Copper does not interact with any other medications (NIH, 2020c).
Fluoride is involved in the development of strong teeth and bones. Fluoride is best known for protecting teeth, by working with phosphorus and calcium to increase resistance to tooth decay. Fluoride also helps to activate and regulate several enzymes and may play a role in reducing the severity of osteoporosis. Fluoride is found in most water systems, unless patients use well water or from fresh sources, which is not supplemented with fluoride. Natural sodium fluoride is found in the ocean, so most seafood contains fluoride. Tea and gelatin contain fluoride. Infants get fluoride through formula, but little is found in breastmilk. A fluoride deficiency may result in dental cavities due to weak bones and teeth. There are no RDAs for fluoride, but AIs include:
- Infants (up to six months): 0.01 mg/d;
- Infants (7 to 12 months): 0.5 mg/d;
- Children (one to three years): 0.7 mg/d;
- Children (four to eight years):1.0 mg/d;
- Children (9 to 13 years): 2.0 mg/d;
- Males (14 to 18 years): 3.0 mg/d; (over 18 years): 4.0 mg/d;
- Females (14 and over): 3.0 mg/d (NLM, 2019a).
Excess fluoride is rare; however, if infants receive too much prior to tooth eruption they may develop changes in their enamel including white lines or streaks on their teeth. To avoid this, patients should be instructed to avoid fluoride supplements or fluoride toothpaste in anyone younger than two years. Parents should use no more than a pea-size amount of fluoride toothpaste for children over two years and avoid fluoride mouth rinses in children under six years (NLM, 2019a).
Iodine is a trace element naturally present in foods and available as a dietary supplement. Iodine is an essential part of thyroid hormones thyroxine (T4) and triiodothyronine (T3). Thyroid stimulating hormone (TSH) secretion increases the thyroid uptake of iodine and stimulates T4 and T3 synthesis. If there is insufficient iodine, TSH levels remain elevated, and goiter (enlargement of the thyroid gland) will develop as the body attempts to trap more iodine from circulation to produce sufficient thyroid hormones. Iodine also plays a role in the immune response and may have a positive impact on mammary dysplasia and fibrocystic breast disease. In the US, iodized salt is a significant source of iodine for most people. In addition to iodized salt, seaweed is one of the best sources for iodine. Grain products, eggs, and dairy products are also high in iodine. Iodine is also present in human breast milk and infant formula. Fruits and vegetables have iodine, but the amount is dependent on the amount of iodine in the soil where they were grown. That variability makes the iodine in fruits and vegetables unreliable. Most multivitamins with minerals contain iodine in the form of potassium iodide or sodium iodide, but supplements with iodine or iodine-containing kelp are also available (NIH, 2020d).
Iodine deficiency has an adverse impact on growth and development and is the most common cause of preventable intellectual disabilities in the world. Due to this potential impact, iodine status is routinely monitored across the US and the world. Iodine levels are measured through urinary iodine since over 90% of iodine is excreted through the urine. Iodine has been monitored in the US population since 1971 to ensure sufficient intake and avoid health issues. For school-aged children and non-pregnant adults, the median urinary concentrations should be higher than 100 mcg/L, and no more than 20% of the population should have values below 50 mcg/L. Since 2000, the dietary intake of the US population appears stable and at expected levels in children and non-pregnant individuals based on monitoring of urinary iodine levels. However, some studies suggest a potential iodine deficiency in pregnant women. During pregnancy and early infancy, an iodine deficiency can cause irreversible effects. Severe and ongoing iodine deficiency in utero can cause cretinism (intellectual disability, deaf-mutism, motor spasticity, stunted growth, delayed sexual maturation, on other potential neurological defects). Maternal iodine deficiency has also been associated with an increased risk of attention deficit hyperactivity disorder (ADHD) in children. As children grow, an iodine deficiency can cause neurodevelopmental deficits, including decreased intelligence. Adults with iodine deficiency can develop impaired mental function and decreased work productivity due to subsequent hypothyroidism. Chronic iodine deficiency is associated with an increased risk of thyroid cancer. The groups most at risk for iodine deficiency include individuals living in areas that have iodine-deficient soils and do not have dietary supplementation in salts or foods through national initiatives (particularly in Southeast Asia and mountainous areas such as the Alps or Himalayas). Individuals who eat a diet high in goitrogens (foods or substances that interfere with the uptake of iodine in the thyroid, including soy, cabbage, broccoli, cauliflower or other cruciferous vegetables) are also at increased risk. Further at risk are those who do not use iodized salt and pregnant women. Due to its vital role in growth, development, and overall health, iodine is needed across the lifespan. Excessive iodine can also cause goiter, as iodine in high levels can also inhibit thyroid hormone synthesis and increase TSH production. This phenomenon is known as iodine-induced hyperthyroidism, and often results from excessive supplemental iodine intake. Thyroiditis, thyroid papillary cancer, or even acute iodine poisoning can result from an overdosing of iodine supplements. Symptoms of acute iodine poisoning include mouth, throat, and stomach burning; fever; abdominal pain; nausea, vomiting, or diarrhea; weak pulse; or coma. Iodine supplements may interact with anti-thyroid medications such as methimazole (Tapazole), angiotensin-converting enzymes (ACE) inhibitors such as benazepril (Lotensin) or Lisinopril (Prinivil), and potassium-sparing diuretics such as spironolactone (Aldactone) (NIH, 2020d).
Iron is an essential component of hemoglobin (red blood cell protein that transfers oxygen from the lungs to tissues) and is available in many foods, or as a supplement. Iron deficiency is common in the US and across the world. The World Health Organization (WHO) estimates that approximately 33% of non-pregnant women, 40% of pregnant women, and 42% of children suffer from anemia caused by iron deficiency (WHO, 2020). The assessment of iron status is dependent on hematological indicators. Iron deficiency can progress from the depletion of iron stores in the body, iron-deficiency erythropoiesis (erythrocyte production), to iron deficiency anemia. Serum ferritin concentration measures the body's iron stores and is the most cost-effective test for diagnosis. Serum ferritin levels decrease in the first stages of iron deficiency and can identify an issue prior to the onset of iron-deficiency anemia. A serum ferritin level below 30 mcg/L is indicative of iron deficiency, and a value below 10 mcg/L suggests iron deficiency anemia. Normal ferritin values in males are 24-336 mcg/L, and females are 11-307 mcg/L (NIH, 2020i). Food sources include lean meats and seafood as the highest source of heme iron (higher bioavailability than nonheme iron); nuts, vegetables, beans, and fortified grain products are nonheme iron sources. The addition of foods high in vitamin C enhances the bioavailability of nonheme iron. Phytate, which is present in beans and grains, added to the diet can decrease the availability of iron from nonheme sources. Breastmilk contains bioavailable iron but is not sufficient for the needs of an older infant (over four months). Infant formulas are fortified with 12 mg/L iron. Iron supplements can be taken as a single ingredient supplement or added to a multivitamin with a mineral supplement. Multivitamin with mineral supplements typically contain 18 mg of iron per daily dose. Iron-only supplements may have as much as 65 mg of iron per daily dose, which is over 300% of the RDA. High doses of iron may cause GI symptoms such as nausea or constipation. There are various types of supplements ranging from ferrous sulfate, ferric gluconate, and ferric sulfate with varying bioavailability. Ferrous iron is more bioavailable than ferric iron. Heme iron polypeptides, or iron amino-acid chelates, typically cause fewer GI complications but are not as bioavailable as the other forms. Calcium can interfere with iron absorption, and it is suggested that these two supplements are taken separately at different times of the day (NIH, 2020e).
Iron deficiency is common in the US and across the world. The WHO (2020) estimates that approximately 33% of non-pregnant women, 40% of pregnant women, and 42% of children suffer from anemia caused by iron deficiency. Groups at the highest risk for inadequacy are pregnant women, infants and young children, women with heavy menstrual bleeding, frequent blood donors, cancer patients (i.e., those with colon cancer or chemotherapy-induced anemia), patients with GI disorders such as IBD or a history of bariatric surgery, and heart failure patients (this may be related to anticoagulation therapy, poor nutrition, defective mobilization of iron storage, or malabsorption). Health risks from excessive iron intake include GI upset, faintness, multisystem organ failure, coma, or even death. Iron supplements can interact with a number of medications. Iron supplementation can decrease the absorption and diminishing the clinical effectiveness of levodopa (Sinemet). Patients on levothyroxine (Synthroid) should be cautioned that iron can reduce its efficacy when taken simultaneously, so the two should be taken at least four hours apart. Finally, proton pump inhibitors such as omeprazole (Prilosec) reduce iron absorption due to the neutralization of the acidity of the stomach contents (NIH, 2020e).
Magnesium is a mineral that is abundant in the body and is responsible for energy production and other biochemical reactions. It plays an active role in calcium and potassium transport across cell membranes that is vital to nerve impulse conduction, normal heart rhythm, and muscle contractions. The average adult body has approximately 25 g of magnesium; over half of this is stored in the bones and the remainder is in soft tissues. Less than 1% is found in the blood. Normal serum magnesium is very consistent, ranging between 0.75 and 0.95 mmol/L. It is difficult to get precise measurements of magnesium in the body; a urinary tolerance test is the ideal method of measuring this. This test assesses magnesium excretion after an infusion of magnesium. Magnesium is found in plant and animal-based foods and beverages, including almonds, spinach, cashews, peanuts, soymilk, black beans, potatoes, rice, yogurt, and fortified breakfast cereals. Tap water, mineral water, and other bottled waters are typically good sources of magnesium but will vary between 1 mg/L to 120 mg/L and should be identified on the label of bottled products. Dietary supplements are available as a single ingredient or within a multivitamin with minerals and come in varying forms. Magnesium oxide, citrate, or chloride are the most common forms, and those dissolving in liquid are most readily absorbed in the gut. Studies have shown that zinc supplements of 142 mg/day or higher can interfere with magnesium absorption (NIH, 2020f).
Magnesium hydroxide is the primary component in laxatives such as milk of magnesia (Phillips) as well as chewable antacids for heartburn or upset stomach (i.e., Rolaids). Magnesium deficiency occurs when the intake falls below the RDA (310-420 mg/d for adults depending on gender), and usually occurs in the following populations:
- Those with GI diseases that decrease absorption such as IBD, celiac disease, or history of bariatric surgery,
- Type 2 diabetics,
- Patients with alcohol use disorder (AUD), or
- Older adults (NIH, 2020f).
Magnesium supplements are often marketed toward those with hypertension and CVD. Studies have shown that supplementation with magnesium for 8 to 26 weeks offered a 2.2 mmHg improvement in diastolic pressure. The magnesium dose in this study ranged from 243-973 mg/d. In a meta-analysis of 22 studies of normotensive and hypertensive adults, the systolic blood pressure was reduced by 3 to 4 mmHg and diastolic by 2 to 3 mmHg after 3 to 24 weeks of supplementation with at least 370 mg/d of magnesium. Dietary changes that promote increased magnesium consumption include fruits and vegetables as well as low-fat or non-fat dairy, which may also decrease systolic and diastolic blood pressure. However, this is not necessarily linked only to the increase in magnesium. Another meta-analysis suggests a correlation between an additional 100 mg/d of dietary magnesium intake and a decrease in stroke risk. There is minimal evidence that magnesium supplements contribute to a decreased risk of stroke. Since magnesium is related to glucose metabolism, diets higher in magnesium may lower the risk of type 2 diabetes. Hypomagnesemia may worsen insulin resistance, which often precedes diabetes. Diabetes also increases the urinary excretion of magnesium, leading to a magnesium deficiency. A meta-analysis of seven studies lasting from 6 to 17 years found that an increase of 100 mg/d of magnesium intake decreased the risk of type 2 diabetes by 15%. Despite these promising results, the American Diabetes Association (ADA) notes insufficient evidence to support the routine use of magnesium to improve glycemic control in diabetes. Other diseases that identify magnesium as a potential supportive therapy include osteoporosis and migraine headaches. While neither disease can provide significant evidence that increasing magnesium can alter the disease course, four small studies note a reduction in the frequency of migraine headaches in patients given supplements up to 600 mg/d. One study suggested 300 mg BID for migraine prophylaxis, but because this dose is higher than the tolerable upper intake level (UL, 350 mg/d), the American Academy of Neurology and the American Headache Society suggest that this treatment only be done under the supervision of a healthcare provider. Magnesium intake from food sources will typically not cause symptoms, as excessive amounts are excreted in the urine. Dangers from excess magnesium intake via supplements or medications include GI symptoms such as diarrhea, nausea, or abdominal cramping. Magnesium toxicity is possible and can be fatal. Risk of toxicity increases in patients with renal failure as the ability to remove excess magnesium is decreased (NIH, 2020f).
Manganese is an essential trace element found in foods and is also a dietary supplement. It is a cofactor for several enzymes and is involved in amino acid, cholesterol, glucose, and carbohydrate metabolism, bone formation, reproduction, blood clotting and homeostasis in relation to vitamin K, as well as the immune response. The human body has about 10 to 20 mg of manganese, and 25 to 40% of this is found in the bones. The brain, liver, pancreas and kidneys also contain manganese. It is excreted by bile into the feces, with a small amount being reabsorbed. Manganese levels are difficult to assess and rarely measured in clinical practice. Manganese is found in a variety of foods that include mussels, clams, oysters and other seafood, whole grains, hazelnuts, pecans, chickpeas, spinach, pineapple, and brown rice. Breast milk has approximately 3 to 10 mcg/L and cow’s milk-based infant formulas have 30 to 100 mcg/L. Soy-based formulas are even higher in manganese at 200 to 300 mcg/L, but the absorption rate is much higher via human milk than soy or cow’s milk. Dietary iron intake and overall iron levels are inversely associated with manganese absorption. Men appear to absorb dietary manganese less effectively than women, possibly due to their higher iron stores. Infants absorb higher proportions of manganese than adults. Manganese supplements are available in different forms and there is little data on which is optimal. Manganese is not always a component of multivitamin with mineral supplements, but if it is a component, the average dose is between 1.0 and 4.5 mg per day. Most single-ingredient manganese dietary supplements contain between 5 and 20 mg. Manganese deficiency is extremely rare, and therefore the signs and symptoms are not well established. Some limited studies have associated manganese deficiency with bone demineralization and poor growth in children; skin rashes, hair depigmentation, decreased serum cholesterol, and increased alkaline phosphatase activity in men; and increased premenstrual pain and altered mood in women. It may also be associated with altered lipid and carbohydrate metabolism and abnormal glucose tolerance. There are no specific groups of people at high risk for manganese deficiency. Bone health and diabetes are likely affected due to the role of manganese as a cofactor to several enzymes. A small study noted a relationship between manganese levels and osteoporosis in women, yet there were no clear associations between plasma manganese levels and bone mineral density in a similar study of men. In another study, the addition of 1000 mg of calcium, 5 mg of manganese, 15 mg of zinc, and 2.5 mg of copper for two years improved spinal bone density in comparison to a placebo in 59 postmenopausal women. It is unknown what role manganese alone played in this study. Several studies have demonstrated an association between increased and decreased blood levels of manganese and the prevalence of type 2 diabetes. A large study in China found a correlation between decreased plasma manganese levels and the incidence of type 2 diabetes. In another Chinese study, individuals with the lowest and highest manganese levels had a higher incidence of type 2 diabetes than those with median levels. Other studies have been unable to find associations between blood manganese levels and diabetes prevalence (NIH, 2020g).
There is no known evidence of toxicity from dietary or supplemental manganese intake. However, manganese toxicity has been recognized in people who work in welding and mining and are exposed to large amounts of inhaled manganese dust. Symptoms of manganese toxicity include central nervous system (CNS) manifestations such as tremor, tinnitus, hearing loss, muscle spasms, mania, depression, headaches, irritability, or reduced hand-eye coordination. Iron deficiency increases manganese absorption and can worsen manganese toxicity symptoms. Chronic liver disease can impair manganese elimination through bile and increase susceptibility to toxicity. There is no know interactions with manganese among medications (NIH, 2020g).
Molybdenum is another essential trace element found naturally in foods and in dietary supplements. Molybdenum is required for the function of four enzymes that are involved in metabolizing drugs and toxins. The kidneys maintain levels of molybdenum and are responsible for excretion via the urine. Molybdenum is not typically measured or assessed in routine clinical situations. Molybdenum is found in many foods, making deficiency rare. Legumes have the highest content of molybdenum, followed by nuts, whole grains, beef liver, or dairy products. A rare genetic metabolic disorder, molybdenum cofactor deficiency prevents biosynthesis and impairs the function of enzymes that metabolize sulfite; this typically leads to seizures and may be fatal within days of birth due to neurological damage. There are no known groups that are at higher risk for molybdenum deficiency due to decreased intake. It is not utilized as a treatment for any disease or disorder and has no interactions with any known medications (NIH, 2020h).
Nickel is a mineral found in nuts, dried beans, peas, soybeans, grains, and chocolate. Nickel is considered a trace element and found in most multivitamin with minerals. Nickel deficiency has not been reported in humans, but it is seen in animals. Osteoporosis and anemia have been linked to potentially low levels of nickel despite little evidence to support this connection. Taking more than 1 mg of nickel daily may be unsafe and cause adverse effects. High doses can be toxic. It is possible to have an allergic reaction to nickel and occupational exposure may result in allergies, lung disorders, and even cancer. Those with renal failure should avoid nickel supplements. Disulfiram (Antabuse), a medication used for the treatment of AUD, may decrease the absorption of nickel. There is no established RDA for nickel. The tolerable UL is 0.3 mg/d in children between the ages of four and eight years, 0.6 mg/d in children between the ages of nine and thirteen years, and 1 mg/d for healthy adults (WebMD, n.d.).
Phosphorus is an essential mineral that is a component of bones, teeth, and genetic material (i.e., DNA and RNA). Phosphorus is also a component of the cell membrane structure and adenosine triphosphate (ATP, the body’s key energy source). It plays a role in gene transcription and the activation of enzymes. Approximately 1% of fat-free mass is made up of phosphorus, the vast majority of which is in bones and teeth. Phosphorus and calcium are interrelated due to hormones such as parathyroid hormone (PTH), estrogen, adrenaline, and vitamin D, which regulate the metabolism of both. The kidneys, intestines, and bones regulate phosphorus homeostasis. Particularly when kidney function is impaired, serum phosphorus levels rise. Phosphorus can be measured in both the serum and plasma. Normal phosphate levels are between 2.5 and 4.5 mg/dL. Food sources for phosphorous includes dairy products, meat, poultry, fish, eggs, legumes, grains, nuts, and vegetables. Yogurt, milk, and salmon each contain more than 200 mg per serving. Dietary supplements are available as a single ingredient or as a combination in a multivitamin with minerals and provide between 10% and 100% of the RDA (NIH, 2020i).
Phosphorus deficiency is not often seen in the US and is rarely due to low dietary intake. Groups at risk for deficiency include preterm newborns and individuals with genetic phosphate regulation disorders or severe malnutrition. People with severe protein or calorie malnutrition can develop refeeding hypophosphatemia within two to five days of initiating enteral or parenteral nutrition related to the shift in metabolism from a catabolic to an anabolic state. Sources of malnutrition that lead to refeeding syndrome include cancer, chronic obstructive pulmonary disease (COPD), liver cirrhosis, extremely low birth weight, anorexia nervosa, or those with chewing or swallowing problems. Typically, prophylactic administration of phosphorus and thiamine prevents this complication. Two diseases in which phosphorus may play a key role include chronic kidney disease and CVD. Several studies have identified the role of phosphorus in chronic kidney disease and bone demineralization with high phosphate levels leading to an increase in mortality. Most clinicians instruct patients to limit phosphorus intake and eat a diet rich in calcium to decrease this risk. Several large studies have linked higher serum phosphate concentrations to the risk of cardiovascular mortality in otherwise healthy adults. A meta-analysis of over 13,000 non-pregnant adults with a mean age of 43 to 45 years found that for every 1 mg of phosphate above 3.5 mg/dL, the risk of death increased by 35% and the risk of cardiovascular death increased by 45% over 14 years. Hyperphosphatemia is rarely due to dietary or supplemental intake. However, those taking more than 1,000 mg/d may develop cardiovascular, kidney, and bone adverse effects as well as an increase in mortality risk (NIH, 2020i).
Phosphorus interacts with several medications and some medications can alter phosphate levels. Antacids that contain aluminum hydroxide (i.e., Maalox HRF, Rulox), bind phosphates in the intestines and can lead to hypophosphatemia. Antacids containing calcium carbonate (i.e., Rolaids, Tums, and Maalox) decrease the intestinal absorption of dietary phosphorus. Enema preparations (i.e., Fleet) may contain sodium phosphate which can increase serum phosphorus levels (NIH, 2020i).
Potassium is the most plentiful intracellular cation; it is present in many foods naturally and available as a supplement. Potassium is present throughout the body and is required for normal cell functioning due to its role in maintaining intracellular and extracellular fluid volume, including plasma volume. Sodium and potassium levels are very interrelated. Most potassium is found intracellularly and is required for proper muscle contraction, nerve transmission, and kidney function. Normal serum potassium levels are between 3.6 and 5 mmol/L; levels outside of this range are rare in healthy adults with normal kidney function. Foods that are rich in potassium include fruits (i.e., apricots, prunes), vegetables (i.e., squash, spinach), legumes, potatoes, meat, fish, milk, yogurt, or nuts. Dietary supplement options include single-ingredient potassium or within a multivitamin with minerals. The typical dose of potassium in a dietary supplement is 80 to 99 mg. The US Food and Drug Administration (FDA) mandates that any supplement containing more than 99 mg potassium must carry a warning label regarding small-bowel lesions which can lead to obstructions, bleeding, or perforation. Salt substitutes may contain potassium chloride as a replacement for sodium chloride, and levels may vary from 440 to 2,800 mg per teaspoon. Individuals with kidney disease should use these products with caution due to the risk of hyperkalemia (NIH, 2020j).
Hypokalemia (potassium deficiency) can increase blood pressure, urinary calcium excretion, bone turnover, and increase the risk of kidney stones and cardiac arrhythmias. Severe hypokalemia (serum potassium level under 2.6 mmol/L) is typically due to the use of diuretics or other medications. Other causes of hypokalemia include diarrhea, laxative abuse, excessive diaphoresis, or dialysis. Magnesium depletion can cause hypokalemia through increased urinary potassium losses. In those with hypomagnesemia and hypokalemia, replacement therapy should be concurrent (NIH, 2020j).
Hypokalemia increases the risk of hypertension and high potassium intake may help decrease blood pressure and the risk of stroke. Low potassium intake impairs calcium reabsorption in the kidneys, increasing calcium excretion, and possibly contributes to the development of hypercalciuria, which can lead to kidney stones. Kidney stones are most common in adults aged 40 to 60. Bone health may be improved by a higher intake of potassium within diets that emphasize vegetables and fruits, but the exact mechanism is not clear. One trial noted that supplementation with 2,346 to 3,519 mg/d of potassium for six months reduced urinary calcium excretion compared to a placebo in healthy men and women over 55 years of age. Bone mineral density at the lumbar spine was also significantly increased in the potassium group. Blood glucose control in patients with type 2 diabetes seems to be associated with the need for potassium to secrete insulin from pancreatic cells. Hypokalemia may impair insulin secretion and can lead to glucose intolerance. Long term use of diuretics or hyperaldosteronism increases urinary potassium loss and may lead to this effect. There are several health risks related to hyperkalemia including weakness, paralysis, heart palpitations, and life-threatening cardiac arrhythmias. Potassium supplements can cause minor GI side effects. Patients should be cautioned that ACE inhibitors (i.e., benazepril [Lotensin]) and angiotensin receptor blockers (ARBs, i.e., losartan [Cozaar]) increase the risk of hyperkalemia. Potassium-sparing diuretics including amiloride (Midamor) and spironolactone (Aldactone) decrease the excretion of potassium through the urine and can also lead to hyperkalemia. Loop diuretics such as furosemide (Lasix) and thiazide diuretics such as chlorothiazide (Diuril) decrease potassium levels and can cause hypokalemia requiring a potassium supplement (NIH, 2020j).
Selenium is one of the trace elements that is naturally found in foods and available as a dietary supplement. It is nutritionally essential and plays a critical role in reproduction, DNA synthesis, thyroid hormone metabolism, and protection from infection. Selenium is found in Brazil nuts, seafood, organ meats, muscle meats, dairy products, grains, and cereals. The soil in which a plant is grown has an impact on the amount of selenium in the food and makes measurement more complex. Selenium is available as a single ingredient supplement or as part of a multivitamin with minerals. Most Americans acquire an adequate amount of selenium in their daily diet. However, deficiencies can occur, particularly in people with HIV and those undergoing renal dialysis. Individuals from low-selenium regions of the world (i.e., parts of China and some European countries) suffer from deficiency more often. Selenium supplementation may be considered for diseases where sufficient levels affect the disease process, such as cancer, cognitive decline, thyroid disease, and CVD. Since selenium plays a role in DNA repair, its antioxidant properties may aid in the prevention of cancer. A Cochrane study suggests selenium deficiency and the risk for developing cancer, including colorectal, lung, skin, esophageal, prostate, bladder, and gastric cancer. Selenium can reduce inflammation and prevent platelet aggregation, thus reducing the risk of CVD. A meta-analysis of 25 observational studies notes that individuals with lower concentrations of selenium have a higher risk of coronary artery disease, but there is no significant link between higher selenium levels and a reduced risk of heart disease or cardiac death. In fact, some studies indicate that higher levels of selenium increase the risk of cardiovascular death. Selenium deficiency has been associated with age-related declines in brain function, possibly due to its antioxidant activity and the decreasing selenium level that occurs with age. An extensive study in France with over 4,000 participants aged 45 to 60 years found that daily supplementation with 120 mg ascorbic acid, 30 mg vitamin E, 6 mg beta-carotene, 100 mcg selenium, and 20 mg zinc for eight years resulted in higher episodic memory and semantic fluency scores up to six years after the study ended. The determination of selenium’s specific role in that increased memory could not be made. There is a high selenium concentration within the thyroid gland; very similar to iodine, selenium has vital functions with the synthesis and metabolism of thyroid hormones. Research has not determined whether an increase in selenium has an effect on thyroid function, yet a study of pregnant women found that an increase in selenium during pregnancy correlated with a decrease of postpartum thyroiditis (NIH, 2020k).
Excessive selenium intake can result in a garlic odor to the breath and a metallic taste in the mouth. Other common signs of high selenium intake include hair loss, brittle nails, skin lesions, nausea, diarrhea, mottled teeth, fatigue, and irritability. Medication interactions with selenium include cisplatin (Platinol), anticoagulants (i.e., clopidogrel [Plavix], enoxaparin [Lovenox], warfarin [Coumadin]), cholesterol-lowering medications (i.e., lovastatin [Mevacor], pravastatin [Pravachol]), barbiturates, and birth control pills (i.e., ethinyl estradiol/levonorgestrel [Triphasil], ethinyl estradiol/norethindrone [Ortho-Novum], NIH, 2020k).
Sodium is a required mineral in the body that is related to the function of nerves and muscles as well as the maintenance of the proper balance of fluids. The kidneys control the amount of sodium in the body; if there is too much sodium intake, or the kidneys cannot excrete it, then hypernatremia can develop and lead to hypertension and other health problems. Most Americans acquire an abundance of sodium in their diet and should be encouraged to choose foods low in sodium to regulate their intake. Dietary guidelines suggest that adults need approximately 2.3 grams of sodium per day, or about a teaspoon. Some groups are more sensitive to excess sodium than others, including African Americans, individuals over 50 years of age, and those with heart failure, diabetes, or kidney disease (NLM, 2019b). Top dietary sources of sodium that should be limited include breads, pizza, cold cuts or cured meats, condensed or canned soups, burritos, tacos, savory snacks (i.e., potato chips), chicken, cheese, and eggs. For instance, a turkey and cheese sandwich on wheat bread has over 1,500 mg of sodium, or over half the RDA (Centers for Disease Control and Prevention [CDC], 2017). Drugs that interact with sodium chloride include lithium (Eskalith, Lithobid) and tolvaptan (Jynarque). Disease processes that are impacted by sodium chloride include electrolyte imbalances and acidosis. Rarely is a supplement of sodium needed; however, excess exercise, vomiting, diuretic use, burns affecting large portions of the body, heart failure, or diarrhea can cause hyponatremia and may require replacement of sodium and other electrolytes (NLM, 2020b).
Zinc is an essential mineral available in dietary sources and as a dietary supplement. Zinc is involved in many facets of cellular metabolism including immune function, wound healing, protein synthesis, DNA synthesis, and cell division. Zinc is vital for growth and development during pregnancy, childhood, and adolescence. Proper sense of taste and smell require zinc. Foods highest in zinc include oysters, red meat, crab, beef, pork, lobsters, beans, nuts, whole grains, fortified cereals, and dairy products. Zinc can be found in individual ingredient supplements or as a component of multivitamins with minerals. Zinc-containing cold lozenges are also labeled as dietary supplements. Many homeopathic medications containing zinc are available over the counter for the treatment and/or prevention of the common cold virus. Zinc-containing nasal gels or sprays can cause long lasting or permanent anosmia (loss of sense of smell) and were removed from the US market by the FDA in 2009. Zinc is present in denture adhesive creams and can lead to toxicity with chronic or excessive use. Zinc deficiency is characterized by a loss of appetite, growth retardation, and impaired immunity. In severe deficiencies, hair loss, impotence, delayed sexual maturation, hypogonadism (in males), eye and skin lesions, weight loss, mental lethargy, or taste abnormalities can occur. Zinc deficiency is uncommon in the US, but it is usually due to inadequate intake or malabsorption related to GI disorders or previous bariatric surgeries. Poor intake is more common in those with vegetarian diets, pregnant or lactating women, exclusively breastfed older infants, or patients with AUD. It is also more common in individuals with sickle cell disease. Zinc is beneficial in immune function and many take supplements to prevent viral illness such as colds; zinc deficiency is associated with increased pneumonia susceptibility. Increased zinc intake has been found to also be beneficial in wound healing, diarrhea, and AMD. Large amounts of supplemental iron can reduce zinc absorption and high zinc intake can inhibit copper absorption. For this reason, most dietary supplements with high levels of zinc may also contain copper. Zinc toxicity can occur both acutely and chronically. Acute symptoms include nausea, vomiting, loss of appetite, diarrhea, abdominal cramps, and headaches. Chronically high zinc levels can lead to various genitourinary problems (NIH, 2020l).
Zinc supplements can have potential interactions with antibiotics including quinolones (ciprofloxacin [Cipro]) and tetracycline (Achromycin, Sumycin). Antibiotics should be taken two hours prior or four to six hours after zinc consumption. Zinc may reduce the absorption and action of penicillamine (Cuprimine, Depen) when taken together and should be separated by at least two hours. Thiazide diuretics such as hydrochlorothiazide (HCTZ) or chlorthalidone (Hygroton) increase urinary zinc excretion up to 60% and the prolonged use of these diuretics can deplete zinc levels. A supplement should be considered with patients on these medications (NIH, 2020l).
Recommended Daily Allowances (RDAs) of Minerals
Males aged 14+
Females aged 14+
(NIH, 2020a, 2020b, 2020c, 2020d, 2020e, 2020f, 2020g, 2020h, 2020i, 2020j, 2020k, 2020l; NLM, 2019a, 2019b, 2020a, 2020b; WebMD, n.d.)
Dietary Supplement and Potential Benefits
Calcium supplementation may be considered with risk of preeclampsia. Supplementation decreases risk of rickets, osteoporosis, and dental problems.
Chloride is needed in large amounts by the human body for proper functioning; it is typically found in the body in combination with sodium and water and maintains extracellular volume and proper osmotic pressure of body fluids
Chromium aids in the digestion of foods, slows loss of calcium to avoid osteoporosis, corrects glucose tolerance and insulin resistance. Body builders use to aid in burning fat and muscle building
Copper is associated with prevention of CVD and AD
Fluoride is involved in strong teeth and bones; it works with phosphorus and calcium to increase resistance to tooth decay. Fluoride activates and regulates enzymes that play a role in reducing osteoporosis.
Iodine is essential in thyroid hormone production;
It plays a role in immune response, mammary dysplasia, and fibrocystic breast disease.
Iron is an essential component of hemoglobin.
Magnesium is responsible for energy production and other biochemical reactions such as the calcium/potassium transport across cell membranes vital to nerve impulse conduction, normal heart rhythm, and muscle contractions.
Manganese is a cofactor for several enzymes and is involved in amino acid, cholesterol, glucose, and carbohydrate metabolism, bone formation, reproduction, blood clotting and homeostasis in relation to vitamin K, as well as the immune response.
Molybdenum is required for the function of four enzymes involved in metabolizing drugs and toxins.
Nickel deficiency has been linked to osteoporosis and anemia.
Phosphorous is an essential mineral that is a component of bones, teeth, and genetic material (i.e., DNA and RNA). Phosphorus is also a component of the cell membrane structure and adenosine triphosphate (ATP, the body’s key energy source).
Potassium is present throughout the body and is required for normal cell functioning due to its role in maintaining intracellular and extracellular fluid volume, including plasma volume. Sodium and potassium levels are very interrelated. Most potassium is found intracellularly and is required for proper muscle contraction, nerve transmission, and kidney function
Selenium is nutritionally essential and plays a critical role in reproduction, DNA synthesis, thyroid hormone metabolism, and protection from infection.
Sodium is a required mineral in the body that is related to the function of nerves and muscles as well as the maintenance of the proper balance of fluids that can lead to hypertension and other health problems, particularly to the cardiovascular system
Zinc is involved in many facets of cellular metabolism including immune function, wound healing, protein synthesis, DNA synthesis, and cell division. It is vital for growth and development during pregnancy, childhood, and adolescence and proper sense of taste and smell require zinc
Dietary supplements of zinc are sold to prevent the common cold and enhance immunity
(NIH, 2020a, 2020b, 2020c, 2020d, 2020e, 2020f, 2020g, 2020h, 2020i, 2020j, 2020k, 2020l; NLM, 2019a, 2019b, 2020a, 2020b; WebMD, n.d.)
National Academies of Sciences, Engineering and Medicine. (2005). Dietary reference intakes for water, potassium, sodium, chloride, and sulfate. The National Academies Press. https://www.nap.edu/read/10925
The National Institutes of Health. (2020a). Calcium. https://ods.od.nih.gov/factsheets/Calcium-HealthProfessional/
The National Institutes of Health. (2020b). Chromium. https://ods.od.nih.gov/factsheets/Chromium-HealthProfessional/
The National Institutes of Health. (2020c). Copper. https://ods.od.nih.gov/factsheets/Copper-HealthProfessional/
The National Institutes of Health. (2020d). Iodine. https://ods.od.nih.gov/factsheets/Iodine-HealthProfessional/
The National Institutes of Health. (2020e). Iron. https://ods.od.nih.gov/factsheets/Iron-HealthProfessional/
The National Institutes of Health. (2020f). Magnesium. https://ods.od.nih.gov/factsheets/Magnesium-HealthProfessional/
The National Institutes of Health. (2020g). Manganese. https://ods.od.nih.gov/factsheets/Manganese-HealthProfessional/
The National Institutes of Health. (2020h). Molybdenum. https://ods.od.nih.gov/factsheets/Molybdenum-HealthProfessional/
The National Institutes of Health. (2020i). Phosphorus. https://ods.od.nih.gov/factsheets/Phosphorus-HealthProfessional/
The National Institutes of Health. (2020j). Potassium. https://ods.od.nih.gov/factsheets/Potassium-HealthProfessional/
The National Institutes of Health. (2020k). Selenium. https://ods.od.nih.gov/factsheets/Selenium-HealthProfessional/
The National Institutes of Health. (2020l). Zinc. https://ods.od.nih.gov/factsheets/Zinc-HealthProfessional/
US National Library of Medicine. (2018). Dietary supplements. https://medlineplus.gov/dietarysupplements.html
US National Library of Medicine. (2019a). Fluoride in diet. https://medlineplus.gov/ency/article/002420.htm
US National Library of Medicine. (2019b). Sodium. https://medlineplus.gov/sodium.html
US National Library of Medicine. (2020a). Chloride. https://medlineplus.gov/ency/article/002417.htm
US National Library of Medicine. (2020b). Low blood sodium. https://medlineplus.gov/ency/article/000394.htm
US National Library of Medicine. (2020c). Minerals. https://medlineplus.gov/minerals.html
WebMD. (n.d.). Nickel. Retrieved on April 22, 2020, from https://www.webmd.com/vitamins/ai/ingredientmono-1223/nickel
The World Health Organization. (2020). WHO guidance helps detect Iron deficiency and protect brain development. https://www.who.int/news-room/detail/20-04-2020-who-guidance-helps-detect-iron-deficiency-and-protect-brain-development
Youdim, A. (2019). Overview of nutrition. Merck Manual. https://www.merckmanuals.com/professional/nutritional-disorders/nutrition-general-considerations/overview-of-nutrition?qt=&sc=&alt=