Natural Standard Bottom Line Monograph, Copyright © 2013 (www.naturalstandard.com). Commercial distribution prohibited. This monograph is intended for informational purposes only, and should not be interpreted as specific medical advice. You should consult with a qualified healthcare provider before making decisions about therapies and/or health conditions.
While some complementary and alternative techniques have been studied scientifically, high-quality data regarding safety, effectiveness, and mechanism of action are limited or controversial for most therapies. Whenever possible, it is recommended that practitioners be licensed by a recognized professional organization that adheres to clearly published standards. In addition, before starting a new technique or engaging a practitioner, it is recommended that patients speak with their primary healthcare provider(s). Potential benefits, risks (including financial costs), and alternatives should be carefully considered. The below monograph is designed to provide historical background and an overview of clinically-oriented research, and neither advocates for or against the use of a particular therapy.
Atomic number 28, Ni, nickel chloride, nickel sulfate, nickelous sulfate, níquel (Spanish), nitinol, trace element.
Nickel is trace element that is necessary for the survival of bacteria, plants, and mammals. It is a hard, bright, silver-white metal that is present in soil, water, cocoa and chocolate, nuts, dried beans, peas, soya beans, spinach, lettuce, oatmeal, grains, fruits (including canned fruits), other vegetables (including canned vegetables) and leguminous seeds, as well as shellfish, salmon, hydrogenated shortenings, eggs, and milk. Drinking water and food are the main sources of nickel. The average American diet contains about 300 micrograms of nickel daily.
Nickel alloys are metals created by combining nickel with another metal, such as titanium, and are used in many medical and dental applications, including dentures, dental crowns, stents, hip replacements, and screws used during bone reconstruction surgery. Nickel is also used to manufacture stainless steel. It is a common component of silver coins, belt buckles, and inexpensive jewelry. It is used in the automobile industry, electronics, chemical processes, nickel-cadmium batteries, and many household products.
Nickel is the most common cause of metal allergy, which affects females more often than males. It may develop at any age and tends to last throughout an individual's lifetime. Symptoms of nickel allergy include an itchy rash at the site where nickel contacted the skin. This reaction may occur after chronic exposure to nickel-containing products, such as eyeglass frames, dental materials, and inexpensive jewelry. Human exposure to highly nickel-polluted environments, such as those associated with nickel refining, electroplating, and welding, may cause skin allergies and cancer of the nose and lung.
The European Union Nickel Directive limits the amount of nickel allowed in consumer products that come into direct and prolonged contact with the skin (e.g., earrings, watchbands, and zippers). There are some indications that this regulation has reduced the amount of nickel allergy in Europe. In North America, where no regulations are in place, the incidence of nickel-induced skin allergy is increasing. Some experts believe that regulations should be in place in the United States and other countries to prevent unnecessary nickel allergies.
Although nickel deficiency may theoretically exist, scientific evidence of any benefit from nickel supplementation in humans is lacking in the available literature.
These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.
No available studies qualify for inclusion in the evidence table.
*Key to grades:A: Strong scientific evidence for this use; B: Good scientific evidence for this use; C: Unclear scientific evidence for this use; D: Fair scientific evidence against this use (it may not work); F: Strong scientific evidence against this use (it likely does not work).
The below uses are based on tradition or scientific theories. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious and should be evaluated by a qualified health care professional.
Adrenal insufficiency, Alzheimer's disease, bone diseases, impaired glucose tolerance (inadequate insulin production), iron absorption enhancement, liver cirrhosis, total parenteral nutrition, vitamin and nutrient deficiency (nickel deficiency).
The below doses are based on scientific research, publications, traditional use, or expert opinion. Many herbs and supplements have not been thoroughly tested, and safety and effectiveness may not be proven. Brands may be made differently, with variable ingredients, even within the same brand. The below doses may not apply to all products. You should read product labels, and discuss doses with a qualified healthcare provider before starting therapy.
Adults (18 years and older)
There is no established recommended daily allowance (RDA) for nickel. Common amounts included in supplements range from 35 to 100 micrograms daily.
Dietary nickel intake is variable, averaging about 150-300 micrograms daily. Dietary nickel comes predominantly from roots and vegetables, grain, and bread. Certain food items, such as cocoa and chocolate, nuts, dried beans, peas, soya beans, spinach, lettuce, oatmeal, grains, fruits (including canned fruits), other vegetables (including canned vegetables) and leguminous seeds, as well as shellfish, salmon, hydrogenated shortenings, eggs, and milk, may have very high nickel contents.
Baking powder and cocoa powder may contain excessive amounts of nickel, due to nickel leaching during the manufacturing process. Consumption of these items in large amounts may increase the nickel intake to 900 micrograms daily or more. Soft drinking water (containing fewer dissolved minerals than hard water) and acid beverages may dissolve nickel from pipes and containers. Leaching or corrosion processes may contribute significantly to oral nickel intake, occasionally up to 1,000 micrograms daily, which is equivalent to the tolerable upper intake level for nickel in adults.
Children (under 18 years old)
Nickel as a dietary supplement is not advised, as excess nickel exposure in children may induce developmental malformations and late-onset diseases. The tolerable upper intake level for children 1-3 years old is 0.2 milligrams daily; for children 4-8 years old, it is 0.3 milligrams daily; and for children 9-13 years old, it is 0.6 milligrams daily. Adolescents 14-18 years old and pregnant or lactating women have the same tolerable upper intake level as adults (1 milligram daily).
The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.
According to the North American Contact Dermatitis Data Group (NACDG), nickel is among the five most prevalent allergens.
Patients can become allergic to nickel at any age. Symptoms typically develop within 20 minutes of exposure to nickel. Patients who are allergic to nickel develop contact dermatitis, which is an itchy rash. The severity varies among individuals. Some patients may develop fluid-filled blisters. In most cases, the affected skin is limited to the area that was exposed to the metal. However, it is possible for the rash to spread to other areas of the body. Symptoms may last anywhere from a few hours to days.
Products, such as silver coins, keys, jewelry (necklaces, earrings, bracelets, rings, and watchbands), belt buckles, zippers, buttons, bra hooks, suspender clips, pens, hair clasps, electric shavers, paper clips, and power tools may contain nickel. Patients who are exposed to nickel on a regular basis have an increased risk of developing nickel allergies. Once an individual is sensitized to nickel, nickel exposures later in life will also cause an allergic reaction.
Typically, an allergic response to nickel is not triggered the first time the body is exposed to it. According to the Centers for Disease Control and Prevention (CDC), the more exposure an individual has to nickel-containing products, the more likely the patient will become allergic to nickel. After the first time, or first several times, the body is exposed to nickel, the immune system becomes sensitized. During this process, the body's white blood cells develop antibodies to the nickel. Once sensitized, the antibodies are able to quickly detect and bind to the nickel allergens when they enter the body. These antibodies also trigger the release of chemicals (such as histamine) that cause allergic symptoms, such as red, itchy, and swollen skin.
The main risk factors for developing nickel allergy are female gender and early exposure (i.e., pierced ears at a young age). Historically, nickel allergy has affected more women than men. Researchers believe that this increased risk may be because women are more likely to have their ears pierced than men and to use cosmetic products that contain nickel. However, as body piercing continues to gain popularity, there have been an increasing number of reports of men with nickel allergies. When the ears or other body parts are pierced, the body is exposed to nickel in the jewelry for several days until the skin heals. An allergic reaction can be prevented if the patient's skin is pierced with jewelry that is hypoallergenic, stainless steel, solid gold, or sterling silver.
Drinking water and eating food that contains high amounts of nickel (such as cocoa and chocolate, nuts, dried beans, peas, soya beans, spinach, lettuce, oatmeal, grains, fruits (including canned fruits), other vegetables (including canned vegetables) and leguminous seeds, as well as shellfish, salmon, hydrogenated shortenings, eggs, and milk) may lead to nickel allergy in extremely sensitive patients. In these patients, a nickel-restricted diet may be recommended.
Some professions are associated with a higher risk of nickel-induced contact dermatitis, including dentists and dental hygienists, hairdressers, cashiers, Danish pottery painters, aircraft construction workers, musicians, electronic assemblers, nurses, sales assistants, and general assemblers. Work-related nickel exposures often cause hand eczema, which is an itchy rash that develops on the hands.
Patients with dental devices that contain nickel, including braces, dentures, and crowns, are exposed to low levels of nickel, as the saliva very slowly causes the metal to corrode. Similarly, nickel-containing metals used in stents, hip replacements, and screws used during bone reconstruction surgery may also release small amounts of nickel into the body. Although this type of nickel exposure does not seem to pose a risk in general, it may cause a serious allergic reaction in individuals that are hypersensitive to nickel. Nickel-free stainless steels have been developed to address the issue of nickel sensitivity. It is important to notify dentists and doctors of a known nickel hypersensitivity.
Although there is no cure for nickel-related allergies, antihistamines, corticosteroid creams and ointments, cool compresses, hydrocortisone creams, and moisturizing creams may help reduce the symptoms. The primary treatment is strict avoidance of nickel exposure, including the removal of nickel-containing dental material. Nickel testing kits may be purchased to identify products that contain nickel. Gloves should be worn by workers that handle nickel objects regularly. Occupational nickel contact dermatitis may require a job change.
There is some evidence that exposure to low levels of nickel, such as would occur in patients with orthodontic appliances, may cause the body to tolerate later nickel exposures without the development of allergic reactions. This is called oral tolerance.
Patients that are allergic to nickel may also be allergic to palladium, cobalt, and aluminum.
Side Effects and Warnings
Nickel exposures may result from cigarette smoke, airborne particles from combustion of fossil fuels, and contact with stainless steel kitchen utensils, stainless steel and nickel-plated articles, and inexpensive jewelry. People working in or living near industries and facilities that manufacture and use nickel may have higher than average exposure. Nickel impurities may be introduced during the manufacturing of food, drugs, and dietary supplements. Nickel alloys are often used in dental and medical procedures. Certain foods contain high nickel levels.
The level of nickel toxicity depends on its chemical form. Insoluble nickel compounds (metallic nickel, nickel sulfides, and nickel oxides) are associated with a higher risk of cancer than water-soluble nickel salts (chloride, nitrate, sulfate). Nickel carbonyl is the most toxic form of nickel. Inhalation of nickel carbonyl over time may cause cancer of the lung and nose. Taking it by mouth may lead to serious complications, including death.
Long-term exposure to nickel compounds is associated with lung and nasal cancer in humans, and it induces tumors in experimental animals. The International Agency for Research on Cancer has classified nickel compounds as carcinogenic to humans.
Skin contact may lead to nickel-induced contact dermatitis. In rare cases, skin reactions may occur at a site on the body other than the point of nickel contact, and asthma may occur. Exposure to nickel-containing dust may cause heart and lung diseases. Nickel exposure may cause variable degrees of kidney and cardiovascular system poisoning. Ingestion of high levels of nickel sulfate has been associated with nausea, vomiting, diarrhea, headache, blurred vision, dizziness, coma, and kidney poisoning.
Use cautiously in patients with diabetes, blood sugar disorders, cancer, heart rate abnormalities, liver disorders, kidney disorders, or immune or autoimmune disorders; in patients taking agents for any of these conditions; and in patients taking blood vessel-widening or -constricting agents, or agents metabolized by cytochrome P450 enzymes.
Use cautiously during radiotherapy, or in combination with cis-platinum, trans-platinum, and mitomycin C, as nickel may enhance their cytotoxicity and genotoxicity.
Avoid excess nickel exposure or consumption.
Children should avoid excess nickel exposure, as early-life exposure to nickel may induce malformations and late-onset diseases. Body piercing should be done using nickel-free studs, especially in children, to prevent nickel hypersensitization.
Pregnant and lactating women should avoid excessive exposure to nickel, because it can cross the placenta and has been demonstrated to be harmful to the fetus, and it may cause spontaneous abortion.
Long-term skin contact with nickel should be avoided, due to the risk of developing contact dermatitis. Gloves should be worn by workers that handle nickel objects.
Patients that are highly sensitive to nickel are advised to strictly avoid nickel exposure, including nickel-containing foods and dental material. Patients with a known allergy to other metals, especially palladium, cobalt, and aluminum, should also limit nickel exposures.
Breathing nickel fumes or dusts should be avoided due to the risk of cancers of the lung, nose, larynx, and prostate, and cardiopulmonary diseases.
Avoid in combination with disulfiram therapy in patients with nickel dermatitis, due to the risk of liver toxicity.
Pregnancy and Breastfeeding
Pregnant and lactating women should avoid exposure to higher than normal levels of nickel. Nickel can cross the placenta and has been demonstrated to be harmful to the fetus, and it may cause spontaneous abortion. High nickel exposure may decrease fertility. Early-life exposure to high levels of nickel may cause developmental malformations and diseases. Nickel is present in human breast milk.
Most herbs and supplements have not been thoroughly tested for interactions with other herbs, supplements, drugs, or foods. The interactions listed below are based on reports in scientific publications, laboratory experiments, or traditional use. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy.
Interactions with Drugs
Nickel may interfere with cytochrome P450-dependent microsomal drug-metabolizing enzymes; this effect may be additive with other metals. As a result, the levels of these drugs may be increased or decreased in the blood and may cause increased effects or potentially serious adverse reactions. Patients using any medications should check the package insert and speak with a qualified healthcare professional, including a pharmacist, about possible interactions.
Nickel may alter the insulin response. Caution is advised when using medications that may affect insulin levels or blood sugar levels. Patients taking insulin or drugs for diabetes by mouth should be monitored closely by a qualified healthcare professional, including a pharmacist. Medication adjustments may be necessary.
Nickel exposure may enhance the toxic effects of ultraviolet radiation and X-rays, as well as cis-platinum, trans-platinum, and mitomycin C.
Nickel should be used cautiously in combination with disulfiram therapy in patients with nickel dermatitis, due to the risk of liver toxicity.
Patients using immunosuppressive drugs who have autoimmune diseases (i.e., multiple sclerosis, psoriasis, systemic lupus erythematosus, or atopic eczema) may be more hypersensitive to nickel than healthy individuals.
Cigarettes and cigarette smoke may contain nickel and thus may increase nickel exposure.
Nickel may also interact with agents that are toxic to the kidney, agents that are toxic to the liver, anticancer agents, blood vessel-widening or -constricting agents, gastrointestinal agents, heart rate-regulating agents, hormonal agents, and neurologic agents.
Interactions with Herbs and Dietary Supplements
Nickel may interfere with cytochrome P450-dependent microsomal drug-metabolizing enzymes; this effect may be additive with other metals. As a result, the levels of other herbs or supplements may become too high or low in the blood. It may also alter the effects that other herbs or supplements possibly have on the P450 system.
Nickel may alter the insulin response. Caution is advised when using herbs or supplements that may affect insulin or blood sugar levels. Patients taking insulin or drugs for diabetes by mouth should be monitored closely by a qualified healthcare professional, including a pharmacist. Medication adjustments may be necessary.
Certain food items, such as cocoa and chocolate, nuts, dried beans, peas, soya beans, spinach, lettuce, oatmeal, grains, fruits (including canned fruits), other vegetables (including canned vegetables) and leguminous seeds, as well as shellfish, salmon, hydrogenated shortenings, eggs, and milk may have very high nickel contents. Patients highly sensitive to nickel may consider limiting these foods in their diets.
Baking powder and cocoa powder may contain excessive amounts of nickel due to nickel leaching during the manufacturing process. Soft drinking water and acid beverages may dissolve nickel from pipes and containers. Leaching or corrosion processes may contribute significantly to oral nickel intake, occasionally up to 1,000 micrograms daily, which is equivalent to the tolerable upper intake level for nickel in adults.
Patients using immune-altering herbs and supplements who have autoimmune diseases (i.e., multiple sclerosis, psoriasis, systemic lupus erythematosus, or atopic eczema) may be more hypersensitive to nickel than healthy individuals.
Tobacco may contain nickel and thus may increase nickel exposure.
Nickel may interfere with the metabolism of other metals and vitamins and minerals, including cadmium, calcium, copper, iodine, iron, magnesium, manganese, vitamin E, and zinc. Depending on the metal, coexposure with nickel may increase or decrease the risk of developing cancer.
Phytates are antioxidant compounds (found in whole grains, legumes, nuts, and seeds) that may decrease nickel absorption. Vitamin C may also reduce intestinal nickel absorption.
Nickel may also interact with agents that are toxic to the kidney, agents that are toxic to the liver, anticancer agents, blood vessel-widening or -constricting agents gastrointestinal agents, heart rate-regulating agents, hormonal agents, and neurologic agents.
This information is based on a systematic review of scientific literature edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).
Natural Standard developed the above evidence-based information based on a thorough systematic review of the available scientific articles. For comprehensive information about alternative and complementary therapies on the professional level, go to www.naturalstandard.com. Selected references are listed below.
Beyersmann D, Hartwig A. Carcinogenic metal compounds: recent insight into molecular and cellular mechanisms. Arch Toxicol. 2008 Aug;82(8):493-512. View Abstract
Das KK, Das SN, Dhundasi SA. Nickel, its adverse health effects & oxidative stress. Indian J Med Res. 2008 Oct;128(4):412-25. View Abstract
Falagiani P. Nickel hyposensitization: a literature review. Int J Immunopathol Pharmacol. 2005 Oct-Dec;18(4 Suppl):3-5. View Abstract
Goodman JE, Prueitt RL, Dodge DG, et al. Carcinogenicity assessment of water-soluble nickel compounds. Crit Rev Toxicol. 2009;39(5):365-417. View Abstract
Goodman JE, Prueitt RL, Thakali S, et al. The nickel ion bioavailability model of the carcinogenic potential of nickel-containing substances in the lung. Crit Rev Toxicol. 2011 Feb;41(2):142-74. View Abstract
Li Q, Zeng Y, Tang X. The applications and research progresses of nickel-titanium shape memory alloy in reconstructive surgery. Australas Phys Eng Sci Med. 2010 Jun;33(2):129-36. View Abstract
Lu LK, Warshaw EM, Dunnick CA. Prevention of nickel allergy: the case for regulation? Dermatol Clin. 2009 Apr;27(2):155-61, vi-vii. View Abstract
Navarro Silvera SA, Rohan TE. Trace elements and cancer risk: a review of the epidemiologic evidence. Cancer Causes Control. 2007 Feb;18(1):7-27. View Abstract
Pazzini CA, Pereira LJ, Marques LS, et al. Allergy to nickel in orthodontic patients: clinical and histopathologic evaluation. Gen Dent. 2010 Jan-Feb;58(1):58-61. View Abstract
Pizzutelli S. Systemic nickel hypersensitivity and diet: myth or reality? Eur Ann Allergy Clin Immunol. 2011 Feb;43(1):5-18. View Abstract
Plotino G, Grande NM, Cordaro M, et al. A review of cyclic fatigue testing of nickel-titanium rotary instruments. J Endod. 2009 Nov;35(11):1469-76. View Abstract
Schram SE, Warshaw EM, Laumann A. Nickel hypersensitivity: a clinical review and call to action. Int J Dermatol. 2010 Feb;49(2):115-25. View Abstract
Thyssen JP, Uter W, McFadden J, et al. The EU Nickel Directive revisited--future steps towards better protection against nickel allergy. Contact Dermatitis. 2011 Mar;64(3):121-5. View Abstract
Thyssen JP, Carlsen BC, Menné T. Nickel sensitization, hand eczema, and loss-of-function mutations in the filaggrin gene. Dermatitis. 2008 Nov-Dec;19(6):303-7. View Abstract
Wild P, Bourgkard E, Paris C. Lung cancer and exposure to metals: the epidemiological evidence. Methods Mol Biol. 2009;472:139-67. View Abstract
Copyright © 2013 Natural Standard (www.naturalstandard.com)
The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.
March 22, 2017