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TABLE 1 Dietary Reference Intakes for Fluoride by Life Stage Group DRI values (mg/day) AIa ULb males females Life stage group 0 through 6 mo 0.01 0.01 0.7 7 through 12 mo 0.5 0.5 0.9 1 through 3 y 0.7 0.7 1.3 4 through 8 y 1 1 2.2 9 through 13 y 2 2 10 14 through 18 y 3 3 10 19 through 30 y 4 3 10 31 through 50 y 4 3 10 51 through 70 y 4 3 10 > 70 y 4 3 10 Pregnancy £ 18 y 3 10 19 through 50 y 3 10 Lactation £ 18 y 3 10 19 through 50 y 3 10 a AI = Adequate Intake. b UL = Tolerable Upper Intake Level. Unless otherwise specified, the UL represents total intake from food, water, and supplements.

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PART III: FLUORIDE 313 FLUORIDE F luoride is vital for the health of teeth and bones. About 99 percent of body fluoride is found in calcified tissues, where it protects against den- tal caries and can stimulate new bone formation. Since data were inadequate to determine an Estimated Average Require- ment (EAR) and thus calculate a Recommended Dietary Allowance (RDA) for fluoride, an Adequate Intake (AI) was instead developed. The AIs for fluoride (for people aged 7 months and older) are based on the prevention of dental caries. The Tolerable Upper Intake (UL) was derived using data on the risk of developing early signs of skeletal fluorosis. DRI values are listed by life stage group in Table 1. Fluoridated water is a primary source of dietary fluoride intake. Average fluoride intakes tend to be higher in communities with fluoridated water com- pared with those with nonfluoridated water. The primary effect of inadequate fluoride intake is an increased risk of dental caries. The potential effects of excess intake are discolored or pitted teeth (in children who consume excess amounts of fluoride prior to the eruption of teeth) and skeletal fluorosis, a very rare effect characterized by elevated bone-ash fluoride concentrations. In the United States and Canada, it is unlikely that older children and adults are ex- ceeding the UL for fluoride. FLUORIDE AND THE BODY Function Fluoride is vital for the health of teeth and bones. Ingesting fluoride during the pre-eruptive phase of tooth development can help prevent dental caries. This is due to the uptake of fluoride in the dental enamel and the formation of fluorhydroxyapatite. Even after teeth have erupted, fluoride can protect against dental caries, but this protection requires frequent exposure to fluoride through- out a person’s lifetime to achieve and maintain adequate concentrations of the ion in dental plaque and enamel. Absorption, Metabolism, Storage, and Excretion In general, 50 percent of dietary fluoride is absorbed from the gastrointestinal tract. In the absence of calcium, which may bind with fluoride, absorption

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DRIs: THE ESSENTIAL GUIDE TO NUTRIENT REQUIREMENTS 314 typically increases to about 80 percent or more. Because of fluoride’s affinity for calcium, about 99 percent of body fluoride is found in calcified tissues. Elimi- nation of absorbed fluoride occurs through the kidneys. The body’s retention of fluoride changes throughout life. In young chil- dren, whose skeletons and teeth are still growing, as much as 80 percent of absorbed fluoride may be retained and only 20 percent excreted. In healthy young and middle-aged adults, approximately 50 percent of absorbed fluoride is retained in the skeleton and 50 percent is excreted in the urine. In older adults, it is likely that the fraction of fluoride excreted is greater than the frac- tion retained. Under most dietary conditions, fluoride balance is positive. When fluoride intake is chronically insufficient to maintain plasma concentrations, fluoride excretion in both infants and adults can exceed the amounts ingested due to mobilization from calcified tissues. DETERMINING DRIS Determining Requirements For fluoride, the data are strong on risk reduction, but the evidence upon which to base an actual requirement is scant. Since data were inadequate to determine an EAR and thus calculate an RDA, an AI was instead developed. The AIs for fluoride (for people aged 7 months and older), are based on the intake values that maximally reduce the occurrence of dental caries in a group of individuals without causing unwanted effects including moderate tooth enamel mottling known as dental fluorosis. Special Considerations Nonfluoridated water: Infants and children who live in areas with nonfluoridated water will not easily achieve the AI for fluoride. Therefore, the American Dental Association, the American Academy of Pediatrics, and the Canadian Paediatric Society have recommended fluoride supplements for these children, with daily doses based on a child’s age and the fluoride concentration of his or her main drinking water source.

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PART III: FLUORIDE 315 Criteria for Determining Fluoride Requirements, by Life Stage Group Life stage group Criterion 0 through 6 mo Human milk content For all other life stage groups Caries prevention The UL The Tolerable Upper Intake Level (UL) is the highest level of daily nutrient intake that is likely to pose no risk of adverse effects for almost all people. Members of the general population should not routinely exceed the UL. The UL value for fluoride represents total intake from food, water, and supplements. The UL for fluoride for individuals aged 9 years and older was derived using data on the risk of developing early signs of skeletal fluorosis, which is associated with a fluoride intake greater than 10 mg/day for a period of 10 years or longer. The UL for infants and children younger than 8 years old was based on a critical adverse effect of developing fluorosis of the anterior teeth, not skeletal fluorosis. Data from studies of fluoride exposure from dietary sources or work envi- ronments showed that a UL of 10 mg/day for a period of 10 years or longer carries only a small risk for an individual to develop preclinical or stage 1 skel- etal fluorosis (see “Excess Intake”). Although the prevalence of enamel fluorosis in both fluoridated and nonfluoridated communities in the United States and Canada is substantially higher than it was when the original epidemiological studies were done some 60 years ago, the severity remains largely limited to the very mild and mild categories. Based on several U.S. studies done in the 1980s, it is estimated that approximately 1 in 100 children exceed the UL in areas where the water fluo- ride concentration is 1.0 mg/L or slightly higher. Any additional intake by chil- dren who are at risk of enamel fluorosis is almost certainly derived from the use of fluoride-containing dental products, especially if they are inadvertently swal- lowed. The virtual absence of evidence showing skeletal changes consistent with a diagnosis of skeletal fluorosis indicates that the UL for older children and adults is not being exceeded in the United States and Canada. DIETARY SOURCES Foods and Water Most foods have fluoride concentrations well below 0.05 mg/100 g. Excep- tions to this include fluoridated water, beverages (including teas), some ma-

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DRIs: THE ESSENTIAL GUIDE TO NUTRIENT REQUIREMENTS 316 rine fish (especially if eating with bones, e.g., sardines), and some infant for- mulas that are made or reconstituted with fluoridated water. Because tea leaves can accumulate fluoride to concentrations exceeding 10 mg/100 g dry weight, brewed tea contains fluoride at concentrations of 1–6 mg/L, depending on the amount of dry tea used, the fluoride concentration of the water, and brewing time. Decaffeinated teas have roughly twice the fluoride concentration of caffeinated teas. Dietary Supplements Fluoride supplements are intended for use by children living in areas with low water fluoride concentrations so that their intake is similar to that of children with access to water fluoride concentrations of approximately 1.0 mg/L. Based on the 1986 National Health Interview Survey (NHIS) data, in the United States approximately 15 percent of children up to age 5 years and 8 percent of those aged 5 to 17 years are given dietary fluoride supplements. Supplements are rarely prescribed for adults. Dental Products Fluoride intake from dental products (such as toothpaste and mouth rinse) can add considerable fluoride content to the diet, often approaching or exceeding intake from foods and water. This is a particular concern in young children who may inadvertently swallow toothpaste or mouth rinses. Bioavailability The bioavailability of fluoride is generally high, but it can be affected by the method in which it is ingested. When a soluble compound such as sodium fluoride is ingested from fluoridated water, absorption is nearly complete. If it is ingested with milk, infant formula, or foods, particularly those with high concentrations of calcium or certain divalent or trivalent ions that form in- soluble compounds, absorption may be reduced by 10–25 percent. The ab- sorption of fluoride from ingested toothpaste, whether added as sodium fluo- ride or monofluorophosphate, is nearly 100 percent. Dietary Interactions There is evidence that fluoride may interact with certain nutrients and dietary substances (see Table 2).

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PART III: FLUORIDE 317 TABLE 2 Potential Interactions with Other Dietary Substances Substance Potential Interaction Notes SUBSTANCES THAT AFFECT FLUORIDE Calcium High concentrations of The rate and extent of fluoride absorption from the calcium ingested with gastrointestinal tract are somewhat reduced by fluoride may reduce ingestion with solid foods and some liquids, fluoride absorption. particularly those rich in calcium, such as milk or infant formulas. INADEQUATE INTAKE AND DEFICIENCY The primary effect of inadequate fluoride intake is an increased risk of den- tal caries. The results of many studies conducted prior to the availability of fluoride-containing dental products showed that the prevalence of dental car- ies in communities with optimal water fluoride concentrations was 40–60 per- cent lower than in areas with low water fluoride concentrations. In a later survey conducted in 1986–1987, the National Caries Program of the National Institute of Dental Research found that the overall difference in caries preva- lence between fluoridated and nonfluoridated regions in the United States was 18 percent. The exclusion of children with reported exposure to fluoride supple- ments increased the difference to 25 percent. EXCESS INTAKE The primary adverse effects associated with chronic excess fluoride intake are the following: • Enamel fluorosis, which occurs during the pre-eruptive development of teeth and results in mainly cosmetic effects in the form of discolored or pitted teeth • Skeletal fluorosis, which results in elevated bone-ash fluoride concen- trations and potentially debilitating symptoms. The following are stages of skeletal fluorosis: Stage 1 skeletal fluorosis: Characterized by occasional stiffness or pain in the joints and some osteosclerosis of the pelvis and vertebrae. Bone-ash fluoride concentrations usually range from 6,000 to 7,000 mg/kg.

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DRIs: THE ESSENTIAL GUIDE TO NUTRIENT REQUIREMENTS 318 Stages 2 and 3 skeletal fluorosis: Symptoms are more severe and may include the calcification of ligaments, osteosclerosis, exostoses, pos- sible osteoporosis of long bones, muscle wasting, and neurological defects due to the hypercalcification of vertebrae. Bone-ash fluoride concentrations typically exceed 7,500–8,000 mg/kg. The development and severity of skeletal fluorosis directly relate to the level and duration of fluoride exposure. Most epidemiological evidence indi- cates that an intake of at least 10 mg/day for a period of 10 years or longer is needed to produce clinical signs of the condition’s milder forms. Crippling skel- etal fluorosis is extremely rare in the United States and Canada. Special Considerations Tropical climates: Reports of relatively marked osteofluorotic signs and symp- toms have been associated with concentrations of fluoride in drinking water of approximately 3 mg/L in tropical climates. These adverse effects have been at- tributed to poor nutrition and hard manual labor leading to excessive sweat loss and compensatory high levels of water intake. Therefore, an increased risk for skeletal fluorosis from excess fluoride intake may exist for malnourished individuals who live in hot climates or tropical environments.

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PART III: FLUORIDE 319 KEY POINTS FOR FLUORIDE Fluoride is vital for the health of teeth and bones. About 99 3 percent of body fluoride is found in calcified tissues, where it protects against dental caries and can stimulate new bone formation. Since data were inadequate to determine an EAR and thus 3 calculate an RDA for fluoride, an AI was instead developed. The AIs for fluoride are based on the prevention of dental 3 caries. The UL for adults was derived using data on the risk of developing early signs of skeletal fluorosis. Infants and children who live in nonfluoridated water areas will 3 not easily achieve the AI for fluoride. Thus, fluoride supplements have been recommended based on life stage and level of water fluoridation. Fluoridated water is a primary source of dietary fluoride intake. 3 The primary effect of inadequate intake is an increased risk of 3 dental caries. The primary adverse effects associated with chronic excess 3 fluoride intake are enamel fluorosis and skeletal fluorosis. Dental products such as toothpaste and mouth rinses can 3 significantly increase fluoride intake, a particular concern in young children if they inadvertently swallow these products. In the United States and Canada, it is unlikely that older 3 children and adults are exceeding the UL for fluoride.