The American Journal of Medicine Volume 118, Issue 1
Skeletal fluorosis and instant tea
Michael P. Whyte MDa, b, , Kevan Essmyer MSb, Francis H. Gannon MDc and William R. Reinus MDd
aDivision of Bone and Mineral Diseases, Washington University School of Medicine at Barnes-Jewish Hospital, St. Louis, Missouri bCenter for Metabolic Bone Disease and Molecular Research, Shriners Hospitals for Children, St. Louis, Missouri cOrthopedic Section, Armed Forces Institute of Pathology, Washington, D.C. dMallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri.
Development of skeletal fluorosis is associated with consumption of well water containing fluoride concentrations in excess of 4 parts per million (ppm).1, 2, 3 and 4 Unprocessed foods contain insufficient fluoride to cause disease.1 Tea, however, is fluoride rich,5, 6 and 7
and skeletal fluorosis occurs in Asia where inferior quality “brick” tea
comprising mature leaves, twigs, and berries of the tea plant Camellia sinensis is drunk.8 Other causes of fluorosis are rare (Table 1).1, 9, 10 and 11
Sources of fluoride toxicity
Fluoride therapy for osteoporosis
Betel nuts and leaves
Chewing tobacco and snuff
Industrial exposure during arc welding, cryolite mining, or manufacture of aluminum, steel, or glass
Tea drinking remains popular in the United States12 and increasingly is suggested to promote health.13 and 14 We caution that skeletal fluorosis can result from consumption of excessive amounts of instant tea because of substantial fluoride levels in some commercial preparations.
A 52-year-old white woman consulted in 1998 for dense lumbar vertebras
discovered after twisting her back. Spinal discomfort and stiffness for 5 years
reflected “disc disease.” She had never had a fracture. Chest radiographs after
exposure to chlorine while manufacturing soap and bleach were unremarkable 16
years previously. She recounted no other chemical or heavy metal exposure. Onset
of menopause was at age 46 years, after which she had estrogen injections, and
then took oral estrogen-methyltestosterone for 3 years. She also took 600 mg of
calcium twice daily for 4 years and a multivitamin daily for 6 months. Review of
family history revealed no skeletal problems. Only intake of unfiltered well
water suggested fluorosis.
The patient appeared well. Spine percussion and rib compression were painless. There was no hepatosplenomegaly. Neurologic examination was intact.
Radiographs from 1993 and 1998 documented the appearance of marked osteosclerosis and cortical thickening throughout the entire spine (especially the lumbar region) and pelvis during this 5-year period (Figure 1). The ribs were similarly affected. Radiographs of the calvarium, hands, proximal femora, and knees were unremarkable. Magnetic resonance imaging showed an L5-S1 herniated nucleus pulposus but no marrow changes. Dual-energy X-ray absorptiometry documented markedly elevated bone mineral density in the lumbar spine but normal density in the hip (Table 2).
Figure 1. (A) Radiograph of the lateral lumbar spine in 1998 showing marked diffuse osteosclerosis with prominent and coarse trabeculae involving not only vertebral bodies but also posterior spinal elements. Vertebral endplates and cortices of the posterior elements are also thickened. Osteophytes are present. Ossification affects the anterior longitudinal ligament (arrow). (B) Radiograph of the anteroposterior pelvis in 1998 showing diffuse osteosclerosis with a coarsened trabecular pattern throughout the lower lumbar spine and pelvic bones. The cortices of the pelvic bones and proximal femur are relatively spared.
* At these times, measurements were taken using QDR-2000 (Hologic, Inc., Waltham, Massachusetts): for lumbar spine, results are L1–L4, and hip studies pertain to total hip.
† At these times, measurements were taken using Excell (Norland Medical Systems, Fort Atkinson, Wisconsin); for lumbar spine, results are L2–L4, and hip studies pertain to femoral neck.
Hemogram values; serum calcium, phosphate, parathyroid hormone, alkaline phosphatase, 25-hydroxyvitamin D, and creatinine levels; and results of protein electrophoresis were unremarkable. The erythrocyte sedimentation rate was 18 mm/h (reference, <30 mm/h). Test results for antibodies to hepatitis C virus were negative.
Skeletal discomfort intensified during the subsequent year, and included new neck and scapular pain and elbow and knee arthralgias. Bone and joint pains, acquired axial osteosclerosis, well water, soap manufacturing, and periodontal disease suggested skeletal fluorosis. Results of iliac crest marrow aspiration and biopsy were consistent with this disorder, and showed normocellular marrow, markedly thickened cortical and trabecular bone, and increased osteoid seam wall thickness. A 24-hour urine collection contained substantial amounts of fluoride at 14 mg/g creatinine, verified at 19 mg/g creatinine (reference, <3 mg/g creatinine) (Figure 2).
Figure 2. Fluoride levels in 24-hour urine collections were markedly elevated and consistent with skeletal fluorosis9 during consumption of instant tea prepared using unfiltered well water. However, correction came only after tea drinking stopped. The bottom shaded area depicts the normal range (<3 mg fluoride/g creatinine).
The patient had begun use of unfiltered well water in 1989. The 2.8 ppm (mg/L) fluoride level reported for water from her tap did not exceed the Environmental Protection Agency (EPA) limit of 4.0 ppm.3 and 4 She had always brushed with fluoridated toothpaste, and for 6 months she had used fluoride-containing mouthwash, but neither dentifrice was intentionally swallowed. There was no exposure to pesticides or fertilizers. She did not drink mineral water or wine, live near a mine, and rarely used Teflon-coated pots. However, 3 months after relocating to where well filtration produced 0.24 ppm of fluoride at the tap (World Health Organization guideline limit, 1.5 ppm),2 urinary fluoride levels decreased little to 13 mg/g creatinine (Figure 2).
Then, the patient reported drinking 1 to 2 gallons of
double-strength instant tea (Lipton; Unilever Bestfoods North America, Englewood
Cliffs, New Jersey) throughout the day during her entire adult life. Her husband
consumed none. In 1991, she switched to the decaffeinated form of the product.
We verified the recipe (1 full measuring cup for each gallon of water). The
first well’s unfiltered water provided approximately 11 to 22 mg of fluoride
daily, which was sufficient to cause mild skeletal fluorosis. However, analysis
of a regular-strength preparation of the instant tea in distilled water using
ion chromatography (St. Louis Testing Laboratories, Inc.; St. Louis, Missouri)
showed a fluoride concentration of 3.3 ppm. Hence, her beverage contained an
additional 26 to 52 mg of fluoride each day from tea. Total fluoride exposure
was 37 to 74 mg per day.
In 1999, her spine and hip density had increased slightly (Table 2). She then switched to lemonade. Soon after, urine fluoride levels nearly corrected at 3.3 mg/g creatinine (Figure 2).
In 2000, her urine fluoride level was 2.4 mg/g creatinine, but she still reported generalized aches accompanied by worse stiffness, especially in the shoulders, neck, back, and knees. Spine and hip density remained unchanged over the next 3 years (Table 2). However, by 2003 she felt completely well and urine fluoride level was 2.2 mg/g creatinine (Figure 2).
To better assess the fluoride levels in instant teas, we commissioned two independent testing laboratories (St. Louis Testing Laboratories, Inc., St. Louis, Missouri; and Kiesel Environmental Laboratories, St. Louis, Missouri), each using ion-specific electrodes with known additions methodology,15 to assay 10 brand-name products purchased at a local supermarket. The teas were made on separate occasions at regular strength per label directions and using distilled water.
Mean fluoride concentrations in the tea solutions (Table 3) ranged from 1.0 to 6.5 ppm. One preparation exceeded the EPA safety limit of 4.0 ppm for drinking water3 and 4 and several surpassed the Food and Drug Administration (FDA) limit of 1.4 to 2.4 ppm for bottled beverages.16
ppm = parts per million. * Prepared regular strength, using distilled water containing <0.1 ppm of fluoride, according to label directions. Assayed in duplicate using separate preparations and ion-specific electrode with known additions methodology.15
Manufacturers for the commercial preparations are as follows: Lipton (Unilever
Bestfoods North America, Englewood Cliffs, New Jersey), Nestea (Nestlé USA,
Inc., Glendale, California), Schnucks (Schnuck Markets, Inc., St. Louis,
Missouri), AriZona (AriZona Beverage Co., Lake Success, New York), and Luzianne
(Reily Foods Co., New Orleans, Louisiana). † Laboratory 1 = St. Louis Testing Laboratories, St. Louis, Missouri; Laboratory 2 = Kiesel Environmental Laboratories, St. Louis, Missouri.
‡ Mean of four determinations (duplicate in both laboratories).
Adults typically consume <0.5 mg of fluoride daily in food.1 Water fluoridation increases intake by about 1 mg/d.1 At least 80% of ingested fluoride is absorbed from the gastrointestinal tract: about 50% enters the skeleton primarily as fluoroapatite crystals and the remainder appears in the urine.1 and 9 About 99% of endogenous fluoride sequesters in calcified tissues,1 where it can enhance osteoblast action, but toxicity produces brittle, dense bones.9, 10 and 11 Skeletal fluorosis causes axial skeletal pain and occasionally spinal rigidity with kyphosis.9 Ligament ossification may compress the spinal cord.17 Painful lower limbs can reflect microfractures.18 Axial osteosclerosis, exostoses, periostitis, and pelvis ligament calcification are typical radiographic findings.9 Osteomalacia can be anticipated on histopathology.9, 10 and 11
There is no established treatment for skeletal fluorosis.9 Calcium and vitamin D supplementation might mineralize or prevent excessive osteoid production.1 and 19 Oral calcium can diminish bone resorption, perhaps by reducing parathyroid hormone secretion,19 but may not block gut absorption of fluoride.20
Intake of at least 10 mg of fluoride daily for 10 years seems
necessary for “preclinical skeletal fluorosis”.1
Accordingly, this exposure is the “no-observed-adverse-effect level” for adults.1
The EPA’s National Primary Drinking Water Regulations stipulate a maximum
contaminant level for fluoride of 4.0 ppm, calculated from the lowest effect
level for crippling skeletal fluorosis of 20 mg/d with continuous exposure for
at least 20 years.1 and 3 Accordingly, the Public Health Service regulates community water fluoridation to prevent dental caries, stipulating optimum levels ranging from 0.7 to 1.2 ppm depending on average air temperature.1 and 21
There are few reports of skeletal fluorosis in the United States.1 However, screening for osteoporosis with dual-energy X-ray absorptiometry has increased the detection of hyperdense skeletons. Our patient manifested the aches and joint stiffness associated with skeletal fluorosis.9 Nonetheless, the little calcification of ligaments or tendons and few exostoses despite marked axial osteosclerosis were atypical.1 and 9
The region where she lived—Missouri—is not endemic for fluorosis,22 and the fluoride level (2.8 ppm) in the water from the first well did not exceed safety limits. Therefore, the elevated level of fluoride in her urine was at first puzzling. When water filtration was not the remedy, the discovery of her excessive consumption of instant tea and the substantial amount of fluoride in some commercial formulations led us to suspect involvement of these two factors. Indeed, the high urinary fluoride levels were corrected upon stopping the intake of instant tea, and skeletal symptoms resolved several years later. The absence of radiographic osteosclerosis in 1993, despite nearly lifelong consumption of instant tea, remains unexplained. Decaffeinated tea can contain twice the fluoride of regular tea,1 and 7 and she had begun drinking decaffeinated tea 7 years before her referral. However, our assays indicated little difference between these products (Table 3). In fact, caffeine may enhance fluoride absorption.1 The fluoride in the water from the first well may have unmasked her bone disease, or the calcium supplementation for 4 years may have mineralized excessive skeletal matrix.9 and 11 Alternatively, fluoride levels in the instant tea may have increased. Others have reported a concentration of 1.0 ppm for this product in 1996.7 Fluoride levels in tea vary due to factors such as growing region and season at harvest,7 which may explain the different amounts of fluoride that we found between the 1999 and 2003 formulations of Lipton nondecaffeinated instant tea.
Although our patient’s pains resolved over several years
after she stopped drinking instant tea, absorptiometry showed no decrement in
bone mineral density. It is not known whether this osteosclerosis is reversible.23 The half-life of fluoride in adult skeletons averages 7 years, and increases with advanced age.9
Daily ingestion of 1 to 2 mg of fluoride reduces dental caries in children.1 In adults, daily consumption of 3 mg for women and 4 mg for men is considered adequate intake to prevent tooth decay.1 Bone mineral density is enhanced in habitual tea drinkers.1 and 24 Accordingly, fluoride in tea seems to have beneficial effects where water fluoride levels are low. Brewed tea reportedly contains 1 to 6 ppm of fluoride, depending in part on the water source and brewing time.1 and 6 Our results were similar for instant teas using distilled water. Nevertheless, the effect of fluoridation on bone health remains controversial.10 and 23
In 2001, one investigation found that ≥4.32 ppm of fluoride in drinking water
increased hip and overall fractures among subjects in rural China.25
Preference for various commercial drinks is diminishing per capita consumption of tap water.1 Our concern is that skeletal fluorosis might result from drinking instant teas, especially when excessive volumes in hot environments or extra-strength preparations are consumed, or when fluoridated or fluoride-contaminated water is used.5, 7 and 23 FDA requirements for bottled beverages or water packaged in the United States stipulate against fluoride levels in excess of 1.4 to 2.4 ppm, depending on the annual average maximum daily air temperature where the products are sold.16 The catechins (antioxidant flavonoids),26 phytoestrogens, and other components found in tea are reported to have beneficial effects.13, 14 and 27 Our encounter with this patient calls for better understanding of the amounts and systemic effects of fluoride in various teas.
The authors thank Eileen Sweeso, RN, who skillfully organized clinical studies, and Becky Whitener, CPS, who provided expert secretarial help.
1Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride,
National Academic Press, Washington, D.C (1997), pp. 288–313.
2 World Heath Organization, Guidelines For Drinking Water Quality: Volume 1. Recommendations (2nd ed), World Health Organization, Geneva, Switzerland (1993), p. 47.
3 U.S. Environmental
Protection Agency: Ground water and drinking water— current drinking water
standards. Available at: http://www.epa.gov/safewater/mcl.html. Accessed January 20, 2004.
4National Research Council Subcommittee on Health Effects of Ingested Fluoride Health Effects of Ingested Fluoride, National Academy Press, Washington, D.C (1993).
5 S.C. Lung, P.K. Hsiao and K.M. Chiang, Fluoride concentrations in three types of commercially packed tea drinks in Taiwan, J Expo Anal Environ Epidemiol13
(2003), pp. 66–73.
6 S.H. Wei, F.N. Hattab and J.R. Mellberg, Concentration of fluoride and selected other elements in teas, Nutrition5
(1989), pp. 237–240.
7 J.T. Chan and S.H. Koh, Fluoride content in caffeinated, decaffeinated and herbal teas, Caries Res30
(1996), pp. 88–92.
8 J. Cao, Y. Zhao and J. Liu et al., Brick tea fluoride as a main source of adult fluorosis, Food Chem Toxicol41
(2003), pp. 535–542.
9 K.A. Krishnamachari, Skeletal fluorosis in humans a review of recent progress in the understanding of the disease, Prog Food Nutr Sci10
(1986), pp. 279–314.
10 G.M. Whitford, Acute and chronic fluoride toxicity, J Dent Res71
(1992), pp. 1249–1254.
11 D. Kuntz, Fluoride therapy in osteoporosis the tide is ebbing, Rev Rheum Engl Ed66
(1999), pp. 67–69.
12 United States Department of Agriculture Economic Research Service. Food Consumption (Per Capita) Data System. Available at: http://ers.usda.gov/Data/FoodConsumption/DataSystem.asp?ERSTab=3. Accessed September 16, 2004.
Hollingsworth, It’s tea time, Food Technol56 (2002), p. 16.
14 L.A. Mitscher and V. Dolby,
The Green Tea Book China’s Fountain of Youth, Avery Publishing Group, Garden City Park, New York (1998).
15 In: L.S. Cresceri, A.E. Greenberg and A.D. Eaton, Editors, Standard Methods for the Examination of Water and Wastewater (20th ed), American Public Health Association, the American Water Works Association and the Water Environment Federation, Washington, D.C (1998).
16 United States Food and Drug Administration. Department of Health and Human Services, Bottled Water
(2003) (codified at 21 CFR §165.110)..
17 R.K. Gupta, P. Agarwal and S. Kumar et al., Compressive myelopathy in fluorosis MRI, Neuroradiology38
(1996), pp. 338–342.
18 C.M. Schnitzler, J.R. Wing and K.A. Gear et al., Bone fragility of the peripheral skeleton during fluoride therapy for osteoporosis, Clin Orthop261
(1990), pp. 268–275.
19 B.A. Dure-Smith, S.M. Farley and S.G. Linkhart et al., Calcium deficiency in fluoride-treated osteoporotic patients despite calcium supplementation, J Clin Endocrinol Metab81
(1996), pp. 269–275.
20 H. Spencer, D. Osis and L. Kramer et al., Effect of calcium and phosphorus on fluoride metabolism in man, J Nutr105
(1975), pp. 733–740.
21 Public Health Service Committee to Coordinate Environmental Health and Related Programs, Review of Fluoride Benefits and Risk, U.S. Department of Health and Human Services, Public Health Service, Washington, D.C (1991).
22 A.J. Felsenfeld and M.A. Roberts, A report of fluorosis in the United States secondary to drinking well water, JAMA265
(1991), pp. 486–488.
23 B. Allolio and R. Lehmann, Drinking water fluoridation and bone, Exp Clin Endocrinol Diabetes107
(1999), pp. 12–20.
24 C.H. Wu, Y.C. Yang, W.J. Yao, F.H. Lu, J.S. Wu and C.J. Chang, Epidemiological evidence of increased bone mineral density in habitual tea drinkers, Arch Intern Med162
(2002), pp. 1001–1006.
25 Y. Li, C. Liang and C.W. Slemenda et al., Effect of long-term exposure to fluoride in drinking water on risks of bone fractures, J Bone Miner Res16
(2001), pp. 932–939.
26 M. Kimura, K. Umegaki and Y. Kasuya et al., The relation between single/double or repeated tea catechin ingestions and plasma antioxidant activity in humans, Eur J Clin Nutr56
(2002), pp. 1186–1193.
27 D.L. McKay and J.B. Blumberg, The role of tea in human health an update, J Am Coll Nutr21
(2002), pp. 1–13.
Supported in part by The Clark and Mildred Cox Inherited Metabolic Bone Disease Research Fund.
Requests for reprints should be addressed to: Michael P. Whyte, MD, Division of Bone and Mineral Diseases, Barnes-Jewish Hospital (North Campus), 660 South Euclid, Box 8301, St. Louis, Missouri 63110.