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Silicate Nephrolithiasis After Ingestion of Supplements Containing Silica Dioxide
Silicate Nephrolithiasis After Ingestion of Supplements Containing Silica Dioxide Jennifer E. Flythe, MD,1 Jose F. Rueda, MD,2 Michael K. Riscoe, PhD,3 and Suzanne Watnick, MD1,2 Silicate calculi are common in some mammals, such as dogs and sheep, but extremely rare in humans. We report a case of silicate calculi in a woman using oral over-the-counter Uncaria tomentosa, Digestive Advantage and FlexProtex supplements. All 3 contained the excipient silica dioxide. Stone analysis showed composition of 100% silicate. The nephrolithiasis promptly abated after discontinuation of the products containing silica, then returned when the patient restarted her supplements. This case emphasizes the importance of stone analysis when obvious causes of nephrolithiasis are unclear and highlights the concerns of using over-the-counter supplements without substantial oversight. Am J Kidney Dis 54:127-130. © 2009 by the National Kidney Foundation, Inc. INDEX WORDS: Silicate; silica; nephrolithiasis; over-the-counter supplements.
S
ilicate calculi are relatively common in some mammals, such as dogs and sheep,1-3 with stones containing greater than 70% silicate accounting for 1% of those submitted to a canine urolith center.2 There are fewer than 50 case reports in the literature of silicate stones in humans. All cases showed a clear precipitant through ingestion of silicate material. Just as there is a correlation between dietary intake of calcium, oxalate, phosphate and urinary excretion of these substances, there is a relationship between silica ingestion and urinary excretion.4,5 Long-term ingestion of the antacid magnesium trisilicate has been linked to silicate stone formation in multiple cases.4,6-13 Renal silicate calculi caused by silicate-containing milk thickener in Japanese infants have been reported more recently.14,15 Others16,17 described cases of silicate urolithiasis without magnesium trisilicate ingestion, raising the question of whether silicate presence in urinary stones is more common than appreciated. We report a case of silicate calculi in a woman using oral over-the-counter Uncaria tomentosa (cat’s claw) supplement for chronic Lyme disease, Digestive Advantage (Ganeden Biotech, Mayfield Heights, OH) supplement for irritable bowel syndrome, and FlexProtex (Nutracea, Phoenix, AZ), a glucosamine and rice bran derivative supplement for joint pain. All 3 contained silica dioxide.
CASE REPORT A 38-year-old white woman was referred to our nephrology clinic for episodic left flank pain associated with reported passage of urinary gravel-like sediment. The first episode of pain with urinary sediment occurred 6 months
before presentation. She initially was evaluated in the emergency department, where she had a normal intravenous pyelogram result. Medical history was significant for Lyme disease, osteoarthritis, gallstones, and irritable bowel syndrome. She had no history of pyelonephritis, hypercalcemia, or gout. Dietary history showed a diet of cereal, fruits, yogurt, occasional red meat, and nuts. Medications included cefuroxime, oxycodone, vitamin B12 injections, methocarbamol, and ibuprofen. Family history was significant for a sister with nephrolithiasis of unknown cause. The patient denied alcohol and tobacco use and performed office work for the family company. She had no known contact with other chemicals. On physical examination, she was a well-appearing woman with blood pressure of 110/64 mm Hg, pulse of 74 beats/ min, temperature of 98.1°F (36.7°C), weight of 115 lbs, and height of 60 inches. Neck, lung, cardiac, abdominal, and extremity examination findings were normal. She had no flank tenderness or skin rash. On laboratory evaluation, serum calcium, phosphorus, uric acid, creatinine, serum carbon dioxide, and parathyroid hormone values were within normal limits. Urinalysis was significant for trace protein, pH 5.0, specific gravity of 1.010, and moderate blood on dipstick. Microscopy showed 0 to 1 white blood cells; no red blood cells, casts, or crystals; and otherwise was within normal limits. A noncontrast helical computed tomographic
From the 1Division of Hospital and Specialty Medicine, Portland VA Medical Center; 2Division of Nephrology and Hypertension, Department of Medicine, Oregon Health & Science University; and 3Research and Development Service, Portland VA Medical Center, Portland, OR. Received August 8, 2008. Accepted in revised form October 29, 2008. Originally published online as doi: 10.1053/j.ajkd.2008.10.042 on December 22, 2008. Address correspondence to Suzanne Watnick, MD, P3NEPH, Portland Veterans Affairs Medical Center, 3710 SW U.S. Veterans Hospital Rd, Portland, OR 97239. E-mail: [email protected] © 2009 by the National Kidney Foundation, Inc. 0272-6386/09/5401-0019$36.00/0 doi:10.1053/j.ajkd.2008.10.042
American Journal of Kidney Diseases, Vol 54, No 1 (July), 2009: pp 127-130
127
128
Flythe et al
scan of the abdomen and pelvis with stone protocol showed no evidence of stones. Her 24-hour urine studies of oxalate, citric acid, calcium, phosphorous, and qualitative cystine were unremarkable (Table 1). Quantitative urine cystine was normal at 140 mol/L/g of creatinine. Urine volume was low during the first collection and adequate during the second. She was advised to increase her fluid intake and strain her urine. Symptoms of flank pain and gravel-like urine sediment recurred. The first specimen was dark brown and tan and weighed less than 10 mg. Stone composition was 100% silicate. The second specimen, submitted 4 months later, was brown and tan and weighed 20 mg. Analysis showed 100% silicate composition (Fig 1). Another more extensive review of medications and diet was performed. She denied long-term use of antacids, ingestion of colloidal silicate, use of milk thickeners, and consumption of magnesium trisilicate. However, she was using several over-the-counter supplements. Supplements included vitamin C, calcium, glutamine, natural gelatin, Chinese herbal “neck formula,” FlexProtex, Digestive Advantage, and Uncaria tomentosa. The latter 3 listed silica dioxide as an ingredient. She reported ingesting 4 capsules of FlexProtex daily, 1 capsule of Digestive Advantage daily, and 2 capsules of Uncaria tomentosa thrice daily for 2 years. She was advised to stop using the supplements, and the flank pain and urinary gravel resolved. These symptoms returned after she restarted the supplements. An independent laboratory then analyzed individual capsules to quantify the silicon composition. Combustion analysis showed that the supplements each contained less than 2% silicon in the form of silicon dioxide. The FlexProtex capsule contained 1.96% silicon as silicon dioxide, the Digestive Advantage capsule contained 1.47% silicon as silicon dioxide, and the Uncaria tomentosa capsule contained 1.47% silicon as silicon dioxide (Table 2). Of note, the Digestive Advantage was found to contain more than 3 times the amount of silicon as silicon dioxide than reported in the product literature. Based on analysis of the capsules, lack of other silica dietary source, interval resolution of nephrolithiasis with discontinuation, and recurrence with resumption of supplements, we concluded that the supplements were the most likely origin of the silicate calculi.
Table 1. Twenty-four–Hour Urine Results
Urine total volume (L/24 h) Urine pH Urine oxalate (mg/24 h) Urine citrate (mg/24 h) Urine calcium (mg/24 h) Urine uric acid (mg/24 h) Urine creatinine (mg/24 h) Urine phosphorus (mg/24 h) Qualitative cystine
First Analysis
Second Analysis (5 mo later)
0.71 6.7 13.7 583 143.4 342.2 710 582 Negative
2.36 6.3 33.2 1,086 92 358.7 920 873 Negative
Figure 1. Silicate stones. Each is approximately 3 mm long, with total weight of 20 mg, displacing less than 0.1 mL of distilled water.
DISCUSSION Silicon is the second most abundant element in the earth’s crust, comprising 26% of its weight.18 In addition to its presence in rocks, sand, and metals, silica is found in plant-based foods and beverages, seafood, and many food and pharmaceutical additives.19 After ingestion and interaction with gastric acid, silica hydroxide precipitates into a gel and colloid. Colloid byproducts are absorbed across the intestinal wall and excreted in urine. Estimates of silica absorption range from 20% to 75%, depending on the compound’s solubility.20 Silica is excreted through the urinary system at a rate of approximately 10 to 16.2 mg/24 h and can increase excretion with increased ingestion.4,5,7,21 As with other absorbed and excreted substances, such as calcium, oxalate, and phosphate, silica can result in urinary calculi, although this is a rare phenomenon. Ingestion of magnesium trisilicate and silicate-containing milk thickeners are causes of silicate urolithiasis.14,15 The urinary excretion rate can reach 500 mg/d in such patients.22 Previously, silica in supplements and pharmaceutical products was believed to have low bioavailability and be virtually inactive. This case shows this might not be true. Now silicon is a
Silicate Nephrolithiasis
129 Table 2. Supplement Composition
Actual Ingestion Silicon as Silicon Dioxide Product Recommended Dose Over 2 y (mg Capsule (%; calculated by Silicon as Silicon Over 2 y (mg silicon as silicon silicon as silicon Weight (mg) combustion analysis) Dioxide/Capsule (mg) dioxide) dioxide)
Uncaria tomentosa FlexProtex Digestive Advantage Totals
20 550 305
1.10 1.96 1.47
primary ingredient in several over-the-counter supplements. Some homeopathic websites tout silica as a remedy for skin infections to splinters, sore throats, menopause, fatigue, acne, and insomnia.23,24 As more health benefits of silica are reported, more individuals may start using silica supplements. A recent report heralds the potential health benefits of silica in bone health, atherosclerosis, and Alzheimer disease.18 Silicon levels in perishable products are regulated by the Food and Drug Administration (FDA). The FDA relies on the no observed adverse effects level and the derived maximum recommended starting dose as benchmarks of safety for pharmaceutical ingredients. The no observed adverse effects level for dietary silica is 50,000 ppm (mg/L), which is equivalent to 2,500 mg/kg body weight daily for a rodent.18 The upper safety level for a 70-kg human man is 1,750 mg/d.18 Our patient was ingesting a minimum of 50 mg/d, a level less than the upper safety limit. Such excipients as silica dioxide in over-the-counter drug products are subject to FDA standards; however, requirements are not specific. FDA requirements for such excipients are found in 21 CFR 330.1(e): “The product contains only suitable inactive ingredients which are safe in the amounts administered. . . .”25-27 The findings of this case argue that silica is not as inert as previously presumed; the FDA may want to consider additional restrictions for silica contents in supplements. This report discusses the case of a 38-year-old woman with silicate nephrolithiasis after ingestion of silica dioxide found in over-the-counter supplements. This emphasizes the importance of stone analysis when obvious causes of nephrolithiasis are unclear. This also highlights the concerns of using supplements without substantial oversight. Although the patient was ingesting amounts of silicate well within the current safety
0.22 10.78 4.48
165.00 31,477.60 3,270.40 34,913.00
963.60 31,477.60 3,270.40 35,711.60
guidelines, she developed silicate stones. This case raises the question of whether some people have a greater propensity toward silicate stone formation. Did her diet contain other significant silicate? Is she a rapid silicate absorber or slow metabolizer? Does her urinary system have structural or biochemical aspects that predispose her to silicate stone formation? As silicon gains popularity as a stand-alone supplement, such unintended consequences as silicate urinary stones may increase.
ACKNOWLEDGEMENTS Support: None. Financial Disclosure: None.
REFERENCES 1. Legendre AM: Silica urolithiasis in a dog. J Am Vet Med Assoc 168:418-419, 1976 2. Osborne CA, Jacob F, Lulich JP, et al: Canine silica urolithiasis: Risk factors, detection, and treatment. Vet Clin North Am Small Anim Pract 29:213-230, 1999 3. Keeler RF: Silicon metabolism and silicon-protein matrix interrelationship in bovine urolithiasisis. Ann NY Acad Sci 104:592-611, 1963 4. Page RC, Heffner RR, Frey A: Urinary excretion of silica in humans following oral administration of magnesium trisilicate. Am J Dig Dis 8:13-15, 1941 5. Dobbie JW, Smith MJB: Urinary and serum silicon in normal and uraemic individuals. Ciba Found Symp 121:194213, 1986 6. Irisawa C, Suzuki K, Nakagawa H, et al: Silicate urolithiasis: A case report [Japanese]. Acta Urol Jpn 37:267271, 1991 7. Farrer JH, Rajfer J: Silicate urolithiasis. J Urol 132:739740, 1984 8. Lee MH, Lee YH, Hsu TH, Chen MT, Chang LS: Silica stone development due to long time oral trisilicate intake. Scand J Urol Nephrol 27:267-269, 1993 9. Herman JR, Goldberg AS: New type of urinary calculus caused by antacid therapy. JAMA 174:1206-1207, 1960 10. Lagergren C: Development of silica calculi after oral administration of magnesium trisilicate. J Urol 87:994-999, 1962 11. Haddad FS, Kouyoumdjian A: Silica stones in humans. Urol Int 41:70-76, 1986
130 12. Joekes AM, Rose AG, Sutor J: Multiple renal silica calculi. Br Med J 1:146-147, 1973 13. Levison DA, Banim S, Crocker P, et al: Silica stones in the urinary bladder. Lancet 8274:704-705, 1982 14. Nishizono T, Eta S, Enokida H, Nishiyama K, Kawahara M, Nakagawa M: Renal silica calculi in an infant. Int J Urol 11:119-121, 2004 15. Ulinski T, Sabot F, Bourlon I, Cochat P: Bilateral urinary calculi after treatment with a silicate-containing milk thickener. Eur J Pediatr 163:239-240, 2004 16. Kim KM, Johnson DR: Siliceous deposits in human urinary calculi—An E. M. Study. Urol Res 11:155-158, 1983 17. Ichiyanagi O, Sasagawa I, Adachi Y, Suzuki H, Kubota Y, Nakada T: Silica urolithiasis without magnesium trisilicate intake. Urol Int 61:39-42, 1998 18. Martin KR: The chemistry of silica and its potential health benefits. J Nutr Health Aging 11:94-97, 2007 19. Pennington J: Silicon in foods and diets. Food Addit Contam 8:97-118, 1991 20. Burns L, Ashwell M, Berry J, et al: UK Food Standards Agency optimal nutrition status workshop: Environmental factors that affect bone health through life. Br J Nutr 89:835-840, 2003 21. King EJ, Stantial H: The biochemistry of silicic acid. Biochem J 27:990-1001, 1933
Flythe et al 22. Menon M, Parulkar BG, Drach GW: Urinary lithiasis: Etiology, diagnosis, and medical management, in Walsh PC, Retik AB, Vaughan ED, Wein AD (eds): Campbells’s Urology, Vol 3 (ed 7). Philadelphia, PA, Saunders, 1998, ch 91, PP 2661-2733 23. 1-800 Homeopathy.com. Silica (silicon dioxide). Available at: http://www.1-800homeopathy.com/products/ details.html?productid⫽SILD. Accessed October 24, 2008 24. PCC Natural Markets.com. Homeopathic remedy silicea (silica). Available at: http://www.pccnaturalmarkets. com/health/Homeo_Homeoix/Silicea.htm. Accessed October 24, 2008 25. FDA: US Food and Drug Administration Center for Food Safety and Applied Nutrition: Dietary Supplement Health and Education Act of 1994. Available at: http:// www.cfsan.fda.gov/⬃dms/dietsupp.html. Accessed October 24, 2008 26. National Institute of Health Office of Dietary Supplements. Dietary supplements: Background information. Available at: http://www.ods.od.nih.gov/Health_Information/ Health_Information.aspx. Accessed October 24, 2008 27. National Institute for Health National Center for Complementary and Alternative Medicine. Herbal supplements: Consider safety, too. Available at: http://nccam.nih. gov/health/supplement-safety/. Accessed October 24, 2008
S
ilicate calculi are relatively common in some mammals, such as dogs and sheep,1-3 with stones containing greater than 70% silicate accounting for 1% of those submitted to a canine urolith center.2 There are fewer than 50 case reports in the literature of silicate stones in humans. All cases showed a clear precipitant through ingestion of silicate material. Just as there is a correlation between dietary intake of calcium, oxalate, phosphate and urinary excretion of these substances, there is a relationship between silica ingestion and urinary excretion.4,5 Long-term ingestion of the antacid magnesium trisilicate has been linked to silicate stone formation in multiple cases.4,6-13 Renal silicate calculi caused by silicate-containing milk thickener in Japanese infants have been reported more recently.14,15 Others16,17 described cases of silicate urolithiasis without magnesium trisilicate ingestion, raising the question of whether silicate presence in urinary stones is more common than appreciated. We report a case of silicate calculi in a woman using oral over-the-counter Uncaria tomentosa (cat’s claw) supplement for chronic Lyme disease, Digestive Advantage (Ganeden Biotech, Mayfield Heights, OH) supplement for irritable bowel syndrome, and FlexProtex (Nutracea, Phoenix, AZ), a glucosamine and rice bran derivative supplement for joint pain. All 3 contained silica dioxide.
CASE REPORT A 38-year-old white woman was referred to our nephrology clinic for episodic left flank pain associated with reported passage of urinary gravel-like sediment. The first episode of pain with urinary sediment occurred 6 months
before presentation. She initially was evaluated in the emergency department, where she had a normal intravenous pyelogram result. Medical history was significant for Lyme disease, osteoarthritis, gallstones, and irritable bowel syndrome. She had no history of pyelonephritis, hypercalcemia, or gout. Dietary history showed a diet of cereal, fruits, yogurt, occasional red meat, and nuts. Medications included cefuroxime, oxycodone, vitamin B12 injections, methocarbamol, and ibuprofen. Family history was significant for a sister with nephrolithiasis of unknown cause. The patient denied alcohol and tobacco use and performed office work for the family company. She had no known contact with other chemicals. On physical examination, she was a well-appearing woman with blood pressure of 110/64 mm Hg, pulse of 74 beats/ min, temperature of 98.1°F (36.7°C), weight of 115 lbs, and height of 60 inches. Neck, lung, cardiac, abdominal, and extremity examination findings were normal. She had no flank tenderness or skin rash. On laboratory evaluation, serum calcium, phosphorus, uric acid, creatinine, serum carbon dioxide, and parathyroid hormone values were within normal limits. Urinalysis was significant for trace protein, pH 5.0, specific gravity of 1.010, and moderate blood on dipstick. Microscopy showed 0 to 1 white blood cells; no red blood cells, casts, or crystals; and otherwise was within normal limits. A noncontrast helical computed tomographic
From the 1Division of Hospital and Specialty Medicine, Portland VA Medical Center; 2Division of Nephrology and Hypertension, Department of Medicine, Oregon Health & Science University; and 3Research and Development Service, Portland VA Medical Center, Portland, OR. Received August 8, 2008. Accepted in revised form October 29, 2008. Originally published online as doi: 10.1053/j.ajkd.2008.10.042 on December 22, 2008. Address correspondence to Suzanne Watnick, MD, P3NEPH, Portland Veterans Affairs Medical Center, 3710 SW U.S. Veterans Hospital Rd, Portland, OR 97239. E-mail: [email protected] © 2009 by the National Kidney Foundation, Inc. 0272-6386/09/5401-0019$36.00/0 doi:10.1053/j.ajkd.2008.10.042
American Journal of Kidney Diseases, Vol 54, No 1 (July), 2009: pp 127-130
127
128
Flythe et al
scan of the abdomen and pelvis with stone protocol showed no evidence of stones. Her 24-hour urine studies of oxalate, citric acid, calcium, phosphorous, and qualitative cystine were unremarkable (Table 1). Quantitative urine cystine was normal at 140 mol/L/g of creatinine. Urine volume was low during the first collection and adequate during the second. She was advised to increase her fluid intake and strain her urine. Symptoms of flank pain and gravel-like urine sediment recurred. The first specimen was dark brown and tan and weighed less than 10 mg. Stone composition was 100% silicate. The second specimen, submitted 4 months later, was brown and tan and weighed 20 mg. Analysis showed 100% silicate composition (Fig 1). Another more extensive review of medications and diet was performed. She denied long-term use of antacids, ingestion of colloidal silicate, use of milk thickeners, and consumption of magnesium trisilicate. However, she was using several over-the-counter supplements. Supplements included vitamin C, calcium, glutamine, natural gelatin, Chinese herbal “neck formula,” FlexProtex, Digestive Advantage, and Uncaria tomentosa. The latter 3 listed silica dioxide as an ingredient. She reported ingesting 4 capsules of FlexProtex daily, 1 capsule of Digestive Advantage daily, and 2 capsules of Uncaria tomentosa thrice daily for 2 years. She was advised to stop using the supplements, and the flank pain and urinary gravel resolved. These symptoms returned after she restarted the supplements. An independent laboratory then analyzed individual capsules to quantify the silicon composition. Combustion analysis showed that the supplements each contained less than 2% silicon in the form of silicon dioxide. The FlexProtex capsule contained 1.96% silicon as silicon dioxide, the Digestive Advantage capsule contained 1.47% silicon as silicon dioxide, and the Uncaria tomentosa capsule contained 1.47% silicon as silicon dioxide (Table 2). Of note, the Digestive Advantage was found to contain more than 3 times the amount of silicon as silicon dioxide than reported in the product literature. Based on analysis of the capsules, lack of other silica dietary source, interval resolution of nephrolithiasis with discontinuation, and recurrence with resumption of supplements, we concluded that the supplements were the most likely origin of the silicate calculi.
Table 1. Twenty-four–Hour Urine Results
Urine total volume (L/24 h) Urine pH Urine oxalate (mg/24 h) Urine citrate (mg/24 h) Urine calcium (mg/24 h) Urine uric acid (mg/24 h) Urine creatinine (mg/24 h) Urine phosphorus (mg/24 h) Qualitative cystine
First Analysis
Second Analysis (5 mo later)
0.71 6.7 13.7 583 143.4 342.2 710 582 Negative
2.36 6.3 33.2 1,086 92 358.7 920 873 Negative
Figure 1. Silicate stones. Each is approximately 3 mm long, with total weight of 20 mg, displacing less than 0.1 mL of distilled water.
DISCUSSION Silicon is the second most abundant element in the earth’s crust, comprising 26% of its weight.18 In addition to its presence in rocks, sand, and metals, silica is found in plant-based foods and beverages, seafood, and many food and pharmaceutical additives.19 After ingestion and interaction with gastric acid, silica hydroxide precipitates into a gel and colloid. Colloid byproducts are absorbed across the intestinal wall and excreted in urine. Estimates of silica absorption range from 20% to 75%, depending on the compound’s solubility.20 Silica is excreted through the urinary system at a rate of approximately 10 to 16.2 mg/24 h and can increase excretion with increased ingestion.4,5,7,21 As with other absorbed and excreted substances, such as calcium, oxalate, and phosphate, silica can result in urinary calculi, although this is a rare phenomenon. Ingestion of magnesium trisilicate and silicate-containing milk thickeners are causes of silicate urolithiasis.14,15 The urinary excretion rate can reach 500 mg/d in such patients.22 Previously, silica in supplements and pharmaceutical products was believed to have low bioavailability and be virtually inactive. This case shows this might not be true. Now silicon is a
Silicate Nephrolithiasis
129 Table 2. Supplement Composition
Actual Ingestion Silicon as Silicon Dioxide Product Recommended Dose Over 2 y (mg Capsule (%; calculated by Silicon as Silicon Over 2 y (mg silicon as silicon silicon as silicon Weight (mg) combustion analysis) Dioxide/Capsule (mg) dioxide) dioxide)
Uncaria tomentosa FlexProtex Digestive Advantage Totals
20 550 305
1.10 1.96 1.47
primary ingredient in several over-the-counter supplements. Some homeopathic websites tout silica as a remedy for skin infections to splinters, sore throats, menopause, fatigue, acne, and insomnia.23,24 As more health benefits of silica are reported, more individuals may start using silica supplements. A recent report heralds the potential health benefits of silica in bone health, atherosclerosis, and Alzheimer disease.18 Silicon levels in perishable products are regulated by the Food and Drug Administration (FDA). The FDA relies on the no observed adverse effects level and the derived maximum recommended starting dose as benchmarks of safety for pharmaceutical ingredients. The no observed adverse effects level for dietary silica is 50,000 ppm (mg/L), which is equivalent to 2,500 mg/kg body weight daily for a rodent.18 The upper safety level for a 70-kg human man is 1,750 mg/d.18 Our patient was ingesting a minimum of 50 mg/d, a level less than the upper safety limit. Such excipients as silica dioxide in over-the-counter drug products are subject to FDA standards; however, requirements are not specific. FDA requirements for such excipients are found in 21 CFR 330.1(e): “The product contains only suitable inactive ingredients which are safe in the amounts administered. . . .”25-27 The findings of this case argue that silica is not as inert as previously presumed; the FDA may want to consider additional restrictions for silica contents in supplements. This report discusses the case of a 38-year-old woman with silicate nephrolithiasis after ingestion of silica dioxide found in over-the-counter supplements. This emphasizes the importance of stone analysis when obvious causes of nephrolithiasis are unclear. This also highlights the concerns of using supplements without substantial oversight. Although the patient was ingesting amounts of silicate well within the current safety
0.22 10.78 4.48
165.00 31,477.60 3,270.40 34,913.00
963.60 31,477.60 3,270.40 35,711.60
guidelines, she developed silicate stones. This case raises the question of whether some people have a greater propensity toward silicate stone formation. Did her diet contain other significant silicate? Is she a rapid silicate absorber or slow metabolizer? Does her urinary system have structural or biochemical aspects that predispose her to silicate stone formation? As silicon gains popularity as a stand-alone supplement, such unintended consequences as silicate urinary stones may increase.
ACKNOWLEDGEMENTS Support: None. Financial Disclosure: None.
REFERENCES 1. Legendre AM: Silica urolithiasis in a dog. J Am Vet Med Assoc 168:418-419, 1976 2. Osborne CA, Jacob F, Lulich JP, et al: Canine silica urolithiasis: Risk factors, detection, and treatment. Vet Clin North Am Small Anim Pract 29:213-230, 1999 3. Keeler RF: Silicon metabolism and silicon-protein matrix interrelationship in bovine urolithiasisis. Ann NY Acad Sci 104:592-611, 1963 4. Page RC, Heffner RR, Frey A: Urinary excretion of silica in humans following oral administration of magnesium trisilicate. Am J Dig Dis 8:13-15, 1941 5. Dobbie JW, Smith MJB: Urinary and serum silicon in normal and uraemic individuals. Ciba Found Symp 121:194213, 1986 6. Irisawa C, Suzuki K, Nakagawa H, et al: Silicate urolithiasis: A case report [Japanese]. Acta Urol Jpn 37:267271, 1991 7. Farrer JH, Rajfer J: Silicate urolithiasis. J Urol 132:739740, 1984 8. Lee MH, Lee YH, Hsu TH, Chen MT, Chang LS: Silica stone development due to long time oral trisilicate intake. Scand J Urol Nephrol 27:267-269, 1993 9. Herman JR, Goldberg AS: New type of urinary calculus caused by antacid therapy. JAMA 174:1206-1207, 1960 10. Lagergren C: Development of silica calculi after oral administration of magnesium trisilicate. J Urol 87:994-999, 1962 11. Haddad FS, Kouyoumdjian A: Silica stones in humans. Urol Int 41:70-76, 1986
130 12. Joekes AM, Rose AG, Sutor J: Multiple renal silica calculi. Br Med J 1:146-147, 1973 13. Levison DA, Banim S, Crocker P, et al: Silica stones in the urinary bladder. Lancet 8274:704-705, 1982 14. Nishizono T, Eta S, Enokida H, Nishiyama K, Kawahara M, Nakagawa M: Renal silica calculi in an infant. Int J Urol 11:119-121, 2004 15. Ulinski T, Sabot F, Bourlon I, Cochat P: Bilateral urinary calculi after treatment with a silicate-containing milk thickener. Eur J Pediatr 163:239-240, 2004 16. Kim KM, Johnson DR: Siliceous deposits in human urinary calculi—An E. M. Study. Urol Res 11:155-158, 1983 17. Ichiyanagi O, Sasagawa I, Adachi Y, Suzuki H, Kubota Y, Nakada T: Silica urolithiasis without magnesium trisilicate intake. Urol Int 61:39-42, 1998 18. Martin KR: The chemistry of silica and its potential health benefits. J Nutr Health Aging 11:94-97, 2007 19. Pennington J: Silicon in foods and diets. Food Addit Contam 8:97-118, 1991 20. Burns L, Ashwell M, Berry J, et al: UK Food Standards Agency optimal nutrition status workshop: Environmental factors that affect bone health through life. Br J Nutr 89:835-840, 2003 21. King EJ, Stantial H: The biochemistry of silicic acid. Biochem J 27:990-1001, 1933
Flythe et al 22. Menon M, Parulkar BG, Drach GW: Urinary lithiasis: Etiology, diagnosis, and medical management, in Walsh PC, Retik AB, Vaughan ED, Wein AD (eds): Campbells’s Urology, Vol 3 (ed 7). Philadelphia, PA, Saunders, 1998, ch 91, PP 2661-2733 23. 1-800 Homeopathy.com. Silica (silicon dioxide). Available at: http://www.1-800homeopathy.com/products/ details.html?productid⫽SILD. Accessed October 24, 2008 24. PCC Natural Markets.com. Homeopathic remedy silicea (silica). Available at: http://www.pccnaturalmarkets. com/health/Homeo_Homeoix/Silicea.htm. Accessed October 24, 2008 25. FDA: US Food and Drug Administration Center for Food Safety and Applied Nutrition: Dietary Supplement Health and Education Act of 1994. Available at: http:// www.cfsan.fda.gov/⬃dms/dietsupp.html. Accessed October 24, 2008 26. National Institute of Health Office of Dietary Supplements. Dietary supplements: Background information. Available at: http://www.ods.od.nih.gov/Health_Information/ Health_Information.aspx. Accessed October 24, 2008 27. National Institute for Health National Center for Complementary and Alternative Medicine. Herbal supplements: Consider safety, too. Available at: http://nccam.nih. gov/health/supplement-safety/. Accessed October 24, 2008