Chapter 17 Hair Mineral Analysis
Introduction
In recent years, several attempts have been made to standardize HA testing techniques,1 but laboratories still do not have an agreement on procedures for handling a hair sample.2–4
HA has been used successfully to test for drug abuse,34–41 and studies have been performed in several locations examining the validity of using HA to test drug use before the reinstatement of driving licenses.42,43 However, drug metabolites are not found on most commercial HAs.
HA appears to offer potential as a correlating diagnostic tool in a few of the listed conditions, although hair mineral patterns should not be used exclusively for diagnosis. For example, the high hair sodium values in infants with cystic fibrosis show very little overlap with those in controls, and one study demonstrated that children with learning disabilities can be diagnosed with 98% accuracy because of a consistent pattern of high hair values of cadmium, manganese, and chromium in conjunction with low values of lithium and cobalt.5 The usefulness of HA as a research tool can hardly be questioned. However, significant controversy exists about using the method for the clinical diagnosis of diseases other than heavy metal toxicity and as an indicator of nutritional status. Moreover, multiple studies question the inter- and intra-laboratory accuracy of HA.44–48 The difference between research and clinical use is significant. Although it may be of interest in a research setting in which patients with various skin conditions have lower mean levels of hair magnesium than controls, the two groups overlap so much that the procedure is diagnostically useless.18 Moreover, even when an altered HA pattern was associated with a disease, generally there have been few investigations as to whether mineral supplementation would affect the clinical condition or even revert the hair mineral pattern to normal.
Wide overlap of values in disease and control groups is frequently the case with HA, resulting in excessive false-positives and false-negative results. For example, mentally retarded patients have been found to have lead, sodium, and potassium hair values approximately twice those of controls,13 but the standard deviations are extremely large for some minerals (for sodium, 1644.71 ± 1814.93 versus 744.43 ± 1987.0018; and for potassium, 870.15 ± 1009.19 versus 408.35 ± 689.99), and the large overlap greatly reduces the clinical use of HA. In addition, many of the altered HA patterns associated with the diseases previously listed are as yet unconfirmed.
Specific Minerals
Calcium and Magnesium
Hair calcium and magnesium values were found to be elevated in patients with fibromyalgia.49 High hair calcium content has been associated with a reduced risk of coronary heart disease.50 Low hair calcium content has been found in the last trimester of pregnancy,51 but hair calcium content increased in response to supplementation during pregnancy.52 Low hair magnesium levels have been reported in autistic children, children with attention deficit hyperactivity disorder, patients with various skin disorders, and patients with several types of leukemia, whereas high levels have been reported in conjunction with dyslexia and Prader-Willi syndrome.12,17,18,53–55 The meaning of these associations remains unknown for the most part.
A 2001 study concluded that analysis of hair calcium and phosphorus content was of value as a complementary detection tool in abnormalities of bone metabolism.56 Elevations in both calcium and magnesium were correlated with a low dietary calcium/magnesium ratio in one study, suggesting that this finding may be indicative of an induced hyperparathyroidism,57 but that hypothesis remains unproven. Hair calcium and magnesium also vary in response to the hardness and pH of the water in which the hair is usually washed.50 Supplementation of dietary magnesium has been reported to increase hair magnesium levels in deficient children.58 Nonetheless, in one study of congenital hypomagnesemia, researchers concluded that hair magnesium level was not a useful tool in monitoring mineral status because the values were higher in affected subjects than in subjects who were not deficient.59
Chromium
Hair chromium content is low in insulin-dependent diabetics,20 although there is much overlap with normal persons. Chromium levels decrease with age,22 but the meaning of this change remains unknown. Hair and tissue chromium levels vary greatly during pregnancy, being very high during the first few months of normal pregnancy and subsequently decreasing.60,61 Late in pregnancy, hair chromium content typically becomes low,62 suggesting deficiency.34 However, high hair chromium value in pregnancy is associated with low birth weight infants.63 In patients with gestational diabetes, hair chromium content is high early in pregnancy but decreases in late pregnancy.61 Increasing dietary intake of chromium has been linked to increasing hair chromium values,64 but supplemental chromium does not seem to alter hair levels.60,65
Copper
Oral contraceptive use is associated with decreased hair copper and increased serum copper.66 High hair copper levels are associated with being female, lactation, idiopathic scoliosis, and pregnancy in some, but not all, studies.67–70 Surprisingly, conditions that affect systemic copper status have been shown not to affect hair levels. Copper deficiency,71 Wilson’s disease,72,73 and cirrhosis74 do not significantly alter hair copper content. Hair copper levels also vary with geographic location.75 However, fur and liver copper values have been found to correlate in rats,74 and one study reported that supplemental copper raises hair copper levels.76 Hair color also has been found to influence the levels of copper in the hair.70,77
At this time, hair copper measurement appears unreliable for clinical application.67
Manganese
Levels of hair manganese in mothers of infants with congenital malformations and their offspring were significantly lower in one study,8 which may allow maternal hair manganese levels to be used as an indicator of the risk for malformations. Both nonsignificantly altered78 and normal levels of manganese79 have been reported in patients with epilepsy.78 Hair manganese values have been reported to be elevated in people with violent behavior, with varying levels of significance.79,80 Evidence that manganese supplementation affects behavior does not appear to exist at present.
Selenium
Levels of selenium in well water and hair show good correlation.81 High hair selenium levels are seen in toxicity,82,83 and low levels are seen in deficiency.84 Low hair selenium values have been reported in babies with neural tube defects and their mothers,9 as well as in patients with phenylketonuria.85 Tissue selenium values reflect short-term variations in intake,40 and hair levels of the element rise significantly after supplementation. 86–88
Sodium and Potassium
It is generally accepted, even by proponents of HA, that hair sodium and potassium do not reflect dietary status. High elevations of hair sodium may be diagnostic in cystic fibrosis,21 but require confirmation. A relatively low sodium/potassium ratio has been reported in celiac disease.88 Although many HA advocates cite low hair sodium and potassium as indicative of “adrenal exhaustion,” the only (preliminary) study exploring this subject reported that hair sodium and potassium did not correlate with adrenal function.89 Except for cystic fibrosis, hair sodium and potassium appear to hold little promise for clinical use.
Zinc
Hair zinc levels have received more research attention than any other mineral. Low hair zinc has been associated with zinc deficiency, anorexia nervosa, hyperactivity, gender, age, atherosclerosis, β-thalassemia, vegetarianism, lung cancer, leukemia, celiac disease, epilepsy in males, epilepsy in general, short stature in childhood, poverty, insulin-dependent diabetes mellitus, neural tube defects, and during pregnancy.* It also has been reported in neonates if the time between pregnancies is short.108
Because a few of these conditions have been associated with potential zinc deficiencies and supplemental zinc has been shown to increase hair zinc levels, practitioners who use HA often rely on hair zinc as an indicator of zinc status. However, one trial reported that hair zinc levels declined after supplementation.†
Other factors that affect hair zinc levels also interfere with the clinical use of this tool. Shampooing and dying affect hair zinc levels,111 as does the sex of the subject,111–115 age,70 and hair growth rate. Malnourished children have shown both low105,116,117 and high118 hair zinc.
Poor correlations between hair zinc and height,119 weight, and zinc consumption also have been reported,76,112 although one study reported a correlation among hair zinc, weight, and zinc consumption.119 Another study found that obese people of both sexes had higher hair zinc than those of normal weight and that there was a correlation between the degree of obesity and higher hair zinc levels.120
Although low hair zinc levels have been reported in patients with insulin-dependent diabetes mellitus,109 generally there is considerable overlap between cases and controls. To further complicate the picture, in a study of female children of non–insulin-dependent diabetes mellitus parents, hair zinc was found to be significantly higher compared with women with no family history of non–insulin-dependent diabetes mellitus.121
Other Minerals
Hair iron was found to correlate positively with serum ferritin,122 although the clinical relevance of this finding is unclear.123 Hair lithium has been reported to show a linear response to extra-dietary sources.7 Low hair levels of lithium have also been reported in conjunction with heart disease, learning disability, and violent behavior.7 However, research findings are far from the point at which hair lithium could be used to help clinicians diagnose or treat these conditions.
Drug Abuse
HA has been used to detect drugs of abuse and their metabolites when urine tests were negative.34,36 HA has been used as evidence in a court of law concerning past drug abuse.35 Although there are concerns about the role of HA in testing for drug abuse,124 HA does seem to be a valuable tool in drug screening.37,38,49,50 As mentioned, drug metabolites, not mineral levels, are measured in these trials, and drug metabolites typically are not reported on most commercially available HAs.
Ratios
The experimental documentation for most of the “ideal” ratios that have been published by several HA companies has not been found. The zinc/copper ratio has been reported to be altered in violent patients.80 This ratio was also elevated in survivors of myocardial infarctions.125 Strong correlations between several mineral ratios and atherosclerosis have also been reported126; however, the clinical significance of these ratios is not known. The magnesium/zinc ratios helped to separate healthy (less than 1:1) from epileptic (more than 1:1) subjects in one study.99
Discussion
Hair mineral analysis is conceptually enticing and potentially a valuable clinical tool. However, problems abound with standardization of sampling, handling, and analysis of hair samples.44,45 Additionally, reference values can differ widely,127,128 and many variables affect the results (see Austin for a review)129:
This is further aggravated by the reporting of different results on the same sample from different laboratories.45,48,135 The distribution of elements within the lipid and nonlipid portions of hair and the treatment of the sample before testing may explain these variances.4,136 As noted, dietary intakes do not consistently correlate with hair levels, and hair color, sex, age, and other variables appear to significantly affect levels of some minerals. Separate norms for age, gender, and hair color are now being established.70,131,137 However, reviews of the literature attempting to establish reference values continue to show a large variance in mean values, standard deviations, and ranges.75,138 Additionally, there is no basis for the nutritional advice suggested by some laboratories.
As a result of the gulf between available information on the one hand, and the clinical interest by some practitioners on the other, several articles have appeared decrying the misuses of HA.44,45,139–141 Hambidge140 said, “There is a wide gulf between the limited and mainly tentative justification for their use on an individual basis and the current exploitation of multi-element chemical analysis of human hair.”
Klevay and associates142 acknowledge the experimental usefulness of HA but go on to say that, “its use in clinical medicine for diagnosis, prognosis, and therapy will remain limited until validation by the standard methods of clinical investigation is achieved.” Steindel and Howanitz141 concluded:
1. Passwater R.A., Cranton E.M. Trace elements, hair analysis and nutrition. New Canaan, CT: Keats Publishing; 1983.
2. Blaurock-Busch E. Attacking and defending hair mineral analysis. Townsend Letter for Doctors & Patients. 2001;251:86–89.
3. Sen J., Das Chaudhuri A.B. Brief communication: choice of washing method of hair samples for trace element analysis in environmental studies. Am J Phys Anthropol. 2001;115:289–291.
4. Bass D.A., Hickok D., Quig D., et al. Trace element analysis in hair: factors determining accuracy, precision and reliability. Altern Med Rev. 2001;6:472–481.
5. Pihl R.O., Parkes M. Hair element content in learning disabled children. Science. 1977;198:204–206.
6. Marlowe M., Moon C. Hair aluminum concentration and nonadaptive classroom behavior. J Adv Med. 1988;1:135–142.
7. Schrauzer G.N., Shrestha K.P., Flores-Arce M.F. Lithium in scalp hair of adults, students, and violent criminals. Effects of supplementation and evidence for interactions of lithium with vitamin B12 and with other trace minerals. Biol Trace Elem Res. 1992;34:161–176.
8. Saner G., Dagoglu T., Ozden T. Hair manganese concentrations in newborns and their mothers. Am J Clin Nutr. 1985;41:1042–1044.
9. Guvenc H., Karatas F., Guvenc M., et al. Low levels of selenium in mothers and their newborns in pregnancies with a neural tube defect. Pediatrics. 1995;95:879–882.
10. Barlow P.J. A pilot study on the metal levels in the hair of hyperactive children. Med Hypotheses. 1983;11:309–318.
11. Barlow P.J., Francois P.E., Goldberg I.J., et al. Trace metal abnormalities in long-stay hyperactive mentally handicapped children and agitated senile dements. J R Soc Med. 1986;79:581–583.
12. Kozielec T., Starobrat-Hermelin B. Assessment of magnesium levels in children with attention deficit hyperactivity disorder (ADHD). Magn Res. 1997;10:143–148.
13. Marlowe M., Moon C., Errera J., et al. Hair mineral content as a predictor of mental retardation. J Orthomol Psychiatry. 1983;12:26–37.
14. Shrestha K.P., Carrera A.E. Hair trace elements and mental retardation among children. Arch Environ Health. 1988;43:396–398.
15. Kracke K. Biochemical bases for behaviour disorders in children. J Orthomol Psychiatry. 1982;11:289–297.
16. Vobecky J., et al. Hair and urine chromium content in 30 hospitalized female psychogeriatric patients and mentally healthy controls. Nutr Rep Int. 1980;22:49–55.
17. Marlowe M., Cossairt A., Stellern J., et al. Decreased magnesium in the hair of autistic children. J Orthomol Psychiatry. 1984;13:117–122.
18. Cotton D.W., Porters J.E., Spruit D. Magnesium content of the hair in alopecia areata atypica. Dermatologica. 1976;152:60–62.
19. Amador M., Hermelo M., Flories P., et al. Hair-zinc concentrations in diabetic children. Lancet. 1975;2:1146.
20. Hambidge K.M., Rodgerson D.O., O’Brien D. Concentration of chromium in the hair of normal children and children with juvenile diabetes mellitus. Diabetes. 1968;17:517–519.
21. Kopito L., Elian E., Shwachman H. Sodium, potassium, calcium, and magnesium in hair from neonates with cystic fibrosis and in amniotic fluid from mothers of such children. Pediatrics. 1972;49:620–624.
22. Dogru U., Arcasoy A., Cavdar A.O. Zinc levels of plasma, erythrocyte, hair and urine in homozygote beta-thalassemia. Acta Haematol. 1979;62:41–44.
23. Man C.K., Zheng Y.H., Mak P.K. Hair analysis of spastic children in Hong Kong. Sci Total Environ. 1996;191:291–295.
24. Majumdar S., Chatterjee J., Chaudhuri K. Ultrastructural and trace metal studies on radiographers’ hair and nails. Biol Trace Elem Res. 1999;67:127–136.
25. Chatterjee J., Mukherjee B.B., De K., et al. Trace metal levels of x-ray technicians’ blood and hair. Biol Trace Elem Res. 1994;46:211–227.
26. Man A.C., Zheng Y.H., Mak P.K. Structural and trace element changes in scalp hair of radiographers. Biol Trace Elem Res. 1998;63:11–18.
27. Leung P.L., Huang H.M. Following the recovery of naso-pharyngeal cancer patients by trace elements in hair using statistical pattern recognition methods. Biol Trace Elem Res. 1998;62:235–253.
28. Leung P.L., Huang H.M. Analysis of trace elements in the hair of volunteers suffering from nasopharyngeal cancer. Biol Trace Elem Res. 1997;57:19–25.
29. Wang J., Yang S., Chen G., et al. Contents of trace elements in the hair of aplastic anemia patients and their treatment based on an overall analysis of symptoms and signs. J Trad Chin Med. 1994;14:98–100.
30. Park S.B., Choi S.W., Nam A.Y. Hair tissue mineral analysis and metabolic syndrome. Bio Trace Elem Res. 2009;130(3):218–228.
31. Joo N.S., Kim S.M., Jung Y.S., et al. Hair iron and other minerals’ level in breast cancer patients. Biol Trace Elem Res. 2009;129(1-3):28–35.
32. Song C.H., Barrett-Connor E., Chung J.H., et al. Associations of calcium and magnesium in serum and hair with bone mineral density in premenopausal women. Biol Trace Elem Res. 2007;118:1–9.
33. Huang H., Hu W., Han Z., et al. Hybrid progressive algorithm to recognise type II diabetics based on hair mineral element contents. Conf Proc IEEE Eng Med Biol Soc. 2005;5:4716–4718.
34. Graham K., Koren G., Klein J., et al. Determination of gestational cocaine exposure by hair analysis. JAMA. 1989;262:3328–3330.
35. Strang J., Marsh A., DeSouza N. Hair analysis for drugs of abuse. Lancet. 1990;335:740.
36. Gaillard Y., Vayssette F., Pepin G. Compared interest between hair analysis and urinalysis in doping controls. Results for amphetamines, corticosteroids and anabolic steroids in racing cyclists. Forensic Sci Int. 2000;107:361–379.
37. Nakahara Y. Hair analysis for abused and therapeutic drugs. J Chromatogr B Biomed Sci Appl. 1999;733:161–180.
38. Gaillard Y., Pepin G. Testing hair for pharmaceuticals. J Chromatogr B Biomed Sci Appl. 1999;733:231–246.
39. Rivier L. Is there a place for hair analysis in doping controls? Forensic Sci Int. 2000;107:309–323.
40. Klien J., Karaskov T., Koren G. Clinical applications of hair testing for drugs of abuse: the Canadian experience. Forensic Sci Int. 2000;107:281–288.
41. Kintz P., Villain M., Cirimele V. Hair analysis for drug detection. Ther Drug Monit. 2006;28:442–446.
42. Kronstrand R., Nyström I., Forsman M., et al. Hair analysis for drugs in driver’s license regranting. A Swedish pilot study. Forensic Sci Int. 2010;196:55–58.
43. Polla M, Stramesi C, Pichini S, et al. Hair testing is superior to urine to disclose cocaine consumption in driver’s license regranting. Forensic Sci Int. 200;189:e41–e43.
44. Barrett S. Commercial hair analysis. Science or scam? JAMA. 1985;254:141–145.
45. Seidel S., Kreutzer R., Smith D., et al. Assessment of commercial laboratories performing hair mineral analysis. JAMA. 2001;285:67–72.
46. Morley N., Ford R. Hair-element analysis–still on the fringe. Child Care Health Dev. 2002;28(Suppl 1):31–34.
47. Shamberger R.J. Validity of hair mineral testing. Biol Trace Elem Res. 2002;87(1-3):1–28.
48. Drasch G., Roider G. Assessment of hair mineral analysis commercially offered in Germany. J Trace Elem Med Biol. 2002;16(1):27–31.
49. Ng S.Y. Hair calcium and magnesium levels in patients with fibromyalgia: a case center study. J Manipulative Physiol Ther. 1999;22:586–593.
50. Noble R.E. Uptake of calcium and magnesium by human scalp hair from waters of different geographic locations. Sci Total Environ. 1999;239:189–193.
51. Huang H.M., Leung P.L., Sun D.Z., et al. Hair and serum calcium, iron, copper, and zinc levels during normal pregnancy at three trimesters. Biol Trace Elem Res. 1999;69:111–120.
52. Leung P.L., Huang H.M., Sun D.Z., et al. Hair concentrations of calcium, iron and zinc in pregnant women and effects of supplementation. Biol Trace Elem Res. 1999;69:269–282.
53. Sahin G., Ertem U., Duru F., et al. High prevalence of chronic magnesium deficiency in T cell lymphoblastic leukemia and chronic zinc deficiency in children with acute lymphoblastic leukemia and malignant lymphoma. Leuk Lymphoma. 2000;39:555–562.
54. Capel I.D., Pinnock M.H., Dorrell H.M., et al. Comparisons of concentrations of some trace, bulk, and toxic metals in the hair of normal and dyslexic children. Clin Chem. 1981;27:879–881.
55. Marlowe M., Medeiros D.M., Errera J., et al. Hair minerals and diet of Prader-Willi syndrome youth. J Autism Dev Disord. 1987;17:365–374.
56. Miekeley N., de Fortes Carvalho L.M., Porto da Silveira C.L., et al. Elemental anomalies in hair as indicators of endocrinologic pathologies and deficiencies in calcium and bone metabolism. J Trace Elem Med Biol. 2001;15:46–55.
57. Bland J. Dietary calcium, phosphorus and their relationships to bone formation and parathyroid activity. J John Bastyr Col Nat Med. 1979;1:185–189.
58. Kozielec T., Salacka A., Radomska K., et al. The influence of magnesium supplementation on magnesium and calcium concentrations in hair of children with magnesium shortage. Magn Res. 2001;14:33–38.
59. Guillard O., Mettey R., Lecron J.C., et al. Congenital hypomagnesemia: alternatives to tissue biopsies for monitoring body magnesium status. Clin Biochem. 1992;25:463–465.
60. Hambidge K.M., Franklin M.L., Jacobs M.A. Changes in hair chromium concentrations with increasing distances from hair roots. Am J Clin Nutr. 1972;25:380–383.
61. Aharoni A., Tesler B., Paltieli Y., et al. Hair chromium content of women with gestational diabetes compared with nondiabetic pregnant women. Am J Clin Nutr. 1992;55:104–107.
62. Jeejeebhoy K.N., Chu R.C., Marliss E.B., et al. Chromium deficiency, glucose intolerance, and neuropathy reversed by chromium supplementation, in a patient receiving long-term total parenteral nutrition. Am J Clin Nutr. 1977;30:531–538.
63. Rowland A. Trace metals leave more than trace effects. Sci News. 1984;125:373.
64. Hunt A.E., Allen K.G.D., Smith B.A. Effect of chromium supplementation on hair chromium concentration and diabetic status. Nutr Res. 1985;5:131–140.
65. Hambidge K.M., Franklin M.L., Jacobs M.A. Hair chromium concentration. Effects of sample washing and external environment. Am J Clin Nutr. 1972;25:384–389.
66. Deeming S.B., Weber C.W. Hair analysis of trace minerals in human subjects as influenced by age, sex, and contraceptive drugs. Am J Clin Nutr. 1978;31:1175–1180.
67. Klevay L.M. Hair as a biopsy material. II. Assessment of copper nutriture. Am J Clin Nutr. 1970;23:1194–1202.
68. Pratt W.B., Phippen W.G. Elevated hair copper levels in idiopathic scoliosis. Preliminary observations. Spine. 1980;5:230–233.
69. Vir S.C., Love A.H., Thompson W. Serum and hair concentrations of copper during pregnancy. Am J Clin Nutr. 1981;34:2382–2388.
70. Bertazzo A., Costa C., Biasiolo M., et al. Determination of copper and zinc levels in human hair: influence of sex, age, and hair pigmentation. Biol Trace Elem Res. 1996;52:37–53.
71. Bradfield R.B., Cordano A., Baertl J., et al. Hair copper in copper deficiency. Lancet. 1980;2:343–344.
72. Medeiros D., Sturniolo G.C., Martin A., et al. Trace elements in human hair. Lancet. 1982;2:608.
73. Watt F., Landsberg J., Powell J.J., et al. Analysis of copper and lead in hair using the nuclear microscope; results from normal subjects, and patients with Wilson’s disease and lead poisoning. Analyst. 1995;120:789–791.
74. Epstein O., Boss A.M., Lyon T.D., et al. Hair copper in primary biliary cirrhosis. Am J Clin Nutr. 1980;33:967.
75. Iyengar V., Woittiez J. Trace elements in human clinical specimens: evaluation of literature data to identify reference values. Clin Chem. 1988;34:474–481.
76. Jacob R.A., Klevay L.M., Logan G.M., Jr. Hair as a biopsy material. V. Hair metal as an index of hepatic metal in rats: copper and zinc. Am J Clin Nutr. 1978;31:477–480.
77. Sturaro A., Parvoli G., Doretti L., et al. The influence of color, age, and sex on the content of zinc, copper, nickel, manganese, and lead in human hair. Biol Trace Elem Res. 1994;40:1–8.
78. Papavasilious P.S., Kutt H., Miller S.T., et al. Seizure disorders and trace metals: manganese tissue levels in treated epileptics. Neurology. 1979;29:1466–1473.
79. Gottschalk L.A., Rebello T., Buchsbaum M.S., et al. Abnormalities in the hair trace elements as indicators of aberrant behavior. Comp Psychiatry. 1991;32:229–237.
80. Cromwell P.F., Abadie B.R., Stephens J.T., et al. Hair mineral analysis: biochemical imbalances and violent criminal behavior. Psychol Rep. 1989;64:259–266.
81. Valentine J.L., Kang H.K., Spivey G.H. Selenium levels in human blood, urine, and hair in response to exposure via drinking water. Environ Res. 1978;17:347–355.
82. Yang G.Q., Wang S.Z., Zhou R.H., et al. Endemic selenium intoxication of humans in China. Am J Clin Nutr. 1983;37:872–881.
83. Srivastava A.K., Gupta B.N., Bihari V., et al. Hair selenium as a monitoring tool for occupational exposures in relation to clinical profile. J Toxicol Environ Health. 1997;51:437–445.
84. Keshan Disease Research Group of the Chinese Academy of Medical Sciences, Beijing. Epidemiological studies on the etiologic relationships of selenium and Keshan disease. Chin Med J. 1979;92:477–482.
85. Jochum F., Terwolbeck K., Meinhold H., et al. Effects of a low selenium state in patients with phenylketonuria. Acta Paediatr. 1997;86:775–777.
86. Gallagher M.L., Webb P., Crounse R., et al. Selenium levels in new growth hair and in whole blood during ingestion of a selenium supplement for six weeks. Nutr Res. 1984;4:577–582.
87. Terada A., Nakada M., Nakada K., et al. Selenium administration to a ten-year-old patient receiving long-term total parenteral nutrition (TPN): changes in selenium concentration in the blood and hair. J Trace Elem Med Biol. 1998;10:1–5.
88. Maugh T.H., II. Hair: a diagnostic tool to complement blood serum and urine. Science. 1978;202:1271–1273.
89. Wright J.V., Severtson R.B. Observations on the interpretations of hair mineral analysis in human medicine. J Intl Acad Prev Med. 1982;April:13–16.
90. Pekarek R.S., Sandstead H.H., Jacob R.A., et al. Abnormal cellular immune responses during acquired zinc deficiency. Am J Clin Nutr. 1979;32:1466–1471.
91. Ward N.I. Assessment of zinc status and oral supplementation in anorexia nervosa. J Nutr Med. 1990;1:171–177.
92. Gibson R.S., Heywood A., Yaman C., et al. Growth in children from the Wosera subdistrict, Papua New Guinea, in relation to energy and protein intakes and zinc status. Am J Clin Nutr. 1991;53:782–789.
93. Zachwieja Z., Chlopicka J., Schlegel-Zawadzka M., et al. Evaluation of zinc content in children’s hair. Biol Trace Elem Res. 1995;47:141–145.
94. Bales C.W., Freeland-Graves J.H., Askey S., et al. Zinc, magnesium, copper and protein concentrations in human saliva: age- and sex-related differences. Am J Clin Nutr. 1990;51:462–469.
95. Strain W.H., Pories W.J. Zinc levels of hair as tools in zinc metabolism. In: Prasad A., ed. Zinc metabolism. Springfield, IL: Charles C Thomas; 1966:363.
96. Freeland-Graves J.H., Bodzy P.W., Eppright M.A. Zinc status of vegetarians. J Am Diet Assoc. 1980;77:655–661.
97. Piccinini L., Borella P., Bargellini A., et al. A case-control study on selenium, zinc, and copper in plasma and hair of subjects affected by breast cancer and lung cancer. Biol Trace Elem Res. 1996;51:23–30.
98. Varkonyi A., Boda M., Endreffy E., et al. Coeliac disease: always something to discover. Scand J Gastroenterol Suppl. 1998;228:122–129.
99. Ashraf W., Jaffar M., Mohammed D., et al. Utilization of scalp hair for evaluating epilepsy in male and female groups of the Pakistan population. Sci Total Environ. 1995;164:69–73.
100. Ilhan A., Uz E., Kali S., et al. Serum and hair trace element levels in patients with epilepsy and healthy subjects: does antiepileptic therapy affect the element concentration of hair? Eur J Neurol. 1999;6:705–709.
101. Bradfield R.B., Hambidge K.M. Problems with hair zinc status as an indicator of body zinc status. Lancet. 1980;1:363.
102. Anonymous. Zinc supplementation in healthy short children. Int Clin Nutr Rev. 1984;4:28–29.
103. Perrone L., Salerno M., Gialanella G., et al. Long-term zinc and iron supplementation in children of short stature: effect of growth and on trace element content in tissues. J Trace Elem Med Biol. 1999;13:51–56.
104. Hambidge K.M., Walravens P.A., Brown R.M., et al. Zinc nutrition of preschool children in the Denver Head Start program. Am J Clin Nutr. 1976;29:734–738.
105. Weber C.W., Nelson G.W., Vasquez de Vaquera M., et al. Trace elements in the hair of healthy and malnourished children. J Trop Pediatr. 1990;36:230–234.
106. Gibson R.S., Vanderkooy P.D., MacDonald A.C., et al. A growth-limiting, mild zinc-deficiency syndrome in some southern Ontario boys with low height percentiles. Am J Clin Nutr. 1989;49:1266–1273.
107. Srinivas M., Gupta D.K., Rathi S.S., et al. Association between lower hair zinc levels and neural tube defects. Indian J Pediatr. 2001;68:519–522.
108. Rathi S.S., Srinivas M., Grover J.K., et al. Zinc levels in women and newborns. Indian J Pediatr. 1999;66:681–684.
109. Greger J.L., Geissler A.H. Effects of zinc supplementation on taste acuity of the aged. Am J Clin Nutr. 1978;31:633–637.
110. Sandstead H.H., Penland J.G., Alcock N.W., et al. Effects of repletion with zinc and other micronutrients on neuropsychologic performance and growth of Chinese children. Am J Clin Nutr. 1998;68:470S–475S.
111. Clanet P., DeAntonio S.M., Katz S.A., et al. Effects of some cosmetics on copper and zinc concentrations in human scalp hair. Clin Chem. 1982;28:2450–2451.
112. McKenzie J.M. Content of zinc in serum, urine, hair, and toenails of New Zealand adults. Am J Clin Nutr. 1979;32:570–579.
113. Heinersdorff N., Taylor T.G. Concentration of zinc in the hair of schoolchildren. Arch Dis Child. 1979;54:958–960.
114. Smit Vanderkooy P.D., Gibson R.S. Food consumption patterns of Canadian preschool children in relation to zinc and growth status. Am J Clin Nutr. 1987;45:609–616.
115. Meng Z. Age- and sex-related differences in zinc and lead levels in human hair. Biol Trace Elem Res. 1998;61:79–87.
116. Weber C.W., Nelson G.W., Vasquez de Vaquera M., et al. Trace elements in the hair of healthy and malnourished children. J Trop Pediatr. 1990;36:230–234.
117. Saner G. Hair trace element concentrations in patients with protein-energy malnutrition. Nutr Rep Int. 1985;32:263–268.
118. Erten J., Arcasoy A., Cavdar A.O., et al. Hair zinc levels in healthy and malnourished children. Am J Clin Nutr. 1978;31:1172.
119. Hogan S.E. Dietary intake and hair zinc status of persons with severe physical and developmental disabilities. Nutr Res. 1996;16:401–412.
120. Taneja S.K., Mahajan M., Arya P. Excess bioavailability of zinc may cause obesity in humans. Experientia. 1996;52:31–33.
121. Taneja S.K., Mahajan M., Gupta S., et al. Assessment of copper and zinc status in hair and urine of young women descendants of NIDDM parents. Biol Trace Elem Res. 1998;62:255–264.
122. Bissé E., Renner F., Sussmann S., et al. Hair iron content: possible marker to complement monitoring therapy of iron deficiency in patients with chronic inflammatory bowel disease? Clin Chem. 1996;42:1270–1274.
123. Beutler E. Hair iron content: possible marker to complement monitoring therapy of iron deficiency in patients with chronic inflammatory bowel disease? Clin Chem. 1997;43:1099–1100.
124. Bailey D.N. Drug screening in an unconventional matrix: hair analysis. JAMA. 1989;262:3331.
125. Bialkowska M., Hoser A., Szostak W.B., et al. Hair zinc and copper concentration in survivors of myocardial infarction. Ann Nutr Metab. 1987;31:327–332.
126. Fernandez-Britto J.E., de la Fuente F., Meitin J.J., et al. Coronary atherosclerosis and chemical trace elements in the hair. A canonical correlation study of autopsy subjects, using an arthrometric system and the x-ray fluorescence analysis. Zentralbl Pathol. 1993;139:61–65.
127. Miekeley N., Dias Carneiro M.T., da Silveira C.L. How reliable are human hair reference intervals for trace elements? Sci Total Environ. 1998;218:9–17.
128. Druyan M.E., Bass D., Puchyr R., et al. Determination of reference ranges for elements in human scalp hair. Biol Trace Elem Res. 1998;62:183–197.
129. Austin S. Hair analysis: a reappraisal. NCNM Rev. 1982;3:21–26.
130. Sakai T., Wariishi M., Nishiyama K. Changes in trace element concentrations in hair of growing children. Biol Trace Elem Res. 2000;77:43–51.
131. Perrone L., Moro R., Caroli M., et al. Trace elements in hair of healthy children sampled by age and sex. Biol Trace Elem Res. 1996;51:71–76.
132. Nowak B., Kozlowski H. Heavy metals in human hair and teeth: the correlation with metal concentration in the environment. Biol Trace Elem Res. 1998;62:213–228.
133. Tommaseo Ponzetta M., Nardi S., Calliari I., et al. Trace elements in the human scalp hair and soil in Irian Jaya. Biol Trace Elem Res. 1998;62:199–212.
134. Batzevich V.A. Hair trace element analysis in human ecology studies. Sci Total Environ. 1995;164:89–98.
135. Spilker B.A., Maugh T.H., II. How useful is hair analysis? J Energy Med. 1980;1:15–19.
136. Attar K.M., Abdel-Aal M.A., Debayle P. Distribution of trace elements in the lipid and non lipid matter of hair. Clin Chem. 1990;36:477–480.
137. Senofonte, Violante N., Caroli S. Assessment of reference values for elements in human hair of urban schoolboys. J Trace Elem Med Biol. 2000;14:6–13.
138. Taylor A. Usefulness of measurements of trace elements in hair. Ann Clin Biochem. 1986;23:364–378.
139. Rivlin R.S. Misuse of hair analysis for nutritional assessment. Am J Med. 1983;75:489–493.
140. Hambidge K.M. Hair analyses: worthless for vitamins, limited for minerals. Am J Clin Nutr. 1982;36:943–949.
141. Steindel S.J., Howanitz P.J. The uncertainty of hair analysis for trace metals. JAMA. 2001;285:83–85.
142. Klevay L.M., Bistrian B.R., Fleming C.R., et al. Hair analysis in clinical and experimental medicine. Am J Clin Nutr. 1987;46:233–236.
