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. 2001 Jan;56(1):48–52. doi: 10.1136/thorax.56.1.48

Effects of β-carotene supplementation for six months on clinical and laboratory parameters in patients with cystic fibrosis

S Renner 1, R Rath 1, P Rust 1, S Lehr 1, T Frischer 1, I Elmadfa 1, I Eichler 1
PMCID: PMC1745899  PMID: 11120904

Abstract

BACKGROUND—Patients with cystic fibrosis (CF) have significantly decreased plasma concentrations of nutrient antioxidant vitamins, especially of β-carotene, which is thought to result from fat malabsorption and chronic pulmonary inflammation. The aim of this double blind, placebo controlled study was to investigate the effect of oral β-carotene supplementation for six months on clinical parameters.
METHODS—Twenty four patients with CF were randomised to receive β-carotene 1 mg/kg/day (maximum 50 mg/day) for three months (high dose supplementation) and 10 mg/day for a further three months (low dose supplementation) or placebo. At monthly follow up visits the plasma β-carotene concentration, total antioxidant capacity, malondialdehyde (MDA) as a marker of lipid peroxidation, and clinical parameters (Shwachmann-Kulczycki score, body mass index (BMI), height, and lung function (FEV1)) were assessed. The number of pulmonary exacerbations requiring antibiotic treatment (in days) three months before and during the study were evaluated.
RESULTS—The plasma concentration of β-carotene increased significantly to the normal range during the three months of high dose supplementation (baseline 0.08 (0.04) µmol/l to 0.56 (0.38) µmol/l; p<0.001) but decreased to 0.32 (0.19) µmol/l in the period of low dose supplementation. Initially raised plasma levels of MDA fell to normal levels and the total antioxidant capacity showed a non-significant trend towards improvement during high dose supplementation. Antibiotic treatment decreased significantly in the supplementation group from 14.5 (14.9) days/patient during the three months before the study to 9.8 (10.3) days/patient during high dose supplementation (p=0.0368) and to 10.5 (9.9) days/patient during low dose supplementation, but increased in the placebo group. The Shwachmann-Kulczycki score, lung function, and BMI did not show any changes in either of the treatment groups. No adverse events were observed during the study period.
CONCLUSION—Oral β-carotene supplementation in a dose of 1 mg/kg/day only was effective in normalising the plasma concentration of β-carotene and resulted in a decrease in pulmonary exacerbations. These data suggest that patients with CF may benefit clinically from supplementation with β-carotene and further studies are warranted.



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Selected References

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  1. Anderson R., Theron A. J. Physiological potential of ascorbate, beta-carotene and alpha-tocopherol individually and in combination in the prevention of tissue damage, carcinogenesis and immune dysfunction mediated by phagocyte-derived reactive oxidants. World Rev Nutr Diet. 1990;62:27–58. doi: 10.1159/000417534. [DOI] [PubMed] [Google Scholar]
  2. Bendich A. Antioxidant micronutrients and immune responses. Ann N Y Acad Sci. 1990;587:168–180. doi: 10.1111/j.1749-6632.1990.tb00144.x. [DOI] [PubMed] [Google Scholar]
  3. Berger M. Inflammation in the lung in cystic fibrosis. A vicious cycle that does more harm than good? Clin Rev Allergy. 1991 Spring-Summer;9(1-2):119–142. doi: 10.1007/978-1-4612-0475-6_8. [DOI] [PubMed] [Google Scholar]
  4. Brown R. K., Kelly F. J. Role of free radicals in the pathogenesis of cystic fibrosis. Thorax. 1994 Aug;49(8):738–742. doi: 10.1136/thx.49.8.738. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Eichler I., Joris L., Hsu Y. P., Van Wye J., Bram R., Moss R. Nonopsonic antibodies in cystic fibrosis. Pseudomonas aeruginosa lipopolysaccharide-specific immunoglobulin G antibodies from infected patient sera inhibit neutrophil oxidative responses. J Clin Invest. 1989 Dec;84(6):1794–1804. doi: 10.1172/JCI114364. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. GIBSON L. E., COOKE R. E. A test for concentration of electrolytes in sweat in cystic fibrosis of the pancreas utilizing pilocarpine by iontophoresis. Pediatrics. 1959 Mar;23(3):545–549. [PubMed] [Google Scholar]
  7. Homnick D. N., Cox J. H., DeLoof M. J., Ringer T. V. Carotenoid levels in normal children and in children with cystic fibrosis. J Pediatr. 1993 May;122(5 Pt 1):703–707. doi: 10.1016/s0022-3476(06)80008-9. [DOI] [PubMed] [Google Scholar]
  8. Homnick D. N., Spillers C. R., Cox S. R., Cox J. H., Yelton L. A., DeLoof M. J., Oliver L. K., Ringer T. V. Single- and multiple-dose-response relationships of beta-carotene in cystic fibrosis. J Pediatr. 1995 Sep;127(3):491–494. doi: 10.1016/s0022-3476(95)70089-7. [DOI] [PubMed] [Google Scholar]
  9. Jakob E., Elmadfa I. Rapid HPLC assay for the assessment of vitamin K1, A, E and beta-carotene status in children (7-19 years). Int J Vitam Nutr Res. 1995;65(1):31–35. [PubMed] [Google Scholar]
  10. Khan T. Z., Wagener J. S., Bost T., Martinez J., Accurso F. J., Riches D. W. Early pulmonary inflammation in infants with cystic fibrosis. Am J Respir Crit Care Med. 1995 Apr;151(4):1075–1082. doi: 10.1164/ajrccm/151.4.1075. [DOI] [PubMed] [Google Scholar]
  11. Lepage G., Champagne J., Ronco N., Lamarre A., Osberg I., Sokol R. J., Roy C. C. Supplementation with carotenoids corrects increased lipid peroxidation in children with cystic fibrosis. Am J Clin Nutr. 1996 Jul;64(1):87–93. doi: 10.1093/ajcn/64.1.87. [DOI] [PubMed] [Google Scholar]
  12. Meyer K. C., Lewandoski J. R., Zimmerman J. J., Nunley D., Calhoun W. J., Dopico G. A. Human neutrophil elastase and elastase/alpha 1-antiprotease complex in cystic fibrosis. Comparison with interstitial lung disease and evaluation of the effect of intravenously administered antibiotic therapy. Am Rev Respir Dis. 1991 Sep;144(3 Pt 1):580–585. doi: 10.1164/ajrccm/144.3_Pt_1.580. [DOI] [PubMed] [Google Scholar]
  13. Mohsenin V., Gee J. L. Oxidation of alpha 1-protease inhibitor: role of lipid peroxidation products. J Appl Physiol (1985) 1989 May;66(5):2211–2215. doi: 10.1152/jappl.1989.66.5.2211. [DOI] [PubMed] [Google Scholar]
  14. Omenn G. S., Goodman G. E., Thornquist M. D., Balmes J., Cullen M. R., Glass A., Keogh J. P., Meyskens F. L., Jr, Valanis B., Williams J. H., Jr Risk factors for lung cancer and for intervention effects in CARET, the Beta-Carotene and Retinol Efficacy Trial. J Natl Cancer Inst. 1996 Nov 6;88(21):1550–1559. doi: 10.1093/jnci/88.21.1550. [DOI] [PubMed] [Google Scholar]
  15. Peters S. A., Kelly F. J. Vitamin E supplementation in cystic fibrosis. J Pediatr Gastroenterol Nutr. 1996 May;22(4):341–345. doi: 10.1097/00005176-199605000-00001. [DOI] [PubMed] [Google Scholar]
  16. Portal B. C., Richard M. J., Faure H. S., Hadjian A. J., Favier A. E. Altered antioxidant status and increased lipid peroxidation in children with cystic fibrosis. Am J Clin Nutr. 1995 Apr;61(4):843–847. doi: 10.1093/ajcn/61.4.843. [DOI] [PubMed] [Google Scholar]
  17. Prader A., Largo R. H., Molinari L., Issler C. Physical growth of Swiss children from birth to 20 years of age. First Zurich longitudinal study of growth and development. Helv Paediatr Acta Suppl. 1989 Jun;52:1–125. [PubMed] [Google Scholar]
  18. Reilly P. M., Schiller H. J., Bulkley G. B. Pharmacologic approach to tissue injury mediated by free radicals and other reactive oxygen metabolites. Am J Surg. 1991 Apr;161(4):488–503. doi: 10.1016/0002-9610(91)91120-8. [DOI] [PubMed] [Google Scholar]
  19. Rice-Evans C., Miller N. J. Total antioxidant status in plasma and body fluids. Methods Enzymol. 1994;234:279–293. doi: 10.1016/0076-6879(94)34095-1. [DOI] [PubMed] [Google Scholar]
  20. Rust P., Eichler I., Renner S., Elmadfa I. Effects of long-term oral beta-carotene supplementation on lipid peroxidation in patients with cystic fibrosis. Int J Vitam Nutr Res. 1998;68(2):83–87. [PubMed] [Google Scholar]
  21. SHWACHMAN H., KULCZYCKI L. L. Long-term study of one hundred five patients with cystic fibrosis; studies made over a five- to fourteen-year period. AMA J Dis Child. 1958 Jul;96(1):6–15. doi: 10.1001/archpedi.1958.02060060008002. [DOI] [PubMed] [Google Scholar]
  22. Salh B., Webb K., Guyan P. M., Day J. P., Wickens D., Griffin J., Braganza J. M., Dormandy T. L. Aberrant free radical activity in cystic fibrosis. Clin Chim Acta. 1989 Apr 28;181(1):65–74. doi: 10.1016/0009-8981(89)90318-5. [DOI] [PubMed] [Google Scholar]
  23. Winklhofer-Roob B. M., Ellemunter H., Frühwirth M., Schlegel-Haueter S. E., Khoschsorur G., van't Hof M. A., Shmerling D. H. Plasma vitamin C concentrations in patients with cystic fibrosis: evidence of associations with lung inflammation. Am J Clin Nutr. 1997 Jun;65(6):1858–1866. doi: 10.1093/ajcn/65.6.1858. [DOI] [PubMed] [Google Scholar]
  24. Winklhofer-Roob B. M. Oxygen free radicals and antioxidants in cystic fibrosis: the concept of an oxidant-antioxidant imbalance. Acta Paediatr Suppl. 1994 Apr;83(395):49–57. doi: 10.1111/j.1651-2227.1994.tb13229.x. [DOI] [PubMed] [Google Scholar]
  25. Winklhofer-Roob B. M., Puhl H., Khoschsorur G., van't Hof M. A., Esterbauer H., Shmerling D. H. Enhanced resistance to oxidation of low density lipoproteins and decreased lipid peroxide formation during beta-carotene supplementation in cystic fibrosis. Free Radic Biol Med. 1995 May;18(5):849–859. doi: 10.1016/0891-5849(94)00203-v. [DOI] [PubMed] [Google Scholar]
  26. Winklhofer-Roob B. M., Schlegel-Haueter S. E., Khoschsorur G., van't Hof M. A., Suter S., Shmerling D. H. Neutrophil elastase/alpha 1-proteinase inhibitor complex levels decrease in plasma of cystic fibrosis patients during long-term oral beta-carotene supplementation. Pediatr Res. 1996 Jul;40(1):130–134. doi: 10.1203/00006450-199607000-00022. [DOI] [PubMed] [Google Scholar]
  27. Winklhofer-Roob B. M., van't Hof M. A., Shmerling D. H. Reference values for plasma concentrations of vitamin E and A and carotenoids in a Swiss population from infancy to adulthood, adjusted for seasonal influences. Clin Chem. 1997 Jan;43(1):146–153. [PubMed] [Google Scholar]
  28. Winklhofer-Roob B. M., van't Hof M. A., Shmerling D. H. Response to oral beta-carotene supplementation in patients with cystic fibrosis: a 16-month follow-up study. Acta Paediatr. 1995 Oct;84(10):1132–1136. doi: 10.1111/j.1651-2227.1995.tb13512.x. [DOI] [PubMed] [Google Scholar]
  29. Wong S. H., Knight J. A., Hopfer S. M., Zaharia O., Leach C. N., Jr, Sunderman F. W., Jr Lipoperoxides in plasma as measured by liquid-chromatographic separation of malondialdehyde-thiobarbituric acid adduct. Clin Chem. 1987 Feb;33(2 Pt 1):214–220. [PubMed] [Google Scholar]
  30. van der Vliet A., Eiserich J. P., Marelich G. P., Halliwell B., Cross C. E. Oxidative stress in cystic fibrosis: does it occur and does it matter? Adv Pharmacol. 1997;38:491–513. doi: 10.1016/s1054-3589(08)60996-5. [DOI] [PubMed] [Google Scholar]

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