Dietary Supplementation with Pressurized Whey in Patients with Cystic Fibrosis

다국어 초록 (Multilingual Abstract)

Cystic fibrosis (CF) is characterized by malnutrition, chronic pulmonary inflammation, and oxidative stress. Whey protein is rich in sulfhydryl groups and is recognized for its ability to increase glutathione and reduce oxidative stress. Previously, we have shown that supplementation with whey increased intracellular glutathione levels in patients with CF. We have subsequently shown that hyperbaric pressure treatment of whey protein promotes the release of novel peptides for absorption, increases intracellular glutathione in healthy subjects, and reduces in vitro production of interleukin (IL)-8. We hypothesized that pressurized whey supplementation in children and adults with CF could have significant nutritional and anti-inflammatory benefits. A pilot open-label study of 1-month dietary supplementation with pressurized whey in CF patients was undertaken to assess the effects. Twenty-seven patients with CF (nine children, 18 adults) were enrolled. The dose of pressurized whey was 20g/day in patients less than 18 years of age and 40g/day in older patients. Anthropometric measures, pulmonary function, serum C-reactive protein (CRP), whole blood glutathione, and whole blood IL-8 and IL-6 responses to phytohemagglutinin (PHA) stimulation were measured at baseline and at 1 month. Three adults withdrew (one with gastrointestinal side effects, two with acute infection). Both children and adults showed enhancements in nutritional status, as assessed by body mass index. Children showed improvement in lung function (forced expiratory volume in 1 second). The majority of patients with an initially elevated CRP showed a decrease. PHA-stimulated IL-8 responses tended to decrease in the adults. Whole blood glutathione levels did not change. Thus, oral supplementation with pressurized whey improves nutritional status and can have additional beneficial effects on inflammation in patients with CF.

참고문헌 (Reference)

1 Sharma R., "Wasting as an independent predictor of mortality in patients with cystic fibrosis" 56 : 746-750, 2001

2 Otterbein LE, "The saga of leucine zippers continues: in response to oxidative stress" 26 : 161-163, 2002

3 Nicodemo A., "The effects of whey proteins on lipoprotein metabolism and oxidative stress: a review of human and animal studies" 4 : 245-302, 2000

4 Roebuck KA, "Stimulus-specific regulation of chemokine expression involves differential activation of the redox-responsive transcription factors AP-1 and NF-kappaB" 65 : 291-298, 1999

5 Wanger J., "Standardisation of the measurement of lung volumes" 26 : 511-522, 2005

6 Morris JF, "Spirometric standards for healthy nonsmoking adults" 103 : 57-67, 1971

7 Geukers VGM, "Short-term protein intake and stimulation of protein synthesis in stunted children with cystic fibrosis" 81 : 605-610, 2005

8 Hanning RM, "Relationships among nutritional status and skeletal and respiratory muscle function in cystic fibrosis: does early dietary supplementation make a difference?" 57 : 580-587, 1993

9 Voynow JA, "Proteases and cystic fibrosis" 40 : 1238-1245, 2008

10 Birrer P., "Proteaseantiprotease imbalance in the lungs of children with cystic fibrosis" 150 : 207-213, 1994

11 Starosta V., "Oxidative changes of bronchoalveolar proteins in cystic fibrosis" 129 : 431-437, 2006

12 Buhl R., "Oxidant-protease interaction in the lung. Prospects for antioxidant therapy" 110 (110): 267S-272S, 1996

13 Lands LC, "Oral non-steroidal anti-inflammatory drug therapy for cystic fibrosis" 4 : CD001505-, 2007

14 Jing Y., "Mechanisms by which whey supplementation increases hepatic glutathione concentrations" McGill University 2004

15 Tramper-Stranders GA, "Maintenance azithromycin treatment in pediatric patients with cystic fibrosis: long-term outcomes related to macrolide resistance and pulmonary function" 26 : 8-12, 2007

16 Lands LC, "Lymphocyte glutathione levels in children with cystic fibrosis" 116 : 201-205, 1999

17 Leavy O., "Lung inflammation: disarming neutrophils in cystic fibrosis" 8 : 8-, 2008

18 Sagel SD, "Induced sputum inflammatory measures correlate with lung function in children with cystic fibrosis" 141 : 811-817, 2002

19 Smountas AA, "Induced sputum in cystic fibrosis: within week reproducibility of inflammatory markers" 37 : 1031-1036, 2004

20 Visca A., "Improvement in clinical markers in CF patients using a reduced glutathione regimen: an uncontrolled, observational study" 7 : 433-436, 2008

21 Grey V., "Improved glutathione status in young adult patients with cystic fibrosis supplemented with whey protein" 2 : 195-198, 2003

22 Janeway CA, "Immunobiology: The Immune System in Health and Disease" Current Biology Ltd 1997

23 Demedts M., "IFIGENIA Study Group: High-dose acetylcysteine in idiopathic pulmonary fibrosis" 353 : 2229-2242, 2005

24 Lands LC, "Highdose ibuprofen in cystic fibrosis: Canadian safety and effectiveness trial" 151 : 249-254, 2007

25 Tirouvanziam R., "High-dose oral N-acetylcysteine, a glutathione prodrug, modulates inflammation in cystic fibrosis" 103 : 4628-4633, 2006

26 Vilela RM, "High hydrostatic pressure enhances whey protein digestibility to generate whey peptides that improve glutathione status in CFTR-deficient lung epithelial cells" 50 : 1013-1029, 2006

27 Lopez-Fandino R., "Functional improvement of milk whey proteins induced by high hydrostatic pressure" 46 : 351-363, 2006

28 Kalnins D., "Failure of conventional strategies to improve nutritional status in malnourished adolescents and adults with cystic fibrosis" 147 : 399-401, 2005

29 Konstan MW, "Effect of highdose ibuprofen in patients with cystic fibrosis" 332 : 848-854, 1995

30 De Groote D., "Direct stimulation of cytokines (IL-1 beta, TNFalpha, IL-6, IL-2, IFN-gamma and GM-CSF) in whole blood. I. Comparison with isolated PBMC stimulation" 4 : 239-248, 1992

31 Anderson ME, "Determination of glutathione and glutathione disulfide in biological samples" 113 : 548-555, 1985

32 Anselmo MA, "Cystic fibrosis: overview, In: Pediatric Respiratory Medicine" Mosby 845-857, 2008

33 Hartl D., "Cleavage of CXCR1 on neutrophils disables bacterial killing in cystic fibrosis lung disease" 13 : 1423-1430, 2007

34 Durnin JVGA, "Body fat assessed from total body density and its estimation from skinfold thickness: measurements on 481 men and women aged from 16 to 72 years" 32 : 277-297, 1974

35 Dauletbaev N., "Antioxidant properties of cystic fibrosis sputum" 288 : L903-L909, 2005

36 Zavorsky GS, "An openlabel dose response study of lymphocyte glutathione levels in healthy men and women receiving pressurized whey protein isolate supplements" 58 : 429-436, 2007

37 Elizur A., "Airway inflammation in cystic fibrosis" 133 : 489-495, 2008

38 Lands LC, "Accuracy of measurements of small changes in soft tissue mass by dualenergy absorptiometry" 19 : 279-285, 1996

39 Miller MR, "ATS=ERS Task Force: Standardisation of spirometry" 26 : 319-338, 2005

40 Eigen H., "A multicenter study of alternate-day prednisone therapy in patients with cystic fibrosis. Cystic Fibrosis Foundation Prednisone Trial Group" 126 : 515-523, 1995