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ARTICLE IN PRESS
YDLD-2592; No. of Pages 2
Digestive and Liver Disease xxx (2014) xxx–xxx
Contents lists available at ScienceDirect
Digestive and Liver Disease journal homepage: www.elsevier.com/locate/dld
Correspondence Cholesterol change in coeliac patients following gluten-free diet depends on baseline levels To the Editor, In their recent paper on Digestive and Liver Disease, Zanini et al. discussed the relevance of a gluten-free diet (GFD) in modifying the cardiovascular (CV) risk of patients with coeliac disease (CD) [1]. Based on the analysis of a large cohort, these authors recognized that “GFD causes significant changes in parameters associated with CV risk” although they concluded that these changes “do not consistently point at a better or worse CV risk profile”. This overcautious assertion was supported by the fact that while HDL cholesterol (HDL-C), triglycerides (TG) and homocysteine improve significantly, others parameters including BMI, total cholesterol (TC) and LDL cholesterol (LDL-C) seem to get worse, as previously reported [2]. However, the authors’ claim that GFD may cause cholesterol levels to rise does not take into account a possible heterogeneity among CD patients at diagnosis [3]. In a recent retrospective study we evaluated 52 patients (94.2% women; median age 41 years), with biopsy-proven CD and free from primary dyslipidemia or other lipid altering conditions. Written informed consent was obtained from the subjects and the study was approved by the Ethics Committee of the local Health Authority. Patients were advised to adhere strictly for 24 months to a standard GFD (2200 kcal/d for females and 3000 kcal/d for males). Fasting TC, HDL-C and TG were assessed before and after GFD. LDL-C was calculated according to the Friedewald formula, VLDL cholesterol was calculated as the difference between TC and HDLC + LDL-C. Patients were divided into two subgroups based on baseline LDL-C levels higher or lower than the target value of 100 mg/dl according to NCEP guidelines [4]. Differences between groups were analyzed with the Mann–Whitney U test, and correlation was expressed by Pearson’s r coefficient, with a 5% significance level.
For the whole sample, no significant differences were observed between pre- and post-GFD lipid parameters. However, LDL-C increased by 20% and decreased by 10% in patient subgroups with initial values below or above 100 mg/dL, respectively (p = 0.0001). A consistent negative correlation (r = −0.566; p = 0.0001) was observed between LDL-C at baseline and the LDL-C difference before and after GFD. TC showed a similar trend, whereas HDL-C, VLDL and TG increased in both subgroups (Table 1). Potential gender differences could not be observed due to the small number of males. Our results show that changes in lipid parameters in GFDtreated CD patients are largely dependent on the initial profile. An inverse correlation exists between the initial values of TC and LDLC and the magnitude of their change. The overall treatment impact is to stabilize the lipid profile at near normal range, thus potentially reducing CV risk. Although untreated CD is usually associated with low TC levels, a subgroup of patients with non-classic presentations and without primary dyslipidemia, such as adults with hypochromic anaemia [5] or with minimal malabsorption, may display mild/moderate hypercholesterolemia at diagnosis, when a concomitant excess intake of dietary fat occurs. A strictly followed GFD implies close control of patient’s eating habits with the unintentional result that, as well as reducing gut inflammation and malabsorption, a coexisting dietary imbalance may be corrected. Thus, it is likely that in newly diagnosed patients displaying overt hypocholesterolemia, the effect of GFD is to increase cholesterol level via enhanced intestinal uptake and reduced steatorrhea. However, in the subset of CD patients whose cholesterol level is increased due to unhealthy eating habits, GFD may lower it even before the effects of increased intestinal absorption become apparent. This hypothesis should be examined in a larger clinical study. We believe that the concern about increased cardiovascular risk in patients following GFD is currently overemphasized.
Table 1 Changes in lipid parameters before and after gluten-free diet. Lipid parameters
Meanbefore (SD)
Meanafter (SD)
TC (mg/dl) HDL-C (mg/dl) TG (mg/dl) LDL-C (mg/dl) VLDL-C (mg/dl) HDL-C/LDL-C ratio
181.1 (38.7) 55.1 (15.7) 73.6 (34.3) 113.6 (38.0) 14.4 (7.2) 0.56 (0.31)
186.0 (39.8) 56.0 (14.8) 78.2 (42.8) 114.3 (32.3) 15.7 (8.5) 0.53 (0.22)
%before–after
P-valuea
LDL-Cbefore < 100 mg/dl
LDL-Cbefore ≥ 100 mg/dl
11.6 5.2 12.9 20.2 12.9 −4.0
−3.7 2.7 10.9 −10.4 10.2 16.0
0.003 0.747 0.938 0.0001 0.984 0.082
TC, total cholesterol; HDL-C, high density lipoprotein-cholesterol; TG, triglycerides; LDL-C, low density lipoprotein-cholesterol; VLDL-C, very low density lipoproteincholesterol. a Mann–Whitney U test. http://dx.doi.org/10.1016/j.dld.2014.02.015 1590-8658/© 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Pes GM, et al. Cholesterol change in coeliac patients following gluten-free diet depends on baseline levels. Dig Liver Dis (2014), http://dx.doi.org/10.1016/j.dld.2014.02.015
G Model YDLD-2592; No. of Pages 2
ARTICLE IN PRESS
2
Correspondence / Digestive and Liver Disease xxx (2014) xxx–xxx
References
Francesco Tolu Endocrinology Unit, AOU Sassari, Italy
[1] Zanini B, Mazzoncini E, Lanzarotto F, et al. Impact of gluten-free diet on cardiovascular risk factors: a retrospective analysis in a large cohort of coeliac patients. Dig Liver Dis 2013;45:810–5. [2] Norsa L, Shamir R, Zevit N. Gluten-free diet in coeliac disease: protective or providing additive risk factors for the development of cardiovascular disease. Nutr Ther Metab 2012;30:1–9. [3] Brar P, Kwon GY, Holleran S, et al. Change in lipid profile in celiac disease: beneficial effect of gluten-free diet. Am J Med 2006;119:786–90. [4] National Cholesterol Education Program: Third report of the expert panel on detection, evaluation and treatment of high blood cholesterol in adults (adult treatment panel III). NIH publication No. 01-3670. Department of Health and Human Services, National Institutes of Health, NHLBI; 2001. [5] Ciacci C, Cirillo M, Giorgetti G, et al. Low plasma cholesterol: a correlate of nondiagnosed celiac disease in adults with hypochromic anemia. Am J Gastroenterol 1999;94:1888–91.
Giovanni Mario Pes ∗ Department of Clinical and Experimental Medicine, University of Sassari, Italy
Monica Bazzu Maria Pina Dore Department of Clinical and Experimental Medicine, University of Sassari, Italy ∗ Corresponding author at: Dipartimento di Medicina Clinica e Sperimentale, Viale San Pietro 8, I-07100 Sassari, Italy. Tel.: +39 347 45 39 532; fax: +39 079 22 82 40. E-mail address: [email protected] (G.M. Pes)
Available online xxx
Please cite this article in press as: Pes GM, et al. Cholesterol change in coeliac patients following gluten-free diet depends on baseline levels. Dig Liver Dis (2014), http://dx.doi.org/10.1016/j.dld.2014.02.015
ARTICLE IN PRESS
YDLD-2592; No. of Pages 2
Digestive and Liver Disease xxx (2014) xxx–xxx
Contents lists available at ScienceDirect
Digestive and Liver Disease journal homepage: www.elsevier.com/locate/dld
Correspondence Cholesterol change in coeliac patients following gluten-free diet depends on baseline levels To the Editor, In their recent paper on Digestive and Liver Disease, Zanini et al. discussed the relevance of a gluten-free diet (GFD) in modifying the cardiovascular (CV) risk of patients with coeliac disease (CD) [1]. Based on the analysis of a large cohort, these authors recognized that “GFD causes significant changes in parameters associated with CV risk” although they concluded that these changes “do not consistently point at a better or worse CV risk profile”. This overcautious assertion was supported by the fact that while HDL cholesterol (HDL-C), triglycerides (TG) and homocysteine improve significantly, others parameters including BMI, total cholesterol (TC) and LDL cholesterol (LDL-C) seem to get worse, as previously reported [2]. However, the authors’ claim that GFD may cause cholesterol levels to rise does not take into account a possible heterogeneity among CD patients at diagnosis [3]. In a recent retrospective study we evaluated 52 patients (94.2% women; median age 41 years), with biopsy-proven CD and free from primary dyslipidemia or other lipid altering conditions. Written informed consent was obtained from the subjects and the study was approved by the Ethics Committee of the local Health Authority. Patients were advised to adhere strictly for 24 months to a standard GFD (2200 kcal/d for females and 3000 kcal/d for males). Fasting TC, HDL-C and TG were assessed before and after GFD. LDL-C was calculated according to the Friedewald formula, VLDL cholesterol was calculated as the difference between TC and HDLC + LDL-C. Patients were divided into two subgroups based on baseline LDL-C levels higher or lower than the target value of 100 mg/dl according to NCEP guidelines [4]. Differences between groups were analyzed with the Mann–Whitney U test, and correlation was expressed by Pearson’s r coefficient, with a 5% significance level.
For the whole sample, no significant differences were observed between pre- and post-GFD lipid parameters. However, LDL-C increased by 20% and decreased by 10% in patient subgroups with initial values below or above 100 mg/dL, respectively (p = 0.0001). A consistent negative correlation (r = −0.566; p = 0.0001) was observed between LDL-C at baseline and the LDL-C difference before and after GFD. TC showed a similar trend, whereas HDL-C, VLDL and TG increased in both subgroups (Table 1). Potential gender differences could not be observed due to the small number of males. Our results show that changes in lipid parameters in GFDtreated CD patients are largely dependent on the initial profile. An inverse correlation exists between the initial values of TC and LDLC and the magnitude of their change. The overall treatment impact is to stabilize the lipid profile at near normal range, thus potentially reducing CV risk. Although untreated CD is usually associated with low TC levels, a subgroup of patients with non-classic presentations and without primary dyslipidemia, such as adults with hypochromic anaemia [5] or with minimal malabsorption, may display mild/moderate hypercholesterolemia at diagnosis, when a concomitant excess intake of dietary fat occurs. A strictly followed GFD implies close control of patient’s eating habits with the unintentional result that, as well as reducing gut inflammation and malabsorption, a coexisting dietary imbalance may be corrected. Thus, it is likely that in newly diagnosed patients displaying overt hypocholesterolemia, the effect of GFD is to increase cholesterol level via enhanced intestinal uptake and reduced steatorrhea. However, in the subset of CD patients whose cholesterol level is increased due to unhealthy eating habits, GFD may lower it even before the effects of increased intestinal absorption become apparent. This hypothesis should be examined in a larger clinical study. We believe that the concern about increased cardiovascular risk in patients following GFD is currently overemphasized.
Table 1 Changes in lipid parameters before and after gluten-free diet. Lipid parameters
Meanbefore (SD)
Meanafter (SD)
TC (mg/dl) HDL-C (mg/dl) TG (mg/dl) LDL-C (mg/dl) VLDL-C (mg/dl) HDL-C/LDL-C ratio
181.1 (38.7) 55.1 (15.7) 73.6 (34.3) 113.6 (38.0) 14.4 (7.2) 0.56 (0.31)
186.0 (39.8) 56.0 (14.8) 78.2 (42.8) 114.3 (32.3) 15.7 (8.5) 0.53 (0.22)
%before–after
P-valuea
LDL-Cbefore < 100 mg/dl
LDL-Cbefore ≥ 100 mg/dl
11.6 5.2 12.9 20.2 12.9 −4.0
−3.7 2.7 10.9 −10.4 10.2 16.0
0.003 0.747 0.938 0.0001 0.984 0.082
TC, total cholesterol; HDL-C, high density lipoprotein-cholesterol; TG, triglycerides; LDL-C, low density lipoprotein-cholesterol; VLDL-C, very low density lipoproteincholesterol. a Mann–Whitney U test. http://dx.doi.org/10.1016/j.dld.2014.02.015 1590-8658/© 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Pes GM, et al. Cholesterol change in coeliac patients following gluten-free diet depends on baseline levels. Dig Liver Dis (2014), http://dx.doi.org/10.1016/j.dld.2014.02.015
G Model YDLD-2592; No. of Pages 2
ARTICLE IN PRESS
2
Correspondence / Digestive and Liver Disease xxx (2014) xxx–xxx
References
Francesco Tolu Endocrinology Unit, AOU Sassari, Italy
[1] Zanini B, Mazzoncini E, Lanzarotto F, et al. Impact of gluten-free diet on cardiovascular risk factors: a retrospective analysis in a large cohort of coeliac patients. Dig Liver Dis 2013;45:810–5. [2] Norsa L, Shamir R, Zevit N. Gluten-free diet in coeliac disease: protective or providing additive risk factors for the development of cardiovascular disease. Nutr Ther Metab 2012;30:1–9. [3] Brar P, Kwon GY, Holleran S, et al. Change in lipid profile in celiac disease: beneficial effect of gluten-free diet. Am J Med 2006;119:786–90. [4] National Cholesterol Education Program: Third report of the expert panel on detection, evaluation and treatment of high blood cholesterol in adults (adult treatment panel III). NIH publication No. 01-3670. Department of Health and Human Services, National Institutes of Health, NHLBI; 2001. [5] Ciacci C, Cirillo M, Giorgetti G, et al. Low plasma cholesterol: a correlate of nondiagnosed celiac disease in adults with hypochromic anemia. Am J Gastroenterol 1999;94:1888–91.
Giovanni Mario Pes ∗ Department of Clinical and Experimental Medicine, University of Sassari, Italy
Monica Bazzu Maria Pina Dore Department of Clinical and Experimental Medicine, University of Sassari, Italy ∗ Corresponding author at: Dipartimento di Medicina Clinica e Sperimentale, Viale San Pietro 8, I-07100 Sassari, Italy. Tel.: +39 347 45 39 532; fax: +39 079 22 82 40. E-mail address: [email protected] (G.M. Pes)
Available online xxx
Please cite this article in press as: Pes GM, et al. Cholesterol change in coeliac patients following gluten-free diet depends on baseline levels. Dig Liver Dis (2014), http://dx.doi.org/10.1016/j.dld.2014.02.015
