Siedlinski M, Boer JMA, Smit HA, Postma DS, Boezen HM. Dietary factors and lung function in the general population: wine and resveratrol intake. Eur Respir J 2012; 39: 385–391; DOI: 10.1183/09031936.00184110
Wine intake is associated with a better lung function in the general population, yet the source of this effect is unknown. Resveratrol, a polyphenol in wine, has anti-inflammatory properties in the lung, its effects being partially mediated via induction of Sirtuin (SIRT)1 activity.
We assessed the impact of wine and resveratrol intake, and SIRT1 single-nucleotide polymorphisms (SNPs) on lung function in the general population. Effects of red and white wine and resveratrol intake on forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC were analysed in the population-based Doetinchem cohort (n = 3,224). Associations of four tagging SIRT1 SNPs with lung function were analysed in the Doetinchem (n = 1,152) and Vlagtwedde–Vlaardingen (n = 1,390) cohorts.
Resveratrol intake was associated with higher FVC levels, and white wine intake with higher FEV1 levels and lower risk of airway obstruction. SIRT1 SNPs were not significantly associated with level or course of lung function, either directly or indirectly via wine or resveratrol intake.
This study shows a positive association of resveratrol intake with lung function in the general population, confirms the previously reported positive association of white wine intake with higher levels of FEV1, and additionally shows an association with a higher FEV1/FVC ratio. These effects probably do not run via SNPs in SIRT1.
Background: Lung disease, especially chronic obstructive pulmonary disease (COPD), is a major cause of morbidity and mortality around the world. While cigarette smoking is by far the major environmental risk factor for COPD, in a previous study Schűnemann et al1 evaluated beverage-specific alcohol intakes for their association with pulmonary function measurements. These authors reported that, overall, there was no association between alcohol intake and pulmonary function. However, wine intake, especially white wine, was associated with better function. This was surprising to the authors, who had thought that red wine, with its greater content of anti-oxidant compounds, would show greater effect.1
In the current study from the Netherlands, performed in the large prospective population-based Doetinchem cohort, the authors sought to replicate the previously reported positive association between wine intake and the level of lung function. Further, they calculated total resveratrol intake and assessed its association with the level and longitudinal decline of lung function. Additionally, they studied the role of SIRT1 genetic variations and their interaction with smoking in relation to lung function in two distinct, prospective cohorts in the Netherlands.
The study reports that resveratrol intake was associated with higher FVC levels, and white wine intake with higher FEV1 levels and lower risk of airway obstruction. The paper states further that SIRT1 SNPs were not significantly associated with level or course of lung function, either directly or indirectly via wine or resveratrol intake.
The doses of resveratrol seen in this study, from population samples, are in the physiological range, very unlike the huge doses of resveratrol being evaluated in pharmaceutical studies. The findings that the benefits were not caused by SIRT helps separate the putative effects of wine from high-dose pharmaceuticals being tested for their effects on metabolic factors and longevity of life.2-4
In a recent publication,5 it was found that total antioxidant capacity (TAC) of food was positively associated with pulmonary function, in particular in non smoking pre-menopausal women, after adjustment for all possible confounders. Alcoholic beverages contributed to 31% of TAC, with coffee the major determinant (accounting for 41%).
Specific comments on the paper: Forum reviewers had a number of concerns regarding the analysis and implications of the authors. As one reviewer stated: “The authors have likely investigated pulmonary function associations with variables other than resveratrol or white wine. The level of adjustment is very poor; non-drinkers are not defined and probably also include ex-drinkers. It is not clear if the group of white wine drinkers is composed of subjects drinking white wine only or also drinking red wine or other types of alcoholic beverages. In the last case, results should be adjusted for other beverages (and for total alcohol content).
“In some countries people drinking white wine tend to consume more fish than meat, a difference that might influence the results observed. Exposure to working toxic substances might be more frequent in people drinking red wine (a more ‘popular’ beverage than white wine): thus the variable ‘social status’ should have been more extensively investigated than it appears from the paper. It is expected that confounding leads to the finding that red wine, that is responsible for the 84% of resveratrol intake, was not associated with lung function. Finally, the power for genetic analysis is quite low, especially considering multiple testing and a recessive model.”
Another Forum reviewer states that “The association between dietary resveratrol and wine consumption is virtually total (as noted in this paper) and previously reported.6 Thus the observed association with lung function could also be related to any other component found mostly in wine, or to wine itself, instead of resveratrol.” Another reviewer adds: “Resveratrol is just the bystander of something else present in wine. On a pure theoretical basis, the sum of different compounds all converging on the activation of Nrf2 could account for the results. Discriminating a single component is definitely an epistemological bias.”
Another reviewer states: “The authors make a confused, confusing, and unwarranted jump to assume that resveratrol was the operative component of red wine that was influencing pulmonary function. Further compounding the confusion are the reported effects associated with white wine.” Another Forum comment: “Since resveratrol was not the key, I question why the authors genotyped for SIRT1. There are many other SNPs with a better relationship to COPD, such as MMP12.”
References for Forum review:
1. Schűnemann HJ, Grant BJ, Freudenheim JL, et al. Beverage specific alcohol intake in a population-based study: evidence for a positive association between pulmonary function and wine intake. BMC Pulm Med 2002; 2: 3.
2. Baur JA, Sinclair DA. Therapeutic potential of resveratrol: the in vivo evidence. Nat Rev Drug Discov 2006;5:493–506.
3. Lagouge M, Argmann C, Gerhart-Hines Z, et al. Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell 2006;127:1109–1122.
4. Pearson KJ, Baur JA, Lewis KN, et al. Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending life span. Cell Metab 2008;8:157–168.
5. di Giuseppe R, Arcari A, Serafini M, Di Castelnuovo A, Zito Fm De Curtis A, Sieri S, Krogh V, Pellegrini N, Schűnemann HJ, Donati MB, de Gaetano G, Iacoviello L, on behalf of theMoli-sani Project Investigators. Total dietary antioxidant capacity and lung function in an Italian population: a favorable role in premenopausal/never smoker women. Eur J Clin Nutr 2011; doi: 10.1038/ejcn.2011.
6. Zamora-Ros R, Urpí-Sardà M, Lamuela-Raventós RM, et al. Resveratrol metabolites in urine as a biomarker of wine intake in free-living subjects: The PREDIMED Study. Free Radic Biol Med 2009;46:1562-1566.
An analysis based on a prospective study in the Netherlands assessed the impact of wine and resveratrol intake on lung function. It also studied genetic factors (affecting sirtuin) that have been found to be mechanisms by which resveratrol relates to metabolism and longevity of life. The authors report that resveratrol intake was associated with higher lung volumes and that white wine intake (but not red wine intake) was associated with lower risk of airway obstruction. They report that the genetic factors studied did not relate to the associations found.
While several previous studies (as does this one) have reported that wine intake improves lung function, Forum reviewers were concerned about several aspects of the paper, and especially with the conclusions of the authors that resveratrol was the key factor in improved lung function. A reviewer stated: “Resveratrol may well be just the bystander of something else present in wine.” The beneficial effects on lung function are probably related to many compounds present in wine, and not just resveratrol.
Based on a number of scientific studies, moderate wine intake appears to have a favorable effect on lung function. The doses of resveratrol seen in these epidemiologic studies are in the physiological range that could be expected from moderate wine consumption, unlike the huge doses of resveratrol being evaluated as a potential life-extending drug in pharmaceutical studies.
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Comments on this critique by the International Scientific Forum on Alcohol Research were provided by the following members:
Fulvio Ursini, MD, Dept. of Biological Chemistry, University of Padova, Padova, Italy
Ulrich Keil, MD, PhD, Institute of Epidemiology and Social Medicine, University of Münster, Münster, Germany
David Vauzour, PhD, Senior Research Associate, Department of Nutrition, Norwich Medical School, University of East Anglia, Norwich, UK
Harvey Finkel, MD, Hematology/Oncology, Boston University Medical Center, Boston, MA, USA
Andrew L. Waterhouse, PhD, Marvin Sands Professor, Department of Viticulture and Enology, University of California, Davis; Davis, CA, USA
R. Curtis Ellison, MD, Section of Preventive Medicine & Epidemiology, Boston University School of Medicine, Boston, MA, USA
Giovanni de Gaetano, MD, PhD, Research Laboratories, Catholic University, Campobasso, Italy