Literature Cited 1. Ye EQ, Chacko SA, Chou EL, Kugizaki M, Liu S. Greater whole-grain intake is associated with lower risk of type 2 diabetes, cardiovascular disease, and weight gain. J Nutr. 2012;142:1304–13. 2. Jones PH, Davidson MH, Stein EA, Bays HE, McKenney JM, Miller E, Cain VA. Blasetto JW for the STELLAR Study Group. Comparison of the efﬁcacy and safety of Rosuvastatin versus Atorvastatin, Simvastatin, and Pravastatin across doses (STELLAR Trail). Am J Cardiol. 2003; 92:152–60. 3. Pins JJ, Geleva D, Keenan JM, Fraxel C, O’Connor PJ, Cherney LM. Do whole-grain oat cereals reduce the need for antihypertensive medications and improve blood pressure control? J Fam Pract. 2002; 51:353–9. 4. Brownlee IA, Moore C, Chatﬁeld M, Richardson DP, Ashby P, Kuznesof SA, Jebb SA, Seal CJ. Markers of cardiovascular risk are not changed by increased whole-grain intake: the WHOLEheart study, a randomised, controlled dietary intervention. Br J Nutr. 2010;104:125–34. 5. Tighe P, Duthie G, Vaughan N, Brittenden J, Simpson WG, Duthie S, Mutch W, Wahle K, Horgan G, Thies F. Effect of increased consumption of whole-grain foods on blood pressure and other cardiovascular risk markers in healthy middle-aged persons: a randomized controlled trial. Am J Clin Nutr. 2010;92:733–40. 6. Brown L, Rosner B, Willett WW, Sacks FM. Cholesterol-lowering effects of dietary ﬁber: a meta-analysis. Am J Clin Nutr. 1999;69:30– 42. 7. Jenkins DJ, Kendall CW, Vuksan V, Augustin LS, Mehling C, Parker T, Vidgen E, Lee B, Faulkner D, Seyler H, et al. Effect of wheat bran on serum lipids; inﬂuence of particle size and wheat protein. J Am Coll Nutr. 1999;18:159–65. 1 Author disclosures: T. M. S. Wolever is president and part owner of Glycemic Index Laboratories, Inc. (GI Labs), a contract research organization; president and part owner of Glycaemic Index Testing, Inc., a corporation which provides consulting services to GI Labs; and received, within the last 3 years, consulting fees from McCain Foods Inc., Bunge, Ltd. and Temasek Polytechnic, Singapore. * To whom correspondence should be addressed: e-mail: thomas.wolever@ utoronto.ca. doi: 10.3945/jn.113.177139. Reply to Wolever Dear Editor, We appreciate the comments made by Dr. Wolever concerning our systematic review on whole grains and health outcomes. There were indeed substantial heterogeneities in the published literature, with intervention trials of metabolic intermediates displaying far greater heterogeneities than pro- spective cohorts linking whole grain intake to disease outcomes of interest. As described in the main text of our paper (RCT section, p. 1308-9), “Characteristics of the whole-grain interventions, control groups, duration, and design varied widely across studies.” “We observed heterogeneity across trials (P < 0.05), which remained signiﬁcant in subgroups after stratiﬁcation by dura- tion, study quality and health status.” Even with a small number of 21 trials identiﬁed, differences in study outcomes across trials were not likely due to sampling variation. While analyzing these heterogeneous studies, we compared the difference in postintervention means, not the difference in differences between intervention and control groups mentioned in Wolever’s letter. To provide some consistent comparison across trials, we also used the standardized mean difference as a summary statistic of effect measures. For example, in the study by Tighe et al. (1), the raw mean difference of LDL- cholesterol in the wheat and oat group compared to the controls is m 1 -m 2 5 3.35–3.5 5 -0.15 mmol/L with a pooled standard deviation of 0.1, 8 < : PSD ¼ ﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃ ðn 1 À 1ÞÂ SD 2 1 þðn 2 À 1ÞÂ SD 2 2 ðn 1 þ n 2 À 2Þ s 9 = ; resulting in a standardized mean difference of -0.15/0.1 5 -1.5 mmol/L. Thus, Wolever’s interpretation of the stan- dardized mean differences as crude mean differences taken directly from the original reports is not correct. In re-checking our database, however, we did correct two conversion errors regarding ﬁndings of total cholesterol levels (2) and LDL cholesterol levels (3). The pooled mean difference in levels of total cholesterol remained the same albeit with a wider 95% CI, while the pooled mean difference in LDL cho- lesterol levels was of -0.82 mmol/L. These changes do not affect the interpretation of ﬁndings from our meta-analysis (revised Supplemental Fig. 2 C, D). While we agree that caution must be exercised in in- tegrating ﬁndings from a pooled analysis of heterogeneous intervention trials particularly concerning the speciﬁc magni- tude of effect, we wish to note that different dietary portfolios have been shown to be effective and powerful medicine as pharmaceuticals, such as statins in terms of reducing CVD risk (1,4,5). Perhaps more importantly, the speciﬁc heteroge- neities identiﬁed in previous intervention trials in our meta- analysis should help design future intervention trials that use regimens that are comparable to those observed in prospective cohort studies (6). Sara A. Chacko Division of General Medicine and Primary Care, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA Yilin Chen University of California, Los Angeles (UCLA), Los Angeles, CA Simin Liu* Departments of Epidemiology and Medicine, Brown University, Providence, RI Literature Cited 1. Ye EQ, Chacko SA, Chou EL, Kugizaki M, Liu S. Greater whole-grain intake is associated with lower risk of type 2 diabetes, cardiovascular disease, and weight gain. J Nutr. 2012;142:1304–13. 2. Pins JJ, Geleva D, Keenan JM, Frazel C, O’Connor PJ, Cherney LM. Do whole-grain oat cereals reduce the need for antihypertensive medications and improve blood pressure control? J Fam Pract. 2002;51:353–9. 3. Brownlee IA, Moore C, Chatﬁeld M, Richardson DP, Ashby P, Kuznesof SA, Jebb SA, Seal CJ. Markers of cardiovascular risk are not changed by 1522 Letters to the Edtitor Downloaded from https://academic.oup.com/jn/article-abstract/143/9/1522/4571650 by guest on 03 March 2019