Response to “Metabolic improvement with fructose restriction: Is it the fructose or the weight loss?”

Obesity Letter to the Editor Response to “Metabolic Improvement with Fructose Restriction: Is It the Fructose or the Weight Loss? ” Robert H. Lustig TO THE EDITOR: Khan and Sievenpiper submit three separate criticisms. We proffer the following responses. 1. They point out that our study design did not incorporate an external control group. We addressed this in the article. Numerous stud- ies document that dietary sugar intake by recall is notoriously underestimated (1). Had we included an external control group, we could not have matched their baseline sugar intake, thus providing flawed results. The only way to correctly match intake would be to directly monitor all home, school, and after-school behaviors for months. Instead, we incorporated five sepa- rate internal controls: (a) a weight- maintaining paradigm; (b) DXA scanning (no change in body fat); (c) repeated meas- ures analysis of covariance adjusted for the small (0.9 kg) weight change; (d) sensitivity analysis, examining those who did not lose weight; and (e) investigator blinding throughout data collection. While lack of an external control group does not permit “categorical proof,” our conclusions as stated in the article are supported. 2. They state the children exhibited “dramatic weight loss. ” Again, this was previously addressed in the article. (a) The children www.obesityjournal. org lost 0.9 kg (95% CI 21.3, 20.6); given a mean baseline weight of 93 kg (0.96%), this is hardly dramatic. (b) The weight loss occurred within the first 4 days, then returned toward baseline. This is not consist- ent with persistent caloric deficit. (c) DXA scanning showed the weight loss occurred within the fat-free mass compartment (water and/or muscle), the loss of either of which would not contribute to improved metabolic health. Indeed, the temporal pattern of weight change and the 5 mmHg reduction of diastolic BP argues for water loss, as hyper- insulinemia causes sodium retention (2). We dismiss this criticism. 3. They argue that pre-post t-testing is the “hallmark of an uncontrolled design,” refer- encing Bland and Altman (3). This would be true if we were comparing pre-post test- ing between two treatment groups; [sic] “when there is a substantial change from baseline with both treatments, both tests against baseline will be significant and we can say nothing about the difference between groups. ” However, we are not reporting difference between two treat- ments. This argument does not apply to our paper. Furthermore, under “Better Approach” in the Bland/Altman paper: “’Not significant’ does not mean that there is no difference; it means that there is insuf- ficient evidence to conclude that a differ- ence exists. This is one of the reasons for the movement to report differences in randomized controlled trials with CIs rather than P values, or at least in addition to them. ” That’s exactly why we reported mean change, CI, and P values in our tables. Khan and Sievenpiper state our study cannot overturn the results of their numerous sys- tematic reviews and meta-analyses. However, these analyses suffer from flaws of their own, including publication bias; between- study heterogeneity; artifact of inadequate GI absorption in fructose-for-glucose exchange studies; random-effects modeling giving more weight to smaller studies; and, impor- tantly, lack of subclassification of industry- sponsored vs. independent studies (4). In fact, the one meta-analysis that accounts for these concerns supports our conclusion (5). We are unmoved by their arguments.O C 2016 The Obesity Society V References 1. Rangan A, Allman-Farinelli M, Donohoe E, Gill T. Misreporting of energy intake in the 2007 Australian Children’s Survey: differences in the reporting of food types between plausible, under- and over-reporters of energy intake. J Hum Nutr Diet 2014;27:450-458. 2. Brands MW, Manhiani MM. Sodium-retaining effect of insulin in diabetes. Am J Physiol Regul Integr Comp Physiol 2012;303:R1101-R1109. 3. Bland JM, Altman DG. Best (but oft forgotten) practices: testing for treatment effects in randomized trials by separate analysis of changes from baseline in each group is a misleading approach. Am J Clin Nutr 2015;102:991-994. 4. Satija A, Yu E, Willett WC, Hu FB. Understanding nutritional epidemiology and its role in policy. Adv Nutr 2015;6:5-18. 5. Imamura F, O’Connor L, Ye Z, et al. Consumption of sugar sweetened beverages, artificially sweetened beverages, and fruit juice and incidence of type 2 diabetes: systematic review, meta-analysis, and estimation of population attributable fraction. BMJ 2015;351:h3576. Department of Pediatrics, University of California, San Francisco, California, USA. Correspondence: Robert H. Lustig (rlustig@peds.ucsf.edu) Disclosure: Dr. Lustig reports author fees from Hudson Street Press. He is also a volunteer advisor to the UK NGO Action on Sugar and the unpaid President of the US nonprofit Institute for Responsible Nutrition. doi: 10.1002/oby.21438 Obesity | VOLUME 00 | NUMBER 00 | MONTH 2016