Clinical Review & Education

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The Link Between Dietary Sugar Intake and Cardiovascular Disease Mortality An Unresolved Question Nikhil V. Dhurandhar, PhD; Diana Thomas, PhD

JAMA INTERNAL MEDICINE Added Sugar Intake and Cardiovascular Diseases Mortality Among US Adults Quanhe Yang, PhD; Zefeng Zhang, MD, PhD; Edward W. Gregg, PhD; W. Dana Flanders, MD, ScD; Robert Merritt, MA; Frank B. Hu, MD, PhD IMPORTANCE Epidemiologic studies have suggested that higher intake of added sugar is associated with cardiovascular disease (CVD) risk factors. Few prospective studies have examined the association of added sugar intake with CVD mortality. OBJECTIVE To examine time trends of added sugar

consumption as percentage of daily calories in the United States and investigate the association of this consumption with CVD mortality. DESIGN, SETTING, AND PARTICIPANTS National Health and Nutrition Examination Survey (NHANES, 1988-1994 [III], 1999-2004, and 2005-2010 [n = 31 147]) for the time trend analysis and NHANES III Linked Mortality cohort (1988-2006 [n = 11 733]), a prospective cohort of a nationally representative sample of US adults for the association study. MAIN OUTCOMES AND MEASURES Cardiovascular disease

mortality. RESULTS Among US adults, the adjusted mean percentage of daily calories from added sugar increased from 15.7% (95% CI, 15.0%-16.4%) in 1988-1994 to 16.8% (16.0%-17.7%; P = .02) in

In the April 2014 issue of JAMA Internal Medicine, Yang et al1 summarized findings from NHANES from 1988 to 2010 showing that there was relatively little change in the consumption of added sugar in terms of the proportion of total calories consumed. At the beginning of the study period (1988-1994), 15.7% (95% CI, 15.0%16.4%) of the total calories consumed were from added sugar (approximately 350 kcal/day), and 14.9% (95% CI, 14.2%-15.5%) of calories consumed were from added sugar (approximately 326 kcal/day) at the end of the observation period (2005-2010). With nearly 15 years of follow-up, there was a significant dosedependent relationship between reported ingestion of added jama.com

1999-2004 and decreased to 14.9% (14.2%-15.5%; P < .001) in 2005-2010. Most adults consumed 10% or more of calories from added sugar (71.4%) and approximately 10% consumed 25% or more in 2005-2010. During a median follow-up period of 14.6 years, we documented 831 CVD deaths during 163 039 person-years. Age-, sex-, and race/ethnicity–adjusted hazard ratios (HRs) of CVD mortality across quintiles of the percentage of daily calories consumed from added sugar were 1.00 (reference), 1.09 (95% CI, 1.05-1.13), 1.23 (1.12-1.34), 1.49 (1.24-1.78), and 2.43 (1.63-3.62; P < .001), respectively. After additional adjustment for sociodemographic, behavioral, and clinical characteristics, HRs were 1.00 (reference), 1.07 (1.02-1.12), 1.18 (1.06-1.31), 1.38 (1.11-1.70), and 2.03 (1.26-3.27; P = .004), respectively. Adjusted HRs were 1.30 (95% CI, 1.09-1.55) and 2.75 (1.40-5.42; P = .004), respectively, comparing participants who consumed 10.0% to 24.9% or 25.0% or more calories from added sugar with those who consumed less than 10.0% of calories from added sugar. These findings were largely consistent across age group, sex, race/ethnicity (except among non-Hispanic blacks), educational attainment, physical activity, health eating index, and body mass index. CONCLUSIONS AND RELEVANCE Most US adults consume more added sugar than is recommended for a healthy diet. We observed a significant relationship between added sugar consumption and increased risk for CVD mortality.

JAMA Intern Med. 2014;174(4):516-524. doi:10.1001/jamainternmed.2013 .13563.

sugar and cardiovascular (CVD) mortality. These findings were consistent across subpopulations, and after adjusting for confounding factors, the associations were strengthened. These observations are interesting because during a time period when the prevalence of obesity was increasing,2 added sugar consumption was relatively stable. However, individuals who reported more than 25% of their total intake as added sugar did have greater CVD mortality (adjusted hazard ratio of 2.75). The Institute of Medicine (IOM) recommendation3 is that less than 25% of total kilocalories come from added sugar. This criterion was met by 83.4% to 91.9% of the participants in the study by (Reprinted) JAMA March 3, 2015 Volume 313, Number 9

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Clinical Review & Education From The JAMA Network

Yang et al.1 Only a small proportion of the population had sugar intake above IOM recommendations. On the other hand, the World Health Organization (WHO) recommends that less than 10% of total kilocalories come from sugar. Only about 22% to 30% of the participants in the study by Yang et al met the WHO recommendations4 for sugar kilocalories. Although substantial debate exists regarding health status and sugar consumption, only a relatively small proportion of the population is overconsuming sugar based on IOM standards. Nevertheless, those who do consume added sugar that composes 25% or more of their total consumption have greater risk for CVD mortality. Two important yet distinct policy questions arise from this analysis: do the results warrant a public health policy change resulting in a population-wide decrease in added sugar consumption, as many have advocated?5 Is there sufficient evidence to recommend reduction in sugar consumption with the goal of reducing CVD mortality? By mandating change, public health policies may influence every individual in the population, independent of their personal riskto-benefit ratio. Therefore, substantial justification is needed to propose a new health policy. There are no universally accepted criteria for the quantity and quality of evidence required to warrant a public policy around a health issue. Nevertheless, implementation of a health policy would be reasonable if a health-related issue is widespread in the population and worsening with time, if the benefits of a health policy outweigh any drawbacks, and if new data emerge that suggest a benefit in change of existing health policy. The study by Yang et al1 demonstrated that a relatively small fraction of the population consumes too much added sugar (ⱖ25% of total consumption). The proportion of patients ingesting this much sugar in the study by Yang et al1 was stable over time. Although overconsumption of sugar was associated with increased mortality, this was experienced in a relatively small number of people in the United ARTICLE INFORMATION Author Affiliations: Department of Nutritional Sciences, Texas Tech University, Lubbock (Dhurandhar); Center for Quantitative Obesity Research, Department of Mathematical Sciences, Montclair State University, Montclair, New Jersey (Thomas).

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States, if the IOM-based standard is used. Thus, the study results do not support application of policies to reduce sugar consumption. What recommendations should be made for individuals who do ingest too much sugar? A recent IOM analysis of risk attributable to added sugar intake did not yield a definitive result.3 Some but not all of the studies the IOM assessed found increased CVD markers in response to ingesting sugar above the IOM standard.3 A metaanalysis of 39 intervention trials of 2 weeks’ to 8 months’ duration found modestly increased concentrations of blood lipids and blood pressure in individuals overconsuming sugar.6 However, changes in cardiometabolic risk factors do not necessarily translate to changes in CVD mortality. This occurred in the Long-term Action for Health in Diabetes (Look AHEAD) study.7 Look AHEAD was a long-term, large-scale randomized clinical trial that implemented weight loss in participants with type 2 diabetes. Weight loss was associated with a significant reduction in cardiovascular risk factors, but these reductions were not associated with fewer cardiovascular events or improved CVD mortality at 10 years of follow-up.7 The study by Yang et al1 is important for what it does and does not imply. The relationship between added sugar intake and CVD mortality remains unresolved. The study by Yang et al1 does not support implementation of health policies limiting sugar intake because a relatively small fraction of the total population ingests excessive amounts of sugar by the IOM criteria. The implications vary substantially based on the criteria used for defining excess sugar consumption. Therefore, consensus may be needed to adopt a single criteria for defining excess consumption of added sugar. Indeed, although added sugar intake may increase CVD risk factors, the causal relationship between sugar ingestion, CVD risk factors, and CVD mortality remains unclear. Laws attempting to limit excess sugar intake have been passed and overturned on legal grounds.5 Aside from the legal questions, there is insufficient scientific evidence to support pursuit of policies limiting sugar intake.

Journal of Obesity, Roche, and Lancet Infectious Diseases and having been granted or having applied for patents related to obesity and metabolic disorders. Dr Thomas reported having been a consultant for Jenny Craig from 2011 to 2013.

4. Nishida C, Uauy R, Kumanyika S, Shetty P. The joint WHO/FAO expert consultation on diet, nutrition and the prevention of chronic diseases: process, product and policy implications. Public Health Nutr. 2004;7(1A):245-250.

REFERENCES

5. Gostin LO, Reeve BH, Ashe M. The historic role of boards of health in local innovation: New York City’s soda portion case. JAMA. 2014;312(15):1511-1512.

Corresponding Author: Nikhil V. Dhurandhar, PhD, Department of Nutritional Sciences, Texas Tech University, 1301 Akron Ave, Ste 402, Lubbock, TX 79409 ([email protected]).

1. Yang Q, Zhang Z, Gregg EW, Flanders WD, Merritt R, Hu FB. Added sugar intake and cardiovascular diseases mortality among US adults. JAMA Intern Med. 2014;174(4):516-524.

Conflict of Interest Disclosures: Both authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Dhurandhar reported having received grants from Vital Health Interventions, American Egg Board, Mathile Institute for the Advancement of Human Nutrition, Novartis Nutrition, Kellogg Company, Genentech, Ortho McNeil, and Roche and fees from the American Egg Board, Vivus, International

2. Flegal KM, Carroll MD, Ogden CL, Curtin LR. Prevalence and trends in obesity among US adults, 1999-2008. JAMA. 2010;303(3):235-241. 3. Institute of Medicine Panel on Macronutrients. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, DC: National Academy Press; 2005.

6. Te Morenga LA, Howatson AJ, Jones RM, Mann J. Dietary sugars and cardiometabolic risk: systematic review and meta-analyses of randomized controlled trials of the effects on blood pressure and lipids. Am J Clin Nutr. 2014;100(1):65-79. 7. Wing RR, Bolin P, Brancati FL, et al; Look AHEAD Research Group. Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes. N Engl J Med. 2013;369(2):145-154.

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The link between dietary sugar intake and cardiovascular disease mortality: an unresolved question.

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