Natasha Tasevska

Urinary Sugars—A Biomarker of Total Sugars Intake

Measurement error in self-reported sugars intake may explain the lack of consistency in the epidemiologic evidence on the association between sugars and disease risk. This review describes the development and applications of a biomarker of sugars intake, informs its future use and recommends directions for future research. Recently, 24 h urinary sucrose and fructose were suggested as a predictive biomarker for total sugars intake, based on findings from three highly controlled feeding studies conducted in the United Kingdom. From this work, a calibration equation for the biomarker that provides an unbiased measure of sugars intake was generated that has since been used in two US-based studies with free-living individuals to assess measurement error in dietary self-reports and to develop regression calibration equations that could be used in future diet-disease analyses. Further applications of the biomarker include its use as a surrogate measure of intake in diet-disease association studies. Although this biomarker has great potential and exhibits favorable characteristics, available data come from a few controlled studies with limited sample sizes conducted in the UK. Larger feeding studies conducted in different populations are needed to further explore biomarker characteristics and stability of its biases, compare its performance, and generate a unique, or population-specific biomarker calibration equations to be applied in future studies. A validated sugars biomarker is critical for informed interpretation of sugars-disease association studies.

Sugars and risk of mortality in the NIH-AARP Diet and Health Study

BACKGROUND Although previous studies have linked intake of sugars with incidence of cancer and other chronic diseases, its association with mortality remains unknown. OBJECTIVE We investigated the association of total sugars, added sugars, total fructose, added fructose, sucrose, and added sucrose with the risk of all-cause, cardiovascular disease, cancer, and other-cause mortality in the NIH-AARP Diet and Health Study. DESIGN The participants (n = 353,751), aged 50-71 y, were followed for up to 13 y. Intake of individual sugars over the previous 12 mo was assessed at baseline by using a 124-item NIH Diet History Questionnaire. RESULTS In fully adjusted models (fifth quartile compared with first quartile), all-cause mortality was positively associated with the intake of total sugars [HR (95% CI): 1.13 (1.06, 1.20); P-trend < 0.0001], total fructose [1.10 (1.04, 1.17); P-trend < 0.0001], and added fructose [1.07 (1.01, 1.13); P-trend = 0.005) in women and total fructose [1.06 (1.01, 1.10); P-trend = 0.002] in men. In men, a weak inverse association was found between other-cause mortality and dietary added sugars (P-trend = 0.04), sucrose (P-trend = 0.03), and added sucrose (P-trend = 0.006). Investigation of consumption of sugars by source showed that the positive association with mortality risk was confined only to sugars from beverages, whereas the inverse association was confined to sugars from solid foods. CONCLUSIONS In this large prospective study, total fructose intake was weakly positively associated with all-cause mortality in both women and men, whereas added sugar, sucrose, and added sucrose intakes were inversely associated with other-cause mortality in men. In our analyses, intake of added sugars was not associated with an increased risk of mortality. The NIH-AARP Diet and Health Study was registered at clinicaltrials.gov as NCT00340015.

Association between sucrose intake and risk of overweight and obesity in a prospective sub-cohort of the European Prospective Investigation into Cancer in Norfolk (EPIC-Norfolk)

Objective The objective of the present study was to investigate associations between sugar intake and overweight using dietary biomarkers in the Norfolk cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Norfolk). Design Prospective cohort study. Setting EPIC-Norfolk in the UK, recruitment between 1993 and 1997. Subjects Men and women (n 1734) aged 39–77 years. Sucrose intake was assessed using 7 d diet diaries. Baseline spot urine samples were analysed for sucrose by GC-MS. Sucrose concentration adjusted by specific gravity was used as a biomarker for intake. Regression analyses were used to investigate associations between sucrose intake and risk of BMI>25·0 kg/m2 after three years of follow-up. Results After three years of follow-up, mean BMI was 26·8 kg/m2. Self-reported sucrose intake was significantly positively associated with the biomarker. Associations between the biomarker and BMI were positive (β=0·25; 95 % CI 0·08, 0·43), while they were inverse when using self-reported dietary data (β=−1·40; 95 % CI −1·81, −0·99). The age- and sex-adjusted OR for BMI>25·0 kg/m2 in participants in the fifth v. first quintile was 1·54 (95 % CI 1·12, 2·12; P trend=0·003) when using biomarker and 0·56 (95 % CI 0·40, 0·77; P trend<0·001) with self-reported dietary data. Conclusions Our results suggest that sucrose measured by objective biomarker but not self-reported sucrose intake is positively associated with BMI. Future studies should consider the use of objective biomarkers of sucrose intake.

Association between urinary biomarkers of total sugars intake and measures of obesity in a cross-sectional study

Obesity is an important modifiable risk factor for chronic diseases. While there is increasing focus on the role of dietary sugars, there remains a paucity of data establishing the association between sugar intake and obesity in the general public. The objective of this study was to investigate associations of estimated sugar intake with odds for obesity in a representative sample of English adults. We used data from 434 participants of the 2005 Health Survey of England. Biomarkers for total sugar intake were measured in 24 h urine samples and used to estimate intake. Linear and logistic regression analyses were used to investigate associations between biomarker-based estimated intake and measures of obesity (body mass intake (BMI), waist circumference and waist-to-hip ratio) and obesity risk, respectively. Estimated sugar intake was significantly associated with BMI, waist circumference and waist-to-hip ratio; these associations remained significant after adjustment for estimated protein intake as a marker of non-sugar energy intake. Estimated sugar intake was also associated with increased odds for obesity based on BMI (OR 1.02; 95%CI 1.00–1.04 per 10g), waist-circumference (1.03; 1.01–1.05) and waist-to-hip ratio (1.04; 1.02–1.06); all OR estimates remained significant after adjusting for estimated protein intake. Our results strongly support positive associations between total sugar intake, measures of obesity and likelihood of being obese. It is the first time that such an association has been shown in a nationally-representative sample of the general population using a validated biomarker. This biomarker could be used to monitor the efficacy of public health interventions to reduce sugar intake.

Associations of Biomarker-Calibrated Intake of Total Sugars With the Risk of Type 2 Diabetes and Cardiovascular Disease in the Women’s Health Initiative Observational Study

The inconsistent findings from epidemiologic studies relating total sugars (TS) consumption to cardiovascular disease (CVD) or type 2 diabetes (T2D) risk may be partly due to measurement error in self-reported intake. Using regression calibration equations developed based on the predictive biomarker for TS and recovery biomarker for energy, we examined the association of TS with T2D and CVD risk, before and after dietary calibration, in 82,254 postmenopausal women participating in the Womens Health Initiative Observational Study. After up to 16 years of follow-up (1993-2010), 6,621 T2D and 5,802 CVD incident cases were identified. The hazard ratio for T2D per 20% increase in calibrated TS was 0.94 (95% confidence interval (CI): 0.77, 1.15) in multivariable energy substitution, and 1.00 (95% CI: 0.85, 1.18) in energy partition models. Multivariable hazard ratios for total CVD were 0.97 (95% CI: 0.87, 1.09) from energy substitution, and 0.91 (95% CI: 0.80, 1.04) from energy partition models. Uncalibrated TS generated a statistically significant inverse association with T2D and total CVD risk in multivariable energy substitution and energy partition models. The lack of conclusive findings from our calibrated analyses may be due to the low explanatory power of the calibration equations for TS, which could have led to incomplete deattenuation of the risk estimates.

The Use of Family Rituals in Eating Behaviors in Hispanic Mothers

Food rituals often abruptly change when Hispanic families migrate to the United States. This report describes changes in rituals of food procurement, preparation, and presentation (food-PPP) in Hispanic women following migration to the United States. Focus groups and face-to-face interviews were conducted with 13 low-income, overweight/obese Hispanic women 27 to 40 years of age. Content analysis was used to analyze cultural and contextual sources for food-PPP. Changes in rituals and traditions in food-PPP occurred, including materials and ingredients for traditional meals. Food rituals may play a role in healthful eating and could, therefore, serve as leverage points for interventions designed to promote healthy eating behaviors.

Association between urinary biomarkers of total sugars and sucrose intake and BMI in a cross-sectional study

Obesity is an important modifiable risk factors for chronic diseases. While there is increasing focus on the role of dietary sugars, there remains a paucity of data establishing the association between sugar intake and obesity in the general public. The objective of this study was to investigate associations of estimated sugar intake with odds for obesity in a representative samples of English adults. We used data from 434 participants of the 2005 Health Survey of England. Biomarkers for total sugar intake were measured in 24h urine samples and used to estimate intake. Linear and logistic regression analyses were used to investigate associations between estimated intake and measures of obesity (BMI, waist circumference and waist-to-hip ratio) and obesity risk., respectively. Estimated sugars intake was significantly associated with BMI, waist circumference and waist-to-hip ratio, and these associations remained significant after adjustment for estimated protein intake. Estimated sugars intake was also associated with increased odds for obesity based on BMI (OR 1.02; 95% CI 1.00; 1.04 per 10 g), waist-circumference (OR 1.03; 95% CI 1.01; 1.05) and waist-to-hip ratio (OR 1.04; 95% CI 1.02; 1.06); all OR estimates remained significant after adjusting for estimated protein intake. Our results show a significant association between biomarker-estimated total sugars intake and both measures of obesity and obesity risk, confirming positive associations between total sugar intake, measures of obesity and obesity risk. This biomarker could be used to monitor the efficacy of public health interventions.

Reply to V Ha et al

Dear Sir: We thank Ha et al for their comments on our findings from the analysis of dietary sugars and mortality risk in a large US cohort study (1). In their letter, Ha et al claim that the positive associations for sugars and cardiovascular vascular disease (CVD) mortality risk in women observed in our study may have been overestimated due to energy underreporting, which is more common in women. First, we would like to clarify that, although we did not find added or total sugars from beverages to be positively associated with CVD mortality risk in men, there was a significant increase in risk with greater intake of fructose from beverages in both men (HR for quartile 5 compared with quartile 1: 1.13; 95% CI: 1.05, 1.22; P-trend = 0.001) and women (HR for quartile 5 compared with quartile 1: 1.14; 95% CI: 1.02, 1.28; P-trend = 0.002). Furthermore, in both men and women, there was a borderline increased risk for CVD mortality with high total sugars and fructose intake (P-trend = 0.08–0.09) (Table 2 in reference 1). Ha et al argue that adjusting for energy intake “reduces the effect of potential confounding variables but does not address the underlying limitation of energy intake measurements: underreporting, which may lead to overestimation of the association between exposure and outcome.” In fact, adjusting for energy intake has been recommended in analyses of nutritional cohort studies as an approach to alleviate measurement error and attenuation of RR estimate in multivariable disease risk models with self-reported dietary variables measured with error (2, 3). We used the nutrient density method to adjust for energy intake, in which total energy and nutrient densities (g/1000 kcal) were entered in the multivariate models. In the Observing Protein and Energy Nutrition (OPEN) study, using the predictive biomarker for total sugars intake, we showed that the disease risk attenuation would be much less severe, albeit still present, when using total sugars density (g/1000 kcal) rather than absolute intake (g/d), as measured by the Diet History Questionnaire (4). Similar to findings for self-reported energy with the use of doubly labeled water (5), we also found that measurement error in self-reported sugars and predicted risk attenuation was greater in women than in men (4). We would, therefore, expect that the risk estimates for sugars observed in our article may have been attenuated and thus underestimated, rather than being overestimated as claimed by Ha et al. More important, to further investigate the possible effect of energy underreporting, the main analyses were re-run after excluding potential energy underreporters identified by the Goldberg cutoffs, which more than halved the sample size and the number of cases in both men and women (1). The RR estimates did not appreciably change; in fact, they increased slightly for some of the observed associations. A significantly positive association between added sugars and CVD mortality risk was also found in a recent prospective analysis of a nationally representative sample of US adults from NHANES III (1988–2006) (6). Compared with persons who consumed ≤8% of energy from added sugars, persons with 17–21% and >21% of energy from added sugars had multivariate HRs for CVD mortality of 1.38 and 2.03, respectively. However, no significant association between added sugars and total mortality was observed. This study population had a wider range of added sugars intake (10th–90th percentile: 7.5–25% of energy intake) than our study sample of educated 50- to 69-y-old adults (10th–90th percentile: 4–18%). Had this intake been higher, we may have more conclusively found higher risks with respect to added sugars and CVD risk. With regard to Ha et al’s discussion on the role of energy as the main mediator in the detrimental effect of fructose, we would like to emphasize that our models investigated the substitution effect of sugars, therefore simulating an isocaloric substitution of individual sugars for other energy-contributing macronutrients. Across all sugars we investigated, the strongest associations with mortality risk were found for total fructose, observed in both men and women. Our analysis thus suggests that the effect of sugars on mortality risk, and fructose in particular, extends beyond energy and may be explained by other mechanisms discussed in our article (1). To conclude, even though the associations found between sugars and mortality risk were stronger and apparent across different types of sugars in women, we also observed positive associations in men. On the basis of our previous investigations of the measurement error structure in self-reported sugars and energy based on predictive and recovery biomarkers, and our sensitivity analyses that excluded energy underreporters, it is unlikely that energy underreporting would have led to overestimation of the association between sugars and mortality risk in our analysis.