Adjustment for energy intake in nutritional research: a causal inference perspective

Abstract

Background Four models are commonly used to adjust for energy intake when estimating the causal effect of a dietary component on an outcome; 1) the “standard model” adjusts for total energy intake, 2) the “energy partition model” adjusts for remaining energy intake, 3) the “nutrient density model” rescales the exposure as a proportion of total energy, and 4) the “residual model” indirectly adjusts for total energy by using a residual. It remains underappreciated that each approach evaluates a different estimand and only partially accounts for confounding by common dietary causes. Objective To clarify the implied causal estimand and interpretation of each model and evaluate their performance in reducing dietary confounding. Design Semi-parametric directed acyclic graphs and Monte Carlo simulations were used to identify the estimands and interpretations implied by each model and explore their performance in the absence or presence of dietary confounding. Results The “standard model” and the mathematically identical “residual model” estimate the average relative causal effect (i.e., a “substitution” effect) but provide biased estimates even in the absence of confounding. The “energy partition model” estimates the total causal effect but only provides unbiased estimates in the absence of confounding or when all other nutrients have equal effects on the outcome. The “nutrient density model” has an obscure interpretation but attempts to estimate the average relative causal effect rescaled as a proportion of total energy intake. Accurate estimates of both the total and average relative causal effects may instead be estimated by simultaneously adjusting for all dietary components, an approach we term the “all-components model.” Conclusion Lack of awareness of the estimand differences and accuracy of the four modelling approaches may explain some of the apparent heterogeneity among existing nutritional studies and raise serious questions regarding the validity of meta-analyses where different estimands have been inappropriately pooled.

Higher Levels of Urinary Thiocyanate, a Biomarker of Cruciferous Vegetable Intake, Were Associated With Lower Risks of Cardiovascular Disease and All-Cause Mortality Among Non-smoking Subjects

“…Finally, our results should be interpreted with caution due to residual confounding. Although we have adjusted total energy intake in multivariate models, consistent with the isocaloric diet/disease relationship of greatest interest, the standard multivariate model failed to completely adjust for confounding from common causes of dietary intake and composition ( 54 ). In addition, there are numerous nutrients and non-nutrients in foods due to the complexity of human diet, and residual confounding of other dietary factors could not be eliminated, although we have adjusted some nutrients and foods intake in multivariate models and observed unaltered results.…”

Seaweed and Iodine Intakes and SLC5A5 rs77277498 in Relation to Thyroid Cancer

“…Seaweed consumption (g/day) of these two items and iodine intake (μg/day) from the whole diet were calculated using the Computer-Aided Nutritional Analysis Program (CAN-Pro) version 4.0 (Korean Nutrition Information Center, Seoul, Korea). In nutritional research, consumption of a diet component will result in a greater total energy intake and quantity of foods and thereby affect several important factors, such as body size and composition [ 20 ]. To account for the effect of a single food that is independent of total energy intake, consumption was estimated using the residual energy adjustment method and categorized into low and high intake based on the median value [ 21 ].…”

Prenatal antioxidant-enriched and pro-oxidant-contained food, IL4 and IL13 pathway genes, and cord blood IgE

“…More than never was defined as any. The fish intake was not energy-adjusted because we did not attempt to estimate the effects of individual dietary components and there has been considerable debate about which of the strategies of energy adjustment is most appropriate 34 .…”