Advances in Nutrition: an International Review Journal
                                                                                   
                             Application of N-of-1 methods in personalized nutrition research
                                                                    --Manuscript Draft--
             Manuscript Number:                            ADVANCES-20-0451R2
             Full Title:                                   Application of N-of-1 methods in personalized nutrition research
             Short Title:                                  N-of-1 methods in nutrition research
             Article Type:                                 Perspective
             Keywords:                                     N-of-1;  precision nutrition;  personalized nutrition;  Ecological Momentary Assessment;
                                                           self-report measures;  study design;  review
             Corresponding Author:                         Baukje de Roos
                                                           University of Aberdeen
                                                           Aberdeen, UNITED KINGDOM
             Corresponding Author Secondary
             Information:
             Corresponding Author's Institution:           University of Aberdeen
             Corresponding Author's Secondary
             Institution:
             First Author:                                 Baukje de Roos
             First Author Secondary Information:
             Order of Authors:                             Baukje de Roos
                                                           Tilly Potter
                                                           Rute Vieira
             Order of Authors Secondary Information:
             Abstract:                                     Personalized and precision nutrition aim to examine and improve health on an
                                                           individual level, and this requires reconsideration of traditional dietary intervention or
                                                           behavioral study designs. The limited frequency of measurements in group-level
                                                           human nutrition trials cannot be used to infer individual response to interventions, while
                                                           in behavioral studies, retrospective data collection does not provide an accurate
                                                           measure of how everyday behaviors affects individual health. This review introduces
                                                           the concept of N-of-1 study designs, which involve the repeated measurement of a
                                                           health outcome or behavior on an individual level. Observational designs can be used
                                                           to monitor a participant’s usual health or behavior in a naturalistic setting, with repeated
                                                           measurements conducted in ‘real time’ using Ecological Momentary Assessment.
                                                           Interventional designs can introduce a dietary or behavioral intervention with predictors
                                                           and outcomes of interest measured repeatedly during, or after, one or more
                                                           intervention and control periods. Due to their flexibility, N-of-1 designs can be applied
                                                           to both short-term physiological studies and longer-term studies of eating behaviors.
                                                           As a growing number of disease markers can be measured outside of the clinic, with
                                                           self-reported data being delivered via electronic devices, it is now easier than ever to
                                                           generate large amounts of data on an individual level. Statistical techniques can be
                                                           utilized to analyze change in single individuals, or aggregate data from sets of N-of-1
                                                           trials, enabling hypotheses to be tested on a small number of heterogeneous
                                                           individuals. Although their design necessitates extra methodological and statistical
                                                           considerations, N-of-1 studies could be used to investigate complex research
                                                           questions and study underrepresented groups. This may help to reveal novel
                                                           associations between participant characteristics and health outcomes, with repeated
                                                           measures providing power and precision to accurately determine individual health
                                                           status.
             Additional Information:
             Question                                      Response
                                 Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation
 Manuscript                           Click here to access/download;Manuscript;N of 1
                                      review_highlighted_07DEC2020.docx
                                                                  1 
           
                   Application of N-of-1 methods in personalized nutrition research 
           
                1        2          1
          Tilly Potter , Rute Vieira , Baukje de Roos  
          1 Rowett Institute, University of Aberdeen  
          2 Institute of Applied Health Sciences, University of Aberdeen  
          Corresponding author:  
          Baukje de Roos  
          Rowett Institute, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD 
          +44 (0)1242 438636 
          b.deroos@abdn.ac.uk 
           
          Wordcount: 6559 
          Number of figures: 4 
          Number of tables: 1 
           
          Running title: N-of-1 methods in nutrition research 
           
          Funding: BBSRC-Unilever CTP PhD grant 
          The authors report no conflicts of interest. 
           
                                                2 
        
       Abbreviations 
        
       EMA  Ecological Momentary Assessment 
       RCT  Randomized Controlled Trial 
       SBP  Systolic Blood Pressure
                                                                                                                                3 
                   
                  Abstract 
            1     Personalized and precision nutrition aim to examine and improve health on an individual level, 
            2     and this requires reconsideration of traditional dietary intervention or behavioral study designs. 
            3     The limited frequency of measurements in group-level human nutrition trials cannot be used to 
            4     infer  individual  response  to  interventions,  while  in  behavioral  studies,  retrospective  data 
            5     collection does not provide an accurate measure of how everyday behaviors affects individual 
            6     health. This review introduces the concept of N-of-1 study designs, which involve the repeated 
            7     measurement of a health outcome or behavior on an individual level. Observational designs 
            8     can be used to monitor a participant’s usual health or behavior in a naturalistic setting, with 
            9     repeated measurements conducted in ‘real time’ using Ecological Momentary Assessment. 
           10     Interventional designs can introduce a dietary or behavioral intervention with predictors and 
           11     outcomes of interest measured repeatedly during, or after, one or more intervention and control 
           12     periods. Due to their flexibility, N-of-1 designs can be applied to both short-term physiological 
           13     studies and longer-term studies of eating behaviors. As a growing number of disease markers 
           14     can be measured outside of the clinic, with self-reported data being delivered via electronic 
           15     devices, it is now easier than ever to generate large amounts of data on an individual level. 
           16     Statistical techniques can be utilized to analyze change in single individuals, or aggregate data 
           17     from sets of N-of-1 trials, enabling hypotheses to be tested on a small number of heterogeneous 
           18     individuals.  Although  their  design  necessitates  extra  methodological  and  statistical 
           19     considerations, N-of-1 studies could be used to investigate complex research questions and 
           20     study underrepresented groups. This may help to reveal novel associations between participant 
           21     characteristics and health outcomes, with repeated measures providing power and precision to 
           22     accurately determine individual health status. 
           23     Key  words:  N-of-1,  precision  nutrition,  personalized  nutrition,  Ecological  Momentary 
           24     Assessment, self-report measures, study design, review