Concept: Complementary and Integrative Health Approaches To Promote Whole Person Health Restoration via Emotional Well-Being Mechanisms

Project Concept Review

Council Approval: March 4, 2025

Program Directors: Erin Burke Quinlan, Ph.D. and Jennifer Baumgartner, Ph.D.

Background

Health and disease are not separate, disconnected states. Rather, they exist on a continuum, wherein a person can move toward or away from a state of health. The process by which individuals travel along this continuum from a less healthy state to a healthier state can be referred to as health restoration. Health restoration is likely complex and multifactorial, involving multiple pathways, mechanisms, and the whole person. One way to assess health restoration is to explore potential positive changes in whole person health (WPH). WPH involves looking at the whole person—not just separate organs or body systems—and considering factors that promote either health or disease. Instead of just treating a specific disease, WPH focuses on restoring health and preventing diseases across the lifespan. In collaboration with the Centers for Disease Control and Prevention, the National Center for Complementary and Integrative Health (NCCIH) has created the Whole Person Health Index (WPH Index) Patient Reported Measure that consists of nine domains asking individuals to rate their overall health, quality of life, social and family connections, physical activity, diet, stress management, sleep, sense of meaning and purpose, and health management.

As noted in NCCIH’s strategic plan, there is a fundamental lack of research on the mechanisms of health restoration in humans. The strategic plan also notes that the evidence base for the efficacy and effectiveness of complementary and integrative health approaches in the context of health restoration is limited. Therefore, NCCIH seeks to advance the understanding of the mechanisms through which complementary and integrative health approaches may promote WPH restoration and their degrees of efficacy and effectiveness.

One malleable factor that has the potential to engage WPH restoration processes is emotional well-being (EWB). EWB is a priority area for NCCIH. In January 2021, NCCIH, along with the National Institute on Aging and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, funded six research networks as part of the Emotional Well-Being Initiative. Those networks defined EWB as a multidimensional composite that encompasses how positive an individual feels generally and about life overall (Park et al., 2022). It includes both experiential features (emotional quality of momentary and everyday experiences) and reflective features (judgments about life satisfaction, sense of meaning and purpose, and ability to pursue goals that can include and extend beyond the self). Positive emotions and EWB have been associated with better health, including improved recovery and survival from physical illness. However, there are few studies assessing the impact of complementary and integrative health approaches on EWB mechanisms implicated in WPH restoration. There are also limited clinical trials, such as multisite feasibility trials, collecting WPH outcomes and emotion regulation mechanisms that could eventually be tested in a fully powered efficacy trial. 

This health restoration initiative will address these fundamental knowledge gaps by supporting the study of the effects of complementary and integrative health approaches on mechanisms of EWB to promote WPH and associated efficacy and effectiveness.

Purpose of Proposed Initiative

The proposed initiative aims to support highly innovative research programs that advance our understanding of how complementary and integrative health approaches impact EWB as the targeted mechanisms and WPH as measured by an integrated WPH restoration outcome (WPH Index highly recommended). The scope of this initiative will include prospective mechanistic clinical trials and other types of clinical trials that assess feasibility, efficacy, or effectiveness. These programs should include, at a minimum, a complementary and integrative health approach, an EWB mechanistic target, and an integrated health restoration outcome (WPH Index) measured at baseline as well as after administration of the intervention. 

Applicants will be required to specify:

• The WPH restoration outcome
  • Applicants will be strongly encouraged to make full use of the nine-item WPH Index or measurement of its individual components to capture movement toward health.
  • Components include overall health, quality of life, social and family connections, physical activity, diet, stress management, sleep, sense of meaning and purpose, and health management.
  • Applicants may also include other clinically relevant health restoration outcomes.
  • The length of the study follow-up period. Recommendation of at least 6 months based on clinical relevance.
  • The EWB mechanism targeted by the complementary and integrative health approach.
  • A clearly defined model to be tested in a future fully powered clinical efficacy trial that delineates the effect of the mind and body intervention on the WPH restoration outcome and the extent to which this can be explained (e.g., mediated) by the EWB pathway.

Objectives

Examples of research topics of interest include, but are not limited to:

• Mechanistic clinical trials testing how complementary and integrative health approaches specifically impact an EWB-related mechanism as the primary outcome and the WPH Index as a secondary outcome. Examples of potential EWB mechanistic categories to be explored are:
  • Emotion regulation
  • Neural circuitry
  • Microbiome
  • Inflammation
  • Epigenetics
  • Gene expression
  • DNA repair

• Mechanistic studies that test whether EWB mechanisms mediate the effect of complementary and integrative health approaches to produce desired WPH restoration outcomes:
• A mindfulness intervention study in adults with high anxiety symptoms that assesses changes in affective brain networks as a potential EWB-related target and associates those brain changes with changes in the integrated WPH Index. Consideration of specific domains of the WPH Index as mediators (e.g. social/family connection, stress management, quality of life) can be addressed as secondary aims.
• A yoga intervention study in individuals with chronic asthma that assesses changes in mitochondrial function and inflammation as a potential EWB-related target and assesses whether these changes mediate the effect of the yoga intervention on changes in the integrated WPH Index with long-term follow up. Consideration of specific domains of the WPH Index as mediators (e.g., physical activity, sleep, health management) can be addressed as secondary aims.
• An acupuncture intervention study in individuals with chronic low-back pain that identifies the brain’s salience network as a potential EWB-related target and tests whether changes in the salience network mediate the effect of the acupuncture intervention on changes in the integrated WPH Index. 
• Mechanistic studies to identify and evaluate EWB measures as potential biomarkers to predict the impact of complementary and integrative health approaches on the WPH Index. 
• Experimental medicine study designs that would identify potential EWB targets or mechanisms and test their engagement and the degrees to which these targets or mechanisms mediate the effect of complementary and integrative health approaches to produce desired WPH restoration outcomes.

• Multisite clinical trials of feasibility, acceptability, and fidelity of delivery of a complementary and integrative health approach, and the collection of WPH restoration outcomes and EWB-related mechanisms. For example:
  • A mindfulness-based intervention that can be delivered with fidelity across two criminal justice settings in correctional officers with high burnout and establishes feasibility of measuring emotion regulation and the WPH Index over time.
  • A group-based music intervention that can be delivered with fidelity across sites in individuals with chronic pain and establishes feasibility of collecting oxytocin as an indicator of social connection, social and physical functioning, and correlate it with the WPH Index over time.
  • A compassion meditation intervention optimized for self-other connections in individuals with depression that can be delivered across sites and establishes feasibility and acceptability of collecting neural indicators of self-referential processing, sense of meaning, and purpose, and correlates this with the WPH Index over time.
  • A multicomponent intervention that can be delivered with fidelity across sites in individuals with high allostatic load and establishes feasibility and acceptability of collecting gut microbiome samples, as well as WPH Index, over time.
  • A yoga intervention that can be delivered with fidelity in community health centers for survivors of a climate-related disaster and establishes feasibility and acceptability of measuring connections between mitochondrial function, positive mood states, and the WPH Index over time.

• Multisite clinical trials to test the impact of complementary and integrative health approaches on WPH restoration outcomes efficacy analyses.

Reference

Park CL, Kubzansky LD, Chafouleas SM, et al. Emotional well-being: what it is and why it matters. Affective Science. 2022;4(1):10-20.