A Proactive Intervention Study in Metabolic Syndrome High-Risk Populations Using Phenome-Based Actionable P4 Medicine Strategy.

ABSTRACT

The integration of predictive, preventive, personalized, and participatory (P4) healthcare advocates proactive intervention, including dietary supplements and lifestyle interventions for chronic disease. Personal profiles include deep phenotypic data and genetic information, which are associated with chronic diseases, can guide proactive intervention. However, little is known about how to design an appropriate intervention mode to precisely intervene with personalized phenome-based data. Here, we report the results of a 3-month study on 350 individuals with metabolic syndrome high-risk that we named the Pioneer 350 Wellness project (P350). We examined (1) longitudinal (two times) phenotypes covering blood lipids, blood glucose, homocysteine (HCY), and vitamin D3 (VD3), and (2) polymorphism of genes related to folic acid metabolism. Based on personalized data and questionnaires including demographics, diet and exercise habits information, coaches identified 'actionable possibilities', which combined exercise, diet, and dietary supplements. After a 3-month proactive intervention, two-thirds of the phenotypic markers were significantly improved in the P350 cohort. Specifically, we found that dietary supplements and lifestyle interventions have different effects on phenotypic improvement. For example, dietary supplements can result in a rapid recovery of abnormal HCY and VD3 levels, while lifestyle interventions are more suitable for those with high body mass index (BMI), but almost do not help the recovery of HCY. Furthermore, although people who implemented only one of the exercise or diet interventions also benefited, the effect was not as good as the combined exercise and diet interventions. In a subgroup of 226 people, we examined the association between the polymorphism of genes related to folic acid metabolism and the benefits of folate supplementation to restore a normal HCY level. We found people with folic acid metabolism deficiency genes are more likely to benefit from folate supplementation to restore a normal HCY level. Overall, these results suggest (1) phenome-based data can guide the formulation of more precise and comprehensive interventions, and (2) genetic polymorphism impacts clinical responses to interventions. Notably, we provide a proactive intervention example that is operable in daily life, allowing people with different phenome-based data to design the appropriate intervention protocol including dietary supplements and lifestyle interventions. Supplementary Information The online version contains supplementary material available at 10.1007/s43657-023-00115-z.