Nuts and Oil Pilot Study

Metabolic syndrome (MetS) is a collection of at least three out of five cardiometabolic risk factors including abdominal obesity, hypertension, elevated blood glucose, hypertriglyceridemia, and low high-density lipoprotein cholesterol. MetS is a major risk factor for cardiovascular disease and is considered a state of prediabetes. Improving metabolic parameters through dietary, behavioral, and pharmacological interventions can improve or reverse MetS. For example, increased consumption of extra virgin olive oil (EVOO) and mixed nuts was shown to reduce cardiovascular event rates and reverse MetS in a 5-year study in Spain (PREDIMED study). However, lower levels of adherence to the PREDIMED intervention was found in participants with a higher number of cardiovascular risk factors, larger waist circumference, and lower physical activity levels at baseline. New strategies to convey one's risk of morbidity and mortality at the onset of a dietary intervention may improve intervention adherence, particularly among individuals meeting the criteria for MetS.

A greater DNA methylation-based predicted age relative to chronological age, often referred to as "epigenetic age acceleration", has been associated with many lifestyle factors, including physical activity and diet, as well as components of MetS, including obesity, blood pressure, HDL cholesterol and blood glucose levels.

The investigators hypothesize that the majority of people with MetS have advanced epigenetic aging, and among those that have advanced epigenetic age, learning one's epigenetic age, and epigenetic age-based predicted risk of morbidity and mortality at the onset of a dietary intervention will improve participant adherence to the dietary intervention. Further, the investigators hypothesize that EVOO and tree nut supplementation in participants with MetS and advanced epigenetic age could help reverse MetS and potentially slow epigenetic aging. Therefore, the investigators plan to conduct a feasibility pilot study to:

1. To determine the proportion of participants with MetS with epigenetic age acceleration
2. To assess adherence to daily EVOO and tree nut consumption over a 4-week intervention in participants informed of epigenetic age acceleration at baseline compared to the control group
3. Qualitatively explore how participants perceive epigenetic age, and how participants' experiences would impact the feasibility of a larger clinical intervention in terms of challenges and motivators
4. Compare epigenetic age acceleration before and after the 4-week intervention

For this study the investigators will recruit ~50 individuals with MetS aged 35 years or older. An in-person assessment visit will be scheduled for a morning time and participants will be asked to be fasting and will be instructed to bring their medications to the visit. Candidates will review the informed consent document at an in-person screening with study staff prior to beginning their participation. For all participants providing informed consent, who were fasting and met the MetS criteria at the initial in-person assessment visit, collected blood samples will be used to calculate epigenetic age acceleration. Other measures to be collected include body weight, height, waist circumference, blood pressure, and questionnaires about demographics, health history and health habits. Participants that meet the inclusion criteria during the in-person screening visit will be contacted to schedule a baseline intervention visit.

At the intervention visit, all participants will receive a 4-week supply of EVOO and tree nuts, including unsalted English walnuts, almonds or pistachios (approximately 10-day supply of each type). Participants will be asked to supplement their normal diets with these products and will be provided recipes and other information that will allow them to replace other foods with the nuts and oil. The investigators will ask participants to consume one ounce of tree nuts per day and two tablespoons of EVOO per day by incorporating these foods into their diet. Dietary adherence diaries will be given to measure incorporation of the study foods.

Participants will be randomized to learn about epigenetic age acceleration (arm 1) or not to learn about epigenetic age acceleration (arm 2) in a 1:1 allocation at the baseline visit. Those in the intervention arm 1 that are to learn about epigenetic age acceleration will receive some educational materials and a brief description of epigenetic age acceleration.

A telephone visit will be scheduled to take place at the end of week 1 for additional diet counseling, to assess safety/potential side effects and to collect adherence diaries. A follow-up phone call for compliance assessment and to answer participant questions will be conducted at the end of week 2. A final measurement visit will be scheduled for the end of week 4 for a morning time and participants will be asked to be fasting. At the final measurement visit, the same measures as listed in the in-person assessment visit will be performed and study questionnaires, with the exception of demographics and health history, will be distributed.

After the intervention, participants will be asked to come in for the end of week 4 visit, For participants in the intervention arm 1 (participants educated about epigenetic age acceleration), a self- administered exit questionnaire will be given to qualitatively explore participants' perception of epigenetic age, and challenges and motivators for behavior change during the intervention, The open-ended questions will be designed to ascertain understanding of epigenetic age, and assess the challenges and motivators participants encounter during the intervention.

Participants in both arms will be administered an Intervention Experience Assessment to explore how participant's experiences would impact the feasibility of a larger clinical intervention in terms of challenges and motivators.

This feasibility study, incorporating epigenetic age estimates with a dietary intervention in individuals with MetS, is an initial step in building our understanding of 1) the relationship between MetS and epigenetic age, 2) how epigenetic age estimates may be perceived by patients at high risk for CVD, and 3) will provide preliminary longitudinal data examining the potential to slow epigenetic age acceleration predictions after a 4-week dietary intervention to provide feasibility for a larger future study.