Protocol for a randomized controlled trial to test the acceptability and adherence to 6-months of walnut supplementation in Chinese adults at high risk of cardiovascular disease

Yishu Liu, Nan Li, Ni Yan, Xiong-Fei Pan, Qiang Li, Renata Micha, Dariush Mozaffarian, Mark D Huffman, Yanfang Wang, Bruce Neal, Maoyi Tian, Yi Zhao, Jason H Y Wu, Yishu Liu, Nan Li, Ni Yan, Xiong-Fei Pan, Qiang Li, Renata Micha, Dariush Mozaffarian, Mark D Huffman, Yanfang Wang, Bruce Neal, Maoyi Tian, Yi Zhao, Jason H Y Wu

Abstract

Background: Consumption of nuts improves cardio-metabolic risk factors in clinical trials and relates to lower risk of cardiovascular disease (CVD) in prospective observational studies. However, there has not been an adequately powered randomized controlled trial to test if nuts supplementation actually reduces incident CVD. In order to establish the feasibility of such a trial, the current study aimed to assess the acceptability and adherence to long-term nut supplementation amongst individuals at high CVD risk in China.

Methods: This protocol described a 6-month trial performed in Ningxia Province in China among participants with a history of CVD or older age (female ≥65 years, male ≥60 years) with multiple CVD risk factors. Participants were randomized to control (received non-edible gift), low dose walnut (30 g/d), or high dose walnut (60 g/d) groups in a 1:1:1 ratio. Walnuts were provided at no cost to participants and could be consumed according to personal preferences. Follow-up visits were scheduled at 2 weeks, 3 months and 6 months. The primary outcome was fasting plasma alpha linolenic acid (ALA) levels used as an indicator of walnut consumption. Secondary outcomes included self-reported walnut intake from the 24 h dietary recalls. The target sample size of 210 provided 90% statistical power with two-sided alpha of 0.05 to detect a mean difference of 0.12% (as percent of total fatty acid) in plasma ALA between randomized groups.

Results: Two hundred and ten participants were recruited and randomized during October 2019. Mean age of participants was 65 years (SD = 7.3), 47% were females, and 94% had a history of CVD at baseline. Across the three study groups, participants had similar baseline demographic and clinical characteristics.

Discussion: This trial will quantify acceptability and adherence to long-term walnut supplementation in a Chinese population at high risk of CVD. The findings will support the design of a future large trial to test the effect of walnut supplementation for CVD prevention.

Trial registration: NCT04037943 Protocol version: v3.0 August 14 2019.

Keywords: Cardiovascular disease; Nuts; Plasma ALA; Randomized controlled trial.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Trial Flowchart. 210 participants with high risk of CVD were recruited from 6 rural villages in Ningxia Province, China. They were randomized in a 1:1:1 ratio to either the control group, or low-dose walnut (30 g/day) intervention group, or high-dose walnut (60 g/day) intervention group; and followed-up for 6 months. Outcome data were collected from participants at study baseline, the interim visits, and at the end of trial visit

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