Preferential Metabolic Improvement by Intermittent Fasting in People with Elevated Baseline Red Cell Distribution Width: A Secondary Analysis of the WONDERFUL Randomized Controlled Trial.

Benjamin D Horne,Kirk U Knowlton,Jeffrey L Anderson,Sterling T Bennett,Joseph B Muhlestein,Heidi T May,Viet T Le,Tami L Bair

doi:10.3390/nu13124407

Abstract

Red cell distribution width (RDW) predicts cardiovascular outcomes, but it is unstudied with regard to intermittent fasting. In WONDERFUL trial subjects, the effect of the interaction between baseline RDW and intermittent fasting on changes in insulin and other cardiometabolic endpoints and the effect of fasting on changes in RDW were evaluated. The subjects enrolled were aged 21–70 years and were free of statins, anti-diabetes medications, and chronic diseases, and had ≥1 metabolic syndrome feature, as well as elevated low-density lipoprotein cholesterol. Subjects were randomized to 24-h, water-only fasting (twice per week for 4 weeks, once per week for 22 weeks) or 26 weeks of ad libitum eating. Subjects (N = 71; n = 38 intermittent fasting, n = 33 controls) had more substantial changes in insulin in intermittent fasting vs. controls (−3.45 ± 2.27 vs. 0.48 ± 3.55 mIU/L) when baseline RDW size distribution (RDW-SD) was ≥median (42.6 fL) than <median (−1.99 ± 2.80 vs. −1.08 ± 3.40 mIU/L) (p-interaction = 0.039). Results were similar but weaker for glucose, HOMA-IR, and metabolic syndrome score. RDW-SD (intermittent fasting: 1.27 ± 9.6 fL vs. control: −0.37 ± 1.76 fL, p = 0.34) was unchanged by fasting at 26 weeks. Intermittent fasting decreased insulin more in subjects with higher baseline RDW. RDW may identify individuals who derive the most health benefits from intermittent fasting and who have the most cause to adhere to a fasting regimen.

Highlights

IntroductionIn some populations, intermittent fasting reduced low-density lipoprotein cholesterol (LDL-C), to caloric restriction [2,3], while, in others, the effect of fasting on LDL-C was not different compared to parallel controls [1,9]
In the WONDERFUL trial [9], N = 71 subjects completed the 6-month follow-up and had complete blood count (CBC) data to be included in this study, with n = 18 fasting and n = 17 controls having Red cell distribution width (RDW)-SD < 42.6 fL and n = 20 fasting and n = 16 controls having RDW size distribution (RDW-SD) ≥ 42.6 fL
Baseline RDW-SD was modestly correlated with age (r = 0.384) and baseline levels of red blood cell (RBC) count (r = −0.313), MCV (r = 0.405), MCHC (r = −0.366), and MPV (r = 0.259), but not with baseline insulin (r = 0.036), glucose (r = 0.089), homeostatic model assessment of insulin resistance (HOMA-IR) (r = 0.034), metabolic syndrome score (MSS)

Summary

Introduction

In some populations, intermittent fasting reduced low-density lipoprotein cholesterol (LDL-C), to caloric restriction [2,3], while, in others, the effect of fasting on LDL-C was not different compared to parallel controls [1,9]. Some people, including those with diagnosed and undiagnosed diseases, may be at risk of serious side effects from fasting, such as the risk of hypoglycemia in people with type II diabetes who are taking certain medications [12], despite the fact that intermittent fasting produces metabolic benefits for such patients [3]

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