Abstract
SummaryCalorie restriction (CR) without malnutrition slows aging in animal models. Oxidative stress reduction was proposed to mediate CR effects. CR effect on urinary F2‐isoprostanes, validated oxidative stress markers, was assessed in CALERIE, a two‐year randomized controlled trial. Healthy volunteers (n = 218) were randomized to prescribed 25% CR (n = 143) or ad libitum control (AL, n = 75) stratifying the randomization schedule by site, sex, and BMI. F2‐isoprostanes were quantified using LC‐MS/MS in morning, fasted urine specimens at baseline, at 12 and 24 months. The primary measure of oxidative status was creatinine‐adjusted 2,3‐dinor‐iPF(2α)‐III concentration, additional measured included iPF(2α)‐III, iPF2a‐VI, and 8,12‐iso‐iPF2a‐VI. Intention‐to‐treat analyses assessed change in 2,3‐dinor‐iPF(2α)‐III using mixed models assessing treatment, time, and treatment‐by‐time interaction effects, adjusted for blocking variables and baseline F2‐isoprostane value. Exploratory analyses examined changes in iPF(2α)‐III, iPF(2α)‐VI, and 8,12‐iso‐iPF(2α)‐VI. A factor analysis used aggregate information on F2‐isoprostane values. In CR group, 2,3‐dinor‐iPF(2α)‐III concentrations were reduced from baseline by 17% and 13% at 12 and 24 months, respectively; these changes were significantly different from AL group (p < .01). CR reduced iPF(2α)‐III concentrations by 20% and 27% at 12 and 24 months, respectively (p < .05). The effects were weaker on the VI‐species. CR caused statistically significant reduction in isoprostane factor at both time points, and mean (se) changes were −0.36 (0.06) and −0.31 (0.06). No significant changes in isoprostane factor were at either time point in AL group (p < .01 between‐group difference). We conclude that two‐year CR intervention in healthy, nonobese men and women reduced whole body oxidative stress as assessed by urinary concentrations of F2‐isoprostanes.
Highlights
Caloric restriction (CR) without malnutrition is the most powerful known intervention to slow aging and protect against cancer, heart disease, type 2 diabetes, and cognitive decline in many eukaryotic organisms, rodents and monkeys (de Cabo, CarmonaGutierrez, Bernier, Hall & Madeo, 2014; Fontana, Partridge & Longo, 2010; Mattison et al, 2017)
There was no difference in urinary creatinine or urinary F2-isoprostane concentrations between the CR and ad libitum control (AL) groups
We examined crude cross-sectional associations between urinary F2-isoprostanes and participant characteristics known to be associated with these biomarkers in other study populations (Table 2) (Il’yasova, Wang, et al, 2012; Kanaya et al, 2011; Keaney et al, 2003)
Summary
Caloric restriction (CR) without malnutrition is the most powerful known intervention to slow aging and protect against cancer, heart disease, type 2 diabetes, and cognitive decline in many eukaryotic organisms, rodents and monkeys (de Cabo, CarmonaGutierrez, Bernier, Hall & Madeo, 2014; Fontana, Partridge & Longo, 2010; Mattison et al, 2017). There are currently no data from randomized controlled trials in humans evaluating the long-term effects of CR on reliable markers of oxidative stress. We measured urinary concentration of 2,3-dinor-iPF(2a)-III, as the primary indicator of oxidative status, and in addition to three F2-isoprostane isomers: iPF (2a)-III, iPF2a-VI, and 8,12-iso-iPF2a-VI. Our primary hypothesis for this analysis—caloric restriction reduces systemic levels of oxidative damage, lipid peroxidation—was based on the effects of long-term caloric restriction in laboratory animals and/or shorterterm human trials (Heilbronn et al, 2006; Sohal & Weindruch, 1996; Walsh et al, 2014). 2,3-dinor-iPF(2a)-III was selected as the primary measure of oxidative stress, because this is a beta-oxidation metabolite of the most frequently measured isomer iPF(2a)-III (Basu, 2008; Milne et al, 2005). Measurements of multiple F2-isoprostane species provided the opportunity to assess the effect of CR intervention on an aggregate F2-isoprostane measure through factor analysis
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
