The authors have declared that no competing interests exist.
Conceived and designed the experiments: MSB NH LJR. Performed the experiments: MSB LJR. Analyzed the data: MSB NH JW SA LJR LW. Contributed reagents/materials/analysis tools: NH. Wrote the paper: MSB JW SA LJR LW.
It is not established to what extent caloric intake must be reduced to lower oxidative stress in humans. The aim of this study was to determine the effect of short-term, moderate caloric restriction on markers of oxidative stress and inflammation in overweight and obese premenopausal women.
Randomized trial comparison of 25% caloric restriction (CR) or control diet in 40 overweight or obese women (body mass index 32±5.8 kg/m2) observed for 28 days and followed for the next 90 days. Weight, anthropometry, validated markers of oxidative stress (F2-isoprostane) and inflammation (C-reactive protein), adipokines, hormones, lipids, interleukins, and blood pressure were assessed at baseline, during the intervention, and at follow-up.
Baseline median F2-isoprostane concentration (57.0, IQR = 40.5–79.5) in the CR group was 1.75-fold above average range for normal weight women (32.5 pg/ml). After starting of the caloric restriction diet, F2-isoprostane levels fell rapidly in the CR group, reaching statistical difference from the control group by day 5 (median 33.5, IQR = 26.0–48.0, P<0.001) and remained suppressed while continuing on the caloric restriction diet. Three months after resuming a habitual diet, concentrations of F2-isoprostane returned to baseline elevated levels in ∼80% of the women.
Oxidative stress can be rapidly reduced and sustained through a modest reduction in caloric intake suggesting potential health benefits in overweight and obese women.
Clinicaltrials.gov
Obesity is associated with increased oxidative stress and chronic low-grade chronic inflammation
Thus, the goal of this controlled clinical trial was to determine whether modest (25%) short-term caloric restriction-induced weight loss affects systemic oxidative stress, as measured by changes in serum F2-isoprostane.
The protocol for this trial and supporting CONSORT checklist are available as supporting information; see
Forty premenopausal overweight and obese women, (18- to 45-years-old; body mass index - BMI: 25.4 to 43.0 kg/m2), were recruited from Nashville’s general population by advertisement in Vanderbilt University’s newspaper, mass emails, and flyers. Inclusion criteria were BMI more than 25 kg/m2 and willingness to abstain from alcohol consumption for the duration of the study, complete an overnight stay at the Clinical Research Center (CRC), and come to the CRC daily to obtain study foods. Volunteers were excluded if they reported having clinically significant illnesses (including type 2 diabetes), smokers, taking lipid-lowering medications, reported recent initiation/change in hormonal birth control or hormone replacement therapy, pregnant or lactating, taking medications or dietary supplements that affect body weight, or regularly engaging in vigorous physical activities. Participants classified their own ethnicity according to investigator-defined options. At a screening visit, all volunteers were measured for height, weight, and waist circumference, and completed a lifestyle questionnaire. Approximately 150 women were screened for eligibility based on the above criteria and 40 were enrolled. All applicable institutional and governmental regulations concerning the ethical use of human volunteers were followed during this research, in accordance with the ethical principles of the Helsinki-II Declaration. The trial (Clinicaltrials.gov Identifier: NCT00808275) was approved by the Institutional Review Board at Vanderbilt University and all participants provided written informed consent.
The study consisted of an experimental group that received a CR diet and a control group that remained on a habitual diet throughout the study. The ratio of women in CR group to the control group was 4 to 1 (allocated via blocked randomization by a statistician not involved in patient recruitment). The study was divided into a 7-day lead in period (Day -6 to Day 0), immediately followed by a 28-day intervention (Day 1 to Day 28), and a 3-month follow-up (Day 29 to Day 118). Dietary intervention in the CR group started during the luteal stage of the menstrual cycle (14–24 d) to control for confounding by menstrual cycle and any associated oxidative and/or inflammatory stress.
The National Health and Nutrition Examination Survey (NHANES) protocols were followed for all anthropometrical measurements
REE was measured at Day 0 and 29 and was defined as the average EE during a 30-min period of lying in a supine position after a 30-min rest following an overnight fast (>10 h) using a whole-room indirect calorimeter. REE was calculated from measured rates of oxygen (O2) consumption and carbon dioxide (CO2) production using Weir’s equation
Participants in the CR group received individualized energy and nutrient controlled diets provided by the CRC metabolic kitchen for consumption at home. Energy needs were calculated as the sum of resting energy expenditure (REE) and energy expenditure of physical activity. Thermic effect of food was estimated as 10% of REE. Each individualized diet, provided in daily portions divided into 3 meals and 3 snacks, contained approximately 75% (±210 kcal) of daily energy requirements, including 52–62% of energy from carbohydrates, 25–29% of energy from fat, 18–23% of energy from protein, and 22–27 g of fiber. All participants received a multivitamin supplement daily (Nature Made, Mission Hills, CA). No restrictions were imposed on the amounts of energy-free foods ingested. Each participant received a written list of foods at daily pick-up. Any uneaten foods and any additional foods eaten by the participants were reported on sheets collected daily. The study dietitian met with each participant weekly to discuss the diet, resolve any barriers or concerns related to food or specimen collection, and encourage compliance. Energy and nutrient intake calculations were performed using the Nutrient Data System for Research (NDSR) software version 2009 developed by the Nutrition Coordinating Center, University of Minnesota, Minneapolis, MN, Food and Nutrient Database
Participants in the control group were asked to follow their habitual diet for the study duration and they received a multivitamin supplement daily (Nature Made, Mission Hills, CA). Their dietary intake was assessed during the intervention (Days 1–28) from three 24-dietary recalls (2 weekdays and 1 weekend day) performed using automated multi-pass method and NDS-R software
Daily physical activity was assessed using an RT3 accelerometer (StayHealthy, Monrovia, CA, US). Participants were instructed to maintain their habitual physical activity level and wore an activity monitor on their right hip while awake for the duration of the intervention and twice for 7 days during the follow-up. Total and physical activity energy expenditure was calculated using energy calculated from the monitor-measured movement and measured REE. Physical activity levels (PAL) for each monitored day were calculated by dividing total energy expenditure by REE.
Blood pressure was measured 3 times a week in the reclining position after 10 min rest with automatically inflating cuff (Dynamap, General Electric, Milwaukee, WI, USA) using a standard protocol.
Venous blood samples were drawn after an overnight fast at baseline and on days 1, 3, 5, 7, 14, 21, 29, 42, and 119, centrifuged immediately at 1 000 g for 10 minutes at 4°C, and the serum was stored in cryovials at –80°C until the assays were performed in batches. Samples obtained at baseline and during the study for each participant were included in the same assay run to avoid inter-assay variability among participants. F2-isoprostane was analyzed using gas chromatography/mass spectrometry (GC/MS), a previously described and validated method
A basic metabolic panel, hematological indices (hemoglobin concentration, hematocrit, red and white blood cell counts), and C-reactive protein were analyzed in the Vanderbilt University Hospital Laboratory using standard methodologies. Blood for measurement of lipids, inflammatory cytokines, and hormones (leptin, insulin, adiponectin) was centrifuged, serum was extracted, and the samples were stored at −80°C until later analyses. Plasma triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) levels were measured using enzymatic kits from Cliniqa Corporation (San Marcos, CA). Free fatty acids (FFA) were measured using the NEFA-C kit by Wako (Nneuss, Germany) and by gas chromatography. Glucose was measured using the Vitros Chemistry analyzer. Insulin and leptin measurements were performed using RIAs. Adiponectin was measured using a kit from Millipore (Billerica, MA) and Luminex multiplexing technology.
Complete 24-h urine samples were collected once weekly. Urine volume and density was measured and a 10 mL sample was frozen at −70°C until further analysis. Urinary calcium, sodium, and potassium were measured using Vitros 250 Analyzer (Ortho-Clinical Diagnostics, Rochester, NY, USA). Urinary nitrogen content was measured using nitrogen analyzer (Antek Instrument Nitrogen System 9000NS, Antek Instruments, Inc., Houston, TX, USA). The nitrogen excretion in the urine was used as a biological marker for protein intake by multiplying the content of nitrogen in the urine by the factor 7.72
Descriptive statistics were presented as mean and standard deviation (SD) or median and IQR or percentage, as appropriate. Daily caloric intake and REE were expressed as the absolute and deficit number of kilocalories per day. Continuous endpoints were compared between the control and intervention group using Wilcoxon rank sum test. The change within group was assessed using Wilcoxon signed rank test. Spearman correlation coefficient was used to assess the correlation between two continuous variables. Multivariable linear model was used to assess the treatment effect at single time point while adjusting for the baseline measures. We performed a linear model using generalized least squares with autocorrelation structure of order 1 (AR1) for the within-subject correlation to assess the F2-isoprostane change within 28 days of study period. The main effects included baseline age, BMI, and F2-isoprostane, time, group, and time by group interaction. Time was modeled as nonlinear relationship to the F2-isoprostane using restricted cubic splines. Residual plot and quantile-quantile (QQ) plots were used to check the model assumptions. The level of statistical significance was set at p<0.05. All analyses were done with STATA 11 (StataCorp, College Station, TX) and the statistical programming language R, version 2.13.1 (R Development Core Team, Vienna, Austria).
Thirty of 32 participants in the CR group and all controls completed the intervention part of the study (i.e., returned for the Day 29 visit). The reasons for study dropout were work related (n = 1) and a family emergency (n = 1). Twenty-six CR and 7 control group participants completed the entire study. The reasons for study dropout were work-related (CR, n = 2; control, n = 1), pregnancy (CR, n = 1), and an unspecified reason (CR, n = 1). The participants who did not complete the CR protocol did not differ from the completers in regards to age, body weight, body fat, CRP, or insulin, but did have lower baseline F2-isoprostane plasma concentrations (38.5, IQR = 20.5–48.2 vs. 63.5, IQR = 45.8–79.0; P = 0.01). Baseline demographic and anthropometric characteristics are shown in
Control diet (n = 8) | CR diet (n = 32) | |
Age (years) | 29.5 (26.8–33.3) | 30.5 (26.0–34.0) |
Body weight (kg) | 86.9 (72.2–96.2) | 85.2 (70.4–99.4) |
Body-mass index (kg/m2) | 30.1 (28.1–38.3) | 32.3 (26.6–36.3) |
Body fat mass (kg) | 39.3 (33.2–44.1) | 38.6 (27.5–49.0) |
|
||
African American | 3 | 9 |
Caucasian | 4 | 22 |
Other (Asian, Hispanic) | 1 | 1 |
Data are presented as median (interquartile range - IQR).
Abbreviations: CR diet, caloric restriction diet.
Intake |
Urinary Excretion |
Ratio of Intake to Excretion | p-value |
|
Protein (g/day) | 85.0±12.0 | 87.9±3.6 | 1.03±0.25 | 0.486 |
Sodium (g/day) | 3.03±0.44 | 3.18±0.83 | 0.95±0.19 | 0.919 |
Potassium (g/day) | 2.93±0.43 | 2.83±0.43 | 1.04±0.32 | 0.553 |
Data are presented as means ± s.d.
Average daily intakes of protein, sodium, and potassium assessed by NDSR (Nutrition Diet System, St. Paul, MN).
Excretion measured from 4 weekly 24-hour urine collections. Protein = urinary nitrogen *7.72 (18), Potassium = urinary potassium *0.77 (19).
Comparison of ratios of intake to excretion; one sample t-test.
We fit a linear model of F2-isoprostane within the 28 days study period using generalized least squares. F2-isoprostane was log transformed since the distribution was skewed. There were statistically significant differences between the CR and control group (P<0.001). The biggest difference appeared at day 14 (control/CR, 1.79, 95% CI: 1.50–2.13) and day 21 (control/CR, 1.82, 95% CI: 1.56–2.11). (
Vertical bars represent 95% bootstrap confidence intervals.
Factor | Effect | 95% CI | p-value |
Baseline age [years] - 34∶26 | 0.95 | 0.89–1.02 | 0.150 |
Baseline BMI [kg/m2] - 36.4∶26.9 | 1.12 | 1.02–1.21 | 0.015 |
Baseline F2-isoprostane (pg/mL) - 78.2∶44.8 | 1.46 | 1.36–1.55 | <0.001 |
Day of intervention - day 21:day 3 | 0.76 | 0.69–0.84 | <0.001 |
Group - Control : CR | 1.60 | 1.36–1.88 | <0.001 |
Effect shown is the F2-isoprostane ratio. BMI - body mass index; CR diet- caloric restriction diet. Adjusted to: Day of intervention = 7, Group = CR.
Time | N | Control diet | CR diet | p-value |
Baseline | 40 | 61.0 (51.8–65.0) | 57.0 (40.5–79.5) | 0.908 |
Day 1 | 40 | 55.0 (48.8–65.0) | 44.0 (35.5–61.2) | 0.153 |
Day 3 | 40 | 56.0 (46.8–73.5) | 39.5 (24.8–50.2) | 0.010 |
Day 5 | 40 | 62.5 (45.0–72.5) | 33.5 (26.0–48.0) | 0.002 |
Day 7 | 40 | 52.0 (45.0–66.0) | 33.5 (23.8–45.8) | 0.007 |
Day 14 | 40 | 50.0 (42.0–67.5) | 34.0 (23.5–43.5) | 0.004 |
Day 21 | 40 | 58.0 (49.2–60.2) | 30.5 (23.8–42.5) | <0.001 |
Day 29 | 38 | 51.0 (49.2–53.5) | 29.5 (23.2–40.8) | <0.001 |
Day 42 | 37 | 61.0 (55.0–65.0) | 33.5 (29.0–53.5) | 0.006 |
Day 119 | 34 | 56.0 (52.0–59.5) | 56.0 (36.0–66.0) | 0.692 |
Data are presented as median (interquartile range- IQR). CR diet, caloric restriction diet.
Wilcoxon rank sum test for differences between Control and CR diets.
The average caloric intake was significantly lower in the CR than in the control group with an average intake of 17.8±2.2 kcal/kg/day vs. 28.2±4.6 kcal/kg/day (P<0.001). By the end of the dietary intervention (Day 29), total body weight and body fat weight decreased in the CR more than in the control group (difference 2.7 kg and 1.1 kg, respectively). However, differences in body weight and body fat between CR and control groups were non-significant at baseline, end of intervention, and day 119 follow-up (
Variable | Time | Control diet | CR diet | p-value |
Body Weight(kg) | Baseline | 86.9 (72.2–96.2) | 85.5 (70.4–99.4) | 0.740 |
Day 29 | 86.9 (71.1–97.6) | 82.8 (68.5–95.8) | 0.504 | |
Day 119 | 87.8 (79.7–98.7) | 84.5 (72.6–96.3) | 0.491 | |
BMI (kg/m2) | Baseline | 30.1 (28.1–38.3) | 32.3 (26.6–36.2) | 0.538 |
Day 29 | 30.1 (27.6–38.8) | 31.5 (25.7–35.3) | 0.438 | |
Day 119 | 30.0 (28.5–39.0) | 32.1 (26.2–35.8) | 0.329 | |
Body Fat (kg) | Baseline | 39.3 (33.2–44.1) | 38.5 (27.4–49.0) | 0.946 |
Day 29 | 39.9 (31.0–44.0) | 38.0 (26.0–47.0) | 0.598 | |
Day 119 | 39.1 (33.5–45.9) | 36.7 (27.8–44.3) | 0.544 |
Data are presented as median (interquartile range - IQR).
Abbreviations: CR diet, caloric restriction diet; BMI, body mass index (kg/m2).
Wilcoxon rank sum test for differences between Control and CR diets.
Variable | Time | Control diet | CR diet | p-value |
|
REE | Baseline | 1.33 (1.22–1.37) | 1.22 (1.18–1.37) | 0.255 | |
(kcal/min) | Day 29 | 1.33 (1.21–1.38) | 1.20 (1.17–1.35) | 0.191 | |
Day 119 | 1.35 (1.27–1.39) | 1.28 (1.19–1.40) | 0.330 | ||
PAEE | Baseline | 502.7 (471.7–514.3) | 519.5 (423.3–542.5) | 0.740 | |
(kcal/day) | Day 29 | 554.0 (511.0–648.1) | 492.8 (463.1–553.9) | 0.057 | |
Day 119 | 505.5 (476.8–540.3) | 497.8 (425.4–514.5) | 0.415 | ||
PAL | Baseline | 1.31 (1.31–1.32) | 1.27 (1.25–1.32) | 0.078 | |
Day 29 | 1.33 (1.31–1.33) | 1.29 (1.25–1.35) | 0.303 | ||
Day 119 | 1.32 (1.31–1.33) | 1.27 (1.25–1.31) | 0.012 |
Data are presented as median (interquartile range -IQR).
Abbreviations: REE, resting energy expenditure; PAEE, physical activity-related energy expenditure calculated as a difference between total and resting energy expenditure; PAL, physical activity level calculated as a ratio of total energy expenditure to REE, CR diet, caloric restriction diet.
Wilcoxon rank sum test for differences between Control and CR diets.
Control diet | CR diet | ||||||
Nutrient | Median | IQR | Median | IQR | |||
Energy (kcal) | 2062.4 | (1906.1–2119.9) | 1543.3 |
(1410.9–1784.1) | |||
Fat (g) | 54.7 | (52.8–67.6) | 44.2 |
(33.5–54.6) | |||
Carbohydrate (g) | 276.1 | (253.5–329.6) | 227.9 |
(213.1–253.9) | |||
Protein (g) | 101.2 | (93.3–124.2) | 82.0 |
(70.9–93.4) | |||
Glycemic Load (bread reference) | 213.7 | (197.3–241.3) | 162.1 |
(141.5–183.4) | |||
Dietary Fiber (g) | 21.9 | (18.8–24.3) | 24.4 | (22.1–27.3) | |||
Vitamin A (retinol equivalents) (mcg) | 1886.8 | (1736.8–2107.2) | 2034.7 | (2202.3–6755.1) | |||
Vitamin D (IU) | 337.4 | (293.4–392.8) | 325.2 | (312.6–355.0) | |||
Vitamin E (IU) | 8.5 | (7.1–12.0) | 7.7 | (6.4–9.3) | |||
Vitamin C (ascorbic acid) (mg) | 87.0 | (73.0–116.3) | 127.1 | (100.9–167.1) | |||
Vitamin B1 (thiamin) (mg) | 1.5 | (1.4–1.7) | 1.2 | (1.0–1.6) | |||
Vitamin B2 (riboflavin) (mg) | 2.2 | (2.1–2.8) | 1.9 | (1.7–2.1) | |||
Vitamin B6 (mg)(piridoxal, piridoxamine, piridoxin) | 2.0 | (1.8–2.1) | 1.5 | (1.3–1.8) | |||
Niacin (mg) | 22.5 | (20.9–24.9) | 19.4 | (15.0–22.5) | |||
Folate (mcg) | 574.3 | (524.8–685.5) | 501.7 | (464.5–552.4) | |||
Vitamin B12 (cobalamin) (mcg) | 6.9 | (5.7–7.6) | 4.6 | (3.4–6.1) | |||
Sodium (mg) | 3588.8 | (3319.3–4209.7) | 2604.4 | (2112.0–3433.0) | |||
Calcium (mg) | 822.3 | (729.1–920.5) | 1008.6 | (881.6–1147.2) | |||
Magnesium (mg) | 509.2 | (451.7–540.7) | 455.3 | (436.8–482.1) | |||
Iron (mg) | 14.4 | (12.1–15.2) | 9.4 | (7.7–11.5) |
Data are presented as median (interquartile range -IQR).
- different from Control diet, p<0.001, Wilcoxon rank sum test.
Daily multivitamin supplement was given during intervention Days 1–28 (Multi Complete, Nature Made, Mission Hills, CA) composition: vitamin A - 2 500 IU, vitamin D3 - 1000 IU, vitamin E - 50 IU, vitamin C - 180 mg, vitamin B1 - 15 mg, vitamin B2 - 1.7 mg, niacin - 20 mg, vitamin B6 - 2 mg, folate - 400 mcg, vitamin B12 - 6 mcg, calcium 162 mg, magnesium - 100 mg, iron - 18 mg, selenium - 70 mcg.
The CR diet did not have a significant effect on either systolic or diastolic blood pressure or serum concentrations of insulin, leptin, adiponectin, total cholesterol, LDL cholesterol, HDL cholesterol, CRP and triglycerides (
Variable | Time | Control diet | CR diet | p-value |
Systolic blood | Baseline | 121.5 (120.1–126.5) | 128.5 (122.8–132.3) | 0.052 |
pressure (mmHg) | Day 29 | 125.0 (123.0–126.0) | 123.0 (117.3–129.0) | 0.648 |
Day 119 | 126.0 (124.5–128.0) | 125.0 (121.5–131.5) | 0.897 | |
Diastolic blood | Baseline | 79.5 (76.5–82.5) | 77.5 (74.0–82.0) | 0.206 |
pressure (mmHg) | Day 29 | 79.0 (78.0–81.5) | 77.0 (73.0–81.0) | 0.116 |
Day 119 | 77.0 (75.0–80.0) | 77.0 (75.0–79.8) | 0.983 | |
Insulin (uU/mL) | Baseline | 13.8 (7.0–16.8) | 11.7 (8.9–17.0) | 0.803 |
Day 29 | 11.1 (8.1–17.0) | 9.8 (6.8–12.6) | 0.514 | |
Day 119 | 11.5 (7.5–16.1) | 10.1 (8.9–15.2) | 0.830 | |
Leptin (ng/mL) | Baseline | 19.5 (16.5–25.6) | 21.1 (15.4–28.0) | 0.974 |
Day 29 | 19.6 (16.4–31.1) | 17.8 (11.6–24.2) | 0.250 | |
Day 119 | 17.8 (15.9–25.9) | 22.6 (15.4–26.8) | 0.784 | |
Adiponectin | Baseline | 9.1 (5.5–10.2) | 10.0 (7.7–13.8) | 0.235 |
(ng/mL) | Day 29 | 7.2 (5.9–11.3) | 12.0 (7.8–15.7) | 0.114 |
Day 119 | 8.1 (7.0–9.9) | 12.1 (8.7–17.7) | 0.243 | |
Triglyceride | Baseline | 134.5 (131.5–154.0) | 138.0 (122.0–153.2) | 0.595 |
(mg/dL) | Day 29 | 142.0 (131.0–157.0) | 132.0 (118.0–144.0) | 0.125 |
Day 119 | 126.0 (124.5–149.0) | 135.0 (121.5–145.0) | 0.587 | |
Totalcholesterol | Baseline | 214.5 (189.5–241.2) | 208.0 (181.0–226.2) | 0.454 |
(mg/dL) | Day 29 | 214.5 (188.8–227.8) | 190.5 (174.2–210.8) | 0.378 |
Day 119 | 215.0 (205.0–231.5) | 209.0 (186.0–220.0) | 0.391 | |
LDL (mg/dL) | Baseline | 148.8 (110.0–167.8) | 132.0 (105.8–150.2) | 0.377 |
Day 29 | 152.0 (122.2–159.2) | 118.5 (107.2–143.8) | 0.208 | |
Day 119 | 149.0 (137.5–153.5) | 125.0 (117.0–142.5) | 0.132 | |
HDL(mg/dL) | Baseline | 45.5 (36.0–53.5) | 46.0 (42.0–54.2) | 0.752 |
Day 29 | 42.0 (35.0–46.0) | 44.0 (35.0–54.0) | 0.515 | |
Day 119 | 48.0 (40.5–50.5) | 46.0 (41.0–52.0) | 0.573 | |
Free fatty acids | Baseline | 0.41 (0.32–0.60) | 0.53 (0.37–0.73) | 0.262 |
(mmol/L) | Day 29 | 0.41 (0.31–0.53) | 0.52 (0.42–0.67) | 0.108 |
Day 119 | 0.38 (0.35–0.55) | 0.49 (0.40–0.65) | 0.156 |
Data are presented as median (interquartile range -IQR).
Abbreviations: LDL, low-density lipoprotein; HDL, high-density lipoprotein.
Wilcoxon rank sum test for differences between Control and CR diets.
Variable | Time | Control diet | CR diet | p-value |
Tumor necrosis | Baseline | 5.67 (1.65–9.25) | 2.88 (0.00–5.22) | 0.310 |
factor -á (ug/dL) | Day 29 | 5.90 (1.40–9.11) | 3.08 (0.00–8.00) | 0.555 |
Day 119 | 7.67 (2.48–8.81) | 4.96 (0.00–5.68) | 0.340 | |
Interleukin -12 | Baseline | 6.47 (5.30–9.52) | 2.75 (0.00–5.68) | 0.027 |
(pg/mL) | Day 29 | 9.53 (5.70–10.39) | 3.19 (0.00–5.81) | 0.027 |
Day 119 | 8.33 (7.48–9.39) | 4.26 (0.00–6.94) | 0.007 | |
Interleukin -8 | Baseline | 8.55 (8.20–17.73) | 5.02 (3.04–8.37) | 0.003 |
(pg/mL) | Day 29 | 9.72 (7.32–39.30) | 6.48 (4.87–8.29) | 0.019 |
Day 119 | 7.41 (7.16–25.88) | 5.94 (2.65–8.55) | 0.075 | |
C-reactiveprotein | Baseline | 6.00 (3.00–9.50) | 3.50 (1.00–6.00) | 0.157 |
(ug/mL) | Day 29 | 4.20 (2.65–7.25) | 2.60 (1.00–6.25) | 0.274 |
Day 119 | 4.70 (1.12–9.10) | 3.00 (1.00–5.07) | 0.776 |
Data are presented as median (interquartile range - IQR). CR, caloric restriction diet.
Wilcoxon rank sum test for differences between Control and CR diets.
The novelty of the present study is that we investigated serial changes in a marker of oxidative stress induced by 28-days of a caloric restriction diet. The main finding is that moderate (25%) CR and modest weight loss causes a rapid decrease in oxidative stress as measured by plasma F2-isoprostane concentrations, to within the normal range exhibited by non-obese adults (35±6 pg/ml). The magnitude of this change was significant in comparison to baseline F2-isoprostane plasma concentrations. This suggests that the potential benefits from reducing the oxidative stress level can be achieved rapidly without restricting caloric intake to a level that overweight and obese people might find difficult to sustain.
CR is hypothesized to lessen oxidative damage by reducing energy flux and metabolism with a consequential lowering of reactive oxygen species and rate of oxidative damage to vital tissues
Our results showing decreased F2-isoprostane with weight loss are consistent with a previous Davi et al
Baseline F2-isoprostane correlated with body fat content. However, the F2-isoprostane decrease during the CR intervention was not correlated with the concurrent changes in body fat. Although we used a clinical trial design, strict diet control, and validated biomarkers
Although our study did not test whether decreases in oxidative stress are linked to an improvement in risk factors for associated chronic diseases, previous data do provide such evidence. Zacardi et al
Our findings extend those of previous studies in several ways. First, our data provide evidence from a controlled trial design that the decrease in oxidative stress biomarkers induced by a modest caloric restriction is rapid. This is important because obese individuals are unable to consistently comply with a long-term daily caloric reduction of 40% (consuming 60% of maintenance), as has been used in most animals studies
However, we do not know whether energy intake-induced weight cycling is affecting oxidative stress level. Our results support the notions that during caloric restriction and subsequent weight loss, oxidative stress level decreases, and in contrast, increases during a positive caloric balance and subsequent weight gain. Thus, we hypothesize that previously mentioned health consequences of weight cycling such as increased risk for metabolic syndrome and cardiovascular disease could be associated, at least in part, with changes in the oxidative stress level. Future clinical studies are necessary to explain whether these associations can be attenuated by frequent weight cycling and what mechanisms (e.g. lipids oxidation, insulin resistance, and inflammation) are involved.
A limitation of the present study is the relatively small number of participants; hence, the results need to be confirmed in larger studies. In addition, individuals in the control group ate their habitual diets, thus it was possible that their intake of antioxidants (e.g., vitamin E,) and other micronutrient would be below the recommended allowances. To prevent this possibility, participants in both groups received a vitamin/mineral supplement daily. As a result, vitamin E intake was similar in the control and CR groups (∼58 international units), which was in line with the daily recommended intake of 22.4 to 50 international units for younger and older adults, respectively
Although the use of F2-isoprostanes as a marker of oxidative stress is a strength
In summary, the results of the present study show that oxidative stress can be rapidly reduced and sustained through a modest (25%) reduction in caloric intake for a relatively short (28-day) period. Simultaneous reduction in markers of inflammation was associated with decreases in body fat and body weight. These changes suggest potential health benefits of modest caloric restriction in overweight and obese women.
(DOC)
(DOCX)