TABLE 2.
Study and participant characteristics with results for markers of inflammation or oxidative stress and key findings from included articles1
| Author, year (ref); country | Study design; overall risk-of-bias judgment | Funding source | Total n enrolled; % male | Mean (SD)2 age, y | Health status; smoking status | Mean (SD)2 BMI (kg/m2); weight status3 | Study duration | 100% OJ group(s); orange variety or type | Comparison group(s) | Results for 100% OJ group(s)4 | Key findings for 100% OJ vs. comparison group(s)5 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Asgary et al., 2014 (41); Iran | Crossover RCT; some concern | Nonprofit | 22; 31.8 | ∼34.5 (11, 12) | 100% healthy; nonsmokers | ∼24.5 (4.3, 5.5); normal or healthy | 10 wk total: 4 wk per intervention and 2-wk washout | 1000 mL/d freshly squeezed OJ; Citrus sinensis | 1000 mL/d commercial OJ from concentrate | Serum VCAM-1: - -Serum E-selectin: - -Serum hs-CRP: - -Serum IL-6: 0 | There were marginally significant differences in serum hs-CRP concentrations after intake of OJ from concentrate (lower hs-CRP at endpoint) and 100% OJ (greater decrease from baseline hs-CRP) |
| Azzini et al., 2017 (36); Italy | Before-after; NA | Government | 20; 0 | 36 (7) | At-risk; nonsmokers | 34.4 (4.8); obese | 12 wk | 500 mL/d commercial pasteurized red OJ; NR | NA | Plasma TAC [FRAP assay]: 0Plasma CRP: 0Plasma TNF-α: 0Plasma leptin: 0 | No comparator |
| Boussetta et al., 2020 (42); Tunisia | Crossover RCT; high | None | 11; NR | 22.5 (0.5) | 100% healthy (soccer players); nonsmokers | 23.2 (0.4); normal or healthy | ∼2 wk total: 2.5 h per intervention, ≥72-h washout, 1 wk between trials (polluted and nonpolluted) | 500 mL fresh blood OJ with no chemical products added; NR | 500 mL placebo juice | [After an intense bout of exercise]Plasma TAC [TAS assay]: ++ (polluted and nonpolluted area)Plasma MDA: ++ (polluted and nonpolluted area) | Compared to placebo juice, consuming 100% OJ before an intense bout of exercise resulted in significantly lower plasma MDA after exercise in both polluted and nonpolluted areas |
| Buscemi et al., 2012 (33); Italy | Crossover RCT; high | None | 21; 52.6 | 48 (13) | At-risk (nondiabetic subjects at increased cardiovascular risk with >2 diagnostic criteria of MetS); some smokers | 32.1 (4.9); obese | ∼2.5 wk total: 1 wk per intervention, 3-d washout | 500 mL/d commercial pasteurized OJ; Citrus sinensis varieties (tarocco, sanguinello, and moro) | 500 mL/d placebo juice with water, orange aroma, colorants (azorubin and tartrazine), sucrose, and citric acid | Serum IL-6: - -Serum TNF-α: - -Serum hs-CRP: - -Plasma protein carbonyl groups: 0 | Compared to placebo juice, consuming 100% OJ significantly reduced inflammation as indicated by lower serum concentrations of IL-6, TNF-α, and hs-CRP |
| Cerletti et al., 2015 (48); Italy | Crossover RCT; some concern | Government | 18; 50 | 36.9 (10.5) | At-risk (≥1 cardiovascular risk factor including 58% with prediabetes); some smokers | 26.8 (4.0); overweight | ∼1 wk total: 2 h per intervention, 7 ± 2-d washout | 1) 1 L commercial pasteurized anthocyanin-rich red OJ; 2) 1 L commercial pasteurized anthocyanin-poor blond OJ; NR | 1 L water | [After consuming a fatty meal]WBC count: 0 (both juices)PMN MPO release: - (blond OJ), - - (red OJ) | Compared to water, consuming blond OJ or red OJ with a fatty meal significantly attenuated rise in WBC counts and moderately attenuated MPO release (P = 0.06 for blond OJ, and P = 0.11 for red OJ vs. water) |
| Chaves et al., 2017 (43); Brazil | Crossover RCT; some concern | Government | 12; 41.7 | NR (NR) | 100% healthy; smoking status NR | Range: 20–25; normal or healthy | ∼2 wk total: 5 h per intervention, ≥1-wk washout between interventions | 500 mL commercial pasteurized 100% OJ; NR | 1) 500 mL water, 2) 500 mL isocaloric beverage (water with glucose) | [After consuming a high-fat, high-carbohydrate meal]Serum IL-4: 0Serum IL-6: decreased (P value NR)Induced PBMC proteins (for 100% OJ): 26S protease regulatory subunit 7, 26S proteasome non-ATPase regulatory subunit 11, serine-protein kinase ATM, de promyelocytic leukemia protein | A high-fat, high-carbohydrate meal with water or the isocaloric beverage increased IL-6, but inflammation was significantly mitigated with 100% OJ which reduced IL-6. Induced PBMC proteins (for all 3 beverages): apolipoprotein A-II, ceruloplasmin, and hemopexin |
| Deopurkar et al., 2010 (40); USA | Nonrandomized parallel controlled intervention; some concern | Government and nonprofit | 48; NR | NR (NR) | 100% healthy; smoking status NR | Range: 21.5–24.4; normal or healthy | 5 h | 300 kcal commercial not from concentrate Florida OJ; NR | 1) 300 kcal glucose, 2) 300 kcal gourmet heavy whipping cream, 3) 300 mL water | TNF-α mRNA: 0IL-1β mRNA: 0IL-6 mRNA: 0NF-κB: 0TLR-2 mRNA or protein: 0TLR-4 mRNA or protein: 0SOCS1 mRNA: 0SOCS3 mRNA or protein: 0SOCS7 mRNA: 0Plasma endotoxin concentrations: 0 (LPS and LBP) | Compared6 to glucose or cream, 100% OJ attenuated acute changes in NF-κB; TNF-α, IL-1β, and SOCS3 mRNA; and SOCS3 protein. Compared6 to cream only, 100% OJ attenuated acute changes in TLR-4 mRNA and protein expressions plus plasma endotoxin concentrations |
| Dong et al., 2016 (32); UK | Crossover RCT; some concern | Industry | 39; 100 | 48 (SEM: 1) | At-risk (≥1 cardiometabolic risk factor including mild hypercholesterolemia); nonsmokers | 28.4 (0.4); overweight | ∼6 wk total: 7 h per intervention, 2-wk washout between interventions | 1) 240 mL commercial pure premium OJ without pulp; 2) 240 mL fresh juice made from lightly blended whole oranges; NR | 1) 240 mL OJ with added orange pomace fiber, and 2) 240 mL isocaloric sugar-matched control | [After consuming a high-fat meal7]Serum CRP: - -Serum IL-6: ++Serum IL-10: -Serum IL-1β: 0Serum TNF-α: 0Plasma oxLDL: 0 | No differences |
| Dourado et al., 2015 (37); Brazil | Before-after; NA | Industry | 50; NR | ∼35.6 (8.6, 10.5) | Generally healthy; smoking status NR | ∼25.9 (1.7, 3.0); overweight | 8 wk | 750 mL/d 100% OJ without added sugars; NR | NA | [Same findings for participants with normal weight and overweight]Lipid peroxidation [TBARS assay] as MDA: - -Serum TAC [DPPH method]: ++Serum hs-CRP: - -Serum IL-4: 0Serum IL-10: 0Serum IL-12: ++Serum TNF-α: 0Serum IFN-γ: 0 | No comparator |
| Ghanim et al., 2010 (50); USA | Nonrandomized parallel controlled intervention; some concern | Government and nonprofit | 30; NR | NR (NR) | 100% healthy; smoking status NR | Range: 20–25; normal or healthy | 5 h | 300 kcal commercial pasteurized not from concentrate OJ; NR | 1) 300 kcal glucose plus 350 mL water, 2) water | [After consuming a high-fat, high-carbohydrate meal]ROS-PMN: ++ROS-MNC: ++p47phox protein: 0TLR2 mRNA or protein: 0TLR4 mRNA or protein: 0SOCS-3 protein: 0SOCS-3 mRNA: only baseline reportedp38 protein: 0MMP-9 mRNA: 0Plasma MMP-9: 0Plasma endotoxins (LPS): 0Phosphorylated p38 protein to p38 ratio: only baseline reported | Compared6 to water and glucose, 100% OJ attenuated acute changes induced by a high-fat, high-carbohydrate meal for these markers: ROS-PMN; MMP-9, TLR2, and TLR4 mRNA expression; SOCS-3, p47phox, p38, and phosphorylated p38 protein expression; plasma MMP-9; plasma endotoxins |
| Guarnieri et al., 2007 (49); Italy | Crossover RCT; some concern | NR | 7; 0 | 26 (2.1) | 100% healthy; nonsmokers | 20.1 (1.4); normal or healthy | ∼4 wk total: 24 h per intervention, 2-wk washout between interventions | 300 mL commercial pasteurized blood OJ; NR | 1) 300 mL vitamin C plus water, 2) 300 mL water with sugars equal to blood OJ content | H2O2-induced MNBC DNA damage (strand breaks): - - | Compared6 to the vitamin C and sugar control beverages, 100% blood OJ attenuated MNBC DNA damage induced by H2O2 |
| Hollands et al., 2018 (39); UK | Crossover RCT; some concern | Government and nonprofit | 45; 48.8 | 52.2 (13.6) | At-risk (all with abdominal obesity based on waist circumference); nonsmokers | 29.0 (5.1); overweight | ∼11 wk total: 4 wk per intervention, ≥3-wk washout | 500 mL/d commercial not from concentrate: 1) standard blond OJ, 2) Sicilian blood OJ; NR | None | Serum hs-CRP: 08 | No difference |
| Johnston et al., 2005 (52); USA | Before-after with multiple arms; NA | Nonprofit | 6; 0 | 36.8 (4.5) | 100% healthy; nonsmokers | 26.8 (3.3); overweight | >2 wk total: 2 h per intervention, 8 d between 100% or comparator OJs 1 and 2, but washout between 100% OJ and comparator trials NR | 237 mL commercial pasteurized not from concentrate 100% pure OJ without pulp: 1) freshly opened, 2) after 8 d of storage; NR | 237 mL OJ reconstituted from frozen concentrate: 1) freshly opened, 2) after 8 d of storage | Plasma LPOs [TBARS assay]: 0 (freshly opened OJ and after 8 days of storage) | Day 1 preparation6: lipid peroxidation (incremental TBARS) decreased with OJ from concentrate and did not change with 100% OJ. Day 8 of storage6: Consumption of both juices increased TBARS. Day 1 and day 8 differences6 were significant for OJ from concentrate and not significant for 100% OJ |
| Perrone et al., 2020 (44); Italy | Nonrandomized parallel controlled intervention; high | NR | 20; 100 | ∼27.3 (2.8, 3.2) | 100% healthy (professional athletes practicing cross-country skiing); nonsmokers | ∼23.4 (2.8, 3.2); normal or healthy | ∼4 wk | Common diet plus 500 mL/d 100% pure bergamot juice; Citrus bergamia | Common diet with no OJ | [After 30 d intensive training]hs-CRP: - -oxLDL: 0 | Compared to no OJ, 100% OJ attenuated increases in oxLDL after 30 d intensive training and significantly improved hs-CRP |
| Pittaluga et al., 2013 (26)9; Italy | Nonrandomized parallel controlled intervention; high | Nonprofit | 22; 0 | ∼68.7 (2.7, 5.1) | Generally healthy; nonsmokers | ∼26.0 (2.1, 3.2); overweight | 4-wk intervention; 24 h per trial with exhaustive exercise | 750 mL/d fresh juice from pigmented red oranges; Citrus sinensis, Sanguinello cultivar | No OJ | [At rest and after a bout of exhaustive exercise9]Plasma GSH: 0 (t0′, t24hr), ++ (t30′)Plasma GSSG: - - (t0′, t30′), 0 (t24hr)GSH/GSSG: 0 (t0′, t24hr), ++ (t30′)Apoptosis of DNA laddering: 0 (t0′, t30′, t24hr)Hemolysis rate: - - (t0′, t30′), 0 (t24hr)Micronuclei rate: 0 (t0′, t30′, t24hr)Serum 8-OHdG: 0 (t0′, t30′, t24hr)Plasma hypoxanthine: 0 (t0′, t24hr), - - (t30′)Plasma xanthine: 0 (t0′, t24hr), - - (t30′)Plasma MDA: 0 (t0′, t24hr), - - (t30′) | Compared6 to no OJ, 100% OJ reduced oxidative stress (GSSG) and hemolysis rate in resting conditions and attenuated acute GSH depletion, lipid oxidation and peroxidation (MDA), and hemolysis rate after a bout of exhaustive exercise. 100% OJ may also attenuate oxypurine concentrations after exhaustive exercise |
| Rangel-Huerta et al., 2015 (45); Spain | Crossover RCT; some concern | Industry | 100; NR | NR (NR) | At-risk (most with alterations in ≥1 clinical sign of metabolic syndrome); nonsmokers | ∼33.2 (0.5, 0.6); obese | 31 wk total: 12 wk per intervention, 7-wk washout | 500 mL/d commercial OJ with normal amount of polyphenols; NR | 500 mL/d commercial OJ enriched with polyphenols extracted from orange albedo and pulp | Plasma GSH: 0Plasma GSSG: 0Urine 8-iso-PGF2α: - -Urine 8-OHdG: - -Plasma oxLDL: 0Plasma LPOs: - -Plasma MDA: 0 | Compared to enriched OJ, consuming 100% OJ resulted in significantly reduced plasma LPO levels and a greater reduction in urine 8-OHdG, but enriched OJ produced significantly lower urine 8-OHdG concentrations |
| Rangel-Huerta et al., 2017 (53)10; Spain | Subgroup analysis of crossover RCT (nonrandom selection of subjects from only sequence 1); NA | Industry | 30; NR | ∼44 (9, 11) | At-risk (most with alterations in ≥1 clinical sign of metabolic syndrome); nonsmokers | ∼32.2 (3.6, 4.2); obese | 12 wk | 500 mL/d commercial OJ with normal amount of polyphenols; NR | 500 mL/d commercial OJ enriched with polyphenols (hesperidin, narirutin, and didymin) obtained from albedo and pulp | 9-HODE + 13-HODE: 0Serum 5-HETE: ++Serum 12-HETE: 0Derivate dihydroxy fatty acids: 0 (12,13-DiHOME), 0 (9,10-DiHOME) | Consuming polyphenol-enriched OJ significantly decreased metabolites 9-HODE + 13-HODE, 12,13-DiHOME, and 9,10-DiHOME; significantly increased 12-HETE; and attenuated increases in 5-HETE seen with 100% OJ.10 Results suggest added protection against oxidative stress and inflammation with polyphenol enriched OJ |
| Ribeiro et al., 2017 (46); Brazil | Parallel RCT; some concern | Industry | 84; 30.8 | 36 (1) | At-risk; smoking status NR | 33 (3); obese | 12 wk | Reduced-calorie diet plus 500 mL/d commercial 100% OJ; Pera Rio oranges | Reduced-calorie diet with no OJ | Serum hs-CRP: - -Serum lipid peroxidation [TBARS assay] as MDA: - -Serum TAC [radical 2,20-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) assay]: 0 | Compared to no OJ, consuming 100% OJ produced significantly lower serum hs-CRP concentrations at 12 wk |
| Riso et al., 2005 (47); Italy | Crossover RCT; high | Government | 16; 0 | NR (NR) | 100% healthy; smoking status NR | Range: 16.0–23.3; normal or healthy | 9–10 wk total: 3–4 wk per intervention (where 1 group had an extra week of juice), 3-wk washout | Standardized diet plus 600 mL/d commercial pasteurized blood OJ; NR | Standardized diet with no OJ | Plasma TAC [reduction by antioxidants, of Cu2+ to Cu+]: 0Plasma MDA: 0Urinary 11-Dehydro-TXB2: 0H2O2-induced DNA damage (% DNA in tail): 0 (21 d juice intake group), - - (28 d juice intake group) | Compared6 to no OJ, consumption of 100% OJ for 28 days (but not 21 d) attenuated H2O2-induced DNA damage |
| Sánchez-Moreno et al., 2003 (51); Spain | Before-after; NA | Government | 12; 50 | 22 (3) | 100% healthy; some smokers | 22.2 (1.6); normal or healthy | 2 wk | 500 mL/d commercial OJ; NR | NA | Plasma 8-epi-PGF2α: - - (men and smokers), 0 (women and nonsmokers) | No comparator |
| Silveira et al., 2015 (38); Brazil | Before-after; NA | Government | 35;54.3 | ∼36 (9.0, 9.4, 10.3, 11.8) | Generally healthy; nonsmokers | ∼26.0 (2, 3); overweight | 8 wk | 500 mL/d frozen, ready-to-drink red OJ; Sanguı ´nea de Mombuca variety | NA | Serum hs-CRP: - - (normal weight and overweight/obese)Serum antioxidant capacity [DPPH method]: ++ (normal weight and overweight/obese) | No comparator |
| Snyder et al., 2011 (35); USA | Crossover RCT; some concern | Nonprofit | 16; NR | 20.1 (NR) | 100% healthy; nonsmokers | 23.8 (range: 20–27.4); normal or healthy | 4 wk total: 3 h per intervention, 1-wk washout between interventions | 591 mL fresh-squeezed OJ; navel oranges | 591 mL placebo juice: 1) with ascorbic acid and sugar mixture (fructose, glucose, and sucrose), 2) comparator juice 1 plus hesperidin, 3) comparator juice 2 plus naringenin, and luteolin | Serum antioxidant capacity [ORAC assay]: - -Serum lipoprotein oxidation: - - (AUC as overall measurement of lipoprotein diene formation), ++ (lag time to onset of diene formation) | Compared6 to the other 3 interventions, consuming 100% OJ resulted in improved serum antioxidant capacity (based on greater ORAC at postprandial 1 h and longer serum lipoprotein oxidation lag time at all time points) and greater oxidative protection (based on lower serum lipoprotein oxidation AUC). Authors point out these results were contrary to 100% OJ having the smallest increase in serum total phenolic content |
1
CRP, C-reactive protein; Dehydro-TXB2, dehydrothromboxane B2; DPPH, 2,2-diphenyl-1-picrylhydrazyl; FRAP, ferric reducing antioxidant power; hs-CRP, high-sensitivity C-reactive protein; DiHOME, dihydroxyoctadecanoic acid; GSH, reduced glutathione; GSH/GSSG, glutathione redox ratio; GSSG, oxidized glutathione; HETE, hydroxyeicosatetraenoic acid; HODE, hydroxyoctadecadienoic acid; iso-, isoprostane; LBP, lipopolysaccharide-binding protein; LPO, lipid peroxidation; MDA, malondialdehyde (a secondary lipid peroxidation marker); MMP, matrix metallopeptidase; MNBC, mononuclear blood cell; MNC, mononuclear cell; NA, not applicable; NR, not reported; OJ, orange juice; ORAC, oxygen radical absorbance capacity; oxLDL, oxidized LDL; PBMC, peripheral blood mononuclear cell; PGF, prostaglandin F; PMN, polymorphonuclear cell; PMN MPO, intracellular polymorphonuclear leukocyte myeloperoxidase; RCT, randomized controlled trial; ref, reference; ROS, reactive oxygen species; SOCS, suppresser of cytokine signaling; TAC, total antioxidant capacity; TAS, total antioxidant status; TBARS, thiobarbituric acid reactive substance; TLR, Toll-like receptor; VCAM, vascular endothelial adhesion molecule; WBC, white blood cell; 8-OHdG, 8-hydroxy-2′-deoxyguanosine.
2
If total mean (SD) was not reported for study participants, the table presents means as calculated weighted averages (indicated by the “∼” symbol) and separate group SDs reported in the original study (presented in parentheses separated by a comma).
3
Categories for weight status based on BMI (kg/m2): normal-weight BMI = 18.5–24.9, overweight BMI = 25.0–29.9, obese BMI = ≥30.0 (25).
4
Results for 100% OJ group: ++, significant increase (P ≤ 0.05); +, marginally significant increase (0.05 < P < 0.10); 0, no effect; -, marginally significant decrease (0.05 < P < 0.10); - -, significant decrease (P ≤ 0.05). Methods or assays used for measuring antioxidant capacity and lipid peroxidation are included in brackets (e.g., [FRAP assay], [ORAC assay], [TAS assay]).
5
Key findings exclude markers showing no difference between intervention groups.
6
Results from statistical tests of treatment arm comparisons with 100% OJ were not reported, so the table presents results of effects as described in each article's text.
7
Results from 2-factor repeated-measures ANOVA where separate treatment effects were not reported. Significance indicates time effects (i.e., change in the marker from baseline) after both meals irrespective of the treatments given with breakfast.
8
Within-group differences not reported. Overlap in reported mean ± SD values for before and after measures suggests no statistically significant changes in within-group hs-CRP for either blood or blond 100% OJ treatments.
9
Blood measures were taken before (t0′) and 30 min (t30′) and 24 h after (t24hr) participants underwent a single bout of exhaustive exercise. In results for 100% OJ, we report comparisons of baseline and post–juice supplementation at each time point (e.g., t30′ baseline compared with t30′ after supplementation).
10
Statistical significance for metabolites related to oxidative stress and inflammation was reported as calculated q-values (false discovery rates accounting for multiple comparisons and estimating reliability of results). For key findings, q ≤ 0.1 was considered statistically significant.