Table 5.

Human research involving oral antioxidant supplementation for the prevention and treatment of preeclampsia.

Study	Antioxidant	Inclusion/exclusion criteria	Dose/time	Outcomes
Banerjee et al. (2009) [67]	Lycopene	Inclusion criteria: primiparous women with singleton pregnancy between 12 and 20 weeks of gestation, with the absence of any medical problems, such as CH, RD, gross obesity, diabetes, thrombophilia, CD, or connective tissue disease. Criteria to PE: blood pressure consistently more than 140/90 mmHg in a previously normotensive woman accompanied with newly onset proteinuria of more than 300 mg/24 h urine collection or, >1+ on clean catch dipstick in a random urine sample in the absence of urinary infection.	2 mg 12-20 weeks until delivery	The supplemented group: ↑ in the incidence of adverse effects of preterm birth and LBW.
Pulido et al. (2016) [73]	L-Arginine	Inclusion criteria: women who had high-risk factors for developing PE (nulliparous, previous history of PE, CH, and BMI ≥ 30). Exclusion criteria: patients with multiple pregnancies or comorbidities (DM, hepatopathy, HD, and collagen disease), alcohol consumption, anti-inflammatory/antioxidant drug ingestion, infections, or concomitant medication.	3 g 3 weeks during gestation and 2 weeks postpartum	Maternal blood pressure and prematurity rates were significantly ↓ in the intervention group, while birth weight was ↑. The Apgar score < 7 to 5 min was not ≠ between the groups, and there was no neonatal or maternal death.
Valdivia-Silva et al. (2009) [74]	L-Arginine	Inclusion criteria: the patients were normotensive during the 1st trimester and had no history of SAH. None of the women had a history of PE or other factors that cause IUGR. Exclusion criteria: women who had a history of being smokers, chronic diseases such as SAH, coronary HD, RD and/or DM, prophylactic treatments with aspirin or fetal malformations detected by ultrasonography, and the presence of some complication that would require an emergency delivery that has not allowed the treatment to continue for at least 3 weeks.	3 g 20 weeks until delivery	The risk of IUGR was 5x ↑ in infants born to mothers with PE without L-arginine therapy and twice as often in babies born to mothers with PE in the intervention group. The fetal biophysical profile and the Apgar score were significantly more favorable in the intervention group.
Teran et al. (2009) [71]	Coenzyme Q10	Inclusion criteria: women between 16 and 20 weeks of pregnancy (established by date of last menstrual period and confirmed by ultrasound), not currently taking medication, and with no known medical disorders. Exclusion criteria: women who were taking vitamin supplements.	200 mg 20 weeks until delivery	There were no ≠ between the groups in the incidence of LBW and mean birth weight. There was no perinatal mortality. Only 2 pregnancies resulted in preterm birth and both were in the placebo group.
Tara et al. (2010) [69]	Selenium	Inclusion criteria: gestational age up to 12 weeks, and with no indications for termination of the pregnancy. Exclusion criteria: in use of any drugs, except routine supplements of folic acid and ferrous sulphate, and a prior history or clinical features of any medical conditions, including thyroid disorders, DM, SAH, and infections.	100 μg 1st trimester until childbirth	Selenium supplementation significantly ↑ serum selenium concentrations in full-term newborns. However, there were no ≠ in systolic and diastolic blood pressure, total serum cholesterol and fractions, triglycerides, and high sensitivity C-reactive protein between the groups.
Aalami-Harandi et al. (2014) [70]	Allicin	Pregnant women at risk for PE, primiparous women, aged 18-40 years old who were carrying singleton pregnancy at 27 weeks of gestation.	400 mg garlic (1 mg allicin) 27 weeks, for 9 weeks	Significant protein ↓ in C-reactive protein and a significant ↑ in plasma GSH levels. No significant effect on serum lipid profiles, plasma levels of total antioxidant capacity and pregnancy outcomes.
Motawei et al. (2016) [72]	N-Acetyl-cysteine	Women with diagnosis of PE and health pregnancy to the control group.	400 mg For 6 weeks	Improvement in pregnancy outcomes, birth weight, and Apgar score among intervention group patients but without ≠ in the incidence of obstetric complications and markers of oxidative stress between the two groups.
Spinnato et al. (2007) [75]	Vits. C and E	Inclusion criteria: women who were 12 0/7 to 19 6/7 weeks pregnant and diagnosed with nonproteinuric chronic hypertension SAH or a prior history of PE in their most recent pregnancy that progressed beyond 20 weeks of gestation. Exclusion criteria: multifetal gestation, allergy to vit. C or E, requirement for aspirin or anticoagulant medication, 24-hour urinary protein 300 mg or more, prepregnancy DM, known fetal anomaly incompatible with life, or prior participation in the study.	1000 mg 400 IU 12-19 weeks until childbirth or disease development	Preterm membrane rupture was ↑ in the intervention group. There was no influence on the frequency of LBW, small for gestational age, stillbirth, birth measurement, asphyxia or Apgar scores.
Xu et al. (2010) [133]	Vits. C and E	Inclusion criteria: women between 12 and 18 completed weeks of pregnancy on the basis of last menstrual period and confirmed by early ultrasound examination. Exclusion criteria: women who regularly consumed supplements 200 mg/day for vit. C and/or 50 IU/day for vit. E; women who took warfarin; women who had known fetal abnormalities or known fetal chromosomal or major malformations in the current pregnancy; women who had a history of medical complications including endocrine disease, RD with altered renal function, epilepsy, any collagen vascular disease, active and chronic LD, HD, cancer, or hematologic disorder; women with repeated spontaneous abortion (women with a previous bleeding in the 1st trimester were included if the site documented a viable fetus at the time of recruitment); and women who used an illicit drug during the current pregnancy.	1000 mg 400 IU 12-18 weeks until delivery	No difference in maternal adverse outcomes between groups, including rates of miscarriage, fetal death, neonatal death, preterm birth, IUGR, or small for gestational age.
Sharma et al. (2003) [68]	Lycopene	Primiparous women with gestation between 16 and 20 weeks with absence of any medical complication such as RD, SAH, HD, DM, or connective tissue disease.	2 mg 16-20 weeks until delivery or development of PE	The mean birth weight was ↑ and there was ↓ of IUGR in the intervention group.
Roberts et al. (2010) [134]	Vits. C and E	Inclusion criteria: pregnant women who had a singleton fetus with a gestational age of less than 16 weeks 0 days at the time of screening. Gestational age at randomization was between 9 weeks 0 days and 16 weeks 6 days. Women were eligible for inclusion if they had not had a previous pregnancy that lasted beyond 19 weeks 6 days. Gestational age was determined before randomization with the use of a previously described algorithm that took into account the date of the last menstrual period (if reliable information was available) and results of the earliest ultrasound examination. Exclusion criteria: women with elevated systolic blood pressure (135 mmHg or higher), elevated diastolic blood pressure (85 mmHg or higher), or proteinuria (300 mg of protein or more, as measured in a 24-hour urine sample, or a urine-dipstick result of 1+ or higher for protein), were taking or had taken antihypertensive medication, or were taking more than 150 mg of vitamin C or more than 75 IU of vit. E daily. DM that was present before the pregnancy, treatment with antiplatelet drugs or nonsteroidal anti-inflammatory agents, uterine bleeding within the week before recruitment, uterine malformation, serious medical condition, known fetal anomaly or aneuploidy, in vitro fertilization resulting in the current pregnancy, or abuse of illicit drugs or alcohol.	1000 mg 400 IU 9-16 weeks, until delivery	Vitamins C and E did not reduce adverse maternal or perinatal outcomes in women at high risk.

Legend: BMI: body mass index; DM: diabetes mellitus; GSH: reduced glutathione; HD: hearth disease; IUGR: intrauterine growth restriction; LBW: low birth weight; LD: liver disease; PE: preeclampsia; ↑: higher; ↓: lower; ≠: difference; RD: renal disease; SAH: systemic arterial hypertension; vits.: vitamins.