Can Extra Virgin Olive Oil Reduce Oxidative Stress in Premature Infants?

Study Overview

The paper, “The Effect of Enteral Organic Extra Virgin Oil Supplementation in Premature Babies on Postnatal Growth, Premature Morbidities, and Oxidative Status,” was published in Children in 2026 by Bayram Ali Dorum and colleagues. It was conducted in a tertiary neonatal intensive care unit between November 2023 and March 2025 and registered at ClinicalTrials.gov as NCT06072625.

Eligible infants were born before 32 weeks of gestation, weighed under 1500 g at birth, and had achieved full enteral feeding before the third postnatal week. Of 110 initially randomized infants, 89 completed the protocol: 48 in the olive-oil group and 41 in the control group. Baseline characteristics were broadly similar, including gestational age (29.07 ± 1.73 vs 29.28 ± 1.45 weeks) and birth weight (1130.54 ± 212.11 g vs 1143.78 ± 218.08 g).

The intervention was specific: 1 mL/kg/day of organic, low-acidity extra virgin olive oil, added once daily to enteral feeds after full feeding was established and continued until discharge. The control group received standard nutrition. Laboratory personnel measuring oxidative markers were blinded to group allocation, although caregivers were not blinded because the nutritional intervention was visible.

The primary clinical outcomes were growth and prematurity-related morbidities. The mechanistic outcomes were serum malondialdehyde (MDA), a marker of lipid peroxidation, and total antioxidant capacity (TAC), measured before intervention and again around 36 weeks postmenstrual age. That design makes this less of an “olive oil makes babies grow faster” study and more of an oxidative-stress biology study.

Key Findings: The Actual Numbers

Growth did not improve. Average daily weight gain was 22.08 ± 5.48 g in the olive-oil group and 22.69 ± 5.34 g in controls (p = 0.529). Discharge weight was also similar: 1989.80 ± 320.11 g versus 2029.45 ± 311.07 g (p = 0.595). Rates of retinopathy of prematurity, bronchopulmonary dysplasia, sepsis, discharge week, total parenteral nutrition days, and hospital stay were not significantly different.

The oxidative-stress results were more interesting. Baseline MDA was similar: median 92 ng/mL in the olive-oil group versus 82.9 ng/mL in controls (p = 0.132). After the intervention, MDA was significantly lower in the olive-oil group: 75.7 ng/mL versus 93.2 ng/mL in controls (p = 0.022). The change score also favored olive oil: median ΔMDA was -18.09 ng/mL with olive oil versus +1.58 ng/mL in controls (p = 0.016).

TAC told the same story from the antioxidant side. Post-intervention TAC alone was not significantly different between groups (0.34 vs 0.29 mmol/L; p = 0.211), but the direction of change was significant: median ΔTAC was +0.16 mmol/L in the olive-oil group versus -0.15 mmol/L in controls (p = 0.006). In plain English, lipid peroxidation moved down and antioxidant capacity moved up.

Safety signals were reassuring within this small sample. The olive-oil group consumed more energy and lipid — 138.22 ± 9.09 vs 127.08 ± 10.29 kcal/kg/day and 7.30 ± 1.02 vs 6.58 ± 0.89 g lipid/kg/day, both p < 0.001 — but triglyceride levels were similar before and after intervention, and the authors reported no hyperlipidemia cases.

Mechanism: Why EVOO Might Matter Here

Very-low-birth-weight infants are prone to oxidative injury because antioxidant enzymes, non-enzymatic antioxidants, lung development, retinal vascular development, and inflammatory control are all immature. Malondialdehyde rises when reactive oxygen species attack polyunsaturated lipids in cell membranes. It is not a perfect clinical endpoint, but it is a reasonable signal of lipid peroxidation pressure.

Extra virgin olive oil brings two relevant biological features. First, it is rich in oleic acid, a monounsaturated fat that is generally less oxidation-prone than polyunsaturated fatty acids. Second, genuine EVOO contains phenolic compounds such as hydroxytyrosol, tyrosol, and oleuropein derivatives. These can donate electrons, modulate oxidative pathways, and influence inflammatory signaling. In adults, these same molecules are often discussed in cardiovascular terms; here, the biological frame is neonatal oxidative vulnerability.

The study cannot prove which component did the work. The intervention increased total calories and lipids as well as providing EVOO-specific compounds. Still, the paired movement — lower MDA and higher TAC change — is mechanistically coherent with an antioxidant-rich fat source. The finding that infants who developed bronchopulmonary dysplasia or retinopathy of prematurity had higher later MDA also reinforces the biological relevance: MDA-2 was 102 vs 80.1 ng/mL for BPD (p = 0.005) and 98.1 vs 77.9 ng/mL for ROP (p = 0.015).

Context: How This Compares With Previous Research

Most olive-oil research focuses on adults: blood pressure, LDL oxidation, glucose control, cardiovascular events, cognition, and inflammatory biomarkers. This paper is unusual because it moves EVOO into neonatal intensive-care nutrition, where the outcomes and risk calculus are completely different. It also follows earlier neonatal nutrition work that looked at olive oil mainly for feeding tolerance or growth, rather than oxidative status.

The result is consistent with a broader pattern in olive-polyphenol research: the most reliable short-term signals tend to appear in oxidative-stress or antioxidant-capacity markers before they appear in hard clinical outcomes. That is not a weakness by itself. It is how nutrition mechanisms often surface first. But it does mean the correct interpretation is “promising biomarker improvement,” not “proven reduction in prematurity complications.”

Compared with adult RCTs using high-polyphenol EVOO or purified hydroxytyrosol, this study is more clinically delicate and less definitive. The population is small, fragile, and medically managed. But the signal is valuable because it shows that a food-based antioxidant strategy can be studied with measurable biochemical endpoints even in a neonatal setting.

Limitations

• • Not fully blinded: caregivers knew group assignment, although laboratory personnel were blinded.
• • Alternating allocation: after the first lottery assignment, infants were allocated alternately, which is weaker than concealed randomization.
• • Underpowered versus plan: the target was 55 per group, but 48 and 41 completed; recalculated power was 73%.
• • Biomarker endpoint: MDA and TAC improved, but growth, ROP, BPD, sepsis, and hospital-stay outcomes did not significantly improve.
• • Energy confounding: the olive-oil group received more calories and lipid, so EVOO-specific effects cannot be perfectly isolated.
• • Single-center neonatal population: results may not generalize to other NICUs, feeding protocols, gestational ages, or adult health decisions.

Our Take

This is a strong “interesting, not practice-changing yet” paper. The best part is the directionally clean oxidative-stress signal: MDA went lower, TAC change went higher, and triglyceride safety did not raise an obvious red flag. The paper also deserves credit for studying a population where oxidative damage is not a wellness buzzword but a real clinical problem tied to lung and retinal morbidity.

The weaker part is methodology. Alternating allocation and lack of caregiver blinding leave more room for bias than a tightly concealed double-blind RCT. And because the intervention added calories and lipid, the study cannot tell us whether the effect came from EVOO phenolics, oleic acid, improved energy delivery, or the whole package.

My read: this is not a reason to market olive oil as neonatal medicine. But it is a meaningful addition to the olive-oil evidence map because it shows a measurable antioxidant effect in an unusually vulnerable clinical group. If replicated in a larger, fully randomized, blinded multicenter trial with standardized EVOO chemistry and clinical endpoints, it could become genuinely important.

Reference

Dorum BA, Erdoğan A, Çakır SÇ, Yarcı E, Özgür T, Ünallı Özmen S, Tutanç M. The Effect of Enteral Organic Extra Virgin Oil Supplementation in Premature Babies on Postnatal Growth, Premature Morbidities, and Oxidative Status. Children (Basel). 2026;13(3):327. doi: 10.3390/children13030327. PMID: 41897040. Full text: PMC13025372.