An eight-week randomized trial found that lactoferrin-fortified yogurt helped maintain ferritin levels without causing iron overload, while modestly shifting selected gut bacteria.
Study: Effects of lactoferrin-enriched dairy product on iron status in women with gestational diabetes mellitus. Image Credit: Anna Brusnicyna
In a recent 'Article in Press' in the journal npj Science of Food, researchers conducted a double-blind, randomized pilot trial to evaluate whether yogurt enriched with lactoferrin (LF) would safely support iron status in 50 pregnant women described by the authors as Caucasian, all of whom had diagnosed gestational diabetes mellitus (GDM) and reduced iron stores.
Decades of research have established that pregnancy increases maternal iron requirements and can deplete iron stores, leading routine prenatal care to commonly include iron supplements. However, a growing body of evidence suggests that altered iron metabolism in GDM may increase the risk of relative iron overload in some women, underscoring the importance of individualized iron supplementation and additional dietary strategies as areas of research.
The trial lasted eight weeks, following which statistical analyses revealed that LF-enriched yogurt helped prevent ferritin decline and was associated with modest changes in selected gut bacteria, without altering overall microbiome diversity. While larger cohorts from distinct ethnic groups will be required to confirm these findings, the findings suggest that yogurt, a commonly consumed fortified food, may provide a practical, well-tolerated addition to routine iron supplementation for women with GDM and low ferritin.
Background
Hemodilution is a normal physiological adaptation during pregnancy, caused by an increase in plasma volume that dilutes red blood cell counts and hemoglobin concentrations. Pregnancy also increases total iron requirements to support the expansion of maternal red blood cell mass and fetal and placental development.
To prevent iron-deficiency anemia, obstetricians have routinely recommended prenatal iron supplementation. However, clinical studies and meta-analyses suggest that iron management may require closer consideration in pregnancies complicated by gestational diabetes mellitus, a form of hyperglycemia first diagnosed during pregnancy.
Previous research has reported that GDM can be associated with altered iron metabolism, including relatively elevated ferritin and other iron-related markers in some women. Excess iron may exacerbate oxidative stress and tissue inflammation, potentially worsening insulin resistance and beta-cell dysfunction. These findings have raised concerns about indiscriminate iron supplementation in susceptible women, although these mechanisms were not directly assessed in the present trial.
There remains, therefore, a clinical need for strategies that preserve maternal iron stores while minimizing the risk of excessive iron accumulation.
About the Study
This study aimed to determine whether lactoferrin, a milk-derived iron-binding glycoprotein with anti-inflammatory and microbiota-modulating properties, could provide a well-tolerated adjunct to routine iron supplementation.
The study’s sample cohort comprised 50 Caucasian women diagnosed with GDM between 24 and 30 weeks of gestation. All enrolled participants had reduced iron stores, defined as serum ferritin levels below 30 µg/L. Known anemia was an exclusion criterion, although some participants met the study’s baseline laboratory definition of anemia.
Study participants were randomly assigned to either the experimental cohort (n = 25), which consumed yogurt fortified with 100 mg of bovine lactoferrin per 125 g serving, or the control cohort (n = 25), which consumed a standard, non-enriched control yogurt.
The study intervention required participants in both groups to consume two daily servings for eight weeks, alongside a routine prenatal supplement containing 30 milligrams of elemental iron, which they had already been taking as part of routine prenatal care.
The study’s primary clinical endpoint was the change in participants’ serum ferritin levels from baseline at study enrolment to the end of the eight-week intervention.
Secondary outcomes included red blood cell metrics, metabolic indicators (including fasting glucose and insulin), maternal-neonatal outcomes, and alterations in the gut microbiome.
Study Findings
Of the 50 women enrolled in the trial, 46 completed the full intervention and were included in the final analytical dataset. Study findings revealed that the fortified yogurt was well tolerated, with no gastrointestinal adverse effects attributable to either yogurt reported. While transferrin levels and red blood cell counts rose in both groups, statistical models revealed a divergence in maternal iron storage metrics between the cohorts.
Specifically, in the control group, ferritin levels declined significantly, with a median reduction of 3.5 µg/L, whereas the lactoferrin experimental group maintained statistically stable levels, with a median increase of 1.5 µg/L and a significant between-group difference (p = 0.011).
In contrast, end-of-trial anemia rates remained statistically comparable between the two cohorts, at 20.8% in the LF group versus 27.3% in controls (p = 0.609). Fasting glucose did not change significantly, whereas insulin and the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) increased in both groups. None of these metabolic measures differed significantly between the groups.
The combined occurrence of any listed maternal, delivery, or neonatal outcome was significantly lower in the lactoferrin group (p = 0.040). However, none of the individual outcomes, including insulin treatment, maternal complications, cesarean delivery, preterm birth, or neonatal complications, differed significantly, making the composite finding exploratory.
Finally, microbiome analyses showed that LF was associated with a higher relative abundance of Lactobacillus (p = 0.020) and lower relative abundances of Eggerthella (p = 0.003) and Actinomyces compared with controls. Overall microbial diversity remained unchanged. These exploratory taxonomic findings require confirmation, as numerous bacterial comparisons were conducted on a small sample.
Conclusions
This pilot study indicates that simple food fortification with lactoferrin was well tolerated and may help preserve maternal ferritin when added to routine iron supplementation in women with GDM and reduced iron stores.
While the study’s sample size of 46 and the lack of broader inflammatory biomarker measurements are notable limitations, other constraints included the absence of hepcidin and soluble transferrin receptor measurements, recruitment of a single ethnic group, short follow-up, and retrospective trial registration. Its findings are encouraging and merit further research with larger, more diverse cohorts and longer follow-up.
Journal reference:
- Goitre, I., et al. (2026). Effects of lactoferrin-enriched dairy product on iron status in women with gestational diabetes mellitus. npj Science of Food, Article in Press. DOI: 10.1038/s41538-026-00998-y, https://www.nature.com/articles/s41538-026-00998-y