Milk protein and plant extract supplement shows promise for preschool anxiety in small trial

Anxiety disorders in preschool children are among the most common and most stubborn mental health problems of early childhood, and a new exploratory study from Italy suggests that a dietary supplement combining a West African plant seed extract with a hydrolyzed milk protein may help reduce symptoms in this notoriously difficult-to-treat age group. The research, conducted at the IRCCS Stella Maris Foundation in Pisa and published in Frontiers in Child and Adolescent Psychiatry, followed 22 children aged three to nearly seven years who received a supplement containing Griffonia seed extract and Lactium for three months, with some continuing for six. The findings, while preliminary, offer a rare glimpse into an underexplored therapeutic avenue for a population in which no pharmacological treatment is currently approved for anxiety disorders.

The scientific rationale behind the supplement rests on two well-characterized neurochemical pathways. Griffonia simplicifolia seeds are exceptionally rich in 5-hydroxytryptophan, a direct metabolic precursor of serotonin, the neurotransmitter most closely associated with mood regulation and the modulation of the brain’s so-called fear circuit centered on the amygdala. Lactium, by contrast, is an industrial hydrolysate of alpha-s1-casein, a milk protein that contains the bioactive peptide alpha-casozepine, a compound that acts on the GABAergic system, the brain’s primary inhibitory neurotransmitter network and the same target engaged by classical benzodiazepines. By combining a serotonergic precursor with a GABA-modulating peptide, the supplement theoretically engages both of the major neurotransmitter systems implicated in anxiety neurobiology, offering a dual mechanism of action that mirrors the logic of conventional pharmacotherapy without the same risk profile.

The clinical picture that brought these children to the researchers’ attention is characteristic of preschool psychopathology, which rarely presents as the verbalized worry seen in older children and adults. Instead, anxiety in very young children frequently manifests as intense emotional and behavioral dysregulation, including screaming, crying, tantrums, and aggression directed at themselves or others. In this sample, 68 percent of the children exhibited symptoms consistent with emotional dysregulation, and the vast majority carried comorbid neurodevelopmental diagnoses, with 86 percent meeting criteria for attention-deficit/hyperactivity disorder and 45 percent for autism spectrum disorder. This level of comorbidity reflects the reality of tertiary care clinical practice, where complex, overlapping symptom presentations are the norm rather than the exception, and it makes the task of isolating treatment effects on anxiety specifically all the more challenging.

The study design was longitudinal, interventional, and single-center, with participants enrolled between May 2022 and January 2025. Twenty-five children initially met inclusion criteria and provided informed consent, though three dropped out very early, leaving 22 in the final analysis. The daily dosage consisted of 75 milligrams of Griffonia extract, providing 15 milligrams of 5-hydroxytryptophan, alongside 150 milligrams of hydrolyzed milk protein. Eight children received the supplement for three months under the initial protocol, while fourteen were enrolled under a revised protocol extending supplementation to six months. Exclusion criteria included an intelligence quotient below 70, lactose intolerance, and concurrent pharmacological treatment, ensuring that any observed effects could not be attributed to other medications.

Assessment relied on a combination of parent-reported and clinician-rated instruments, a methodological choice the researchers emphasize as a strength given that preschool children may behave differently across relational contexts. Parents completed the Preschool Anxiety Scale, a 28-item questionnaire covering generalized anxiety, social anxiety, obsessive-compulsive symptoms, fears of physical injury, and separation anxiety. Clinicians independently rated global functioning using the Children’s Global Assessment Scale and overall illness severity and improvement using the Clinical Global Impression scale. Statistical analysis employed linear mixed models with random intercepts to account for within-subject correlation over time, and p values were corrected for multiple comparisons using the false discovery rate procedure, a relatively rigorous approach for a study of this size.

The results after three months of supplementation were notable across multiple domains. Parents reported a statistically significant reduction in the total anxiety score, with a standardized effect corresponding to roughly five points on the scale, as well as significant decreases in the social anxiety and fears of physical injury subscales. Clinician-rated global functioning, as measured by the Children’s Global Assessment Scale, increased by approximately 7.7 points, a change that reached a p value below 0.0001 and that the researchers describe as clinically meaningful given the scale’s range from 1 to 100. Perhaps most strikingly, these improvements were maintained at a follow-up assessment conducted three months after the supplement was discontinued, suggesting that the benefits persisted beyond the period of active supplementation rather than simply reflecting a temporary pharmacological effect.

When the researchers compared children who received the supplement for six months with those who received it for only three, the between-group differences on the parent-reported anxiety measures did not reach statistical significance. However, on the clinician-rated improvement scale assessed three months after discontinuation, the six-month group showed significantly better outcomes, with mean improvement scores indicating greater sustained benefit. This finding, while requiring confirmation in larger samples, hints at a dose-duration relationship in which longer exposure to the supplement’s active compounds may consolidate clinical gains more durably. The researchers also noted that girls maintained improvements in overall functioning to a significantly greater extent than boys at the post-discontinuation follow-up, a gender difference that emerged despite the absence of baseline differences in anxiety expression between the sexes.

In an additional exploratory analysis conducted outside the main protocol, the researchers compared the developmental trajectory of the supplemented children with a retrospectively reconstructed trajectory of 15 preschool children with anxiety symptoms who had not received the supplement, recruited from a naturalistic clinical setting between 2021 and 2024. At the end of the respective observation periods, children who had taken the supplement scored significantly higher on the clinician-rated global functioning measure, with an F statistic of 15.15 and a p value of 0.01. The researchers are careful to note that this comparison involved non-contemporaneous, non-randomized groups and should be considered purely exploratory, but it provides a preliminary signal that the supplement may confer advantages beyond what would be expected from natural clinical course alone.

Safety data from the study were reassuring, with no adverse events observed in any participant during the entire observation period. The only known risk associated with excessive intake of the supplement is a mild laxative effect, a profile that stands in stark contrast to the side-effect burden of conventional anxiolytic medications. Six participants did drop out over the course of the study, four due to parental withdrawal of consent, one due to clinical worsening requiring pharmacological treatment, and one due to difficulties with the taste of the supplement, but none of these discontinuations were attributed to safety concerns.

The researchers are unequivocal that these findings should be interpreted as exploratory rather than definitive. The sample was small, the design was open-label and single-arm without a placebo control, the follow-up period was relatively short, and the high rate of psychiatric comorbidity may have contributed to symptom overlap that limits generalizability. Nevertheless, the study represents a meaningful contribution to a field in which fewer than 15 percent of young children with impairing anxiety disorders receive any mental health evaluation or treatment, and in which the developmental stakes are extraordinarily high, given that preschool anxiety predicts persistence into school age and adolescence and interferes with later social and academic functioning. The researchers call for randomized controlled trials with larger samples and longer follow-up periods to confirm whether this combination of a serotonergic plant precursor and a GABA-modulating milk peptide can truly reshape the developmental trajectory of early-onset anxiety, but for now, the results offer a cautious note of optimism for one of pediatric mental health’s most underserved populations.

Subject of Research: A brief research report on the efficacy of Griffonia and Lactium supplementation in a clinical preschool sample with anxiety disorders and emotional dysregulation

Article Title: A brief research report on the efficacy of Griffonia and Lactium supplementation in a clinical preschool sample with anxiety disorders and emotional dysregulation

Article References: A brief research report on the efficacy of Griffonia and Lactium supplementation in a clinical preschool sample with anxiety disorders and emotional dysregulation. (n.d.). https://doi.org/10.3389/frcha.2026.1905412

Image Credits: AI Generated

DOI: 10.3389/frcha.2026.1905412

Keywords: brief, research, report, efficacy, Griffonia, Lactium, supplementation, clinical, preschool, sample, anxiety, disorders