Circulating Polyamines and Metabolic Changes Following a Mediterranean Diet with or Without Naltrexone/Bupropion in Breast Cancer Survivors: An Exploratory Secondary Analysis.

Background/

Objectives

The Mediterranean diet is widely recognized for its cardiovascular and metabolic benefits, including weight reduction; however, the metabolic mechanisms underlying these effects remain incompletely understood. This study investigated whether changes in circulating polyamines are associated with metabolic improvements following a Mediterranean diet intervention, particularly in breast cancer survivors.

Methods

This exploratory secondary analysis used stored paired serum samples from a previously reported 8-week controlled intervention conducted in three groups: Group A (breast cancer survivors following a Mediterranean diet alone, n = 21), Group B (breast cancer survivors following a Mediterranean diet combined with naltrexone/bupropion, n = 23), and Group C (non-cancer participants receiving the combined intervention, n = 28). Paired polyamine data were available for 16, 9, and 16 participants, respectively. Breast cancer survivors were randomized to Groups A and B, whereas Group C was enrolled as a non-randomized active comparison group. Serum metabolic profiles were analyzed using liquid chromatography-mass spectrometry-based untargeted metabolomics, and nine polyamines were quantified using targeted analysis. An exploratory indirect-effect analysis examined associations between changes in serum polyamines and clinical outcomes, including body composition and lipid parameters.

Results

Body weight, fat mass, and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) decreased significantly within all three groups after the 8-week intervention (median changes: -1.9 to -2.8 kg, -1.9 to -2.8 kg, and -0.3 to -0.7, respectively). LDL cholesterol decreased significantly only within the two groups receiving naltrexone/bupropion (median changes: -20.6 and -10.1 mg/dL). However, between-group differences in these changes were not statistically significant. N-acetylspermine increased nominally in all groups (p < 0.01), whereas spermine increased only in the Mediterranean diet alone group (p = 0.015).

Conclusions

Mediterranean diet-related metabolic improvements were accompanied by changes in circulating polyamines. Spermine and N-acetylspermine may represent candidate metabolic response markers associated with nutritional and pharmacological interventions in breast cancer survivorship.