A groundbreaking clinical trial published in Antioxidants examined a three-part treatment aimed at addressing the phenomenon of inflammaging, an age-related, low-grade inflammation characterized by chronic, systemic inflammation and associated immune dysfunction.

Components of the Treatment

The researchers focused on three key components, each selected for its potential immunomodulatory properties:

  • AM3: A core ingredient in the Inmunoferon supplement and recognized as an immunomodulator that may bolster the immune response against infections [1].
  • Spermidine: A polyamine known to enhance autophagy, thereby mitigating immunosenescence and restoring healthy gut function by polarizing macrophages away from an inflammatory state [3].
  • Hesperidin: A flavonoid with reported benefits against various diseases, including metabolic disorders, attributed to its anti-inflammatory effects, such as the suppression of Matrix Metalloproteinase-9 (MMP-9) [9].

All three supplements are considered generally non-toxic and were well-tolerated by participants, with no significant side effects reported.

Study Design and Results

The study involved 35 healthy participants aged between 30 and 60 years who underwent treatment over a two-month period. Each participant received:

  • AM3: 150 mg
  • Hesperidin: 50 mg
  • Spermidine: 0.6 mg

To measure the primary outcome of biological age related to immune function, the researchers utilized the metric known as ImmunolAge, which assesses factors like neutrophil activity [11]. Initial measurements showed that participants had an ImmunolAge that was, on average, 20 years older than their chronological age, potentially influenced by reported stress levels.

Key Findings

The most significant improvements were observed in the treatment group, which showed a notable reduction in ImmunolAge by approximately 10 years. While still elevated compared to chronological age, this finding indicates a promising avenue for intervention in age-related immune dysfunction. Noteworthy outcomes included:

Biomarker Effect Significance
Neutrophil Activity Increased responsiveness Significant improvement
Lymphocyte Response Enhanced threat response Statistically significant
Inflammatory Factors (TNF-α, IL-1β) Decreased levels Significant
Anti-Inflammatory Factor (IL-10) Increased levels Significant
Oxidative Stress (Glutathione) Increased activity of reduced form Significant

Considerations and Limitations

Despite the encouraging findings, the trial had several limitations. Being a pilot study with only 35 participants, it lacks the robustness typical of larger Phase 2 or Phase 3 clinical trials. Key biomarkers related to cellular senescence were not directly analyzed, nor was an epigenetic clock implemented. Additionally, the impact of dietary factors was minimized as participants maintained their usual diets.

Furthermore, the extent to which these findings can translate to older populations remains uncertain, necessitating further exploration in diverse age groups.

Directions for Future Research

The study underscores the need for extensive future research to validate these findings. Potential research directions include:

  • Conducting larger, multi-phase clinical trials to confirm results.
  • Exploring the direct effects of the supplement combination on lifespan.
  • Investigating the underlying mechanisms of action of each component.

As researchers articulated, understanding the interplay between immune function and aging could provide avenues for extending not just lifespan but healthspan as well.

References

[1] JA, G. M., & Schamann, F. (1992). Immunologic clinical evaluation of a biological response modifier, AM3, in the treatment of childhood infectious respiratory pathology. Allergologia et Immunopathologia, 20(1), 35-39.

[2] Villarrubia, V. G., et al. (1997). The immunosenescent phenotype in mice and humans can be defined by alterations in the natural immunity reversal by immunomodulation with oral AM3. Immunopharmacology and Immunotoxicology, 19, 53-74.

[3] Zhang, H., & Simon, A. K. (2020). Polyamines reverse immune senescence via the translational control of autophagy. Autophagy, 16(1), 181-182.

[4] Niechcial, A., et al. (2023). Spermidine ameliorates colitis via induction of anti-inflammatory macrophages and prevention of intestinal dysbiosis. Journal of Crohn’s and Colitis, 17(9), 1489-1503.

[5] Li, S., et al. (2023). A systematic study on the treatment of hepatitis B-related hepatocellular carcinoma. Infectious Agents and Cancer, 18(1), 41.

[6] Mirzaei, A., et al. (2023). Promising influences of hesperidin against diabetes: a systematic review of molecular effects. EXCLI Journal, 22, 1235.

[7] Xiong, H., et al. (2019). Hesperidin: A therapeutic agent for obesity. Drug Design, Development and Therapy, 3855-3866.

[8] Morshedzadeh, N., et al. (2023). A narrative review on the role of hesperidin on metabolic parameters. Food Science & Nutrition, 11(12), 7523-7533.

[9] Lee, H. J., et al. (2018). The flavonoid hesperidin exerts anti-photoaging effect by downregulating MMP-9. BMC Complementary and Alternative Medicine, 18, 1-9.

[10] Camps-Bossacoma, M., et al. (2017). Influence of hesperidin on immune response. Nutrients, 9(6), 580.

[11] Martínez de Toda, I., et al. (2021). The immunity clock. The Journals of Gerontology: Series A, 76(11), 1939-1945.

[12] Miquel, J. (2009). An update of the oxidation-inflammation theory of aging. Current Pharmaceutical Design, 15(26), 3003-3026.

[13] Lifespan.io