Multi-Supplement Lowers Stress and Reduces Immune System Aging by 15 Years, New Study Shows

Highlights

• The multi-supplement intervention improves immune cell function and reduces biological age by an average of 15 years. 
• Supplementation normalizes stress hormone levels, which could explain the improvements in immune system health.  

In the evolving landscape of longevity research, the paradigm is shifting towards sophisticated multi-compound interventions that target multiple aging processes. This is in contrast to single compounds that only target one age-related process, such as low NAD+ levels. A recent study published in Biomolecules exemplifies the former approach, demonstrating how a carefully devised combination of compounds can reverse biological aging markers in postmenopausal women.

Beyond Single-Agent Interventions

Longevity research has seen a succession of compounds (e.g., resveratrol, metformin, rapamycin), each initially heralded as a potential singular solution to the complex challenge of aging. However, as our understanding of aging biology has matured, so too has the recognition that aging represents not one process but a multifaceted constellation of interconnected biological phenomena, including mitochondrial dysfunction, cellular senescence, and DNA damage. 

Each biological phenomenon represents a potential intervention target, so multiple interventions can cover multiple targets. Moreover, certain compounds demonstrate enhanced efficacy when administered in combination, producing effects greater than the sum of their individual actions. This synergistic effect can allow for lower doses of multiple compounds with fewer adverse effects than higher doses of single agents.

Multi-Supplement Combo Reduces Biological Age 

The Biomolecules study provides a compelling illustration of the multi-compound approach. Researchers investigated a supplement called UNAMINA, comprising 39 distinct bioactive compounds administered in three servings, either dissolved in water or in capsule form:  

• UNAMINA A (powder): Focuses on structural support through collagen precursors (glycine, L-lysine, L-arginine, L-proline, L-leucine, L-isoleucine, L-valine, L-tryptophan) and hydrolyzed collagen, complemented by methyl-sulfonyl-methane and mineral cofactors (magnesium citrate, calcium carbonate).
• UNAMINA B (capsule): Targets cellular metabolism through a combination of amino acids (L-ornithine, L-beta-alanine, N-acetyl L-cysteine, L-threonine, L-histidine, L-glutamine, L-taurine, thiamine), B vitamins (riboflavin, niacin, pantothenic acid, pyridoxine, biotin, folate, and cobalamin), and other compounds (zinc sulphate hydrate, sodium selenate, magnesium, manganese sulphate, chondroitin sulphate, glucosamine sulphate, sodium hyaluronate, and ferrous fumarate).  
• UNAMINA C (powder): Includes cell metabolism stimulants (citric, malic, and ascorbic acids). 

After just one month of supplementation, participants demonstrated significant improvements across multiple aging biomarkers. Immune cell function, such as the ability of immune cells to respond to an infection, improved substantially. Moreover, the immune cell function results were used to calculate biological age using the Immunity Clock. Astonishingly, the calculation showed that biological age decreased by an average of 15 years. 

“Maintaining a younger biological age may help individuals to lower their risk of age-related diseases and increase their overall lifespan,” said the authors.

Multi-Supplement Combo Reduces Stress

Supplementation led to a decrease in the stress hormone cortisol and an increase in a hormone called DHEA (dehydroepiandrosterone). While cortisol suppresses the immune system, DHEA enhances it. Still, cortisol tends to increase with age as DHEA declines, both contributing to chronic stress. Thus, these findings suggest that the multi-supplement combo can counteract the hormonal changes that lead to chronic stress and immune system dysfunction. 

Aberrant changes in cortisol and DHEA are associated with oxidative stress, the damage caused to our cells by excessive levels of molecules called oxidants. However, the researchers found that the multi-supplement combination reduced oxidative stress by decreasing oxidant levels and increasing antioxidant levels. These findings suggest that supplementation counters immune system dysfunction by normalizing stress hormone levels and preventing oxidative stress.

Does Stress Cause Aging? 

The study’s findings support the neuroendocrine hypothesis of immunosenescence, which emphasizes the imbalance between cortisol and DHEA as the main determinant of immune system decline. Cortisol is secreted by the adrenals, glands that sit atop the kidneys. A structure in the brain, sometimes referred to as the aging center of the brain, called the hypothalamus, initiates adrenal cortisol release by signaling to a brain structure called the pituitary gland. This signaling cascade is called the HPA (hypothalamic-pituitary-adrenal) axis. 

Normally, high cortisol levels halt the HPA cascade so that cortisol is no longer released. However, according to the hypothesis, chronic stress, which elevates cortisol, leads to the degeneration of key brain regions, including the hypothalamus. This makes the hypothalamus less sensitive to detecting cortisol, which keeps cortisol levels high by allowing the HPA cascade to persist. Chronically high cortisol levels, combined with age-related DHEA decline, exacerbate the degeneration of the hypothalamus, according to theory. 

Furthermore, high cortisol and low DHEA can promote thymic involution — the age-related shrinking of the thymus. The thymus is an immune system organ that normally produces T cells, a type of white blood cell that helps the immune system fight off infections. A reduction in new T cells contributes to the age-related immune system dysfunction referred to as immunosenescence. In turn, immunosenescence is linked to chronic low-grade inflammation, which underlies nearly every chronic age-related disease, including cardiovascular disease, neurodegenerative diseases, and cancer. 

Study Limitations 

The researchers state the limitations of their study: 

“Firstly, the sample size is small, which limits the generalizability of the findings to a broader population. Additionally, the lack of a placebo control group prevents ruling out the influence of other uncontrolled factors on the observed effects. Also, a key limitation of the study is the absence of traditional clinical markers… ….as well as the inability to determine the individual impact of UNAMINA’s components or whether the detected benefits are the result of a synergistic effect. Moreover, the study duration was limited to one month, so it cannot be concluded whether the effects persist in the long term. Finally, since the research focused exclusively on postmenopausal women, it is not possible to extrapolate these results to other population groups, such as men or women in different life stages.”

Multi-Compound Interventions: The Future of Aging Research  

The UNAMINA study, while preliminary, illustrates the potential of the multi-intervention paradigm. By simultaneously addressing multiple facets of aging biology — immune function, oxidative stress, and hormonal balance — this approach achieved measurable rejuvenation effects in a relatively short timeframe. 

As research continues, multi-compound interventions may increasingly define the cutting edge of anti-aging science. Rather than seeking the elusive single compound that addresses all aspects of aging, the future likely belongs to sophisticated combinations that collectively support the intricate biological symphony that determines how we age.