High-contact sports, such as football, involve a high risk of concussive injury and a higher risk of repeated subconcussive head impacts, impacts that do not meet the threshold for a concussion diagnosis. Although the long-term effects of concussive injury have been associated with chronic traumatic encephalopathy a progressive neurodegenerative disorder, the long-term effects of cumulative subconcussive head impacts on brain structure, function, and mental health are unclear and a growing concern. In a 2019 position statement, the American Medical Society for Sports Medicine commented that subconcussive head impacts may create a risk of long-term neurological sequelae, and future research should include developing technologies that can assess brain changes following repetitive asymptomatic head trauma in living subjects.

The brain is highly enriched in long-chain (>20 carbon) omega-3 highly polyunsaturated fatty acids such as docosahexaenoic acid. DHA is a primary structural and functional component of neuronal cell membranes; it regulates neurological processes involved in brain development and repair, including neuronal survival, synaptogenesis, myelination, neuronal plasticity, and neuroinflammation.

With limited research on the effects of fish oil supplementation on axonal injury from subconcussive head impacts in contact sports athletes, the primary aim of this clinical trial was to determine if omega-3 supplementation is effective in mitigating the biomarkers of adverse effects (axonal injury and inflammation) from subconcussive head impacts in collegiate American football athletes (the University of Arizona football team) over the course of the football season. 

Gamma-Linolenic acid (GLA) is an omega-6, 18-carbon PUFA found in several seed oils, including evening primrose [∼10% of total fatty acids (FAs)] and borage (∼21%). While many types of studies (animal and human) have shown that GLA-containing oils reduce inflammatory processes and impact inflammatory diseases (rheumatoid arthritis, asthma and atopic dermatitis), there is large unexplained heterogeneity in results of clinical studies, and recent meta-analyses have called into question the efficacy of these oils.

Given the confusion in the scientific literature, a critical next step was to complete a prospective clinical trial to determine if there were genetic variations in humans that made GLA effective in some individuals and not others. Specifically, we examined the impact of variation of a fatty acid desaturase (FADS1)  on the capacity of GLA to be converted to pro- and anti-inflammatory fatty acids in non-Hispanic white individuals.

Sixty-four healthy adults participated in a randomized, double-blind, crossover intervention. These individuals were subgrouped by their genotype in the FADS1 region. Together, the results from our clinical trial raised important questions regarding the impact of supplementation with GLA-containing oils in diverse populations. Importantly, they suggest that a generalized “one size fits all” dietary supplementation approach may not be appropriate or safe.

A key finding from the study was that the impact of GLA consumption and its subsequent metabolism to pro- or anti-inflammatory fatty acids depend on FADS1 variant–associated metabolic efficiency. Specifically, an inefficient conversion phenotype would result in the accumulation of anti-inflammatory fatty acids. In contrast, the efficient converter phenotype would exhibit increased pro-inflammatory fatty acids at the expense of anti-inflammatory fatty acids.  Again, studies such as this make a powerful case for a precision nutrition approach to dietary supplementation.

The adaptive stress response is an evolutionary response of cells, and entire organisms, to moderate environmental stresses. As of yet, the molecular mechanisms responsible for the adaptive stress response in living, healthy humans have yet to be determined. Stress for humans can come from environmental factors such as exercise, heat, and calorie restriction. In fact, recent research has shown that there may be beneficial effects of exercising in a heated environment, like hot yoga, that improve various markers of health. Dr. Chilton’s laboratory is focused on understanding the underlying molecular mechanisms of how adaptive stress, and specifically hot yoga, can improve human health.

The research team has used the commonly practiced, safe, and accessible intervention of hot yoga to expose the study participants to mild heat stress and moderate exercise for six weeks. The study participants were women, aged -- to ---. The team monitored a wide range of physiological parameters, including resting and active heart rates, sleep quality, and blood oxygen levels. Additionally, blood samples were taken from participants at varying time points to evaluate the impact of the intervention on blood cell numbers and percentages, immune cell function, and dozens of inflammatory and cardiometabolic biomarkers.

The data from this study is currently being analyzed. However, the research team is optimistic that this small pilot clinical trial will provide a basic understanding of how hot yoga and adaptive stress improve human health. This study could pave the way for much larger clinical trials exploring this exciting area of research.