Fatty acids and athletic performance
By Rebecca Guenard
- Omega-3 fatty acids have a solid reputation for contributing positively to the immune system, particularly as anti-inflammatory agents.
- Decades of research have failed to produce a direct link between fatty acid consumption and improved athletic performance, though enticing correlations exist.
- Related research, on animal models and in human tissue, shows that athletes require fatty acids for very specific functions, from healing brain injuries to opening airways.
- However, the question of whether athletes can gain an advantage through supplementation and dietary choices remains unanswered.
Athletes have myriad nutritional needs. They must stay hydrated and consume enough protein and carbohydrates to build and maintain the muscle strength and energy to perform in their sport. Among all the nutritional factors athletes must consider, how important are fatty acids in maximizing performance?
Fatty acids possess immunomodulatory and anti-inflammatory properties that improve immune function and benefit human health. Consequently, researchers have been investigating whether omega-3 supplements can be used to prevent or treat detrimental inflammatory responses like diabetes and cardiovascular disease. By extension, some scientists developed the hypothesis that omega-3 supplements would improve recovery during athletic training or after competition.
Meta-analyses of a decade’s worth of research are inconclusive (Table 1). Depending on the team conducting the review, the conclusion may be that omega-3 supplements benefit athletes (https://doi.org/10.3390/nu11010046) or that they have no measurable effect on healthy, young competitors (https://doi.org/10.1016/j.metabol.2016.10.007).
Simultaneously, mounting research results have failed to produce evidence that omega-3 supplements reduce the incidence of diabetes and cardiovascular disease in the general population. Likewise, most reports conclude that omega-3 supplements do not improve recovery or endurance in athletes. They are undoubtably important despite remaining questions about whether or not athletes can capitalize on fatty acid activity in the body by increasing consumption. In fact, the latest fatty acids research reveals that their influence on athletic performance is likely indirect and definitely complex.
“Athletes have well-regulated and understood diets to try to increase their performance, but the molecular mechanisms behind many of these processes is unknown,” says Andrew Tobin, a cellular biology professor at the University of Glasgow, Scotland. Fatty acids, for instance, are more than just an energy source.
“Fatty acids are like food hormones,” Tobin says. “When you eat certain foods, they enter the circulatory system and they activate receptor proteins.”
Hormones and neurotransmitters are signaling molecules that maintain human homeostasis by evoking a cellular response in organs and tissue. The molecules work by interacting with specific receptors in the cell, the largest and most diverse being the G protein-coupled receptors. This superfamily of receptors participates in virtually all aspects of human physiology. Some endocrine diseases occur because of mutations in these receptors. Considering this and their physiological relevance, G protein-coupled receptors are a popular drug target.
|551 mg eicosapentaenoic acid (EPA) and 551 mg docosahexaenoic acid (DHA) twice daily, during five weeks of pre-season rugby training||Reduced fatigue in countermovement jump tests (Eur. J. Sport Sci. 18: 1357–1367, 2018).|
|24-h exposure with 100 microM EPA in human myotubes||Augmented adaptability and upregulation of specific genes implicated in fatty acid beta-oxidation with global improvement in muscle metabolic flexibility (J. Lipid Res. 51: 2090–2104, 2010).|
|Four-week supplementation with n-3 PUFAs, 1.1 g per day||Significant increase in maximal oxygen uptake (VO2-max) and in endothelial function (PLoS ONE 10: e0117494, 2015).|
|14-days diet enriched with 5% cod liver oil followed by 14 days immobilization||Reduced myosin heavy chain loss during 14 days of hind limb immobilization (Appl. Physiol. Nutr. Metab. 35: 310–318, 2010).|
|Six-months supplementation with 1.8 g EPA, 1.5 g DHA daily||Increased hand grip and muscle strength (Am. J. Clin. Nutr. 102: 115–122, 2015).|
|Three-week supplementation with 3.2 g of EPA and 2.0 g of DHA||Reduced eicosanoids and pro-inflammatory cytokines concentration in the sputum of asthmatic athletes (Chest 129: 39–49, 2006).|
|Six-months supplementation with 3.36 g/day of n-3 PUFAs||Increased muscle mass and strength in older people (Am. J. Clin. Nutr., 102: 115–122, 2015).|
Free fatty acids from dietary fats act as both an energy source and, surprisingly, as signaling molecules. They bind to G protein-coupled receptors throughout the body that are associated with human metabolism.
What is this thing doing in the lung?
Tobin explains that receptors for the long-chain fatty acids reside in the gut, as well as on fat cells and in pancreatic cells. In most cases, they induce activity associated with digestion. “By acting on these cell types, long-chain fatty acids control fat storage and blood glucose levels in the body,” he says. So, the food we eat dictates how our body responds to food.
However, Tobin is not interested in how G protein-coupled receptors interact with free fatty acids to manage food; he wants to know the interaction’s effect on air. His research group studies the Free Fatty Acid Receptor 4 (FFA4). They were curious to know if the receptor resided beyond the digestive system and were surprised to find large numbers in the lungs. “When you find them in the lung, groups like ours get excited.” Tobin says. “We think, what on earth is this thing doing in the lung?”
The group cultured lung tissue to perform experiments that would reveal the receptors’ function. They found that FFA4 activated a mechanism similar to asthma, contracting the airway. Stimulating the receptor with a long-chain fatty acid molecule, like linoleic acid, relaxed the smooth muscle and opened the airway.
Then Tobin’s group altered the DNA of mice so their cells would not contain FFA4. When the restricted airways of these model mice were stimulated with a long-chain fatty acid molecule, the airways did not open. It was definitive, FFA4 could be targeted to relieve symptoms of asthma.
“This does not mean that taking in a load of corn oil will help you recover from asthma,” says Tobin. “We have absolutely no evidence for that.” In fact, he is not sure what role diet plays in the process. He says, there is still a question regarding where the endogenous free fatty acids come from to regulate lung function through this receptor. Diet does not make sense as a direct source, because that would mean our breathing would depend on what we eat.
FFA4 and athletes
For now, Tobin’s group is working on developing a treatment for asthma, chronic obstructive pulmonary disease, or other airway diseases by synthesizing a molecular similar to a free fatty acid. They tested the compound on human and mouse models and found it effective in reducing inflammation and inducing muscle relaxation in the lungs.
Along with helping exercise-induced asthma suffers, this research could lead to a better understanding for how fatty acids improve oxygen intake—something that is particularly important for endurance athletes. Tobin says his group is also interested in finding out if these receptors are present in the brain. Meanwhile, they will work on starting drug trials for their compound to help asthma patients who do not respond to current treatments.
If there are FFA4 receptors in the brain, it would indicate that the organ has a built-in ability to reduce inflammation. New research is making it clear that omega-3s do have an impact on how the brain handles inflammation.
Omega-3s and sports-related concussions
When brain tissue is torn or bruised during a concussion, polyunsaturated fatty acids (PUFAs) escape from neural membranes. Animal studies indicate that recovery can depend on the brain’s DHA levels.
“Our brain is made of a great deal of fat, and a lot of that fat is omega-3s, the majority of that being DHA,” says David Ma, health and nutritional science professor at the University of Guelph in Ontario, Canada. “The principle of structure and function says, if there is a large amount of a certain molecule it has to be doing something.”
This Spring, Ma and his graduate student Cody Lust published a review paper on the effects of fatty acids and traumatic brain injury (https://doi.org/10.1139/apnm-2019-0555). His research team found that PUFAs can be beneficial or harmful depending on their composition.
In one of the only studies that analyzed human cerebrospinal fluid of brain injured patients, researchers discovered that higher levels of the omega-6 PUFA, arachidonic acid, resulted in a worse outcome (https://doi.org/10.1016/s0304-3940(03)00803-6). In another study, the author showed that release of arachidonic acid during injury initiates a proinflammatory response in mice, but when DHA levels were elevated in their tissue—through dietary supplementation or pretreatment—less of the inflammation-causing fatty acid was released (https://doi.org/10.7205/milmed-d-14-00162).
Omega-6 and -3 PUFAs compete for the same enzymes that lead to either a pro- or an anti-inflammatory response. Consuming more DHA means that more neuroprotective compounds are formed, and harmful inflammation is inhibited. However, Ma says that data indicates there are multiple mechanisms to explain why omega-3s help with brain injury recovery. “For our future studies, we want to define clearly which type of omega-3 is better,” he says. “I suspect both EPA and DHA are important, but they probably work in tandem through different mechanisms.”
Other researchers are concentrating on how to increase DHA in human brains to assist recovery. Specific transporters and pathways grant DHA access across the blood brain barrier. Scientists are studying these entry points as possible therapeutic targets for brain injuries (https://doi.org/10.1016/j.biochi.2016.07.011).
Athletes are a unique group, according to Ma. He says more research is needed to understand their precise needs and how adding omega-3s can help them in terms of injury recovery. “When you are talking about athletic performance, typically it brings to mind running faster or jumping higher,” he says. “Injury prevention and management of treatment is part of performance, as well.”
Fatty acids and endurance
While a lot of fatty acids research looks at the importance of these molecules in reducing inflammation for athletic recovery, a new study reminds us of their primary role as an energy source. A team of scientists at Harvard in Boston, Massachusetts, USA, discovered that altering the fatty acid metabolism of mice turned them into endurance athletes (https://doi.org/10.1016/j.cmet.2020.06.017).
During exercise, muscles retrieve glucose from cells and use it for quick bursts of energy. However, the cells carry a limited supply, and when glucose is depleted triglycerides stored in muscle and fat tissue take over. Fats act as a long-term source of energy since they contain double the calories of glucose.
The researchers discovered that an enzyme called prolyl hydroxylase 3 (PHD3) inhibits fat breakdown when cells have an abundance of glucose. “We previously found that PHD3 regulates mitochondrial fatty acid oxidation in a subset of cancers,” the study’s lead researcher, Marcia Haigis, told BioSpace.com (https://tinyurl.com/biospacefattyacids). Muscle function also relies on mitochondria, she says, and that led them to wondered how the PHD3 enzyme was involved in energy use during exercise.
First, they found that mice with low glucose during fasting had less PHD3 activity, because a different enzyme was operating: one that converts fatty acids into fuel. Next, they genetically altered mice so they had no PHD3 enzyme. With the ability to oxidize more fat as an energy source, the mice were able to run longer and further than normal mice (Fig.1).
In another set of experiments, the researchers narrowed the effect of increased exercise capacity to just eliminating PHD3 in skeletal muscle with the enzyme unaltered in the rest of the body. These findings indicate that increasing the fatty acid use of skeletal muscles is one key to enhancing athletic performance. However, more research is needed to understand why these enzymes work this way and whether other signaling mechanisms are involved.
It is early days for each of the research projects discussed here. In every case, the results of the fatty acid experiments have led to more questions that will be addressed in future experiments. As with previous conclusions about fatty acids, these latest findings were determined through mouse studies. A complementary result is not guaranteed when the human body becomes the test subject. Nonetheless, they home in on how essential fatty acids are to optimal athletic performance, down to the cellular level. The next question to address is how dietary choices might maximize this process.
Rebecca Guenard is the associate editor of INFORM at AOCS. She can be contacted at email@example.com.
Sports-related concussions and subconcussive impacts in athletes: incidence, diagnosis, and the emerging role of EPA and DHA, Lust, C.A.C., et al., Appl Physiol Nutr Metab. 45: 886–892, 2020.
PHD3 Loss promotes exercise capacity and fat oxidation in skeletal muscle, Yoon, H., et al., Cell Metab. 32: 215–228, 2020.
Omega-3 polyunsaturated fatty acids: benefits and endpoints in sport, Gammone, M.A., et al., Nutrients 11: 46, 2019.
Relationship between fatty acids and the endocrine and neuroendocrine system, Bhathena, S.J., Nutr Neurosci, 9: 1–10, 2006.