At low levels, reactive oxygen species (ROS) originating from both immune cells and mitochondria are important signaling molecules for the immune system and for the regulation of cell growth and death. However, ROS production tends to increase with age as a result of damaged mitochondria, metabolic dysfunction, and decreased antioxidant defenses, leading to a state of imbalance between oxidants and antioxidant capacity known as oxidative stress. Oxidative stress underlies a variety of age-associated diseases, including neurodegenerative disease, cancer, osteoarthritis, and sarcopenia.⁶

Inflammation and oxidative stress are inextricably linked by the interplay of their respective signaling molecules in the progression of inflammatory processes. Mitochondrial ROS are an important driver of pro-inflammatory cytokine production⁷. Likewise, inflammatory processes provoke immune cells, including phagocytes and nonphagocytic cells, to produce ROS and other reactive species.⁸ With age, the capability of the immune system to resolve inflammation is dampened, making it more difficult to shut down the damaging cycle whereby oxidative stress and inflammation feed each other.

Given the significant role oxidative stress plays in aging and inflammation, assessing oxidative damage and individual genetic susceptibility can provide valuable insights. With the Vibrant Wellness Oxidative Stress Profile, you can measure 16 biomarkers of oxidative damage and 32 genetic variants that are known to impact the individual response to oxidative stress, enabling you to create targeted and personalized interventions for your clients.

Table of Contents

The Role of Omega-3 Fatty Acids in Inflammation

The presence of omega-3 fatty acids in cell membranes can help turn down pro-inflammatory cytokine production and resolve inflammation.

Both the omega-3 fatty acid eicosapentaenoic acid (EPA) and the omega-6 fatty acid arachidonic acid (AA) are antecedents of eicosanoids, a diverse group of lipid signaling molecules that regulate the immune response. Eicosanoids derived from omega-3 fats can help turn down inflammation in the body via enzymatic conversion to less inflammatory prostaglandins and leukotrienes.

Docosahexaenoic acid (DHA), which can be produced endogenously via elongation and desaturation of EPA or found from marine sources including algae and coldwater fish, is a precursor to anti-inflammatory compounds including docosanoids, which exert anti-inflammatory effects by activating nuclear transcription factors via peroxisome proliferator-activated receptors (PPARs).⁹

Additionally, both DHA and EPA are precursors to inflammation-quenching derivatives known as specialized pro-resolving mediators, which are well-recognized in relieving pain associated with inflammation¹⁰.

Omega-3 Fatty Acids and Muscle: Clinical Studies

Recent research has shown that omega-3 fatty acids can play a role in reducing oxidative stress in muscle cells and improving muscle strength and mass.

Study 1: Impact of Omega-3 on Mitochondrial Function and Muscle Strength

A 2017 open-label study illustrated the concept that omega-3 fatty acids can have a beneficial effect on oxidative stress by quantifying the muscle-specific mitochondria effects of omega-3 supplementation.¹¹ This study involved a group of men and women aged 65-85 who completed standardized strength tests before and after four months of omega-3 supplementation. The omega-3 supplement consisted of four capsules per day, with each capsule containing 675 mg of EPA and 300 mg of DHA. The total daily dosage of omega-3 fats was 3.9 grams, and the ratio of EPA: DHA was 2.25:1. Notable findings of this study were that omega-3 fatty acid supplementation significantly reduced mitochondrial production of ROS and boosted the anabolic response to food and to exercise, as measured by muscle, mitochondrial, and myofibrillar protein synthesis rates.

Interestingly, this study found that omega-3 supplementation did not reduce systemic inflammatory markers TNFα, CRP, or IL-6, whereas inflammation-related genes were downregulated at the muscle tissue level. Therefore, this finding may reflect the healthy status of the participants and/or indicate that inflammation at the tissue level was modulated without affecting systemic markers.

Study 2: Omega-3 Effects on Muscle Strength and Volume

A second study in a group of adults aged 60-85 found that six months of omega-3 supplementation led to significantly improved handgrip strength and 1-repetition maximum muscle strength, as well as increased thigh muscle volume compared to an age-matched placebo group.¹² The dosage used was 1.86 g EPA and 1.5 g DHA per day, delivered in divided doses among four capsules. The degree of improvement in measured parameters over the six-month study was equivalent to the prevention of roughly 2-3 years of "normal" age-associated losses in muscle mass and functionality.

A follow-up study utilizing muscle biopsies from a subset of the participants in the above study found that omega-3 supplementation significantly, but with a very small effect size, affected two genes related to mitochondrial function: UQCRC1 (part of electron transport chain complex II) and UCP3 (an uncoupling protein). UCP3 is associated with prolonged exercise and increased metabolic flexibility, particularly for fatty acid oxidation.¹³ More research is needed to clarify the extent to which omega-3 fatty acids may affect gene transcription in muscle cells.

Study 3: Omega-3 Combined with Strength Training

A third study compared the neuromuscular effects of strength training to the effects of that same strength training with the addition of fish oil supplementation for either 90 or 150 days in a group of women with an average age of 64.¹⁴ The fish oil supplementation consisted of 0.4 g EPA and 0.3 g DHA per day, given in divided doses with meals. This study found that fish oil supplementation, in addition to strength training, compared to strength training alone, led to greater increases in peak torque as measured by isometric contraction, muscle contractility as measured by electromyography, and functional capacity as estimated by chair-rise performance.

Therapeutic Considerations

As functional practitioners, many of us recognize the value of a food-first approach. In the case of omega-3 fatty acids, the therapeutic doses utilized in some, but not all, research studies are greater than what can be realistically obtained from diet on a daily basis. For example, Smith et al. (2015)⁹ notes that the 3.86 grams of combined EPA and DHA used in their study is equivalent to what would be found in roughly 200-400 grams (7-14 ounces) of fatty fish such as salmon, herring, and sardines. However, it is also important to counsel our patients that we cannot supplement our way out of an inflammatory diet containing refined oils and oxidized fats. The quality of all the fats in our diet is a foundation of health that should not be overlooked.

When choosing an omega-3 supplement specifically as part of a plan to support muscle maintenance or reversal of muscle loss, try choosing one with a greater relative amount of EPA as compared to DHA.

EPA competes with the same enzymes in the eicosanoid pathway as does arachidonic acid (AA), another 20-carbon fatty acid which is the precursor to primarily pro-inflammatory eicosanoids. Therefore, EPA has a unique potential to exert anti-inflammatory effects both by stimulating the production of anti-inflammatory eicosanoids and by blocking the production of pro-inflammatory eicosanoids, which are downstream of AA. The three studies cited above-utilized ratios of EPA: DHA ranging from 1.24:1 to 2.25:1.  

The Vibrant Wellness Micronutrient Panel provides a detailed profile of the omega-3 and omega-6 fatty acid content of red blood cells that can help you and your clients design diet and supplement interventions that bring these essential cell membrane components into optimal balance with each other.

Notably, two of the three studies discussed here did not employ exercise training in their intervention, which speaks to the tangible benefits that reducing inflammation alone can have for muscle health. However, we know that the body is more likely to preserve muscle that is actively engaged, and it is also true that pain and mobility impairments can prevent older adults from using their muscles. Omega-3 fats can be part of a plan to reduce pain, increase mobility, and enhance muscle health through decreased inflammation and increased capacity for movement.

No serious adverse events were reported in the research cited here. However, it should be noted that these studies involved small sample sizes and employed exclusion criteria for participants. Individual factors, including medications and health conditions, should be taken into account prior to recommending supplementation of any kind to patients.

The Bottom Line

Inflammation and oxidative stress are key drivers of sarcopenia and frailty in aging muscle, with chronic inflammation impairing anabolic pathways essential for muscle health. For functional providers, incorporating omega-3 supplementation as part of a comprehensive approach to muscle maintenance in older adults can help reduce inflammation, improve functional capacity, and support overall muscle health.

Additionally, clinicians can assess oxidative stress and nutrient deficiencies contributing to muscle loss with tests like the Oxidative Stress Profile and Micronutrient Panel, providing valuable insights for personalized treatment plans. However, individual patient considerations are crucial, as therapeutic doses may exceed typical dietary intake.

About the Author

Becky Buck Douville, MS, CN is a clinical nutritionist, and the founder of Osa Integrative Health, where she specializes in helping middle-aged and older adults optimize their metabolic health using functional medicine principles and personalized nutrition and lifestyle interventions. She is passionate about helping her clients uncover new pathways to healing and empowering her community with evidence-based information that cuts through the noise of wellness trends.

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