#81 Chris McGlory, PhD, on the Anabolic Potential of Omega-3 Fatty Acids
This episode is available in a convenient podcast format.
These episodes make great companion listening for a long drive.
The Omega-3 Supplementation Guide
A blueprint for choosing the right fish oil supplement — filled with specific recommendations, guidelines for interpreting testing data, and dosage protocols.
Dr. Chris McGlory is an assistant professor at Queen's University in Kingston, Ontario, Canada. Known for his work in the field of muscle physiology and aging, Dr. McGlory's research focuses on elucidating the molecular mechanisms underlying muscle protein synthesis and degradation, with a particular emphasis on the roles that omega-3 fatty acids play in maintaining muscle health in older adults.
In this episode, Dr. McGlory and I discuss...
- Why atrophy is worse for the old than the young
- - Why reduced movement can insidiously mimic short-term immobilization
- - Does high-dose omega-3 hold the key to fighting atrophy? (5g/day)
- - Who benefits the most from the anti-catabolic effects of omega-3?
- - Does omega-3 enhance strength?
- - Sex differences in gaining mass and strength
- - Do omega-3s boost tired, dysfunctional mitochondria?
- - Why we need an "omega-3 index" for muscle
- - Why the inflammation from cancer wastes muscle
(See Timeline tab for more)
The older we get, the harder it is to recover from muscle atrophy.
"Younger folks can recover from [disuse] relatively quickly, [but it] becomes a little bit more of a problem as you get older. [That] rapid muscle loss may not always come back to baseline in the older folks."- Chris McGlory, PhD. Click To Tweet
If you've ever worn a cast to immobilize a broken bone or spent an extended period in bed recovering from an illness, you've likely experienced muscle disuse atrophy. Also known as muscle wasting, muscle disuse atrophy occurs when muscles shrink and weaken due to periods of immobilization or physical inactivity. If you were young, you probably regained your muscle mass and strength soon after the cast was removed or you were back on your feet. But if you were in your later years, you might have experienced considerable challenges in recouping your losses – or perhaps never fully recovered.
Disuse atrophy studies suggest high-dose omega-3 fatty acids could combat anabolic resistance, offering potential benefits for sarcopenia.
"As we age, there is anabolic resistance to protein ingestion [...] that may lead to decline. And that is independent of physical inactivity, which would accelerate that natural biological decline."- Chris McGlory, PhD. Click To Tweet
Nutritional support – in the form of adequate protein intake – and regular exercise are essential for rebuilding and maintaining muscle mass. Unfortunately, as we age, our bodies become less responsive to the anabolic effects of protein and exercise, driving sarcopenia – the age-related loss of muscle mass and strength. But emerging evidence points to some surprising players in the nutrition-muscle mass maintenance story: omega-3 fatty acids.
A growing body of evidence demonstrates incredibly diverse roles for omega-3s in supporting and maintaining human health across a diverse array of organ systems and tissues (from brain to heart and more). They are perhaps best known for their canonical role in dampening inflammation. However, Dr. McGlory's work highlights a new suite of effects that may be attributable to omega-3 fatty acids. In high doses, they seem to reduce anabolic resistance, at least within the context of his trials of disuse atrophy.
The first hint that omega-3s might have muscle-protective effects came when he and his colleagues gave young women 5 grams of omega-3 fatty acids (3 grams of EPA + 2 grams of DHA) or a placebo daily for four weeks. Then they asked the women to wear a brace on one leg for two weeks so they could study the effects that omega-3s had on muscle protein synthesis during immobilization. They found that women who took the omega-3s lost roughly half as much muscle.
Omega-3 fatty acids may enhance muscle protein synthesis partly independently of their anti-inflammatory role, potentially extending dual benefits to the elderly.
"A growing body of evidence suggests omega-3s are anabolic. And they seem to be anabolic, particularly in older adults, not just from a protein synthetic point of view but also from the perspective of mitigating declines in muscle mass and size."- Chris McGlory, PhD. Click To Tweet
McGlory believes that the muscle-protective effects of omega-3s he and his team observed stem from their capacity to enhance muscle protein synthesis by improving the body's response to amino acids. And omega-3s' anti-inflammatory qualities could play a role, too, especially in the setting of sarcopenia, where inflammation is a driver. Interestingly, some studies have shown that omega-3s work independently of their anti-inflammatory effects. Regardless of the mechanisms involved, omega-3 could have far-reaching benefits that extend beyond periods of immobilization or inactivity, particularly for older adults, who are vulnerable to what's often referred to as a catabolic crisis.
Intervening in catabolic crises, decelerating the path towards escalating disability and early mortality.
"[In the] catabolic crisis model, [...with each insult] that older people have with periods of inactivity and immobilization, they lose muscle. It may not come back, and then they lose a little bit more. And all of a sudden they reach a threshold beyond which they cannot perform activities of daily living."- Chris McGlory, PhD. Click To Tweet
A catabolic crisis is a theoretical concept that defines periods of accelerated declines in muscle mass and functional capacity. It can occur at any age, but it's more common among older adults, for whom injuries, surgeries, or prolonged illnesses dictate long and perhaps frequent periods of physical inactivity or immobilization. These cumulative insults drive older adults toward a "disability threshold" from which they might not recover. Research suggests many older adults experienced catabolic crises during the quarantines of the recent pandemic.
The key players in a catabolic crisis are catabolism and its counterpart, anabolism – complementary, dynamic forces that support muscle growth and strength. As we age, the equilibrium between these two forces wanes, creating an imbalance in muscle protein turnover. And because older adults often consume less than adequate amounts of protein and might not engage in resistance training (the two anabolic stimuli needed for muscle protein synthesis), the perfect conditions for a catabolic crisis converge. Omega-3s may provide a means to prevent a catabolic crisis, potentially prolonging healthspan and improving quality of life in older adults.
Omega-3 fatty acids may support strength gains, enhance glycemic control, and quicken gait speed, according to several studies.
"There is evidence that EPA treatment may protect against cancer cachexia or the loss of muscle with cancer."- Chris McGlory, PhD. Click To Tweet
But omega-3s' effects on muscle extend beyond muscle building and maintenance: One of Dr. McGlory's most recent studies showed that omega-3s also improve muscle strength. When healthy young adults took fish oil supplements – which are rich in omega-3s – while engaging in a resistance training program, they showed greater strength gains than those who took a placebo. His group's findings align with those of another, which demonstrated that fish oil supplementation induced a 50 percent increase in muscle protein synthesis.
The trickle-down effect of these gains can't be dismissed. Muscle mass and strength protect older adults against falls – the leading cause of injury in seniors – and promote better glycemic control. And there might be a place for omega-3s in the setting of cachexia – a muscle disuse atrophy syndrome associated with chronic diseases like cancer and emphysema.
Dr. McGlory cautions that you can't "out-nutrition" physical inactivity or immobilization, however. Protein, omega-3s, and resistance training form a synergistic triad that works to build and maintain muscle. Remove one component, and it's considerably less effective.
Supporting the energy-demanding process of muscle protein synthesis by boosting mitochondrial function.
"There seems to be some kind of mitochondrial cytosolic crosstalk. [Muscle protein synthesis] is a very energetically expensive process. So, if the mitochondria are not working properly, then there may not be the energy to mount a protein synthetic response."- Chris McGlory, PhD. Click To Tweet
Omega-3s also seem to influence the health and function of mitochondria. This is important in the context of muscle because, as Dr. McGlory points out, muscle protein synthesis is an energetically expensive process. Tired, dysfunctional mitochondria might not have the energy to mount and support muscle protein synthesis. But encouraging evidence suggests that omega-3s support ADP-stimulated respiration in the mitochondria, facilitating protein synthesis.
Challenges and future directions in omega-3 research
"The omega-3 index has been established in blood and is related to CVD risks. We have not really got something similar in skeletal muscles. So, we do not know what the [optimal] level of omega-3s or EPA or DHA is."- Chris McGlory, PhD. Click To Tweet
Although the science supporting the use of omega-3s in bolstering muscle protein synthesis is growing, many questions and challenges remain. For example, because older adults don't recover from immobilization as quickly as younger ones, intentionally restricting an older person's limb for the purposes of study carries some inherent risks. Consequently, much of Dr. McGlory's research has focused on younger people. Future research that includes people of all ages will provide better insights into omega-3s' muscle-protective effects.
Another challenge in researching the effects of omega-3s stems from study designs, which are plagued with methodological flaws, such as short duration, inadequate dosing, and failure to establish clearly defined outcome measures. Identifying biomarkers in muscle tissue similar to the Omega-3 Index, which correlates to cardiovascular risk, could help standardize the research.
In this episode, Dr. Chris McGlory and I discuss the many roles that omega-3 fatty acids play in preserving muscle mass, strength, and function in aging.
Notable and relevant publications
- Omega‐3 fatty acid supplementation attenuates skeletal muscle disuse atrophy during two weeks of unilateral leg immobilization in healthy young women (2019)
- Declines in muscle protein synthesis account for short-term muscle disuse atrophy in humans in the absence of increased muscle protein breakdown (2022)
- The influence of omega-3 fatty acids on skeletal muscle protein turnover in health, disuse, and disease (2019)
- Transcriptomic links to muscle mass loss and declines in cumulative muscle protein synthesis during short‐term disuse in healthy younger humans (2021)
- Neither load nor systemic hormones determine resistance training-mediated hypertrophy or strength gains in resistance-trained young men (2016)
Related FoundMyFitness resources
Articles:
Episodes:
- Brad Schoenfeld, PhD: Resistance Training for Time Efficiency, Body Composition & Maximum Hypertrophy
- Stuart Phillips, PhD, on Building Muscle with Resistance Exercise and Reassessing Protein Intake
- Dr. Bill Harris on the Omega-3 Index, Increasing Omega-3 to Improve Longevity & Heart Disease Risk
About Dr. Chris McGlory
People mentioned in this episode
- Stuart Galloway, Ph.D.
- Stuart Gray, Ph.D.
- Graham Holloway, Ph.D.
- Vera Mazurak, Ph.D.
- Bettina Mittendorfer, Ph.D.
- Daniel Moore, Ph.D.
- Stuart Phillips, Ph.D.
-
Introduction
-
-
Why atrophy is worse for the old than the young
-
Can dietary protein prevent atrophy?
-
Why reduced movement can insidiously mimic short-term immobilization
-
How a meta-analysis revealed that declines in muscle mass occur rapidly within the first seven days of inactivity in healthy people. 1
-
How in a study of older adults with pre-diabetes, a two-week reduction in daily step count to below 1,000 steps resulted in a down-regulation of muscle protein synthesis and compromised insulin sensitivity, which did not recover fully even after returning to normal activity levels. 1
-
How pandemic-related movement restrictions impacted sarcopenia in people with and without COVID-19 infection. 1
-
How seasonal reductions in activity, potentially due to weather or fall concerns, may contribute to the catabolic crisis model in older adults, intensifying disuse atrophy particularly during colder months.
-
The disability threshold — when atrophy may actually be deadly
-
How in older adults, the combination of biological muscle mass and strength decline, known as sarcopenia, with inactivity can notably accelerate muscle loss, leading to decreased independence.
-
Does high-dose omega-3 hold the key to fighting atrophy? (5g/day)
-
How omega-3 fatty acids can render muscle tissue more anabolically sensitive to the provision of amino acids. Dr. McGlory describes his research in young women showing that omega-3 supplementation helped reduce the decline in muscle size during single-leg immobilization. 1
-
Increasing the muscle protein synthetic response with omega-3
-
Does omega-3 help muscle respond more optimally to low protein?
-
The potential role of LAT1 upregulation in atrophy resistance
-
How a study in pigs showed that omega-3s altered the gene expression of LAT1, a gene that codes for an amino acid transporter for leucine. 1
-
How the accumulation of fatty acids in cell membranes can alter certain transporters, for example, DHA deficiency alters GLUT1 transporters at the protein level in rodents. 1
-
Why Dr. McGlory's laboratory did not examine LAT1 protein expression, but how this may be an avenue for future work.
-
Who benefits the most from the anti-catabolic effects of omega-3?
-
Dr. McGlory explains the absence of current studies investigating the influence of omega-3s on disuse atrophy in older adults while emphasizing the potential insights this kind of research could provide.
-
How rodent studies show that a high fish oil diet protects against disuse atrophy.
-
How trial design is a crucial aspect of research, encompassing proper dosage, timing, choice of biomarkers, and population selection. For instance, discerning the impact of omega-3 supplementation might be challenging in individuals with an Omega-3 Index of 8%, while it's likely more observable in those with omega-3 levels below 4%.
-
Dr. McGlory comments on ways to bridge the gap between research and clinical practice.
-
Dr. McGlory postulates that omega-3s don't impart their effects acutely by resolving inflammation; instead, they incorporate and alter phospholipid membranes of the target tissues. 1
-
Why omega-3 must be preloaded for 4 to 6 weeks
-
Time course studies show that omega-3s appear in muscles around four weeks after administration, while omega-3-derived specialized pro-resolving mediators, which combat inflammation, act rapidly in the bloodstream. 1
-
Dr. McGlory reiterates why it was important to preload the muscle with omega-3s in his immobilization trial.
-
Why omega-3 trials have conflicting results
-
Why muscle mass and strength are imperfectly correlated (muscle mass vs. strength)
-
Why it is difficult for older adults to gain muscle mass from resistance training, but they can gain strength.
-
Whether there is a role for omega-3s in increasing strength response to resistance exercise, some research suggests that omega-3s increased the strength response to resistance training in older women but not men. In another study, omega-3s potentiates resistance exercise-induced strength gains in older women in a female-only cohort. Researchers also followed up these findings using krill oil. 1, 2, 3
-
Does omega-3 enhance strength?
-
Sex differences in gaining mass and strength
-
Whether estrogen plays a role in the body's ability to convert ALA to EPA and DHA.
-
How single nucleotide polymorphisms affect omega-3 fatty acid metabolism. 1
-
Improvements in gait speed and balance (muscle performance / physical performance battery)
-
Omega-3 and muscle performance – meta-analysis showed gait/walk speed is enhanced by omega-3s. 1
-
How to act on mixed evidence — and should we?
-
Drs. McGlory and Patrick address the challenges of reconciling evidence-based medicine requirements with the potential of promising and emerging research.
-
Though the benefits might not be fully established, consuming additional omega-3s is generally low risk, especially if sourced from high-quality supplements or fatty fish, which also provides the added benefit of protein.
-
Why omega-3 may reduce frailty in old age
-
How numerous factors lead to sarcopenia in older adults, such as anabolic resistance, reduced activity, inadequate nutrition, inflammation, hormonal imbalances, oxidative stress, and mitochondrial dysfunction. While protein consumption and resistance training are significant factors in managing this condition, it's worth investigating the potential roles of DHA and EPA.
-
Does high-dose omega-3 enhance anabolic potential?
-
How a series of landmark papers revealed enhanced protein synthetic response to amino acid infusion with omega-3s in younger and older adults. This growing body of evidence suggests omega-3s are anabolic particularly in older adults. 1
-
How increased strength and muscle thickness were observed. 1
-
Why the anabolic mechanisms are counterintuitive (going beyond the canonical anti-inflammatory role of omega-3)
-
Aging entails an inherent inflammatory component, termed "inflammaging." Inflammation also plays a significant role in sarcopenia, underscoring the link between aging and this muscle degenerative condition. Could omega-3s serve a dual purpose in this context? Low-grade inflammation can impinge on proteins that regulate protein synthesis. For example, EIF-2 alpha – when phosphorylated, can impinge on the ability to mount a protein synthetic response.
-
Are the drivers of disuse atrophy intracellular or extracellular in nature?
-
How measuring amino acid concentrations within muscle cells is challenging, and why these values are hard to interpret. 1
-
Why Dr. McGlory changed his mind about the mechanism of how omega-3s exert their effects. 1
-
Do omega-3s boost tired, dysfunctional mitochondria?
-
Dr. McGlory is most excited about exploring how EPA and DHA accumulate in mitochondrial membranes and modulate muscle protein synthesis.
-
How feeding omega-3s to younger people can affect ADP sensitivity and respiration. 1
-
Emerging evidence suggests that there is some mitochondrial-cytosolic crosstalk. Mitochondrial proteins or translation initiation factors that regulate muscle protein synthesis might feed in as a signal to the cytosol and regulate protein synthesis.
-
Preclinical evidence (in worms) suggests that the translation of mitochondrial proteins acts as a signal to cell (cytosol) factors that regulate protein synthesis.
-
Dr. McGlory's laboratory researches whether mitochondrial-cytosolic crosstalk happens in humans. He believes understanding the workings of omega-3s is crucial to establishing their importance and clinical benefits.
-
Increasing metabolic rate by up to 27% — an effect of 3g/day omega-3 supplementation?
-
-
Does high-dosage supplementation of omega-3 uniquely promote a slight metabolic shift away from carbohydrate metabolism and towards fat oxidation?
-
Omega-3 dosage — Is there a difference between optimal vs. normal dietary intake?
-
How feasible is it to get an adequate omega-3 dose from food?
-
How the Omega-3 Index, used to measure omega-3 content of blood, may not be relevant for evaluating omega-3s in muscle tissue. 1
-
Why we need an "omega-3 index" for muscle
-
Anabolic signaling pathways — Does omega-3 enhance mTOR in muscle?
-
-
Dr. McGlory explains his current theory of how omega-3s impact muscle tissue.
-
Why the inflammation from cancer wastes muscle
-
How high inflammation can negatively impact protein synthesis in skeletal muscle and whether omega-3s might play a role in mitigating inflammation-induced muscle atrophy.
-
Cancer cachexia
-
Does omega-3 reduce atrophy from cancer cachexia?
-
Evidence regarding EPA's potential role in guarding against cancer cachexia, a condition involving muscle loss with cancer. Despite some conflicting data, some promising human studies have shown results with dosages ranging from 2 grams to 2.5 grams per day. Preclinical studies suggest that omega-3 helps mitigate the negative side effects of chemotherapy. 1
-
How some preclinical evidence suggest that omega-3 helps mitigate the negative side effects of chemotherapy that promote atrophy.
-
Ongoing clinical trials
-
Dr. McGlory's ongoing research delves into the potential benefits of high-dose omega-3s in several scenarios. He's examining if omega-3s can offset muscle mass and strength losses during bed rest in healthy individuals. Concurrently, he is investigating the impact of omega-3s on young and middle-aged people undergoing knee surgery, a situation typically characterized by high inflammation.
-
Does aerobic exercise impede "gains?" (the chronic interference effect)
-
Traditional research from 1980 proposed that aerobic exercise might hinder the increase in muscular strength. However, such a proposition has yet to be confirmed through studies involving humans. 1
-
Why aerobic exercise may enhance hypertrophy from resistance exercise
-
How some evidence, somewhat in disagreement with a "chronic interference effect," suggests that endurance training may enhance nutrient delivery to muscles making them more receptive to the benefits of resistance exercise. Moreover, some evidence suggests aerobic exercise activates satellite cells, actively promoting hypertrophy from resistance exercise. 1
-
How the benefits of aerobic exercise include improvements in cardiovascular health and increased VO2 max – a predictor of mortality. 1
-
Dr. McGlory discusses the possible interference between aerobic and resistance training, countering potential synergistic benefits from their combination. He underscores the need for both exercise forms for overall health, acknowledging that research continues.
-
Evidence reveals that aerobic training does not impede the benefits of strength training, particularly with cycling. Unless a person engages in exceptionally high volumes of endurance training, it's unlikely to affect the positive outcomes of resistance exercises. 1
This transcript is reserved for members.
FoundMyFitness Members get access to exclusive content not available anywhere else, including a transcript of this episode.
You wouldn't believe how cool being a premium member of the world's best cross-disciplinary science-focused website and podcast really is.
A multifunctional protein that is often upregulated in pathological conditions. When ATF4 binds to a protein called CCAAT/enhancer binding protein, it forms complexes that, in turn, promote skeletal muscle atrophy.[1]
A collective term that describes essential and routine tasks that most healthy people can perform without assistance, such as eating, bathing, and dressing. The inability to perform essential ADLs may contribute to injuries and poor quality of life.
A molecule composed of a ribonucleoside and two phosphate groups. ADP is an intermediary molecule between adenosine monophosphate (AMP) and adenosine triphosphate (ATP) and plays essential roles in cellular energy processes.
A naturally occurring substance present in the human body and in some foods. ALA is a powerful antioxidant that amplifies the beneficial effects of other antioxidants in the body such as glutathione and coenzyme Q10. It also participates in metabolism by helping to protect mitochondria from oxidative stress, thus ensuring that energy production in the body remains efficient. Some research suggests that ALA may be useful for treating cataracts, liver disease, and some complications of diabetes such as neuropathy.
Chemical compounds that serve as the building blocks of proteins. Approximately 500 amino acids exist in nature, but only 22[1] are found in the human body. Thirteen of the amino acids can be synthesized in the body and are referred to as "non-essential." The remaining nine must be obtained in the diet and are referred to as "essential."
An enzyme that plays multiple roles in cellular energy homeostasis. AMP kinase activation stimulates hepatic fatty acid oxidation, ketogenesis, skeletal muscle fatty acid oxidation, and glucose uptake; inhibits cholesterol synthesis, lipogenesis, triglyceride synthesis, adipocyte lipolysis, and lipogenesis; and modulates insulin secretion by pancreatic beta-cells.
The reduced sensitivity of muscle to the effects of hypertrophic stimuli. Anabolic resistance creates an imbalance between anabolism and catabolism, thereby blunting muscle protein synthesis. The primary drivers of anabolic resistance are low dietary protein intake and inactivity.[1]
A ligament in the center of the knee. The ACL prevents the tibia from sliding out in front of the femur and provides the knee rotational stability. ACL injuries are common in athletes, especially females, who are two to eight times more likely to experience a torn ACL.[1]
An amino acid having aliphatic side-chains with a branch (a central carbon atom bound to three or more carbon atoms). Among the proteinogenic amino acids, there are three BCAAs: leucine, isoleucine and valine.
A complex wasting disorder characterized by extreme muscle mass loss, with or without fat mass loss. The pathophysiology of cachexia is multifactorial and may include factors that promote increased metabolic rate and energy expenditure, reduced nutrient intake or availability, increased muscle breakdown, and the inhibition of muscle growth. Cachexia is a common feature of advanced cancer, but it is also associated with other chronic diseases, including chronic obstructive pulmonary disease, heart failure, kidney disease, and inflammatory diseases, including AIDS.[1]
A theoretical concept that defines periods of accelerated declines in muscle mass and functional capacity.[1] Catabolic crisis can occur at any age, but it is most common among older adults, for whom injuries, surgeries, or prolonged illnesses dictate long and perhaps frequent periods of physical inactivity or immobilization. Strategies to reduce the risk of a catabolic crisis include providing adequate nutritional support and physical therapy.[1]
Dual-energy X-ray absorptiometry, a radiological procedure used to assess body composition.[1] DEXA facilitates the visual separation of body mass into bone mineral, fat tissue, and fat-free soft tissue.
An omega-3 fatty acid found in the human brain and the meat of fatty fish. DHA plays a key role in the development of eye and nerve tissues, and is essential for normal brain function in humans. DHA may also reduce the risk of Alzheimer’s disease1 and cardiovascular disease, and may be useful in treating certain inflammatory conditions, such as rheumatoid arthritis. Dietary sources of DHA include krill oil and the meat and roe of salmon, flying fish, and pollock. [1] Patrick, Rhonda P. "Role of phosphatidylcholine-DHA in preventing APOE4-associated Alzheimer’s disease." The FASEB Journal (2018): fj-201801412R.
An omega-3 fatty acid found in the meat of fatty fish. EPA reduces inflammation in the body and helps counter oxidative stress in cells. It is crucial for modulating behavior and mood and has demonstrated beneficial effects in managing anxiety and depression. EPA may reduce risk of developing certain chronic diseases such as cancer or cardiovascular disease. Dietary sources of EPA include herring, salmon, eel, shrimp and sturgeon.
One of three subunits of a polypeptide that catalyzes the first regulated step of protein synthesis initiation. EIF-2 phosphorylation facilitates muscle stem cell (satellite cell) self-renewal.[1] EIF-2 alpha plays a critical role in synthesizing muscle protein and subsequent muscle mass maintenance and hypertrophy.
A protein that facilitates glucose transport into cells, including red blood cells and cells in the brain. GLUT1 expression at the blood-brain barrier diminishes with aging, driving poor glucose uptake into the brain and impaired cognitive function.[1]
An insulin-responsive protein that facilitates glucose transport into fat and muscle cells. Because GLUT4 activity dictates postprandial glucose clearance, impaired or reduced GLUT4 activity is associated with type 2 diabetes.[1]
Facilitates the transport of glucose across the cell membrane of skeletal muscles and adipose tissue cells, thereby removing glucose from the bloodstream.
A physiological condition in which cells fail to respond to the normal functions of the hormone insulin. During insulin resistance, the pancreas produces insulin, but the cells in the body become resistant to its actions and are unable to use it as effectively, leading to high blood sugar. Beta cells in the pancreas subsequently increase their production of insulin, further contributing to a high blood insulin level.
A measure of how sensitive the body's tissues are to the effects of insulin. Insulin sensitivity defines a relationship between insulin production and glucose uptake. Poor insulin sensitivity promotes increased pancreatic insulin production, which can lead to increased risk for high blood pressure, heart disease and heart failure, obesity, osteoporosis, and even cancer.
An essential amino acid that plays important roles in muscle building and repair. Leucine is one of three branched-chain amino acids, so named for their branching structures. It is a ketogenic amino acid, meaning that it serves as a precursor for ketones produced in the body. Leucine is found in many foods and is particularly abundant in protein powders derived from whey, soy, or peas.
A multifunctional protein that facilitates the transport of large neutral amino acids such as leucine into muscle cells, thereby stimulating protein synthesis and anabolic signaling.[1] LAT1 expression is upregulated during the progression of several types of cancer.[2] It also carries some drugs and prodrugs across the blood-brain barrier and may provide an effective drug-delivery mechanism for various neurodegenerative disorders.[3]
A member of the specialized pro-resolving mediator family of polyunsaturated fatty acid metabolites. Maresin is produced in macrophages during the metabolism of docosahexaenoic acid (DHA). It exerts anti-inflammatory properties.
An enzyme that participates in genetic pathways that sense amino acid concentrations and regulate cell growth, cell proliferation, cell motility, cell survival, protein synthesis, autophagy, and transcription. mTOR integrates other pathways including insulin, growth factors (such as IGF-1), and amino acids. It plays key roles in mammalian metabolism and physiology, with important roles in the function of tissues including liver, muscle, white and brown adipose tissue, and the brain. It is dysregulated in many human diseases, such as diabetes, obesity, depression, and certain cancers. mTOR has two subunits, mTORC1 and mTORC2. Also referred to as “mammalian” target of rapamycin.
Rapamycin, the drug for which this pathway is named (and the anti-aging properties of which are the subject of many studies), was discovered in the 1970s and is used as an immunosuppressant in organ donor recipients.
Tiny organelles inside cells that produce energy in the presence of oxygen. Mitochondria are referred to as the "powerhouses of the cell" because of their role in the production of ATP (adenosine triphosphate). Mitochondria are continuously undergoing a process of self-renewal known as mitophagy in order to repair damage that occurs during their energy-generating activities.
An increase in the size of muscle cells that occurs with exercise and physical activity.
An ongoing assessment of the health and nutritional status of adults and children in the United States. NHANES data include findings from standardized physical examinations, laboratory tests, and interviews that cover various health-related topics.
A measure of torque, commonly assessed via an isokinetic dynamometer to determine muscle strength.
A broad class of drugs used to treat pain, fever, and inflammation. NSAIDs work by inhibiting the enzyme cyclooxygenase and often elicit off-target effects that affect the gut, kidneys, liver, blood, and cardiovascular system. Evidence suggests long-term use of NSAIDs increases the risk of heart attacks and strokes.[1]NSAIDs are available as either prescription or over-the-counter medications.
A type of polyunsaturated fat that is essential for human health. Omega-3 fatty acids influence cell membrane integrity and affect the function of membrane-bound cellular receptors. They participate in pathways involved in the biosynthesis of hormones that regulate blood clotting, contraction and relaxation of artery walls, and inflammation. They have been shown to help prevent heart disease and stroke, may help control lupus, eczema, and rheumatoid arthritis, and may play protective roles in cancer and other conditions. Omega-3 fatty acids include alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). ALA is found mainly in plant oils such as flaxseed, soybean, and canola oils. DHA and EPA are found in fish and other seafood. The human body can convert some ALA into EPA and then to DHA, but the efficiency of the process varies between individuals.
A measure of red blood cell omega-3 fatty acid concentration. The omega-3 Index is a measurable risk factor for sudden cardiac death. People who have high blood concentrations (8 to 12 percent) of omega-3s are far less likely to die from all causes of premature death.[1]
The process of generating energy that occurs when mitochondria couple oxygen with electrons that have been derived from different food sources including glucose, fatty acids, and amino acids.
A protein that regulates cell growth by inducing protein synthesis. P70-S6 kinase 1 is a downstream target of mTOR and is highly sensitive to nutrient availability and rapamycin inhibition.[1]
A health condition in which blood glucose levels are higher than normal, but not high enough to indicate a diagnosis of type 2 diabetes. Prediabetes can be halted or reversed with dietary and lifestyle modifications, including weight loss, exercise, and stress reduction.
A member of the specialized pro-resolving mediator family of polyunsaturated fatty acid metabolites. Protectin is produced during the metabolism of the omega-3 polyunsaturated fatty acids docosahexaenoic acid and n–3 docosapentaenoic acid. It exerts anti-inflammatory and neuroprotective properties.
A study in which people are randomly allocated to receive one of several clinical interventions. One of these interventions is the standard of comparison or control. The control may be a standard practice, a placebo, or no intervention at all.
A member of the specialized pro-resolving mediator family of polyunsaturated fatty acid metabolites. Resolvin is produced during the metabolism of omega-3 fatty acids, primarily eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), as well as docosapentaenoic acid (DPA) and clupanodonic acid. It exerts anti-inflammatory effects.
The loss of skeletal muscle tissue with age. Sarcopenia is one of the most important causes of functional decline and loss of independence in older adults.
Skeletal muscle stem cells. Satellite cells are typically dormant, but if the muscle is stressed or injured, they play essential roles in the regenerative growth of new muscle fibers. They have chemotactic properties, which means they can migrate from one location within a muscle fiber to another, where they can participate in the process of developing a new muscle fiber.
An assessment tool for evaluating balance, lower extremity strength, and functional capacity in older adults. SPPB scores strongly correlate with physical fitness measures in older adults and are robust predictors of all‐cause mortality and disability.[1]
A change in one nucleotide DNA sequence in a gene that may or may not alter the function of the gene. SNPs, commonly called "snips," can affect phenotype such as hair and eye color, but they can also affect a person's disease risk, absorption and metabolism of nutrients, and much more. SNPs differ from mutations in terms of their frequency within a population: SNPs are detectable in >1 percent of the population, while mutations are detectable in <1 percent.
Byproducts of omega-3 fatty acid metabolism. SPMs reduce the inflammation that drives many chronic diseases. Four families of SPMs have been identified and include the resolvins, lipoxins, protectins, and maresins. The SPMs promote apoptosis, regulate leukocyte (white blood cell) activity, and reduce the production of proinflammatory mediators.
A tool used in research to investigate mammalian carbohydrate, fat, and protein metabolism in vivo. Scientists create a stable isotope tracer by labeling a molecule (e.g., glucose, fatty acid, or amino acid) with one or more atoms to distinguish it from the naturally occurring molecule.
A metabolic disorder characterized by high blood sugar and insulin resistance. Type 2 diabetes is a progressive condition and is typically associated with overweight and low physical activity. Common symptoms include increased thirst, frequent urination, unexplained weight loss, increased hunger, fatigue, and impaired healing. Long-term complications from poorly controlled type 2 diabetes include heart disease, stroke, diabetic retinopathy (and subsequent blindness), kidney failure, and diminished peripheral blood flow which may lead to amputations.
The maximum rate of oxygen consumption as measured during incremental exercise and indicates the aerobic fitness of an individual, and plays a role in endurance capacity during prolonged, submaximal exercise.
Member only extras:
Learn more about the advantages of a premium membership by clicking below.
Get email updates with the latest curated healthspan research
Support our work
Every other week premium members receive a special edition newsletter that summarizes all of the latest healthspan research.
Omega-3 News
- Omega-3s protect the heart and muscles against damage incurred during endurance running.
- BDNF emerges as a critical marker of omega-3 fatty acid levels in the brain.
- Study shows people with a high omega-3 DHA level in their blood are at 49% lower risk of Alzheimer’s
- High-dose 2.4g EPA/DHA omega-3 in third trimester of pregnancy decreased the risk of wheeze & asthma during first 5 years of child's life by 54%
- Eating fish rich in omega-3 fatty acids reduces risk of asthma in some children.
As a primary care physician, very eager to incorporate this type of translational information, know at least your message is getting to at least some practicing internal medicine physicians- and thank you for this truly outstanding fascinating discussion