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FoundMyFitness · 2023-07-03 · Rhonda Patrick (host), Chris McGlory

Chris McGlory, PhD, on the Anabolic Potential of Omega-3 Fatty Acids

54 research-tied claims examined: 2 overstated 50 supported 2 unverified

2

Overstated

0:39:01Chris McGloryoverstatedmoderate

Meta-analyses support that omega-3 supplementation improves muscle mass in humans.

"There are a couple of papers that have shown, you know, if you feed omega-3s, that improves muscle mass. There's meta-analyses supporting this" (said at 0:39:01)

While at least one meta-analysis of randomized trials in older adults reported a modest increase in muscle mass (weighted mean gain of ~0.33 kg, increasing to ~0.67 kg at doses >2 g/day), the majority of subsequent meta-analyses across healthy adults and older populations have found that omega-3 supplementation does not produce statistically significant gains in muscle or lean body mass. Some meta-analyses do, however, report small positive effects on muscle strength or physical performance measures.

1:12:30Rhonda Patrick (host)overstatedlow

Studies have shown that DHA and EPA increase resting metabolic rate by 19% and exercise fat oxidation by 27% in older women.

"So there's a few studies, like limited I'd say limited evidence showing that DHA and EPA can increase the metabolic rate of both resting and during exercise in older women. ... And these effects were even more profound in like fat oxidation, so it was like a 19% increase in in resting metabolic rate and 27% increase during exercise for fat oxidation." (said at 1:12:30)

A 12-week randomized controlled trial in 24 older females (Logan et al., 2015) found that 3 g/day of EPA and DHA increased the rate of resting fat oxidation by 19% (not resting metabolic rate, which increased by 14%) and exercise fat oxidation by 27% (energy expenditure during exercise increased by 10%). The speaker slightly misattributed the 19% figure to resting metabolic rate rather than resting fat oxidation. Furthermore, the evidence base is small and mixed, as a subsequent randomized trial in older adults (PMID: 32342642) found no significant effect of 12 weeks of fish oil supplementation on resting metabolic rate or fat oxidation.

50

Supported by research

0:00:00Chris McGlorysupportedhigh

Studies by Bettina Mittendorfer's group showed that omega-3 fatty acid supplementation enhances the muscle protein synthetic response to amino acid infusion in both younger and older adults.

"You know, the series of papers by Bettina Mittendorfer's group I think were the landmark papers in this field where, you know, they were the ones that did the showing there's enhanced protein synthetic response to amino acid infusion with omega-3s, and they replicated that in younger people and older people." (said at 0:00:00)

Randomized clinical trials conducted by Bettina Mittendorfer's group directly substantiate the claim. In two 2011 trials, 8 weeks of dietary omega-3 polyunsaturated fatty acid supplementation (4 g/day) had no effect on basal muscle protein synthesis rates, but significantly augmented the muscle fractional synthetic rate in response to hyperaminoacidemic-hyperinsulinemic infusion clamps in both older adults (PMID: 21159787) and healthy young/middle-aged adults (PMID: 21501117).

0:00:25Chris McGlorysupportedmoderate

A six-month longitudinal trial administering 2 grams per day of EPA and DHA showed significant increases in muscle mass and strength.

"And then they followed up with a longitudinal feed, and I think it was six months of 2 grams per day of EPA and DHA, and the changes there were quite significant. I believe it was in—I believe it was mass and also strength." (said at 0:00:25)

A 6-month randomized controlled trial by Smith et al. (2015) evaluated omega-3 PUFA supplementation (4 g/day of fish oil containing ~1.86 g EPA and 1.50 g DHA) versus corn oil in 60 healthy older adults aged 60–85. Compared to the control group, 6 months of omega-3 supplementation significantly increased thigh muscle volume (by 3.6%), handgrip strength (by 2.3 kg), and one-repetition maximum muscle strength (by 4.0%).

0:00:50Chris McGlorysupportedhigh

Stuart Gray published a study using krill oil supplementation that replicated findings of enhanced muscle mass and strength in a similar cohort over a similar duration.

"Well, Stuart Gray then published the paper with krill oil, similar participant cohort, similar duration, and replicated what had been shown by Bettina Mittendorfer's group." (said at 0:00:50)

In 2022, Stuart Gray and colleagues published a double-blind randomized controlled trial evaluating 6 months of krill oil supplementation (4 g/day) in 102 healthy older adults (>65 years). The trial found statistically significant increases in knee extensor maximal torque (9.3%), grip strength (10.9%), and vastus lateralis muscle thickness (3.5%) compared to the control group, replicating previous findings by Bettina Mittendorfer's group demonstrating that 6 months of omega-3 supplementation enhances muscle size and strength in older adults.

0:03:24Rhonda Patrick (host)supportedmoderate

As little as two weeks of leg immobilization can result in nearly a 15 percent loss in quadriceps muscle cross-sectional area.

"As little as two weeks could result in nearly 15 percent loss in the cross-sectional area of your quadricep muscle." (said at 0:03:24)

Human immobilization studies and systematic reviews demonstrate that 14 days (two weeks) of lower limb disuse or casting induces substantial quadriceps atrophy. In healthy individuals, 14 days of unilateral knee immobilization causes an average reduction of approximately 6.5% to 10% in quadriceps/vastus cross-sectional area (CSA), with individual reductions frequently approaching 14% to 15% (e.g., vastus group CSA decreased by 9.6 ± 4.6%). In clinical or critical care settings, disuse muscle loss can be even more rapid.

0:06:11Rhonda Patrick (host)supportedhigh

In Dr. McGlory's 2019 study, participants received a total dose of 5 grams of omega-3 per day.

"Just to give you a little context, in Dr. McGlory's 2019 study, participants received a total of 5 grams of omega-3 per day." (said at 0:06:11)

In the 2019 randomized controlled trial led by Dr. Chris McGlory evaluating the effect of omega-3 fatty acid supplementation on disuse atrophy during unilateral leg immobilization in young women, participants in the intervention group received 5 g/day of omega-3 fatty acids (specifically 3 g EPA and 2 g DHA) starting 4 weeks prior to immobilization.

0:13:14Chris McGlorysupportedvery low

A study out of Laval demonstrated that infusing growing steers with omega-3 fatty acids altered whole-body protein balance.

"I think the study—it may not be horses, it may be horses, but the one I can think of is in growing steers, and it was out of Laval where they fed growing steers the omega-3s, they infused them, and showed how it affected whole-body protein balance." (said at 0:13:14)

A 2007 study conducted at Laval University (Gingras et al.) investigated the effects of continuous abomasal infusion of omega-3-rich menhaden oil compared to an iso-energetic control oil mixture in growing steers. The researchers found that long-chain omega-3 fatty acid infusion potentiated insulin action, doubled insulin-stimulated whole-body disposal of amino acids, activated the Akt-mTOR-S6K1 pathway in skeletal muscle, and reduced whole-body phenylalanine flux and protein oxidation, directly demonstrating altered whole-body protein metabolism and balance in growing steers.

0:15:07Chris McGlorysupportedhigh

Disuse muscle atrophy occurs primarily because of a reduction in muscle protein synthesis rates in both the fasted state and in response to amino acid feeding.

"And it's a point—well, maybe not a point of contention anymore, but one of the reasons that we think that occurs is because there's a reduction in the rate at which we create new muscle proteins in the form of muscle protein synthesis. So when you reduce muscle protein synthesis in both the fasted state and in response to amino acids, it leads to a negative balance of skeletal muscle over time that kind of reduces the size of muscle that you have." (said at 0:15:07)

Human in vivo tracer studies demonstrate that disuse skeletal muscle atrophy is primarily driven by declines in muscle protein synthesis (MPS) rather than chronic increases in muscle proteolysis. During immobilization or disuse, MPS decreases in both the postabsorptive (fasted) state and in response to feeding/amino acid provision (a phenomenon known as anabolic resistance), resulting in a sustained negative net muscle protein balance.

0:16:30Chris McGlorysupportedmoderate

Muscle strength and muscle size serve as predictors of all-cause mortality and disability.

"And we also know that muscle strength in and of itself and to some degree muscle size is a predictor of all-cause mortality and disability." (said at 0:16:30)

Large systematic reviews and meta-analyses of prospective cohort studies confirm that both muscle strength and muscle mass/size are significant independent predictors of all-cause mortality and functional disability. Low muscular strength is consistently associated with an elevated risk of all-cause mortality across general and clinical populations (hazard ratio approximately 1.80 for lowest vs. highest strength categories), as is low muscle mass or muscle wasting (relative risk approximately 1.36 for all-cause mortality). Muscular weakness is also well established as a major predictor of functional limitations and physical disability.

0:20:01Chris McGlorysupportedmoderate

A meta-analysis led by Nick Pszczolkowski showed that muscle mass decline during disuse occurs rapidly within the first 7 days, reaching up to 7 to 10 percent loss, and further declines from 7 to 14 days before tapering out.

"So we've recently just published a meta-analysis—Nick Pszczolkowski led that—and we looked at the decline in muscle mass and size in healthy people. And what Nick did is he differentiated between 0 to 7 days, 7 to 14, and 14 onwards. And this is in generally healthy people. And what we found was that there was a rapid decline after 7 days, a greater decline or a further decline from 7 to 14, then it tapered out." (said at 0:20:01)

A systematic review and meta-analysis on the time course of disuse muscle atrophy in the lower limbs found that muscle loss occurs most rapidly during the early phases of immobilization (with substantial loss occurring within the initial 7 to 14 days) and that the rate of atrophy slows down (tapers off) across subsequent weeks in healthy individuals.

0:21:10Chris McGlorysupportedmoderate

In a 2017 study by Tanner Stokes and Chris McGlory in older pre-diabetic individuals, reducing daily steps below 1,000 for two weeks downregulated muscle protein synthesis and compromised insulin sensitivity, which failed to recover after two weeks of normal activity.

"I did a study as a postdoc with Tanner Stokes when we were in Stu Phillips's lab where we subjected older people to reduced daily step counts. I believe it was below a thousand steps per day, and that kind of mimicked what people would experience during, say, the pandemic when they were being quarantined for two weeks, or influenza, or the step count typically experienced in hospital. And what we found was that there was a downregulation of protein synthesis, and this was in older, pre-diabetic populations. And it wasn't fully recovered after two weeks of returning to activities." (said at 0:21:10)

A prospective clinical trial conducted in Stuart Phillips's laboratory by McGlory, Stokes, and colleagues investigated the effects of 14 days of step reduction (<1,000 steps/day) followed by 14 days of habitual activity recovery in 22 overweight, prediabetic older adults (mean age 69 years). The study confirmed that 2 weeks of acute physical inactivity significantly lowered integrated muscle protein synthesis rates and impaired glycemic control and insulin sensitivity (elevating HOMA-IR and glucose/insulin AUC, while lowering the Matsuda insulin sensitivity index). Crucially, neither muscle protein synthesis nor insulin sensitivity returned to baseline levels after 14 days of resuming normal activity.

0:28:40Chris McGlorysupportedmoderate

In Dr. McGlory's study on young women, four weeks of high-dose omega-3 supplementation mitigated the decline in muscle size during two weeks of single-leg immobilization and accelerated muscle mass recovery afterwards.

"And what we really found was very surprising to us. It seemed like the omega-3s were completely protective, at least from a mass point of view, and they took the edge off the decline in muscle size as measured by MRI... And, you know, there was that protection, and then the important thing I think when we look at it is that actually it helped the people in the omega-3 group recover their muscle earlier than the people in the control group." (said at 0:28:40)

A randomized controlled trial led by Dr. Chris McGlory (PMID: 30629458) evaluated 20 healthy young women who consumed either 5 g/day of omega-3 fatty acids or a control oil starting 4 weeks before 2 weeks of unilateral leg immobilization, followed by 2 weeks of recovery. The decline in muscle volume following immobilization was significantly attenuated in the omega-3 group compared to the control group (8% vs. 14%), and muscle volume returned to pre-immobilization baseline levels during recovery in the omega-3 group but remained significantly reduced in controls.

0:29:35Chris McGlorysupportedmoderate

Dr. McGlory's immobilization study measured muscle protein synthesis rates using deuterium and found higher rates of protein synthesis in the omega-3 group compared to control.

"And from a mechanistic point of view, we used deuterium to assess rates of muscle protein synthesis, and consistent with the previous work by Bettina Mittendorfer's group and Gordon Smith, we found that in the omega-3 group, there was higher rates of protein synthesis, which would kind of again corroborate the mechanisms of action of omega-3s, which is to enhance the protein synthetic response to daily protein feeding." (said at 0:29:35)

In a randomized trial by McGlory et al. (2019), 20 healthy young women underwent 2 weeks of unilateral leg immobilization preceded by 4 weeks of supplementation with either 5 g/day of omega-3 fatty acids or a sunflower oil control. Using deuterium oxide tracer methodology to evaluate integrated daily rates of myofibrillar protein synthesis (MyoPS), researchers found that MyoPS was significantly higher in the omega-3 supplementation group compared to the control group at all measured timepoints, which coincided with attenuated muscle atrophy.

0:27:39Chris McGlorysupportedmoderate

Approximately four weeks of high-dose omega-3 supplementation is required to see a substantial increase in the omega-3 profile of human skeletal muscle.

"Using a protocol that we'd worked on in Scotland where we knew it took around four weeks of high-dose omega-3s to see a substantial increase in the omega-3 profile of the muscle" (said at 0:27:39)

High-dose omega-3 supplementation (e.g., 5 g/day of fish oil) progressively increases omega-3 polyunsaturated fatty acid (n-3 PUFA) incorporation into human skeletal muscle lipid and phospholipid pools over a 4-week period. In a time-course trial tracking muscle lipid changes at 1, 2, and 4 weeks of high-dose fish oil supplementation, skeletal muscle n-3 PUFA content increased significantly by week 2 and continued to rise through week 4, establishing a 4-week loading period as standard protocol in subsequent human immobilization and muscle physiology trials.

0:06:44Rhonda Patrick (host)supportedmoderate

Between 80 and 90 percent of people, especially in the United States, would benefit from higher omega-3 intake.

"It is thought that between 80 and 90 percent of people, especially in the United States, would benefit from higher omega-3 intake." (said at 0:06:44)

Analysis of biomarker data from representative population surveys confirms that between 80% and over 90% of adults in the United States have suboptimal blood concentrations of long-chain omega-3 fatty acids (EPA and DHA). In a National Health and Nutrition Examination Survey (NHANES) study, 80.6% of U.S. adults had plasma long-chain omega-3 levels below concentrations recommended for cardiovascular health, and 95.7% fell below levels associated with maximal cardiovascular protection. Furthermore, a global review of blood EPA and DHA levels identified North America as a region with very low blood levels (Omega-3 Index ≤ 4%), supporting the claim that a vast majority of the population, particularly in the U.S., has intakes below beneficial thresholds.

0:31:17Chris McGlorysupportedmoderate

A 30-gram dose of protein maximally saturates the muscle protein synthetic response.

"We gave them 30 grams of protein, which we know maximally saturates the response." (said at 0:31:17)

Randomized physiological research demonstrates that a ~30 g serving of high-quality dietary protein (e.g., 113 g lean beef) robustly stimulates skeletal muscle protein synthesis (MPS) rates, with larger doses (such as 90 g of protein) failing to provide any further increase in MPS over a standard postprandial assessment period (5 hours). Consequently, ~20 to 30 g of high-quality intact protein is widely recognized as the quantity that maximally stimulates or saturates the acute muscle protein synthetic response per meal.

0:33:39Chris McGlorysupportedvery low

A study in pigs found that omega-3 fatty acids altered the gene expression of the amino acid transporter LAT1 in skeletal muscle.

"And I did notice a paper in actual pigs where they'd seen omega-3 fatty acids altered the gene expression of an amino acid transporter called LAT1." (said at 0:33:39)

A 2015 randomized study in 96 finishing pigs evaluated the effects of different dietary n-6:n-3 polyunsaturated fatty acid (PUFA) ratios (1:1, 2.5:1, 5:1, and 10:1) on muscle characteristics and transporter expression. The authors reported that lower n-6:n-3 ratios (higher omega-3 content, specifically 1:1 and 2.5:1) significantly up-regulated mRNA expression of the amino acid transporter LAT1 (as well as SNAT2) in the longissimus dorsi (skeletal muscle). Because this evidence comes solely from an animal model, certainty is rated as very low.

0:33:55Chris McGlorysupportedhigh

LAT1 is an amino acid transporter for the branched-chain amino acid leucine.

"LAT1 gene expression, so that's an amino acid transporter for branched-chain amino acid leucine." (said at 0:33:55)

L-type amino acid transporter 1 (LAT1, encoded by the SLC7A5 gene) is a well-established sodium-independent amino acid transporter that mediates the uptake of large neutral amino acids across cell membranes, with the branched-chain amino acid L-leucine serving as one of its primary substrates.

0:35:10Rhonda Patrick (host)supportedvery low

DHA deficiency in rodents significantly alters GLUT1 transporter protein levels at the blood-brain barrier.

"And if you, for example, cause DHA deficiency in rodents, you will significantly alter at the protein level the GLUT1 transporters that are responsible for transporting glucose across the blood-brain barrier." (said at 0:35:10)

Animal and cell studies demonstrate that n-3 polyunsaturated fatty acid (specifically DHA) deficiency alters glucose transporter 1 (GLUT1) protein levels and activity at the blood-brain barrier. In rodent models, dietary n-3 PUFA deficiency led to a significant 23% reduction in endothelial GLUT1 protein expression in cerebral cortex microvessels as measured by Western blot, along with reduced cytochalasin B binding capacity, while supplementation increased GLUT1 expression and glucose transport. Because this evidence is derived exclusively from rodent and in vitro models, the GRADE certainty is very low.

0:37:25Chris McGlorysupportedvery low

Rodents fed a high-fish-oil diet are protected against disuse muscle atrophy.

"The only other study that I'm aware of with this is in rodents, where they fed with a high-fish-oil diet and they're protected against disuse atrophy in that context" (said at 0:37:25)

The claim is supported by rodent research. In a 2010 study using a rat hindlimb immobilization model of disuse muscle atrophy, feeding rats a fish-oil-based diet prior to and during 10 days of cast immobilization significantly attenuated the loss of soleus muscle mass and myosin heavy chain content compared to a control diet, mediated by modulation of Akt/p70s6k signaling and downregulation of ubiquitin ligases MAFbx and MuRF1. Because the evidence is derived exclusively from preclinical animal models, the GRADE certainty is very low.

0:37:41Chris McGlorysupportedhigh

Women are more susceptible to ACL injuries than men.

"secondly, they're more susceptible to ACL injuries, so it's an at-risk population." (said at 0:37:41)

Extensive epidemiological research and multiple systematic reviews and meta-analyses confirm that female athletes have a significantly higher incidence and risk of anterior cruciate ligament (ACL) injuries compared to male athletes participating in similar sports. Meta-analyses of team sports find that female athletes experience approximately 2 to 3 times the rate of ACL injuries per exposure hour compared to male peers, particularly during non-contact mechanisms and jumping or cutting maneuvers.

0:43:15Chris McGlorysupportedmoderate

Supplementation with approximately 5 grams of omega-3s takes about 4 weeks to induce a significant change in skeletal muscle phospholipid profile, plateauing between 6 and 8 weeks.

"And in skeletal muscle, we know if you take around 5 grams of omega-3s—3 grams of EPA, 2 grams of DHA, say, as a combination—you'll probably see a small change after about two weeks in the muscle. You see a rapid change in the blood, but it takes around four weeks before you start to see the kind of big difference. And with that dose, it typically will level off. We've seen this in the FASEB paper we did with disuse atrophy—it wasn't the primary aim of the paper, but between six and eight weeks, it seemed to level off. And this is in the muscle phospholipid profile." (said at 0:43:15)

Human clinical trials evaluating high-dose omega-3 polyunsaturated fatty acid supplementation (~5 g/day of EPA and DHA) demonstrate that EPA and DHA are incorporated into human skeletal muscle phospholipid membranes over several weeks. A clinical study examining the kinetics and sex differences of 5 g/day EPA+DHA supplementation across 8 weeks (with muscle sampling at baseline, week 6, and week 8) confirmed significant muscle phospholipid enrichment that peaks or levels off between weeks 6 and 8. Previous clinical trials by McGlory and colleagues using 5 g/day of omega-3 fatty acids in human disuse atrophy protocols similarly demonstrated time-dependent muscle phospholipid incorporation leading to clinical attenuation of disuse atrophy.

0:49:59Chris McGlorysupportedmoderate

Older adults exhibit anabolic resistance to an acute bout of resistance exercise across a wide range of load spectrums.

"what we do know is that older folks tend to be not just resistant to the anabolic influence of protein or amino acid ingestion or essential amino acid ingestion, they seem to be anabolically resistant to resistance exercise or an acute bout of resistance exercise across a like a a wide range of loading spectrums." (said at 0:49:59)

Published human physiological studies demonstrate that older adults exhibit anabolic resistance (attenuated muscle protein synthesis and blunted downstream mTORC1 anabolic signaling) following an acute bout of resistance exercise across a wide spectrum of exercise intensities (20% to 90% of 1-repetition maximum) when compared to younger adults.

0:50:23Chris McGlorysupportedhigh

Adults up to the age of 90 can gain muscle strength from participating in resistance exercise.

"But you can, you know, people up to the age of 90 can certainly gain strength when engaging with resistance exercise." (said at 0:50:23)

Multiple clinical trials, including randomized controlled trials in nonagenarians (aged 90 to 97 years), confirm that resistance exercise training leads to significant improvements in muscle strength, muscle mass, and functional mobility in this age group.

0:51:35Chris McGlorysupportedmoderate

A study by Stuart Gray's group in Glasgow found that omega-3 supplementation enhanced strength gains from resistance training in older women, but not in older men.

"there's been a couple of papers out there where Stuart Gray's paper that comes to mind from from Glasgow, where they fed omega-3s to older people during resistance training and found only in women that it enhanced the the strength response to to a period of resistance training in women, and that was omega-3s." (said at 0:51:35)

A randomized controlled trial led by Stuart Gray's group (Da Boit et al., 2017) investigated the sex-specific effects of 18 weeks of omega-3 supplementation (3 g/day fish oil) combined with resistance exercise training in 50 older men and women (mean age ~71 years). The study found that fish oil supplementation significantly enhanced gains in maximal isometric torque (strength) and muscle quality in older women compared to placebo, but did not produce these enhancements in older men.

0:51:50Chris McGlorysupportedmoderate

A study by Rodacki and colleagues published in AJCN found that omega-3 supplementation potentiated strength gains during resistance training in older women.

"There's been other papers as well, one from a group in Brazil, again looking at the effect of omega-3s with resistance training in older women, showing that it potentiated the strength gains." (said at 0:51:50)

A 2012 randomized controlled trial by Rodacki and colleagues from Brazil, published in The American Journal of Clinical Nutrition, evaluated 45 elderly women (mean age 64) randomized to strength training alone or strength training combined with 2 g/day of fish oil supplementation (for 90 or 150 days). The study found that fish oil supplementation significantly enhanced the gains in muscle peak torque, rate of torque development, and functional capacity compared to strength training alone.

  • supports: Fish-oil supplementation enhances the effects of strength training in elderly women. (The American journal of clinical nutrition 2012) · cited 272x in the literature
    "The peak torque and rate of torque development for all muscles (knee flexor and extensor, plantar and dorsiflexor) increased from pre- to posttraining in all groups. However, the effect was greater in the ST90 and ST150 groups than in the ST group. The activation level and electromechanical delay of the muscles changed from pre- to posttraining only for the ST90 and ST150 groups. Chair-rising performance in the FO groups was higher than in the ST group. Strength training increased muscle strength in elderly women. The inclusion of FO supplementation caused greater improvements in muscle strength and functional capacity." (abstract, results and conclusions, passage verified)
    pubmedfull study (doi)
0:53:35Chris McGlorysupportedmoderate

Krill oil supplementation has been shown to increase muscle strength or size in older adults.

"Stuart's done some work, Stuart Gray, with krill oil that has replicated some findings from Bettina Mittendorfer's group with increases in strength with omega-3 supplementation—or size, sorry." (said at 0:53:35)

A double-blind randomized controlled trial led by Stuart Gray's group evaluated the effect of 6 months of krill oil supplementation (4 g/day) versus control in 94 healthy older adults (aged >65 years). The study found statistically significant increases in knee extensor maximal torque (9.3%), grip strength (10.9%), and vastus lateralis muscle thickness (3.5%) compared to control, directly supporting the claim that krill oil increases muscle strength and size in older adults.

0:54:27Rhonda Patrick (host)supportedmoderate

Females convert the plant omega-3 ALA into EPA and DHA more efficiently than males due to estrogen.

"there is a sex difference with respect to converting the plant omega-3, you know, what you get from plants, ALA, into EPA and DHA. So estrogen really plays a big role in increasing the conversion of ALA into EPA and DHA." (said at 0:54:27)

Human stable isotope tracer studies demonstrate that women convert alpha-linolenic acid (ALA) to eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) at substantially higher rates than men. In tracer studies, young women exhibited fractional conversion of ALA to DHA of around 9%, whereas conversion to DHA in men is typically trace or undetectable (<1%). Mechanistic and observational research indicates this sex difference is driven in part by estrogen, which upregulates the expression and activity of key desaturase and elongase enzymes involved in long-chain polyunsaturated fatty acid synthesis.

0:56:38Chris McGlorysupportedmoderate

A meta-analysis found that omega-3 supplementation in older adults improved gait speed or walking performance.

"But there was a meta-analysis recently published suggesting that I think it was either gait speed or walking speed was improved in older people with with omega-3 supplementation, suggesting that there may be an enhanced effect in terms of function." (said at 0:56:38)

A 2020 systematic review and meta-analysis of randomized controlled trials in older adults (Huang et al., Nutrients) reported that omega-3 fatty acid supplementation improved functional performance on the Timed Up and Go test, and subgroup analysis indicated a significant improvement in walking speed in trials lasting longer than 6 months. However, broader subsequent meta-analyses have found mixed results across physical function measures, with some reporting improvements in sit-to-stand and Timed Up and Go tests or lower-body strength, but no overall significant effect on walking speed across all trial durations.

0:59:38Rhonda Patrick (host)supportedmoderate

Sarcopenia is associated with a two- to threefold increased risk of falls, frailty, and disability in older adults.

"This is called sarcopenia, and there's all sorts of problems. It's associated with a two- to threefold increased risk of falls, frailty, disability, I mean on and on, as you mentioned, mortality." (said at 0:59:38)

Large systematic reviews, meta-analyses, and umbrella reviews of observational studies confirm that sarcopenia in older adults is associated with a roughly 1.6- to 3.6-fold increased risk of adverse outcomes including falls, physical disability, and all-cause mortality. Specifically, umbrella review evidence demonstrates an increased risk for disability (OR = 3.04, 95% CI 1.80–5.12), mortality in community-dwelling older adults (OR = 3.60, 95% CI 2.96–4.37), and falls (OR = 1.60 to 1.89), aligning closely with the speaker's stated range of a two- to threefold risk increase.

0:53:10Chris McGlorysupportedmoderate

Research by Bettina Mittendorfer's group showed that omega-3 fatty acid supplementation increases muscle size in older adults.

"Stuart's done some work, Stuart Gray, with krill oil that has replicated some findings from Bettina Mittendorfer's group with increases in strength with omega-3 supplementation—or size, sorry." (said at 0:53:10)

A randomized controlled trial led by Bettina Mittendorfer's research group evaluated 6 months of fish oil-derived omega-3 fatty acid supplementation (n-3 PUFA) in healthy older adults aged 60 to 85. Compared to corn oil control, omega-3 supplementation significantly increased thigh muscle volume by 3.6%, handgrip strength, and upper- and lower-body 1-repetition maximum muscle strength. Subsequent clinical trial work by Stuart Gray's group similarly demonstrated that 6 months of omega-3 supplementation via krill oil significantly increased muscle strength and size in adults aged 65 and older.

0:55:20Chris McGlorysupportedhigh

Relative muscle mass and strength adaptations from resistance exercise training do not differ significantly between younger men and younger women.

"And in terms of the general training adaptations between younger, there's no difference really, from my knowledge, in terms of younger men and younger women with the gains, despite some dogma out there, is that the gains are pretty much quite similar." (said at 0:55:20)

A systematic review and meta-analysis comparing resistance training adaptations between young to middle-aged males and females found that relative gains in muscle hypertrophy and lower-body strength showed no statistically significant differences between sexes. For relative upper-body strength, females exhibited significantly greater relative gains compared to males.

1:01:00Chris McGlorysupportedmoderate

Studies by Bettina Mittendorfer's group, led by Gordon Smith, demonstrated an enhanced muscle protein synthetic response to amino acid infusion following omega-3 supplementation in both younger and older adults.

"the series of papers by Bettina Mittendorfer's group I think were the landmark papers in this field, where, you know, they were the ones that did the showing there's enhanced protein synthetic response to amino acid infusion with omega-3s, and they replicated that in in younger people and older people. And that's like the landmark study that really got me interested when I was in Scotland and studying this. And that was published in AJCN with Gordon Smith as the lead author." (said at 1:01:00)

Studies led by Gordon I. Smith in Bettina Mittendorfer's laboratory investigated the effects of 8 weeks of omega-3 fatty acid supplementation on muscle protein synthesis during hyperaminoacidemic-hyperinsulinemic clamps. In a randomized controlled trial published in The American Journal of Clinical Nutrition (PMID 21159787), omega-3 supplementation significantly augmented the muscle protein synthetic response to amino acid and insulin infusion in healthy older adults compared to corn oil control. A companion study published in Clinical Science (PMID 21501117) demonstrated the same enhancing effect on muscle protein synthesis and anabolic signaling in healthy young and middle-aged adults.

1:01:30Chris McGlorysupportedmoderate

A six-month longitudinal feeding study with 2 grams per day of EPA and DHA resulted in significant improvements in muscle mass or strength.

"And then they followed up with a longitudinal feeding, and I think it was six months of two grams per day of EPA and DHA, and the changes there were quite significant. I believe it was in—I believe it was mass, I'm not too sure, strength." (said at 1:01:30)

A 6-month randomized controlled trial in healthy older adults (60–85 years old) evaluated omega-3 PUFA supplementation (Lovaza, providing long-chain EPA and DHA) compared to a corn oil control. Supplementation for 6 months resulted in statistically significant increases in thigh muscle volume (3.6%), handgrip strength (2.3 kg), and 1-repetition maximum (1-RM) muscle strength (4.0%) compared to the control group.

1:01:55Chris McGlorysupportedhigh

Stuart Gray published a study using krill oil that replicated the muscle mass and strength findings seen with fish oil supplementation.

"Stuart Gray then published the paper with krill oil, similar participant cohort, similar duration, and replicated what had been shown by Bettina Mittendorfer's group." (said at 1:01:55)

Stuart R. Gray and colleagues published a randomized, double-blind, controlled trial in 2022 examining the effects of 6 months of krill oil supplementation (4 g/day) in healthy older adults (aged >65 years). The study demonstrated statistically significant increases in knee extensor maximal torque (9.3%), grip strength (10.9%), and vastus lateralis muscle thickness (3.5%) compared to control, replicating earlier findings on omega-3 supplementation and muscle mass/strength in older populations.

1:04:12Chris McGlorysupportedhigh

The enhanced muscle protein synthetic response to omega-3s in Gordon Smith and Bettina Mittendorfer's studies occurred without significant changes in circulating inflammatory markers.

"the studies that I just talked about from Bettina Mittendorfer's group with Gordon Smith as the lead author, they saw these changes in the absence of any real change in in circulating inflammatory markers." (said at 1:04:12)

Randomized and metabolic clamp studies led by Gordon I. Smith and Bettina Mittendorfer demonstrated that 8 weeks of dietary long-chain omega-3 PUFA supplementation (4 g/day) significantly augmented the muscle protein fractional synthetic rate and mTOR/p70s6k anabolic signaling during hyperinsulinemic-hyperaminoacidemic conditions in both healthy older adults and young/middle-aged adults. These anabolic enhancements occurred without systemic alterations in baseline muscle protein synthesis or major shifts in circulating inflammatory markers in these healthy populations.

1:04:50Chris McGlorysupportedhigh

Phosphorylation of the initiation factor eIF2-alpha impairs the muscle cell's ability to mount a protein synthetic response.

"So one, for example, is eIF2-alpha. So when that's phosphorylated, it can impinge on the ability to mount a protein synthetic response." (said at 1:04:50)

Phosphorylation of the alpha subunit of eukaryotic initiation factor 2 (eIF2α) at serine 51 is a canonical molecular mechanism that inhibits translation initiation and reduces global protein synthesis in eukaryotic cells, including skeletal muscle. Phosphorylated eIF2α acts as a competitive inhibitor of its guanine nucleotide exchange factor (eIF2B), blocking the recycling of eIF2-GDP to active eIF2-GTP and preventing assembly of the 43S preinitiation complex. In muscle tissue and cultured myotubes, stress-induced phosphorylation of eIF2α directly suppresses the muscle cell's protein synthetic rate and contributes to muscle wasting.

1:05:55Chris McGlorysupportedmoderate

A study by Luc van Loon's group led by Ben Wall showed that intracellular stable isotope tracer enrichment was higher after immobilization, indicating that disuse-induced protein synthesis decline is intracellular rather than caused by impaired membrane transport.

"Luc van Loon's group with Ben Wall as the lead author did a paper where they labeled with a stable isotope—they labeled the drink that people were consuming before and after immobilization. And what they found was that the enrichment, which is basically the ratio of the tracer compared to the tracee—so it's a carbon tracer which is labeled—the ratio actually wasn't altered too much. In fact, it was higher after immobilization in intracellular space, which would suggest that there's actually not an impairment in transport across the membrane, and that the impairment in protein synthesis with disuse is actually intracellular." (said at 1:05:55)

A clinical study led by Ben Wall in Luc van Loon's laboratory investigated the effects of 5 days of unilateral leg immobilization in 12 healthy young men using continuous infusions of amino acid tracers alongside the ingestion of intrinsically L-[1-13C]phenylalanine- and L-[1-13C]leucine-labeled dietary protein. The study demonstrated that short-term disuse induced anabolic resistance and reduced postabsorptive and postprandial myofibrillar protein synthesis rates (by 41% and 53%, respectively) with lower protein-bound tracer incorporation, despite preserved or elevated intracellular free tracer availability, indicating that the impairment in muscle protein synthesis during disuse occurs at the intracellular signaling/synthetic level rather than from defective amino acid delivery or membrane transport.

  • supports: Short-term muscle disuse lowers myofibrillar protein synthesis rates and induces anabolic … (American journal of physiology. Endocrinology and metabolism 2016) · cited 168x in the literature
    "Continuous infusions of l-[ring-(2)H5]phenylalanine and l-[1-(13)C]leucine were combined with the ingestion of a 25-g bolus of intrinsically l-[1-(13)C]phenylalanine- and l-[1-(13)C]leucine-labeled dietary protein to assess myofibrillar muscle protein fractional synthetic rates in the immobilized and nonimmobilized control leg... Following protein ingestion, myofibrillar protein bound l-[1-(13)C]phenylalanine enrichments were 53 ± 18% lower in the immobilized compared with the control leg (0.007 ± 0.002 and 0.015 ± 0.002 mole% excess, respectively, P < 0.05). We conclude that 5 days of muscle disuse substantially lowers postabsorptive myofibrillar protein synthesis rates and induces anabolic resistance to protein ingestion." (abstract, results, passage verified)
    pubmedfull study (doi)
1:09:55Chris McGlorysupportedmoderate

Graham Holloway showed that feeding omega-3s to younger people alters ADP sensitivity and ADP-stimulated respiration in human skeletal muscle mitochondria.

"For example, Graham has shown a number of years ago that feeding omega-3s in younger people can affect ADP sensitivity, or ADP-stimulated respiration, in the mitochondria in human skeletal muscle." (said at 1:09:55)

Studies led or co-authored by Dr. Graham Holloway demonstrated that dietary omega-3 fatty acid supplementation in young healthy humans alters mitochondrial function in skeletal muscle. Specifically, a 2014 clinical study in young healthy men showed that 12 weeks of omega-3 fish oil supplementation significantly increased mitochondrial membrane EPA and DHA content and enhanced mitochondrial ADP sensitivity (reduced apparent Km) in permeabilized skeletal muscle fibers. In addition, a 2019 trial in young healthy women demonstrated that omega-3 supplementation mitigated disuse-induced decreases in ADP-stimulated skeletal muscle mitochondrial respiration.

1:11:00Chris McGlorysupportedvery low

Preclinical studies in worms demonstrate that mitochondrial translation signals to cytosolic translation factors that regulate protein synthesis via an ATF4-dependent pathway.

"And there's been some papers in worms, in preclinical models, showing that mitochondrial translation, or the translation of mitochondrial proteins, in and of itself will feed in as a signal to the cytosolic factors that regulate protein synthesis in an ATF4-dependent fashion." (said at 1:11:00)

Preclinical studies in Caenorhabditis elegans and mammalian models demonstrate that inhibiting mitochondrial translation triggers an ATF4-dependent (or atf-5-dependent in worms) signaling pathway that coordinates and represses cytosolic translation. Because this evidence is derived from animal and cell culture experiments, the GRADE certainty is very low.

1:13:20Chris McGlorysupportedmoderate

Studies from Australia showed that omega-3 supplementation, particularly DHA, can reduce the oxygen cost of exercise and lower heart rate.

"I've seen some work from Australia where they've shown feeding omega-3s can—I think it was particularly DHA—can reduce the oxygen cost of exercise and reduce heart rate." (said at 1:13:20)

Randomized, double-blind controlled trials conducted by researchers at the University of Wollongong in Australia have demonstrated that omega-3 supplementation reduces exercise heart rate and the oxygen cost of exercise. In trained cyclists, 8 weeks of fish oil supplementation significantly lowered submaximal exercise heart rate, rate-pressure product, and whole-body oxygen consumption. A subsequent trial specifically evaluating DHA-rich tuna fish oil found that DHA supplementation increased the omega-3 index and significantly reduced relative oxygen consumption during a cycling time trial.

1:19:00Chris McGlorysupportedhigh

In animal and cell studies, as well as Bettina Mittendorfer's human studies, omega-3 potentiation of muscle protein synthesis is associated with activation of the mTOR-p70S6K signaling pathway.

"But in the studies in which there was the potentiation of protein synthesis, both in, um, Bettina Mittendorfer's work in humans, but also going back to, you know, the the steers that we talked about, the the calves at the very start of of the podcast, is it seemed to be affecting the mTOR-p70 pathway." (said at 1:19:00)

The claim is directly supported by published animal and human clinical trials. Randomized controlled human trials conducted by Bettina Mittendorfer and colleagues demonstrated that dietary omega-3 polyunsaturated fatty acid supplementation augmented the hyperaminoacidemic-hyperinsulinemic stimulation of muscle protein synthesis in both older and young-to-middle-aged adults, accompanied by enhanced phosphorylation of mTOR (Ser2448) and p70S6K (Thr389). Similarly, earlier animal studies in growing steers demonstrated that omega-3 supplementation enhanced whole-body amino acid disposal and activated the Akt-mTOR-S6K1 signaling pathway in skeletal muscle.

1:22:25Chris McGlorysupportedvery low

Research by Vera Mazurak in rodent models demonstrates that feeding omega-3 fatty acids protects against chemotherapy-induced muscle atrophy.

"And there's, um, Vera Mazurak in in Alberta, in Canada, who's doing some really excellent work about looking at how omega-3s can actually protect against the negative impact of chemotherapy. So we know that chemotherapy in and of itself is toxic and can have a negative effect on muscle. And in preclinical models, what in rodents what Vera's showing is that actually feeding omega-3s in those animals may actually protect against the negative impacts of chemotherapy on muscle." (said at 1:22:25)

Preclinical research led by Vera Mazurak demonstrates that dietary omega-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid from fish oil) mitigate chemotherapy-induced myotoxicity and help maintain muscle homeostasis in rodent models of cancer. In tumor-bearing rats subjected to chemotherapy, supplementation with fish oil attenuated chemotherapy-induced alterations in muscle gene expression and suppressed pro-inflammatory pathways contributing to muscle damage. Because this evidence comes directly from animal models, the grade of certainty for the preclinical finding is very low.

1:28:35Chris McGlorysupportedhigh

Robert Hickson's classic research suggested an interference effect between concurrent endurance and resistance training on strength gains.

"the classic work by Hickson a while ago was suggesting that there may be an interference effect between performing both, particularly with strength gains." (said at 1:28:35)

Robert C. Hickson's seminal 1980 study evaluated the adaptations of concurrent strength and endurance training compared to strength or endurance training alone over 10 weeks. The study demonstrated that while maximal oxygen uptake (VO2max) improvements were unaffected by concurrent training, strength gains plateaued and subsequently declined in the concurrent training group compared to the strength-only group, establishing the 'interference effect' on strength development.

1:29:14Chris McGlorysupportedmoderate

Endurance exercise promotes capillarization in skeletal muscle, enhancing blood flow and nutrient delivery, and activates satellite cells to donate nuclei that support hypertrophy from resistance exercise.

"you precondition or you perform aerobic exercise and that may enhance capillarization, so, you know, facilitating blood delivery to the to the muscle cell. And then when you perform resistance exercise, the muscle is is primed to receive more nutritional, you know, insulin and and amino acids to enhance the response, the protein synthetic response, to the to resistance exercise. ... And endurance exercise may not only enhance nutrient delivery, but also activate satellite cells where they can donate their nuclear material to and to support the growth response to resistance training." (said at 1:29:14)

The claim is supported by clinical trials investigating aerobic preconditioning and capillarization in muscle hypertrophy. Research demonstrates that performing aerobic/endurance conditioning prior to resistance training increases capillary density and satellite cell content in skeletal muscle, which enhances muscle fiber cross-sectional area and myonuclear responses during subsequent resistance training (PMID: 35971745, PMID: 27897408).

1:05:43Chris McGlorysupportedmoderate

A study by Alisa Glover and Stuart Phillips showed that branched-chain amino acid concentrations increase in the intracellular space of muscle tissue.

"Now, Alisa Glover, when she was working with Stu Phillips, Dr. Phillips, and they published a paper—I think it's in J Phys—and if you look at the branched-chain concentrations in the intracellular space in one of the tables, that would suggest there may be an increase." (said at 1:05:43)

Alisa Glover and Stuart Phillips (along with colleagues) published a 2008 study in The Journal of Physiology (PMID 18955382) investigating the effects of limb immobilization and graded amino acid infusions on human muscle protein synthesis. In the study, infusion of amino acids increased amino acid availability and stimulated myofibrillar protein synthesis in skeletal muscle tissue.

1:07:44Chris McGlorysupportedhigh

In rodent studies, omega-3 supplementation has positive effects on insulin sensitivity and glucose regulation, but evidence in humans is mixed and less convincing.

"So if you look at the rodent literature, it seems to have quite positive effects on insulin sensitivity and glucose regulation. The work in humans is not as convincing." (said at 1:07:44)

Preclinical and clinical reviews consistently demonstrate that omega-3 polyunsaturated fatty acids (such as EPA and DHA) robustly improve insulin sensitivity and glucose homeostasis in rodent models of obesity and metabolic syndrome. In contrast, randomized controlled trials and intervention studies in humans show mixed, marginal, or null effects on glycemic control and insulin sensitivity in people with insulin resistance or type 2 diabetes.

  • supports: The effect of n-3 fatty acids on glucose homeostasis and insulin sensitivity. (Physiological research 2014) · cited 185x in the literature
    "This review focuses on the effects of long-chain n-3 polyunsaturated fatty acids (omega-3) on insulin sensitivity and glucose homeostasis, which are improved by omega-3 in many animal models of metabolic syndrome, but remain frequently unaffected in humans. Here we focus on: (i) mechanistic aspects of omega-3 action, reflecting also our experiments in dietary obese mice; and (ii) recent studies analysing omega-3's effects in various categories of human subjects. Most animal experiments document beneficial effects of omega-3 on insulin sensitivity and glucose metabolism even under conditions of established obesity and insulin resistance." (abstract, passage verified)
    pubmedfull study (doi)
  • supports: Insulin-Sensitizing Effects of Omega-3 Fatty Acids: Lost in Translation? (Nutrients 2016) · cited 137x in the literature
    "Recent studies support a growing consensus that there are beneficial effects of n-3 PUFA on insulin sensitivity in rodents. Observational studies in humans are encouraging, however, the vast majority of human intervention studies fail to demonstrate the benefit of n-3 PUFA in type 2 diabetes or insulin-resistant non-diabetic people." (abstract, passage verified)
    pubmedfull study (doi)
1:15:55Rhonda Patrick (host)supportedmoderate

NHANES data show that Americans generally do not consume fatty fish on a weekly basis.

"They don't even eat it weekly. Like, it's that's like we have We have NHANES studies on that. They're not They're not eating fish a lot of a lot of, especially in America, um, in the United States." (said at 1:15:55)

Analyses of nationally representative National Health and Nutrition Examination Survey (NHANES) data confirm that the vast majority of Americans do not meet dietary recommendations for fish or seafood intake, particularly for fatty (omega-3-rich) fish. NHANES analyses indicate that 80% to 90% of Americans fail to meet recommended seafood intake guidelines, with median intakes of long-chain omega-3 fatty acids from dietary sources falling well below levels equivalent to weekly or biweekly consumption of fatty fish. Intake of seafood high in long-chain omega-3 polyunsaturated fatty acids averages only 21 to 47 grams per week across income groups, which is substantially less than a single standard serving (approx. 100 to 112 grams).

1:28:43Chris McGlorysupportedhigh

Human research by Scandinavian groups, including Tommy Lundberg, demonstrates that concurrent aerobic exercise does not exert an interference effect on muscle hypertrophy from resistance training.

"And I think whilst that may be the case in cells and rodents, the human work really hasn't that's not it's not washed out in the in the human work at all. Doesn't seem to be an interference effect, at least when it comes to muscle hypertrophy. And there's been some good work by some Scandinavian groups there, Tommy Lundberg being one of them" (said at 1:28:43)

A systematic review and meta-analysis co-authored by Swedish researcher Tommy R. Lundberg and colleagues evaluated 43 studies comparing concurrent aerobic and strength training with strength training alone in healthy adults. The analysis found that concurrent aerobic and strength training did not compromise whole-muscle hypertrophy (standardized mean difference -0.01, 95% CI -0.16 to 0.18, p = 0.919) or maximal strength development, although explosive strength gains were attenuated.

1:30:46Chris McGlorysupportedmoderate

Cardiorespiratory/exercise capacity is a predictor of mortality and is important for maintaining cardiovascular health and function.

"capacity is very is a predictor of mortality, and it's also important to to maintain cardiovascular health and function." (said at 1:30:46)

Cardiorespiratory fitness (exercise capacity) is a well-established, independent predictor of all-cause and cardiovascular mortality, as well as incident cardiovascular conditions. Large systematic reviews and meta-analyses comprising millions of participants consistently show strong, dose-dependent inverse associations between cardiorespiratory fitness and mortality risk, where each 1-metabolic equivalent of task (MET) higher fitness level is associated with approximately an 11% to 17% reduction in all-cause mortality and significant reductions in cardiovascular disease mortality and heart failure.

1:32:50Chris McGlorysupportedhigh

A meta-analysis by Tommy Lundberg suggests that concurrent training with cycling does not significantly compromise or interfere with resistance training adaptations.

"And there is a meta-analysis out there by, I think, Tommy Lundberg suggesting that, you know, um, like certainly, at least with cycling, it doesn't seem to have that much of an effect." (said at 1:32:50)

A 2022 systematic review and meta-analysis co-authored by Tommy Lundberg (PMID: 35476184) evaluated muscle fiber hypertrophy in response to concurrent aerobic and strength training compared to strength training alone. The meta-analysis found a significant negative interference effect on type I muscle fiber hypertrophy when aerobic training was performed via running, but no such interference effect was observed when aerobic training was performed by cycling. Additionally, Lundberg's accompanying meta-analysis on whole-muscle adaptations (PMID: 34757594) found that concurrent aerobic and strength training does not compromise whole-muscle hypertrophy or maximal strength development overall.

2

No source found (not proven false)

0:47:52Rhonda Patrick (host)unverifiedvery low

Specialized pro-resolving mediators (SPMs) appear in the bloodstream rapidly following omega-3 ingestion and persist for approximately 24 hours.

"So there's some clinical studies showing that these SPMs are in the bloodstream pretty immediately after taking them and they can last like 24 hours." (said at 0:47:52)

No published record matching the claim that specialized pro-resolving mediators appear in the bloodstream rapidly following omega-3 ingestion and persist for approximately 24 hours was located; this does not prove the claim false.

0:45:12Chris McGloryunverifiedvery low

In a time-course study of young men, skeletal muscle lipid incorporation of omega-3 fatty acids showed a statistically detectable increase after two weeks of supplementation, but not after one week.

"So we did a time-course study in younger men when I was in Stirling where we just basically fed young men omega-3s and biopsies at minus two, zero, so they act as their own internal control, and then I believe it was one, two, and four weeks. And we didn't see anything at one week, but we did at two." (said at 0:45:12)

No published record matching the specific time-course study described (evaluating human skeletal muscle biopsies at minus two, zero, one, two, and four weeks of omega-3 supplementation in young men) was located; this does not prove the claim false.

Unverified means no publication matching the claim was located; it does not prove the claim false. Spotted an error? See the corrections policy - disputes from the people quoted are prioritized.