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Cited by 104Fatty Acid Research and HealthMuscle Physiology and DisordersMuscle metabolism and nutrition

Potential Roles of n-3 PUFAs during Skeletal Muscle Growth and Regeneration

Open access
Tachtsis, Bill, Camera, Donny, Lacham-Kaplan, Orly·2018·Nutrients
DOI 10.3390/nu10030309PMC PMC5872727
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Abstract

Omega-3 polyunsaturated fatty acids (n-3 PUFAs), which are commonly found in fish oil supplements, are known to possess anti-inflammatory properties and more recently alter skeletal muscle function. In this review, we discuss novel findings related to how n-3 PUFAs modulate molecular signaling responsible for growth and hypertrophy as well as the activity of muscle stem cells. Muscle stem cells commonly known as satellite cells, are primarily responsible for driving the skeletal muscle repair process to potentially damaging stimuli, such as mechanical stress elicited by exercise contraction. To date, there is a paucity of human investigations related to the effects of n-3 PUFAs on satellite cell content and activity. Based on current in vitro investigations, this review focuses on novel mechanisms linking n-3 PUFA’s to satellite cell activity and how they may improve muscle repair. Understanding the role of n-3 PUFAs during muscle growth and regeneration in association with exercise could lead to the development of novel supplementation strategies that increase muscle mass and strength, therefore possibly reducing the burden of muscle wasting with age.

AI snapshot

Written from the paper’s full text.

TL;DR

This narrative review synthesizes in vitro and human evidence on how the n-3 PUFAs EPA and DHA may modulate skeletal muscle growth, regeneration, and satellite cell activity through anti-inflammatory, anabolic-signalling, and myogenic mechanisms. It concludes that n-3 PUFAs plausibly support muscle repair and strength, but that direct human evidence for effects on satellite cells is largely absent.

Key findings

  • n-3 PUFAs (EPA, DHA) are proposed to reduce muscle wasting by inhibiting NF-κB activation and pro-inflammatory eicosanoid/cytokine production while increasing PPARγ, PPARδ, and PGC-1α signalling; in C2C12 myotubes, 50 μM EPA/DHA for 24 h produced the greatest increase in PGC-1α expression, and 400–600 µM EPA or DHA increased PPARγ and reduced muscle breakdown.
  • In vitro, n-3 PUFAs modulate myogenesis in a dose- and time-dependent manner: 20–100 µM EPA/DHA for 24 h slowed C2C12 growth by preventing G1→S transition (DHA more pronounced), while 50 μM EPA/DHA promoted myogenic responses during differentiation; very high doses (200–600 μM EPA for up to 10 days) induced transdifferentiation to adipocytes.
  • Human trials report strength/muscle benefits: 2 g/day for 90 days with strength training in older women increased peak torque and rate of torque development beyond training alone; 4 g/day for six months in older men and women increased whole thigh muscle area, 1-RM strength, and isokinetic power; greater muscle-quality improvement was seen in older women versus men with fish oil plus resistance exercise.
  • n-3 PUFA supplementation (5 g/day for eight weeks) did not further enhance MPS in young adults when combined with resistance exercise and protein, and attenuated Akt and p70S6K1 activity; the authors suggest this may reflect increased anabolic kinase efficiency rather than reduced anabolism.

Methods

  • Narrative review; no systematic search strategy, inclusion criteria, or database list is reported in the text.
  • Evidence base comprises in vitro cell-culture studies (predominantly C2C12 myoblasts/myotubes, plus L6 rat cells) and in vivo human and animal studies, summarized by the authors in Tables 1–3 (tables not reproduced in the provided text).
  • The review discusses mechanisms (eicosanoid synthesis, NF-κB, PPARs, PGC-1α, mTOR/p70S6K1, MAPK/ERK1/2, MRFs) and human outcomes (MPS, strength, muscle area, satellite cell content) qualitatively rather than via meta-analysis.

Limitations

  • Stated by the paper: there is a "paucity of human investigations" on n-3 PUFA effects on satellite cell content and activity; the capacity of n-3 PUFAs to activate satellite cells in human skeletal muscle "remains to be determined."
  • Stated by the paper: human studies vary widely in n-3 PUFA dose and supplementation duration (Table 3), making the optimal dose/duration unclear; in vitro effects are dose- and time-dependent and inconsistent parameters may explain divergent published reports.
  • Stated by the paper: in vitro myogenesis "more closely resembles embryonic muscle development" and may not recapitulate adult muscle repair after injury or exercise; specific study-level limitations noted include McGlory et al. not measuring total Akt/p70S6K1 protein content or post-translational modifications, Smith et al. not controlling diet and not collecting muscle biopsies, and the oestrogen-like explanation for sex differences being based on an animal model and described as "highly speculative."
  • Evident from the text (not framed as a limitation by the authors): the review is non-systematic, so the selection and weighting of cited studies is not transparent.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.3390/nu10030309

Cites

153 of 153 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 223 cited sources checked · 0 supported · 0 flagged

  • Premisecitation

    n-3 PUFAs alter skeletal muscle function.

    “and more recently alter skeletal muscle function”
    • Also stated in: § 1. Introduction · hedged
      “Accumulating evidence now indicates that n-3 PUFAs may additionally stimulate rates of muscle protein synthesis (MPS) by increasing both the intracellular activities of signalling molecules that are involved in the maintenance of skeletal muscle mass [46,47] and possibly satellite cell activity [48].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [46] McGlory, 2016, Fish oil supplementation suppresses resistance exercise and feeding-induced increases in anabolic signaling without affecting myofibrillar protein synthesis in young men, Physiol. Rep. source

      Not checked in the free run.

    • cites [47] Smith, 2011, Dietary omega-3 fatty acid supplementation increases the rate of muscle protein synthesis in older adults: A randomized controlled trial, Am. J. Clin. Nutr. source

      Not checked in the free run.

    • cites [48] Bhullar, 2016, Potential role of omega-3 fatty acids on the myogenic program of satellite cells, Nutr. Metab. Insights source

      Not checked in the free run.

  • Premisecitation

    Reduced sensitivity to anabolic stimuli, termed anabolic resistance, is implicated in the etiology of sarcopenia.

    “It is thought that this reduced sensitivity to anabolic stimuli, termed ”anabolic resistance”, is implicated in the etiology of sarcopenia, which is the gradual loss of muscle mass with age [2,3,4,5,6,7].”
    Quote in the paperSubstantial claim0 of 6 sources checked
    • cites [2] Cuthbertson, 2005, Anabolic signaling deficits underlie amino acid resistance of wasting, aging muscle, FASEB J. source

      Not checked in the free run.

    • cites [3] Wall, B.T., Gorissen, S.H., Pennings, B., Koopman, R., Groen, B.B., Verdijk, L.B., and van Loon, L.J. (2015). Aging is accompanied by a blunted muscle protein synthetic response to protein ingestion. PLoS ONE, 10. source

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    • cites [4] Brook, 2016, Synchronous deficits in cumulative muscle protein synthesis and ribosomal biogenesis underlie age-related anabolic resistance to exercise in humans, J. Physiol. source

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    • cites [5] Fry, 2011, Aging impairs contraction-induced human skeletal muscle mtorc1 signaling and protein synthesis, Skelet Muscle source

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    • cites [6] Rosenberg, 1997, Sarcopenia: Origins and clinical relevance, J. Nutr. source

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    • cites [7] Volpi, 2000, The response of muscle protein anabolism to combined hyperaminoacidemia and glucose-induced hyperinsulinemia is impaired in the elderly, J. Clin. Endocrinol. Metab.

      Not checked in the free run.

  • Premisecitation

    Satellite cells are primarily responsible for driving skeletal muscle repair in response to damaging stimuli such as exercise contraction.

    “Muscle stem cells commonly known as satellite cells, are primarily responsible for driving the skeletal muscle repair process to potentially damaging stimuli, such as mechanical stress elicited by exercise contraction.”
    • Also stated in: § 1. Introduction · plain
      “Satellite cells are muscle specific stem cells primarily responsible for the repair of muscle in response to injury [18,19,20].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [18] Relaix, 2009, Muscle stem cells, Curr. Opin. Cell Biol. source

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    • cites [19] Sambasivan, 2011, Pax7-expressing satellite cells are indispensable for adult skeletal muscle regeneration, Development source

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    • cites [20] McCarthy, 2011, Effective fiber hypertrophy in satellite cell-depleted skeletal muscle, Development source

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  • Premisecitation

    Throughout the lifespan of satellite cell depleted mice, sarcopenia is neither exacerbated nor accelerated.

    “However, throughout the lifespan of satellite cell depleted mice, sarcopenia is neither exacerbated nor accelerated [28,29].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [28] Keefe, 2015, Muscle stem cells contribute to myofibers in sedentary adult mice, Nat. Commun. source

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    • cites [29] Fry, 2015, Inducible depletion of satellite cells in adult, sedentary mice impairs muscle regenerative capacity but does not contribute to sarcopenia, Nat. Med. source

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  • Premisecitation

    n-3 PUFAs possess anti-inflammatory properties.

    “Omega-3 polyunsaturated fatty acids (n-3 PUFAs), which are commonly found in fish oil supplements, are known to possess anti-inflammatory properties”
    • Also stated in: § 1. Introduction · boosted
      “The n-3 PUFAs EPA and DHA are well known for their anti-inflammatory properties [41,42].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [41] Morin, 2017, Eicosapentaenoic acid monoglyceride resolves inflammation in an ex vivo model of human peripheral blood mononuclear cell, Eur. J. Pharmacol. source

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    • cites [42] Vedin, 2008, Effects of docosahexaenoic acid-rich n-3 fatty acid supplementation on cytokine release from blood mononuclear leukocytes: The omegad study, Am. J. Clin. Nutr. source

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  • May combine two claims. 56
  • Classified as probably not a substantial claim. 14

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    Premisecitation

    Satellite cells play a role in skeletal muscle repair, but their role in muscle hypertrophy is equivocal.

    “Satellite cells play a role in skeletal muscle repair; however their role in muscle hypertrophy is still equivocal (for reviews see [23,24]).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [23] Fukada, S.I. (2018). The roles of muscle stem cells in muscle injury, atrophy, and hypertrophy. J. Biochem. source

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    • cites [24] Murach, 2018, Starring or supporting role? Satellite cells and skeletal muscle fiber size regulation, Physiology source

      Not checked in the free run.

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    Premisecitation

    Sarcopenia is contributed to by reductions in circulating sex hormones, physical inactivity, low-grade inflammation, impairments to neuromuscular junctions, and reduced satellite cell number and function.

    “Other factors that are known to contribute to sarcopenia include reductions in circulating sex hormones [8], physical inactivity [9], low grade inflammation [10,11], impairments to neuromuscular junctions [12], and reduced muscle stem cell (i.e., satellite cell) number and function [13].”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [8] Janssen, 2002, Vitamin d deficiency, muscle function, and falls in elderly people, Am. J. Clin. Nutr. source

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    • cites [9] Szulc, 2004, Hormonal and lifestyle determinants of appendicular skeletal muscle mass in men: The minos study, Am. J. Clin. Nutr. source

      Not checked in the free run.

    • cites [10] Visser, 2002, Relationship of interleukin-6 and tumor necrosis factor-alpha with muscle mass and muscle strength in elderly men and women: The health abc study, J. Gerontol. A Biol. Sci. Med. Sci. source

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    • cites [11] McKay, 2013, Elevated SOCS3 and altered IL-6 signaling is associated with age-related human muscle stem cell dysfunction, Am. J. Physiol. Cell Physiol. source

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  • May combine two claims.

    Premisecitation

    Satellite cell depletion appears to cause dysregulation in the surrounding muscle environment leading to increased fibrosis with ageing and reduced muscle quality and function.

    “While satellite cell depleted mice do not show signs of increased muscle loss, satellite cell depletion appears to cause a dysregulation in the surrounding muscle environment leading to increased fibrosis with ageing and a reduction in muscle quality and function.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [26] Fry, 2014, Regulation of the muscle fiber microenvironment by activated satellite cells during hypertrophy, FASEB J. source

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    • cites [30] Fry, 2017, Myogenic progenitor cells control extracellular matrix production by fibroblasts during skeletal muscle hypertrophy, Cell Stem Cell source

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    • cites [31] Murphy, 2011, Satellite cells, connective tissue fibroblasts and their interactions are crucial for muscle regeneration, Development source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Myogenesis is regulated by changes in expression of myogenic transcriptional regulatory factors that dictate satellite cell state.

    “Myogenesis is regulated by changes in the expression of myogenic transcriptional regulatory factors (MRF) that dictate whether satellite cells are in a quiescent, activated, committed, or differentiated state [21,22] (Figure 1).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [21] Olguin, 2004, Pax-7 up-regulation inhibits myogenesis and cell cycle progression in satellite cells: A potential mechanism for self-renewal, Dev. Biol. source

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    • cites [22] Venuti, 1995, Myogenin is required for late but not early aspects of myogenesis during mouse development, J. Cell Biol. source

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    Premisecitation

    Sarcopenia is phenotypically associated with decreased muscle fiber size and a shift from fast to slow fiber type, resulting in decreased maximal muscle force production.

    “Sarcopenia is phenotypically associated with decreased muscle fiber size and shifts in fiber type change from fast to slow, resulting in a decrease in maximal muscle force production [14,15].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [14] Verdijk, 2007, Satellite cell content is specifically reduced in type II skeletal muscle fibers in the elderly, Am. J. Physiol. Endocrinol. Metab. source

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    • cites [15] Larsson, 1978, Histochemical and biochemical changes in human skeletal muscle with age in sedentary males, age 22–65 years, Acta Physiol. Scand. source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Skeletal muscle is highly malleable and can alter its phenotype in response to exercise and nutrient availability.

    “Skeletal muscle is a highly malleable tissue with the capacity to alter its phenotype in response to exercise and nutrient availability [1].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [1] Hawley, 2014, Integrative biology of exercise, Cell source

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  • May combine two claims.

    Interpretationreasoning

    Predominating evidence indicates that the presence and activation/myogenic capacity of satellite cells are indispensable for supporting training adaptations and may be implicated in events leading to sarcopenia.

    “Although the extent to which satellite cells facilitate muscle hypertrophic response is still a topic of debate, predominating evidence indicates that the presence and more likely the cells’ activation and myogenic capacity are indispensable for supporting training adaptations and may be implicated in the events leading to sarcopenia.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Upon activation, satellite cells enter the cell cycle, proliferate, differentiate to myoblasts and myocytes in myogenesis, and fuse to damaged muscle fibers.

    “Upon their activation, satellite cells enter the cell cycle, proliferate, differentiate to myoblasts and myocytes in a process termed myogenesis, and fuse to damaged muscle fibers.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [18] Relaix, 2009, Muscle stem cells, Curr. Opin. Cell Biol. source

      Not checked in the free run.

    • cites [19] Sambasivan, 2011, Pax7-expressing satellite cells are indispensable for adult skeletal muscle regeneration, Development source

      Not checked in the free run.

    • cites [20] McCarthy, 2011, Effective fiber hypertrophy in satellite cell-depleted skeletal muscle, Development source

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  • May combine two claims.

    Premisecitation

    Eicosanoids derived from n-3 PUFAs are considered less potent and reduce the intensity and duration of inflammatory responses by immune cells.

    “Conversely, eicosanoids derived from n-3 PUFAs are considered to be less potent, reducing the intensity and duration of the inflammatory responses by immune cells [62].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [62] Wada, 2007, Enzymes and receptors of prostaglandin pathways with arachidonic acid-derived versus eicosapentaenoic acid-derived substrates and products, J. Biol. Chem. source

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  • May combine two claims.

    Premisecitation

    Activation of NFκB increases expression of the atrogenes MuRF1 and atrogin-1, promoting muscle wasting.

    “Activation of NFκB subsequently increases the expression of the atrogenes muscle RING-finger protein-1 (MuRF1) and atrogin-1, promoting muscle wasting [68].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [68] Cai, 2004, Ikkbeta/nf-kappab activation causes severe muscle wasting in mice, Cell source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Only ALA is truly essential to the human diet; EPA and DHA can be synthesised from ALA in liver endoplasmic reticulum, though conversion is limited by enzyme availability.

    “Only ALA is considered truly essential to the human diet as both EPA and DHA can be synthesised in the endoplasmic reticulum in liver cells through conversion from ALA, though this conversion is limited due to enzyme availability [38,39,40].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [38] Burdge, 2002, Eicosapentaenoic and docosapentaenoic acids are the principal products of alpha-linolenic acid metabolism in young men, Br. J. Nutr. source

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    • cites [39] Burdge, 2002, Conversion of alpha-linolenic acid to eicosapentaenoic, docosapentaenoic and docosahexaenoic acids in young women, Br. J. Nutr. source

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    • cites [40] Arterburn, 2006, Distribution, interconversion, and dose response of n-3 fatty acids in humans, Am. J. Clin. Nutr. source

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    Premisecitation

    Eicosanoids derived from n-3 PUFAs are less biologically active than n-6 PUFAs and have weaker affinity for eicosanoid receptors.

    “This divergent behaviour is due to the fact that eicosanoids derived from n-3 PUFAs are less biologically active than n-6 PUFAs, and possess a weaker affinity for eicosanoid receptors [63,64,65].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [63] Kelley, 1997, Effects of dietary arachidonic acid on human immune response, Lipids source

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    • cites [64] Kelley, 1998, Arachidonic acid supplementation enhances synthesis of eicosanoids without suppressing immune functions in young healthy men, Lipids source

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    • cites [65] Phang, 2009, Inhibition of platelet aggregation by omega-3 polyunsaturated fatty acids is gender specific-redefining platelet response to fish oils, Prostaglandins Leukot Essent Fatty Acids source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    ALA is most abundant in plant foods, while EPA and DHA are abundant in cold-water fish.

    “ALA is most commonly abundant in plant foods, such as flax seed and nuts, while EPA and DHA are abundant in cold-water fish, such as salmon and tuna [36].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [36] Baker, 2016, Metabolism and functional effects of plant-derived omega-3 fatty acids in humans, Prog. Lipid Res. source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    DPA is an emerging n-3 PUFA that possesses a similar structure to EPA and is biochemically active.

    “In addition, Docosapentaenoic acid (DPA) is an emerging, but lesser known, n-3 PUFA that possesses a similar structure to EPA and is also biochemically active [37].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [37] Kaur, 2011, Docosapentaenoic acid (22:5n-3) down-regulates the expression of genes involved in fat synthesis in liver cells, Prostaglandins Leukot Essent Fatty Acids source

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  • May combine two claims.

    Interpretationreasoning

    The anti-inflammatory effects of n-3 PUFAs on skeletal muscle may be most beneficial to older individuals suffering from sarcopenia and may complement exercise and protein supplementation to combat sarcopenia.

    “As such, the anti-inflammatory effects of n-3 PUFAs on skeletal muscle may be most beneficial to older individuals suffering from sarcopenia [32,50,51] and may complement other strategies, such as exercise and protein supplementation, to combat sarcopenia.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [32] Smith, 2015, Fish oil-derived n-3 pufa therapy increases muscle mass and function in healthy older adults, Am. J. Clin. Nutr. source

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    • cites [50] Millward, 2012, Nutrition and sarcopenia: Evidence for an interaction, Proc. Nutr. Soc. source

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    • cites [51] Phillips, 2015, Nutritional supplements in support of resistance exercise to counter age-related sarcopenia, Adv. Nutr. source

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    Premisecitation

    TNF-α and IL-6 inhibition of differentiation involves downregulation of MyoD and Myogenin; TNF-α receptor double knockout and IL-6 knockout mice show impaired myogenic differentiation and hypertrophy during functional overloading.

    “This inhibition involves the down regulation of the MRFs, MyoD and Myogenin [73,74,75], with TNF-α receptor double knock out mice [74] and with IL-6 non-specific knock out mice [73] shown to present impaired myogenic differentiation and hypertrophy when compared to wild type mice during functional overloading.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [73] Serrano, 2008, Interleukin-6 is an essential regulator of satellite cell-mediated skeletal muscle hypertrophy, Cell Metab. source

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    • cites [74] Chen, 2005, Role of tnf-{alpha} signaling in regeneration of cardiotoxin-injured muscle, Am. J. Physiol. Cell Physiol. source

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    • cites [75] Langen, 2004, Tumor necrosis factor-alpha inhibits myogenic differentiation through myod protein destabilization, FASEB J. source

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    Premisecitation

    Failure to resolve inflammation at its onset, resulting in chronic inflammation, can be detrimental and is associated with insulin resistance, obesity, and muscle wasting.

    “However, failure to effectively resolve inflammation at its onset which results in a chronic state of inflammation can be detrimental and is associated with insulin resistance, obesity, and muscle wasting [56,57,58].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [56] Sindhu, S., Thomas, R., Shihab, P., Sriraman, D., Behbehani, K., and Ahmad, R. (2015). Obesity is a positive modulator of IL-6R and IL-6 expression in the subcutaneous adipose tissue: Significance for metabolic inflammation. PLoS ONE, 10. source

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    • cites [57] Feinstein, 1993, Tumor necrosis factor-alpha suppresses insulin-induced tyrosine phosphorylation of insulin receptor and its substrates, J. Biol. Chem. source

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    • cites [58] Hotamisligil, 1993, Adipose expression of tumor necrosis factor-alpha: Direct role in obesity-linked insulin resistance, Science source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    EPA, DHA, and ALA are the most commonly found n-3 PUFAs in the human diet.

    “Eicosapentaenoic acid (EPA), Docosahexaenoic acid (DHA), and α-linolenic acid (ALA) are the most commonly found n-3 PUFAs in the human diet [35].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [35] Simopoulos, 2000, Human requirement for n-3 polyunsaturated fatty acids, Poult. Sci. source

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  • May combine two claims.

    Premisecitation

    DHA treatment of C2C12 myoblasts attenuates inhibitory effects of palmitate on PGC-1α activity and preserves oxidative capacity by maintaining citrate synthase activity.

    “Likewise, others have shown that DHA treatment of C2C12 myoblasts attenuates the inhibitory effects of palmitate on PGC-1α activity and preserves oxidative capacity by maintaining citrate synthase activity [96].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [96] Bryner, 2012, Docosahexaenoic acid protects muscle cells from palmitate-induced atrophy, ISRN Obes.

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    Premisecitation

    The protective effects of EPA are associated with increases in PPARγ expression and decreases in NF-κB.

    “These protective effects of EPA are associated with increases in PPARγ expression and decreases in NF-κB [88].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [88] Magee, 2012, Ppargamma as a molecular target of epa anti-inflammatory activity during tnf-alpha-impaired skeletal muscle cell differentiation, J. Nutr. Biochem. source

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  • May combine two claims.

    Interpretationcitation

    n-3 PUFAs may assist in muscle regeneration in older individuals by reducing excessive inflammation and promoting a systemic environment more conducive to growth.

    “Therefore, n-3 PUFAs may assist in muscle regeneration in older individuals by reducing excessive inflammation and promoting a systemic environment more conducive to growth [99] (see Section 2.3).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [99] Rieu, 2009, Reduction of low grade inflammation restores blunting of postprandial muscle anabolism and limits sarcopenia in old rats, J. Physiol. source

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  • May combine two claims.

    Interpretationreasoning

    The anti-inflammatory properties of n-3 PUFAs and their incorporation into membrane phospholipids may underpin other beneficial effects in muscle, such as altering protein metabolism, increasing muscle strength, and modulating myogenesis.

    “The anti-inflammatory properties of n-3 PUFAs and their incorporation into membrane phospholipids may also underpin some of their other beneficial effects in muscle, such as altering protein metabolism, increasing muscle strength and modulating myogenesis.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Lipids such as n-3 PUFAs can bind to PPARs, inducing activation and altering expression of pro-inflammatory genes.

    “Recent evidence suggests that lipids, such as n-3 PUFAs, are capable of binding to PPARs inducing their activation and altering the expression of pro-inflammatory genes [86].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [86] Fritsche, 2015, The science of fatty acids and inflammation, Adv. Nutr. source

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    Premisecitation

    PPARδ is abundantly expressed in skeletal muscle and has a role in regulating satellite cell activity.

    “PPARδ is another isoform of PPAR abundantly expressed in skeletal muscle that has a novel role in regulating satellite cell activity [89].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [89] Angione, 2011, Pparδ regulates satellite cell proliferation and skeletal muscle regeneration, Skeletal Muscle source

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    Premisecitation

    Overexpressing PGC-1α in C2C12 cells promotes differentiation and increases MyoD and Myogenin expression.

    “Moreover, overexpressing PGC-1α in C2C12 cells has been shown to promote differentiation and increase the expression of MyoD and Myogenin, however, it remains to be seen whether n-3 PUFAs can elicit similar responses in both PGC-1α and MRF expression during differentiation [93].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [93] Lin, 2014, Pgc-1α is associated with c2c12 myoblast differentiation, Cent. Eur. J. Biol.

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    Premisecitation

    PGC-1α can repress transcriptional activity of NF-kB, lowering inflammation in muscle cells.

    “Like PPARs, the peroxisome proliferator-activated receptor gamma co-activator 1-alpha (PGC-1α) is also capable of repressing the transcriptional activity of NF-kB lowering inflammation in muscle cells [90].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [90] Eisele, 2013, The peroxisome proliferator-activated receptor gamma coactivator 1α/β (PGC-1) coactivators repress the transcriptional activity of NF-κB in skeletal muscle cells, J. Biol. Chem. source

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  • May combine two claims.

    Interpretationreasoning

    n-3 PUFAs are able to increase expression of PPAR and reduce expression of NF-κB in skeletal muscle, resulting in reduced muscle wasting.

    “These findings collectively indicate that n-3 PUFAs are able to increase the expression of PPAR and reduce the expression of NF-κB in skeletal muscle resulting in reduced muscle wasting [69,72].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [69] Wang, 2013, Dha inhibits protein degradation more efficiently than epa by regulating the ppargamma/nfkappab pathway in c2c12 myotubes, Biomed. Res. Int.

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    • cites [72] Huang, 2011, EPA inhibits the inhibitor of kappabalpha (IκBα)/NF-κB/muscle ring finger 1 pathway in C2C12 myotubes in a PPARγ-dependent manner, Br. J. Nutr. source

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  • May combine two claims.

    Premisecitation

    Elevations in circulating pro-inflammatory cytokines in older individuals negatively impact muscle regeneration by impairing satellite cell differentiation and fusion and increasing NF-κB activation, contributing to deterioration of muscle mass with age.

    “Elevations in circulating pro-inflammatory cytokines reported in older individuals negatively impacts muscle regeneration by impairing satellite cell differentiation and fusion and by increasing NF-κB activation. These factors contribute to deterioration of muscle mass with age [59,77].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [59] Merritt, 2013, Heightened muscle inflammation susceptibility may impair regenerative capacity in aging humans, J. Appl. Physiol. source

      Not checked in the free run.

    • cites [77] Carnac, 2014, The influence of systemic inflammation on skeletal muscle in physically active elderly women, Age source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    n-3 PUFAs EPA and DHA can reduce inflammation via incorporation into membrane phospholipids, inhibiting production of pro-inflammatory eicosanoids and reducing activation of immune cells and release of pro-inflammatory cytokines.

    “In summary, the n-3 PUFAs EPA and DHA can reduce inflammation via their incorporation into membrane phospholipids, where they inhibit the production of pro-inflammatory eicosanoids, reducing of activation of immune cells and the associated release of pro-inflammatory cytokines [71,97,98].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [71] Williams-Bey, Y., Boularan, C., Vural, A., Huang, N.N., Hwang, I.Y., Shan-Shi, C., and Kehrl, J.H. (2014). Omega-3 free fatty acids suppress macrophage inflammasome activation by inhibiting nf-κb activation and enhancing autophagy. PLoS ONE, 9. source

      Not checked in the free run.

    • cites [97] Endres, 1989, The effect of dietary supplementation with n-3 polyunsaturated fatty acids on the synthesis of interleukin-1 and tumor necrosis factor by mononuclear cells, N. Engl. J. Med. source

      Not checked in the free run.

    • cites [98] Oh, 2010, GPR120 is an omega-3 fatty acid receptor mediating potent anti-inflammatory and insulin-sensitizing effects, Cell source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationcitation

    Increases in mitochondrial biogenesis following n-3 PUFA treatment could be compensatory to dispose of excess fatty acids more efficiently.

    “As fatty acid oxidation occurs within mitochondria, the increases in mitochondrial biogenesis seen following n-3 PUFA treatment could be compensatory as a means of disposing of excess fatty acids more efficiently, which requires more mitochondria [94].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [94] Hancock, 2008, High-fat diets cause insulin resistance despite an increase in muscle mitochondria, Proc. Natl. Acad. Sci. USA source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Changes in membrane lipid composition impact membrane fluidity and assist myoblast fusion during myotube formation, allowing n-3 PUFAs to modulate several signalling pathways.

    “These changes impact membrane fluidity and assist in myoblast fusion during myotube formation [81], allowing for n-3 PUFAs to simultaneously modulate several signalling pathways.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [81] Mukai, 2009, Dynamic clustering and dispersion of lipid rafts contribute to fusion competence of myogenic cells, Exp. Cell Res. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    EPA and DHA ameliorate lipotoxic effects of palmitate in fully formed myotubes and increase expression of mitochondrial β-oxidation markers CPT1α and CPT1β.

    “Indeed, EPA and DHA ameliorate the lipotoxic effects of other fatty acids such as palmitate in fully formed myotubes and increase the expression that is associated with mitochondrial-β oxidation, such as carnitine palmitol transferase 1α and β (CPT1α; CPT1β) [95].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [95] Pinel, 2016, N-3pufa differentially modulate palmitate-induced lipotoxicity through alterations of its metabolism in C2C12 muscle cells, Biochim. Biophys. Acta source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Treating C2C12 myotubes with high concentrations (400-600 μM) of EPA or DHA increases PPARγ gene expression and reduces muscle breakdown.

    “Moreover, treating C2C12 myotubes with high concentrations (400–600 µM) of EPA or DHA has also been shown to increase the gene expression of PPARγ and reduce muscle breakdown (Huang et al., 2011; Wang et al., 2013).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Huang et al., 2011 source

      Not checked in the free run.

    • cites Wang et al., 2013

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    PPARs are nuclear receptors that prevent metabolic disorders, promote skeletal muscle adaptations following fasting and exercise, and regulate satellite cell activity.

    “One such pathway involves the Peroxisome proliferator-activated receptors (PPARs), which are a group of nuclear receptors that are well characterised in preventing metabolic disorders, promoting adaptations to skeletal muscle following fasting and physical exercise, and have a novel role in regulating satellite cell activity [82,83,84].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [82] Grimaldi, 2005, Regulatory role of peroxisome proliferator-activated receptor delta (ppar delta) in muscle metabolism. A new target for metabolic syndrome treatment?, Biochimie source

      Not checked in the free run.

    • cites [83] Chandrashekar, 2015, Inactivation of pparbeta/delta adversely affects satellite cells and reduces postnatal myogenesis, Am. J. Physiol. Endocrinol. Metab. source

      Not checked in the free run.

    • cites [84] Deng, 2016, Myod promotes porcine ppargamma gene expression through an e-box and a myod-binding site in the ppargamma promoter region, Cell Tissue Res. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In response to injury, PPARδ-KO mice display reductions in proliferating satellite cell number and increases in differentiating cell number compared to wild type.

    “In response to injury PPARδ-KO mice when compared to wild type mice, display reductions in proliferating satellite cell number and increases in differentiating cell number [89].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [89] Angione, 2011, Pparδ regulates satellite cell proliferation and skeletal muscle regeneration, Skeletal Muscle source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The combination of resistance exercise and protein ingestion maximally stimulates rates of muscle protein synthesis and leads to increases in satellite cell activity and content in younger men.

    “The combination of resistance exercise and protein ingestion is known to maximally stimulate rates of muscle protein synthesis (MPS) [100,101,102] and also lead to increases in satellite cell activity [103] and content in younger men [104].”
    Quote in the paperNot a substantial claim0 of 5 sources checked
    • cites [100] Moore, 2009, Ingested protein dose response of muscle and albumin protein synthesis after resistance exercise in young men, Am. J. Clin. Nutr. source

      Not checked in the free run.

    • cites [101] MacDougall, 1995, The time course for elevated muscle protein synthesis following heavy resistance exercise, Can. J. Appl. Physiol. source

      Not checked in the free run.

    • cites [102] Witard, 2014, Myofibrillar muscle protein synthesis rates subsequent to a meal in response to increasing doses of whey protein at rest and after resistance exercise, Am. J. Clin. Nutr. source

      Not checked in the free run.

    • cites [103] Hulmi, 2008, The effects of whey protein on myostatin and cell cycle-related gene expression responses to a single heavy resistance exercise bout in trained older men, Eur J. Appl. Physiol. source

      Not checked in the free run.

    • cites [104] Farup, 2014, Whey protein supplementation accelerates satellite cell proliferation during recovery from eccentric exercise, Amino Acids source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductcitation

    A major limitation of McGlory et al. is that they did not measure total protein content of Akt and p70S6K1 nor specific post-translational modifications of these proteins.

    “While it is possible that changes to protein signalling efficiency occur, a major limitation of the study conducted by McGlory et al. [46] is that they did not measure any changes in the total protein content of Akt and p70S6K1 nor did they measure any specific post-translational modifications of these proteins (i.e., altered phosphorylation at numerous sites).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [46] McGlory, 2016, Fish oil supplementation suppresses resistance exercise and feeding-induced increases in anabolic signaling without affecting myofibrillar protein synthesis in young men, Physiol. Rep. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Circulating growth factors GDF11 and myostatin, as well as inflammatory markers TNF-α and IL-6, increase with age, impairing regenerative capacity of satellite cells in human skeletal muscle.

    “For instance, circulating growth factors, such as GDF11 and myostatin, as well as inflammatory markers, such as TNF-α and IL-6, increase with age, impairing the regenerative capacity of satellite cells in human skeletal muscle [10,115].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [10] Visser, 2002, Relationship of interleukin-6 and tumor necrosis factor-alpha with muscle mass and muscle strength in elderly men and women: The health abc study, J. Gerontol. A Biol. Sci. Med. Sci. source

      Not checked in the free run.

    • cites [115] Egerman, 2015, Gdf11 increases with age and inhibits skeletal muscle regeneration, Cell Metab. source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductcitation

    In the study by Smith et al., diet was not controlled, which may magnify and misrepresent the effects of n-3 PUFA supplementation on muscle area.

    “However, in the study that was conducted by Smith et al. diet was not controlled, which may magnify and thus misrepresent the effects of n-3 PUFA supplementation on muscle area [32].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [32] Smith, 2015, Fish oil-derived n-3 pufa therapy increases muscle mass and function in healthy older adults, Am. J. Clin. Nutr. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    After four weeks of supplementation, EPA and DHA levels continue to rise in muscle, whereas blood levels plateau at two weeks.

    “Previously, the same group has shown that after four weeks of supplementation, levels of EPA and DHA continue to rise in muscle (~3.0% of total fatty acids in muscle at week 2 and ~5.0% of total fatty acids in muscle at week 4), whereas levels of EPA and DHA in blood plateau at two weeks with no further increase at four weeks (~8.0% at week 2 and ~8.0% at week 4) [106].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [106] McGlory, 2014, Temporal changes in human skeletal muscle and blood lipid composition with fish oil supplementation, Prostaglandins Leukot Essent Fatty Acids source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Parabiosis experiments in mice indicate that ageing reduces satellite cell activity, and exposing cells to a more youthful systemic environment improves regenerative capacity, indicating that age-related reduction in satellite cell activity can be modulated by systemic factors that change with age.

    “Further evidence from parabiosis experiments in mice indicate that ageing reduces satellite cell activity; however exposing cells to a more youthful systemic environment and improves the regenerative capacity of satellite cells indicating that the age-related reduction in satellite cell activity can be modulated by systemic factors that change with age [116,117].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [116] Conboy, 2005, Rejuvenation of aged progenitor cells by exposure to a young systemic environment, Nature source

      Not checked in the free run.

    • cites [117] Calder, 2017, Health relevance of the modification of low grade inflammation in ageing (inflammageing) and the role of nutrition, Ageing Res. Rev. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Supplementation of 4 g/day for six months increases whole thigh muscle area, 1-RM strength, and isokinetic power.

    “Indeed, supplementation of 4 g/day for six months results in increased whole thigh muscle area, 1-RM strength and isokinetic power [32].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [32] Smith, 2015, Fish oil-derived n-3 pufa therapy increases muscle mass and function in healthy older adults, Am. J. Clin. Nutr. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    EPA and DHA increase nerve conduction velocity in young and older individuals through modulation of sarcolemma ion channels, improving contractile activity of muscle.

    “These fatty acids are known to increase nerve conduction velocity in both young and older individuals through the modulation of sarcolemma ion channels which, in turn, improves contractile activity of the muscle [106,107,108,109,110].”
    Quote in the paperSubstantial claim0 of 5 sources checked
    • cites [106] McGlory, 2014, Temporal changes in human skeletal muscle and blood lipid composition with fish oil supplementation, Prostaglandins Leukot Essent Fatty Acids source

      Not checked in the free run.

    • cites [107] Lauretani, 2007, Omega-6 and omega-3 fatty acids predict accelerated decline of peripheral nerve function in older persons, Eur J. Neurol. source

      Not checked in the free run.

    • cites [108] Kang, 1994, Effects of long-chain polyunsaturated fatty acids on the contraction of neonatal rat cardiac myocytes, Proc. Natl. Acad. Sci. USA source

      Not checked in the free run.

    • cites [109] Perez, 2002, Direct and indirect modulation of rat cardiac sarcoplasmic reticulum function by n-3 polyunsaturated fatty acids, J. Physiol. source

      Not checked in the free run.

    • cites [110] Lewis, 2015, 21 Days of mammalian omega-3 fatty acid supplementation improves aspects of neuromuscular function and performance in male athletes compared to olive oil placebo, J. Int. Soc. Sports Nutr. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    n-3 PUFAs may have the potential to preserve muscle mass by keeping cells in a quiescent state, preserving the satellite pool, or at least delaying their inevitable activation following induction of differentiation in vitro.

    “Thus, n-3 PUFAs may have the potential to preserve muscle mass by keeping cells in a quiescent state preserving the satellite pool or at least delay their inevitable activation following the induction of differentiation in vitro.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    EPA has no effect on proliferation rate of C2C12 cells at concentrations of 0.1-10 μM even when treated for 48 h, while DHA proliferative stimulation starts at 10 μM.

    “In contrast, EPA has no effect on proliferation rate of C2C12 cells at concentration of 0.1–10 µM even though treated for 48 h, while DHA proliferative stimulation starts at 10 µM [140].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [140] Lee, 2009, Modulation of proliferation and differentiation of c2c12 skeletal muscle cells by fatty acids, Life Sci. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Interpretationreasoning

    Dose discrepancies may arise due to regional differences in availability of certain n-3 PUFA supplements, whereas duration discrepancies may be due to the research question being asked.

    “These dose discrepancies may arise due to regional differences in the availability of certain n-3 PUFA supplements, whereas discrepancies in the duration of the supplementation may due to the research question being asked (i.e., acute MPS responses vs chronic changes in lean mass).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationnone given

    Studying in vitro myogenesis provides mechanistic insight into processes underlying muscle development and regeneration, but it more closely resembles embryonic muscle development and does not necessarily recapitulate what occurs during myogenesis in adult muscle following injury or exercise.

    “Furthermore, while studying in vitro myogenesis provides mechanistic insight into the processes underlying muscle development and regeneration, it more closely resembles embryonic muscle development and does not necessarily recapitulate what occurs during myogenesis in adult muscle following injury or exercise.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    EPA exclusively augments leucine-induced MPS in fully differentiated C2C12 myotubes and increases phosphorylation of p70S6K1, with no changes in phosphorylation of other anabolic mTOR pathway members.

    “However, EPA exclusively augments leucine induced MPS in fully differentiated C2C12 myotubes and increases the phosphorylation of p70S6K1, with no changes in the phosphorylation of any of the other anabolic mTOR pathway members [122].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [122] Kamolrat, 2013, The effect of eicosapentaenoic and docosahexaenoic acid on protein synthesis and breakdown in murine C2C12 myotubes, Biochem. Biophys. Res. Commun. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Changes to p70S6K1 activity and phosphorylation can occur without prior changes to Akt, suggesting n-3 PUFAs are capable of modulating differentiation and MPS independently of canonical mTOR signalling.

    “The fact that changes to p70S6K1 activity [46] and phosphorylation [79] can occur without prior changes to Akt, suggests that n-3 PUFAs are capable of modulating differentiation and MPS independently of canonical mTOR signalling.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [46] McGlory, 2016, Fish oil supplementation suppresses resistance exercise and feeding-induced increases in anabolic signaling without affecting myofibrillar protein synthesis in young men, Physiol. Rep. source

      Not checked in the free run.

    • cites [79] Briolay, 2013, Myogenic differentiation and lipid-raft composition of l6 skeletal muscle cells are modulated by pufas, Biochim. Biophys. Acta source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    During proliferation, ERK1/2 expression is increased, promoting proliferation and inhibiting differentiation.

    “During proliferation, ERK1/2 expression is increased, promoting proliferation and inhibiting differentiation [127,128].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [127] Volonte, 2005, The modulation of caveolin-1 expression controls satellite cell activation during muscle repair, FASEB J. source

      Not checked in the free run.

    • cites [128] Kook, 2008, Cyclic mechanical stress suppresses myogenic differentiation of adult bovine satellite cells through activation of extracellular signal-regulated kinase, Mol. Cell. Biochem. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    When C2C12 cells are proliferated in the absence of n-3 PUFAs for 24 h, they continue through the cell cycle, demonstrating that n-3 PUFAs can regulate a return to quiescence, keeping cells in G1 phase.

    “When the same cells are proliferated in the absence of n-3 PUFAs for 24 h, they continue through the cell cycle, which is noteworthy as it demonstrates that n-3 PUFAs can regulate a return to quiescence, keeping the cells in the G1 phase.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [131] Peng, 2012, Different effects of omega-3 fatty acids on the cell cycle in c2c12 myoblast proliferation, Mol. Cell. Biochem. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Exposure to EPA and DHA at higher concentrations (20-100 μM) for 24 h slows down cell growth rate by preventing transition of C2C12 cells from G1 to S phase, with DHA having a more pronounced effect.

    “Exposure to EPA and DHA at higher concentrations (20–100 µM) for 24 h slows down the cell growth rate by preventing the transition of C2C12 cells from G1 to S phase of the cell cycle with DHA having a more pronounced effect [131].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [131] Peng, 2012, Different effects of omega-3 fatty acids on the cell cycle in c2c12 myoblast proliferation, Mol. Cell. Biochem. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    EPA and DHA can elicit both similar and differential effects during various stages of myogenesis and in fully differentiated myotubes.

    “It is evident that EPA and DHA can elicit both similar and differential effects during various stages of myogenesis (Table 1), but also in full differentiated myotubes (Table 2).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    The effects of n-3 PUFA in vitro are dose and time dependent, and an accurate balance between those parameters is required to significantly augment in vitro proliferation, differentiation, and post-differentiation events.

    “It is important to highlight that the effects of n-3 PUFA in vitro are dose and time dependent and an accurate balance between those parameters is required to significantly augment in vitro proliferation, differentiation, and post-differentiation events.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisenone given

    50 μM of both EPA and DHA promote myogenic responses during differentiation in C2C12 cells, while other cell lines such as L6 rat cells are sensitive to 20 μM of EPA and DHA.

    “While 50 μM of both EPA and DHA promote myogenic responses during differentiation in C2C12 cells (Table 1), other cell lines such as L6 rat cells are sensitive to 20 μM of EPA and DHA.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    DPA is a biologically active n-3 PUFA with similar properties to DHA and EPA and can also be readily converted to EPA.

    “This represents an area for future investigations as DPA is a biologically active n-3 PUFA with similar properties to DHA and EPA and can also be readily converted to EPA [37,149,150].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [37] Kaur, 2011, Docosapentaenoic acid (22:5n-3) down-regulates the expression of genes involved in fat synthesis in liver cells, Prostaglandins Leukot Essent Fatty Acids source

      Not checked in the free run.

    • cites [149] Pawar, 2003, Unsaturated fatty acid regulation of peroxisome proliferator-activated receptor alpha activity in rat primary hepatocytes, J. Biol. Chem. source

      Not checked in the free run.

    • cites [150] Kishida, 2006, Docosahexaenoic acid enrichment can reduce l929 cell necrosis induced by tumor necrosis factor, Biochim. Biophys. Acta source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationnone given

    The in vitro effects of DPA on myogenesis remain largely understudied.

    “Furthermore, the in vitro effects of DPA on myogenesis remain largely understudied.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Interpretationreasoning

    n-3 PUFAs may possess the capacity to alter satellite cell activity directly by altering proliferation and differentiation or indirectly via changes to the ECM.

    “Thus, n-3 PUFAs may possess the capacity to alter satellite cell activity directly by altering proliferation and differentiation or indirectly via changes to the ECM.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Interpretationnone given

    The optimal dosage and duration required to elicit beneficial responses in skeletal muscle remains unclear.

    “Firstly, the optimal dosage and duration required to elicit beneficial responses in skeletal muscle remains unclear.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisenone given

    The anti-lipotoxic and anti-cytotoxic properties of EPA and DHA during in vitro myogenesis have been established, with 50 μM being an effective concentration to induce protective effects.

    “The anti-lipotoxic and anti-cytotoxic properties of EPA and DHA during in vitro myogenesis have been established with 50 µM being an effective concentration to induce protective effects.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Interpretationcitation

    Small n-3 PUFA-induced transcriptional changes in pathways related to growth and ECM organization could modulate satellite cell function given the reciprocal relationship between fibroblasts and satellite cells.

    “These small n-3 PUFA-induced transcriptional changes in pathways related to growth and ECM organization could modulate satellite cell function given the reciprocal relationship between fibroblasts and satellite cells [31].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [31] Murphy, 2011, Satellite cells, connective tissue fibroblasts and their interactions are crucial for muscle regeneration, Development source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Interpretationnone given

    Several questions remain unanswered regarding n-3 PUFA supplementation and human skeletal muscle metabolism.

    “However, several questions remain unanswered regarding n-3 PUFA supplementation and human skeletal muscle metabolism.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Interpretationnone given

    Other sexual dimorphisms may also exist following n-3 PUFA supplementation, such as changes to anabolic signalling activity and rates of MPS, though no study to date has been able to detect these changes.

    “Other sexual dimorphisms may also exist following n-3 PUFA supplementation, such as changes to anabolic signalling activity and rates of MPS, though no study to date has been able to detect these changes.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    n-3 PUFAs are capable of reducing systemic inflammation by inhibiting release of pro-inflammatory cytokines from immune cells and improving signalling efficiency of proteins involved in growth and hypertrophy.

    “n-3 PUFAs are also capable of reducing systemic inflammation by inhibiting the release of pro-inflammatory cytokines from immune cells [151,152,153] and improving the signalling efficiency of proteins that are involved in growth and hypertrophy [46,72,79].”
    Quote in the paperSubstantial claim0 of 6 sources checked
    • cites [151] Lo, 2000, Fish oil modulates macrophage p44/p42 mitogen-activated protein kinase activity induced by lipopolysaccharide, JPEN J. Parenter Enter. Nutr. source

      Not checked in the free run.

    • cites [152] Weldon, 2007, Docosahexaenoic acid induces an anti-inflammatory profile in lipopolysaccharide-stimulated human thp-1 macrophages more effectively than eicosapentaenoic acid, J. Nutr. Biochem. source

      Not checked in the free run.

    • cites [153] Mullen, 2010, Anti-inflammatory effects of epa and dha are dependent upon time and dose-response elements associated with lps stimulation in thp-1-derived macrophages, J. Nutr. Biochem. source

      Not checked in the free run.

    • cites [46] McGlory, 2016, Fish oil supplementation suppresses resistance exercise and feeding-induced increases in anabolic signaling without affecting myofibrillar protein synthesis in young men, Physiol. Rep. source

      Not checked in the free run.

    • cites [72] Huang, 2011, EPA inhibits the inhibitor of kappabalpha (IκBα)/NF-κB/muscle ring finger 1 pathway in C2C12 myotubes in a PPARγ-dependent manner, Br. J. Nutr. source

      Not checked in the free run.

    • cites [79] Briolay, 2013, Myogenic differentiation and lipid-raft composition of l6 skeletal muscle cells are modulated by pufas, Biochim. Biophys. Acta source

      Not checked in the free run.

64 of 64

  • The paper relies on this without support.

    There is a paucity of human investigations related to the effects of n-3 PUFAs on satellite cell content and activity.

    “To date, there is a paucity of human investigations related to the effects of n-3 PUFAs on satellite cell content and activity.”

  • The paper relies on this without support.

    The precise molecular mechanisms responsible for sarcopenia are yet to be elucidated.

    “The precise molecular mechanisms responsible for sarcopenia are yet to be elucidated, however, accumulating evidence indicates that nutritional supplements, in particular the omega 3 polyunsaturated fatty acids (n-3 PUFAs), have the potential to reduce muscle wasting and increase the functional capacity of muscle in older individuals by augmenting intracellular anabolic signalling [32,33,34].”

  • The paper relies on this without support.

    No study to date has demonstrated a causal link between GDF11 and myostatin and their ability to affect the regenerative capacity of muscle.

    “Though it is important to note that while GDF11 and myostatin have been correlated with increased ageing in humans, no study to date has demonstrated a causal link between these circulating factors and their ability to affect the regenerative capacity of muscle.”
3 of 3

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • EPA and DHA act as substrates for the synthesis of lipid-derived mediators of inflammation, eicosanoids, whose ability to mediate inflammation varies by substrate; eicosanoids derived from arachidonic acid, an omega-6 PUFA, are considered pro-inflammatory.

    “EPA and DHA act as substrates for the synthesis of lipid-derived mediators of inflammation. These mediators, termed eicosanoids, vary in their ability to mediate inflammation depending on the substrate used for their synthesis. For example, eicosanoids derived from arachidonic acid, an omega-6 PUFA, are considered to be pro-inflammatory [28].”

    From Novel Insights on Intake of Fish and Prevention of Sarcopenia: All Reasons for an Adequate Consumption (2020) · cites this paper as [28]

  • Omega-3 PUFAs are able to reduce muscle wasting by increasing functional capacity in the elderly by growing the intracellular metabolic signal.

    “Several evidences indicate that omega-3 PUFAs are able to reduce muscle wasting by increasing the functional capacity in the elderly by growing the intracellular metabolic signal [27,28].”

    From Novel Insights on Intake of Fish and Prevention of Sarcopenia: All Reasons for an Adequate Consumption (2020) · cites this paper as [28]

  • In the elderly, a high presence of pro-inflammatory cytokines prevents proper muscle regeneration by impairing satellite cell differentiation and fusion and by increasing activation of NF-KB transcription factors, thereby contributing to deterioration of muscle mass with age.

    “In the elderly, a high presence of pro-inflammatory cytokines prevents proper muscle regeneration by impairing satellite cell differentiation and fusion and by increasing the activation of nuclear factor-KB (NF-KB) transcription factors, thereby contributing to the deterioration of muscle mass with age [28].”

    From Novel Insights on Intake of Fish and Prevention of Sarcopenia: All Reasons for an Adequate Consumption (2020) · cites this paper as [28]

  • The most common omega-3 PUFAs in the diet are ALA, present in plants and seeds, and DHA and EPA, present especially in cold water fish such as salmon and tuna.

    “The most common omega-3 PUFAs in the diet are α-linolenic acid (ALA) present in plants and seeds, and docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) that are both present especially in cold water fish species such as salmon and tuna [28].”

    From Novel Insights on Intake of Fish and Prevention of Sarcopenia: All Reasons for an Adequate Consumption (2020) · cites this paper as [28]

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Authors
Tachtsis, B., Camera, D., & Lacham-Kaplan, O.
Affiliations
  • Australian Catholic University (AU)
  • Mary MacKillop Institute for Health Research, Exercise and Nutrition Research Program, Australian Catholic University, Melbourne, VIC 3000, Australia
ORCID
Venue
Nutrients
Publisher
MDPI AG
Published
2018-03-05
Volume
10
Issue
3
Pages
309
ISSN
2072-6643 (ISSN-L)
DOI
10.3390/nu10030309
PMC
PMC5872727
OpenAlex
W2793735505
Cited by
104
References
153
Citations by year
2026: 2 · 2025: 11 · 2024: 13 · 2023: 16 · 2022: 12 · 2021: 13 · 2020: 18 · 2019: 14 · 2018: 4 · 2017: 1
FWCI
1.57
Type
journal article
Language
en
Open access
Licence
Locations
  • Nutrients (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Research Bank (Australian Catholic University) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Australian Catholic University
Topics
  • Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
Keywords
omega-3 fatty acids, fish oil supplementation, skeletal muscle growth, muscle hypertrophy, muscle regeneration, satellite cells, muscle stem cells, anti-inflammatory signaling, physical activity, muscle atrophy, muscle mass and strength
MeSH terms
Animals, Energy Metabolism, Humans, Hypertrophy, Regeneration, Signal Transduction, Fatty Acids, Omega-3, Muscle, Skeletal, Muscle Development, Satellite Cells, Skeletal Muscle, Muscle Strength, Sarcopenia

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-10.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-10.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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