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Current Landscape of Pharmacotherapies for Sarcopenia
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<blockquote data-quote="madman" data-source="post: 275537" data-attributes="member: 13851"><p><em><strong>*In conclusion, omega-3 fatty acids may improve sarcopenia, but well-designed, large prospective cohort studies and randomized controlled trials are needed to confirm these findings.</strong></em></p><p></p><p></p><p></p><h3>2.3. Omega-3 fatty acids</h3><p><em>Omega-3 fatty acids (also known as n-3 fatty acids) are polyunsaturated fatty acids with many potential health benefits and are available in three main dietary forms: alpha-linolenic acid (ALA; 18:3n-3), eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3). ALA is considered an essential fatty acid because it cannot be synthesized in the human body and is found in nuts, seeds, canola oil, etc. EPA and DHA are mainly found in fish oil.</em></p><p></p><h4><strong>2.3.1. Mechanisms</strong></h4><p><em>Skeletal muscle atrophy involves an inflammatory phase that leads to cell death and tissue remodeling and activates endoplasmic reticulum stress (ERS) and autophagy (<a href="https://www.frontiersin.org/articles/10.3389/fnut.2023.1189522/full#B96" target="_blank">96</a>, <a href="https://www.frontiersin.org/articles/10.3389/fnut.2023.1189522/full#B97" target="_blank">97</a>).<strong> Both EPA and DHA potentially attenuate ERS and autophagy in skeletal muscles undergoing atrophy by attenuating the increase in PERK and ATG14 expression (<a href="https://www.frontiersin.org/articles/10.3389/fnut.2023.1189522/full#B98" target="_blank">98</a>). In addition, DHA promotes mitochondrial biogenesis and skeletal muscle fiber remodeling (<a href="https://www.frontiersin.org/articles/10.3389/fnut.2023.1189522/full#B99" target="_blank">99</a>) and delays muscle wasting by stimulating intermediate oxidative stress and inhibiting proteasomal degradation of muscle proteins (<a href="https://www.frontiersin.org/articles/10.3389/fnut.2023.1189522/full#B100" target="_blank">100</a>).</strong></em></p><p></p><p></p><p></p><h4><strong>2.3.2. Related studies</strong></h4><p><em>It has been proposed that elevated plasma levels of proinflammatory cytokines affect muscle catabolic and anabolic signaling pathways and thus may play a key role in the development and progression of sarcopenia, with data showing significantly elevated levels of IL-6 and TNFα in elderly Chinese individuals with sarcopenia (<a href="https://www.frontiersin.org/articles/10.3389/fnut.2023.1189522/full#B101" target="_blank">101</a>). <strong>Therefore, reducing chronic inflammation associated with aging is emerging as a potential therapeutic target for sarcopenia, </strong>and NSAIDs may not be recommended for the treatment of sarcopenia due to the high risk of adverse events that may occur with their use in elderly individuals.<strong> Increasing evidence indicates that omega-3 polyunsaturated fatty acids reduce the expression of inflammatory genes and have anti-inflammatory activity (<a href="https://www.frontiersin.org/articles/10.3389/fnut.2023.1189522/full#B102" target="_blank">102</a>), particularly eicosapentaenoic acid, docosahexaenoic acid, and alpha-linolenic acid. <u>It was concluded from a systematic evaluation and meta-analysis that omega-3 fatty acid supplementation promotes lean body mass, skeletal muscle mass, and isometric contraction maximal muscle strength in the quadriceps</u> (<a href="https://www.frontiersin.org/articles/10.3389/fnut.2023.1189522/full#B103" target="_blank">103</a>).</strong> Dietary omega-3 fatty acid levels are negatively associated with sarcopenia (<a href="https://www.frontiersin.org/articles/10.3389/fnut.2023.1189522/full#B104" target="_blank">104</a>), and more than 2 g/day of omega-3 fatty acids may increase muscle mass and improve walking speed, especially for those with sarcopenia who have been receiving the intervention for more than 6 months (<a href="https://www.frontiersin.org/articles/10.3389/fnut.2023.1189522/full#B105" target="_blank">105</a>).<strong> However, linear regression analysis concluded that there was no association between plasma omega-3 levels and grip strength in older adults (<a href="https://www.frontiersin.org/articles/10.3389/fnut.2023.1189522/full#B106" target="_blank">106</a>). When cancer patients were supplemented with omega-3 fatty acids, their muscle maintenance, quality of life, and body weight were not improved (<a href="https://www.frontiersin.org/articles/10.3389/fnut.2023.1189522/full#B107" target="_blank">107</a>).</strong> <strong><u>According to expert opinions (<a href="https://www.frontiersin.org/articles/10.3389/fnut.2023.1189522/full#B108" target="_blank">108</a>), doses of 3,000 mg/day DHA plus EPA or more (with preferably more than 800 mg/day EPA) may be required for positive physical performance in older adults (<a href="https://www.frontiersin.org/articles/10.3389/fnut.2023.1189522/full#B109" target="_blank">109</a>, <a href="https://www.frontiersin.org/articles/10.3389/fnut.2023.1189522/full#B110" target="_blank">110</a>), because lower doses have no significant effects on muscle strength (<a href="https://www.frontiersin.org/articles/10.3389/fnut.2023.1189522/full#B111" target="_blank">111</a>). In conclusion, omega-3 fatty acids may improve sarcopenia, but well-designed, large prospective cohort studies and randomized controlled trials are needed to confirm these findings</u>.</strong></em></p></blockquote><p></p>
[QUOTE="madman, post: 275537, member: 13851"] [I][B]*In conclusion, omega-3 fatty acids may improve sarcopenia, but well-designed, large prospective cohort studies and randomized controlled trials are needed to confirm these findings.[/B][/I] [HEADING=2]2.3. Omega-3 fatty acids[/HEADING] [I]Omega-3 fatty acids (also known as n-3 fatty acids) are polyunsaturated fatty acids with many potential health benefits and are available in three main dietary forms: alpha-linolenic acid (ALA; 18:3n-3), eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3). ALA is considered an essential fatty acid because it cannot be synthesized in the human body and is found in nuts, seeds, canola oil, etc. EPA and DHA are mainly found in fish oil.[/I] [HEADING=3][B]2.3.1. Mechanisms[/B][/HEADING] [I]Skeletal muscle atrophy involves an inflammatory phase that leads to cell death and tissue remodeling and activates endoplasmic reticulum stress (ERS) and autophagy ([URL='https://www.frontiersin.org/articles/10.3389/fnut.2023.1189522/full#B96']96[/URL], [URL='https://www.frontiersin.org/articles/10.3389/fnut.2023.1189522/full#B97']97[/URL]).[B] Both EPA and DHA potentially attenuate ERS and autophagy in skeletal muscles undergoing atrophy by attenuating the increase in PERK and ATG14 expression ([URL='https://www.frontiersin.org/articles/10.3389/fnut.2023.1189522/full#B98']98[/URL]). In addition, DHA promotes mitochondrial biogenesis and skeletal muscle fiber remodeling ([URL='https://www.frontiersin.org/articles/10.3389/fnut.2023.1189522/full#B99']99[/URL]) and delays muscle wasting by stimulating intermediate oxidative stress and inhibiting proteasomal degradation of muscle proteins ([URL='https://www.frontiersin.org/articles/10.3389/fnut.2023.1189522/full#B100']100[/URL]).[/B][/I] [HEADING=3][B]2.3.2. Related studies[/B][/HEADING] [I]It has been proposed that elevated plasma levels of proinflammatory cytokines affect muscle catabolic and anabolic signaling pathways and thus may play a key role in the development and progression of sarcopenia, with data showing significantly elevated levels of IL-6 and TNFα in elderly Chinese individuals with sarcopenia ([URL='https://www.frontiersin.org/articles/10.3389/fnut.2023.1189522/full#B101']101[/URL]). [B]Therefore, reducing chronic inflammation associated with aging is emerging as a potential therapeutic target for sarcopenia, [/B]and NSAIDs may not be recommended for the treatment of sarcopenia due to the high risk of adverse events that may occur with their use in elderly individuals.[B] Increasing evidence indicates that omega-3 polyunsaturated fatty acids reduce the expression of inflammatory genes and have anti-inflammatory activity ([URL='https://www.frontiersin.org/articles/10.3389/fnut.2023.1189522/full#B102']102[/URL]), particularly eicosapentaenoic acid, docosahexaenoic acid, and alpha-linolenic acid. [U]It was concluded from a systematic evaluation and meta-analysis that omega-3 fatty acid supplementation promotes lean body mass, skeletal muscle mass, and isometric contraction maximal muscle strength in the quadriceps[/U] ([URL='https://www.frontiersin.org/articles/10.3389/fnut.2023.1189522/full#B103']103[/URL]).[/B] Dietary omega-3 fatty acid levels are negatively associated with sarcopenia ([URL='https://www.frontiersin.org/articles/10.3389/fnut.2023.1189522/full#B104']104[/URL]), and more than 2 g/day of omega-3 fatty acids may increase muscle mass and improve walking speed, especially for those with sarcopenia who have been receiving the intervention for more than 6 months ([URL='https://www.frontiersin.org/articles/10.3389/fnut.2023.1189522/full#B105']105[/URL]).[B] However, linear regression analysis concluded that there was no association between plasma omega-3 levels and grip strength in older adults ([URL='https://www.frontiersin.org/articles/10.3389/fnut.2023.1189522/full#B106']106[/URL]). When cancer patients were supplemented with omega-3 fatty acids, their muscle maintenance, quality of life, and body weight were not improved ([URL='https://www.frontiersin.org/articles/10.3389/fnut.2023.1189522/full#B107']107[/URL]).[/B] [B][U]According to expert opinions ([URL='https://www.frontiersin.org/articles/10.3389/fnut.2023.1189522/full#B108']108[/URL]), doses of 3,000 mg/day DHA plus EPA or more (with preferably more than 800 mg/day EPA) may be required for positive physical performance in older adults ([URL='https://www.frontiersin.org/articles/10.3389/fnut.2023.1189522/full#B109']109[/URL], [URL='https://www.frontiersin.org/articles/10.3389/fnut.2023.1189522/full#B110']110[/URL]), because lower doses have no significant effects on muscle strength ([URL='https://www.frontiersin.org/articles/10.3389/fnut.2023.1189522/full#B111']111[/URL]). In conclusion, omega-3 fatty acids may improve sarcopenia, but well-designed, large prospective cohort studies and randomized controlled trials are needed to confirm these findings[/U].[/B][/I] [/QUOTE]
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