Functional Foods to Ameliorate Neurogenic Muscle Atrophy: Comparison
View Latest Version
Please note this is a comparison between Version 2 by Jason Zhu and Version 1 by Viviana Moresi.

Neurogenic muscle atrophy is a debilitating condition that occurs from nerve trauma in association with diseases or during aging, leading to reduced interaction between motoneurons and skeletal fibers. Therapeutic approaches aiming at preserving muscle mass in a scenario of decreased nervous input include physical activity and employment of drugs that slow down the progression of the condition yet provide no concrete resolution. Nutritional support appears as a precious tool, adding to the success of personalized medicine, and could thus play a relevant part in mitigating neurogenic muscle atrophy.

  • nutraceuticals
  • natural compounds
  • muscle wasting

1. Introduction

Functional foods are considered as either fresh or processed foods that naturally promote health and prevent or ameliorate diseases beyond their basic nutritional functions [85][1]. Functional foods or ingredients with protective, therapeutic outcomes against neurogenic muscle atrophy have recently received increasing consideration, being suitable for long-term treatment and potentially free from side effects.

2. Protein or Amino Acids

High daily protein intake (1.0–1.2 g/kg/day) correlates with the maintenance of muscle mass with aging [86][2]. Such assumption persists even though contrasting data were reported from randomized clinical trials employing protein or amino acid supplements [87[3][4][5][6][7],88,89,90,91], probably due to the heterogeneity of the initial populations and to the difficulty in measuring the effective protein intake throughout the studies. Similarly, a positive correlation has been found between the length of survival of ALS patients and the amount of protein consumed, especially at the early stage of the disease [92][8]. However, dietary supplementation with creatine or amino acids has not been proven to be effective in improving the prognosis of ALS patients [93][9].
When the studies are stratified by the specific amino acids used, the most interesting results are the following:
  • Branched-chain amino acids (BCAAs), i.e., leucine, isoleucine, and valine, are three of the nine essential amino acids and are found in protein-rich foods such as eggs, meat, and dairy products. A BCAA-enriched diet has been shown to be protective against sarcopenia in both slow and fast muscles of old mice [94][10] and in elderly subjects [89,95,96][5][11][12], by promoting mitochondrial genesis, thus improving muscle endurance, and decreasing oxidative stress. In contrast, treatment of ALS patients with BCAAs or L-threonine for six months failed to show beneficial effects on disease progression [97][13].
  • Leucine is an essential BCAA present in all protein-rich foods, but is more abundant in those of animal origin [98][14]. A leucine-enriched exclusive diet prevented neurogenic muscle atrophy in denervated rat soleus (slow) muscle, by increasing the AKT/mTOR anabolic pathway and decreasing the AMPK-catabolic one [99][15]. Leucine supplementation is potentially useful to increase protein synthesis for counteracting muscle sarcopenia in elderly subjects [100,101][16][17].
As for the mechanism underlying their beneficial effects, the dietary intake of essential amino acids increases the expression of several miRNAs in the skeletal muscle, including miR-1, miR-23a, miR-208b, miR-499, and miR-27a, regulating the expression of muscle-specific growth-related genes and thereby promoting muscle mass [102,103][18][19].
  • Beta-Hydroxy-Beta-Methyl Butyrate (HMB) is a natural metabolite of the amino acid leucine, and is found in small quantities in grapefruit, alfalfa, and catfish. In humans, 2–10% of dietary L-leucine is converted to HMB, corresponding to about 0.3 g/day; however, when taken as a supplement the doses are 10–20-fold higher [104][20]. As a derivate of a BCAA, HMB is thought to act as pro-anabolic and anti-catabolic compound for skeletal muscle, and early studies showed a positive impact of HMB supplementation in counteracting the age-related losses of skeletal muscle mass in elderly subjects [105,106,107][21][22][23]. However, two recent articles published opposite results: according to a review, the current evidence is inconclusive with regard to any positive effects of HMB supplementation on functional outcome measurements or muscle mass in elderly human subjects and in hospitalized patients [108][24], while a meta-analysis concluded that HMB supplementation helps increase muscle strength in elderly people [109][25].
  • Creatine is a compound derived from glycine and arginine which is mostly present in skeletal muscle, where it is used as an energy store, and can be found in red meat and seafood. Abundant evidence indicates that creatine supplementation increases skeletal muscle mass and strength if associated with resistance training [110][26], due to its beneficial effects on decreasing muscle protein breakdown, inflammation, and oxidative stress; interestingly, this also holds true with aging [111,112][27][28]. Despite the positive effects on skeletal muscle homeostasis, current literature suggests that exogenous creatine supplementation appears to be poorly effective in treating ALS [113,114][29][30].
  • Carnitine is a quaternary ammonium compound required for the transport of long-chain fatty acids into mitochondria for energy production. Carnitine can be mainly found in animal products such as meat, fish, poultry, and milk, and is involved in skeletal muscle protein homeostasis by regulating both protein synthesis and breakdown, being an antioxidant and anti-inflammatory compound [115][31]. Interestingly, denervation and aging decrease carnitine levels in both slow and fast rat skeletal muscles [116][32], suggesting a causative role for carnitine in the atrophic program. Carnitine supplementation, alone or in combination with physical exercise, counteracts the age-dependent decline of mitochondrial function in the soleus rat muscle, improving muscle energy production and body protein mass [117,118,119][33][34][35]. The positive effects of carnitine supplementation were also reported in a murine model of ALS [120][36], as well as in a phase II clinical trial [121][37], proving to be effective in slowing down the progression of muscle weakness and prolonging mouse and patient survival.
  • Carnosine is a dipeptide composed of the beta-alanine and histidine amino acids and mainly present in meats. Carnosine exerts numerous positive actions in skeletal muscle, including antioxidant and antiglycation activity, enhanced calcium sensitivity, and H+ buffering [122][38] that may affect muscle performance and maintenance in aging and neuromuscular diseases [123,124,125][39][40][41]. In elderly subjects, an increase in carnosine intake counteracted cognitive decline and improved physical capacity, probably due to its anti-inflammatory action [126,127][42][43]. Further studies are needed to clarify the effects of carnosine supplementation on skeletal muscle proteolysis and synthesis in a denervation-dependent condition such as in aging or ALS.

3. Lipids

Unsaturated fatty acids have been reported to protect against muscle wasting in response to various pathological conditions. In particular, the replacement of saturated fatty acids (SFAs) by either mono- (MUFAs) or poly-unsaturated (PUFAs) has been associated with a lower sarcopenia risk score in a regression analysis that involved almost a thousand participants [129][44].
Several possible signaling pathways activated by PUFAs may underpin the beneficial effects on counteracting neurogenic muscle atrophy. Indeed, PUFAs exert a well-recognized anti-inflammatory action, increase nerve conduction, improve mitochondrial function, and stimulate muscle protein synthesis [133,134][45][46] while modulating autophagy and countering protein degradation [86,135][2][47].
Another aspect to which omega-3-fatty-acids may contribute to mitigation of atrophy is by beneficially modulating neuromuscular function, playing a suggested role on both the nerve and on the muscle fiber, altering membrane fluidity and sensitivity to acetylcholine (reviewed by [142][48]).
  • Medium-chain triglycerides (MCT) are six-twelve carbon fatty acid esters of glycerol that can be found in coconut oil and products, palm oil, and dairy products. In mice, an MCT-enriched diet triggers glucose and lipid metabolism pathways and mitochondrial biogenesis in the skeletal muscle, thus improving muscle function under high-temperature conditions [143][49]. MCTs alone, or in combination with leucine and vitamin D, increase muscle strength and function in elderly adults [144,145][50][51]. However, MCT administration is detrimental for the heart of healthy or dystrophic mice [146,147][52][53]. Thus, careful examination of the systemic effects of MCT administration is encouraged in clinical studies.
  • Alkylresorcinols (ARs), differently from PUFA, are amphiphilic phenolic lipids present in many kinds of cereals. Interestingly, AR dietary supplementation prevented neurogenic muscle atrophy in mice by affecting the autophagic pathway and thereby the lipid metabolism, but not the UPS activation [148][54]. This finding is intriguing, confirming that challenging metabolism may be an efficient therapeutic approach for maintaining muscle homeostasis, as suggested in ALS [149][55] and already described in other muscle pathologies [35,150,151][56][57][58].

4. Vitamins

Vitamins are essential micronutrients that cannot be synthesized by the organism, therefore, they must be obtained via the diet. Vitamins prevent skeletal muscle atrophy mainly for their anti-inflammatory properties and by buffering oxidative stress, thus affecting both protein synthesis and catabolism [152][59]. As for neurogenic muscle atrophy, however, uncertain findings have been reported on the effectiveness of vitamin supplementation.
  • β-carotene is a red-orange pigment found in fruits and vegetables. The human body converts β-carotene into vitamin A. β-carotene attenuates ROS-dependent muscle atrophy in C2C12 myotubes by repressing the activation of atrogin-1 and MuRF1 [153][60]. In the elderly, high plasma concentrations of β-carotene and other similar antioxidants correlate with preserved muscle function [154][61], which would support their clinical use. However, weak data were reported about the effectiveness against neurogenic muscle atrophy in vivo, as β-carotene supplementation is only effective at the early stage of soleus muscle atrophy upon denervation [155][62].
  • As for vitamin C, both dietary and circulating levels positively correlate with skeletal muscle mass measurements in middle- and older-aged subjects, suggesting that dietary vitamin C intake may be protective against sarcopenia [156][63]. Coherently, mice with defective vitamin C biosynthesis (SMP30-knockout mice) develop muscle atrophy in both fast and slow muscles, with high expression of muscle-specific E3-ubiquitin ligases, atrogin-1 and MuRF1, and high levels of ROS. Vitamin C supplementation was able to recover the SMP30-knockout muscle atrophy phenotype [157][64], highlighting its direct involvement in the maintenance of skeletal muscle homeostasis.
  • Vitamin D certainly plays an important role in skeletal muscle physiology. Vitamin D deficiency in humans leads to muscle weakness and myalgia that can be reverted by vitamin D replenishment [158][65]. Vitamin D supplementation is associated with a significant increase in muscle mass and function in older adults with sarcopenia, especially for those with a significant baseline vitamin D deficiency [159,160,161,162][66][67][68][69]. At the molecular levels, skeletal muscle seems to express the vitamin D receptor, which mediates vitamin D-dependent signaling affecting calcium handling [163][70]. In addition to beneficial effects on age-related sarcopenia (revised in [164][71]), vitamin D helps muscle recovery following strenuous muscular activity. However, when vitamin D was supplemented in ALS, negative results prevailed over beneficial findings [165,166,167,168][72][73][74][75].
  • Trolox, the cell-permeable derivative of vitamin E, was not able to exert any protective effects on neurogenic muscle atrophy in mice [62][76], despite evidence that the combined supplementation of whey protein, vitamin D and E can significantly improve muscle mass, strength, and markers of protein anabolism in sarcopenic subjects [169][77]. Two studies acknowledged the importance of oxidative stress in neurogenic muscle atrophy: the divergent conclusions come from different treatments (single or combined) and different models (mice vs. humans).

5. Plant-Derived Ingredients

Several plant-derived ingredients prevent or reduce muscle atrophy, especially by inhibiting muscle protein degradation while enhancing muscle synthesis, and/or exerting anti-inflammatory and anti-oxidative functions [171,172][78][79].
  • Geranylgeraniol (GGOH), is a plant-derived isoprenoid with some beneficial effects for skeletal muscle mass. GGOH administration reduced the loss of myofiber size upon denervation in rat gastrocnemius muscle by affecting the expression of atrogin-1 [173][80], without enhancing muscle growth, even though it had previously shown a positive effect on C2C12 myoblast differentiation in vitro [174][81]. In addition, GGOH may interfere with the NF-κB and/or testosterone signaling in skeletal muscle, as demonstrated in other cell types [174,175][81][82], thus contributing to the protection against neurogenic muscle atrophy.
  • Capsaicin is a chili pepper-derived extract with analgesic properties. Its protective action against neurogenic muscle atrophy has been described in a study [176][83]. Capsaicin administration, used as an agonist of the transient receptor potential cation channel, subfamily V, member 1 (TRPV1), induced muscle hypertrophy and alleviated denervation-induced atrophy in both fast and slow murine muscles. Activated TRPV1 increased intracellular Ca2+ concentration leading to mTOR activation and muscle biosynthesis [176][83].
  • Polyphenols are a wide group of plant-derived organic compounds found in fruits, vegetables, coffee, tea, and whole grains. They are believed to be potential therapeutic agents for inhibiting muscle atrophy and improving muscle mass and strength [172][79]. Polyphenols act primarily as antioxidants and anti-inflammatory agents, thus inhibiting muscle atrophy-related genes and promoting the activation of the IGF-1 signaling pathway [172,[79177]][84]. In addition, in vitro and in vivo observations proved the neuroprotective effects of these bioactive compounds by improving mitochondrial biogenesis and function, reducing toxic protein aggregates and microglia and astrocytes inflammation, and overall favoring motor neuron survival [178][85]. Some examples are reported below.
Isoflavones are a type of polyphenol mainly found in legumes, such as soybeans and other fruits and nuts. The administration of isoflavones has been shown to counteract TNF-α-induced C2C12 myotube atrophy by reducing MuRF1 promoter activity, and to prevent neurogenic muscle atrophy in vivo, when mice were pre-treated with isoflavones before denervation, mainly by interfering with apoptosis-dependent signaling [179,180][86][87].
Curcumin is extracted from the rhizome of turmeric, from the ginger family of plants, and displays anti-aging properties [181][88], by increasing the activity of SOD enzyme and increasing lifespan [182][89]. Accordingly, curcumin counteracts sarcopenia in mice [183][90], and clinical trials with healthy elderly subjects are ongoing [184][91]. Since curcumin is an antioxidant, as also reported above [185][92], it would be an ideal candidate as a nutraceutical for ALS and other neurodegenerative diseases. Indeed, a curcumin derivative, GT863, has been proven to slower motor dysfunction in a murine model of ALS [186][93]. In a different study exploiting the same SOD1 model, curcumin reduced the cytotoxicity of the amylogenic pathway [187][94]. Interestingly, curcumin protects the peripheral nervous system after injury [188][95] and promotes nerve regeneration [189][96]. The clinical use of curcumin in neurological disorders has been reviewed recently [190][97].
Resveratrol is a polyphenol found in grapes, red wine, and berries. It has been shown to inhibit protein degradation and protect skeletal muscle against atrophy in different in vivo models, including cancer, diabetes, chronic kidney disease, and disuse [191,192,193,194][98][99][100][101]. Dietary resveratrol supplementation prevented neurogenic muscle atrophy in mice, likely by interfering with the activation of UPS and autophagic pathways [195][102], in addition to its neuroprotective functions [196][103]. Moreover, resveratrol affects muscle mass by promoting muscle cell differentiation and PGC-1α activation through the concomitant up-regulation of miR-21 and miR27-b and downregulation of miR-133b, miR-30b, and miR-149 [197][104]. Convincing data on the effects of resveratrol on muscle mass in experimental models of neurodegenerative diseases are still missing.
Avenanthramides (AVNs), also known as N-cinnamoylanthranilate alkaloids or anthranilic acid amides, are a group of low molecular weight phenolic amides found mainly in the whole grain oat [198][105]. AVNs are effective in inhibiting NF-kB activation, ROS production, and proinflammatory cytokine expression in several cell types, including muscle cells [199,200,201][106][107][108]. In particular, AVNs bind and inhibit IKKβ activity, thereby inhibiting the NFκB-mediated inflammatory response in muscle cells [202][109] and TNF-α-induced myotube atrophy [199][106].
Among polyphenolic compounds, flavonoids are a subgroup generally having a 15-carbon skeleton. Both polyphenols and flavonoids exert anti-inflammatory and antioxidant actions and some flavonoids have been reported to possess protective functions, specifically with regard to neurogenic muscle atrophy.
Quercetin is a flavonoid found in many fruits and vegetables, such as in red wine, onions, green tea, apples, and berries. Quercetin has been shown to play protective functions against the muscle wasting that accompanies a variety of conditions. Regarding neurogenic muscle atrophy, quercetin suppresses TNF-α-induced C2C12 myotube atrophy by interfering with the activation of NF-κB and the consequent activation of the ubiquitin ligases atrogin-1 and MuRF-1, and by activating the Heme Oxygenase 1 (HO-1) [203][110]. Moreover, the administration of quercetin before denervating mice prevents neurogenic muscle atrophy by increasing mitochondriogenesis and function via PGC-1α [204][111].
Epicatechin is one of the most abundant flavonoids present in different fruits and green tea. Dietary supplementation of epicatechin prevents muscle loss in sarcopenic mice by increasing the expression of the myogenic marker MyoD and the antioxidant stress-related enzymes SOD and catalase, while reducing the expression of the catabolic marker genes, such as FoxO3a, myostatin, and MuRF1 [205][112]. Similarly, dietary supplementation with another green tea polyphenol, i.e., epigallocatechin-3-gallate, increases skeletal muscle mass and size in aged rats by downregulating the expression of the E3-ubiquitin ligases, MuRF1 and atrogin-1, and myostatin, and by increasing IGF-1 [206][113].
Apigenin is a flavonoid found in plants such as parsley, celery, and grapefruit. An apigenin-supplemented diet was able to prevent neurogenic muscle atrophy in both fast and slow murine muscles by inhibiting denervation-induced MuRF1 and IL-6 expression, thus affecting the activation of UPS and inflammatory processes within the muscle [207][114].
Genistein is a flavonoid derived from legumes. Dietary genistein supplementation attenuated the denervation-induced muscle atrophy in slow muscles in mice by interfering with the estrogen receptor-mediated activation of MuRF1 and atrogin1 expression [208][115].
8-prenylnaringenin is a prenylated flavonoid found in hops. Dietary ingestion of 8-prenylnaringenin prevents neurogenic muscle atrophy in mouse gastrocnemius muscles by stimulating the activation of Akt phosphorylation and preventing the induction of the key ubiquitin ligase involved in muscle atrophy atrogin-1 [209][116].
  • Tomatidine is the metabolite obtained from α-tomatine, a glycoalkaloid abundantly present in tomato plants. Strikingly, the mRNA expression signature of tomatidine negatively correlates to that one of skeletal muscle atrophy upon fasting and spinal cord injury [210][117], suggesting that tomatidine might exert an anti-atrophic effect on skeletal muscle. Indeed, tomatine administration induced functional muscle hypertrophy, both in vitro and in vivo, accompanied by reduced adiposity, by activating mTORC1 signaling [210][117]. By enhancing protein synthesis and mitochondriogenesis, tomatidine also prevented muscle atrophy induced by fasting or immobilization in mice [210][117]. In C. elegans, tomatidine improves muscle function during aging by activating mitophagy and antioxidant cellular defenses [211][118]. Based on these promising findings, the use of tomatidine to counteract neurogenic muscle atrophy should be further investigated, along with the delineation of the molecular mechanisms underpinning the atrophy rescue.
  • Tinospora cordifolia is a plant found in tropical and sub-tropical parts of Asia, Africa, and Australia, whose extract (TCE) has been widely used in ancient Ayurvedic and Tibetan medicine due to its high antioxidant activity [212][119]. TCE supplementation prevented neurogenic muscle atrophy by enhancing protein synthesis by antagonizing the proteolytic pathways (calpain and UPS), and by enhancing the oxidative stress response in both slow and fast mouse muscles [213][120].
  • Salidroside is a glucoside of tyrosol extracted from the plant Rhodiola rosea with anti-inflammatory, anti-oxidative, and anti-apoptotic properties [214,215][121][122]. Salidroside protects skeletal muscle from neurogenic muscle atrophy due to its anti-inflammatory properties [216][123].

6. Prebiotics, Probiotics and Dietary Fibers

Skeletal muscle wasting conditions, in addition to aging, deeply affect the intestinal mucosa [218][124] and are associated to changes in the gut biota [219,220][125][126]. Vice-versa, the gut microbiota can potentially affect skeletal muscle mass by modulating systemic inflammation and immunity, energy metabolism, and insulin sensitivity [221][127]. The importance of gut microbiota for the maintenance of skeletal muscle physiology and homeostasis has been recently demonstrated by comparing germ-free and pathogen-free mice [222][128]. The former, lacking a gut microbiota, showed skeletal muscle atrophy with clear molecular signs of muscle denervation, a phenotype that was reversed by transplanting the gut microbiota of the pathogen-free mice. Transplantation of the gut microbiota from pathogen-free mice into germ-free mice affects both slow and fast muscles, reducing the skeletal muscle atrophy markers atrogin-1 and MuRF1, and increasing mitochondriogenesis and oxidative metabolism, thus restoring skeletal muscle mass [222][128]. Additional studies have directly or indirectly proved a certain relationship between muscle mass and gut microbiota [223,224,225][129][130][131]. Although the pre and probiotics’ mechanisms for rescuing muscle mass are not yet well defined, gut microbiota may potentially influence muscles via endocrine and insulin sensitivity, energy metabolism, immunity, and inflammation [226][132]. Microbiota composition can be modified with the diet by increasing the consumption of prebiotics, i.e., non-digestible carbohydrates fermented in the lower part of the gut that stimulates the growth and/or activity(ies) of bacteria, or probiotics, i.e., live microorganisms, thus conferring a health benefit on the host. Often prebiotics have pleiotropic effects, regulating metabolism while acting on fat tissue and lean mass [227][133].
Since a dietary intervention alters the gut microbiota, it may be used as a potent tool to heal elderly subjects [228][134]. Indeed, dietary fiber administration is protective against age-related muscle loss by improving glucose metabolism, muscle function and lean body mass in adult subjects [229,230][135][136]. Such positive effects on skeletal muscle maintenance are attributed to dietary fiber’s ability to rapidly and reproducibly change the composition of microbiota, i.e., living members forming the microbiome, and microbiome, i.e., all of the genetic material within a microbiota [231,232,233][137][138][139]. For example, high dietary fiber intake increases the gut microbiota production of short-chain fatty acids [231][137], which are important regulators of skeletal muscle mass, metabolism, and function [234][140]. Beneficial effects of fiber supplementation have also been reported in metabolic disease conditions due to the decrease of insulin resistance [235,236][141][142] and pro-inflammatory cytokine concentration [237[143][144],238], which are two mechanisms directly involved in sarcopenia. In keeping with the approach of affecting microbiota, the administration of a prebiotic composed of a mixture of inulin and fructooligosaccharides for 13 weeks increased some skeletal muscle functional parameters in a randomized controlled double-blind study in elderly people [239][145].
Similarly to aging, the gut microbiota varies between ALS patients and healthy subjects; moreover, it changes further during the progression of the disease, with a decrease of potentially protective microbial groups, such as Bacteroidetes, and an increase of those groups with potential neurotoxic or pro-inflammatory activity, such as Cyanobacteria [240][146]. Supplementation with a probiotic formulation, consisting of a mixture of five lactic acid bacteria, for 6 months, despite regulating the intestinal microbiota of patients, did not influence the progression of the disease, as evaluated by ALS Functional Rating Scale–Revised (ALSFRS-R) score [240][146].

References

  1. Scientific Concepts of Functional Foods in Europe. Consensus Document-PubMed. Available online: https://pubmed.ncbi.nlm.nih.gov/10999022/ (accessed on 29 July 2022).
  2. Dupont, J.; Dedeyne, L.; Dalle, S.; Koppo, K.; Gielen, E. The Role of Omega-3 in the Prevention and Treatment of Sarcopenia. Aging Clin. Exp. Res. 2019, 31, 825–836.
  3. Tieland, M.; Franssen, R.; Dullemeijer, C.; van Dronkelaar, C.; Kim, H.K.; Ispoglou, T.; Zhu, K.; Prince, R.L.; van Loon, L.J.C.; de Groot, L.C.P.G.M. The Impact of Dietary Protein or Amino Acid Supplementation on Muscle Mass and Strength in Elderly People: Individual Participant Data and Meta-Analysis of RCT’s. J. Nutr. Health Aging 2017, 21, 994–1001.
  4. Mitchell, C.J.; Milan, A.M.; Mitchell, S.M.; Zeng, N.; Ramzan, F.; Sharma, P.; Knowles, S.O.; Roy, N.C.; Sjödin, A.; Wagner, K.H.; et al. The Effects of Dietary Protein Intake on Appendicular Lean Mass and Muscle Function in Elderly Men: A 10-Wk Randomized Controlled Trial. Am. J. Clin. Nutr. 2017, 106, 1375–1383.
  5. Cawood, A.L.; Elia, M.; Stratton, R.J. Systematic Review and Meta-Analysis of the Effects of High Protein Oral Nutritional Supplements. Ageing Res. Rev. 2012, 11, 278–296.
  6. Tieland, M.; van de Rest, O.; Dirks, M.L.; van der Zwaluw, N.; Mensink, M.; van Loon, L.J.C.; de Groot, L.C.P.G.M. Protein Supplementation Improves Physical Performance in Frail Elderly People: A Randomized, Double-Blind, Placebo-Controlled Trial. J. Am. Med. Dir. Assoc. 2012, 13, 720–726.
  7. Zhu, K.; Kerr, D.A.; Meng, X.; Devine, A.; Solah, V.; Binns, C.W.; Prince, R.L. Two-Year Whey Protein Supplementation Did Not Enhance Muscle Mass and Physical Function in Well-Nourished Healthy Older Postmenopausal Women. J. Nutr. 2015, 145, 2520–2526.
  8. Kim, B.; Jin, Y.; Kim, S.H.; Park, Y. Association between Macronutrient Intake and Amyotrophic Lateral Sclerosis Prognosis. Nutr. Neurosci. 2018, 23, 8–15.
  9. Genton, L.; Viatte, V.; Janssens, J.P.; Héritier, A.C.; Pichard, C. Nutritional State, Energy Intakes and Energy Expenditure of Amyotrophic Lateral Sclerosis (ALS) Patients. Clin. Nutr. 2011, 30, 553–559.
  10. D’Antona, G.; Ragni, M.; Cardile, A.; Tedesco, L.; Dossena, M.; Bruttini, F.; Caliaro, F.; Corsetti, G.; Bottinelli, R.; Carruba, M.O.; et al. Branched-Chain Amino Acid Supplementation Promotes Survival and Supports Cardiac and Skeletal Muscle Mitochondrial Biogenesis in Middle-Aged Mice. Cell Metab. 2010, 12, 362–372.
  11. Bai, G.H.; Tsai, M.C.; Tsai, H.W.; Chang, C.C.; Hou, W.H. Effects of Branched-Chain Amino Acid-Rich Supplementation on EWGSOP2 Criteria for Sarcopenia in Older Adults: A Systematic Review and Meta-Analysis. Eur. J. Nutr. 2022, 61, 637–651.
  12. Buondonno, I.; Sassi, F.; Carignano, G.; Dutto, F.; Ferreri, C.; Pili, F.G.; Massaia, M.; Nisoli, E.; Ruocco, C.; Porrino, P.; et al. From Mitochondria to Healthy Aging: The Role of Branched-Chain Amino Acids Treatment: MATeR a Randomized Study. Clin. Nutr. 2020, 39, 2080–2091.
  13. Tandan, R.; Bromberg, M.B.; Forshew, D.; Fries, T.J.; Badger, G.J.; Carpenter, J.; Krusinski, P.B.; Betts, E.F.; Arciero, K.; Nau, K. A Controlled Trial of Amino Acid Therapy in Amyotrophic Lateral Sclerosis: I. Clinical, Functional, and Maximum Isometric Torque Data. Neurology 1996, 47, 1220–1226.
  14. Rondanelli, M.; Nichetti, M.; Peroni, G.; Faliva, M.A.; Naso, M.; Gasparri, C.; Perna, S.; Oberto, L.; Di Paolo, E.; Riva, A.; et al. Where to Find Leucine in Food and How to Feed Elderly With Sarcopenia in Order to Counteract Loss of Muscle Mass: Practical Advice. Front. Nutr. 2021, 7, 383.
  15. Ribeiro, C.B.; Christofoletti, D.C.; Pezolato, V.A.; de Cássia Marqueti Durigan, R.; Prestes, J.; Tibana, R.A.; Pereira, E.C.L.; de Sousa Neto, I.V.; Durigan, J.L.Q.; da Silva, C.A. Leucine Minimizes Denervation-Induced Skeletal Muscle Atrophy of Rats through Akt/Mtor Signaling Pathways. Front. Physiol. 2015, 6, 73.
  16. Martínez-arnau, F.M.; Fonfría-vivas, R.; Cauli, O. Beneficial Effects of Leucine Supplementation on Criteria for Sarcopenia: A Systematic Review. Nutrition 2019, 11, 2504.
  17. Martínez-Arnau, F.M.; Fonfría-Vivas, R.; Buigues, C.; Castillo, Y.; Molina, P.; Hoogland, A.J.; van Doesburg, F.; Pruimboom, L.; Fernández-Garrido, J.; Cauli, O. Effects of Leucine Administration in Sarcopenia: A Randomized and Placebo-Controlled Clinical Trial. Nutrition 2020, 12, 932.
  18. Drummond, M.J.; Glynn, E.L.; Fry, C.S.; Dhanani, S.; Volpi, E.; Rasmussen, B.B. Essential Amino Acids Increase MicroRNA-499, -208b, and -23a and Downregulate Myostatin and Myocyte Enhancer Factor 2C MRNA Expression in Human Skeletal Muscle. J. Nutr. 2009, 139, 2279.
  19. Soares, R.J.; Cagnin, S.; Chemello, F.; Silvestrin, M.; Musaro, A.; De Pitta, C.; Lanfranchi, G.; Sandri, M. Involvement of MicroRNAs in the Regulation of Muscle Wasting during Catabolic Conditions. J. Biol. Chem. 2014, 289, 21909–21925.
  20. Zanchi, N.E.; Gerlinger-Romero, F.; Guimarães-Ferreira, L.; De Siqueira Filho, M.A.; Felitti, V.; Lira, F.S.; Seelaender, M.; Lancha, A.H. HMB Supplementation: Clinical and Athletic Performance-Related Effects and Mechanisms of Action. Amino Acids 2011, 40, 1015–1025.
  21. Baier, S.; Johannsen, D.; Abumrad, N.; Rathmacher, J.A.; Nissen, S.; Flakoll, P. Year-Long Changes in Protein Metabolism in Elderly Men and Women Supplemented with a Nutrition Cocktail of Beta-Hydroxy-Beta-Methylbutyrate (HMB), L-Arginine, and L-Lysine. JPEN. J. Parenter. Enteral Nutr. 2009, 33, 71–82.
  22. Rahman, A.; Wilund, K.; Fitschen, P.J.; Jeejeebhoy, K.; Agarwala, R.; Drover, J.W.; Mourtzakis, M. Elderly Persons with ICU-Acquired Weakness: The Potential Role for β-Hydroxy-β-Methylbutyrate (HMB) Supplementation? J. Parenter. Enter. Nutr. 2014, 38, 567–575.
  23. De Angelus, N.; Riela, C.; Moeme, M.; Guimarães, A.; Oliveira De Almeida, D.; Maria Queiroz Araujo, E.; Maria, E.; Araujo, Q. Effects of Beta-Hydroxy-Beta-Methylbutyrate Supplementation on Elderly Body Composition and Muscle Strength: A Review of Clinical Trials of Nutrition Course and GENUT, Professor at Post-Graduation Program Interactive Process of Organs and Systems, Salvador, Brazil. Rev. Artic. Ann. Nutr. Metab. 2008, 77, 16–22.
  24. Phillips, S.M.; Lau, K.J.; D’Souza, A.C.; Nunes, E.A. An Umbrella Review of Systematic Reviews of β-Hydroxy-β-Methyl Butyrate Supplementation in Ageing and Clinical Practice. J. Cachexia. Sarcopenia Muscle 2022, 13, 2265–2275.
  25. Lin, Z.; Zhao, A.; He, J. Effect of β-Hydroxy-β-Methylbutyrate (HMB) on the Muscle Strength in the Elderly Population: A Meta-Analysis. Front. Nutr. 2022, 9, 914866.
  26. Candow, D.G.; Chilibeck, P.D.; Forbes, S.C. Creatine Supplementation and Aging Musculoskeletal Health. Endocrine 2014, 45, 354–361.
  27. Chilibeck, P.; Kaviani, M.; Candow, D.; Zello, G.A. Effect of Creatine Supplementation during Resistance Training on Lean Tissue Mass and Muscular Strength in Older Adults: A Meta-Analysis. Open access J. Sport. Med. 2017, 8, 213–226.
  28. Candow, D.G.; Forbes, S.C.; Chilibeck, P.D.; Cornish, S.M.; Antonio, J.; Kreider, R.B. Effectiveness of Creatine Supplementation on Aging Muscle and Bone: Focus on Falls Prevention and Inflammation. J. Clin. Med. 2019, 8, 488.
  29. Ellis, A.C.; Rosenfeld, J. The Role of Creatine in the Management of Amyotrophic Lateral Sclerosis and Other Neurodegenerative Disorders. CNS Drugs 2004, 18, 967–980.
  30. Adhihetty, P.J.; Beal, M.F. Creatine and Its Potential Therapeutic Value for Targeting Cellular Energy Impairment in Neurodegenerative Diseases. Neuromolecular Med. 2008, 10, 275–290.
  31. Ringseis, R.; Keller, J.; Eder, K. Mechanisms Underlying the Anti-Wasting Effect of l-Carnitine Supplementation under Pathologic Conditions: Evidence from Experimental and Clinical Studies. Eur. J. Nutr. 2013, 52, 1421–1442.
  32. Czyzewski, K.; Stern, L.Z.; Sadeh, M.; Bahl, J.J. Altered Rat Skeletal Muscle Carnitine with Age and after Denervation. Muscle Nerve 1985, 8, 34–37.
  33. Pesce, V.; Fracasso, F.; Cassano, P.; Lezza, A.M.S.; Cantatore, P.; Gadaleta, M.N. Acetyl-L-Carnitine Supplementation to Old Rats Partially Reverts the Age-Related Mitochondrial Decay of Soleus Muscle by Activating Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1alpha-Dependent Mitochondrial Biogenesis. Rejuvenation Res. 2010, 13, 148–151.
  34. Iossa, S.; Pina Mollica, M.; Lionetti, L.; Crescenzo, R.; Botta, M.; Barletta, A.; Liverini, G. Acetyl-L-Carnitine Supplementation Differently Influences Nutrient Partitioning, Serum Leptin Concentration and Skeletal Muscle Mitochondrial Respiration in Young and Old Rats. J. Nutr. 2002, 132, 636–642.
  35. Bernard, A.; Rigault, C.; Mazue, F.; Le Borgne, F.; Demarquoy, J. L-Carnitine Supplementation and Physical Exercise Restore Age-Associated Decline in Some Mitochondrial Functions in the Rat. J. Gerontol. A Biol. Sci. Med. Sci. 2008, 63, 1027–1033.
  36. Kira, Y.; Nishikawa, M.; Ochi, A.; Sato, E.; Inoue, M. L-Carnitine Suppresses the Onset of Neuromuscular Degeneration and Increases the Life Span of Mice with Familial Amyotrophic Lateral Sclerosis. Brain Res. 2006, 1070, 206–214.
  37. Beghi, E.; Pupillo, E.; Bonito, V.; Buzzi, P.; Caponnetto, C.; Chiò, A.; Corbo, M.; Giannini, F.; Inghilleri, M.; Bella, V.L.; et al. Randomized Double-Blind Placebo-Controlled Trial of Acetyl-L-Carnitine for ALS. Amyotroph. Lateral Scler. Front. Degener. 2013, 14, 397–405.
  38. Perim, P.; Marticorena, F.M.; Ribeiro, F.; Barreto, G.; Gobbi, N.; Kerksick, C.; Dolan, E.; Saunders, B. Can the Skeletal Muscle Carnosine Response to Beta-Alanine Supplementation Be Optimized? Front. Nutr. 2019, 6, 135.
  39. Hipkiss, A.R.; Brownson, C. A Possible New Role for the Anti-Ageing Peptide Carnosine. Cell. Mol. Life Sci. CMLS 2000, 57, 747–753.
  40. Stuerenburg, H.J. The Roles of Carnosine in Aging of Skeletal Muscle and in Neuromuscular Diseases. Biochemistry 2000, 65, 862–865.
  41. Solana-Manrique, C.; Sanz, F.J.; Martínez-Carrión, G.; Paricio, N. Antioxidant and Neuroprotective Effects of Carnosine: Therapeutic Implications in Neurodegenerative Diseases. Antioxidants 2022, 11, 848.
  42. Budzeń, S.; Szcześniak, D.; Kopeć, W.; Rymaszewska, J. Anserine and Carnosine Supplementation in the Elderly: Effects on Cognitive Functioning and Physical Capacity. Arch. Gerontol. Geriatr. 2014, 59, 485–490.
  43. Hisatsune, T.; Kaneko, J.; Kurashige, H.; Cao, Y.; Satsu, H.; Totsuka, M.; Katakura, Y.; Imabayashi, E.; Matsuda, H. Effect of Anserine/Carnosine Supplementation on Verbal Episodic Memory in Elderly People. J. Alzheimers. Dis. 2016, 50, 149–159.
  44. Montiel-rojas, D.; Santoro, A.; Nilsson, A.; Franceschi, C.; Capri, M.; Bazzocchi, A.; Battista, G.; de Groot, L.C.P.G.M.; Feskens, E.J.M.; Berendsen, A.A.M.; et al. Beneficial Role of Replacing Dietary Saturated Fatty Acids with Polyunsaturated Fatty Acids in the Prevention of Sarcopenia: Findings from the NU-AGE Cohort. Nutrition 2020, 12, 3079.
  45. Smith, G.I.; Atherton, P.; Reeds, D.N.; Mohammed, B.S.; Rankin, D.; Rennie, M.J.; Mittendorfer, B. Dietary Omega-3 Fatty Acid Supplementation Increases the Rate of Muscle Protein Synthesis in Older Adults: A Randomized Controlled Trial. Am. J. Clin. Nutr. 2011, 93, 402–412.
  46. Smith, G.I.; Julliand, S.; Reeds, D.N.; Sinacore, D.R.; Klein, S.; Mittendorfer, B. Fish Oil-Derived n-3 PUFA Therapy Increases Muscle Mass and Function in Healthy Older Adults. Am. J. Clin. Nutr. 2015, 102, 115–122.
  47. Lipina, C.; Hundal, H.S. Lipid Modulation of Skeletal Muscle Mass and Function. J. Cachexia. Sarcopenia Muscle 2017, 8, 190–201.
  48. Ochi, E.; Tsuchiya, Y. Eicosapentaenoic Acid (EPA) and Docosahexaneoic Acid (DHA) in Muscle Damage and Function. Nutrients 2018, 10, 552.
  49. Wang, Y.; Liu, Z.; Han, Y.; Xu, J.; Huang, W.; Li, Z. Medium Chain Triglycerides Enhances Exercise Endurance through the Increased Mitochondrial Biogenesis and Metabolism. PLoS ONE 2018, 13, e0191182.
  50. Abe, S.; Ezaki, O.; Suzuki, M. Medium-Chain Triglycerides (8:0 and 10:0) Are Promising Nutrients for Sarcopenia: A Randomized Controlled Trial. Am. J. Clin. Nutr. 2019, 110, 652–665.
  51. Abe, S.; Ezaki, O.; Suzuki, M. Medium-Chain Triglycerides in Combination with Leucine and Vitamin D Increase Muscle Strength and Function in Frail Elderly Adults in a Randomized Controlled Trial. J. Nutr. 2016, 146, 1017–1026.
  52. Miyagawa, Y.; Mori, T.; Goto, K.; Kawahara, I.; Fujiwara-Tani, R.; Kishi, S.; Sasaki, T.; Fujii, K.; Ohmori, H.; Kuniyasu, H. Intake of Medium-Chain Fatty Acids Induces Myocardial Oxidative Stress and Atrophy. Lipids Health Dis. 2018, 17, 1–7.
  53. Fujikura, Y.; Kimura, K.; Yamanouchi, K.; Sugihara, H.; Hatakeyama, M.; Zhuang, H.; Abe, T.; Daimon, M.; Morita, H.; Komuro, I.; et al. A Medium-Chain Triglyceride Containing Ketogenic Diet Exacerbates Cardiomyopathy in a CRISPR/Cas9 Gene-Edited Rat Model with Duchenne Muscular Dystrophy. Sci. Rep. 2022, 12, 1–9.
  54. Hiramoto, S.; Yahata, N.; Saitoh, K.; Yoshimura, T.; Wang, Y.; Taniyama, S.; Nikawa, T.; Tachibana, K.; Hirasaka, K. Dietary Supplementation with Alkylresorcinols Prevents Muscle Atrophy through a Shift of Energy Supply. J. Nutr. Biochem. 2018, 61, 147–154.
  55. Siva, N. Can Ketogenic Diet Slow Progression of ALS? Lancet Neurol. 2006, 5, 476.
  56. Moresi, V.; Carrer, M.; Grueter, C.E.; Rifki, O.F.; Shelton, J.M.; Richardson, J.A.; Bassel-Duby, R.; Olson, E.N. Histone Deacetylases 1 and 2 Regulate Autophagy Flux and Skeletal Muscle Homeostasis in Mice. Proc. Natl. Acad. Sci. USA 2012, 109, 1649–1654.
  57. White, Z.; Theret, M.; Milad, N.; Tung, L.W.; Chen, W.W.H.; Sirois, M.G.; Rossi, F.; Bernatchez, P. Cholesterol Absorption Blocker Ezetimibe Prevents Muscle Wasting in Severe Dysferlin-Deficient and Mdx Mice. J. Cachexia. Sarcopenia Muscle 2022, 13, 544–560.
  58. Reggio, A.; Rosina, M.; Krahmer, N.; Palma, A.; Petrilli, L.L.; Maiolatesi, G.; Massacci, G.; Salvatori, I.; Valle, C.; Testa, S.; et al. Metabolic Reprogramming of Fibro/Adipogenic Progenitors Facilitates Muscle Regeneration. Life Sci. Alliance 2020, 3, e202000646.
  59. Wang, Y.; Liu, Q.; Quan, H.; Kang, S.G.; Huang, K.; Tong, T. Nutraceuticals in the Prevention and Treatment of the Muscle Atrophy. Nutrition 2021, 13, 1914.
  60. Zhiyin, L.; Jinliang, C.; Qiunan, C.; Yunfei, Y.; Qian, X. Fucoxanthin Rescues Dexamethasone Induced C2C12 Myotubes Atrophy. Biomed. Pharmacother. 2021, 139, 111590.
  61. Semba, R.D.; Blaum, C.; Guralnik, J.M.; Moncrief, D.T.; Ricks, M.O.; Fried, L.P. Carotenoid and Vitamin E Status Are Associated with Indicators of Sarcopenia among Older Women Living in the Community. Aging Clin. Exp. Res. 2003, 15, 482–487.
  62. Ogawa, M.; Kariya, Y.; Kitakaze, T.; Yamaji, R.; Harada, N.; Sakamoto, T.; Hosotani, K.; Nakano, Y.; Inui, H. The Preventive Effect of β-Carotene on Denervation-Induced Soleus Muscle Atrophy in Mice. Br. J. Nutr. 2013, 109, 1349–1358.
  63. Lewis, L.N.; Hayhoe, R.P.G.; Mulligan, A.A.; Luben, R.N.; Khaw, K.T.; Welch, A.A. Lower Dietary and Circulating Vitamin C in Middle- and Older-Aged Men and Women Are Associated with Lower Estimated Skeletal Muscle Mass. J. Nutr. 2020, 150, 2789–2798.
  64. Takisawa, S.; Funakoshi, T.; Yatsu, T.; Nagata, K.; Aigaki, T.; Machida, S.; Ishigami, A. Vitamin C Deficiency Causes Muscle Atrophy and a Deterioration in Physical Performance. Sci. Rep. 2019, 9, 1–10.
  65. Gunton, J.E.; Girgis, C.M. Vitamin D and Muscle. Bone Rep. 2018, 8, 163–167.
  66. Zhu, K.; Austin, N.; Devine, A.; Bruce, D.; Prince, R.L. A Randomized Controlled Trial of the Effects of Vitamin D on Muscle Strength and Mobility in Older Women with Vitamin D Insufficiency. J. Am. Geriatr. Soc. 2010, 58, 2063–2068.
  67. Bauer, J.M.; Verlaan, S.; Bautmans, I.; Brandt, K.; Donini, L.M.; Maggio, M.; McMurdo, M.E.T.; Mets, T.; Seal, C.; Wijers, S.L.; et al. Effects of a Vitamin D and Leucine-Enriched Whey Protein Nutritional Supplement on Measures of Sarcopenia in Older Adults, the PROVIDE Study: A Randomized, Double-Blind, Placebo-Controlled Trial. J. Am. Med. Dir. Assoc. 2015, 16, 740–747.
  68. Muir, S.W.; Montero-Odasso, M. Effect of Vitamin D Supplementation on Muscle Strength, Gait and Balance in Older Adults: A Systematic Review and Meta-Analysis. J. Am. Geriatr. Soc. 2011, 59, 2291–2300.
  69. Uusi-Rasi, K.; Patil, R.; Karinkanta, S.; Kannus, P.; Tokola, K.; Lamberg-Allardt, C.; Sievänen, H. Exercise and Vitamin D in Fall Prevention among Older Women: A Randomized Clinical Trial. JAMA Intern. Med. 2015, 175, 703–711.
  70. Girgis, C.M.; Clifton-Bligh, R.J.; Hamrick, M.W.; Holick, M.F.; Gunton, J.E. The Roles of Vitamin D in Skeletal Muscle: Form, Function, and Metabolism. Endocr. Rev. 2013, 34, 33–83.
  71. Garcia, M.; Seelaender, M.; Sotiropoulos, A.; Coletti, D.; Lancha, A.H. Vitamin D, Muscle Recovery, Sarcopenia, Cachexia, and Muscle Atrophy. Nutrition 2019, 60, 66–69.
  72. Trojsi, F.; Siciliano, M.; Passaniti, C.; Bisecco, A.; Russo, A.; Lavorgna, L.; Esposito, S.; Ricciardi, D.; Monsurrò, M.R.; Tedeschi, G.; et al. Vitamin D Supplementation Has No Effects on Progression of Motor Dysfunction in Amyotrophic Lateral Sclerosis (ALS). Eur. J. Clin. Nutr. 2020, 74, 167–175.
  73. Blasco, H.; Madji Hounoum, B.; Dufour-Rainfray, D.; Patin, F.; Maillot, F.; Beltran, S.; Gordon, P.H.; Andres, C.R.; Corcia, P. Vitamin D Is Not a Protective Factor in ALS. CNS Neurosci. Ther. 2015, 21, 651–656.
  74. Yang, J.; Park, J.S.; Oh, K.W.; Oh, S.I.; Park, H.M.; Kim, S.H. Vitamin D Levels Are Not Predictors of Survival in a Clinic Population of Patients with ALS. J. Neurol. Sci. 2016, 367, 83–88.
  75. Lanznaster, D.; Bejan-Angoulvant, T.; Gandía, J.; Blasco, H.; Corcia, P. Is There a Role for Vitamin D in Amyotrophic Lateral Sclerosis? A Systematic Review and Meta-Analysis. Front. Neurol. 2020, 11, 697.
  76. Pigna, E.; Greco, E.; Morozzi, G.; Grottelli, S.; Rotini, A.; Minelli, A.; Fulle, S.; Adamo, S.; Mancinelli, R.; Bellezza, I.; et al. Denervation Does Not Induce Muscle Atrophy Through Oxidative Stress. Eur. J. Transl. Myol. 2017, 27, 43–50.
  77. Bo, Y.; Liu, C.; Ji, Z.; Yang, R.; An, Q.; Zhang, X.; You, J.; Duan, D.; Sun, Y.; Zhu, Y.; et al. A High Whey Protein, Vitamin D and E Supplement Preserves Muscle Mass, Strength, and Quality of Life in Sarcopenic Older Adults: A Double-Blind Randomized Controlled Trial. Clin. Nutr. 2019, 38, 159–164.
  78. Kim, C.; Hwang, J.K. Flavonoids: Nutraceutical Potential for Counteracting Muscle Atrophy. Food Sci. Biotechnol. 2020, 29, 1619–1640.
  79. Salucci, S.; Falcieri, E. Polyphenols and Their Potential Role in Preventing Skeletal Muscle Atrophy. Nutr. Res. 2020, 74, 10–22.
  80. Miyawaki, A.; Rojasawasthien, T.; Hitomi, S.; Aoki, Y.; Urata, M.; Inoue, A.; Matsubara, T.; Morikawa, K.; Habu, M.; Tominaga, K.; et al. Oral Administration of Geranylgeraniol Rescues Denervation-Induced Muscle Atrophy via Suppression of Atrogin-1. In Vivo 2020, 34, 2345–2351.
  81. Matsubara, T.; Urata, M.; Nakajima, T.; Fukuzaki, M.; Masuda, R.; Yoshimoto, Y.; Addison, W.N.; Nakatomi, C.; Morikawa, K.; Zhang, M.; et al. Geranylgeraniol-Induced Myogenic Differentiation of C2C12 Cells. In Vivo 2018, 32, 1427–1432.
  82. Nakayama, Y.; Ho, H.J.; Yamagishi, M.; Ikemoto, H.; Komai, M.; Shirakawa, H. Cysteine Sulfoxides Enhance Steroid Hormone Production via Activation of the Protein Kinase A Pathway in Testis-Derived I-10 Tumor Cells. Molecules 2020, 25, 4694.
  83. Ito, N.; Ruegg, U.T.; Kudo, A.; Miyagoe-Suzuki, Y.; Takeda, S. Activation of Calcium Signaling through Trpv1 by NNOS and Peroxynitrite as a Key Trigger of Skeletal Muscle Hypertrophy. Nat. Med. 2013, 19, 101–106.
  84. Li, W.; Swiderski, K.; Murphy, K.T.; Lynch, G.S. Role for Plant-Derived Antioxidants in Attenuating Cancer Cachexia. Antioxidants 2022, 11, 183.
  85. Novak, V.; Rogelj, B.; Župunski, V. Therapeutic Potential of Polyphenols in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Antioxidants 2021, 10, 1328.
  86. Hirasaka, K.; Maeda, T.; Ikeda, C.; Haruna, M.; Kohno, S.; Abe, T.; Ochi, A.; Mukai, R.; Oarada, M.; Teshima-Kondo, S.; et al. Isoflavones Derived from Soy Beans Prevent MuRF1-Mediated Muscle Atrophy in C2C12 Myotubes through SIRT1 Activation. J. Nutr. Sci. Vitaminol. 2013, 59, 317–324.
  87. Tabata, S.; Aizawa, M.; Kinoshita, M.; Ito, Y.; Kawamura, Y.; Takebe, M.; Pan, W.; Sakuma, K. The Influence of Isoflavone for Denervation-Induced Muscle Atrophy. Eur. J. Nutr. 2019, 58, 291–300.
  88. Shen, L.R.; Parnell, L.D.; Ordovas, J.M.; Lai, C.Q. Curcumin and Aging. Biofactors 2013, 39, 133–140.
  89. Shen, L.R.; Xiao, F.; Yuan, P.; Chen, Y.; Gao, Q.K.; Parnell, L.D.; Meydani, M.; Ordovas, J.M.; Li, D.; Lai, C.Q. Curcumin-Supplemented Diets Increase Superoxide Dismutase Activity and Mean Lifespan in Drosophila. Age 2013, 35, 1133–1142.
  90. Gorza, L.; Germinario, E.; Tibaudo, L.; Vitadello, M.; Tusa, C.; Guerra, I.; Bondì, M.; Salmaso, S.; Caliceti, P.; Vitiello, L.; et al. Chronic Systemic Curcumin Administration Antagonizes Murine Sarcopenia and Presarcopenia. Int. J. Mol. Sci. 2021, 22, 11789.
  91. Varma, K.; Amalraj, A.; Divya, C.; Gopi, S. The Efficacy of the Novel Bioavailable Curcumin (Cureit) in the Management of Sarcopenia in Healthy Elderly Subjects: A Randomized, Placebo-Controlled, Double-Blind Clinical Study. J. Med. Food 2021, 24, 40–49.
  92. Simioni, C.; Zauli, G.; Martelli, A.M.; Vitale, M.; Sacchetti, G.; Gonelli, A.; Neri, L.M. Oxidative Stress: Role of Physical Exercise and Antioxidant Nutraceuticals in Adulthood and Aging. Oncotarget 2018, 9, 17181–17198.
  93. Kato, H.; Sato, H.; Okuda, M.; Wu, J.; Koyama, S.; Izumi, Y.; Waku, T.; Iino, M.; Aoki, M.; Arawaka, S.; et al. Therapeutic Effect of a Novel Curcumin Derivative GT863 on a Mouse Model of Amyotrophic Lateral Sclerosis. Amyotroph. Lateral Scler. Frontotemporal Degener. 2021, 23, 489–495.
  94. Bhatia, N.K.; Srivastava, A.; Katyal, N.; Jain, N.; Khan, M.A.I.; Kundu, B.; Deep, S. Curcumin Binds to the Pre-Fibrillar Aggregates of Cu/Zn Superoxide Dismutase (SOD1) and Alters Its Amyloidogenic Pathway Resulting in Reduced Cytotoxicity. Biochim. Biophys. Acta 2015, 1854, 426–436.
  95. Noorafshan, A.; Omidi, A.; Karbalay-Doust, S. Curcumin Protects the Dorsal Root Ganglion and Sciatic Nerve after Crush in Rat. Pathol. Res. Pract. 2011, 207, 577–582.
  96. Ma, J.; Liu, J.; Yu, H.; Wang, Q.; Chen, Y.; Xiang, L. Curcumin Promotes Nerve Regeneration and Functional Recovery in Rat Model of Nerve Crush Injury. Neurosci. Lett. 2013, 547, 26–31.
  97. Mohseni, M.; Sahebkar, A.; Askari, G.; Johnston, T.P.; Alikiaii, B.; Bagherniya, M. The Clinical Use of Curcumin on Neurological Disorders: An Updated Systematic Review of Clinical Trials. Phytother. Res. 2021, 35, 6862–6882.
  98. Shadfar, S.; Couch, M.E.; McKinney, K.A.; Weinstein, L.J.; Yin, X.; Rodriguez, J.E.; Guttridge, D.C.; Willis, M. Oral Resveratrol Therapy Inhibits Cancer-Induced Skeletal Muscle and Cardiac Atrophy in Vivo. Nutr. Cancer 2011, 63, 749–762.
  99. Sun, L.J.; Sun, Y.N.; Chen, S.J.; Liu, S.; Jiang, G.R. Resveratrol Attenuates Skeletal Muscle Atrophy Induced by Chronic Kidney Disease via MuRF1 Signaling Pathway. Biochem. Biophys. Res. Commun. 2017, 487, 83–89.
  100. Huang, Y.; Zhu, X.; Chen, K.; Lang, H.; Zhang, Y.; Hou, P.; Ran, L.; Zhou, M.; Zheng, J.; Yi, L.; et al. Resveratrol Prevents Sarcopenic Obesity by Reversing Mitochondrial Dysfunction and Oxidative Stress via the PKA/LKB1/AMPK Pathway. Aging 2019, 11, 2217–2240.
  101. Wang, D.; Sun, H.; Song, G.; Yang, Y.; Zou, X.; Han, P.; Li, S. Resveratrol Improves Muscle Atrophy by Modulating Mitochondrial Quality Control in STZ-Induced Diabetic Mice. Mol. Nutr. Food Res. 2018, 62, 1700941.
  102. Asami, Y.; Aizawa, M.; Kinoshita, M.; Ishikawa, J.; Sakuma, K. Resveratrol Attenuates Denervation-Induced Muscle Atrophy Due to the Blockade of Atrogin-1 and P62 Accumulation. Int. J. Med. Sci. 2018, 15, 628–637.
  103. Zhang, J.; Ren, J.; Liu, Y.; Huang, D.; Lu, L. Resveratrol Regulates the Recovery of Rat Sciatic Nerve Crush Injury by Promoting the Autophagy of Schwann Cells. Life Sci. 2020, 256, 117959.
  104. Lançon, A.; Kaminski, J.; Tili, E.; Michaille, J.J.; Latruffe, N. Control of MicroRNA Expression as a New Way for Resveratrol to Deliver Its Beneficial Effects. J. Agric. Food Chem. 2012, 60, 8783–8789.
  105. Yu, Y.; Zhou, L.; Li, X.; Liu, J.; Li, H.; Gong, L.; Zhang, J.; Wang, J.; Sun, B. The Progress of Nomenclature, Structure, Metabolism, and Bioactivities of Oat Novel Phytochemical: Avenanthramides. J. Agric. Food Chem. 2022, 70, 446–457.
  106. Yeo, D.; Kang, C.; Zhang, T.; Ji, L.L. Avenanthramides Attenuate Inflammation and Atrophy in Muscle Cells. J. Sport Health Sci. 2019, 8, 189.
  107. Sur, R.; Nigam, A.; Grote, D.; Liebel, F.; Southall, M.D. Avenanthramides, Polyphenols from Oats, Exhibit Anti-Inflammatory and Anti-Itch Activity. Arch. Dermatol. Res. 2008, 300, 569–574.
  108. Guo, W.; Wise, M.L.; Collins, F.W.; Meydani, M. Avenanthramides, Polyphenols from Oats, Inhibit IL-1β-Induced NF-ΚB Activation in Endothelial Cells. Free Radic. Biol. Med. 2008, 44, 415–429.
  109. Kang, C.; Shin, W.S.; Yeo, D.; Lim, W.; Ji, L.L. Anti-Inflammatory Effect of Avenanthramides via NF-ΚB Pathways in C2C12 Skeletal Muscle Cells. Free Radic. Biol. Med. 2018, 117, 30–36.
  110. Kim, Y.; Kim, C.S.; Joe, Y.; Chung, H.T.; Ha, T.Y.; Yu, R. Quercetin Reduces Tumor Necrosis Factor Alpha-Induced Muscle Atrophy by Upregulation of Heme Oxygenase-1. J. Med. Food 2018, 21, 551–559.
  111. Mukai, R.; Matsui, N.; Fujikura, Y.; Matsumoto, N.; Hou, D.X.; Kanzaki, N.; Shibata, H.; Horikawa, M.; Iwasa, K.; Hirasaka, K.; et al. Preventive Effect of Dietary Quercetin on Disuse Muscle Atrophy by Targeting Mitochondria in Denervated Mice. J. Nutr. Biochem. 2016, 31, 67–76.
  112. Hong, K.B.; Lee, H.S.; Kim, D.H.; Moon, J.M.; Park, Y. Tannase-Converted Green Tea Extract with High (-)-Epicatechin Inhibits Skeletal Muscle Mass in Aged Mice. Evid. Based. Complement. Alternat. Med. 2020, 2020, 1–10.
  113. Meador, B.M.; Mirza, K.A.; Tian, M.; Skelding, M.B.; Reaves, L.A.; Edens, N.K.; Tisdale, M.J.; Pereira, S.L. The Green Tea Polyphenol Epigallocatechin-3-Gallate (EGCg) Attenuates Skeletal Muscle Atrophy in a Rat Model of Sarcopenia. J. Frailty Aging 2015, 4, 1–7.
  114. Choi, W.H.; Jang, Y.J.; Son, H.J.; Ahn, J.; Jung, C.H.; Ha, T.Y. Apigenin Inhibits Sciatic Nerve Denervation–Induced Muscle Atrophy. Muscle Nerve 2018, 58, 314–318.
  115. Aoyama, S.; Jia, H.; Nakazawa, K.; Yamamura, J.; Saito, K.; Kato, H. Dietary Genistein Prevents Denervation-Induced Muscle Atrophy in Male Rodents via Effects on Estrogen Receptor-α. J. Nutr. 2016, 146, 1147–1154.
  116. Mukai, R.; Horikawa, H.; Fujikura, Y.; Kawamura, T.; Nemoto, H.; Nikawa, T.; Terao, J. Prevention of Disuse Muscle Atrophy by Dietary Ingestion of 8-Prenylnaringenin in Denervated Mice. PLoS ONE 2012, 7, e45048.
  117. Dyle, M.C.; Ebert, S.M.; Cook, D.P.; Kunkel, S.D.; Fox, D.K.; Bongers, K.S.; Bullard, S.A.; Dierdorff, J.M.; Adams, C.M. Systems-Based Discovery of Tomatidine as a Natural Small Molecule Inhibitor of Skeletal Muscle Atrophy. J. Biol. Chem. 2014, 289, 14913–14924.
  118. Fang, E.F.; Waltz, T.B.; Kassahun, H.; Lu, Q.; Kerr, J.S.; Morevati, M.; Fivenson, E.M.; Wollman, B.N.; Marosi, K.; Wilson, M.A.; et al. Tomatidine Enhances Lifespan and Healthspan in C. Elegans through Mitophagy Induction via the SKN-1/Nrf2 Pathway. Sci. Rep. 2017, 7, 46208.
  119. Ilaiyaraja, N.; Khanum, F. Antioxidant Potential of Tinospora Cordifolia Extracts and Their Protective Effect on Oxidation of Biomolecules. Pharmacogn. J. 2011, 3, 56–62.
  120. Sharma, B.; Dutt, V.; Kaur, N.; Mittal, A.; Dabur, R. Tinospora Cordifolia Protects from Skeletal Muscle Atrophy by Alleviating Oxidative Stress and Inflammation Induced by Sciatic Denervation. J. Ethnopharmacol. 2020, 254, 112720.
  121. Lai, W.; Zheng, Z.; Zhang, X.; Wei, Y.; Chu, K.; Brown, J.; Hong, G.; Chen, L. Salidroside-Mediated Neuroprotection Is Associated with Induction of Early Growth Response Genes (Egrs) Across a Wide Therapeutic Window. Neurotox. Res. 2015, 28, 108–121.
  122. Sun, Y.; Xun, L.; Jin, G.; Shi, L. Salidroside Protects Renal Tubular Epithelial Cells from Hypoxia/Reoxygenation Injury in Vitro. J. Pharmacol. Sci. 2018, 137, 170–176.
  123. Wu, C.; Tang, L.; Ni, X.; Xu, T.; Fang, Q.; Xu, L.; Ma, W.; Yang, X.; Sun, H. Salidroside Attenuates Denervation-Induced Skeletal Muscle Atrophy through Negative Regulation of pro-Inflammatory Cytokine. Front. Physiol. 2019, 10, 665.
  124. Costa, R.G.F.; Caro, P.L.; de Matos-Neto, E.M.; Lima, J.D.C.C.; Radloff, K.; Alves, M.J.; Camargo, R.G.; Pessoa, A.F.M.; Simoes, E.; Gama, P.; et al. Cancer Cachexia Induces Morphological and Inflammatory Changes in the Intestinal Mucosa. J. Cachexia. Sarcopenia Muscle 2019, 10, 1116–1127.
  125. Mangiola, F.; Nicoletti, A.; Gasbarrini, A.; Ponziani, F.R. Gut Microbiota and Aging. Eur. Rev. Med. Pharmacol. Sci. 2018, 22, 7404–7413.
  126. Ubachs, J.; Ziemons, J.; Soons, Z.; Aarnoutse, R.; van Dijk, D.P.J.; Penders, J.; van Helvoort, A.; Smidt, M.L.; Kruitwagen, R.F.P.M.; Baade-Corpelijn, L.; et al. Gut Microbiota and Short-Chain Fatty Acid Alterations in Cachectic Cancer Patients. J. Cachexia. Sarcopenia Muscle 2021, 12, 2007–2021.
  127. Bindels, L.B.; Delzenne, N.M. Muscle Wasting: The Gut Microbiota as a New Therapeutic Target? Int. J. Biochem. Cell Biol. 2013, 45, 2186–2190.
  128. Lahiri, S.; Kim, H.; Garcia-Perez, I.; Reza, M.M.; Martin, K.A.; Kundu, P.; Cox, L.M.; Selkrig, J.; Posma, J.M.; Zhang, H.; et al. The Gut Microbiota Influences Skeletal Muscle Mass and Function in Mice. Sci. Transl. Med. 2019, 11, 502.
  129. Chen, Y.M.; Wei, L.; Chiu, Y.S.; Hsu, Y.J.; Tsai, T.Y.; Wang, M.F.; Huang, C.C. Lactobacillus Plantarum TWK10 Supplementation Improves Exercise Performance and Increases Muscle Mass in Mice. Nutrition 2016, 8, 205.
  130. Ticinesi, A.; Nouvenne, A.; Cerundolo, N.; Catania, P.; Prati, B.; Tana, C.; Meschi, T. Gut Microbiota, Muscle Mass and Function in Aging: A Focus on Physical Frailty and Sarcopenia. Nutrition 2019, 11, 1633.
  131. Giron, M.; Thomas, M.; Dardevet, D.; Chassard, C.; Savary-Auzeloux, I. Gut Microbes and Muscle Function: Can Probiotics Make Our Muscles Stronger? J. Cachexia. Sarcopenia Muscle 2022, 13, 1460–1476.
  132. Zhao, J.; Huang, Y.; Yu, X. A Narrative Review of Gut-Muscle Axis and Sarcopenia: The Potential Role of Gut Microbiota. Int. J. Gen. Med. 2021, 14, 1263–1273.
  133. Nehmi, V.A.; Murata, G.M.; de Moraes, R.C.M.; Lima, G.C.A.; De Miranda, D.A.; Radloff, K.; Costa, R.G.F.; de Jesus, J.d.C.R.; De Freitas, J.A.; Viana, N.I.; et al. A Novel Supplement with Yeast β-Glucan, Prebiotic, Minerals and Silybum Marianum Synergistically Modulates Metabolic and Inflammatory Pathways and Improves Steatosis in Obese Mice. J. Integr. Med. 2021, 19, 439–450.
  134. Claesson, M.J.; Jeffery, I.B.; Conde, S.; Power, S.E.; O’connor, E.M.; Cusack, S.; Harris, H.M.B.; Coakley, M.; Lakshminarayanan, B.; O’sullivan, O.; et al. Gut Microbiota Composition Correlates with Diet and Health in the Elderly. Nature 2012, 488, 178–184.
  135. Montiel-Rojas, D.; Nilsson, A.; Santoro, A.; Franceschi, C.; Bazzocchi, A.; Battista, G.; de Groot, L.C.P.G.M.; Feskens, E.J.M.; Berendsen, A.; Pietruszka, B.; et al. Dietary Fibre May Mitigate Sarcopenia Risk: Findings from the NU-AGE Cohort of Older European Adults. Nutrients 2020, 12, 1075.
  136. Frampton, J.; Murphy, K.G.; Frost, G.; Chambers, E.S. Higher Dietary Fibre Intake Is Associated with Increased Skeletal Muscle Mass and Strength in Adults Aged 40 Years and Older. J. Cachexia. Sarcopenia Muscle 2021, 12, 2134–2144.
  137. David, L.A.; Maurice, C.F.; Carmody, R.N.; Gootenberg, D.B.; Button, J.E.; Wolfe, B.E.; Ling, A.V.; Devlin, A.S.; Varma, Y.; Fischbach, M.A.; et al. Diet Rapidly and Reproducibly Alters the Human Gut Microbiome. Nature 2014, 505, 559–563.
  138. So, D.; Whelan, K.; Rossi, M.; Morrison, M.; Holtmann, G.; Kelly, J.T.; Shanahan, E.R.; Staudacher, H.M.; Campbell, K.L. Dietary Fiber Intervention on Gut Microbiota Composition in Healthy Adults: A Systematic Review and Meta-Analysis. Am. J. Clin. Nutr. 2018, 107, 965–983.
  139. Muegge, B.D.; Kuczynski, J.; Knights, D.; Clemente, J.C.; González, A.; Fontana, L.; Henrissat, B.; Knight, R.; Gordon, J.I. Diet Drives Convergence in Gut Microbiome Functions across Mammalian Phylogeny and within Humans. Science 2011, 332, 970–974.
  140. Frampton, J.; Murphy, K.G.; Frost, G.; Chambers, E.S. Short-Chain Fatty Acids as Potential Regulators of Skeletal Muscle Metabolism and Function. Nat. Metab. 2020, 2, 840–848.
  141. Li, S.; Guerin-Deremaux, L.; Pochat, M.; Wils, D.; Reifer, C.; Miller, L.E. NUTRIOSE Dietary Fiber Supplementation Improves Insulin Resistance and Determinants of Metabolic Syndrome in Overweight Men: A Double-Blind, Randomized, Placebo-Controlled Study. Appl. Physiol. Nutr. Metab. 2010, 35, 773–782.
  142. Solà, R.; Bruckert, E.; Valls, R.M.; Narejos, S.; Luque, X.; Castro-Cabezas, M.; Doménech, G.; Torres, F.; Heras, M.; Farrés, X.; et al. Soluble Fibre (Plantago Ovata Husk) Reduces Plasma Low-Density Lipoprotein (LDL) Cholesterol, Triglycerides, Insulin, Oxidised LDL and Systolic Blood Pressure in Hypercholesterolaemic Patients: A Randomised Trial. Atherosclerosis 2010, 211, 630–637.
  143. Aliasgharzadeh, A.; Dehghan, P.; Gargari, B.P.; Asghari-Jafarabadi, M. Resistant Dextrin, as a Prebiotic, Improves Insulin Resistance and Inflammation in Women with Type 2 Diabetes: A Randomised Controlled Clinical Trial. Br. J. Nutr. 2015, 113, 321–330.
  144. Dehghan, P.; Gargari, B.P.; Jafar-Abadi, M.A.; Aliasgharzadeh, A. Inulin Controls Inflammation and Metabolic Endotoxemia in Women with Type 2 Diabetes Mellitus: A Randomized-Controlled Clinical Trial. Int. J. Food Sci. Nutr. 2014, 65, 117–123.
  145. Buigues, C.; Fernández-Garrido, J.; Pruimboom, L.; Hoogland, A.J.; Navarro-Martínez, R.; Martínez-Martínez, M.; Verdejo, Y.; Carmen Mascarós, M.; Peris, C.; Cauli, O. Effect of a Prebiotic Formulation on Frailty Syndrome: A Randomized, Double-Blind Clinical Trial. Int. J. Mol. Sci. 2016, 17, 932.
  146. Di Gioia, D.; Bozzi Cionci, N.; Baffoni, L.; Amoruso, A.; Pane, M.; Mogna, L.; Gaggìa, F.; Lucenti, M.A.; Bersano, E.; Cantello, R.; et al. A Prospective Longitudinal Study on the Microbiota Composition in Amyotrophic Lateral Sclerosis. BMC Med. 2020, 18, 153.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)
Video Production Service
Feedback