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Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia
Open accessAbstract
Mitochondrial dysfunction and low nicotinamide adenine dinucleotide (NAD + ) levels are hallmarks of skeletal muscle ageing and sarcopenia 1–3 , but it is unclear whether these defects result from local changes or can be mediated by systemic or dietary cues. Here we report a functional link between circulating levels of the natural alkaloid trigonelline, which is structurally related to nicotinic acid 4 , NAD + levels and muscle health in multiple species. In humans, serum trigonelline levels are reduced with sarcopenia and correlate positively with muscle strength and mitochondrial oxidative phosphorylation in skeletal muscle. Using naturally occurring and isotopically labelled trigonelline, we demonstrate that trigonelline incorporates into the NAD + pool and increases NAD + levels in Caenorhabditis elegans , mice and primary myotubes from healthy individuals and individuals with sarcopenia. Mechanistically, trigonelline does not activate GPR109A but is metabolized via the nicotinate phosphoribosyltransferase/Preiss–Handler pathway 5,6 across models. In C. elegans , trigonelline improves mitochondrial respiration and biogenesis, reduces age-related muscle wasting and increases lifespan and mobility through an NAD + -dependent mechanism requiring sirtuin. Dietary trigonelline supplementation in male mice enhances muscle strength and prevents fatigue during ageing. Collectively, we identify nutritional supplementation of trigonelline as an NAD + -boosting strategy with therapeutic potential for age-associated muscle decline.
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TL;DR
Trigonelline, a natural alkaloid related to nicotinic acid, is identified as an NAD+ precursor that boosts NAD+ via the NAPRT/Preiss–Handler pathway and improves mitochondrial and muscle function during ageing across human, mouse and C. elegans models. Serum trigonelline is reduced in human sarcopenia and correlates with muscle strength, mitochondrial oxidative phosphorylation and muscle NAD+.
Key findings
- In the MEMOSA Singapore Sarcopenia Study, serum trigonelline was lower in individuals with sarcopenia than in healthy controls (n = 20 per group) and correlated positively with ALMI, grip strength and gait speed; it was also associated with skeletal muscle NAD+ and mitochondrial oxidative phosphorylation, with replication in the Bushehr elderly health cohort.
- Trigonelline increased NAD+ in human skeletal muscle myotubes (EC50 = 315 µM in control cells; EC50 = 110 µM in FK866-treated cells), in primary myotubes from healthy donors and donors with sarcopenia, in aged mouse myotubes, in C. elegans and in mouse tissues; isotopically labelled trigonelline was directly incorporated into NAD+ as M + 1 NAD+.
- Trigonelline required NAPRT/Preiss–Handler pathway activity: NAPRT knockdown or 2-OHNA blocked trigonelline-driven NAD+ increases and mitochondrial rescue, whereas NR still worked; trigonelline did not activate GPR109A up to 1 mM, while nicotinic acid had an EC50 = 2.5 µM.
- In C. elegans, trigonelline extended lifespan, improved mobility, reduced paralysis and improved myofibre integrity through nprt-1 and sir-2.1; in aged mice, 12-week dietary trigonelline increased grip strength and prevented approximately 50% of age-related fatigue decline without changing muscle mass or maximal tetanic force.
Methods
- Human studies included the MEMOSA Singapore Sarcopenia Study (20 Chinese men aged 65–79 years with sarcopenia and 20 age-matched healthy controls), the Bushehr elderly health cohort (186 older men aged ≥60 years) and the Hertfordshire Sarcopenia Study Extension for primary myotubes; serum metabolites were measured by LC–MS/MS, muscle RNA-seq was used for pathway enrichment, and muscle mass/function were assessed by DXA, grip strength and gait speed.
- Cell and animal experiments used human skeletal muscle myotubes, primary human and mouse myotubes, HepG2, C2C12 and PTEC cells; NAPRT shRNA, FK866 and 2-OHNA treatments; isotopically labelled trigonelline; C. elegans N2 and RNAi strains; and aged C57BL/6JRj mice given acute or chronic trigonelline at 300 mg kg−1 per day, with Seahorse respirometry, LC–HRMS metabolomics, qPCR, immunoblot, histology and in situ muscle contractility.
- Statistical analyses used two-tailed unpaired Student’s t-tests, one-way or two-way ANOVA with post hoc tests, log-rank tests for lifespan, and Spearman correlations, with data expressed as mean ± s.e.m.
Limitations
- The paper states that no trigonelline demethylase is known, that the SHMT2 correlation requires further exploration, that trigonelline cannot reverse all causes of sarcopenia and should be combined with other nutrients such as protein, vitamin D or omega-3 fatty acids, and that preclinical muscle function tests do not always translate to human performance.
- The paper also notes heterogeneity and complexity in systemic NAD+ metabolism and calls for future comparative studies with different precursors in specific models and in humans.
- Evident from the text: the human sarcopenia association is cross-sectional and cannot establish causality; the main MEMOSA serum analysis is small (n = 20 per group) and restricted to Chinese male participants; the mouse supplementation studies used male mice; and chronic trigonelline exposure flattened muscle NAD+ and oxidative phosphorylation protein effects compared with acute exposure, suggesting long-term physiological compensation.
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![Fig. 4 Trigonelline supplementation enhances mitochondrial activity and muscle function in aged mice. a, Mitochondrial complex I activity normalized to citrate synthase activity (UCI × UCS−1) in gastrocnemius muscle of aged mice (20 months) after a 5-day dietary supplementation of trigonelline (unpaired, two-tailed Student’s t-test, n = 7–8 biological replicates per group). b, Mitochondrial complex I (NDUFB8) protein levels in the same samples as in a (unpaired, two-tailed Student’s t-test, n = 6 biological replicates per group). c, Succinate dehydrogenase (SDH) activity in the quadriceps muscle of the same groups as in a (unpaired, two-tailed Student’s t-test, n = 7 biological replicates per group). d, Mitochondrial complex II (succinate dehydrogenase [ubiquinone] iron-sulphur subunit, mitochondrial (SDHE)) protein levels in the same samples as in a (unpaired, two-tailed Student’s t-test, n = 6 biological replicates per group). e, Plasma trigonelline levels measured in aged mice (22–24 months) after 12 weeks of trigonelline supplementation (unpaired, two-tailed Student’s t-test, n = 13 and 15 biological replicates per group). f, LC–HRMS measurement of trigonelline levels in gastrocnemius muscle and liver of the same mice groups as in e (unpaired, two-tailed Student’s t-test; gastrocnemius: n = 5 and 6, liver: n = 13 and 16 biological replicates per group); <LOQ, below the level of quantification. g, Lean mass normalized to body weight of aged mice after 12 weeks of treatment as in e (unpaired, two-tailed Student’s t-test, n = 13 and 15 biological replicates per group). h, Tibialis anterior muscle mass of aged mice after 12 weeks of treatment as in e (unpaired, two-tailed Student’s t-test, n = 13 and 15 biological replicates per group). i, Grip strength of aged mice after 12 weeks of treatment as in e (unpaired, two-tailed Student’s t-test, n = 13 and 15 biological replicates per group). j, In situ muscle contractility normalized to initial force after supramaximal stimulation of the tibialis anterior muscle in young controls and aged mice after 12 weeks of treatment as in e (two-way ANOVA followed by uncorrected Fisher’s least significant difference tests; n = 11–14 biological replicates per group). All data are expressed as the mean ± s.e.m. with *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. Individual P values are reported in Fig. 4 of the Source data. Source data](/paper-figures/24e3531fef804be5b8fee5532e2b2744/trigonelline-is-an-nad-precursor-that-improves-muscle-function-during-ageing-and-figure-4.jpg)
Verification
Claims the paper makes
90 Own result · 26 Own interpretation · 20 Not checked yet · 10 Own method · 7 No basis given · 1 Supported · 1 Partly supported · 1 Couldn’t confirm · accuracy not yet measured
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“Mechanistically, trigonelline does not activate GPR109A but is metabolized via the nicotinate phosphoribosyltransferase/Preiss–Handler pathway5,6 across models.”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Abstract
What the sources say
- Could not verifycites [5] Lee, Y., Jeong, H., Park, K. H. & Kim, K. W. Effects of NAD+ in Caenorhabditis elegans models of neuronal damage. Biomolecules 10, 993 (2020). sourceExperimental — accuracy not yet measured
Section 1, “NAD+ Biosynthesis Pathway in C. elegans” (page unavailable), describes nicotinic acid entering the Preiss–Handler pathway, and Section 3.1 names a C. elegans NAPRT ortholog. Neither passage addresses whether trigonelline is metabolized through that pathway across models. Searches for trigonelline with NAPRT, Preiss–Handler and GPR109A found no passage establishing that claim. (LLM, conf=0.73)
- Could not verifycites [6] Ruggieri, S., Orsomando, G., Sorci, L. & Raffaelli, N. Regulation of NAD biosynthetic enzymes modulates NAD-sensing processes to shape mammalian cell physiology under varying biological cues. Biochim. Biophys. Acta 1854, 1138–1149 (2015). sourceExperimental — accuracy not yet measured
Section 4.4 describes NAPRT as salvaging nicotinic acid, and Section 3 describes the Preiss–Handler pathway, but neither passage addresses trigonelline. Searches for “trigonelline” and for a methylated nicotinic-acid substrate found no passage establishing its metabolism through this pathway across models. No page numbers were available in our copy. (LLM, conf=0.76)
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Every source the paper cites for this claim was checked and supports it.
In the paper
“Similarly, the NAPRT inhibitor 2-hydroxynicotinic acid (2-OHNA)39 blocked the conversion of trigonelline to NAD+ in HSMMs”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Main
What the sources say
- Supportedcites [39] Piacente, F. et al. Nicotinic acid phosphoribosyltransferase regulates cancer cell metabolism, susceptibility to NAMPT inhibitors, and DNA repair. Cancer Res. 77, 3857–3869 (2017). source
The citation is attached to the identification of 2-hydroxynicotinic acid as a NAPRT inhibitor. In the section on NAPRT inhibition, the paper reports that 2-HNA significantly inhibited NAPRT activity; the citation does not appear to attribute the HSMM trigonelline experiment to this source. (LLM, conf=0.92)
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In the paper
“Dietary records indicate that serum trigonelline levels are independent of dietary caffeine and vitamin B3 intake in this cohort, but possibly linked to other dietary factors, such as folate and fibre intake (Extended Data Fig. 1c and Extended Data Table 3).”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Main
hedged- Asserted: passes — The authors put it forward as true.
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In the paper
“Similarly, trigonelline also increased NAD+ levels in primary myotubes derived from aged mice (Fig. 1h).”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Main
plaindirect- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Dietary trigonelline supplementation in male mice enhances muscle strength and prevents fatigue during ageing.”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“SHMT2, which is involved in mitochondrial one-carbon metabolism, had the strongest association with serum trigonelline (Extended Data Fig. 1k)”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Main
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Trigonelline levels were positively correlated with muscle mass assessed via Appendicular Lean Mass Index (ALMI) measured using dual-energy X-ray absorptiometry (DXA), grip strength and gait speed, all parameters used in the clinical definition of sarcopenia3,9 (Fig. 1b).”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Main
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In the paper
“whereas NR and NMN rapidly disappeared within hours after conversion to NAM (Extended Data Fig. 1i).”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Main
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In the paper
“and also increased NAD+ levels after prolonged treatment (Extended Data Fig. 1e)”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Main
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Trigonelline increased NAD+ in control cells (half maximal effective concentration (EC50) = 315 µM) (Fig. 1e)”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Main
plaindirect- Asserted: passes — The authors put it forward as true.
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- It may state two separate claims as one. 54
- Probably not a substantial claim. 24
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In the paper
“Treating primary myotubes from different donors with sarcopenia and aged-matched healthy controls35 raised cellular NAD+ (Fig. 1g) with comparable efficiency between groups (Extended Data Fig. 1j).”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Main
What the sources say
- Partly supportedcites [35] Patel, H. P. et al. Hertfordshire sarcopenia study: design and methods. BMC Geriatr. 10, 43 (2010). sourceExperimental — accuracy not yet measured
The citation is attached to the donor description, not the reported NAD+ result. The Discussion (page not available) describes muscle biopsies from older participants, supporting the study as a source of muscle tissue. It does not establish that the donors were divided into sarcopenia and age-matched healthy-control groups or that primary myotubes were derived from them; it also does not report trigonelline treatment or comparable NAD+ responses. (LLM, conf=0.78)
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- Partly supported
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In the paper
“In C. elegans, trigonelline improves mitochondrial respiration and biogenesis, reduces age-related muscle wasting and increases lifespan and mobility through an NAD+-dependent mechanism requiring sirtuin.”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“fully rescued NAD+ deficiency in FK866-treated cells (EC50 = 110 µM) (Fig. 1f)”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Main
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In the paper
“When compared to other NAD+ precursors in primary human muscle cells, trigonelline and the salvage precursor NAM induced NAD+ by approximately 50% while the NRK pathway precursors NR and NMN33 increased NAD+ levels approximately twofold (Extended Data Fig. 1f).”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Main
What the sources say
- Not checked yetcites [33] Bogan, K. L. & Brenner, C. Nicotinic acid, nicotinamide, and nicotinamide riboside: a molecular evaluation of NAD+ precursor vitamins in human nutrition. Annu. Rev. Nutr. 28, 115–130 (2008). source
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In the paper
“while all precursors had similar efficacy in renal proximal tubular epithelial cells (PTECs) (Extended Data Fig. 1h).”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Main
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
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In the paper
“and were largely cleared after an overnight wash-out (Extended Data Fig. 2a).”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Main
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“After trigonelline gavage, Nampt and Nrk1 expression was downregulated in the liver, while Nrk1 and Nrk2 were upregulated in muscle in both treatment groups (Extended Data Fig. 2o).”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Main
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Acute dosing of trigonelline in wild-type (WT) and Naprt KO mice40 (Fig. 2k and Extended Data Fig. 2j) equally increased trigonelline in tissues (Extended Data Fig. 2k), distal NAD+ metabolite fluxes in the liver and blood (Extended Data Fig. 2l,m) and tissue NAD+ levels (Extended Data Fig. 2l–n).”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Main
What the sources say
- Not checked yetcites [40] Yaku, K. et al. BST1 regulates nicotinamide riboside metabolism via its glycohydrolase and base-exchange activities. Nat. Commun. 12, 6767 (2021). source
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In the paper
“However, in Naprt KO mice treated with trigonelline, NA accumulated in the blood and liver (Fig. 2l), while NAMN was strongly downregulated (Fig. 2m)”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Main
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In the paper
“LC–HRMS analysis also confirmed that 2-OHNA blocks increased NAD+ after trigonelline treatment (Fig. 2g), without affecting cellular trigonelline levels in the treated groups (Extended Data Fig. 2h).”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Main
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In the paper
“Administration of isotopically labelled trigonelline in mice was highly bioavailable with high levels of the parent trigonelline molecule detected in the liver, gastrocnemius muscle, kidney, blood and urine 2 h after oral intake”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Main
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In the paper
“After trigonelline treatment, the Preiss–Handler pathway-related metabolites nicotinic acid adenine dinucleotide (NAAD) and NAMN downstream of NAPRT6,33 were increased and blocked by NAPRT inhibition with 2-OHNA (Fig. 2h,i)”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Main
What the sources say
- Not checked yetcites [6] Ruggieri, S., Orsomando, G., Sorci, L. & Raffaelli, N. Regulation of NAD biosynthetic enzymes modulates NAD-sensing processes to shape mammalian cell physiology under varying biological cues. Biochim. Biophys. Acta 1854, 1138–1149 (2015). source
- Not checked yetcites [33] Bogan, K. L. & Brenner, C. Nicotinic acid, nicotinamide, and nicotinamide riboside: a molecular evaluation of NAD+ precursor vitamins in human nutrition. Annu. Rev. Nutr. 28, 115–130 (2008). source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Like the 24-h treatment (Extended Data Fig. 2g), trigonelline boosted NAD+ and this effect was blocked by NAPRT inhibition with 2-OHNA (Fig. 2o)”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Main
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“while 2-OHNA abolished the effects of trigonelline but not NR (Fig. 2p).”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Main
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Conversely, various levels of cellular NAD+ depletion by blocking NAD+ salvage with FK866 for 24 h were rescued by trigonelline (Fig. 1f and Extended Data Fig. 2f), but not when co-treating with 2-OHNA (Extended Data Fig. 2g).”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Main
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In the paper
“activated the expression of genes linked to mitochondrial respiration and proteostasis (Fig. 3e), similar to NR (Extended Data Fig. 3c and14,43)”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Main
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In the paper
“trigonelline raised NAD+ levels in aged nematodes (Fig. 3c); its NAD+-boosting effects were comparable to NA and NAM, and partially lower than NR and NMN (Extended Data Fig. 3b).”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Main
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In the paper
“Trigonelline significantly extended the lifespan, with comparable effects to equimolar levels of NR (Fig. 3b and Extended Data Fig. 3a).”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Main
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Knockdown of nprt-1 or sir-2.1 (Extended Data Fig. 3j), the predominant sirtuin in N2 worms (Extended Data Fig. 3k), both blunted the lifespan-extending effects and mobility benefits of trigonelline (Fig. 3l–n)”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Main
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In the paper
“In contrast, NR was still able to bypass NAPRT inhibition and increase respiration (Fig. 2q).”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Main
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In the paper
“which was also rescued by trigonelline but blocked when trigonelline was co-treated with 2-OHNA (Fig. 2q).”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Main
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Finally, respirometry performed with mitochondrial complex inhibitors revealed higher levels of complex II-driven and complex IV-driven respiration in trigonelline-treated cells, again dependent on NAPRT (Extended Data Fig. 2q).”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Main
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Body composition was not impacted by the treatment, with no changes in lean and fat mass distribution in trigonelline-treated mice (Fig. 4g and Extended Data Fig. 4e)”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Main
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In the paper
“Trigonelline treatment in aged mice increased different domains of muscle performance that mobilize both leg and arm muscles by improving both muscle fatigue and grip strength”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Main
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In the paper
“we showed that trigonelline is metabolized via the Preiss–Handler pathway and requires NAPRT to boost NAD+, stimulate mitochondrial metabolism and increase mobility and lifespan during ageing.”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Main
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In the paper
“our correlation analyses did not detect an association between circulating trigonelline and dietary caffeine intake levels in a population from the Middle East, possibly because coffee consumption is low in this population.”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Main
hedged- Asserted: passes — The authors put it forward as true.
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In the paper
“the dietary intake of folate and fibre was linked to circulating trigonelline levels.”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Main
plaincorrelational- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
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In the paper
“our comparative studies demonstrate that trigonelline has similar cellular and physiological benefits to NA and NR in cells or nematodes, most probably because of its higher stability than ribosylated precursors.”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Main
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“However, patients with sarcopenia had lower circulating concentrations of trigonelline, a natural alkaloid found in plants4 and animals, including in humans29,30 (Fig. 1a).”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Main
What the sources say
- Not checked yetcites [4] Ashihara, H. et al. Trigonelline and related nicotinic acid metabolites: occurrence, biosynthesis, taxonomic considerations, and their roles in planta and in human health. Phytochem. Rev. 14, 765–798 (2015). source
- Not checked yetcites [29] Barton, W. et al. The microbiome of professional athletes differs from that of more sedentary subjects in composition and particularly at the functional metabolic level. Gut 67, 625–633 (2018).
- Not checked yetcites [30] Calvani, R. et al. Gut microbiome-derived metabolites characterize a peculiar obese urinary metabotype. Int. J. Obes. 34, 1095–1098 (2010). source
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
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In the paper
“Collectively, we identify nutritional supplementation of trigonelline as an NAD+-boosting strategy with therapeutic potential for age-associated muscle decline.”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
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- Rests on an assumption: The effects of trigonelline on muscle ageing observed in C. elegans and mice are predictive of therapeutic benefit in humans.
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In the paper
“Mitochondrial dysfunction and low nicotinamide adenine dinucleotide (NAD+) levels are hallmarks of skeletal muscle ageing and sarcopenia1–3”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Abstract
What the sources say
- Not checked yetcites [1] Gomes, A. P. et al. Declining NAD+ induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during aging. Cell 155, 1624–1638 (2013). source
- Not checked yetcites [2] Janssens, G. E. et al. Healthy aging and muscle function are positively associated with NAD+ abundance in humans. Nat. Aging 2, 254–263 (2022). source
- Not checked yetcites [3] Migliavacca, E. et al. Mitochondrial oxidative capacity and NAD+ biosynthesis are reduced in human sarcopenia across ethnicities. Nat. Commun. 10, 5808 (2019). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Altogether, our in vitro and in vivo results indicate that trigonelline is metabolized through the Preiss–Handler pathway via NAPRT and promotes NAD+ biosynthesis via both direct and indirect mechanisms.”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Main
hedgeddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Altogether, these results demonstrate that trigonelline is a bona fide NAD+ precursor that is directly incorporated in NAD+ in cells and multiple tissues.”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Main
boosteddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“This suggests that trigonelline engages the Preiss–Handler pathway during first-pass metabolism and that secondary compensations through the NR–NMN–NRK pathway also contribute to NAD+ in Naprt KOs.”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Main
hedgeddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“with hepatic incorporation being faster probably because of a first-pass effect (Extended Data Fig. 2c).”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Main
hedgedconditional- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
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In the paper
“SHMT2 is unlikely to directly demethylate trigonelline because it is not a N-methyltransferase and is known to cross-talk with NAD+ metabolism indirectly37,38.”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Main
What the sources say
- Not checked yetcites [37] Ye, J. et al. Serine catabolism regulates mitochondrial redox control during hypoxia. Cancer Discov. 4, 1406–1417 (2014). source
- Not checked yetcites [38] Zhang, Y. et al. SHMT2 promotes cell viability and inhibits ROS-dependent, mitochondrial-mediated apoptosis via the intrinsic signaling pathway in bladder cancer cells. Cancer Gene Ther. 29, 1514–1527 (2022). source
hedged- Asserted: passes — The authors put it forward as true.
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In the paper
“As expected, trigonelline increased NAD+ levels after sir-2.1 knockdown because sirtuins act as NAD+ sensors downstream of NAD+ biosynthesis and sir-2.1 knockdown did not change baseline NAD+ levels (Extended Data Fig. 3l).”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Main
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“proteins (Fig. 4b,d and Extended Data Fig. 4p) were flattened in chronic versus acute exposure, probably because of long-term physiological compensation as observed in clinical studies in muscle with dietary administration of other NAD+ precursors46,47.”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Main
What the sources say
- Not checked yetcites [46] Elhassan, Y. S. et al. Nicotinamide riboside augments the aged human skeletal muscle NAD+ metabolome and induces transcriptomic and anti-inflammatory signatures. Cell Rep. 28, 1717–1728 (2019). source
- Not checked yetcites [47] Yoshino, M. et al. Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. Science 372, 1224–1229 (2021). source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Our previous profiling of muscle biopsies from patients with sarcopenia versus age-matched healthy controls revealed that mitochondrial dysfunction and reduced NAD+, two well-established molecular hallmarks of organismal ageing11, are prominent features of pathological progression and sarcopenia3.”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Main
What the sources say
- Not checked yetcites [3] Migliavacca, E. et al. Mitochondrial oxidative capacity and NAD+ biosynthesis are reduced in human sarcopenia across ethnicities. Nat. Commun. 10, 5808 (2019). source
- Not checked yetcites [11] López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M. & Kroemer, G. Hallmarks of aging: an expanding universe. Cell 186, 243–278 (2023). source
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Its synthesis from NA via methylation confers protective and adaptive functions4,48, without an established reutilization as a Preiss–Handler substrate49,50.”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Main
What the sources say
- Not checked yetcites [4] Ashihara, H. et al. Trigonelline and related nicotinic acid metabolites: occurrence, biosynthesis, taxonomic considerations, and their roles in planta and in human health. Phytochem. Rev. 14, 765–798 (2015). source
- Not checked yetcites [48] Ashihara, H., Ludwig, I.A. and Crozier, A. Physiological aspect and biotechnology of trigonelline. In Plant Nucleotide Metabolism: Biosynthesis, Degradation, and Alkaloid Formation (eds Ashihara, H., Ludwig, I. A. and Crozier, A.) 351–365 (John Wiley & Sons, 2020). source
- Not checked yetcites [49] Li, W. et al. A Novel N-methyltransferase in Arabidopsis appears to feed a conserved pathway for nicotinate detoxification among land plants and is associated with lignin biosynthesis. Plant Physiol. 174, 1492–1504 (2017). source
- Not checked yetcites [50] Wu, R. et al. MeNA, controlled by reversible methylation of nicotinate, is an NAD precursor that undergoes long-distance transport in Arabidopsis. Mol. Plant 11, 1264–1277 (2018). source
plaindirect- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“chronic trigonelline administration mitigates muscle decline during ageing by stimulating mitochondria and increasing muscle performance and resistance to fatigue during high-intensity contraction.”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Main
plaindirect- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“probably because tetanic force relies on muscle mass and neuromuscular coupling, both of which were not affected by trigonelline.”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Main
hedgedconditional- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Collectively, these results demonstrate that trigonelline functionally rescues NAD+ deficiency and confirm that trigonelline requires NAPRT and a functional Preiss–Handler pathway for physiological activity on mitochondrial bioenergetics.”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Main
boosteddirect- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Together, these results validate the physiological requirement of the Preiss–Handler pathway for longevity, mitochondrial and functional benefits of trigonelline in an in vivo model, and demonstrate that the observed benefits on ageing and health span require the NAD+-dependent sirtuin deacetylase.”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Main
boosteddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“trigonelline is particularly abundant in plant-derived food products, such as coffee beans and fenugreek seeds, which have been reported to modulate endogenous trigonelline levels in humans4,51,52.”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Main
What the sources say
- Not checked yetcites [4] Ashihara, H. et al. Trigonelline and related nicotinic acid metabolites: occurrence, biosynthesis, taxonomic considerations, and their roles in planta and in human health. Phytochem. Rev. 14, 765–798 (2015). source
- Not checked yetcites [51] Midttun, Ø., Ulvik, A., Nygård, O. & Ueland, P. M. Performance of plasma trigonelline as a marker of coffee consumption in an epidemiologic setting. Am. J. Clin. Nutr. 107, 941–947 (2018). source
- Not checked yetcites [52] Gadgil, M. D. et al. Diet patterns are associated with circulating metabolites and lipid profiles of South Asians in the United States. J. Nutr. 152, 2358–2366 (2022). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the benefits of trigonelline on muscle performance did not arise from structural adaptations in the skeletal muscle architecture, such as myofibre cross-sectional area, vascularization and fibrosis, but were linked to functional improvements of the mitochondrial respiratory activity of complexes I and II.”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Main
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“fatigue and grip strength are also well-established measures of sarcopenia and physical frailty54,55 and are commonly used to assess the pathological impairment of quality of life in older people in clinical practice.”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Main
What the sources say
- Not checked yetcites [54] Cruz-Jentoft, A. J. et al. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing 48, 16–31 (2019). source
- Not checked yetcites [55] Fried, L. P. et al. Frailty in older adults: evidence for a phenotype. J. Gerontol. A Biol. Sci. Med. Sci. 56, M146–M156 (2001). source
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. It may state two separate claims as one.
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In the paper
“Trigonelline was proposed as a biomarker of metabolic health or physical fitness because urinary trigonelline levels decrease during obesity and increase in professional athletes29,30.”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Main
What the sources say
- Not checked yetcites [29] Barton, W. et al. The microbiome of professional athletes differs from that of more sedentary subjects in composition and particularly at the functional metabolic level. Gut 67, 625–633 (2018).
- Not checked yetcites [30] Calvani, R. et al. Gut microbiome-derived metabolites characterize a peculiar obese urinary metabotype. Int. J. Obes. 34, 1095–1098 (2010). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“we conclude that trigonelline cannot reverse all causes of sarcopenia and will have to be combined with other nutrients that support muscle mass, such as protein, vitamin D or omega 3 fatty acids, or for the nutritional management of sarcopenia7.”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Main
What the sources say
- Not checked yetcites [7] Cruz-Jentoft, A. J. & Sayer, A. A. Sarcopenia. Lancet 393, 2636–2646 (2019). source
plain- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“sarcopenia is a multifactorial disease where both muscle mass and function decline beyond pathological thresholds7,8.”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Main
What the sources say
- Not checked yetcites [7] Cruz-Jentoft, A. J. & Sayer, A. A. Sarcopenia. Lancet 393, 2636–2646 (2019). source
- Not checked yetcites [8] Cruz-Jentoft, A. J. et al. Sarcopenia: European consensus on definition and diagnosis: report of the European Working Group on Sarcopenia in Older People. Age Ageing 39, 412–423 (2010). source
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“suggests that trigonelline could cross-talk with the S-adenosyl-L-methionine-dependent methyltransferase activity of SHMT2 and folate/one-carbon metabolism”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Main
hedgedconditional- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“demonstrates the benefits of its therapeutic dietary supplementation for mitochondrial function, muscle health and mobility during ageing.”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Main
boosteddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Although high coffee consumption has been associated with a lower prevalence of sarcopenia in some populations53”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Main
What the sources say
- Not checked yetcites [53] Chung, H. et al. Association of coffee consumption with sarcopenia in Korean elderly men: analysis using the Korea National Health and Nutrition Examination Survey, 2008–2011. Korean J. Fam. Med. 38, 141–147 (2017). source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Equal protein load (20 µg per well) and consistent gel transfer was verified by Revert Total Protein Stain (LI-COR).”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Methods > RNA and immunoblot analyses in rodent tissues
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Respiration rates were normalized to the number of worms in each well and averaged over five measurements.”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Methods > C. elegans experiments
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“NAD+ levels were normalized on the protein content.”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Methods > C. elegans experiments
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“trigonelline can protect from metabolic dysfunction and improve glucose tolerance both in mice and humans62,63.”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Main
What the sources say
- Not checked yetcites [62] van Dijk, A. E. et al. Acute effects of decaffeinated coffee and the major coffee components chlorogenic acid and trigonelline on glucose tolerance. Diabetes Care 32, 1023–1025 (2009). source
- Not checked yetcites [63] Yoshinari, O. & Igarashi, K. Anti-diabetic effect of trigonelline and nicotinic acid, on KK-Ay mice. Curr. Med. Chem. 17, 2196–2202 (2010). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Isotopically labelled internal standards, including fully labelled 13C yeast extract and nicotinamide-d4, were included for data normalization.”
- Also stated in: § Metabolomics analyses in cells and rodent tissues · plain
“Additionally, isotopically labelled acyl-carnitines (NSK-B, Cambridge Isotope Laboratories) were added for normalization in cell metabolomics.”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Methods > Metabolomics analyses in cells and rodent tissues
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Also stated in: § Metabolomics analyses in cells and rodent tissues · plain
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Trigonelline concentrations were determined using calibration curves ranging from 10 µM to 1,000 µM.”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Methods > Metabolomics analyses in cells and rodent tissues
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“In vivo treatments were performed with trigonelline monohydrate (Laurus Labs) after internal quality control using MS, showing more than 99.9% purity”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Methods > Animal studies
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Protein layers from cells, liver and muscle samples were quantified using a bicinchoninic acid assay (Thermo Fisher Scientific) for normalization.”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Methods > Metabolomics analyses in cells and rodent tissues
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Our preclinical experiments demonstrated that trigonelline is an NAD+ precursor that optimizes mitochondrial function to improve muscle strength and prevent fatigue during ageing.”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Main
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The heterogeneity of NAD+ biosynthesis and metabolism also suggests that some physiological specificity may exist between different precursors across organs”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Main
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“For worms, two housekeeping genes were used to normalize the expression data, that is, actin (act-1) and peroxisomal membrane protein 3 (pmp-3).”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Methods > C. elegans experiments
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The normality of each readout was assessed based on historical values of the laboratory for this readout.”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Methods > Statistics
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Because of its high bioavailability and serum stability, trigonelline can reach the brain and impact cognitive performance in mice with Alzheimer’s disease61”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Main
What the sources say
- Not checked yetcites [61] Farid, M. M., Yang, X., Kuboyama, T. & Tohda, C. Trigonelline recovers memory function in Alzheimer’s disease model mice: evidence of brain penetration and target molecule. Sci. Rep. 10, 16424 (2020). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Results are representative of data obtained from at least two independent experiments.”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Methods > C. elegans experiments
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Therefore, trigonelline is a nutritional geroprotector with therapeutic potential to manage sarcopenia and other age-related pathologies.”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Main
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper relies on this without support.
The effects of trigonelline on muscle ageing observed in C. elegans and mice are predictive of therapeutic benefit in humans.
“Collectively, we identify nutritional supplementation of trigonelline as an NAD+-boosting strategy with therapeutic potential for age-associated muscle decline.”
The paper relies on this without support.
Serum trigonelline levels reflect the availability of trigonelline to skeletal muscle in humans.
“Serum levels of trigonelline are also associated with NAD+ levels in skeletal muscle (Extended Data Fig. 1a), which we previously found to be linked with clinical measures of sarcopenia and muscle health3.”
The paper relies on this without support.
Trigonelline can be produced by the microbiome.
“In addition, trigonelline can be produced by the microbiome.”
The paper relies on this without support.
The prominent factors that drive inter-individual susceptibility to sarcopenia and disability versus healthy ageing are poorly understood for therapeutic intervention.
“the prominent factors that drive the inter-individual susceptibility to sarcopenia and disability versus healthy ageing are poorly understood for therapeutic intervention.”
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Similarly, SIRT1 activators like resveratrol and NAD+ precursors have been shown to enhance mitochondrial biogenesis and oxidative metabolism, leading to improved muscle function and recovery”
From Exercise-Induced Muscle–Fat Crosstalk: Molecular Mediators and Their Pharmacological Modulation for the Maintenance of Metabolic Flexibility in Aging (2025) · cites this paper as [126]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Main
“b, NAD+ levels measured using LC–HRMS in the liver, gastrocnemius muscle and whole blood 2 h or 16 h (overnight) after labelled trigonelline gavage in young mice”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Methods > Animal studies
“For the in vivo tracer experiments, 12-week-old C57BL/6JRj male mice were given an acute dose of 300 mg kg−1 labelled [13C,2H3]-trigonelline M + 4 iodide by oral gavage; after 2 h and 24 h, blood, urine, muscle and liver were sampled.”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Main
“b, Association of serum trigonelline levels with ALMI, grip strength and gait speed; the Pearson correlation coefficient and its P value were calculated on n = 40 serum samples from the SSS.”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Methods > Statistics
“Associations between two continuous variables were determined using Spearman rank correlations.”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Main
“h, Relative NAD+ levels in primary myotubes from aged mice (22 months) treated ex vivo with trigonelline”
§ Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia > Methods > Cell cultures and reagents
“Primary myotubes from aged male C57BL/6JRj mice (24 months; Janvier Labs) were generated from freshly sorted muscle stem cells isolated using flow cytometry as described previously69.”
Citations
Cites
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“Briefly, after excluding one sample with an abnormally low percentage of uniquely mapped reads and after removing genes with a mean expression lower than 20 reads, data were normalized by the trimmed mean of M-values as implemented in the edgeR 67 function calcNormFactors.”
MethodFrailty in Older Adults: Evidence for a Phenotype
Fried, L. P., Tangen, C. M., Walston, J., Newman, A. B., Hirsch, C., Gottdiener, J., Seeman, T., Tracy, R., Kop, W. J., Burke, G., et al. (2001) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/56.3.m146 · Cited by 24,907 · cited 2×
“Imaging of muscle structure was performed on RW1596 myo-3 ( st386) worms 55 .”
BackgroundMethodSarcopenia: revised European consensus on definition and diagnosis
Cruz-Jentoft, A. J., Bahat, G., Bauer, J., Boirie, Y., Bruyère, O., Cederholm, T., Cooper, C., Landi, F., Rolland, Y., Sayer, A. A., et al. (2019) · Age and Ageing · doi:10.1093/ageing/afy169 · Cited by 13,818 · cited 1×
“…of muscle function used do not always directly translate to human performance, fatigue and grip strength are also well-established measures of sarcopenia and physical frailty 54,55 and are commonly used to assess the pathological impairment of quality of life in older people in clinical practice.”
BackgroundSarcopenia: European consensus on definition and diagnosis
Cruz-Jentoft, A. J., Baeyens, J. P., Bauer, J. M., Boirie, Y., Cederholm, T., Landi, F., Martin, F. C., Michel, J.-P., Rolland, Y., Schneider, S. M., et al. (2010) · Age and Ageing · doi:10.1093/ageing/afq034 · Cited by 11,601
Hallmarks of aging: An expanding universe
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“…profiling of muscle biopsies from patients with sarcopenia versus age-matched healthy controls revealed that mitochondrial dysfunction and reduced NAD + , two well-established molecular hallmarks of organismal ageing 11 , are prominent features of pathological progression and sarcopenia 3 .”
BackgroundCruz-Jentoft, A. J., & Sayer, A. A. (2019) · The Lancet · doi:10.1016/s0140-6736(19)31138-9 · Cited by 3,905 · cited 3×
“…in muscle mass and maximal tetanic strength, we conclude that trigonelline cannot reverse all causes of sarcopenia and will have to be combined with other nutri-ents that support muscle mass, such as protein, vitamin D or omega 3 fatty acids, or for the nutritional management of sarcopenia 7 .”
BackgroundGoodpaster, B. H., Park, S. W., Harris, T. B., Kritchevsky, S. B., Nevitt, M., Schwartz, A. V., Simonsick, E. M., Tylavsky, F. A., Visser, M., Newman, A. B., et al. (2006) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/61.10.1059 · Cited by 3,083 · cited 1×
“Clinically, sarcopenia is characterized by the pathological decrease of muscle mass, strength and gait speed 3,8,9 , and arises from myofibre wasting and a combination of molecular and cellular hallmarks of ageing that collectively impair contraction 10–12 .”
BackgroundCruz-Jentoft, A. J., Landi, F., Schneider, S. M., Zuniga, C., Arai, H., Boirie, Y., Chen, L.-K., Fielding, R. A., Martin, F. C., Michel, J.-P., et al. (2014) · Age and Ageing · doi:10.1093/ageing/afu115 · Cited by 1,963 · cited 2×
“Trigonelline levels were positively correlated with muscle mass assessed via Appendicular Lean Mass Index (ALMI) measured using dual-energy X-ray absorptiometry (DXA), grip strength and gait speed, all parameters used in the clinical definition of sarcopenia 3,9 (Fig.”
BackgroundMethodGomes, A. P., Price, N. L., Ling, A. J. Y., Moslehi, J. J., Montgomery, M. K., Rajman, L., White, J. P., Teodoro, J. S., Wrann, C. D., Hubbard, B. P., et al. (2013) · Cell · doi:10.1016/j.cell.2013.11.037 · Cited by 1,482
Decline in skeletal muscle mitochondrial function with aging in humans
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Cited by
Sorted by citations
Items 101–144 of 144
Effect of Sevelamer versus Bifidobacterium longum on Insulin Sensitivity in Subjects with ObesityPreprint
Baeuerle, E., Semwal, M. K., Nie, J., Zhang, N., Liang, H., Ganapathy, V., Sathavarodom, N., Fernandez, R. A., Wang, C.-P., Espinoza, S. E., et al. (2025) · medRxiv · doi:10.1101/2025.06.23.25327556
Acoustofluidics-Enhanced Sers Detection of Nicotinic Acid with Increased Sensitivity and SpeedPreprint
Wu, L., Zhang, W., Xu, Z., et al. (2025) · SSRN Electronic Journal · doi:10.2139/ssrn.5378286
Coffee and the Body’s Efficiency: Natural Doping
Paskert, M. C., Naylor, J. B., & Lowery, L. M. (2025) · Springer eBooks · doi:10.1007/978-3-031-93459-9_28
Kajiya, K., Kuroda, R., Sasaki, M., et al. (2025) · Journal of Smooth Muscle Research · doi:10.1540/jsmr.61.93
“Membrez et al. reported that trigonelline contributes to the recovery of muscle mass and strength (28), but they concluded that it is unlikely that intake of coffee directly drives the link between trigonelline and sarcopenia.”
Salgueiro, D. F. D. S., Barbosa, W., Vieira, T., Júnior, P. B., Júnior, O. A., & Figueira, T. R. (2025) · Metabolomics · doi:10.1007/s11306-025-02348-7
“This compound, primarily derived from the dietary intake of vegetables, is structurally and functionally related to niacin, occurs at low µM levels in serum, and serves as a precursor of NAD + in humans (Membrez et al., 2024).”
Campelj, D. G., Philp, A. M., Ritenis, E. J., Padilha, C. S., Alldritt, I., Sligar, J., Cree, T., Alexopoulos, S. J., Santos, W. L., Joanisse, S., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.10.30.685477
Metabolomic biomarkers predict long-term physical function in survivors of acute respiratory failure
Haastrup, A. I., Roberts, J. T., Gandotra, S., Hartsell, E. M., Daly, G. T., Pastukh, V. M., Purcell, L. D., Benton, R., Files, D. C., Stevens, T., et al. (2025) · Respiratory Research · doi:10.1186/s12931-025-03423-2
“1A) [51].”
Perego, J., Mannella, V., Manuto, L., Valles‐Colomer, M., Asnicar, F., Piperni, E., García-Valiente, A., Bonanomi, M., Gaglio, D., Montini, F., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2025.11.30.691404
“Decreased trigonelline levels in urine may reflect alterations in metabolic or physiological processes linked to muscle health 63 , NAD+ metabolism, and visceral fat dynamics.”
Ghaffari, M. H., Hemmert, K. J., Ostendorf, C. S., Schuchardt, S., Koch, C., & Sauerwein, H. (2025) · Journal of Dairy Research · doi:10.1017/s0022029925101374
“…a microbial and host-derived NAD ⁺ precursor, increases during weaning to support energy metabolism and muscle function (Calvani et al , 2010; Membrez et al , 2024), while the indolemetabo-lites 3-IPA and 3-IAA, known to maintain mucosal homeostasis, reflect the increased activity of…”
Shi, F.-E., Yu, Z., Huang, Z., Cao, L., Chi, C., & Zhu, J. (2025) · Medicine · doi:10.1097/md.0000000000046592
“[6] .”
The non-coding facet of Pink1 mRNA regulates mitochondria homeostasisPreprint
Wu, X., Liu, Y., Ma, R., Wang, H., Fan, R., Wang, H., Yang, W., Li, X., Xu, G., Cheng, H., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.01.05.697839
Hebi, M., Ajebli, M., Mankour, Z., Bouadid, I., Akdad, M., Moukafih, B., Latique, S., Yaagoubi, O. M. E., Ousaaid, D., Eddouks, M., et al. (2026) · Scientific African · doi:10.1016/j.sciaf.2026.e03263 · Cited by 1
赵思静 (2026) · Advances in Clinical Medicine · doi:10.12677/acm.2026.1631123
Long, Y. L., Hu, X., Cheng, Z., Guo, K., Pan, Z., & Wen, J. (2026) · Microchemical Journal · doi:10.1016/j.microc.2026.117781
MOSAIC: a longitudinal phenotypic clock to dissect organismal aging trajectories in C. elegansPreprint
Vaudano, A. P., Pierron, M., Stojkovic, L., Membrez, M., Bourgeois, M., Neal, C., Chimen, M., Verbakel, L., Cornaglia, M., Solari, F., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.04.23.720365
Self-citationZhang, S., Wang, L., He, C.-Y., Chen, Y.-B., Wang, Y., Li, Y., He, R., Ding, Y., Wang, X.-L., Zhou, Q.-H., et al. (2026) · Journal of the American Chemical Society · doi:10.1021/jacs.6c01000
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Targeting Mitochondria in Aging‐Related Diseases: Therapeutic Potential and Obstacles
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“Among these, trigonelline, a plant-derived alkaloid structurally related to nicotinic acid, has attracted attention because circulating levels decline in individuals with sarcopenia and correlate positively with muscle strength and mitochondrial oxidative phosphorylation [115].”
Metabolomic Signatures of Commercial Ready-to-Drink Beverages by Dual-Mode Untargeted LC–MS/MS
Blaženović, I., Bresnahan, K., & Wang, S. (2026) · Metabolites · doi:10.3390/metabo16060404
“Five compounds achieved Suggestive-level evidence (trigonelline [21], theobromine [22], ferulic acid [23], naringin [24], and resveratrol [25]) and three achieved Preclinical-level evidence (myricetin, gallic acid, and protocatechuic acid) after this screening.”
Alterations in Cardiac and Systemic Metabolism in Heart Failure
Bertero, E., Capone, F., Costa, A., Maack, C., & Ameri, P. (2026) · Circulation Heart Failure · doi:10.1161/circheartfailure.125.013766
Kołodziejska, R., Godlewski, A., Tafelska‐Kaczmarek, A., Kuk, J., Moritz, M., Sergot, K., Kurhaluk, N., Ткаченко, Г. М., & Woźniak, A. (2026) · Cells · doi:10.3390/cells15121103
“Another promising compound is trigonelline, which demonstrates beneficial effects in models of aging and cognitive impairment [170–172].”
Lin, D., Qiu, X., Wang, Y., Xiang, Y., & Huang, C. (2026) · Redox Biology · doi:10.1016/j.redox.2026.104279 · Cited by 1
侯, 永. (2026) · Advances in Clinical Medicine · doi:10.12677/acm.2026.1662443
Morena, F., Viggars, M. R., Bohmke, N. J., Ewachiw, T. E., & Esser, K. A. (2026) · Life Metabolism · doi:10.1093/lifemeta/loag021
Jiang, Z., & Ding, Y. (2026) · Journal of Translational Medicine · doi:10.1186/s12967-026-08662-5 · Cited by 1
“The coffee-induced elevation of cellular NAD + levels activates the NAD + -depen- dent deacetylase SIRT1 [42].”
Huang, X., 李, 函., Ling, K., et al. (2026) · Journal of Biomedical Research · doi:10.7555/jbr.40.20260283
Hu, Y., Zhang, X., Xu, Y., Fan, W., Xue, Z., Wang, Y., Wang, Z., Zhang, F., Hu, J., & Qiu, Z. (2026) · Antioxidants · doi:10.3390/antiox15080944
“Trigonelline, an NAD + precursor, stimulates respiration and biogenesis via sirtuins [24].”
Xu, C.-J., Wang, X., Zhan, H., et al. (2026) · Agronomy · doi:10.3390/agronomy16151509
Chen, K., Zhang, H., Tian, G., et al. (2026) · Foods · doi:10.3390/foods15162817
“Existing research confirms it acts as an NAD + precursor that benefits skeletal muscle health; its serum concentration declines in patients with sarcopenia, indicating valuable physiological activity [18].”
Jiang, X., Zhang, W., Pan, C., et al. (2026) · SSRN Electronic Journal · doi:10.2139/ssrn.7268679
Zhao, Q., He, Q., Wang, S., Wang, H., Zhang, Z., Shang, Z., & Dong, Y. (2026) · Cell Biochemistry and Biophysics · doi:10.1007/s12013-026-02138-5
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Metadata
- Authors
- Membrez, M., Migliavacca, E., Christen, S., Yaku, K., Trieu, J., Lee, A. K., Morandini, F., Giner, M. P., Stiner, J., Makarov, M. V., Garratt, E. S., Vasiloglou, M. F., Chanvillard, L., Dalbram, E., Ehrlich, A. M., Sanchez-Garcia, J. L., Canto, C., Karagounis, L. G., Treebak, J. T., Migaud, M. E., Heshmat, R., Razi, F., Karnani, N., Ostovar, A., Farzadfar, F., Tay, S. K. H., Sanders, M. J., Lillycrop, K. A., Godfrey, K. M., Nakagawa, T., Moco, S., Koopman, R., Lynch, G. S., Sorrentino, V., & Feige, J. N.
- Affiliations
- Nestlé (Switzerland) (CH)
- University of Toyama (JP)
- The University of Melbourne (AU)
- USA Mitchell Cancer Institute (US)
- University Hospital Southampton NHS Foundation Trust (GB)
- University of Copenhagen (DK)
- University of Bern (CH)
- Endocrinology and Metabolism Population Sciences Institute (IR)
- Metabolomics and Genomics Research Center (IR)
- Agency for Science, Technology and Research (SG)
- Endocrinology and Metabolism Clinical Sciences Institute (IR)
- National University Hospital (SG)
- National University of Singapore (SG)
- Corresponding author
- Sorrentino, Vincenzo
- ORCID
- Membrez, Mathieu
- Migliavacca, Eugenia
- Christen, Stefan
- Yaku, Keisuke
- Trieu, Jennifer
- Morandini, Francesco
- Giner, Maria Pilar
- Makarov, Mikhail V.
- Garratt, Emma S.
- Vasiloglou, Maria F.
- Chanvillard, Lucie
- Dalbram, Emilie
- Ehrlich, Amy M.
- Canto, Carles
- Karagounis, Leonidas G.
- Treebak, Jonas T.
- Migaud, Marie E.
- Heshmat, Ramin
- Razi, Farideh
- Karnani, Neerja
- Ostovar, Afshin
- Farzadfar, Farshad
- Tay, Stacey K. H.
- Sanders, Matthew J.
- Lillycrop, Karen A.
- Godfrey, Keith M.
- Nakagawa, Takashi
- Moco, Sofia
- Koopman, René
- Lynch, Gordon S.
- Sorrentino, Vincenzo
- Feige, Jerome N.
- Venue
- Nature Metabolism
- Published
- 2024-03-19
- Volume
- 6
- Issue
- 3
- Pages
- 433-447
- ISSN
- 2522-5812 (ISSN-L)
- PMC
- PMC10963276
- OpenAlex
- W4392956639
- Semantic Scholar
- 50a16e3631e2d843ea2846a55e7d62f9c10be710
- Cited by
- 148
- References
- 88
- Citations by year
- 2026: 55 · 2025: 59 · 2024: 34
- FWCI
- 40.99
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Nature Metabolism (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by)
- ePrints Soton (University of Southampton) (acceptedVersion)
- National University of Singapore (submittedVersion)
- BORIS (University Library Bern) (submittedVersion, cc-by)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Pure Amsterdam UMC (submittedVersion, cc-by)
- VU Research Portal (submittedVersion, other-oa)
- Open Access CRIS of the University of Bern
- Funders
- Japan Agency for Medical Research and Development (23gm6710007h0002)
- National Institute for Health and Care Research (MC_UU_12011/4, NF-SI-0515-10042, 598488-EPP-1-2018-1-DE-EPPKA2-CBHE-JP, SP/F/21/150013, U24AG047867, RG/15/17/3174, NIHR203319)
- British Heart Foundation (598488-EPP-1-2018-1-DE-EPPKA2-CBHE-JP, SP/F/21/150013, MC_UU_12011/4, NF-SI-0515-10042, RG/15/17/3174)
- European Commission (RG/15/17/3174, NF-SI-0515-10042, SP/F/21/150013, ImpENSA 598488-EPP-1-2018-1-DE-EPPKA2-CBHE-JP, 598488-EPP-1-2018-1-DE-EPPKA2-CBHE-JP, MC_UU_12011/4, 598488-EPP-1-2018-1)
- Agency for Science, Technology and Research (NF-SI-0515-10042, RG/15/17/3174, 598488-EPP-1-2018-1-DE-EPPKA2-CBHE-JP, MC_UU_12011/4)
- National University of Singapore (NUHSRO/2022/047/Startup/11)
- Singapore Institute for Clinical Sciences (RG/15/17/3174, MC_UU_12011/4, NF-SI-0515-10042, 598488-EPP-1-2018-1-DE-EPPKA2-CBHE-JP)
- University of Melbourne
- Novo Nordisk (NNF18CC0034900)
- Novo Nordisk Fonden (NNF 18 CC0034900)
- National University Health System (NUHSRO/2022/047/Startup/11,)
- Centro de Investigação em Biomedicina
- National Institute for Health Research Southampton Biomedical Research Centre (NIHR203319, NF-SI- 0515-10042, SP/F/21/150013, MC_UU_12011/4, 598488-EPP-1-2018-1-DE-EPPKA2-CBHE-JP, RG/15/17/3174)
- National Institutes of Health
- Directorate for Biological Sciences
- HORIZON EUROPE Framework Programme (101073251)
- Medical Research Council (RG/15/17/3174, 598488-EPP-1-2018-1-DE-EPPKA2-CBHE-JP, MC_UU_12011/4, NF-SI-0515-10042, SP/F/21/150013, NIHR203319)
- Economic and Social Research Council (ES/M00919X/1)
- Japan Society for the Promotion of Science (10042, 21K11593, 22H03505)
- Erasmus+ (ImpENSA 598488-EPP-1-2018-1-DE-EPPKA2-CBHE-JP, 598488-EPP-1-2018-1-DE-EPPKA2-CBHE-JP)
- National Institute on Aging (U24AG047867)
- National Center for Complementary and Integrative Health (R21AT009908)
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Health Sciences › Medicine › Physiology (medical) › Nutrition and Health in Aging
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Keywords
- trigonelline, NAD+ precursors, sarcopenia, skeletal muscle aging, mitochondrial dysfunction, oxidative phosphorylation, NAPRT, Preiss-Handler pathway, GPR109A, sirtuins, mitochondrial biogenesis, muscle strength, muscle fatigue, dietary supplementation, lifespan, Caenorhabditis elegans, myotubes
- MeSH terms
- Aging, Alkaloids, Animals, Humans, Male, NAD, Caenorhabditis elegans, Muscle, Skeletal, Mice, 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.
A language model drew the claims from the paper on 2026-10-09, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-09 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
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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