Oral single-ingredient NR × muscle mass — an increase is not established
research showsAs of 2026-09-16, evidence is insufficient to establish that oral single-ingredient NR increases muscle mass in general adults with sarcopenia or low muscle mass. A crossover trial in Werner syndrome with low DXA skeletal muscle index analyzed 6 of 9 randomized participants and found no significant increase; its small sample and unavailable between-condition confidence interval also do not exclude benefit. D/28 describes the current evidence for an increase, not an exact zero effect or an absence of human research. [S01]
ads claimThe inference “raising NAD therefore builds muscle” is not accepted as a clinical conclusion; this is not a quotation from a particular advertisement. NR is not treated as interchangeable with nicotinic acid, nicotinamide, NMN, NAD+, NRH or multicomponent NR supplements. [S01][S09][S13]
Four separate assessment dimensions
| Effect direction and size | As of 2026-09-16, evidence is insufficient to establish that oral single-ingredient NR increases muscle mass in general adults with sarcopenia or low muscle mass. A crossover trial in Werner syndrome with low DXA skeletal muscle index analyzed 6 of 9 randomized participants and found no significant increase; its small sample and unavailable between-condition confidence interval also do not exclude benefit. D/28 describes the current evidence for an increase, not an exact zero effect or an absence of human research. [S01] |
|---|---|
| Evidence certainty | Very limited; not a formal GRADE assessment |
| Applicability | Planned: adults with sarcopenia/low mass; actual closest: Werner syndrome with low SMI; other adult groups indirect |
| Safety | Safety: Caution. The Werner trial reported7 NR-phase and12 placebo-phase adverse events, not numbers of affected people or an arm-specific risk ratio. In obese men, minor adverse events over12 weeks affected4/20 with NR and2/20 with placebo. Absence of reported serious NR-related events in small trials does not establish long-term safety, safety during pregnancy or childhood, severe liver/kidney disease or polypharmacy. High-dose nicotinic-acid toxicity is not copied as proven NR toxicity. Trial doses are not dosing advice. [S01][S03][S04] |
Chamgap rule-based indicator; not treatment success probability, percent effect, or external certification
Useful facts when choosing a product
- The NR studies with numerical extraction used oral single-ingredient supplements. Some named NIAGEN, but trial-specific salt, batch and purity were not all verified. NR chloride in another paper is not copied into each study. [S01–S05]
- 1000 mg/day for 6 or26 weeks and 2000 mg/day for 12 weeks are study exposures, not personal dosing instructions. Comparisons with common exercise are kept separate. [S01–S04]
- These were not verified treatment trials for diagnosed vitamin B3 deficiency. Low NAD or genetic progeria does not itself diagnose nutritional deficiency. Total intake, concurrent vitamins and medications are recorded as verified or unreported for each study. [S01–S05]
Chamgap Semantic Classification Code
Permanent code issued
S.nicotinamide-riboside.oral.low-muscle-mass-method-specific-mass.increase.study-specific-placebo-exercise-and-prepostSubstances and nutrients > Nicotinamide riboside > Oral > Low muscle mass; method-specific mass > Increase claim > Study-specific placebo, common exercise and pre/post separately
Technical identifiers bound to unchanged ChatGPT D/28, Caution and study-specific boundaries. The code identifies the intervention and claim; it never contains the evidence grade, score, or safety result.
Exact Claim Classification
These independent facets prevent evidence from different forms, routes, populations, effects, and comparators from being mixed.
| Intervention class | S · Supplement or nutraceutical |
|---|---|
| Canonical ingredient or intervention | nicotinamide riboside |
| Source or part used | Single molecule; botanical species/part not applicable; manufacturing source unverified |
| Formulation or processing | Oral single NR; trial-specific salt/batch unverified |
| Route | oral |
| Dose | Study-specific1000–2000mg/day; not personal advice |
| Duration | Study-specific6weeks,12weeks,26weeks/52-week crossover,5months |
| Population | Planned: adults with sarcopenia/low mass; actual closest: Werner syndrome with low SMI; other adult groups indirect |
| Effect or condition | increase in muscle mass |
| Primary endpoint | Page question: preferably appendicular lean mass, separating methods; closest actual outcome: DXA SMI (trial secondary outcome) |
| Comparator | placebo; common exercise-only comparison and uncontrolled pre/post separately |
| Duplicate-detection key | R01|nicotinamide-riboside|oral|MUSCLE|adults-with-sarcopenia-or-low-muscle-mass |
What the research actually shows
# TASK-1019 / R01-059 · Oral single-ingredient NR × muscle mass
Cutoff: 2026-09-16T22:50:00+09:00
## 1. Thirty-second answer As of 2026-09-16, evidence is insufficient to establish that oral single-ingredient NR increases muscle mass in general adults with sarcopenia or low muscle mass. A crossover trial in Werner syndrome with low DXA skeletal muscle index analyzed 6 of 9 randomized participants and found no significant increase; its small sample and unavailable between-condition confidence interval also do not exclude benefit. D/28 describes the current evidence for an increase, not an exact zero effect or an absence of human research. [S01]
## 2. Fixed question and actual participants The planned question concerns oral single-ingredient NR and increased muscle mass in adults with sarcopenia or low mass, with placebo/appropriate comparators. Appendicular lean mass is preferred, not presumed to be a registered trial primary outcome. Werner syndrome with a low cohort mean SMI is directly relevant to low mass but is not ordinary age-related sarcopenia. Obese adults, cancer survivors and twins are separate indirect populations. [S01–S05]
Appendicular lean mass, total DXA lean mass, DXA skeletal muscle index, BIA-estimated muscle mass and fat-free mass as a percentage of body weight are distinct measurements. Blood NAD, strength, walking and MRI-measured fat are not substituted for increased muscle mass. [S01–S05]
## 3. Expert evidence table | Source/design | Denominator | Outcome | Verified result | Applicability | |---|---|---|---|---| | S01 Werner syndrome crossover RCT | 9 randomized;6 paired | DXA SMI,kg/m² | Δ0.0±0.1 vs0.0±0.3(SD),P=0.671;CI unavailable | Closest low-mass evidence | | S02 Healthy overweight/obese crossover RCT | 15 recruited;13 completed | BodPod FFM,% | 62.65±2.49 vs61.32±2.58(SE);+1.34±0.50 pp,P=0.02 | Indirect positive; not muscle kg | | S03 Obese men parallel RCT | 20/20 completed | Total DXA lean mass,kg | No significant improvement; precise Fig3B means/CI unverified | Indirect population; no invented graph values | | S04 Adult childhood-cancer survivors; common exercise RCT | 10/10 randomized;Ex8,Ex+NR9 analyzed | BIA muscle mass,lb | Ex+NR−0.3(−1.3,1.9),Ex−0.8(−2.3,5.2),median(range),P=0.70 | Exercise add-on stratum; indirect population | | S05 NR twin pre/post cohort | Main analysis 32 people/16 pairs | Total DXA lean mass,kg | 54.0±10.2→54.5±10.5(SD),P=0.197 | Not an NR-placebo treatment contrast |
SD and SE are labeled rather than interchanged. Two crossover phases do not create two sets of people: n=6 is not 12, and n=13 is not 26. Ranges in S04 are not confidence intervals. Numeric extraction and source positions are retained in sources.json. [S01–S04]
## 4. Exposure, comparator and nutrition S01 used 1000 mg oral NR once daily,26 weeks per phase/52 weeks total, with matching cellulose placebo and no washout. Its analyzed baseline DXA SMI was4.22±0.95 kg/m². Individual concomitant medications/vitamins and dietary niacin were not recovered; diagnosed B3 deficiency was not an established entry requirement. [S01]
S02 used 1000 mg/day for 6 weeks per phase,4–7 weeks washout and usual diet/activity. S03 used 1000 mg twice daily (2000 mg/day),12 weeks, in obese insulin-resistant men without prescribed medication. Both populations were not selected for low mass or diagnosed B3 deficiency; total dietary niacin was not verified. NIAGEN branding does not independently verify each trial's salt/batch/purity. [S02][S03]
S04 added1000 mg/day (250 mg NIAGEN capsules) for 6 weeks to the same resistance-exercise program in both groups:3 sessions/week,approximately 30 min/session. This is a separate add-on comparison, not a multicomponent supplement and not NR alone. Glucose-lowering medications/recent NAD precursor use were exclusion criteria; complete dietary niacin and other vitamin exposure were unreported. [S04]
S05 escalated daily NR250→1000 mg during month 1, with 5 months total exposure. In its 32-person main cohort, dietary niacin equivalents were 44.5(36.1–49.9) before and 40.1(35.4–49.8)mg/day after, median(IQR), P=0.295. Dietary niacin equivalents were not added to NR milligrams as though chemically identical. The separate 4-pair NR/placebo experiment is distinct from the main both-treated cohort. [S05]
NR is not merged with nicotinic acid, nicotinamide, NMN, NAD+, NRH or NR combinations. Trial-specific counterion, batch/purity and manufacturing source remain unverified when absent from the intervention description. “Chloride” in a cited reference title does not establish the current trial's form. No dedicated laboratory-interference investigation was verified; this is not proof of no interference. Biochemical NAD changes are separate from clinical or mass outcomes. [S01–S05][S09][S13]
## 5. Numeric checks and alternative evidence In the Werner trial, DXA skeletal muscle index changed by 0.0±0.1 with NR versus 0.0±0.3 kg/m² with placebo (SD), paired n=6, P=0.671. The zeros are rounded. Methods specify 26 weeks per phase, while 24- and 28-week statements also appear in the article. [S01]
There is a positive adjacent result. In 13 healthy overweight/obese adults, a 6-week crossover comparison of NR 1000 mg/day versus placebo increased BodPod fat-free mass percentage by 1.34±0.50 percentage points (SE), P=0.02. This is not an appendicular muscle-kg gain in sarcopenia, and the investigators retained the need to confirm actual muscle mass. [S02]
Using the published 1.34±0.50 pp and t(df12), an author-calculated 95%CI is approximately 0.251–2.429 pp. It is reconstructed from rounded numbers, not reported by the trial. d_av reconstructed from marginal SEs is 0.147, not paired d_z. Rounded arm means subtract to 1.33 pp rather than the published 1.34 pp; this is compatible with rounding. Mean weight times mean FFM percentage was not converted into muscle kg. Weight dispersion wording conflicts between the paragraph and general figure caption and was not used for conversion. [S02; audits/calculations.json]
The NMN meta-analysis is not assigned to NR. The 2026 muscle epigenetic study reuses the twin NR cohort and is not counted as an independent muscle-mass trial. Nonsignificant randomized comparisons and uncontrolled pre/post results are not merged into repeated definitive refutation. [S05][S06][S09]
S04 separately reported BIA FFM median changes of−1.5(−3.1,2.8)lb with exercise+NR versus−1.2(−2.5,8.4)lb with exercise alone, P=0.63. These are medians/ranges, not means/SD or CIs. Strength is a separate endpoint. Ultrasound size results were described as nonsignificant, but unavailable supplement numbers were not invented. [S04]
## 6. Final grade and classification The supplied S/R1/I1/E0/B2/CX profile was applied: one directly relevant trial, mixed public support/manufacturer supplies, a nonsignificant mass-index result, small sample and completer analysis, and no verified between-condition CI. E0 is an internal no-demonstrated-increase code, not proof of zero effect. The original calculator derives D; zero strength axes select the fixed anchor 28, without discretionary adjustment.
The supplied bias list explicitly counts n<200 and completer analysis/substantial exclusion. The 3/9=33.3% exclusion was not counted twice under two names. Manufacturer supply is assigned to I1 only and missing CI to CX, not counted again as bias. Incompatible populations/methods are not RX; benefit has not been excluded (no C1 or F). R1 is the supplied single-trial category, not certification of a large confirmatory trial. [S01; supplied scoring document]
All seven strength flags (H,R2,I2,E+,C1,B0,big_hard_rct) are absent, selecting D28. This is not a treatment success probability, percentage benefit or formal GRADE score. KindS/category sports are final under the existing taxonomy. R01/NUT are work/module labels; a new site ID, URL or semantic code was not issued.
## 7. Safety and applicability Safety: Caution. The Werner trial reported 7 NR-phase and 12 placebo-phase adverse events, not numbers of affected people or an arm-specific risk ratio. In obese men, minor adverse events over 12 weeks affected 4/20 with NR and 2/20 with placebo. Absence of reported serious NR-related events in small trials does not establish long-term safety, safety during pregnancy or childhood, severe liver/kidney disease or polypharmacy. High-dose nicotinic-acid toxicity is not copied as proven NR toxicity. Trial doses are not dosing advice. [S01][S03][S04]
S01's NR-phase mild events included pain, AST elevation, subcutaneous hemorrhage, hyperkeratosis, pruritic rash, ulcer and hypotension. Overall SAF9 is not assigned as the number exposed in each phase. S04 reported one person with minor muscle pain on exercise, and one with fatigue plus a different person with nausea/rash on exercise+NR. Randomized 10/10 is kept separate from analyzed 8/9; the narrative calling9 “randomized” is retained as a denominator inconsistency. Available safety data stay within their6-,12-,26-/52-week exposure contexts. [S01][S03][S04]
## 8. Search, limitations and revision The 29 literal web queries, prior 5 NR records, primary articles and official-index/registry access are logged. No exhaustive subscription Embase search, complete native PubMed systematic export or author contact was performed. The 2026 paper is a repeated twin-cohort epigenetic analysis, not a new mass trial. Registrations without verified numerical outcomes are not counted as successful or failed efficacy trials. [S06][S10–S12]
Original registry-primary-outcome history, some supplements, unrounded paired SMI/CI, trial salts and complete concomitant drug/vitamin exposure remain limited. Independently verified registered primary outcomes are kept separate from paper-reported primary outcomes: safety in S01, insulin sensitivity in S03 and feasibility in S04 are not mass-primary efficacy successes. [S01–S04][S14]
Revision triggers are an eligible adult sarcopenia/low-mass RCT with method-specific between-arm estimates/CIs, recovered original registration/supplement/paired data, relevant corrections/retractions, numerical error or formulation-boundary clarification. These are disclosed evidence limitations, not outstanding clinical decisions. Content, grade, safety and classification are complete; technical receipt/ID/path/build/deployment work only is handed over.
## Sources - [S01] Shoji et al. (2025). Nicotinamide Riboside Supplementation Benefits in Patients With Werner Syndrome: A Double-Blind Randomized Crossover Placebo-Controlled Trial. DOI: 10.1111/acel.70093. https://onlinelibrary.wiley.com/doi/full/10.1111/acel.70093 — Publisher PDF: Fig 1 p3; Table1 p4; Table2 p8; sections2.2,2.3,3.10,5.1–5.3; funding p1. - [S02] Remie et al. (2020). Nicotinamide riboside supplementation alters body composition and skeletal muscle acetylcarnitine concentrations in healthy obese humans. DOI: 10.1093/ajcn/nqaa072. https://pure.amsterdamumc.nl/ws/files/107460914/nqaa072.pdf — AJCN112:413–426; PDFp3–6 Methods; p9/article420 body composition; p12/article423 Fig5 and limitations. - [S03] Dollerup et al. (2018). A randomized placebo-controlled clinical trial of nicotinamide riboside in obese men: safety, insulin-sensitivity, and lipid-mobilizing effects. DOI: 10.1093/ajcn/nqy132. https://www.brennerlab.net/files/dollerup18.pdf — Author PDFp2 methods; Fig3B p6; results/safety p6–7; funding p1 and declarations p10; final bibliographic pagination343–353 verified in PubMed. - [S04] Bhandari et al. (2025; online2024). Feasibility of telehealth exercise and nicotinamide riboside supplementation in survivors of childhood cancer at risk for diabetes: A pilot randomized controlled trial. DOI: 10.1002/pbc.31369. https://www.brennerlab.net/files/Bhandari25.pdf — PDFp2–3 Methods; p3–4 flow and safety; p6 Table2; p7 funding/conflicts. - [S05] Lapatto et al. (2023). Nicotinamide riboside improves muscle mitochondrial biogenesis, satellite cell differentiation, and gut microbiota in a twin study. DOI: 10.1126/sciadv.add5163. https://pmc.ncbi.nlm.nih.gov/articles/PMC9839336/ — Tables1–3; Methods interventions/body composition; safety discussion. - [S06] Heikkinen et al. (2026). The Divergent Effects of Nicotinamide Riboside and High-Intensity Exercise Training on Skeletal Muscle Epigenetic Aging. DOI: 10.1111/acel.70638. https://onlinelibrary.wiley.com/doi/full/10.1111/acel.70638 — Abstract; human cohorts; epigenetic-clock analyses - [S07] Martens et al. (2018). Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. DOI: 10.1038/s41467-018-03421-7. https://www.nature.com/articles/s41467-018-03421-7 — Main text results, body composition reference to supplementary table7 - [S08] Elhassan et al. (2019). Nicotinamide Riboside Augments the Aged Human Skeletal Muscle NAD+ Metabolome and Induces Transcriptomic and Anti-inflammatory Signatures. DOI: 10.1016/j.celrep.2019.07.043. https://www.cell.com/cell-reports/fulltext/S2211-1247(19)30940-4 — Preserved929 source extraction; bibliographic match - [S09] Prokopidis et al. (2025). The Effect of Nicotinamide Mononucleotide and Riboside on Skeletal Muscle Mass and Function: A Systematic Review and Meta-Analysis. DOI: 10.1002/jcsm.13799. https://onlinelibrary.wiley.com/doi/full/10.1002/jcsm.13799 — Intervention-specific results and study map - [S10] Song et al. (2022). Exercise training and NR supplementation to improve muscle mass and fitness in adolescent and young adult hematopoietic cell transplant survivors: a randomized controlled trial. DOI: 10.1186/s12885-022-09845-1. https://link.springer.com/article/10.1186/s12885-022-09845-1 — Protocol design/outcomes - [S11] NADage registry / existing3093 study map. DOI: not applicable / not verified. https://clinicaltrials.gov/study/NCT06208527 — supplied native verdict 3093.json; official registry shell - [S12] NR-VET trial registry. DOI: not applicable / not verified. https://clinicaltrials.gov/study/NCT04691986 — Registry search body-composition reference; record not parsed beyond shell - [S13] Jensen et al. (2022). A randomized placebo-controlled trial of nicotinamide riboside and pterostilbene supplementation in experimental muscle injury in elderly individuals. DOI: 10.1172/jci.insight.158314. https://insight.jci.org/articles/view/158314 — Intervention identity/abstract; no new efficacy extraction of this excluded combination - [S14] Independent registration access checks. DOI: not applicable / not verified. https://jrct.mhlw.go.jp/en-latest-detail/jRCTs031190141 — Official jRCT endpoints failed; ClinicalTrials.gov pages rendered only shell
Why this is classified as D (28)
The supplied S/R1/I1/E0/B2/CX profile was applied: one directly relevant trial, mixed public support/manufacturer supplies, a nonsignificant mass-index result, small sample and completer analysis, and no verified between-condition CI. E0 is an internal no-demonstrated-increase code, not proof of zero effect. The original calculator derives D; zero strength axes select the fixed anchor 28, without discretionary adjustment.
Counterpoint. The NMN meta-analysis is not assigned to NR. The 2026 muscle epigenetic study reuses the twin NR cohort and is not counted as an independent muscle-mass trial. Nonsignificant randomized comparisons and uncontrolled pre/post results are not merged into repeated definitive refutation. [S05][S06][S09]
Rejudgment record. No demonstrated mass increase; benefit not excluded and exact zero not established — Supplied original calculator and fixed score anchors
| Endpoint | S | Surrogate marker - laboratory or imaging measures Case application: S:DXA mass proxy |
| Replication | R1 | Single confirmatory trial Case application: R1:one directly relevant low-SMI randomized cohort, other outcomes indirect |
| Independence | I1 | Mixed funding sources |
| Effect size | E0 | Null |
| Precision | CX | No pooled confidence interval could be confirmed Case application: CX:paired CI unavailable, no invented MCID/benefit exclusion |
Stored derived and displayed grades match; this is not a current recalculation or validity check (D).
Review performed and remaining limitations
Unverified paired CI, supplement, original registry outcomes; conflicting duration wording; limited generalizability
Preliminary RoB 2-informed review — not a complete formal assessment
| Randomization | S01 central allocation/minimization, sex-stratified; matching capsules; drug-handling staff separated from participants |
|---|---|
| Deviations from assigned interventions | S01 no crossover washout; adherence/medication details incompletely recovered |
| Missing outcome data | S01 6/9 complete-case FAS=PPS; 3/9=33.3% not analyzed; not full ITT |
| Outcome measurement | S01 objective DXA index; appendicular numerator/scanner unverified; outcomes not interchangeable |
| Selection of the reported result | Mass is secondary; multiple endpoints; original registry history inaccessible;24/26/28-week conflict retained |
Reasons for the certainty judgment — not formal GRADE
| Risk of bias | Two provided-rule defects: n<200 and complete-case/exclusion |
|---|---|
| Inconsistency | Different populations/methods are indirect variation, not R0 or RX proof |
| Indirectness | Werner genetic progeria differs from ordinary aging; other cohorts not low-mass selected |
| Imprecision | No paired mass CI; potential benefit not excluded |
| Publication bias | Cannot assess reliably with small heterogeneous evidence; registration-only leads retained |
Search scope and limitations. 2026-09-16 web/primary sources;29 literal queries and access limits in audits/search_log.json; no exhaustive subscription database claim
Evidence Table
| Study | Design | Sample | Funding | Endpoint | Result | Weight |
|---|---|---|---|---|---|---|
| Shoji et al. (2025). Nicotinamide Riboside Supplementation Benefits in Patients With Werner Syndrome: A Double-Blind Randomized Crossover Placebo-Controlled Trial | Werner syndrome crossover RCT | 9 randomized;6 paired | Public grants plus manufacturer supply | DXA SMI,kg/m² | Δ0.0±0.1 vs0.0±0.3(SD),P=0.671;CI unavailable | Closest low-mass evidence |
| Remie et al. (2020). Nicotinamide riboside supplementation alters body composition and skeletal muscle acetylcarnitine concentrations in healthy obese humans | Healthy overweight/obese crossover RCT | 15 recruited;13 completed | Public/EU support plus manufacturer supply | BodPod FFM,% | 62.65±2.49 vs61.32±2.58(SE);+1.34±0.50pp,P=0.02 | Indirect positive; not muscle kg |
| Dollerup et al. (2018). A randomized placebo-controlled clinical trial of nicotinamide riboside in obese men: safety, insulin-sensitivity, and lipid-mobilizing effects | Obese men parallel RCT | 20/20 completed | Foundation/public support plus product supply; adviser/stock/grant ties | Total DXA lean mass,kg | No significant improvement; precise Fig3B means/CI unverified | Indirect population; no invented graph values |
| Bhandari et al. (2025; online2024). Feasibility of telehealth exercise and nicotinamide riboside supplementation in survivors of childhood cancer at risk for diabetes: A pilot randomized controlled trial | Adult childhood-cancer survivors; common exercise RCT | 10/10 randomized;Ex8,Ex+NR9 analyzed | NIH/NCI plus manufacturer; manufacturer-advisor author | BIA muscle mass,lb | Ex+NR−0.3(−1.3,1.9),Ex−0.8(−2.3,5.2),median(range),P=0.70 | Exercise add-on stratum; indirect population |
| Lapatto et al. (2023). Nicotinamide riboside improves muscle mitochondrial biogenesis, satellite cell differentiation, and gut microbiota in a twin study | NR twin pre/post cohort | Main analysis32people/16pairs | Detailed funding extraction limited | Total DXA lean mass,kg | 54.0±10.2→54.5±10.5(SD),P=0.197 | Not an NR-placebo treatment contrast |
Receipt — 14 References
Evidence access cutoff: 2026-09-16. Each citation states its actual access level (full-text transcription, abstract, index, or other) and remaining limitations. Bibliographic checking does not certify the study results or treatment efficacy.
Technical integration by: Codex · Evidence date: 2026-09-16 · Corrections: none
Cite this verdict
[Chamgap] Oral single-ingredient NR × muscle mass — an increase is not established — Evidence Grade D·28. 14 cited sources checked. Source: https://chamgap.com/en/verdicts/sports/oral-nicotinamide-riboside-low-muscle-mass-method-specific-evidence/ · CC BY 4.0CC BY 4.0 — free to use with attribution; do not distort grades, numbers, or verdict meaning.
What this document does and does not do
Chamgap is an information source. It reports what research has and has not confirmed; it does not tell readers what to take or buy. That decision belongs to readers and, when needed, medical or legal professionals. This verdict reflects literature available up to the search date and may change as new research appears. Nothing here is medical advice.