The Science
Human research on the ingredients and pathways CELLSHE works with, including NMN, creatine monohydrate, resveratrol and NAD+ biology. We explain the findings clearly for women in midlife and link major conclusions to their sources.
Written by CELLSHE Editorial Team· Editorial standards
Our approach
Every paper is read in context and recorded with the details that determine what it can support.
Human intervention studies and strong syntheses usually carry the most weight for consumer questions. Study quality, population and endpoint fit determine their weight. Mechanistic and preclinical research stays clearly labeled.
Sex, life stage, health status, dose, duration and primary endpoint stay attached to each result.
Evidence records link to PubMed, DOI or available full text. Funding and material conflicts are recorded with the study.
Evidence map
Start with the topic you care about. Each area connects to the full evidence library and a deeper guide when one is available.
β-Nicotinamide mononucleotide
An NAD+ precursor studied in humans for its effect on circulating NAD-related metabolites.
Evidence libraryStrongest human finding
Across several human trials, oral NMN increased circulating NAD-related metabolites.
Women-specific evidence
Direct research includes a randomized trial in postmenopausal women and smaller women-only studies.
Creatine monohydrate
A supplement ingredient studied across a large human research base on strength and training.
Evidence libraryStrongest human finding
Human trials support creatine monohydrate for strength and training-related muscle outcomes.
Women-specific evidence
Direct female studies span young active women through postmenopausal women, including resistance-training trials.
Dietary polyphenol
A polyphenol studied across antioxidant, metabolic and vascular outcomes in humans.
Evidence libraryStrongest human finding
Human studies show measurable changes in selected antioxidant and inflammatory biomarkers. Results vary across biomarkers and populations.
Women-specific evidence
Postmenopausal trials have examined cognition, cerebrovascular function, bone and metabolic outcomes.
Nicotinamide adenine dinucleotide
A cellular coenzyme central to energy metabolism and used by multiple enzyme systems.
Evidence libraryHuman evidence
Human NAD+ measurements vary by tissue and population, so blood and muscle findings need separate interpretation.
Women-specific evidence
Women are represented in several precursor trials. Female-specific aging patterns remain an active research question.
NAD+ and precursors
NAD+ (nicotinamide adenine dinucleotide) is a coenzyme used throughout cellular metabolism. It also serves as a substrate for enzymes involved in DNA repair, cell signaling and stress responses.
NMN and NR are precursors. The body can use them within NAD+ biosynthetic pathways. Human studies repeatedly show that oral NMN and NR can increase circulating or cellular NAD-related biomarkers.
| Route | What human evidence shows | Current evidence status |
|---|---|---|
| Oral NMN | Multiple controlled human studies report increases in whole-blood or circulating NAD-related metabolites after supplementation. | Repeated target engagement |
| Oral NR | Human trials also show increases in NAD-related biomarkers. A 2026 comparison found similar circulatory NAD+ increases with NR and NMN over 14 days. | Repeated target engagement |
| Direct oral NAD+ | Direct studies remain sparse. A small 2025 double-blind cognition study in women found no advantage over placebo. A 2026 randomized trial of a specialized oral NAD+ formulation reported higher intracellular whole-blood NAD+, while plasma NAD+ stayed unchanged. | Early and formulation-specific |
| IV NAD+ | Intravenous studies evaluate NAD+ delivered directly into the bloodstream. They answer a separate delivery question from oral supplementation. | Separate administration route |
Target engagement means a measurable change in NAD-related biomarkers. Clinical benefits require their own outcome evidence.
Direct answers
The route matters, the tissue matters, and biomarker changes are only one part of the clinical picture.
Yes. Multiple human trials show increases in whole-blood or circulating NAD-related metabolites after oral NMN. A 2022 randomized trial found higher whole-blood NAD+ after 12 weeks at 250 mg/day.
Frontiers in Nutrition 2022, PMID 35479740 · Nature Metabolism 2026, PMID 41540253
The evidence is early. A small 28-day double-blind study in women found no cognitive advantage over placebo. A 2026 randomized trial of a specialized oral NAD+ formulation reported higher intracellular whole-blood NAD+, while plasma NAD+ stayed unchanged.
The published trial was short and formulation-specific. Direct oral NAD+ therefore remains on a much smaller evidence base than NMN or NR.
Innovation in Aging 2025, conference-supplement abstract · GeroScience 2026, PMID 42530810
IV NAD+ enters the bloodstream directly. Oral NAD+ passes through digestion and absorption first. Each route therefore needs its own human evidence.
A 2026 systematic review found that human NAD-augmentation trials were dominated by oral precursors such as NMN and NR. The review found no eligible IV or IM NAD+ wellness outcome trials during its search period.
Ageing Research Reviews 2026, PMID 41655607
Human findings depend on the tissue and population measured. Across seven cohorts, whole-blood NAD+ remained stable with age in a 2026 study. Sarcopenic muscle has shown lower NAD+ and reduced NAD+ biosynthetic capacity compared with age-matched controls.
Nature Metabolism 2026, PMID 42135539 · Nature Communications 2019, PMID 31862890
NMN research tests whether supplementation changes NAD metabolism. Human trials repeatedly show that it does at the biomarker level. Clinical outcomes remain a separate question and vary by endpoint and population.
CELLSHE full-text NMN evidence review · NMN for Women research guide
Both are NAD+ precursors with human target-engagement evidence. In a 2026 study of 65 healthy adults, 14 days of NMN or NR produced comparable increases in circulatory NAD+.
That study supports pathway engagement for both precursors. It does not establish broad clinical superiority for either one.
Nature Metabolism 2026, PMID 41540253
CELLSHE Evidence Library
CELLSHE publishes the papers it evaluates for ingredient research. Each record keeps the study design, population, result, limitations, funding and source together.
The library keeps supportive, contextual, mixed, null, safety, preclinical, regulatory and quality evidence in the same system. Publication records are not automatically independent trials; secondary analyses and comments retain shared trial or cohort family IDs. Study type and population stay visible on every record.
A direct female null study for this low-dose swimming protocol.
Mixed-sex exercise context with limited female-specific inference.
A core direct female creatine-monohydrate resistance-training study.
Mixed-sex contextual evidence with female representation.
Direct women-only null evidence for this short repeated-Wingate protocol.
Direct female swimming evidence showing a null response in this protocol.
Direct female strength evidence with clear outcome specificity.
Broader training context with female representation.
Direct female repeated-work evidence with mixed strength outcomes.
Direct female training and strength evidence.
Direct female evidence for neuromuscular fatigue-threshold work capacity.
Mixed-sex high-intensity exercise context with female representation.
Direct elite-female evidence for selected high-intensity tasks.
Useful null high-intensity running context.
Supportive female power evidence with a design-quality downgrade.
Mixed-sex contextual evidence with female representation.
Direct women-only anaerobic evidence; chemical-form inference remains limited.
Mixed-sex loading evidence with plain creatine and creatine-plus-phosphate arms; the women-specific interaction was null.
A key direct female null trial showing that training improvements can occur without a detectable additive supplement effect.
Direct female swimming evidence with a null between-group result.
Supportive women-only strength and power evidence from a concurrent-training study; chemical-form inference remains limited.
Female alternative-form null evidence.
Contextual mixed-sex resistance-training evidence.
A broad direct female trial that prevents one isolated power result from becoming a universal claim.
Women-only alternative-form null evidence.
Broader human exercise evidence with substantial female representation and no female-specific treatment estimate.
Direct female high-intensity and training evidence.
Direct female null evidence for additional benefit during this HIIT program.
One of the clearer direct female high-intensity creatine-monohydrate studies.
Direct women-only evidence for repeated resistance-set work capacity.
A cornerstone study for separating body-water change from new muscle tissue.
Direct but narrow evidence that menstrual phase may modify selected recovery responses.
Supportive women-only training evidence with a reporting-quality downgrade for the inconsistent dosing description.
Current direct female data on a CrM gummy delivery format with lower causal weight because both groups knew their supplementation status.
Direct women-only fatigue-threshold evidence for di-creatine citrate, kept separate from CrM.
Alternative-form evidence against broad aerobic enhancement.
Timing-only evidence; creatine-versus-placebo efficacy was outside this study design.
Supportive direct older-women strength evidence.
Supports the creatine-plus-training strategy without implying that creatine alone reproduces training adaptations.
Important direct null evidence against extrapolating higher-dose training studies to 1 g/day alone.
A supportive individual bone study that must remain inside the larger pooled bone evidence.
A key additive-effect-unclear trial in older women.
Large long-duration evidence against a general claim that creatine alone increases bone density.
The largest dedicated exercise-and-bone RCT centers postmenopausal creatine evidence on muscle and strength; BMD findings remained limited.
The strongest current map of female exercise research, used together with other reviews because no single review captures the full corpus.
Essential corpus-reconciliation source because it captures female trials missing from the newer 34-study table.
The anchor synthesis for postmenopausal muscle and strength. Bone density remains a separate weaker outcome.
Strong female-specific tolerability context for studied nonpregnant women.
Direct evidence that body-water shifts and scale-weight change are different outcomes.
Emerging women-only clinical evidence that belongs in a distinct treatment-adjunct category.
Pregnancy biology context only. Routine supplementation during pregnancy remains a separate clinical question.
Useful cognition synthesis, but the headline estimates should be interpreted with the later methodological critique.
A required companion record that downgrades confidence in broad cognition estimates.
Independent reason to keep cognition as an emerging research area below the muscle and strength evidence.
Supports explaining creatinine as a measurement issue that needs biochemical context.
RCT-focused kidney-safety context that separates a creatinine shift from pooled urea and eGFR findings.
Current broad evidence for explaining why creatinine can move without demonstrating kidney damage.
Reassuring direct follicle data with indirect relevance to women.
Supports keeping chemical form visible in every database record and treating CrM as the reference form.
Reference source for chemical-form hierarchy in the evidence library.
Useful practical dosing context without converting research doses into a universal prescription.
Supports keeping precise timing as a low-priority practical variable.
Useful map of women-specific creatine research; outcome-specific trials carry the efficacy conclusions.
Current lifespan framework for organizing women-specific creatine evidence without treating every life stage as equally studied.
Additional female-focused synthesis used to reconcile the public evidence library.
Supplementary safety context alongside kidney-specific meta-analyses and the female adverse-event synthesis.
A useful synthesis separating reliable biomarker engagement from less consistent clinical outcomes.
High-authority context for separating biological plausibility from demonstrated human benefit.
A current high-level reference for tissue specificity and the limits of translating precursor target engagement into broad healthy-aging benefits.
Supports a tissue-specific view of NAD+ aging and rejects simple universal decline curves.
Useful ovarian-biology context that keeps mechanistic interest separate from proven human fertility outcomes.
Mechanistic ovarian-aging context. It should not be used as evidence of NMN fertility efficacy in women.
Useful age-context evidence showing why matrix and metabolite choice matter.
Supports tissue-specific NAD aging biology. Skin findings cannot define a universal whole-body NAD trajectory.
Strong human ovarian-aging biology. It cannot establish NMN supplementation efficacy.
Keeps menopause and hormone-therapy biology distinct from NMN supplementation evidence.
Useful for assay and target-engagement context. It should not be used to claim a universal age decline or to define an optimal NMN dose.
A central current reference against simple whole-blood NAD+ decline curves. Tissue-specific findings remain separate.
Strong current head-to-head evidence that both NMN and NR engage the NAD pathway in humans.
A broad current synthesis supporting precursor target engagement while keeping clinical effectiveness and route-specific evidence separate.
Useful broad context, but a weak source for claims about swallowing intact NAD+ itself.
Direct oral NAD+ evidence in women with a null cognition result. It answers cognition only and does not establish oral NAD+ pharmacokinetics.
The strongest current direct oral NAD+ target-engagement study, now peer-reviewed. Its result applies to LNAD+ and should not be generalized to standard oral NAD+ products.
This is the strongest direct female NMN trial in the current library. Its metabolic finding applies to postmenopausal women with prediabetes and overweight or obesity.
Useful direct female context for hormones and subjective outcomes. It provides no controlled evidence for estrogen restoration or menopause symptom treatment.
Preliminary women-only hair evidence. The design supports hypothesis generation, not an established hair-growth benefit.
A mixed exercise trial with positive submaximal signals. It does not establish a broad physical-function benefit for midlife women.
A key human target-engagement trial supporting the statement that oral NMN can raise whole-blood NAD+.
High-dose short-term tolerability evidence. It informs the safety horizon, not long-term safety.
Useful for sleep and function context. The result pattern does not establish a universal benefit or an ideal dosing time.
Supports human NAD target engagement. Functional findings require caution because of the trial's allocation error.
Useful target-engagement and short-term safety evidence. Consumer conclusions should stay with the measured endpoints.
Strong formulation-specific target-engagement evidence with equal male/female enrollment. It cannot be generalized to every NMN formulation.
A key dose-ranging target-engagement trial. Its strongest durable result is the increase in blood NAD+ across tested doses.
A useful null cardiovascular trial. It prevents biomarker changes from being translated into an arterial-stiffness claim.
A relatively long but very small null trial. It should remain confined to older men with diabetes and impaired function.
Strong target-engagement evidence for MIB-626. Clinical outcome signals need confirmation in larger studies.
A useful example of target engagement with mixed functional outcomes. The primary endpoint remains central to interpretation.
Adds high-dose short-duration tolerability evidence. It cannot establish long-term safety.
A mechanistic human study showing that inflammatory biomarkers and recovery biology can move in different directions.
Useful for acute human pharmacokinetic and tolerability context. It does not address repeated dosing or women-specific outcomes.
Supports pharmacodynamic context while offering limited evidence for metabolic outcomes.
Mechanistically interesting hypertension evidence. The small clinical subgroup should stay separate from healthy-aging conclusions.
Supports PBMC target engagement with limited clinical-outcome evidence. Timing cannot be generalized from this design.
Useful for the historical human-trial landscape and for identifying gaps that individual trials cannot answer.
Strong evidence against a broad glucose-control or lipid-improvement claim for NMN.
Current pooled evidence supports short-term tolerability while keeping broad metabolic claims limited.
Important pooled context for keeping NMN muscle-function claims restrained.
Blood-pressure evidence remains mixed and endpoint-specific.
Regulatory safety context for a specific ingredient and use condition. It should stay separate from U.S. regulatory status and dose optimization.
A key boundary source for fertility content. It explains scientific interest without supporting a human fertility claim.
Explains why NMN and reproductive aging are studied. It provides no direct evidence of fertility benefit in women.
Preclinical metabolic context only.
Supports mechanistic interest in oocyte biology, not a human fertility claim.
Mechanistic reproductive evidence only.
Preclinical oocyte evidence without direct human efficacy inference.
Preclinical reproductive context only.
Laboratory reproductive evidence only.
Strong preclinical ovarian evidence. It cannot establish fertility preservation in women receiving chemotherapy.
Important published scrutiny of the landmark female NMN trial. It stays attached to the parent trial instead of being counted as new efficacy evidence.
Keeps the scientific exchange around the landmark women-specific trial visible and connected to the parent study.
Adds individual-response context without increasing the independent NMN trial count.
Useful for NAD biomarker context and individual variability. It must share the parent trial identity in public counts.
Expands human mechanistic understanding of NAD-linked RNA biology without establishing a clinical benefit.
Adds formulation-specific target-engagement data in a clinical population while showing no clear clinical-outcome advantage in this trial.
Direct human support for measurable antioxidant-status change in a defined population.
Supports antioxidant activity at the biomarker level, with substantial variation across oxidative-stress markers.
A necessary companion to other antioxidant meta-analyses because pooled biomarker conclusions differ.
Supports an inflammatory-biomarker signal while keeping the claim at the measured biomarker level.
Shows that inflammatory-marker effects depend on the marker and studied population.
Shows that inflammatory-marker effects differ by marker and studied population.
The broadest current evidence map, useful for preventing isolated pooled findings from becoming universal claims.
A quality-control source showing that meta-analysis volume and evidentiary certainty are separate questions.
Authority context for the size of the human literature while keeping claims endpoint-specific.
The anchor synthesis for postmenopausal resveratrol evidence. It keeps positive individual trials inside a broader mixed pooled picture.
Direct women-specific cerebrovascular and cognition evidence that should be read with the later 10-RCT postmenopause synthesis.
Long-duration women-specific evidence from the RESHAW cohort.
Parent RESHAW record for long-duration postmenopausal cognition/cerebrovascular evidence.
Important bone-specific publication that stays linked to the parent RESHAW trial to prevent duplicate trial counting.
Useful short-term tolerability evidence in older adults.
A major direct female null trial that prevents broad metabolic claims in healthy postmenopausal women.
Human evidence showing that antioxidant-related biology and training adaptation can diverge.
Exercise-adaptation evidence with female representation, kept as mixed-sex context.
The current human synthesis found no significant SIRT1 effect across measured expression and circulating outcomes.
Mechanistic evidence supporting a more cautious interpretation of resveratrol and direct SIRT1 activation.
Independent mechanistic support for retiring direct-SIRT1 activation language.
Historically important longevity research that stays explicitly preclinical.
Mechanistic context that should remain separate from human consumer claims.
Broad cognition context supporting outcome-specific interpretation across a heterogeneous literature.
Older-adult synthesis showing both potential signals and substantial outcome heterogeneity.
Additional human evidence that resveratrol can interact with training adaptation in outcome-specific ways.
Women in the evidence
Sex and life stage can change how a study applies. This view isolates women-only human research and keeps menopause status visible when authors report it.
Creatine monohydrate
Women-only trials cover strength, repeated high-intensity work and training outcomes. Postmenopausal research is strongest for muscle and strength when creatine accompanies resistance training.
More perimenopause-specific trials would clarify how responses vary across the menopause transition.
Nicotinamide adenine dinucleotide
Women appear in precursor and direct oral NAD+ research, with female-specific evidence concentrated in a small number of studies and secondary analyses.
Tissue-specific human studies can map how blood, muscle and other NAD pools change across female aging.
β-Nicotinamide mononucleotide
Direct female evidence includes a randomized trial in postmenopausal women, alongside smaller women-only studies. The clearest controlled finding is improved skeletal-muscle insulin sensitivity in the studied population.
Larger women-only trials across broader midlife outcomes would strengthen life-stage-specific interpretation.
trans-Resveratrol
Postmenopausal trials have examined cognition, cerebrovascular function, bone, pain and metabolic outcomes. Individual trials report favorable findings across several domains, while pooled results vary by endpoint.
Larger independent trials can help reconcile cognition, vascular, bone and metabolic findings after menopause.
Counts refer to published evidence records tagged to each topic. Secondary analyses retain their shared trial or cohort identifier, keeping publication counts distinct from independent-trial counts.
How we evaluate research
We record the details that determine what a study can support. Those details stay attached to the public evidence record.
Evidence roles
Evidence weight depends on the question, study quality and consistency across independent research.
| Evidence type | Best used for | What we check |
|---|---|---|
| Human intervention | Testing whether an intervention changes a biomarker, symptom, function or safety outcome in people. | Population, comparator, allocation, dose, duration, primary endpoint and between-group result. |
| Systematic review or meta-analysis | Seeing whether findings repeat across studies and estimating a pooled effect when studies are sufficiently comparable. | Included trials, overlap, heterogeneity, outcome alignment, risk of bias and statistical method. |
| Human contextual evidence | Understanding physiology, aging patterns, tissue measurements and associations in people. | Study design, tissue or biological matrix, population and the boundary between association and intervention. |
| Preclinical evidence | Exploring mechanisms, biological pathways and hypotheses before or alongside human research. | Species or model, experimental dose, administration route and relevance to the human question. |
| Regulatory or scientific opinion | Evaluating a defined safety question, ingredient, proposed claim or condition of use. | Jurisdiction, exact ingredient, use conditions, evidence question and assessment date. |
A strong meta-analysis can clarify a mature question. A weak or highly heterogeneous review can remain less informative than a well-designed trial. We evaluate the evidence that best fits the question.
From paper to claim
A study enters the library with its boundaries intact. The wider evidence base decides how much weight it receives.
We confirm publication identity and read the strongest available source. Full text is the standard for claim-level interpretation when available.
Population, formulation, route, dose, duration and endpoint define the exact scientific statement the paper can support.
Supportive, mixed and null findings stay together. Replication and higher-quality syntheses can change the weight of a conclusion.
Evidence update log
| Evidence library updated | September 10, 2026 |
| New records added | 0 |
| Records materially reclassified | 2 |
| Corrections or retractions identified | 0 |
Direct answers
Each answer starts with the conclusion, then links to the source and the deeper evidence.
It means CELLSHE confirmed the publication identity and read the full paper for claim-level interpretation when full text was available. The status describes source verification, not whether the study itself is strong, positive or independently replicated.
CELLSHE method: Full text is the standard for claim-level interpretation when it is available. Verification status remains separate from evidence strength and result direction.
Yes. Multiple human trials show that oral NMN can increase whole-blood or circulating NAD-related metabolites. That target engagement is the most consistent human NMN finding.
Sources: Okabe et al., Frontiers in Nutrition 2022, PMID 35479740. Christen et al., Nature Metabolism 2026, PMID 41540253.
One trial can produce a primary report, secondary analysis, follow-up paper, comment or response. CELLSHE stores publication records separately, links related records with a shared trial or cohort family ID when known, and flags secondary publications so paper counts are not treated as independent trial counts.
CELLSHE method: Publication records are not automatically counted as independent trials. Trial or cohort family IDs and secondary-publication flags preserve related-paper context.
Not by itself. Ingredient research can support a bounded ingredient statement when the studied formulation, dose, route, population, duration and endpoint fit the claim. It does not automatically establish the performance of a specific CELLSHE finished product. When finished-product evidence exists, we identify it separately.
Evidence boundary: Ingredient evidence and finished-product evidence stay separate throughout CELLSHE Science and claim review.
Creatine monohydrate is best supported for strength, resistance-training outcomes and repeated high-intensity work. Direct female trials include both favorable and null results, with the clearest pattern around strength and training.
Source: Lin, Zhu & Hong, Frontiers in Nutrition 2026. DOI 10.3389/fnut.2026.1921827.
The strongest postmenopausal evidence is for muscle and strength alongside resistance training. A 2026 meta-analysis of seven randomized trials found about 0.37 kg more lean mass and a 7.5 kg leg-press advantage. Overall bone mineral density did not improve consistently.
Source: Naddafha et al., Journal of the International Society of Sports Nutrition 2026. PMID 42141930.
Human resveratrol research shows measurable changes in selected antioxidant and inflammatory biomarkers. Pooled results vary by biomarker, population and study, so the strongest conclusion stays specific to the outcome measured.
Sources: Omidian et al. 2020, PMID 31738139. Sun et al. 2026, PMID 41987155.
Direct women-only NMN research currently includes a randomized trial in 25 postmenopausal women and smaller uncontrolled studies. The controlled trial found improved skeletal-muscle insulin sensitivity in women with overweight or obesity and prediabetes.
Key controlled study: Yoshino et al., Science 2021, PMID 33888596. The women-only NMN records are indexed in the CELLSHE Evidence Library.
Human lifespan extension has not been demonstrated for NMN, creatine or resveratrol. Their human evidence addresses specific biomarkers, physiological outcomes, function, safety and clinical endpoints.
Evidence context: The full CELLSHE Evidence Library separates biomarker, functional, clinical and preclinical outcomes by study type.
We match the evidence to the question. Population, design, comparator, formulation, route, dose, duration and primary endpoint determine what a study can support. Replication, systematic reviews, limitations, funding and conflicts shape its final weight.
CELLSHE method: The methodology section explains the classification, endpoint, funding, conflict and update rules used across this page.
Deeper research
The Science page maps the evidence. Dedicated guides turn each research area into a focused decision resource.
NMN
Women-specific trials, NAD+ biology, menopause context, doses used in research, safety and practical decisions.
Explore the NMN guide →Creatine monohydrate
Strength, training, lean mass, menopause, water weight, kidney evidence, dosing and creatine forms.
Explore the creatine guide →Supplement library
Evidence-based guides built to answer the practical question before the buying decision.
Explore all supplement guides →CELLSHE Journal
Longer articles on healthy aging, physiology, supplements and the questions surrounding the evidence.
Browse the Journal →From the Journal
A small selection of CELLSHE articles chosen for scientific depth, evidence interpretation and relevance to this hub.
Use the research
Supplement Guides translate the research into focused answers on ingredients, doses used in studies, life-stage evidence and practical use.
Scientific scope. This page is general education. Study findings apply to the population, ingredient, formulation, dose, duration, route and endpoints actually studied.
Ingredient and product evidence. Ingredient evidence and finished-product evidence stay separate. When finished-product evidence exists, we identify it explicitly.
Health decisions. Supplements can interact with medications and may be unsuitable in some circumstances. Discuss personal use with a qualified healthcare professional when you are pregnant, nursing, taking medication or managing a medical condition.
