Meta Information
ID:nr
Name:
Schema Version:2.4_uniform_evidence_2026_06_18
Created
2026-05-21T22:30:00Z
Model
phase-a-upgrade-claude-sonnet-4.6
Interactions
Target id:
/circadian/wake
Target name:
Waking Up
Severity:
minor
Interaction type:
synergistic
Nature:
temporal
Temporal spacing:
Hours before target:
null
Hours after target:
2
Description:
Taking Nicotinamide Riboside in the morning aligns with the body's natural circadian rhythm of NAD+ production, which is highest during the day to support energy and activity.
Actionable advice:
A daily dose is generally best taken in the morning to support natural energy cycles.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
NR enhances BMAL1 chromatin binding genome-wide through PER2K680 deacetylation, which in turn primes PER2 phosphorylation within a domain that controls nuclear transport and stability and that is mutated in human advanced sleep phase syndrome.
Label source:
PubMed: Molecular cell (2020)
Source url:
Exact phrase from label:
SIRT3 activity being nicotinamide adenine dinucleotide (NAD)+ level-dependent, we show that NAD+ is orchestrated by both feeding rhythms and the circadian clock through the NAD+ salvage pathway but also via the nicotinamide riboside pathway.
Label source:
PubMed: Cell reports (2017)
Source url:
Exact phrase from label:
NAD(+) biosynthesis, particularly mediated by nicotinamide phosphoribosyltransferase (NAMPT), and SIRT1 function together to regulate metabolism and circadian rhythm.
Label source:
PubMed: Trends in cell biology (2014)
Action type:
informational_none
Target id:
/circadian/sleep
Target name:
Going to Sleep
Severity:
minor
Interaction type:
adverse
Nature:
temporal
Temporal spacing:
Hours before target:
4
Hours after target:
null
Description:
As a precursor to the energy-related molecule NAD+, taking Nicotinamide Riboside close to bedtime may be stimulating for some individuals and could potentially interfere with sleep onset.
Actionable advice:
Nicotinamide Riboside is generally best taken more than 4 hours before intended bedtime.
Validation status:
validated_via_class_inference
Evidence tier:
tier_c
Evidence basis:
class_inference_summary
Evidence anchors:
Source url:
Established mechanism / class pharmacology (no single primary source quoted)
Exact phrase from label:
Mechanistic/timing heuristic: NAD+/NAMPT show circadian oscillation (cited PMC2886185), so some take NR earlier in the day. FLAG: that NR is 'stimulating' or interferes with sleep is not evidenced - speculative.
Label source:
Class inference
Action type:
separate
Target id:
/intervention/betaine
Target name:
Betaine (TMG)
Severity:
moderate
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
The metabolism of NAD+ precursors like NR consumes methyl groups. Co-supplementing with a methyl donor like TMG helps replenish these groups, supporting healthy methylation cycles and preventing potential increases in homocysteine.
Actionable advice:
Consider taking a methyl donor like TMG, especially when using higher doses of Nicotinamide Riboside.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Exact phrase from label:
While NR-recipients exhibited a slight initial rise in serum homocysteine levels, the integrity of the methyl donor pool remained intact.
Label source:
NR-SAFE trial, PMC10684646. Supports that NR transiently raises homocysteine (methyl-group consumption), the rationale for co-supplementing betaine/TMG; note the trial found the methyl pool remained intact, so the concern is real but modest.
Action type:
informational_none
Target id:
/intervention/resveratrol
Target name:
Resveratrol
Severity:
moderate
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
NR increases NAD+ levels, which acts as essential fuel for sirtuin enzymes. Resveratrol is a sirtuin-activating compound (STAC), so combining them may create a synergistic effect on cellular health and metabolism.
Actionable advice:
Consider taking Resveratrol alongside Nicotinamide Riboside to potentially enhance sirtuin activity.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
In contrast, pharmaceutical and nutraceutical therapies, including metformin, melatonin, resveratrol, and agents that increase NAD+ levels, may reverse ovarian deterioration and reactivate SIRT1-Nrf2 activity.
Label source:
PubMed: Oxidative Stress and SIRT1-Nrf2 Anti-Ferroptotic Pathways in Granulosa Cells: A Molecular Key to Follicular Atresia and Ovarian Aging. (PMID 41596597)
Action type:
informational_none
Target id:
/intervention/pterostilbene
Target name:
Pterostilbene
Severity:
moderate
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Pterostilbene, a compound similar to resveratrol, activates sirtuin enzymes. Combining it with NR, which provides the NAD+ fuel for sirtuins, may produce a synergistic effect on cellular health.
Actionable advice:
Consider taking Pterostilbene alongside Nicotinamide Riboside to potentially enhance sirtuin activity.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
PTE had no significant effect on the expression of the glucocorticoid receptor (P>.05), but significantly upregulated the protein expression of Sirt1 and p-AMPK (P<.05), promoted the expression of lipid autophagy genes MAP1LC3B and lipolytic genes LPL, but inhibited the expression of fatty acid synthesis genes SREBP-1c, ACC, and SCD (P<.05).
Label source:
PubMed: Ameliorative effect of phenolic compound-pterostilbene on corticosterone-induced hepatic lipid metabolic disorder in broilers. (PMID 39645170)
Action type:
informational_none
Target id:
/intervention/apigenin
Target name:
Apigenin
Severity:
moderate
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Apigenin inhibits the CD38 enzyme, which is a primary consumer of NAD+. Combining it with NR, which boosts NAD+ production, creates a 'two-pronged' approach to increasing and maintaining cellular NAD+ levels.
Actionable advice:
Consider taking Apigenin with Nicotinamide Riboside to help preserve the NAD+ that is produced.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Exact phrase from label:
we characterize two CD38 inhibitors: quercetin and apigenin... pharmacological inhibition of CD38 results in higher intracellular NAD+ levels.
Label source:
Escande et al. 2013, PMC3609577. Supports apigenin as a CD38 (NAD+ase) inhibitor that raises NAD+; pairing with NR is a complementary two-pronged rationale.
Action type:
informational_none
Target id:
/class/chemotherapy-radiation
Target name:
Cytotoxic Cancer Therapies (Chemotherapy & Radiation)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Boosting NAD+ levels with NR may enhance cellular DNA repair and stress resistance pathways. This could theoretically reduce the effectiveness of chemotherapy and radiation, which rely on inducing damage in cancer cells.
Actionable advice:
Nicotinamide Riboside should not be taken during active cancer treatment without explicit approval from an oncologist.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
In the placebo group, one patient with FIGO Stage IB cancer received radiation therapy and the patient with FIGO Stage IVB cancer received chemotherapy and hormonal therapy.
Label source:
Action type:
avoid
Target id:
/class/parp-inhibitors
Target name:
PARP Inhibitors
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
PARP inhibitors are cancer drugs that work by blocking an NAD+-dependent DNA repair enzyme. Supplementing with NR could increase NAD+ levels, potentially counteracting the therapeutic effect of these medications.
Actionable advice:
Nicotinamide Riboside should be avoided completely when taking a PARP inhibitor medication for cancer.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Exact phrase from label:
Upregulation of intracellular NAD+ levels by the addition of nicotinamide also induced resistance to olaparib and talazoparib... upregulation of intracellular NAD+ is one of the factors underlying the acquisition of PARP inhibitor resistance.
Label source:
Sasaki et al. 2024, PMC11020856. Supports that raising NAD+ can counteract PARP-inhibitor efficacy - a meaningful oncology caution.
Action type:
avoid
Target id:
/condition/pregnancy
Target name:
Pregnancy
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
The safety of high-dose Nicotinamide Riboside supplementation during pregnancy has not been established. It should be avoided out of an abundance of caution.
Actionable advice:
Nicotinamide Riboside supplements should not be taken during pregnancy.
Validation status:
anecdotal
Evidence tier:
tier_d
Evidence basis:
anecdotal_summary
Evidence anchors:
Exact phrase from label:
It is not known if or how nicotinamide riboside could affect pregnancy or harm a fetus.
Label source:
Anecdotal: WebMD
Action type:
avoid
Target id:
/condition/lactation
Target name:
Breastfeeding (Lactation)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
It is unknown if high doses of Nicotinamide Riboside or its metabolites pass into breast milk. Due to a lack of safety data, it should be avoided while breastfeeding.
Actionable advice:
Nicotinamide Riboside supplements should not be taken while breastfeeding.
Validation status:
anecdotal
Evidence tier:
tier_d
Evidence basis:
anecdotal_summary
Evidence anchors:
Exact phrase from label:
It is not known if nicotinamide riboside passes into breast milk, but vitamin B3 passes into breast milk.
Label source:
Anecdotal: WebMD
Action type:
avoid
Target id:
/class/antidiabetic-medications
Target name:
Diabetes Medications
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Nicotinamide Riboside may improve insulin sensitivity and glucose control. When taken with medications for diabetes, this could have an additive effect, potentially increasing the risk of low blood sugar (hypoglycemia).
Actionable advice:
If you take diabetes medication, monitor your blood sugar closely when starting NR and consult your doctor.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization.
Label source:
Action type:
monitor
Target id:
/condition/hepatic-impairment
Target name:
Hepatic Impairment
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Nicotinamide Riboside is metabolized by the body, involving the liver. In cases of severe liver impairment, metabolic capacity may be reduced, warranting caution and medical supervision.
Actionable advice:
It is important to consult a doctor before taking Nicotinamide Riboside for those with significant liver disease.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
The correction of glycolysis and fatty acid metabolism defects in CITRIN KO cells by reducing cytoplasmic NADH:NAD+ levels suggests this may be a novel strategy to treat some of the metabolic defects of CD and other mitochondrial diseases.
Label source:
PubMed: Nicotinamide riboside rescues dysregulated glycolysis and fatty acid β-oxidation in a human hepatic cell model of citrin deficiency. (PMID 36881658)
Action type:
informational_none
Target id:
/intervention/nmn
Target name:
NMN (Nicotinamide Mononucleotide)
Severity:
minor
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Both NR and NMN are precursors to NAD+ and function via similar pathways. Taking them together is redundant and unlikely to provide benefits beyond what an adequate dose of one alone would offer.
Actionable advice:
Either NR or NMN is generally best chosen; taking both together is generally not necessary or cost-effective.
Validation status:
validated_via_class_inference
Evidence tier:
tier_c
Evidence basis:
class_inference_summary
Evidence anchors:
Source url:
Established mechanism / class pharmacology (no single primary source quoted)
Exact phrase from label:
Pharmacological inference: NR and NMN are both NAD+ precursors acting through overlapping salvage steps, so combining them is largely redundant. Cited PMID 27721479 confirms NR raises NAD+ but does not compare it to NMN.
Label source:
Class inference
Action type:
informational_none
Target id:
/intervention/niacin
Target name:
Niacin (Vitamin B3)
Severity:
minor
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
NR and Niacin are both forms of Vitamin B3 that increase NAD+. Using them together is redundant for NAD+ boosting purposes and may increase the burden on metabolic pathways.
Actionable advice:
Either NR or Niacin is generally best for NAD+ support, not both concurrently.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
At the doses used to treat hyperlipidemia, these metabolic pathways are saturable, which explains the nonlinear relationship between niacin dose and plasma concentrations following multiple-dose niacin extended-release tablets administration.
Label source:
Action type:
informational_none
Target id:
/intervention/quercetin
Target name:
Quercetin
Severity:
minor
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Quercetin can inhibit the CD38 enzyme, a major consumer of cellular NAD+. Taking it with NR, an NAD+ precursor, may synergistically increase and sustain NAD+ levels.
Actionable advice:
Consider taking Quercetin with Nicotinamide Riboside to help preserve the NAD+ that is produced.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
In this study, we established a novel approach to effectively utilize NAD+ for skin anti-aging by enhancing the pharmacological efficacy of exogenous NAD+ using a phytochemical complex consisting of quercetin, and enoxolone through inhibition of CD38. Through the comprehensive in vitro experiments based on human fibroblasts, we observed that exogenous NAD+ could exert protective effects against both extrinsic aging induced by ultraviolet light exposure and intrinsic aging. Additionally, we found that its effects were significantly boosted by quercetin and enoxolone.
Label source:
PubMed: Novel Approach to Skin Anti-Aging: Boosting Pharmacological Effects of Exogenous Nicotinamide Adenine Dinucleotide (NAD+) by Synergistic Inhibition of CD38 Expression. (PMID 39513906)
Action type:
informational_none
Target id:
/intervention/exercise
Target name:
Exercise
Severity:
minor
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Exercise naturally increases NAD+ levels and consumption. Supplementing with NR ensures an adequate supply of this crucial coenzyme to meet the metabolic demands of physical activity and support recovery.
Actionable advice:
Nicotinamide Riboside can be a supportive supplement to a regular exercise routine.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Exercise requires a higher energy expenditure than a resting state, thus a state of NAD+ insufficiency with reduced energy metabolism, could result in an inadequate exercise response.
Label source:
PubMed: Experimental gerontology (2020)
Source url:
Exact phrase from label:
By modulating NAD+-sensing enzymes, NAD+ controls hundreds of key processes from energy metabolism to cell survival, rising and falling depending on food intake, exercise, and the time of day.
Label source:
PubMed: Cell metabolism (2018)
Source url:
Exact phrase from label:
Treatment of ANT1-deficient mice with nicotinamide riboside increased NAD+ levels in skeletal muscle and liver, which increased the exercise capacity and the mitochondrial respiration.
Label source:
PubMed: Molecular metabolism (2022)
Action type:
informational_none
Target id:
/intervention/intermittent-fasting
Target name:
Intermittent Fasting
Severity:
minor
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Intermittent fasting is known to increase NAD+ levels. Taking NR during your eating window provides the building blocks to further enhance NAD+ pools, potentially amplifying the benefits.
Actionable advice:
Nicotinamide Riboside is generally best taken during the eating window when practicing intermittent fasting.
Validation status:
validated_via_class_inference
Evidence tier:
tier_c
Evidence basis:
class_inference_summary
Evidence anchors:
Source url:
Established mechanism / class pharmacology (no single primary source quoted)
Exact phrase from label:
Mechanistic inference: fasting/caloric restriction raises NAD+, so NR taken in the eating window could add substrate. FLAG: the cited PMID 39117797 is actually a spermidine/autophagy paper unrelated to NAD+ - wrong citation; the fasting-NAD+ premise must be sourced elsewhere.
Label source:
Class inference
Action type:
informational_none
Target id:
/condition/renal-impairment
Target name:
Renal Impairment
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Metabolites of Nicotinamide Riboside are cleared by the kidneys. While no direct toxicity is known, caution is advised in severe kidney disease due to altered clearance.
Actionable advice:
It is a good idea to talk to a doctor before using Nicotinamide Riboside with severe kidney disease.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Using plasma and erythrocyte extracts obtained from children with chronic renal failure we show that the concentration of 4PyTP is increased, as well as other soluble NAD(+) metabolites (nicotinamide, N(1)-methylnicotinamide and 4Py-riboside) and the major nicotinamide metabolite N(1)-methyl-2-pyridone-5-carboxamide (2PY), with increasing degrees of renal failure.
Label source:
PubMed: 4-Pyridone-3-carboxamide-1-β-D-ribonucleoside triphosphate (4PyTP), a novel NAD metabolite accumulating in erythrocytes of uremic children: a biomarker for a toxic NAD analogue in other tissues? (PMID 22069723)
Action type:
informational_none
Target id:
/intervention/levodopa
Target name:
Levodopa
Severity:
minor
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Preclinical research suggests that increasing NAD+ levels may support mitochondrial health and offer neuroprotective effects, which could theoretically complement the action of medications like Levodopa for Parkinson's disease.
Actionable advice:
It is a good idea to talk to a neurologist before adding Nicotinamide Riboside to a Parkinson's disease treatment regimen.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
We report that increasing NAD+ via the NAD+ precursor nicotinamide riboside (NR) significantly ameliorates mitochondrial function in patient neurons. Human neurons require nicotinamide phosphoribosyltransferase (NAMPT) to maintain the NAD+ pool and utilize NRK1 to synthesize NAD+ from NAD+ precursors. Remarkably, NR prevents the age-related dopaminergic neuronal loss and motor decline in fly models of GBA-PD.
Label source:
PubMed: Cell reports (2018)
Source url:
Exact phrase from label:
NR augmented the NAD metabolome and induced transcriptional upregulation of processes related to mitochondrial, lysosomal, and proteasomal function in blood cells and/or skeletal muscle. Furthermore, NR decreased the levels of inflammatory cytokines in serum and cerebrospinal fluid. Our findings nominate NR as a potential neuroprotective therapy for PD, warranting further investigation in larger trials.
Label source:
PubMed: Cell metabolism (2022)
Source url:
Exact phrase from label:
NR therapy was associated with clinical improvement of total MDS-UPDRS scores. However, this change was also associated with a shorter interval since the last levodopa dose.
Label source:
PubMed: Nature communications (2023)
Action type:
informational_none