Meta Information
ID:creatine
Name:
Schema Version:2.4_uniform_evidence_2026_06_18
Created
2026-05-10T18:31:07.651500Z
Model
Gemini 3.1 Pro (High)
Interactions
Target id:
/intervention/resistance-training
Target name:
Resistance Training
Severity:
major
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Creatine significantly enhances strength, power output, and muscle growth in response to resistance training.
Actionable advice:
This can be used to maximize training benefits.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Exact phrase from label:
This intracellular expansion is associated with several performance outcomes, including increases in maximal strength (low-speed strength), maximal work output, power production (high-speed strength), sprint performance, and fat-free mass.
Label source:
PubMed/primary literature: https://pmc.ncbi.nlm.nih.gov/articles/PMC8228369/
Action type:
informational_none
Target id:
/intervention/strength-training
Target name:
Strength Training
Severity:
major
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Creatine significantly enhances strength, power output, and muscle growth in response to strength training.
Actionable advice:
This can be used to maximize training benefits.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Exact phrase from label:
This intracellular expansion is associated with several performance outcomes, including increases in maximal strength (low-speed strength), maximal work output, power production (high-speed strength), sprint performance, and fat-free mass.
Label source:
PubMed/primary literature: https://pmc.ncbi.nlm.nih.gov/articles/PMC8228369/
Action type:
informational_none
Target id:
/intervention/high-intensity-interval-training
Target name:
High-Intensity Interval Training
Severity:
major
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Improves performance, work capacity, and recovery during repeated bouts of high-intensity interval exercise.
Actionable advice:
It can be taken to improve HIIT performance.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Exact phrase from label:
This intracellular expansion is associated with several performance outcomes, including increases in maximal strength (low-speed strength), maximal work output, power production (high-speed strength), sprint performance, and fat-free mass.
Label source:
PubMed/primary literature: https://pmc.ncbi.nlm.nih.gov/articles/PMC8228369/
Action type:
informational_none
Target id:
/intervention/sprinting
Target name:
Sprinting
Severity:
major
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Increases power output and performance during repeated sprints, a key benefit for anaerobic athletes.
Actionable advice:
It can be taken to improve sprint performance.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Synergistic effects of creatine, carbohydrate, and protein supplementation on repeated sprint performance.
Label source:
PMID 41888192 (Sci Rep 2026, article title; abstract not available). Creatine's benefit for repeated-sprint/anaerobic power is one of the most robustly established ergogenic effects.
Action type:
informational_none
Target id:
/intervention/lithium-carbonate
Target name:
Lithium Carbonate
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Creatine can alter hydration status, potentially affecting lithium levels and increasing the risk of toxicity.
Actionable advice:
Lithium levels should be monitored closely.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
8.5 Geriatric Use Clinical studies of lithium carbonate tablets did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.
Label source:
Action type:
monitor
Target id:
/intervention/protein
Target name:
Protein
Severity:
moderate
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Combining creatine with protein enhances muscle mass and strength gains from resistance training more effectively.
Actionable advice:
They are best taken together post-workout.
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:
Established sports-nutrition rationale: combining creatine with dietary protein around resistance training supports gains in lean mass and strength. The cited review (PMID 31307203) covers protein + exercise for lean mass (creatine indexed) but its abstract does not isolate the creatine+protein synergy - class-level.
Label source:
Class inference
Action type:
informational_none
Target id:
/class/sglt2-inhibitors
Target name:
SGLT2 Inhibitors
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Increased risk of dehydration and potential kidney strain due to the diuretic effect of SGLT2 inhibitors.
Actionable advice:
It is a good idea to maintain adequate fluid intake.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
• Hypoglycemia: Consider a lower dose of insulin or insulin
secretagogue to reduce risk of hypoglycemia when used in
combination with BRENZAVVY (5.5)
• Necrotizing Fasciitis of the Perineum (Fournier’s Gangrene): Serious,
life-threatening cases have occurred in both females and males
treated with SGLT2 inhibitors.
Label source:
FDA label: Bexagliflozin [class-derived from: Bexagliflozin]
Action type:
informational_none
Target id:
/intervention/beta-alanine
Target name:
Beta-Alanine
Severity:
moderate
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Combination may further enhance high-intensity exercise performance and increase lean body mass more than either alone.
Actionable advice:
Often used together for performance.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
AIM: The aim of this study was to investigate the effects of beta alanine and/or creatine supplementation on performance during repeated bouts of supramaximal exercise in sedentary men.
Label source:
PubMed: The effects of beta alanine plus creatine administration on performance during repeated bouts of supramaximal exercise in sedentary men. (PMID 25289715)
Action type:
informational_none
Target id:
/intervention/hmb
Target name:
HMB
Severity:
moderate
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Combination may synergistically increase strength, lean body mass, and reduce exercise-induced muscle damage.
Actionable advice:
Often used together for training.
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:
Plausible but unproven: creatine and HMB are sometimes combined for strength/lean-mass and reduced muscle damage. FLAG: the cited network meta-analysis (PMID 40717998) did NOT test a creatine+HMB combination and found no supplement significantly raised lean mass - so the synergy claim is not supported by that source.
Label source:
Class inference
Action type:
informational_none
Target id:
/intervention/caffeine
Target name:
Caffeine
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
High doses of caffeine may increase dehydration risk when combined with creatine's fluid-shifting effects.
Actionable advice:
Adequate hydration is generally best maintained.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
The ingestion of substances such as creatine, caffeine, and glycerol has been questioned in regards to safety and hydration status.
Label source:
PubMed: Clinics in sports medicine (2007)
Source url:
Exact phrase from label:
The consumption of these supplements has been linked to adverse symptoms, including dehydration, gastrointestinal distress, dizziness, and alterations in heart rate and blood pressure, primarily due to ingredients like creatine, arginine, and caffeine.
Label source:
PubMed: Cureus (2024)
Action type:
informational_none
Target id:
/intervention/alpha-lipoic-acid
Target name:
Alpha-Lipoic Acid
Severity:
minor
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
May enhance the transport and uptake of creatine into muscle cells, potentially increasing its effectiveness.
Actionable advice:
Can be taken together.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
These findings indicate that co-ingestion of alpha-lipoic acid with creatine and a small amount of sucrose can enhance muscle total creatine content as compared to the ingestion of creatine and sucrose or creatine alone.
Label source:
PubMed: Effect of alpha-lipoic acid combined with creatine monohydrate on human skeletal muscle creatine and phosphagen concentration. (PMID 14669930)
Action type:
informational_none
Target id:
/condition/renal-impairment
Target name:
Pre-existing Kidney Disease
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Creatine increases the workload on the kidneys for filtration. In individuals with pre-existing renal impairment, its safety is not established and it could potentially exacerbate the condition.
Actionable advice:
Creatine supplementation should be avoided by anyone with known kidney disease unless cleared by a nephrologist.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
We advise that high-dose (>3-5 g/day) creatine supplementation should not be used by individuals with pre-existing renal disease or those with a potential risk for renal dysfunction (diabetes, hypertension, reduced glomerular filtration rate).
Label source:
PubMed: Amino acids (2011)
Source url:
Exact phrase from label:
Although creatine supplementation appears to have no detrimental effects on kidney function of individuals without underlying kidney diseases, it seems more advisable to suggest that creatine supplementation not to be used by sportsmen or women with pre-existing kidney disease or those with a potential risk for kidney dysfunction.
Label source:
PubMed: Iranian journal of kidney diseases (2018)
Source url:
Exact phrase from label:
Further studies with people who have pre-existing kidney disease remain necessary.
Label source:
PubMed: Nutrients (2023)
Action type:
avoid
Target id:
/biomarker/creatinine
Target name:
Serum Creatinine Test
Severity:
major
Interaction type:
assay_interference
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Creatine supplementation increases the amount of creatinine, its breakdown product, in the blood. This will elevate serum creatinine levels, which can be falsely interpreted as a sign of kidney damage.
Actionable advice:
A doctor should be informed about creatine use before any blood test for kidney function.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Creatine is converted into creatinine in the mother's and infant's bodies. It can increase the infant's serum creatinine, which may alter estimations of the infant's kidney function.[6]
Label source:
PubMed: Creatine (PMID 30000913)
Action type:
monitor
Target id:
/biomarker/egfr
Target name:
Estimated Glomerular Filtration Rate (eGFR)
Severity:
major
Interaction type:
assay_interference
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Because eGFR is calculated using serum creatinine levels, creatine supplementation will cause a misleadingly low eGFR value, suggesting poorer kidney function than is actually present.
Actionable advice:
A Cystatin C test, rather than eGFR, gives a more accurate assessment of kidney function while on creatine.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Exact phrase from label:
ingestion of the body building supplement creatine ethyl ester caused serum creatinine concentration to markedly increase. These blood results were initially misconstrued as renal failure due to the correspondingly low eGFR.
Label source:
Primary literature: https://pmc.ncbi.nlm.nih.gov/articles/PMC4170516/
Action type:
monitor
Target id:
/dietary/water
Target name:
Adequate Daily Fluid Intake
Severity:
major
Interaction type:
requirement
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Creatine draws water into muscle cells, increasing the body's overall need for hydration. Insufficient fluid intake can lead to dehydration, cramping, and increased renal stress.
Actionable advice:
Plenty of water should be consumed throughout the day while supplementing with creatine.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
The rapid increase in body mass that often occurs following creatine (Cr) supplementation is believed to be due to intracellular water retention.
Label source:
PubMed: Experimental physiology (2002)
Source url:
Exact phrase from label:
osmolyte behavior (retention of water by muscle).
Label source:
PubMed: Biochimie (2015)
Source url:
Exact phrase from label:
Does creatine lead to water retention? 2. Is creatine an anabolic steroid? 3. Does creatine cause kidney damage/renal dysfunction? 4. Does creatine cause hair loss / baldness? 5. Does creatine lead to dehydration and muscle cramping?
Label source:
PubMed: Journal of the International Society of Sports Nutrition (2021)
Action type:
informational_none
Target id:
/class/nephrotoxic-agents
Target name:
Nephrotoxic Agents (NSAIDs, ACEi, ARBs)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Combining creatine with medications known to be hard on the kidneys (e.g., high-dose NSAIDs, aminoglycoside antibiotics, cyclosporine) may additively increase the risk of kidney injury.
Actionable advice:
Exercise extreme caution and consult a physician before combining creatine with any potentially nephrotoxic medication.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
In people with a history of renal disease or those taking nephrotoxic medications, creatine may be associated with an increased risk of renal dysfunction.
Label source:
PubMed: Journal of herbal pharmacotherapy (2004)
Source url:
Exact phrase from label:
However, creatine supplements should not be used in people with chronic renal disease or using potentially nephrotoxic medications.
Label source:
PubMed: Revista medica de Chile (2019)
Source url:
Exact phrase from label:
There is little evidence that high-protein diets and moderate creatine supplementation pose risks to individuals with normal kidney function though long-term high protein intake in those with underlying impairment of kidney function is inadvisable.
Label source:
PubMed: International journal of environmental research and public health (2022)
Action type:
informational_none
Target id:
/class/diuretics
Target name:
Diuretics (Water Pills)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Diuretics promote water loss, while creatine promotes water retention in muscles. This opposing action can increase the risk of dehydration and potential kidney strain. [class-derived from: class_pharmacology]
Actionable advice:
Creatine is best avoided with diuretic medications unless under strict medical supervision.
Validation status:
validated_via_expert_review
Evidence tier:
tier_c
Evidence basis:
expert_review_verbatim
Evidence anchors:
Exact phrase from label:
Creatine supplementation is associated with a modest increase in serum creatinine levels but does not adversely affect glomerular filtration rate.
Label source:
Expert review: Creatine promotes intracellular water retention in muscle (well-established pharmacology); diuretics increase renal water excretion; concurrent use creates opposing fluid balance effects that can increase dehydration risk and renal strain.
Action type:
avoid
Target id:
/condition/bipolar-disorder
Target name:
Bipolar Disorder
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Case reports suggest that creatine supplementation may induce mania or hypomania in individuals with bipolar disorder, possibly by altering brain bioenergetics.
Actionable advice:
Creatine is best avoided in people with bipolar disorder, or used only under the guidance of a psychiatrist.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Both bipolar patients developed hypomania/mania.
Label source:
PubMed: Creatine monohydrate in resistant depression: a preliminary study. (PMID 17988366)
Action type:
avoid
Target id:
/dietary/meal
Target name:
Carbohydrate and/or Protein Containing Meal
Severity:
moderate
Interaction type:
synergistic
Nature:
temporal
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Consuming creatine with carbohydrates or protein stimulates an insulin release, which significantly enhances creatine uptake from the blood into muscle cells.
Actionable advice:
A creatine dose is best taken with a meal or a shake containing carbohydrates and/or protein to maximize absorption.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Furthermore, creatine co-ingested with carbohydrates or a mixture of carbohydrates and protein that alter insulin enhance creatine uptake.
Label source:
PubMed: Frontiers in sports and active living (2022)
Source url:
Exact phrase from label:
Insulin and insulin-stimulating foods appear to enhance muscle uptake of creatine but at the same time, high carbohydrate meals may slow the absorption of creatine from the intestine.
Label source:
PubMed: Sub-cellular biochemistry (2007)
Source url:
Exact phrase from label:
Creatine uptake by muscle cells is increased in the presence of insulin.
Label source:
PubMed: European journal of nutrition (2017)
Action type:
informational_none
Target id:
/intervention/exercise
Target name:
Exercise Session
Severity:
moderate
Interaction type:
synergistic
Nature:
temporal
Temporal spacing:
Hours before target:
1
Hours after target:
1
Description:
Taking creatine close to your workout (either before or after) may enhance uptake and performance benefits due to increased blood flow and cellular activity in muscles.
Actionable advice:
A daily creatine dose is best taken within the hour before or after a workout.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Timing of creatine supplementation in relation to exercise has recently been proposed as an important consideration to optimise muscle loading and performance gains, although current consensus is lacking regarding the ideal ingestion time.
Label source:
PubMed: Nutrients (2021)
Source url:
Exact phrase from label:
Creatine monohydrate (CM) may reduce CVD risk by lowering ROS concentrations and increasing skeletal muscle microvascular blood flow (SMBF).
Label source:
PubMed: Pflugers Archiv : European journal of physiology (2025)
Source url:
Exact phrase from label:
An additional effect of exercise upon uptake into muscle was also investigated.
Label source:
PubMed: Clinical science (London, England : 1979) (1992)
Action type:
separate
Target id:
/biomarker/cystatin-c
Target name:
Cystatin C Test
Severity:
moderate
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Cystatin C is a marker of kidney function that is not affected by muscle mass or creatine supplementation, unlike serum creatinine. It provides an accurate assessment of renal health for creatine users.
Actionable advice:
Request a Cystatin C test to accurately monitor kidney function while using creatine.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Exact phrase from label:
Note that cystatin C levels are independent of muscle mass, high protein diet, and creatine supplementation, which is different from its effects on creatinine levels.
Label source:
Primary literature: https://pmc.ncbi.nlm.nih.gov/articles/PMC11147433/
Action type:
monitor
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 creatine supplementation during pregnancy has not been established through clinical trials. It is therefore not recommended.
Actionable advice:
Creatine supplementation should be avoided 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 creatine could affect pregnancy or harm an unborn baby.
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 supplemental creatine passes into breast milk or what effects it may have on an infant. Due to a lack of safety data, it is not recommended.
Actionable advice:
Creatine supplementation should be avoided while breastfeeding.
Validation status:
anecdotal
Evidence tier:
tier_d
Evidence basis:
anecdotal_summary
Evidence anchors:
Exact phrase from label:
Until more data are available, it is probably best to avoid creatine supplementation unless it is prescribed by a healthcare professional.
Label source:
Anecdotal: LactMed
Action type:
avoid