Creatinol-O-phosphate (COP)

Q: Does COP improve exercise performance?

There is no oral or sports evidence to check. A 1975 controlled trial on muscular performance exists, but no abstract is available, so its route and results are unknown, and no trial with available results has tested COP taken by mouth.

Q: Is COP safe?

Single IV doses up to 3,060 mg did not change blood pressure, heart rate or ECG in volunteers but raised blood phosphate. Long-term oral safety is not studied.

Q: Is creatinol-O-phosphate the same as creatine?

No. COP is a phosphorylated form of creatinol, developed as a heart drug. It is a different molecule from creatine monohydrate.

Q: What did the heart trials find?

Small 1979 Italian trials of injected COP reported fewer premature heartbeats and lower heart-damage enzymes after heart attacks. None measured survival.

Also called COP, creatinol O-phosphate, creatinol phosphate, N-methyl-N-(beta-hydroxyethyl)guanidine O-phosphate.

Best grade D across 3 graded outcomes Other Last checked Oct 21, 2026

The short answer

From 7 sources

Creatinol-O-phosphate was developed as an injected heart drug in the 1970s and is now sold in some sports supplements. All controlled human trials found date from 1975-1979: small Italian studies in people with heart disease, mostly given by injection, with fewer irregular heartbeats and lower heart-damage enzymes. There is no oral or sports evidence: no trial with checkable results has tested COP taken by mouth or for exercise performance.

Every graded outcome on this page

3 rows · line = participants

Grade DHeart-damage enzymes after acute heart attackHeart attackn 46
Grade DRhythm disturbances, chest pain and heart function in coronary diseaseCoronary diseasen 25
Grade DPremature ventricular contractions on Holter ECGHeart rhythmn 10

Key facts

Evidence age: Every controlled human trial found was published between 1975 and 1979^1,2,3,7
Irregular heartbeats: 1,020 mg injected twice daily for 3 days lowered premature ventricular contractions vs a solvent control in 10 heart patients (P < 0.01)²
Heart attack enzymes: Six heart-damage enzymes were 33-49% lower with 3.06 g/day IV COP added to standard care in 46 heart attack patients³
Sports use: No checkable evidence: a 1975 trial on muscular performance has no abstract, so its route and results cannot be verified, and no trial with available results has tested oral COP⁷
Lab effects: IV doses of 2,040-3,060 mg raised blood phosphate and urine creatinine in healthy volunteers⁵

What it is

Creatinol-O-phosphate (COP) is a synthetic creatine-like compound developed in Italy in the 1970s as a heart drug and later sold in some sports supplements.

How it works

Proposed

COP is dephosphorylated in the kidney and liver and concentrates in heart muscle cells. 1970s researchers proposed a protective "membrane effect" on heart cells during low oxygen, improving ion balance and contraction. The work is old and mostly from animal hearts.^6,2

Forms, side by side

2 forms named in our sources. The rest show what our data holds, and say plainly where it holds nothing yet.

Creatinol-O-phosphate (COP) forms compared

2 forms

Creatinol-O-phosphate (COP) forms compared: 2 forms by 3 attributes. Empty cells are labelled No data yet, or Not graded in the evidence row.
2 forms	Injected COP (intravenous or intramuscular)	Oral COP in sports supplements
Absorption in people	Absorption after intramuscular injection is complete; COP is dephosphorylated in the kidney and liver and excreted in urine.^6,5	No oral absorption data were found in the cited abstracts.^7,6
GI tolerance	IV doses up to 3,060 mg caused no change in blood pressure, heart rate or ECG in volunteers; blood phosphate rose.^6,5	Not studied in the cited abstracts.^7,6
Studied for	Heart disease (1970s drug use)	Exercise performance (marketing claim; no checkable trial)

Injected COP (intravenous or intramuscular)
Absorption in people
Absorption after intramuscular injection is complete; COP is dephosphorylated in the kidney and liver and excreted in urine.^6,5
GI tolerance
IV doses up to 3,060 mg caused no change in blood pressure, heart rate or ECG in volunteers; blood phosphate rose.^6,5
Studied for
Heart disease (1970s drug use)
Oral COP in sports supplements
Absorption in people
No oral absorption data were found in the cited abstracts.^7,6
GI tolerance
Not studied in the cited abstracts.^7,6
Studied for
Exercise performance (marketing claim; no checkable trial)

What the human research says

Human trials only, one row per outcome. The form line shows what each trial actually tested. Grades follow our evidence-grading policy.

Trial map

3 graded outcomes, largest study first

All 3 graded outcomes found an improvement. The largest, a 1979 open-label trial of 46 people on Heart-damage enzymes after acute heart attack, found an improvement.

By sizeTable

1Heart-damage enzymes after acute heart attack

Improved · Grade D · Open-label trial, 46 people, 1979

Patients with acute myocardial infarction (two groups of 23)

Dose, result and source

Every graded outcome on this page, largest study first
Outcome	Found	People	Study	Who was studied
Heart-damage enzymes after acute heart attack	Improved	46	Grade D · Open-label trial, 1979	Patients with acute myocardial infarction (two groups of 23)
Rhythm disturbances, chest pain and heart function in coronary disease	Improved	25	Grade D · RCT, 1979	12 patients after a recent heart attack and 13 with angina (Italy)
Premature ventricular contractions on Holter ECG	Improved	10	Grade D · Crossover RCT, 1979	Patients with ischaemic heart disease and frequent premature ventricular contractions

Every graded row

3 rows

Grade DHeart-damage enzymes after acute heart attackHeart attack33-49% lower enzymesOpen-label trial
n 46 · 1979

Improved GOT, GPT, LDH, HBDH, CK and MB-CK were 33-49% lower in the COP group than in controls (P < 0.01).

Design: Open-label trial, n = 46, 1979
Population: Patients with acute myocardial infarction (two groups of 23)
Form: Glucose-insulin-potassium (GIK) plus intravenous COP vs GIK alone
Dose: 3.06 g/24 h (intravenous)
Duration: 3 days
Source: Reference 3 · PubMed 575498 (opens PubMed)

Grade DRhythm disturbances, chest pain and heart function in coronary diseaseCoronary diseaseFewer symptomsRCT
n 25 · 1979

Improved COP improved rhythm disturbances, chest pain and symptoms of contractility failure to a statistically significant degree.

Design: RCT, n = 25, 1979
Population: 12 patients after a recent heart attack and 13 with angina (Italy)
Form: COP vs its solvent as a reference substance, double-blind
Dose: Not stated in the abstract
Duration: Not stated in the abstract
Source: Reference 1 · PubMed 395958 (opens PubMed)

Grade DPremature ventricular contractions on Holter ECGHeart rhythmFewer extra beatsCrossover RCT
n 10 · 1979

Improved Premature ventricular contractions were significantly lower with COP than with the reference substance (P < 0.01); heart rate, PQ and QTc did not change.

Design: Crossover RCT, n = 10, 1979
Population: Patients with ischaemic heart disease and frequent premature ventricular contractions
Form: COP vs solvent, intramuscular, random order
Dose: 1,020 mg twice daily (intramuscular)
Duration: 3 days per treatment
Source: Reference 2 · PubMed 94266 (opens PubMed)

What the numbers add up to

Each point is worked out from the data and the sources numbered on this page, with the arithmetic shown under it. It adds no new data and is not medical advice.

An old heart drug, not a tested sports supplement

The checkable human data are five small 1979 studies, four in heart patients and one tolerance study in volunteers, all published in one journal issue and all using injected COP where the route is stated. No trial with available results has tested COP taken by mouth or for training.^1,2,3,4,5

Studied doses

Doses used in research, shown against the official limits. They describe the studies, not a recommendation for you.

Studied doses in research, not advice. These are amounts used in research, not personal advice. Your clinician or pharmacist can say what fits you.

Doses studied in human trials

Doses studied in human trials ranged from 1,020 mg injected twice daily for 3 days to 3,060 mg/day intravenously; single IV doses up to 3,060 mg were tested for tolerance. No oral doses were reported in the abstracts. These are research doses, not recommendations.^2,3,5

Interactions and safety

Published interactions only: each row cites a source. No row means none was found in our sources, not that a combination is safe.

Interactions

0 agents

None found in our sources.

Check with what you take

Kept on this device only

Add what you take. We list every interaction our evidence profiles cite between Creatinol-O-phosphate and your picks, and between your picks.

Add a supplement or medicine

Most cited:

Add a supplement or medicine you take to check it against Creatinol-O-phosphate.

Starting from one medicine? The interaction checker rates how serious each pair is, on a curated list of 19 entries for 11 medicines. This cabinet has no severity rating: it lists every interaction row our supplement pages cite.

Who should be careful

5 groups

Kidney disease: COP raised blood phosphate and urinary creatinine and phosphate in volunteers and is dephosphorylated in the kidney; people with kidney disease were excluded from the tolerance study.^5,6
Blood and urine tests: Because COP releases phosphate and creatinine, it may change phosphate and creatinine test results (inferred from the tolerance study).⁵
Heart disease: The trials gave injected COP to heart patients under medical care; they do not support self-managing heart rhythm problems with oral supplements.^2,4
Drug interactions: No published drug-interaction studies were found, and neither LiverTox nor LactMed has a creatinol-O-phosphate entry; one 1979 trial suggested studying COP alongside antiarrhythmic drugs.⁴
Pregnancy and breastfeeding: No reliable data. None of the cited studies included pregnant or breastfeeding women, and LactMed has no creatinol-O-phosphate entry.⁵

How to read the label

What to check on the Supplement Facts panel.

How to read the label

2 checks

Not creatine

COP is a phosphorylated creatinol, a different molecule from creatine monohydrate, and none of the cited trials compared the two.⁶

Oral vs injected

Every trial with results in its abstract used injected COP; doses on supplement labels have no matching oral trial.^2,3,5

Have the bottle? Photograph its Supplement Facts panel and see each line, creatinol-o-phosphate (cop) included, beside the doses and forms the trials used in Label X-Ray.

Frequently asked questions

Short answers to common questions; the numbers link to the sources below.

Common questions

4 answers

Does COP improve exercise performance?

There is no oral or sports evidence to check. A 1975 controlled trial on muscular performance exists, but no abstract is available, so its route and results are unknown, and no trial with available results has tested COP taken by mouth.⁷

Is COP safe?

Single IV doses up to 3,060 mg did not change blood pressure, heart rate or ECG in volunteers but raised blood phosphate. Long-term oral safety is not studied.⁵

Is creatinol-O-phosphate the same as creatine?

No. COP is a phosphorylated form of creatinol, developed as a heart drug. It is a different molecule from creatine monohydrate.⁶

What did the heart trials find?

Small 1979 Italian trials of injected COP reported fewer premature heartbeats and lower heart-damage enzymes after heart attacks. None measured survival.^2,3,4

Sources

7 sources: trial abstracts, NIH fact sheets and reference databases. Numbers in the text link here.

Sources cited on this page

7 sources

1Creatinol O-phosphate therapy in patients with inadequate coronary circulation. Double-blind clinical trial.RCT Arzneimittelforschung, 1979 · PMID 395958
2Antiarrhythmic effectiveness of creatinol O-phosphate in man.Crossover RCT Arzneimittelforschung, 1979 · PMID 94266
3Effects of creatinol O-phosphate on serum enzymes in acute myocardial infarction.Open-label trial Arzneimittelforschung, 1979 · PMID 575498
4Activity of creatinol O-phosphate on persistent ventricular premature beats in ischemic heart disease. Double blind clinical trial.RCT Arzneimittelforschung, 1979 · PMID 395959
5Acute clinical tolerance of creatinol O-phosphate.RCT Arzneimittelforschung, 1979 · PMID 575490
6Pharmacological and toxicological properties of creatinol O-phosphate. A review.Review Arzneimittelforschung, 1979 · PMID 395957
7Creatinol O-phosphate (COP) and muscular performance: a controlled clinical trial.RCT Curr Ther Res Clin Exp, 1975 · PMID 808375

What changed

Every dated change to this page: what changed, who made it and why.

Change log

3 entries

Dated changes to this page
Date	Change	Who and why
Oct 21, 2026who should avoid, questions, related	Re-searched PubMed for human studies of creatinol-O-phosphate: nothing after 1979 (later records are lab, animal or materials-science work), so the evidence table is unchanged. Checked LactMed and LiverTox (no entry) and found no documented drug interactions, so the interactions list stays empty; the pregnancy and interaction notes now say so. Added page questions and a link to the performance goal hub.	Writer: Kymata Health EditorialTrigger: A–Z audit against docs/supplements/AUDIT-STANDARD.md
Oct 14, 2026all	Initial editorial evidence review (first draft). Every PMID checked against NCBI E-utilities esummary (titles and years taken from the record, none retracted) and the abstract read for each cited row. Studied doses are reported as research doses, not dosing advice.	Writer: Kymata Health EditorialTrigger: new page
Oct 14, 2026all	Adversarial review: stated plainly that there is no oral or sports evidence (the 1975 muscular-performance trial, PMID 808375, has no abstract and an unknown route), replacing wording that implied only modern oral trials were missing; corrected the insight's study count description.	Writer: Kymata Health EditorialTrigger: adversarial review

Supplement & Nutrient Encyclopedia. Educational information only; it is not medical advice and does not replace a clinician. Dietary supplements are not intended to diagnose, treat, cure or prevent any disease. Statements about supplements have not been evaluated by the FDA.