reptides / 1,3-DMAA

1,3-DMAA

Human studies found no 10-km benefit, acute blood-pressure increases, and no significant group-level abnormalities over 12 weeks. The trials were too small to settle long-term performance or uncommon harms.

Small-molecule sympathomimetic stimulant

  • 1,3-DMAA is methylhexanamine; 1,4-DMAA is a different isomer.
  • FDA warns about blood-pressure, cardiac, and neurological risks.
  • The 12-week safety study had 13 DMAA-only completers; the small 10-km running trial was neutral.
Which DMAA Human exposure Why pressure matters Documented risk What was in products

What is 1,3-DMAA?

1,3-DMAA, also called methylhexanamine, is a stimulant. FDA says it has found no reliable science showing that DMAA occurs naturally in plants.

Products may describe it as geranium extract. The related names 1,4-DMAA, DMBA and DMHA refer to different substances.

FDA: DMAA in products marketed as supplements

Official regulatory and safety statement

US FDA. DMAA in Products Marketed as Dietary Supplements.

FDA advises against DMAA-containing products, citing cardiovascular and neurological risks, and considers DMAA added to supplements an unsafe food additive.

Participants / model
United States marketed products
Study design
Regulatory safety statement

The statement concerns 1,3-DMAA; it is not a human trial of 1,4-DMAA.

Read the original source
PubChem: 1,3-DMAA chemical identity

Government chemical identity database

National Library of Medicine. PubChem CID 7753.

C7H17N; molecular weight 115.22 g/mol.

Participants / model
Chemical record
Follow-up
Living database
Study design
Curated structure record

Formula and molecular weight establish the recorded structure, not the contents of a retail product or an effective dose.

Read the original source

What happened in the controlled human studies?

The small studies found no 10-km benefit, no significant group-level changes over 12 weeks, and acute blood-pressure increases. None measured fat loss.

A four-condition crossover in 12 exercise-trained participants found no significant 10-km advantage. Mean times were 52.55 minutes with placebo, 52.00 with caffeine, 52.02 with DMAA and 52.46 with the combination. Acute glycerol or free-fatty-acid changes are not measured fat loss.

Fifty healthy young men completed a 12-week placebo/caffeine/DMAA study, including only 13 in the DMAA-only arm. Reported cardiovascular, ECG, body-composition and blood measures showed no significant group-by-time differences. That argues against large common changes under those conditions; it was not an equivalence trial and cannot exclude uncommon events.

A separate ten-person acute crossover had no inert placebo condition. Blood pressure rose with exposure, with the largest combined DMAA/caffeine peaks around 20% systolic and 17% diastolic. Heart rate and measured circulating catecholamines did not significantly increase. These are physiological findings, not a measured heart-attack incidence.

The earlier single-exposure PK study analyzed seven men, excluded one for an unexplained high starting level and had manufacturer funding. It provides limited resting-exposure data rather than a general safety result.

Bloomer et al., 12-week placebo/caffeine/DMAA experiment

Randomized controlled human trial

Bloomer RJ, Farney TM, Harvey IC, Alleman RJ. Safety profile of caffeine and 1,3-dimethylamylamine supplementation in healthy men. Human & experimental toxicology. 2013. DOI 10.1177/0960327113475680.

Fifty healthy young men completed: placebo 11, caffeine 14, DMAA 13 and combination 12. There were no significant group-by-time differences across reported cardiovascular, ECG, body-composition, blood and metabolic measures. This is evidence against large common changes under those study conditions. It is not powered to establish rare-event safety, and a nonsignificant result is not an equivalence result. The abstract does not report enough detail to resolve randomization concealment, attrition before completion, adherence, or all funding relationships.

Study design
Randomized controlled trial; blinding and comparator details are stated in the source result.
Read the original source
Bloomer et al., acute hemodynamic crossover

Randomized controlled human trial

Bloomer RJ, Harvey IC, Farney TM, Bell ZW, Canale RE. Effects of 1,3-dimethylamylamine and caffeine alone or in combination on heart rate and blood pressure in healthy men and women. The Physician and sportsmedicine. 2011. DOI 10.3810/psm.2011.09.1927.

Ten healthy men and women completed five blinded conditions involving DMAA, caffeine or both. There was no inert-placebo condition. Blood pressure and rate-pressure product increased in a dose-related manner; the largest combined-exposure peaks were about 20% systolic, 17% diastolic and 9% rate-pressure product. Heart rate and measured circulating norepinephrine/epinephrine did not increase significantly. This is a physiological hazard signal, not an estimate of heart-attack incidence.

Study design
Randomized controlled trial; blinding and comparator details are stated in the source result.
Read the original source
McCarthy et al., 10-km running and lipolysis crossover

Primary human study

McCarthy et al., 10-km running and lipolysis crossover. https://journals.sagepub.com/doi/full/10.1089/jcr.2011.0019

Twelve exercise-trained participants underwent placebo, caffeine, DMAA and combination conditions. Mean run times were 52.55, 52.00, 52.02 and 52.46 minutes respectively, without a significant performance benefit. Exercise-associated glycerol and free-fatty-acid changes cannot be substituted for fat-mass loss; the reported between-condition glycerol contrast was DMAA versus combination, not a universal benefit over placebo. Small size and acute exposure limit generalization.

Read the original source
Physiological and pharmacokinetic effects of oral 1,3-dimethylamylamine administration in men.

Primary human study

Schilling BK et al. BMC pharmacology & toxicology. 2013. PMID 24090077. DOI 10.1186/2050-6511-14-52.

Seven analyzed men had an average terminal half-life of 8.45 hours after a single oral exposure; resting vital signs were largely unchanged.

Participants / model
Eight healthy men recruited; seven analyzed after one baseline-contamination exclusion
Follow-up
24-hour sampling
Study design
Single-dose pharmacokinetic and physiological experiment
Funding
USPlabs funded the study, paid salary/direct/indirect costs and publication fees, and was consulted on design.

A single resting exposure in seven healthy men cannot establish safety during exercise, repeated use or co-use with other stimulants. No placebo arm.

Read the original source

How does it act as a stimulant?

Indirect sympathomimetic effects are plausible, but a simple claim that DMAA directly activates adrenergic receptors is too strong.

Human-dopamine-transporter cell experiments found competitive uptake inhibition and substrate-like endocytosis. A separate receptor study found no adrenergic-receptor activation up to 300 micromolar and only weak TAAR1 activity at that high concentration. These cell results refine the mechanism; they do not quantify a useful human cognitive effect.

DMAA interaction with the human dopamine transporter, 2023

Primary preclinical study

Small C, Cheng MH, Belay SS, Bulloch SL, Zimmerman B, Sorkin A, Block ER. The Alkylamine Stimulant 1,3-Dimethylamylamine Exhibits Substrate-Like Regulation of Dopamine Transporter Function and Localization. The Journal of pharmacology and experimental therapeutics. 2023. DOI 10.1124/jpet.122.001573.

Experiments in human-DAT-transfected cells found competitive dopamine-uptake inhibition and substrate-like transporter endocytosis, with pharmacological and docking support. “Human DAT” means a human protein in a cell experiment, not a human administration trial. It supports biological activity without proving a useful cognitive effect or the magnitude of in-vivo dopamine release.

Read the original source
Human adrenergic receptor and TAAR1 assays, 2024

Primary preclinical study

Pinckaers NET, Blankesteijn WM, Mircheva A, Shi X, Opperhuizen A, Schooten FV, Vrolijk MF. In Vitro Activation of Human Adrenergic Receptors and Trace Amine-Associated Receptor 1 by Phenethylamine Analogues Present in Food Supplements. Nutrients. 2024. DOI 10.3390/nu16111567.

In the tested receptor systems, 1,3-DMAA did not activate adrenergic receptors up to 300 micromolar; weak partial TAAR1 activity appeared only at 300 micromolar, which the authors considered physiologically irrelevant. This complicates direct-receptor explanations without contradicting indirect sympathomimetic effects. The experiment tested 1,3-DMAA, not its 1,4 isomer.

Read the original source

How strong is the evidence of harm?

Blood-pressure effects are directly measured. Serious case reports and FDA’s scientific review add concern, but mixed products and missing denominators prevent a reliable isolated-DMAA event rate.

The small 12-week null study belongs in the assessment. It cannot settle uncommon cardiovascular or neurological risk, long-term exposure or interactions during strenuous exercise. Regulatory status alone is not an efficacy argument, and a stimulant sensation is not proof of better work or athletic performance.

Bloomer et al., 12-week placebo/caffeine/DMAA experiment

Randomized controlled human trial

Bloomer RJ, Farney TM, Harvey IC, Alleman RJ. Safety profile of caffeine and 1,3-dimethylamylamine supplementation in healthy men. Human & experimental toxicology. 2013. DOI 10.1177/0960327113475680.

Fifty healthy young men completed: placebo 11, caffeine 14, DMAA 13 and combination 12. There were no significant group-by-time differences across reported cardiovascular, ECG, body-composition, blood and metabolic measures. This is evidence against large common changes under those study conditions. It is not powered to establish rare-event safety, and a nonsignificant result is not an equivalence result. The abstract does not report enough detail to resolve randomization concealment, attrition before completion, adherence, or all funding relationships.

Study design
Randomized controlled trial; blinding and comparator details are stated in the source result.
Read the original source
Bloomer et al., acute hemodynamic crossover

Randomized controlled human trial

Bloomer RJ, Harvey IC, Farney TM, Bell ZW, Canale RE. Effects of 1,3-dimethylamylamine and caffeine alone or in combination on heart rate and blood pressure in healthy men and women. The Physician and sportsmedicine. 2011. DOI 10.3810/psm.2011.09.1927.

Ten healthy men and women completed five blinded conditions involving DMAA, caffeine or both. There was no inert-placebo condition. Blood pressure and rate-pressure product increased in a dose-related manner; the largest combined-exposure peaks were about 20% systolic, 17% diastolic and 9% rate-pressure product. Heart rate and measured circulating norepinephrine/epinephrine did not increase significantly. This is a physiological hazard signal, not an estimate of heart-attack incidence.

Study design
Randomized controlled trial; blinding and comparator details are stated in the source result.
Read the original source
FDA scientific assessment of DMAA safety

Official scientific or regulatory record

FDA CFSAN. Scientific memorandum, 3 October 2016.

The assessment integrates cardiovascular physiology, case reports and gaps in submitted toxicology. It questions whether small manufacturer-associated studies establish safety. Multi-ingredient cases and missing denominators prevent a reliable compound-specific incidence estimate. The regulatory conclusion is context; the empirical findings carry the argument.

Participants / model
Published DMAA evidence assessed for use in conventional foods
Follow-up
Review finalized October 2016
Study design
Regulatory safety assessment
Funding
US Food and Drug Administration.
Read the original source
FDA: DMAA in products marketed as supplements

Official regulatory and safety statement

US FDA. DMAA in Products Marketed as Dietary Supplements.

FDA advises against DMAA-containing products, citing cardiovascular and neurological risks, and considers DMAA added to supplements an unsafe food additive.

Participants / model
United States marketed products
Study design
Regulatory safety statement

The statement concerns 1,3-DMAA; it is not a human trial of 1,4-DMAA.

Read the original source

Do supplement labels identify the stimulant reliably?

A laboratory survey found several different stimulants in selected products, including a product containing both DMAA isomers.

The paper measured product composition, not an effective or safe dose.

Four experimental stimulants found in sports and weight loss supplements: 2-amino-6-methylheptane (octodrine), 1,4-dimethylamylamine (1,4-DMAA), 1,3-dimethylamylamine (1,3-DMAA) and 1,3-dimethylbutylamine (1,3-DMBA).

Primary analytical study

Cohen PA et al. Clinical toxicology (Philadelphia, Pa.). 2018. PMID 29115866. DOI 10.1080/15563650.2017.1398328.

Two laboratories found multiple stimulant compounds in six selected supplement brands, including distinct 1,3- and 1,4-DMAA.

Participants / model
Six selected supplement brands, not trial participants
Follow-up
Cross-sectional product testing
Study design
Independent laboratory chemical analysis with reference standards

This convenience sample cannot estimate market-wide prevalence or identify which ingredient caused a clinical event.

Read the original source

Studies and sources

FDA: DMAA in products marketed as supplements

Official regulatory and safety statement

US FDA. DMAA in Products Marketed as Dietary Supplements.

FDA advises against DMAA-containing products, citing cardiovascular and neurological risks, and considers DMAA added to supplements an unsafe food additive.

Participants / model
United States marketed products
Study design
Regulatory safety statement

The statement concerns 1,3-DMAA; it is not a human trial of 1,4-DMAA.

Read the original source
Physiological and pharmacokinetic effects of oral 1,3-dimethylamylamine administration in men.

Primary human study

Schilling BK et al. BMC pharmacology & toxicology. 2013. PMID 24090077. DOI 10.1186/2050-6511-14-52.

Seven analyzed men had an average terminal half-life of 8.45 hours after a single oral exposure; resting vital signs were largely unchanged.

Participants / model
Eight healthy men recruited; seven analyzed after one baseline-contamination exclusion
Follow-up
24-hour sampling
Study design
Single-dose pharmacokinetic and physiological experiment
Funding
USPlabs funded the study, paid salary/direct/indirect costs and publication fees, and was consulted on design.

A single resting exposure in seven healthy men cannot establish safety during exercise, repeated use or co-use with other stimulants. No placebo arm.

Read the original source
Four experimental stimulants found in sports and weight loss supplements: 2-amino-6-methylheptane (octodrine), 1,4-dimethylamylamine (1,4-DMAA), 1,3-dimethylamylamine (1,3-DMAA) and 1,3-dimethylbutylamine (1,3-DMBA).

Primary analytical study

Cohen PA et al. Clinical toxicology (Philadelphia, Pa.). 2018. PMID 29115866. DOI 10.1080/15563650.2017.1398328.

Two laboratories found multiple stimulant compounds in six selected supplement brands, including distinct 1,3- and 1,4-DMAA.

Participants / model
Six selected supplement brands, not trial participants
Follow-up
Cross-sectional product testing
Study design
Independent laboratory chemical analysis with reference standards

This convenience sample cannot estimate market-wide prevalence or identify which ingredient caused a clinical event.

Read the original source
PubChem: 1,3-DMAA chemical identity

Government chemical identity database

National Library of Medicine. PubChem CID 7753.

C7H17N; molecular weight 115.22 g/mol.

Participants / model
Chemical record
Follow-up
Living database
Study design
Curated structure record

Formula and molecular weight establish the recorded structure, not the contents of a retail product or an effective dose.

Read the original source
FDA scientific assessment of DMAA safety

Official scientific or regulatory record

FDA CFSAN. Scientific memorandum, 3 October 2016.

The assessment integrates cardiovascular physiology, case reports and gaps in submitted toxicology. It questions whether small manufacturer-associated studies establish safety. Multi-ingredient cases and missing denominators prevent a reliable compound-specific incidence estimate. The regulatory conclusion is context; the empirical findings carry the argument.

Participants / model
Published DMAA evidence assessed for use in conventional foods
Follow-up
Review finalized October 2016
Study design
Regulatory safety assessment
Funding
US Food and Drug Administration.
Read the original source
Bloomer et al., 12-week placebo/caffeine/DMAA experiment

Randomized controlled human trial

Bloomer RJ, Farney TM, Harvey IC, Alleman RJ. Safety profile of caffeine and 1,3-dimethylamylamine supplementation in healthy men. Human & experimental toxicology. 2013. DOI 10.1177/0960327113475680.

Fifty healthy young men completed: placebo 11, caffeine 14, DMAA 13 and combination 12. There were no significant group-by-time differences across reported cardiovascular, ECG, body-composition, blood and metabolic measures. This is evidence against large common changes under those study conditions. It is not powered to establish rare-event safety, and a nonsignificant result is not an equivalence result. The abstract does not report enough detail to resolve randomization concealment, attrition before completion, adherence, or all funding relationships.

Study design
Randomized controlled trial; blinding and comparator details are stated in the source result.
Read the original source
Bloomer et al., acute hemodynamic crossover

Randomized controlled human trial

Bloomer RJ, Harvey IC, Farney TM, Bell ZW, Canale RE. Effects of 1,3-dimethylamylamine and caffeine alone or in combination on heart rate and blood pressure in healthy men and women. The Physician and sportsmedicine. 2011. DOI 10.3810/psm.2011.09.1927.

Ten healthy men and women completed five blinded conditions involving DMAA, caffeine or both. There was no inert-placebo condition. Blood pressure and rate-pressure product increased in a dose-related manner; the largest combined-exposure peaks were about 20% systolic, 17% diastolic and 9% rate-pressure product. Heart rate and measured circulating norepinephrine/epinephrine did not increase significantly. This is a physiological hazard signal, not an estimate of heart-attack incidence.

Study design
Randomized controlled trial; blinding and comparator details are stated in the source result.
Read the original source
McCarthy et al., 10-km running and lipolysis crossover

Primary human study

McCarthy et al., 10-km running and lipolysis crossover. https://journals.sagepub.com/doi/full/10.1089/jcr.2011.0019

Twelve exercise-trained participants underwent placebo, caffeine, DMAA and combination conditions. Mean run times were 52.55, 52.00, 52.02 and 52.46 minutes respectively, without a significant performance benefit. Exercise-associated glycerol and free-fatty-acid changes cannot be substituted for fat-mass loss; the reported between-condition glycerol contrast was DMAA versus combination, not a universal benefit over placebo. Small size and acute exposure limit generalization.

Read the original source
DMAA interaction with the human dopamine transporter, 2023

Primary preclinical study

Small C, Cheng MH, Belay SS, Bulloch SL, Zimmerman B, Sorkin A, Block ER. The Alkylamine Stimulant 1,3-Dimethylamylamine Exhibits Substrate-Like Regulation of Dopamine Transporter Function and Localization. The Journal of pharmacology and experimental therapeutics. 2023. DOI 10.1124/jpet.122.001573.

Experiments in human-DAT-transfected cells found competitive dopamine-uptake inhibition and substrate-like transporter endocytosis, with pharmacological and docking support. “Human DAT” means a human protein in a cell experiment, not a human administration trial. It supports biological activity without proving a useful cognitive effect or the magnitude of in-vivo dopamine release.

Read the original source
Human adrenergic receptor and TAAR1 assays, 2024

Primary preclinical study

Pinckaers NET, Blankesteijn WM, Mircheva A, Shi X, Opperhuizen A, Schooten FV, Vrolijk MF. In Vitro Activation of Human Adrenergic Receptors and Trace Amine-Associated Receptor 1 by Phenethylamine Analogues Present in Food Supplements. Nutrients. 2024. DOI 10.3390/nu16111567.

In the tested receptor systems, 1,3-DMAA did not activate adrenergic receptors up to 300 micromolar; weak partial TAAR1 activity appeared only at 300 micromolar, which the authors considered physiologically irrelevant. This complicates direct-receptor explanations without contradicting indirect sympathomimetic effects. The experiment tested 1,3-DMAA, not its 1,4 isomer.

Read the original source

Why is 1,3-DMAA in F tier?

F: weak performance results, measured blood-pressure increases and unreliable supplement contents. The small 12-week study found no significant abnormalities, but its DMAA-only arm had 13 completers. It cannot settle uncommon harm or long-term safety.

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