Hermetica Superfood Encyclopedia
The Short Answer
Gramine is a naturally occurring indole alkaloid found primarily in barley (Hordeum vulgare) and other grasses, where it functions as a plant defense compound. It acts on monoamine-related pathways due to its structural similarity to tryptamine, though no confirmed therapeutic applications in humans have been established.
CategoryNamed Bioactive Compounds
GroupCompound
Evidence LevelModerate
Primary Keywordwhat is gramine
Synergy Pairings3
Gramine — botanical close-up
Health Benefits
Origin & History
Natural habitat
Gramine is an indole alkaloid (3-(dimethylaminomethyl)indole) first isolated in 1935 from Arundo donax L. (giant reed) and found in other plants including silver maple, lupinus seeds, and barley cultivars (up to 8 mg/g dry weight). It is extracted using ultrasonic methods from A. donax (1% yield) or synthesized via Mannich reaction with yields of 70-98%.
“No historical or traditional medicinal uses of gramine are documented in the sources. It is primarily noted for modern discovery (1935 onward) and phytochemical research rather than ethnomedical contexts.”Traditional Medicine
Scientific Research
No human clinical trials, randomized controlled trials (RCTs), or meta-analyses for gramine were identified in the available sources. Research is limited to preclinical extraction, synthesis, and toxicity studies in animals, with no PubMed PMIDs for human studies provided.
Preparation & Dosage
Traditional preparation
No clinically studied dosage ranges or forms are available as human trials are absent. Only extraction yields (1% from A. donax) and synthesis yields (70-98%) have been documented. Consult a healthcare provider before starting any new supplement.
Nutritional Profile
Gramine (3-(dimethylaminomethyl)indole) is a naturally occurring indole alkaloid, not a nutritional ingredient. It contains no macronutrients (zero caloric value as a pure compound), no dietary fiber, no vitamins, and no essential minerals in its isolated form. As a bioactive compound, gramine is found endogenously in barley (Hordeum vulgare) at concentrations ranging approximately 0.1–0.5% dry weight in young seedlings, and in reed canary grass (Phalaris arundinacea) at concentrations up to 0.2% dry weight. Chemically, it has a molecular weight of 174.24 g/mol and contains a dimethylaminomethyl side chain attached to an indole ring system, giving it structural similarity to tryptamine derivatives. It acts as a serotonin receptor antagonist and acetylcholinesterase inhibitor in laboratory contexts. Bioavailability in biological systems is documented in Wistar rat toxicity studies, indicating it is absorbed systemically, but human pharmacokinetic data (absorption rate, metabolism pathway specifics, elimination half-life) are not established. No nutritional contribution to human diet has been documented. Its presence in barley-based foods is incidental and at trace levels well below isolated compound concentrations used in research settings.
How It Works
Mechanism of Action
Gramine (3-(dimethylaminomethyl)indole) shares structural homology with tryptamine and serotonin, suggesting potential interaction with serotonergic and adrenergic receptors, though no confirmed receptor-binding studies in humans exist. In vitro studies indicate it may inhibit monoamine oxidase (MAO) activity and interfere with cellular transport mechanisms, particularly affecting amino acid uptake across membranes. Its cytotoxic effects observed in cell studies are hypothesized to involve disruption of mitochondrial membrane potential, though the precise molecular cascade remains uncharacterized.
Clinical Evidence
As of available literature, no human clinical trials investigating gramine's therapeutic effects have been identified or published. Toxicity data is limited to rodent studies, specifically Wistar rat models, with outcomes and dosing thresholds not fully disclosed in accessible research. In vitro studies have examined gramine's cytotoxic and antimicrobial properties, but these findings have not been translated into human safety or efficacy data. The overall evidence base is preclinical and insufficient to support any health claims.
Safety & Interactions
Gramine is considered potentially toxic based on animal and in vitro data; it has demonstrated cytotoxic activity in cell models, raising concern about safe human dosing thresholds. No established safe dose for human consumption exists, and no formal drug interaction studies have been conducted. Given its structural similarity to tryptamine and potential MAO-inhibiting properties, theoretical interactions with serotonergic drugs, MAO inhibitors, and antidepressants cannot be ruled out. Gramine should be avoided during pregnancy and breastfeeding due to a complete absence of safety data in these populations.
Synergy Stack
Hermetica Formulation Heuristic
Also Known As
3-(dimethylaminomethyl)indoleN,N-dimethyl-1H-indole-3-methanamine3-(N,N-dimethylaminomethyl)indoledonaxineindole alkaloid gramine
Frequently Asked Questions
What plant does gramine come from?
Gramine is most abundantly found in barley (Hordeum vulgare), particularly in the seedlings and leaves. It also occurs in other Poaceae grasses and some species of Lupinus and Arundo donax. In these plants, it serves as a natural pest and pathogen deterrent rather than a nutritional compound.
Is gramine safe for humans to take?
There is currently no established safe dose of gramine for human consumption, and it is not approved as a dietary supplement ingredient by the FDA. Toxicity studies have only been conducted in Wistar rats, and the outcomes of those studies are not fully published in accessible literature. Until robust human safety data exist, gramine should not be intentionally consumed.
Does gramine have any proven health benefits?
No human clinical trials have documented health benefits of gramine, and no traditional medicinal use has been recorded for this compound. While in vitro studies have explored its antimicrobial and cytotoxic properties, these findings cannot be extrapolated to human therapeutic effects. At this time, gramine has no evidence-supported health benefits.
What is the chemical structure of gramine?
Gramine is chemically identified as 3-(dimethylaminomethyl)indole, with the molecular formula C11H14N2 and a molecular weight of approximately 174.24 g/mol. Its indole core is structurally related to tryptamine and serotonin, which informs hypotheses about its potential biological activity. This structural similarity is the basis for theoretical—but unconfirmed—interactions with monoamine pathways.
Can gramine interact with antidepressants or serotonin medications?
No formal drug interaction studies involving gramine and pharmaceutical agents have been conducted in humans. However, its structural resemblance to tryptamine and its theorized MAO-inhibiting properties suggest a potential risk of serotonergic interaction if combined with SSRIs, SNRIs, or MAO inhibitors. Until interaction data are available, combining gramine with any serotonergic medication is inadvisable.
What does current research tell us about the quality of evidence for gramine?
Clinical research on gramine in humans is extremely limited, with no published human trials demonstrating health benefits. Existing studies have focused primarily on extraction and chemical synthesis methods rather than therapeutic efficacy or safety outcomes. The only toxicity data available comes from rat studies with unspecified results, making it difficult to draw conclusions about human safety. This lack of robust evidence means gramine cannot be recommended for any specific health purpose at this time.
Who should avoid taking gramine supplements?
Due to the absence of human clinical trials and minimal safety data, gramine should be avoided by pregnant women, nursing mothers, children, and anyone with underlying health conditions until further research is conducted. Individuals taking medications that affect neurotransmitter levels should be particularly cautious, as gramine's chemical structure suggests potential interactions with serotonergic systems. Anyone considering gramine supplementation should consult with a healthcare provider first, given the limited evidence base.
What forms of gramine are available as supplements, and does the form matter?
Gramine is primarily available through research chemical suppliers rather than established supplement manufacturers, and no standardized supplement formulations with proven bioavailability have been developed for consumer use. Since research has focused on extraction and synthesis methods rather than supplement efficacy, there is no evidence comparing different forms or establishing which would be most bioavailable if consumed. Without human studies on absorption and metabolism, the relevance of supplement form remains entirely unknown.
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