TRIGONELLINE
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What Is TRIGONELLINE?
Trigonelline is a plant alkaloid found in coffee and fenugreek that functions as an NAD+ precursor through the Preiss-Handler pathway. It supports mitochondrial function, muscle health, and metabolic homeostasis while demonstrating neuroprotective, anti-diabetic, and anti-inflammatory properties.
TRIGONELLINE Research & Studies
01 Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia ▸
Trigonelline supplementation increased NAD+ levels, improved mitochondrial respiration, reduced age-related muscle wasting, and enhanced muscle strength in aging mice. In C. elegans, it increased lifespan and mobility through NAD+-dependent mechanisms.
View Study (PubMed)02 Inhibition of key digestive enzymes related to diabetes and hyperlipidemia and protection of liver-kidney functions by trigonelline in diabetic rats ▸
Trigonelline reduced blood glucose by 46% through inhibition of intestinal α-amylase and maltase, while also decreasing serum triglycerides and cholesterol levels and protecting pancreatic β-cells in diabetic rats.
View Study (PubMed)03 Experimental diabetes treated with trigonelline: effect on key enzymes related to diabetes and hypertension, β-cell and liver function ▸
Trigonelline inhibited DPP-4 and α-glucosidase activities in plasma and intestine, increased GLP-1 levels, reduced blood pressure by normalizing ACE activity, and improved lipid profiles while protecting pancreatic islet cells.
View Study (PubMed)04 Trigonelline inhibits intestinal microbial metabolism of choline and its associated cardiovascular risk ▸
Trigonelline prevented gut microbiota conversion of choline to pro-atherosclerotic TMAO, suggesting cardiovascular protective effects by modulating gut bacterial metabolism.
View Study (PubMed)05 Efficacy of a novel extract of fenugreek seeds in alleviating vasomotor symptoms and depression in perimenopausal women ▸
Fenugreek extract containing trigonelline reduced hot flashes by 25.9%, night sweats by 26.5%, depression by 31.8%, and insomnia by 21.6% while improving hormonal balance in perimenopausal women over 42 days.
View Study (PubMed)06 A review on therapeutic potentials of Trigonella foenum graecum (fenugreek) and its chemical constituents in neurological disorders ▸
Trigonelline from fenugreek shows beneficial effects in Alzheimer's disease and other neurological conditions through neuroprotective, anti-inflammatory, and NAD+-boosting mechanisms.
View Study (PubMed)07 Coffee variety, origin and extraction procedure: Implications for coffee beneficial effects on human health ▸
NMR analysis revealed trigonelline as a major bioactive compound in coffee, with hydroalcoholic extraction being most efficient for obtaining beneficial low molecular weight compounds including chlorogenic acids.
View Study (PubMed)TRIGONELLINE User Reviews & Experiences
*Based on large scale analysis of publicly available user experiences
Users report noticeable improvements in muscle function, energy levels, and cognitive performance from trigonelline supplementation. The majority view it as an effective NAD+ booster with minimal side effects, though some express concerns about formaldehyde production during metabolism.
TRIGONELLINE Benefits, Dosage & Side Effects
- Muscle Function: Users and studies report enhanced muscle strength, reduced fatigue, and improved endurance during physical activity and aging
- Energy & Stamina: Significant improvements in daily energy levels and ability to sustain physical and mental activities throughout the day
- Metabolic Health: Notable reductions in blood glucose levels and improvements in lipid profiles including triglycerides and cholesterol
- Cognitive Support: Enhanced mental clarity, reduced brain fog, and neuroprotective effects particularly in age-related cognitive decline
- NAD+ Boosting: Works through the distinct Preiss-Handler pathway rather than competing with NR/NMN, with particular effectiveness in muscle tissue
- Dosage Response: Studies used 250-500mg doses with effects appearing within weeks; one user self-experiment found no NAD+ increase at 500mg daily
- Synergistic Benefits: When combined with other NAD+ precursors or as part of fenugreek extract, demonstrates enhanced effects on hormonal balance and metabolic function
- Age-Related Decline: Particularly effective for sarcopenia and age-associated muscle wasting, with circulating levels naturally declining with age
- Standard Research Dose: 250-500mg daily used in most human and animal studies showing metabolic and muscle benefits
- Fenugreek Source: 1 teaspoon fenugreek seeds in morning smoothies reported by users as an alternative natural source
- Timing: Can be taken with meals; studies used twice-daily dosing (250mg x2) for hormonal and metabolic effects
- Duration: Benefits observed within 2-6 weeks in studies, with long-term supplementation (months) showing sustained improvements
- Formaldehyde Concerns: Demethylation produces formaldehyde as a byproduct, raising theoretical concerns about DNA damage at higher supplemental doses
- Minimal Reported Issues: Most studies and users report good tolerance with few adverse effects at standard doses
- Heavy Metal Risk: As with other supplements, quality and purity testing is important to avoid contamination from plant sources
- Individual Variation: Some users may not respond to trigonelline's NAD+ boosting effects based on individual metabolic differences
- Natural Sources: Abundantly available in coffee (especially green coffee beans) and fenugreek seeds; CO2 decaf extraction preserves higher trigonelline content
- Supplement Form: Available as isolated trigonelline supplements (500mg capsules) from various manufacturers, though less common than NR/NMN
- Quality Considerations: Users recommend reputable brands with third-party testing due to potential for heavy metal contamination in plant-derived products
Related Compounds
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