What COMT Does in Your Body
Catechol-O-methyltransferase (COMT) is an enzyme that breaks down catecholamines — the neurotransmitters dopamine, norepinephrine, and epinephrine. Genetic variations in the COMT gene produce two distinct metabolic types: the Val/Val variant (often called the Warrior genotype) clears catecholamines quickly, producing higher dopamine peaks but lower baseline dopamine levels; the Met/Met variant (the Worrier genotype) clears catecholamines more slowly, resulting in higher baseline dopamine but lower peak dopamine response and higher vulnerability to stress-induced catecholamine accumulation.
Why This Affects Your Supplement Strategy
People with the Met/Met COMT variant tend to be more stress-sensitive and may benefit from supplements that support GABA (to buffer catecholamine excess) and magnesium (to reduce NMDA receptor activity stimulated by catecholamines). People with the Val/Val variant may benefit more from stimulants like caffeine and from compounds that sustain dopamine levels. Testing for COMT polymorphisms is available through most genetic testing services and provides useful information for personalising both supplement strategy and lifestyle recommendations for stress management.
KSM-66 vs Other Extracts: Why the Form Matters
Not all ashwagandha extracts are created equal. The KSM-66 extract, standardised to greater than 5% withanolides and derived from roots only, has the largest and most rigorous trial database, demonstrating meaningful reductions in perceived stress scores within 8-12 weeks in multiple randomised controlled trials. Many commercial products use whole-root powders or low-potency leaf extracts containing minimal withanolides. Evidence-based supplementation requires a standardised extract at 300-600mg per day of KSM-66 or equivalent.
Mechanism: How Withanolides Calm the Nervous System
The active constituents bind GABA-A receptors, producing anxiolytic effects without sedation, inhibit cortisol synthesis in adrenal cortex cells, and reduce neuroinflammation via NF-kB and TNF-alpha suppression. Unlike pharmaceutical anxiolytics, standard doses do not impair cognitive performance or create physical dependence. The cortisol-lowering effect is particularly relevant for people whose stress manifests as metabolic dysfunction.
KSM-66 vs Other Extracts: Why the Form Matters
Not all ashwagandha extracts are created equal. The KSM-66 extract, standardised to greater than 5% withanolides and derived from roots only, has the largest and most rigorous trial database, demonstrating meaningful reductions in perceived stress scores within 8-12 weeks in multiple randomised controlled trials. Many commercial products use whole-root powders or low-potency leaf extracts containing minimal withanolides. Evidence-based supplementation requires a standardised extract at 300-600mg per day of KSM-66 or equivalent.
Mechanism: How Withanolides Calm the Nervous System
The active constituents bind GABA-A receptors, producing anxiolytic effects without sedation, inhibit cortisol synthesis in adrenal cortex cells, and reduce neuroinflammation via NF-kB and TNF-alpha suppression. Unlike pharmaceutical anxiolytics, standard doses do not impair cognitive performance or create physical dependence. The cortisol-lowering effect is particularly relevant for people whose stress manifests as metabolic dysfunction.
KSM-66 vs Other Extracts: Why the Form Matters
Not all ashwagandha extracts are created equal. The KSM-66 extract, standardised to greater than 5% withanolides and derived from roots only, has the largest and most rigorous trial database, demonstrating meaningful reductions in perceived stress scores within 8-12 weeks in multiple randomised controlled trials. Many commercial products use whole-root powders or low-potency leaf extracts containing minimal withanolides. Evidence-based supplementation requires a standardised extract at 300-600mg per day of KSM-66 or equivalent.
Mechanism: How Withanolides Calm the Nervous System
The active constituents bind GABA-A receptors, producing anxiolytic effects without sedation, inhibit cortisol synthesis in adrenal cortex cells, and reduce neuroinflammation via NF-kB and TNF-alpha suppression. Unlike pharmaceutical anxiolytics, standard doses do not impair cognitive performance or create physical dependence. The cortisol-lowering effect is particularly relevant for people whose stress manifests as metabolic dysfunction.
KSM-66 vs Other Extracts: Why the Form Matters
Not all ashwagandha extracts are created equal. The KSM-66 extract, standardised to greater than 5% withanolides and derived from roots only, has the largest and most rigorous trial database, demonstrating meaningful reductions in perceived stress scores within 8-12 weeks in multiple randomised controlled trials. Many commercial products use whole-root powders or low-potency leaf extracts containing minimal withanolides. Evidence-based supplementation requires a standardised extract at 300-600mg per day of KSM-66 or equivalent.
Mechanism: How Withanolides Calm the Nervous System
The active constituents bind GABA-A receptors, producing anxiolytic effects without sedation, inhibit cortisol synthesis in adrenal cortex cells, and reduce neuroinflammation via NF-kB and TNF-alpha suppression. Unlike pharmaceutical anxiolytics, standard doses do not impair cognitive performance or create physical dependence. The cortisol-lowering effect is particularly relevant for people whose stress manifests as metabolic dysfunction.
A quality supplement routine can make a real difference to your results.
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