5-HTP
Direct precursor to serotonin, which converts to melatonin. Derived from Griffonia simplicifolia seeds. Raises serotonin levels more directly than tryptophan.
We review the evidence behind supplements for specific health conditions. Every supplement gets honest ratings — including those with weak evidence.
Direct precursor to serotonin, which converts to melatonin. Derived from Griffonia simplicifolia seeds. Raises serotonin levels more directly than tryptophan.
Acetylated form of L-carnitine that crosses the blood-brain barrier. Supports mitochondrial energy production in neurons. Evidence for neuropathy, cognitive decline, and depression.
Garlic aged for 20 months, converting allicin to S-allyl cysteine and other stable compounds. Better tolerated than raw garlic. Kyolic brand is the most studied. Some evidence for arterial calcification reduction.
Key intermediate in the Krebs cycle. Animal studies showed significant lifespan extension. Rejuvant LifeAKG human trial suggested biological age reversal via DNA methylation clocks, but remains controversial.
Plant-based source of DHA and EPA from microalgae — the same source fish get their omega-3s from. Suitable for vegetarians/vegans. Equivalent bioavailability to fish oil.
Most bioavailable choline source for the brain. Crosses blood-brain barrier efficiently. Used in Europe as a prescription drug for cognitive decline (Gliatilin). Supports acetylcholine synthesis.
Potent antioxidant that works in both water and fat-soluble environments. R-form is the biologically active isomer. Evidence for diabetic neuropathy and blood sugar support.
A flavonoid found in chamomile, parsley, and celery. Binds to GABA receptors as a mild sedative. Also inhibits CD38, an NAD+-consuming enzyme. Popularized by Andrew Huberman for sleep onset.
Specific combination of vitamin C (500mg), vitamin E (400 IU), lutein (10mg), zeaxanthin (2mg), zinc (80mg), and copper (2mg) validated by the NIH-funded AREDS2 trial for slowing AMD progression.
Traditional Mediterranean remedy for liver and digestive health. Contains cynarin and chlorogenic acid. Evidence for cholesterol reduction and liver enzyme improvement.
Adaptogenic herb from Ayurvedic medicine. Reduces cortisol, supports sleep, and may improve metabolic markers. KSM-66 and Sensoril are the most-studied standardized extracts.
Carotenoid from microalgae — gives salmon and flamingos their color. Estimated 6,000x stronger than vitamin C in singlet oxygen quenching. Crosses blood-brain and blood-retinal barriers.
Combination of all eight B vitamins. Supports energy metabolism, nerve function, and methylation. Often used as a baseline supplement. Quality varies significantly between brands.
Ayurvedic nootropic herb with 3,000+ years of traditional use. Modern RCTs confirm memory-enhancing effects, particularly for learning rate and memory consolidation. Requires sustained use.
Rich source of dietary nitrate, which converts to nitric oxide. Improves blood vessel dilation, blood pressure, and exercise performance. One of the best evidence-based ergogenic supplements.
Alkaloid from goldenseal and barberry. Activates AMPK, same pathway as metformin. Strong evidence for blood sugar and lipid management. Sometimes called 'nature's metformin.'
Provitamin A carotenoid. Was included in original AREDS formula for AMD but removed in AREDS2 due to increased lung cancer risk in smokers. Replaced by lutein/zeaxanthin.
Soluble fiber found in oats, barley, and yeast. Oat beta-glucan has an FDA-approved health claim for cholesterol reduction. Also modulates immune function.
European relative of blueberry. Rich in anthocyanins. WWII-era claims about RAF pilots' night vision drove popularity. Modern evidence is modest for eye health.
Short-chain fatty acid normally produced by gut bacteria fermenting fiber. Fuels colon cells, reduces inflammation, and supports gut barrier integrity. Supplemental forms bypass the need for microbial production.
Essential mineral for bone health. Controversial for cardiovascular safety — some meta-analyses suggest increased MI risk with supplements (not dietary calcium). Citrate form better absorbed.
Dipeptide found in muscle and brain. Acts as an intracellular buffer, antioxidant, and anti-glycation agent. Levels decline with age. May be supplemented directly or via beta-alanine.
Non-psychoactive cannabinoid from hemp. Interacts with endocannabinoid system. Popular for sleep and anxiety but clinical evidence is still catching up to consumer adoption. Legal status varies.
Traditional calming herb used for centuries as tea. Contains apigenin, which binds GABA receptors. Most evidence is from chamomile extract capsules rather than tea.
Trace mineral involved in insulin signaling. Once heavily promoted for blood sugar control. More recent evidence suggests benefits are modest and mainly in deficient individuals.
Common spice with blood sugar-lowering properties. Ceylon (true) cinnamon preferred over cassia due to lower coumarin content. Modest evidence for fasting glucose reduction.
Naturally occurring brain compound that provides both choline and cytidine. Supports cell membrane synthesis and neurotransmitter production. Better studied for stroke recovery and cognitive function than most nootropics.
Essential trace mineral. Included in AREDS2 formula to offset copper depletion from high-dose zinc. Most people get adequate copper from diet.
Essential coenzyme in mitochondrial energy production. Levels decline with age and are depleted by statins. Ubiquinol is the active reduced form with better bioavailability.
Medicinal mushroom traditionally used in Chinese medicine. Modern cultivated Cordyceps militaris has replaced the rare wild Cordyceps sinensis. Supports energy, exercise performance, and kidney function.
Best known for urinary tract health. Proanthocyanidins (PACs) prevent bacterial adhesion to urinary tract walls. Cochrane review supports use for UTI prevention in women.
One of the most studied supplements in existence. Beyond muscle performance, emerging evidence for cognitive function — the brain uses creatine for energy-intensive tasks. May be especially beneficial for sleep-deprived cognition.
Active compound in turmeric with broad anti-inflammatory and antioxidant effects. Poor bioavailability requires enhanced formulations (piperine, phytosome, nanoparticle). One of the most researched natural compounds.
A stereoisomer of inositol involved in insulin signaling. Often used alongside myo-inositol in a 40:1 ratio for PCOS and metabolic support.
Simple sugar that prevents E. coli from adhering to urinary tract walls. Used for UTI prevention. Does not affect blood sugar at therapeutic doses. Different mechanism than cranberry.
Traditional herbal remedy for liver and kidney support. Root is used for liver/digestion; leaf as a natural diuretic. Limited but growing clinical evidence.
Essential fatty acids the body cannot produce. EPA and DHA support cardiovascular health, reduce triglycerides, and have anti-inflammatory effects. One of the most studied supplements in existence.
Essential B vitamin critical for DNA synthesis, methylation, and homocysteine metabolism. Methylfolate (5-MTHF) is the active form, preferred over folic acid especially for MTHFR variants.
The brain's primary inhibitory neurotransmitter. Oral supplementation is controversial — debate over whether it crosses the blood-brain barrier. Some evidence for stress reduction and sleep onset.
One of the oldest medicinal plants. Allicin is the primary active compound formed when garlic is crushed. Evidence for modest blood pressure and cholesterol reduction.
Traditional anti-nausea and anti-inflammatory remedy with modern clinical validation. Gingerols and shogaols are the active compounds. Evidence for nausea, pain, and metabolic markers.
The most-studied supplement specifically for tinnitus. Improves cochlear blood flow. Cochrane review found mixed evidence, but European trials show benefit with standardized EGb 761 extract. Widely prescribed in France and Germany.
Water-soluble fiber from konjac root. Absorbs enormous amounts of water, promoting satiety. EU-approved weight loss claim at 3g/day. Also lowers cholesterol and blood sugar.
The simplest amino acid. Building block for collagen, glutathione, creatine, and inhibitory neurotransmitters. At 3g bedtime doses, lowers core body temperature and promotes NREM sleep quality.
Concentrated polyphenol from green tea. EGCG is the primary active catechin. Supports metabolic rate, fat oxidation, and has neuroprotective properties. Liver safety concerns at high doses.
Naturally-derived acetylcholinesterase inhibitor from Chinese club moss. Works like a mild version of Aricept (donepezil). Used in China as a drug for Alzheimer's disease.
Essential for thyroid hormone production. Deficiency affects cognitive development and metabolic rate. Most people in developed countries get adequate iodine from iodized salt.
Essential mineral for oxygen transport and energy production. Deficiency is common (especially in women) and causes fatigue, cognitive impairment, and hearing issues. Do NOT supplement without confirmed deficiency.
Amino acid derivative that shuttles fatty acids into mitochondria for energy production. Different forms have different targets: L-carnitine for heart/muscle, acetyl-L-carnitine for brain.
Amino acid that converts to L-arginine, then to nitric oxide. More effective at raising arginine levels than arginine supplementation itself (better oral bioavailability). Supports blood vessel health.
Amino acid found naturally in green tea. Promotes alpha brain wave activity associated with calm alertness. Reduces anxiety without sedation. May help tinnitus via stress/anxiety reduction pathway.
Oral lavender oil preparation (Silexan/Lavela) is one of the best-studied herbal anxiolytics. Multiple RCTs show efficacy comparable to low-dose benzodiazepines for generalized anxiety, with secondary sleep benefits.
Mixture of phospholipids including phosphatidylcholine, phosphatidylserine, and phosphatidylinositol. Common food additive also used as a supplement. Source of choline and phospholipids.
Mint-family herb traditionally used for calming and sleep. Inhibits GABA transaminase, increasing GABA availability. Often combined with valerian in European herbal preparations.
Medicinal mushroom that stimulates nerve growth factor (NGF) production. One of few natural compounds shown to promote neurogenesis. Growing evidence for cognitive function and nerve repair.
Heavily marketed specifically for tinnitus. Contains bioflavonoids and B vitamins. Despite ubiquitous advertising, clinical evidence for tinnitus relief is minimal. One small, older trial cited by the manufacturer; no independent replication.
Carotenoid pigments forming macular pigment that filters blue light and protects photoreceptors. The only carotenoids found in the human lens and retina. AREDS2 validated their role.
The most bioavailable form of magnesium for sleep and relaxation. Glycine itself has calming properties. US Army studies showed magnesium reduced noise-induced hearing damage. Addresses widespread deficiency — estimated 50% of Americans are magnesium deficient.
Endogenous hormone regulating circadian rhythm. Specifically studied for tinnitus-related sleep disruption, with some evidence for reducing tinnitus perception itself. One of the most evidence-backed sleep supplements.
Most widely used liver-protective herb. Silymarin is the active flavonolignan complex. Used historically for mushroom poisoning. Strong mechanistic evidence for hepatoprotection.
A carbocyclic sugar involved in insulin signaling and neurotransmitter function. Strong evidence for PCOS and metabolic markers. Also used for anxiety and sleep at higher doses.
Precursor to glutathione, the body's master antioxidant. Originally a mucolytic drug, now used for liver protection (acetaminophen overdose antidote), respiratory health, and cochlear protection. One of the most versatile supplements.
Vitamin B3 in its nicotinic acid form. Most effective supplement for raising HDL. Fell out of favor after AIM-HIGH and HPS2-THRIVE trials questioned cardiovascular outcomes despite lipid improvement.
Form of vitamin B3 that serves as NAD+ precursor. NAD+ levels decline with age. NR raises NAD+ effectively without niacin flushing. Whether NAD+ elevation translates to health benefits is the key question.
Another NAD+ precursor, popularized by David Sinclair. Debates NR vs NMN. Recent human trial from University of Washington showed improved muscle insulin sensitivity. Regulatory status has been uncertain.
Polyphenols from olive leaves and extra virgin olive oil. Oleuropein and hydroxytyrosol are key active compounds. Part of the Mediterranean diet's cardioprotective mechanism.
Traditional anxiolytic and sleep herb. One head-to-head trial showed comparable efficacy to oxazepam for anxiety with fewer side effects. Mechanism involves GABA modulation.
Major phospholipid in cell membranes and a source of choline. Supports liver cell membrane integrity and bile function. Polyenylphosphatidylcholine (PPC) form is most studied for liver.
Phospholipid making up significant portion of brain cell membranes. Supports memory, cognitive function, and cortisol regulation. FDA-qualified health claim for cognitive function.
Naturally occurring compounds in plants that block cholesterol absorption. FDA-approved health claim for heart disease risk reduction. One of the most evidence-backed supplements for LDL.
Rich source of punicalagins and ellagitannins. Gut bacteria convert these to urolithin A, which activates mitophagy. Evidence for cardiovascular and cognitive benefits.
Essential electrolyte. Most Americans don't get enough from diet. Critical for blood pressure, heart rhythm, and kidney function. OTC supplements are limited to 99 mg per dose (FDA regulation).
Micronutrient that stimulates mitochondrial biogenesis — the creation of new mitochondria. Found in small amounts in foods. Relatively new supplement with growing but still limited evidence base.
Non-digestible fibers that feed beneficial gut bacteria. Inulin and FOS are the most common. Support gut microbiome diversity and short-chain fatty acid production.
Live beneficial bacteria. Effects are highly strain-specific — different strains do different things. Gut microbiome influences virtually every organ system. Quality and strain selection matter enormously.
Soluble fiber from Plantago ovata seeds. One of the most evidence-backed supplements for cholesterol and blood sugar management. FDA-approved health claim for heart disease risk reduction.
Flavonoid found in onions, apples, and berries with anti-inflammatory and senolytic properties. When combined with dasatinib, selectively clears senescent cells. Phytosome form improves poor bioavailability.
Fermented rice containing monacolin K, which is chemically identical to lovastatin. Effective for cholesterol but controversial due to variable monacolin content and regulatory concerns.
One of the most revered medicinal mushrooms in Asian medicine. Contains triterpenes and polysaccharides. Traditionally used for calming, liver support, and immune modulation.
Polyphenol found in red wine, grape skins, and Japanese knotweed. Activates SIRT1 and AMPK pathways. Dramatic longevity effects in animal models have not clearly translated to humans.
Essential for energy production and antioxidant function. Best known for migraine prevention at high doses. Some evidence linking deficiency to hearing issues.
Expensive spice with surprisingly strong evidence for depression and emerging evidence for AMD. Crocin and safranal are the active compounds. Multiple well-designed RCTs.
Universal methyl donor involved in 200+ metabolic reactions. Prescription drug in Europe for depression and liver disease. Supports methylation, cartilage repair, and liver function.
Adaptogenic berry used in Traditional Chinese Medicine for 2,000+ years. Name means 'five-flavor berry.' Contains lignans (schisandrins) with hepatoprotective and cognitive-enhancing properties.
Essential trace mineral with antioxidant properties. Necessary for thyroid function and glutathione production. Excess can be toxic — narrow therapeutic window.
Blue-green microalgae with exceptional nutrient density. Rich in protein, B vitamins, iron, and phycocyanin (unique blue pigment with anti-inflammatory properties). One of the most nutrient-dense foods on Earth.
Most potent natural activator of Nrf2 pathway — the body's master antioxidant defense system. Derived from broccoli sprouts. Upregulates hundreds of protective genes.
Combination of probiotics and prebiotics in a single product. The prebiotic component feeds the probiotic strains, theoretically improving colonization and efficacy.
Conditionally essential amino acid abundant in brain, heart, and muscle. 2023 Science paper showed lifespan extension across multiple species. Supports GABA-ergic signaling and cardiovascular function.
Essential for energy metabolism and nerve function. Deficiency causes Wernicke-Korsakoff syndrome. Benfotiamine is a fat-soluble form with better tissue penetration.
Essential amino acid and precursor to serotonin and melatonin. The original 'turkey drowsiness' molecule. Supplementation raises serotonin more gradually than 5-HTP.
One of the oldest herbal sleep remedies, used since ancient Greece. Acts on GABA receptors. Evidence is mixed — some meta-analyses find modest benefit while others find no significant effect vs. placebo.
Essential fat-soluble vitamin for vision, immune function, and cell growth. Preformed vitamin A (retinol) has toxicity risk. Beta-carotene is the safer provitamin A form.
Essential for nerve function, DNA synthesis, and red blood cell formation. B12 deficiency is associated with tinnitus, hearing loss, and cognitive decline. Methylcobalamin form preferred for neurological applications.
Active form (P5P) is involved in neurotransmitter synthesis and over 100 enzyme reactions. Deficiency affects nerve function. High doses of pyridoxine (not P5P) can cause neuropathy.
Essential antioxidant vitamin. Included in AREDS2 formula for AMD. Supports immune function, collagen synthesis, and iron absorption. Megadose claims are largely unsupported.
Fat-soluble vitamin functioning like a hormone, affecting 1,000+ genes. Widespread deficiency (40% of US adults). Critical for bone, immune, and cardiovascular health.
Fat-soluble antioxidant. Part of AREDS2 formula for AMD. SELECT trial raised concerns about prostate cancer risk at high doses. Mixed tocopherols may be safer than alpha-tocopherol alone.
Directs calcium to bones and away from arteries. Works synergistically with D3. MK-7 form has longest half-life.
Essential trace mineral involved in over 300 enzymatic reactions. Zinc deficiency is linked to tinnitus in multiple studies. Also critical for immune function, wound healing, and retinal health.