The biohacking supplement market has expanded faster than the underlying evidence. Most lists you find online are vendor-led: "12 supplements you must take" with the link to the vendor's own brand of each one. This guide is vendor-agnostic. Every recommendation is sourced from the compound-level evidence on biox compound pages, ranked by replicated human trial data, not by sponsorship.
What is biohacking?
Biohacking is the practice of systematically intervening on biological inputs (training, nutrition, sleep, environmental exposure, supplementation) to improve specific outputs (cognition, energy, body composition, longevity, sleep quality). The label has expanded from a niche subculture (early-2010s Silicon Valley quantified-self enthusiasts) to a mainstream consumer category covering everything from cold plunge tubs to NMN powders.
Within biohacking, supplements are one lever among many. The order of effect size goes roughly: sleep > exercise > nutrition > stress management > supplements > everything else. The reason supplements get most of the attention is they are easy to buy and ship. The reason they should not get most of your effort is they are smaller-leverage than the four behaviors that precede them on the list.
This guide assumes you already have the behaviors handled. If sleep is fragmented, training is sporadic, or your protein intake is half what it should be, no supplement stack will compensate.
The big three: creatine, omega-3, vitamin D3+K2
These three are the foundation. Each has decades of trial data, broad applicability across goals, and a low-cost-high-evidence profile.
Creatine monohydrate is the most-replicated supplement in human research. Kreider 2017 (the ISSN position stand) summarized the evidence base across hundreds of trials Kreider et al. 2017 . The case for daily 5 g/day is broader than the original muscle-building thesis: cognitive benefit under sleep deprivation, modest neuroprotective signals in aging cohorts, and a clean safety record across long-term studies. See the creatine living review for the full evidence map. Five grams per day, no cycling, indefinite continuation.
Omega-3 EPA + DHA at 2 to 3 g/day combined drives cardiovascular outcomes (REDUCE-IT for icosapent ethyl), reduces triglycerides 15 to 30%, and contributes to brain phospholipid composition relevant to mood and cognition. See the omega-3 EPA/DHA post and the omega-3 compound page for the dose detail. Triglyceride form is more bioavailable than ethyl ester.
Vitamin D3 + K2 at 5,000 IU + 100 mcg MK-7 daily covers the bone, immune, and metabolic case for adults with limited sun exposure. Adding K2 directs calcium to bone rather than arterial wall, which is the mechanistic basis for the combination. See the vitamin D + K2 stack post for the framing. Test 25-OH vitamin D annually; target 30 to 60 ng/mL serum.
The fourth foundation pick most biohackers add: magnesium glycinate at 200 to 400 mg/day for sleep onset, blood pressure modulation, and addressing the common dietary inadequacy. The L-threonate form has cognitive evidence under specific conditions; for general daily use, glycinate is the first pick.
These four together cost roughly 30 to 50 dollars per month at quality brands and cover the bulk of supplement-leveraged biohacking outcomes. Everything beyond this layer adds smaller incremental benefit at meaningfully higher cost.
Tier-A biohacking supplements (robust evidence)
Beyond the big three, a small set of compounds have replicated human trial data and broad applicability.
| Compound | Dose | Primary use | Evidence |
|---|---|---|---|
| Creatine monohydrate | 5 g/day | Muscle, cognition, aging | A |
| Omega-3 EPA + DHA | 2 to 3 g/day | Cardiovascular, brain, mood | A |
| Vitamin D3 + K2 | 5,000 IU + 100 mcg/day | Bone, immune, metabolic | A |
| Magnesium glycinate | 200 to 400 mg/day | Sleep, BP, deficiency correction | A |
| Whey protein isolate | 25 g per training day | Muscle protein synthesis | A |
| Caffeine | 100 to 200 mg AM | Cognition, performance | A |
These six form the Tier-A list. None are exotic. All are inexpensive (~50 to 100 dollars per month total). The depth of human evidence on each is the reason they qualify; the lack of marketing glamour is the reason they tend to be underrepresented in influencer stacks.
Tier-B biohacking supplements (moderate evidence)
The next layer adds compounds with replicated mechanistic data and several positive trials, but smaller effect sizes or more selective populations.
- L-theanine at 100 to 200 mg paired with caffeine. Replicated acute focus stack with 1:1 ratio at 100 to 200 mg of each.
- Berberine at 1,500 mg/day divided. Comparable glycemic effect to low-dose metformin in pre-diabetic adults; activates AMPK and lowers fasting glucose 5 to 15%.
- Ashwagandha (KSM-66 standardized) at 300 to 600 mg/day. Stress and anxiety reduction is the strongest signal; cognitive effects come secondarily through reduced stress.
- Melatonin micro-dose at 0.3 mg sublingually 1 hour before bed. The Brzezinski 2005 dose; supermarket 5 to 10 mg products are pharmacologic and counterproductive.
- Lion's mane at 750 to 1,000 mg/day. One MCI trial signal (Mori 2009); broader cognitive case is mostly mechanistic.
- Coenzyme Q10 at 100 to 200 mg/day, particularly for adults on statins. Modest exercise-tolerance and cardiovascular signals.
- Curcumin at 500 to 1,000 mg/day with piperine for absorption. Anti-inflammatory and joint-pain signals.
| Compound | Dose | Primary use |
|---|---|---|
| L-theanine | 100 to 200 mg | Cognition (with caffeine) |
| Berberine | 1,500 mg/day | Glycemic control, AMPK |
| Ashwagandha | 300 to 600 mg | Stress, anxiety, sleep |
| Melatonin micro | 0.3 mg | Sleep onset (timing) |
| Lion's mane | 750 to 1,000 mg | Cognition (long-horizon) |
| CoQ10 | 100 to 200 mg | Mitochondrial, statin offset |
| Curcumin + piperine | 500 to 1,000 mg | Anti-inflammatory |
| Glycine | 3 g pre-bed | Sleep onset, body temp drop |
| Apigenin | 50 mg | Sleep, GABA modulation |
| Alpha-GPC | 300 to 600 mg | Choline donor, focus |
This layer adds roughly 50 to 100 dollars per month and is best added selectively (one or two compounds for one or two specific goals), not all at once.
Tier-C biohacking supplements (preliminary or mechanistic)
These are the longevity-class compounds: mechanistically interesting, smaller human evidence base, often higher cost, and at the leading edge of the field rather than the settled core.
- NMN at 250 to 500 mg/day. Plasma NAD+ rises consistently in trials; tissue effects and hard outcomes are still missing. See the NMN compound page.
- Spermidine at 1 to 6 mg/day. Largest human safety data in this tier; autophagy-induction mechanism is the strongest case.
- Urolithin-A at 500 to 1,000 mg/day. Mitophagy promoter with one moderate human trial showing improved muscle endurance; emerging cardiovascular signal.
- Fisetin at the Mayo pulsed dose (20 mg/kg for 2 days monthly). The senolytic case rests on Hickson 2019 (n=10); see the senolytics post for the protocol detail.
- Rapamycin (Rx) at 5 to 7 mg weekly. Strongest preclinical longevity case; human off-label use is increasingly common but lacks long-horizon human safety data.
- Resveratrol at 500 to 2,000 mg/day. Mechanistically interesting at concentrations far above what oral supplementation reaches; the David Sinclair-Sirtris program rested on a misread of cell-culture potency.
- TUDCA at 250 to 500 mg/day. Bile-acid signaling and ER-stress reduction; established for cholestasis, emerging for mitochondrial and longevity claims. See TUDCA compound and the TUDCA benefits post.
The Tier-C layer adds 100 to 300 dollars per month at typical doses. Whether it produces meaningful additional benefit beyond Tier-A and Tier-B is the open question of contemporary longevity supplementation. Anyone using this layer should accept the early-stage evidence framing rather than treating these compounds as settled clinical recommendations.
The skip list: popular biohacker supplements with thin evidence
A roughly equal-length list of compounds widely sold in this space with disproportionately weak human evidence at typical doses.
- Most "anti-aging blends" that combine 8 to 12 ingredients at sub-clinical doses. The marketing appeal is convenience; the evidence is that no single compound in the blend reaches its trial-validated dose.
- Proprietary multi-ingredient stacks (Athletic Greens, Bryan Johnson's Blueprint stack, etc.) where the per-ingredient dose is undisclosed or sub-clinical. The Tier-A foundation can be assembled for under 30 dollars per month from generic brands; proprietary blends typically run 100+ dollars and add ingredients the buyer cannot evaluate.
- High-dose collagen peptides for joint health. Modest signal in trials; the protein intake from food matters far more than collagen-specific supplementation.
- CBD at typical retail doses (15 to 25 mg). Effective doses for anxiety and sleep in trials are 100 to 600 mg, far above what most products provide; the marketing dose is essentially placebo.
- Greens powders as a multivitamin substitute. Vitamins and minerals from whole vegetables are not bioequivalent to powdered concentrates at the doses provided.
- Polyphenol mega-stacks (resveratrol + quercetin + curcumin + EGCG simultaneously). The combination is a marketing win; the human evidence does not support stacked benefit.
- Daily senolytic mega-doses (continuous high-dose fisetin or quercetin). The senolytic biology is hit-and-run; daily dosing may select for resistant senescent cells rather than clear them.
- Untested peptide nootropics outside specific clinical contexts. Cerebrolysin, semax, selank: regulatory grey zones with sparse human RCT data in healthy adults.
- Most "testosterone booster" blends at retail doses. The few compounds with real testosterone effects (clomiphene, clinical TRT) are prescription; OTC blends are mostly placebo at the doses provided.
Treating this list as a hard skip list saves the typical biohacker 200 to 500 dollars per month and removes interaction surface area.
Biohacking for beginners: where to actually start
The fastest path from zero to credible biohacker.
- Fix sleep first. 7 to 9 hours, consistent timing, dark room, cool (~18 to 20°C). The sleep architecture primer covers the framework. Without this, no supplement matters.
- Train consistently. 150+ minutes per week including zone 2, at least 2 resistance-training sessions per week. The resistance-training minimum effective dose is the floor.
- Eat with restraint. Mediterranean-style with adequate protein (1.6 g/kg/day per the protein targets post). Time-restricted eating at 14:10 or 16:8 if it fits your schedule.
- Start the Tier-A foundation. Creatine 5 g/day, omega-3 2 to 3 g/day, vitamin D3+K2 5,000 IU + 100 mcg/day, magnesium glycinate 200 to 400 mg/day. Cost ~30 to 50 dollars per month.
- Order baseline bloodwork. ApoB, Lp(a), HbA1c, hsCRP, vitamin D, ferritin, fasting glucose, fasting insulin, full lipid panel. See what your doctor isn't testing. Use the bloodwork tracker to log them.
- Add Tier-B selectively. One or two compounds for one or two specific goals (e.g. caffeine + L-theanine for cognition, ashwagandha for stress, melatonin micro for sleep).
- Skip Tier-C until the foundation is dialed in. The longevity-class compounds (NMN, spermidine, urolithin-a, fisetin, rapamycin) are optimization on the margins. They will not outperform the basics.
That sequence covers the bulk of credible biohacking outcomes for a fraction of the cost of a typical influencer stack.
What biohackers eat for breakfast
The biohacker breakfast is often skipped: time-restricted eating with the first meal at 11 AM or noon. When eaten, the pattern is protein-and-fat-led:
- Eggs (2 to 4) plus avocado plus smoked salmon plus mixed greens.
- Plain Greek yogurt with nuts, berries, and a drizzle of olive oil.
- Bryan Johnson's "super veggie" (broccoli + cauliflower + black lentils + extra-virgin olive oil) is the public-protocol example.
- Coffee plus 100 to 200 mg L-theanine for the cognition stack.
The common features: minimize refined carbohydrate, hit a protein target (~30 g for the first meal), include high-polyphenol foods (extra-virgin olive oil, berries, dark chocolate), and avoid the standard breakfast that spikes insulin (cereal, pastries, sweetened yogurt). See the meal timing post for the timing case.
Stack design: avoid mTOR/AMPK over-stacking
A common mistake in biohacker stacks is layering compounds that send conflicting cellular signals. AMPK activators (metformin, berberine, fasting, exercise) and mTOR activators (high-protein meals, leucine, post-workout shake, rapamycin off-day) are reciprocal. Activating both heavily at the same time partially blunts both.
A defensible weekly framework:
- Most days: moderate AMPK state (regular exercise, time-restricted eating, modest carbohydrate intake). Tier-A supplements are AMPK-neutral.
- Training days: moderate mTOR state in the post-workout window (protein-rich meal, adequate calories). Avoid AMPK-activating supplements (berberine, metformin if applicable) immediately around the training session per Konopka 2019 evidence on metformin blunting exercise adaptations Konopka et al. 2018, n=53 .
- Rapamycin users: on the rapamycin day, lean into AMPK activation (fasting, light training). Off-rapamycin days, protein-led mTOR activation for muscle.
- Avoid simultaneous heavy AMPK and mTOR signals: e.g. taking metformin + post-workout shake + rapamycin all in the same window. The cellular machinery does not respond well to mixed signals.
The AMPK activators post covers the pull-push relationship in detail.
Verdict and practical 90-day sequence
A starter sequence for someone new to evidence-led biohacking supplementation.
Days 0 to 30, Foundation: Order the Tier-A four (creatine, omega-3, vitamin D3+K2, magnesium glycinate). Order baseline bloodwork. Establish sleep, training, and protein-intake baselines. No other supplements.
Days 31 to 60, Tier-B selective: Add one or two Tier-B compounds based on the goal that matters most to you (caffeine + L-theanine if cognition, ashwagandha if stress, melatonin micro if sleep onset). Run a 4-week trial; assess subjective effect plus objective markers.
Days 61 to 90, Tier-C optional: If foundation is dialed in, baseline bloodwork is favorable, and you accept the early-stage evidence framing, add one Tier-C compound (most defensible: spermidine continuous, urolithin-a, or pulsed fisetin). Skip rapamycin without a knowledgeable prescriber.
Re-test bloodwork at 90 days. Adjust. Document what changed and what did not. This is the supplement-stack equivalent of the n=1 nootropic trial framework: disciplined, sequential, measured.
