Evidence

Don't trust anyone's claims until you verify the studies...

...and their doses. Ours included. Your mitochondria run a cycle every day. Essential supports all five stages of it. Here is each stage, the dose that carries it, and the human study behind that dose.

Mitochondria support in five stages: the mitochondrial cycle

Signal

To neurons: grow and become robust.
To synapses: connect and adapt.

In aged mice, two months of lion's mane standardised for erinacine A and hericenones C and D raised hippocampal neurogenesis and reversed recognition-memory decline.⁴⁸

5 mg

Erinacine A¹

10 mg

Hericenones C+D+E⁴²

Induces

NGF

nerve growth factor

BDNF

brain-derived neurotrophic factor

Build

Mitochondria to answer the power demands of both.

1,000 mg

NMN²

20 mg

PQQ²⁶

1,500 mg

TMG²³

50 mg

Apigenin⁴⁷

250 mg

Pterostilbene³⁵

Induces

NAD⁺

nicotinamide adenine dinucleotide

Fuel

Because running out is what you feel as fatigue.

5 g

Creatine³

100 mg

Ubiquinol²⁷

1,500 mg

Taurine⁵⁰

170 mg

Rhodiola⁵¹

Induces

ATP

adenosine triphosphate

Protect

Because high demand drives burnout from oxidation and inflammation.

25 mg

Ergothioneine²⁴

100 mg

Ubiquinol⁴⁵

1,500 mg

Taurine⁴⁹

200 mg

Luteolin⁵²

Acts as

Antioxidant

Anti-inflammatory

Clear

And when their time is up, recycle — so the cycle begins anew.

24 mg

Spermidine¹³

Induces

Autophagy

cell-wide recycling

Mitophagy

mitochondria only

The label, in numbers

Every dose, next to its human study.

One row per active: our dose in Essential and in Essential Plus, the dose its human study used, and the ratio between them.

17/ 17

Essential

22/ 22

Essential Plus

doses at or above what their human studies used.

Active

Essential

Essential Plus

Study dose

Ratio

Lion's mane mycelium

grain-free · 5 mg erinacine A

1,000mg

3.44 mg erinacine A

Creatine monohydrate

5,000mg

9,000mg

2.25× study

4,000 mg × 8 wk

MCT

as 6 g of 70% powder

4,200mg

2,000 mg × 2 wk

NMN

1,000mg

1,000 mg RCT arm

PQQ disodium

20mg

20 mg

Ubiquinol

100mg

200mg

2× study

100 mg

Betaine anhydrous

TMG

1,500mg

1,500 mg

Lion's mane

fruiting body · hericenones C + D + E, 9.2 mg

1,000mg

7.4 mg hericenone C · ≤2.9 mg in the 2.9 g trial powder

Pterostilbene

250mg

250 mg

L-theanine

200mg

200 mg

Ergothioneine

25mg

25 mg

Luteolin

200mg

95 mg × 15 d

Apigenin

50mg

50 mg × 2 wk

Taurine

1,500mg

1,500 mg × 16 wk

Rhodiola rosea

170mg

170 mg × 2 wk

Riboflavin

10mg

RDA 1.3 mg

Spermidine — Clear

in the mug

24mg

24 mg × 48 wk

Essential Plus only

Cordyceps sinensis

Cs-4 mycelium

—

2,000mg

1,680 mg × 8 wk

Cordyceps militaris

5.1 mg cordycepin

—

500mg

2.85 mg cordycepin

Reishi

fruiting body · β-glucan and triterpenes

—

500mg

150 mg β-glucan · 15.75 mg triterpenes

Collagen peptides

types I & III, grass-fed

—

5,000mg

5,000 mg × 12 wk

Phosphatidylserine

sunflower, 20%

—

400mg

400 mg × 6 wk

All seventeen actives in Essential, and all twenty-two in Essential Plus, meet or exceed what their human studies used. Lion's mane is compared on erinacine A and on hericenone C — the fractions the trials dosed.

Third-party assay per batch

The whole label, one morning sachet.

Every dose above, in the mug. Essential, $3 a mug — $2 a mug if you rate every day. Essential Plus, $4 a mug — $3 a mug if you rate every day.

Buy Essential · $14 a pack Buy Essential Plus · $21 a pack

Clear, in depth

Mechanism — where each ingredient acts, step by step¹⁴

Mitophagy, all four steps.

Mitophagy, step by step — where each ingredient acts, and why Clear is spermidine. Show

A typical mitophagy product

step 2 only

Essential™

steps 1–2 triggers in the mug · steps 3–4 machinery, spermidine

Damage sensing

Depolarised membrane; PINK1 accumulates on the outer membrane.

Pterostilbene · caffeine¹⁴

Tagging

PINK1 phosphorylates ubiquitin Ser65, Parkin amplifies; or receptor-mediated via BNIP3/NIX/FUNDC1.

Pterostilbene · caffeine¹⁴

Engulfment

ULK1, BECN1/VPS34 nucleation, ATG7/ATG5, LC3 lipidation, p62/OPTN adaptors.

Spermidine

Digestion

Lysosome fusion, acidification, cathepsins — the rate-limiting step under load.

Spermidine (primary)

↺

Then: Build

PGC-1α → NRF1/TFAM biogenesis replaces what was cleared.

Every morning — NMN³¹

Steps 1–2 are induction; 3–4 are capacity. Step 4 is where clearance backs up under load — flagging more than the lysosome can digest is not clearance. That is the step spermidine serves, at the POLYCAD dose¹³.

Why Clear is spermidine.

Clear has to finish the job — steps 3 and 4, digestion — and it has to do it in the brain. Spermidine is the compound with a human protocol for exactly that¹³. Urolithin A tags damaged mitochondria well, in muscle⁸. We built Clear on spermidine, the one that reaches the finish.

Why Protect and Clear are one job.

A mitochondrion under oxidative load leaks fragments of its own DNA — oxidised — through pores in its membranes. The cell's innate immune system reads that DNA as a bacterial invader and fires the NLRP3 inflammasome and the cGAS–STING interferon pathway: low-grade inflammation from the inside. Two things stop the leak at its source. Less oxidation of the DNA — ergothioneine concentrates in the matrix where that oxidation happens, with ubiquinol alongside. And removal of the mitochondria that have begun to leak — PINK1/Parkin mitophagy, the pathway spermidine serves. Lose mitophagy and the leak drives a loop: the inflammasome switches Parkin off, damage accumulates, more DNA escapes. Circulating mitochondrial DNA rises in people after 50 and tracks with their inflammatory cytokines⁴⁴.

Five bottles, priced

Buying the pathway one stage at a time.

The nearest product to each stage, at its own list price¹⁰, per day at our doses.

Signal

ErinaMax — two capsules a day for our 5 mg of Erinacine A⁴

$1.83

Build

Tru Niagen — 300 mg NR; rough equivalent of our 1,000 mg NMN

$1.63

Fuel

MitoQ — two a day $2.07

Thorne Creatine — 5 g a day²⁰ $0.49

$2.56

Protect

Life Extension Ergothioneine — 25 mg a day¹⁸ $0.95

Swanson Apigenin — 50 mg a day¹⁹ $0.22

$1.17

Clear

Timeline — urolithin A; can't match our spermidine

$4.17

Five products

a day of each, at our doses

$11.36

Essential™

all five stages · one mug a day

List price ÷ the label's servings, one day at our dose¹⁰ — ErinaMax two capsules, Thorne 5 g of a 450 g tub, the rest a capsule or two. Two of the five have no dose match on the market. Riboflavin, PQQ, TMG and spermidine you would still have to buy.

Buy Essential · $14 a pack

30%

of adults are functionally short on riboflavin⁷

Why one formula, not five bottles

The cheapest ingredient in Essential gates the most expensive ones.

Riboflavin 10 mg

→ becomes

FMN · FAD

→ without which

Complex I & II

→ cannot use

MCT · ubiquinol · NAD⁺

Riboflavin costs a fraction of a cent per serving, and Complex I and II of the respiratory chain cannot run without the FMN and FAD it becomes⁶. In a riboflavin-short person, the chain that regenerates NAD⁺ from NADH is compromised — and buying more NAD⁺ precursor alone cannot fix the ratio the sirtuins actually read. That dependency is why the five stages ship as one formula.

Citation index

Sources.

Numbered as cited across the site. Each entry reports what that study found, in its own population, at its own dose.

Li IC et al. Front Aging Neurosci 2020;12:155, PMID 32581767 — randomised double-blind placebo-controlled, n=49 adults with mild Alzheimer's disease, three 350 mg erinacine A-enriched Hericium erinaceus mycelium capsules a day at 5 mg/g = 5.25 mg erinacine A/day × 49 weeks: cognitive scores (MMSE, CASI) and daily-living function (IADL) improved against placebo, with brain-atrophy biomarkers moving the same way. The deficit is what it corrects; the trial ran on 5.25 mg a day and we ship 5 mg. Erinacine C, in the same mycelium: Rascher M, Wittstein K, Winter B et al. Biomolecules 2020;10:1440, PMID 33066380 — human 1321N1 astrocytoma cells, 5 µg/mL for 6–48 h: erinacine C induced both NGF-β and BDNF, and medium from treated cells grew neurites on rat PC12 cells through the TrkA receptor. Kawagishi H, Shimada A, Shirai R et al. Tetrahedron Lett 1994 — mouse astroglial cells at 1.0 mM: NGF secreted was erinacine C 299.1, erinacine A 250.1, and erinacine B 129.7 pg/mL, ranking C the strongest of the three. PubMed 32581767 ↗

NMN at 1,000 mg, and what doubles. Christen S et al. Nat Metab 2026, doi 10.1038/s42255-025-01421-8 — randomised, n=65 healthy adults 18–50: NMN 1 g/day × 14 days raised whole-blood NAD⁺ by 43.1 µM (95% CI 32.7–53.4, P<0.001), about 2×; NR 1 g gave +49.4 µM. Dose confirmed in older adults: Pencina KM et al. J Gerontol A 2023;78:90, doi 10.1093/gerona/glac049 — 1,000 mg once daily, n=32, ages 55–80, phase-1 PK; “substantial dose-related increases” in NAD⁺. doi:10.1038/s42255-025-01421-8 ↗

Hersch SM et al. Neurology 2006, PMID 16434666 — randomised double-blind placebo-controlled, n=64 adults with Huntington's disease, 8 g/day creatine × 16 weeks. Brain creatine by MRS +13% occipital (p=0.05), +7.5% frontal; serum 8-OH-dG fell (p=0.0042). Dechent P et al. Am J Physiol 1999;277:R698, doi 10.1152/ajpregu.1999.277.3.R698 — 20 g/day × 4 weeks in healthy adults, brain total creatine +8.7%. The brain literature runs 8–20 g; 8 g over 16 weeks produced the larger rise — duration beat dose. PubMed 16434666 ↗

Dose check, per each label's own public page. ErinaMax (Nootropics Depot), product page and Supplement Facts panel captured 1 Sep 2026: serving size 2 capsules = 1,000 mg liquid-culture Hericium erinaceus mycelium standardised to 5 mg erinacine A, so 2.5 mg per 500 mg capsule; frequency once daily; 60 ct or 120 ct bottles = 30 or 60 servings; $54.99 at 60 ct. RealMycelium (Real Mushrooms) — standardised 5 mg erinacine A per serving, Amazon listing noted 14 Aug 2026. Marks are their owners'.

Cuomo J, Appendino G, Dern AS, et al. J Nat Prod 2011;74(4):664–9, doi:10.1021/np1007262 — randomised, double-blind, crossover, human: total curcuminoid absorption ~29× higher for the phospholipid (lecithin) formulation than the same unformulated curcuminoids. doi:10.1021/np1007262 ↗

Complex I contains FMN and oxidises NADH at that flavin; Complex II is FAD-dependent (Biochim Biophys Acta 2020; BBA 2015).

Ward M et al. BMC Medicine 2020, doi 10.1186/s12916-020-01780-x — JINGO project (TUDA + NANS cohorts), n=6,076 generally healthy adults aged 18–102, Ireland. Riboflavin status by EGRac: 30.0% deficient (≥1.40) and a further 30.2% low — about 60% low-or-deficient. doi:10.1186/s12916-020-01780-x ↗

Timeline / Mitopure claims, captured 1 Sep 2026 from timeline.com: “18 Years of research”, “80 Patents”, “25 Human clinical trials” — the last qualified “completed and ongoing”. Stated by them as flat figures.

Qualia Mitochondria+ panel and dose adjudication, captured 2 Sep 2026: 8 capsules per serving, 20 servings, $179.00, 33 distinct actives (Qualia’s formulation page counts 36 by listing dual forms separately). Each ingredient checked against Qualia’s own numbered reference lists, with each cited study’s dose read at primary source: 11 reach a dose a human trial used; 20 are below; 2 have no human dose at all. No Hericium erinaceus and no erinacine on the panel. Example: Gynostemma pentaphyllum is the one ingredient on the panel with a human trial that measured mitochondrial respiration — 450 mg/day (Nayyar 2023, Nutrients 15:4721) — and they dose 100 mg.

Competitor prices, US list, captured 14 Aug 2026: Tru Niagen $49, MitoQ ~$62, Timeline $125, ErinaMax $54.99/60 ct = 30 servings (ref 4 carries the panel, captured 1 Sep 2026), Qualia Mitochondria+ ~$169 (superseded by ref 17). Pack sizes: ErinaMax 60 ct and Qualia 20 servings (ref 9) are the only servings counts in this capture. Serving sizes used to put the five-product stack on a per-day basis, list price ÷ servings per label: ErinaMax 60 ct at 2.5 mg erinacine A a capsule ($0.9165 each), two capsules a day for Essential's 5 mg = $1.83 a day; Tru Niagen 300 mg, 30 ct, one a day = $1.63; MitoQ Pure 5 mg, 60 ct, two a day = $2.07; Timeline Mitopure softgels, 60 softgels, two a day = $4.17 (Timeline's own page states 60 softgels last a month); Life Extension ergothioneine 30 ct, one a day = $0.95; Swanson apigenin 50 mg, 90 ct, one a day = $0.22 (ref 19); Thorne creatine 450 g at 5 g/day = $0.49. Total $11.36 a day. Essential™ at $3 a day is list price ÷ sachets ($21 ÷ 7). Tru Niagen, MitoQ and Timeline pack sizes were not recorded, so the five-bottle figure is a floor.

PQQ 20 mg: PGC-1α protein increased in humans at this dose — Hwang PS et al. J Am Coll Nutr 2020, PMID 31860387, n=23 sedentary men, 6 weeks with endurance training. A second human trial at the same 20 mg: Nakano M et al. Funct Foods Health Dis 2016, n=20 healthy adults 50–70 × 12 weeks — right-prefrontal haemoglobin by tNIRS up vs placebo (p<0.05). PubMed 31860387 ↗

Schroeder et al. 2021 — d8-spermidine reaches aged-mouse brain at 1 week and climbs through 4 and 8 weeks to ~30% of blood levels. Every spermidine outcome study to date (lifespan, cardiac, cognition, mitophagy loss-of-function) dosed continuously. Basis for nightly, not pulsed, Clear. doi:10.1016/j.celrep.2021.108985 ↗

POLYCAD — randomised, double-blind, placebo-controlled: 24 mg/day spermidine (3 × 8 mg) × 48 weeks, n=187, age ≥65. NCT06186102; protocol Trials 2025, doi 10.1186/s13063-025-09176-z. The longest continuous human spermidine exposure protocol on record; basis for the 24 mg Clear dose in the morning mug. doi:10.1186/s13063-025-09176-z ↗

Mitophagy — where a human concentration is reached, and where an oral animal dose scales. Caffeine: Tian L et al. Front Pharmacol 2023;14:1155414 — 0–80 µM series in AT1 cells with mitophagy-specific readouts (mitochondrial-fraction PINK1 and Parkin, p-Parkin Ser65, BNIP3L, FUNDC1, TOM20/LAMP1 colocalisation, flux confirmed with chloroquine); 15 µM optimal, inverted U. Blanchard J & Sawers SJ, Eur J Clin Pharmacol 1983, PMID 6832208 — 5 mg/kg oral caffeine gives Cmax 51.5 µM, so a ~110 mg cup peaks near 16 µM. Pterostilbene, orally, in animals: Metti S et al. 2020, PMID 33134297 — mice, 90.2 mg/kg gavage × 5 days, BNIP3 up in tibialis anterior (human-equivalent ~513 mg). López-Blanch R et al. 2024, PMID 38241160 — ALS mice, pterostilbene 30 mg/kg/day in feed with nicotinamide riboside 185 mg/kg/day, late-stage mitophagy up by mito-lysosome colocalisation; human-equivalents ~171 mg pterostilbene and ~1,053 mg NR against our 250 mg and 1,000 mg NMN. Shi Q et al. J Pharmacol Sci 2022;148:19 — PINK1-dependent mitophagy at 5–10 µM in cells and intraperitoneal in mice. doi:10.3389/fphar.2023.1155414 ↗

Mushroom-coffee label check, per each brand’s public label or listing, captured 1 Sep 2026: Ryze Dark Roast 2,000 mg six-mushroom proprietary blend, no split (MCT and prebiotic fibre amounts not disclosed); MUD\WTR 30-serving tin 2,240 mg as four mushrooms at 560 mg each — “mushrooms and mycelium cultured on organic oats and/or organic sorghum” per their own ingredient line (cacao and spice amounts not disclosed); Four Sigmatic Focus Instant 500 mg lion’s mane + chaga combined, no split; Everyday Dose Coffee+ 1,500 mg lion’s mane + chaga combined, with 4,000 mg collagen and 150 mg L-theanine. Essential: lion's mane 2,000 mg — mycelium 1,000 mg (5.1 mg erinacine A) and fruiting body 1,000 mg (7.4 mg hericenone C). None of the four names a standardised active. Marks are their owners’.

Spermidine cellular retention: brain spermidine turnover, half-life ~22 days (mouse; radiolabel decay after intraventricular putrescine) — Shaw GG, Neurochem Res 1979;4(2):269–275, doi 10.1007/BF00964150. Basis for the daily-pool framing. doi:10.1007/BF00964150 ↗

Qualia Mitochondria+ product page and Supplement Facts, captured 28 Aug 2026 — list price $179 (was $169 on 14 Aug 2026; the later capture governs). No Signal-stage ingredient (no erinacines / Hericium mycelium) on the panel.

Single-stage ergothioneine, per each seller's own listing, captured 1 Sep 2026: Life Extension Mega L-Ergothioneine, 25 mg per capsule, 30 capsules, $28.50 one-time (Amazon listing) — the figure used in the stack; ProHealth Longevity Ergothioneine, 25 mg, 30 capsules, $39.95 (Vitacost) is the same dose at a higher price. Marks are their owners'.

Single-stage apigenin, per the seller's own product page, captured 11 Oct 2026: Swanson Apigenin, 50 mg per capsule, 90 capsules = 90 servings, $19.99 list — $0.22 a day at our 50 mg. Marks are their owners'.

Thorne Creatine, micronized creatine monohydrate, 5 g per serving × 90 servings = 450 g, NSF Certified for Sport, $44.00 — per Walmart and iHerb listings, captured 1 Sep 2026. At Essential's 5 g a day one tub runs 90 days. Marks are their owners'.

Hidese S et al. Nutrients 2019, PMID 31623400 — randomised double-blind placebo-controlled crossover, n=30 healthy adults (mean age 48), 200 mg L-theanine daily × 4 weeks. Depression score (SDS p=0.019), trait anxiety (p=0.006), sleep quality (PSQI p=0.013) and verbal fluency (p=0.001) improved. Exact-dose match for Essential's 200 mg. Stress and anxiety across nine trials at 200–400 mg: ref 22. PubMed 31623400 ↗

Williams JL et al. Plant Foods Hum Nutr 2020, PMID 31758301 — systematic review of nine randomised controlled trials of L-theanine supplements against control: 200–400 mg a day helped reduce stress and anxiety in people under stressful conditions. doi:10.1007/s11130-019-00771-5 ↗

Olthof MR et al. J Nutr 2003, PMID 14652361 — four-arm randomised placebo-controlled, n=76 healthy adults 30–50 selected for higher plasma homocysteine, 6 weeks. 1.5 g betaine a day lowered fasting homocysteine 12%. PubMed 14652361 ↗

Zajac IT et al. Nutraceuticals 2025 — randomised double-blind placebo-controlled, n=147 adults 55–79 with subjective memory complaints, ergothioneine 10 or 25 mg daily × 16 weeks. At 25 mg: subjective prospective memory and sleep initiation improved dose-dependently; plasma ergothioneine ×16. doi:10.3390/nutraceuticals5030015 ↗

Hwang PS et al. J Am Coll Nutr 2020, PMID 31860387 — see ref 11. The human PQQ trial at 20 mg: PGC-1α up. PubMed 31860387 ↗

Tamakoshi M et al. Food Funct 2023, doi 10.1039/D2FO01515C, UMIN000034459 — randomised double-blind placebo-controlled, healthy Japanese adults 20–65, 20 mg BioPQQ daily × 12 weeks. On Cognitrax, overall composite memory (P=0.003) and verbal memory (P=0.001) improved. The PGC-1α trial at the same 20 mg: ref 25. doi:10.1039/D2FO01515C ↗

Mizuno K et al. Nutrients 2020, PMID 32498248 — randomised double-blind, n=62 healthy adults 20–64 with mild daily fatigue, ubiquinol 100 or 150 mg daily × 12 weeks. At 100 mg: subjective fatigue and sleepiness after a cognitive task improved (p<0.05). PubMed 32498248 ↗

Yi L et al. GeroScience 2022, doi 10.1007/s11357-022-00705-1 — randomised multicentre double-blind placebo-controlled, n=80 healthy middle-aged adults, NMN 300, 600 or 900 mg daily × 60 days, blood NAD⁺ and six-minute walking distance rose dose-dependently against placebo. doi:10.1007/s11357-022-00705-1 ↗

Černelič Bizjak M et al. J Funct Foods 2024 — randomised double-blind placebo-controlled, n=33 healthy adults, 3 g/day erinacine-A-enriched Hericium erinaceus delivering 3.44 mg erinacine A (HPLC, ISO 17025 lab) × 8 weeks. Non-verbal processing-speed test improved at 8 weeks (F=4.6, p<0.05). Essential's 5 mg erinacine A is 1.5× this. doi:10.1016/j.jff.2024.106120 ↗

Owen GN et al. Nutr Neurosci 2008, PMID 18681988 — double-blind placebo-controlled crossover, n=27 healthy adults, single dose 50 mg caffeine + 100 mg L-theanine: attention-switching speed and accuracy improved at 60 minutes and susceptibility to distraction fell at 60 and 90 minutes. For L-theanine on its own at our 200 mg, see ref 21. PubMed 18681988 ↗

Lapatto HAK et al. Sci Adv 2023;9:eadd5163, PMID 36638183 — nicotinamide riboside escalated 250→1,000 mg/day, then 1 g/day for 5 months; 20 BMI-discordant and 4 concordant monozygotic twin pairs, ~40 y. Skeletal-muscle mitochondrial number increased on biopsy, with improved satellite-cell differentiation. NR and NMN are both NAD⁺ precursors. The strongest human mitochondrial evidence behind anything on this label. PubMed 36638183 ↗

Alsaleh G et al. Aging Cell 2026, doi 10.1111/acel.70545, NCT05421546 — 6 mg/day spermidine as wheat-germ extract × 13 weeks, n=40 adults 65–81. Single-cell RNA-seq: TFEB-target and autophagy genes up, with directly measured autophagic flux elevated — the first in-vivo demonstration of spermidine inducing autophagy in humans, at a quarter of the Clear dose. doi:10.1111/acel.70545 ↗

Brain mitochondrial protein turnover — the twelve-week clock. Sci Rep 2023;13, doi 10.1038/s41598-023-38484-0 — deuterated-leucine labelling in C57BL/6J mice: striatal synaptic mitochondrial proteins have a 25.7-day half-life (hepatic 3.5 days). Eighty-four days is 3.27 half-lives — 89.6% replaced. doi:10.1038/s41598-023-38484-0 ↗

Creatine and strength. Kreider RB et al. J Int Soc Sports Nutr 2017;14:18 — the ISSN position stand, drawing on several hundred trials: 3–5 g/day maintenance with resistance training increases strength and lean mass in young and older adults. The one long trial in older women, Chilibeck PD et al. Med Sci Sports Exerc 2023, PMID 37144634 — 0.14 g/kg/day × 2 years, n=237 postmenopausal women with resistance training and walking — femoral geometry and walking speed improved, and lean mass rose (P=0.046). doi:10.1186/s12970-017-0173-z ↗

Riche DM et al. Evid Based Complement Alternat Med 2014;2014:459165, NCT01267227 — four arms, n=80 adults with hypercholesterolaemia, 6–8 weeks; 125 mg twice daily = 250 mg/day, our dose exactly. Systolic blood pressure −7.8 mmHg vs placebo (P<0.01). LDL rose 17.1 mg/dL on pterostilbene alone (P=0.001); a co-administered grape extract prevented the rise. Both the benefit and the LDL finding are at our dose, and both are printed. doi:10.1155/2014/459165 ↗

Moridpour AH et al. Phytother Res 2024, PMID 37818728 — systematic review and dose–response meta-analysis, 24 RCTs in type 2 diabetes: fasting glucose, HOMA-IR and HbA1c fell vs control. PubMed 37818728 ↗

Yoshino M, Yoshino J, Kayser BD, et al. Science 2021;372:1224, PMID 33888596, NCT03151239 — randomised double-blind placebo-controlled, n=25 postmenopausal women with prediabetes, overweight or obese, NMN 250 mg/day × 10 weeks. Primary met: insulin-stimulated muscle glucose disposal (hyperinsulinaemic-euglycaemic clamp) increased after NMN and not after placebo; muscle AKT and mTOR phosphorylation up. A quarter of our dose. PubMed 33888596 ↗

Gualano B et al. Med Sci Sports Exerc 2011;43:770, PMID 20881878 — randomised double-blind placebo-controlled, n=25 adults with type 2 diabetes, creatine 5 g/day with supervised exercise training × 12 weeks. Primary met: HbA1c −1.1 points vs placebo (P=0.004); glucose AUC lower (P=0.05); GLUT-4 translocation up. PubMed 20881878 ↗

Mori K et al. Phytother Res 2009;23:367, PMID 18844328 — randomised double-blind placebo-controlled, n=30 randomised / 29 analysed, Japanese adults 50–80 with mild cognitive impairment (HDS-R-based scale 22–25 of 30), twelve 250 mg tablets of 96% Hericium erinaceus fruiting-body dry powder a day — 2.9 g — × 16 weeks, then 4 weeks off. Scores separated from placebo at weeks 8, 12 and 16 and rose with duration; in the four weeks after intake stopped they fell significantly from the week-16 level. The authors’ own reading: the effect is reversible and continuous intake is necessary to maintain it. The dose comparison is made on hericenone C, ref 42. PubMed 18844328 ↗

MCT as fuel, and its dose. Ketogenic effects of medium-chain triglycerides containing formula and its correlation to breath acetone in healthy volunteers, Front Nutr 2023 — acute dose–response in healthy adults: plasma ketones rise within the hour of an MCT dose and scale with it. The 4.2 g here is set by the fat phase the formula needs (a 6 g fill of 70% MCT powder on acacia). Human outcome trials run 6 g/day × 90 days for muscle in frail older adults (Front Nutr 2023, combined analysis) and 12–20 g/day for cognition. As a coffee ingredient — ketones beside glucose in the first hours — it is on the home page with caffeine and L-theanine. doi:10.3389/fnut.2023.1224740 ↗

Creatine, and how fast. At our dose: Kondo DG et al. Amino Acids 2016, PMID 26907087 — dose-ranging ³¹P-MRS, n=33 adolescent females with SSRI-resistant depression (human; frontal lobe), creatine 2, 4 or 10 g/day × 8 weeks: frontal phosphocreatine rose at every dose, +4.1 % at 4 g. Above our dose: Watanabe A et al. Neurosci Res 2002;42:279, PMID 11985880 — double-blind placebo-controlled, n=24, 8 g/day × 5 days: mental fatigue on a repeated calculation task fell and task-evoked cortical oxy-Hb dropped, read as more efficient oxygen use. Above our dose, the acute effect is unambiguous: Gordji-Nejad A et al. Sci Rep 2024;14:4937, doi 10.1038/s41598-024-54249-9 — randomised double-blind crossover, n=15, a single 0.35 g/kg dose during 21 h awake: brain creatine (tCr/tNAA) rose, subjective fatigue fell and cognition held against placebo from 3 h; replicated at 0.2 g/kg, n=29 — Nutrients 2026;18:1192, PMID 42075005. Our 5 g is ≈0.07 g/kg. A 5 g dose peaks in plasma within the hour (Harris RC et al. Clin Sci 1992;83:367). Read together: creatine reaches the brain and acts on fatigue within hours of a dose, within a week at ours; ref 3 is the slow, well-measured brain-loading floor. PubMed 11985880 ↗

Lion's mane fruiting body, dosed by hericenone C rather than by powder mass. Tang Y, Kahraman O, Goos AJ, Fields C. Molecules 2026;31:569, doi 10.3390/molecules31030569 — analytical study (no species; Hericium erinaceus fruiting-body raw materials and finished products), single-laboratory validated UHPLC-UV: across the fruiting-body materials measured, hericenones and hericenes ranged 0.005 to 1 mg/g, with many commercial products below the limit of quantification. At the top of that range the 2.9 g/day of dried fruiting-body powder in ref 39 carries at most 2.9 mg hericenone C; our 1 g of fruiting-body extract carries 7.4 mg hericenone C, 1.6 mg hericenone D*, and 0.2 mg hericenone E* (*scaled from concentrated-batch assay performed by Omnient Labs 2026). doi:10.3390/molecules31030569 ↗

Creatine and memory. Avgerinos KI, Spyrou N, Bougioukas KI, Kapogiannis D. Exp Gerontol 2018;108:166, PMID 29704637 — systematic review of six randomised controlled trials, n=281 healthy adults, oral creatine monohydrate 2–20 g/day: short-term memory and intelligence/reasoning improved; effects larger in vegetarians and older adults. Our 5 g sits inside the studied range. PubMed 29704637 ↗

Mitochondrial DNA release and innate immunity. Newman LE, Shadel GS. Annu Rev Biochem 2023;92:299, PMID 37001140, doi 10.1146/annurev-biochem-032620-104401 — review; the primary data are mouse and human cell lines. Oxidised mtDNA fragments exit through mPTP/VDAC pores and activate NLRP3; whole nucleoids exit through BAK/BAX pores and activate cGAS–STING; every intervention reported to block the NLRP3 route lowers mitochondrial ROS. Mitophagy: Sliter DA et al. Nature 2018;561:258, PMID 30135585 — Parkin- or PINK1-null mice, exhaustive exercise, STING-dependent inflammation; the inflammasome-to-Parkin feed-forward loop is Yu J et al. (ref 111 therein), mouse macrophage. Human: Pinti M et al. Eur J Immunol 2014;44:1552, PMID 24470107 — circulating cell-free mtDNA in plasma rises after age 50 in a Caucasian cohort, n=831, and is highest in those with the highest TNF-α, IL-6, RANTES, and IL-1ra. Ergothioneine's mitochondrial concentration is ref 18; spermidine's mitophagy evidence is refs 13 and 14. doi:10.1146/annurev-biochem-032620-104401 ↗

Ubiquinol on the Protect side — it reduces mitochondrial ROS in human muscle at 200–300 mg. Acton JP et al. Eur J Appl Physiol 2026, doi 10.1007/s00421-026-06275-w, open access PMC13541835 — human, skeletal muscle (vastus lateralis biopsy), randomised double-blind, n=54 healthy men, ubiquinol (Kaneka QH) 300 mg a day × 6 weeks: complex I leak respiration fell and the inverse respiratory control ratio dropped from 0.073 to 0.044, a smaller share of respiration lost as leak, which the authors attribute to less electron leak as ROS and less lipid peroxidation of the inner membrane. Pham T et al. Eur J Appl Physiol 2020;120:1657, PMID 32458156 — human, skeletal muscle biopsy, n=20 men aged 50, ubiquinol 200 mg a day × 6 weeks: mitochondrial H₂O₂ emission during leak respiration fell; MitoQ 20 mg did the same. The fatigue trial under Fuel is ref 27. doi:10.1007/s00421-026-06275-w ↗

Apigenin and CD38. Escande C, Nin V, Price NL, et al. Diabetes 2013;62(4):1084–93, PMID 23172919, doi 10.2337/db12-1139 — cell and animal study (mouse; liver): apigenin inhibits CD38, the enzyme that consumes most cellular NAD+, in vitro and in vivo; in cultured cells it raised intracellular NAD+ and lowered protein acetylation, and in obese mice it raised liver NAD+, lowered protein acetylation, and improved glucose and lipid homeostasis. doi:10.2337/db12-1139 ↗

Gradolatto A, Basly JP, Berges R, et al. Drug Metab Dispos 2005;33:49, PMID 15466493 — apigenin pharmacokinetics in mammals (rat), single oral dose: slow elimination, blood half-life about 92 hours. A dose every morning therefore accumulates to a plateau in about three weeks. doi:10.1124/dmd.104.000893 ↗

Ratto D, Corana F, Mannucci B, et al. Nutrients 2019;11(4):715, PMID 30934760 — animal study (mouse, wild-type, frail with ageing; hippocampus and cerebellum): two months of oral Hericium erinaceus extract, standardised by HPLC-UV-ESI/MS for erinacine A and hericenones C and D, reversed the age-related decline in recognition memory, and PCNA and doublecortin staining showed more new neurons in the hippocampus and cerebellum. doi:10.3390/nu11040715 ↗

Abud GF, De Carvalho FG, Batitucci G, et al. Nutrition 2022;101:111706, PMID 35700594 — controlled double-blind trial, human, n=24 women aged 55–70 (mean BMI 31.4), taurine 1.5 g a day or 1.5 g starch × 16 weeks: blood taurine and the antioxidant enzyme superoxide dismutase rose in the taurine group, and superoxide dismutase ended higher than in the comparison group; the lipid-oxidation marker malondialdehyde rose only in the comparison group. Our dose exactly. doi:10.1016/j.nut.2022.111706 ↗

Beyranvand MR, Kadkhodai Khalafi M, Dabidi Roshan V, et al. J Cardiol 2011;57(3):333–337, PMID 21334852 — randomised single-blind trial with starch placebo, human, n=29 adults with heart failure (NYHA II–III, LVEF under 50%), taurine 500 mg three times a day = 1,500 mg a day × 2 weeks, our dose exactly. On a treadmill test in the taurine group, exercise time rose from 7.3 to 10.1 minutes, workload from 6.3 to 8.0 METs, and distance from 603 to 805 m (all P<0.001). Each group was tested against its own starting values, before and after. The deficit is what it corrects. doi:10.1016/j.jjcc.2011.01.007 ↗

Darbinyan V, Kteyan A, Panossian A, Gabrielian E, Wikman G, Wagner H. Phytomedicine 2000;7(5):365–371, PMID 11081987 — randomised double-blind placebo-controlled crossover, human, n=56 healthy young physicians on night duty, standardised Rhodiola rosea extract SHR-5 170 mg a day × 2 weeks, our dose. Mental performance before and after night duty — associative thinking, short-term memory, calculation, concentration, and speed of audio-visual perception, combined as a Fatigue Index — improved significantly on rhodiola in the first two-week period. The deficit is what it corrects. doi:10.1016/S0944-7113(00)80055-0 ↗

Gelabert-Rebato M, Wiebe JC, Martin-Rincon M, et al. Nutrients 2019;11(2):344, PMID 30736383 — randomised double-blind placebo-controlled crossover, human, n=12 healthy physically active men; tissue measured: skeletal muscle (oxygen extraction) and brain (oxygenation). Peanut-husk extract (95% luteolin) 50 or 100 mg a day — 47.5–95 mg luteolin — with mango-leaf extract (mangiferin 100 or 300 mg a day), for 48 hours and for 15 days. Sprint performance after ischaemia improved, muscle oxygen extraction and brain oxygenation rose, and VO₂ during the sprints was 6% lower than on placebo (p=0.010); both doses alike. Our 200 mg is 2.1× the 95 mg arm. Luteolin was given with mangiferin; its own share is not separable. doi:10.3390/nu11020344 ↗

Qualia Mitochondria+ — retail equivalent, 11 October 2026. Each of the 33 actives in ref 9, at Qualia’s amount per serving, priced on Amazon: the Best Seller, else the first in-stock unsponsored result; mg per serving read from each product’s Supplement Facts panel, never the title. Cost a day = Qualia’s amount × price per mg (price ÷ servings × mg per serving), pro rata with no capsule rounding. Where Qualia’s branded form has no retail twin (14 of 33), the nearest generic of the same ingredient. By section: vitamins and minerals 207 mg, $0.34; amino acids and metabolites 780 mg, $0.13; botanicals and fulvic 1,695 mg, $1.42; creatine, CoQ10, R-lipoic acid, PQQ, and spermidine 1,177 mg, $0.69. All 33: $2.59 a day, against Qualia’s $8.95. Those five at their studied doses (creatine 2,300 mg, R-lipoic acid 200 mg, CoQ10 90 mg, PQQ 20 mg, spermidine 0.9 mg): $1.16 a day. Products: Vitamin K2: Sports Research K2 MK-7 100 mcg; Thiamine: BulkSupplements Thiamine HCl; Riboflavin: Nutricost Vitamin B2 400 mg; Niacin: Nutricost Niacinamide 500 mg; Vitamin B6: Pure Encapsulations P5P 50; Folate: Thorne 5-MTHF 1 mg; Vitamin B12: Nature Made B12 1000 mcg; Biotin: Nutricost Biotin 10,000 mcg; Pantothenic acid: NOW Pantothenic Acid 500 mg; Magnesium: NatureWise Marine Magnesium (Aquamin); Creatine: Nutricost Micronized Creatine 500 g; Cocoa: Cocoa Flavanols 750 mg; Rosemary: Nutricost Rosemary Extract 20:1; L-carnitine: Nutricost L-Carnitine Tartrate; Cinnamon: Zazzee Ceylon Cinnamon 20:1; Grape: Zazzee Grape Seed 50:1; Myo-inositol: Zazzee Myo-Inositol Powder; Betaine: Nutricost Betaine Anhydrous 500 g; Ashwagandha: Nootropics Depot Sensoril 125 mg; R-lipoic acid: Life Extension Super R-Lipoic Acid; Gynostemma: Nusa Pure Jiaogulan 20:1; L-cystine: BulkSupplements L-Cystine; L-tryptophan: Nutricost L-Tryptophan 500 mg; Fulvic: LM-32 HC Pure Fulvic Acid; Pomegranate: Zazzee Pomegranate 20:1; Kaempferia: INCAS Thai Black Ginger; CoQ10: Qunol Ultra CoQ10 100 mg; Nobiletin: Nootropics Depot Nobiletin; Rutin: NOW Rutin 450 mg; Apigenin: Swanson Apigenin 50 mg; PQQ: Nutricost PQQ 20 mg; D-chiro-inositol: Zazzee D-Chiro-Inositol 50 mg; Spermidine: Neurogan Spermidine 3HCl 10 mg.

Essential Plus — Cordyceps sinensis. Jung SJ et al. BMC Complement Altern Med 2019, doi 10.1186/s12906-019-2483-y — randomised double-blind placebo-controlled, human, n=80 healthy adults 20–75 with slight immune decrease, CBG-CS-2 Cordyceps mycelium extract 1.68 g/day × 8 weeks. Pre-specified primary, NK-cell cytotoxic activity: met, +38.8% vs placebo (p=0.019). Essential Plus’s 2 g delivers ~630 mg polysaccharide against their ~538 mg. doi:10.1186/s12906-019-2483-y ↗

Essential Plus — phosphatidylserine and the stress response. Hellhammer J et al. Lipids Health Dis 2014, PMID 25081826 — randomised placebo-controlled, human, n=75 men 20–45, 400 mg phosphatidylserine + 400 mg phosphatidic acid daily × 42 days, then acute stress test. ACTH and cortisol response normalised in chronically stressed men (p=0.010, 0.035); Parker AG et al. JISSN 2011, doi 10.1186/1550-2783-8-16: 400 mg PS alone × 14 days in unstressed young men — calculation speed +20% (p=0.001). Essential Plus’s 400 mg PS is sunflower-derived with phosphatidic acid from lecithin; Benton D et al. Nutr Neurosci 2001, PMID 11842886 — 300 mg PS × 1 month, young adults under a mental-arithmetic stressor: less stress and better mood in those higher in neuroticism. The deficit is what it corrects. PubMed 25081826 ↗

Essential Plus — reishi and immune cells. Chen SN et al. Foods 2023;12:659, PMID 36766186 — randomised double-blind placebo-controlled, human, n=135 healthy adults 18–55, 200 mg/day of a Megazyme-assayed 75.2% β-glucan Ganoderma lucidum material = 150.4 mg β-glucan × 84 days: CD3+, CD4+, CD8+ T-cells, CD4/CD8 ratio, NK-cell counts, NK cytotoxicity and serum IgA increased vs placebo. Essential Plus’s 500 mg of 30.24% β-glucan fruiting-body extract delivers 151 mg — the trial dose. The triterpene comparison, 1.3×, is ref 57. PubMed 36766186 ↗

Essential Plus — reishi and the liver. Chiu HF et al. Pharm Biol 2017;55:1041, PMID 28183232 — randomised double-blind placebo-controlled crossover, human, n=42 randomised / 39 analysed, adults 40–54 with mildly raised liver enzymes and fatty liver, one 225 mg capsule daily × 6 months per arm, one-month washout. Each capsule 7% triterpenoid-ganoderic acid (A, B, C, C5, C6, D, E, G) and 6% polysaccharide peptides — 15.75 mg triterpenes a day, and their independent assay returned 15.3 mg. TEAC, thiols, TBARS, 8-OH-dG and liver enzymes improved. Essential Plus’s 500 mg at 4.22% triterpenes delivers 21.1 mg — 134%. PubMed 28183232 ↗

Essential Plus — collagen peptides. Zdzieblik D, Oesser S, Gollhofer A, König D. Appl Physiol Nutr Metab 2017;42:588, PMID 28177710 — randomised placebo-controlled, human, n=139 young athletic adults with activity-related knee pain and no joint disease, 5 g/day specific bioactive collagen peptides × 12 weeks. Primary met: activity-related pain fell more than placebo on participant (P=0.046) and physician (P=0.021) scales. PubMed 28177710 ↗

Essential Plus — reishi on stress and mood. Mitra S et al. Int J Med Mushrooms 2024;26(11):51, PMID 39241163 — double-blind randomised placebo-controlled, human, n=78 healthy women aged ~20, Ganoderma lucidum 500 or 1,000 mg daily × 30 days: anxiety, depression, vitality, and positive well-being scores improved at 1,000 mg, with VO₂max and work capacity rising dose-dependently. Ours is standardised to 4.22% triterpenes and 30.24% β-glucan — 21.1 mg and 151 mg in 500 mg. Dried fruiting body carries about 3.5% triterpenoids at most (Bioresour Bioprod 2026, doi 10.3390/bioresourbioprod2020005), so 21.1 mg is what roughly 1–2 g of powder carries: on triterpenes we sit above the 1 g arm. Tang W et al. J Med Food 2005;8:53, PMID 15857210 — randomised double-blind placebo-controlled, n=123 adults with neurasthenia, 5.4 g/day polysaccharide extract × 8 weeks: fatigue and well-being scores separated from placebo (CGI improvement P=0.002). doi:10.1615/IntJMedMushrooms.2024055300 ↗

Essential Plus — phosphatidylserine and memory. Vakhapova V, Cohen T, Richter Y, Herzog Y, Korczyn AD. Dement Geriatr Cogn Disord 2010;29:467, PMID 20523044 — randomised double-blind placebo-controlled, human, n=157 non-demented older adults with memory complaints, 300 mg/day phosphatidylserine (as PS-DHA, omega-3 on the backbone) × 15 weeks: verbal immediate recall improved against placebo and more participants responded. Kato-Kataoka A et al. J Clin Biochem Nutr 2010;47:246, PMID 21103034 — randomised double-blind, n=78 Japanese adults 50–69 with memory complaints, soy phosphatidylserine 100 or 300 mg/day × 6 months: memory scores rose on PS in those who started low. Ours is 400 mg, 1.3× the 300 mg arms. PubMed 20523044 ↗

Essential Plus — Cordyceps militaris, compared on cordycepin rather than on mass. Ontawong A, Pengnet S, Thim-Uam A et al. Sci Rep 2024 — randomised, double-blind, placebo-controlled, n=40 healthy Thai adults aged 25–60 (human), a fermented Cordyceps militaris beverage delivering 2.85 mg cordycepin/day × 8 weeks: natural-killer-cell activity rose 34.11% at week 4 in men (p=0.04). Kang C et al. 2015 reaches the same daily cordycepin from the other direction: 1.5 g of militaris assayed at 1.9 mg/g = 2.85 mg/day (full text on file). Our 500 mg at 1.02% cordycepin carries 5.1 mg — 1.8× both. Mass is the wrong axis for this material: cordycepin is the marker the trials dose and the one we assay. doi:10.1038/s41598-024-58742-z ↗

Apigenin at our dose in people. Mastrofini GF, Romersi RF, Lombardi MG, et al. J Int Soc Sports Nutr 2026;23:2740227, PMID 42829807 — randomised double-blind placebo-controlled, human, n=103 healthy physically active adults, two weeks: an evening blend of 50 mg apigenin, our dose, with 2 g magnesium L-threonate and 200 mg L-theanine, beside a morning adaptogen blend. The morning blend improved perceived stress and sleep quality; the evening blend's own effects were small over two weeks in healthy adults. Cited for the dose: 50 mg apigenin, taken daily by people in a controlled trial. PubMed 42829807 ↗

Apigenin from food, and what it did. Nielsen SE, Young JF, Daneshvar B, et al. Br J Nutr 1999;81(6):447–55, PMID 10615220 — randomised crossover, human, n=14 healthy adults, one week of parsley on a low-flavone diet, 3.73–4.49 mg apigenin per MJ of food, about 40 mg a day at a usual intake, under our 50 mg. Erythrocyte glutathione reductase and superoxide dismutase rose (p<0.005). PubMed 10615220 ↗

MCT at 2 g, and what it did. Tsujino S, Nosaka N, Sadamitsu S, Kato K. Nutrients 2022;14(3):536, PMID 35276897 — randomised double-blind placebo-controlled crossover, human, sedentary adults with a BMI of 25 to 30, 2 g MCT a day for two weeks against long-chain fat: fat oxidation during light activity rose and the respiratory exchange ratio fell. Our 4.2 g is 2.1× this dose. doi:10.3390/nu14030536 ↗

Nosaka N, Tsujino S, Kato K. Nutrients 2022;14(5):1119, PMID 35268094 — randomised double-blind crossover, human, the same group and the same 2 g a day for two weeks: after a test meal, energy expenditure and the burning of the meal's own fat rose against canola oil. doi:10.3390/nu14051119 ↗

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