Brett Boettcher's 'High-ROI' 7-Supplement Stack
Supplements I actively take or cycle through: 1) NAC (detox and reduce oxidation) 2) Creatine Monohydrate (cognition/performance) 3) Black seed oil (anti-inflammatory/anti-oxidant) 4) Magnesium glycinate/chloride (Recovery) 5) Collagen peptides (joint health and repair) 6) Vitamin D + K2 (optimizing vit D in winter) All cheap, safe and high ROI to add to a healthy lifestyle 7) Forgot the best one, Nattokinase daily for blood pressure, plaque reversal and lipids
A defensible, modestly-framed supplement stack with the actual evidence base behind most of the picks. Creatine, magnesium glycinate, and D3+K2 are gold-standard 'high-ROI' commodity supplements; NAC, collagen peptides, and nattokinase have moderate evidence for the claimed uses. The 'plaque reversal' line on nattokinase is the only real overclaim — there's no human RCT showing fibrinolytic enzymes regress atherosclerosis. Otherwise an honest, low-cost stack worth roughly what the author says it is.
| Goal | Score | Grade | Weight | Why |
|---|---|---|---|---|
| Longevity | 82 | B- | 50% | Solid CV/oxidative-stress portfolio: D3+K2, NAC, nattokinase, and black seed oil all hit real mechanisms. The 'plaque reversal' claim on nattokinase is the only overstatement — fibrinolytic activity is real, plaque regression isn't shown. |
| Cognition | 80 | B- | 20% | Creatine has good cognitive evidence especially under sleep deprivation; NAC has psychiatric/OCD signal; magnesium adequacy supports cognition. No nootropic dosed specifically for it, but the foundation is solid. |
| Sleep & recovery | 80 | B- | 20% | Magnesium glycinate is the recovery/sleep workhorse; collagen peptides have moderate evidence for joint pain in active populations. Defensible coverage of the axis without going exotic. |
| Energy & metabolism | 75 | C | 10% | Creatine for ATP regeneration during performance and black seed oil's mild glycemic effect touch this axis, but it isn't where the stack is aimed and the doses aren't disclosed. |
| Body recomposition | — | Not targeted | — | Not targeted: no anabolic agent, no protein target, no resistance-training stimulus on the list. |
Ingredients (8)
NAC
- Dose
- unspecified
- Mechanism
- N-acetyl cysteine is a precursor to glutathione, the body's primary intracellular antioxidant; also has direct mucolytic activity and modulates glutamate signaling.
- Take
- Dose not stated. Standard supplement dosing is 600–1,800 mg/day. The 'detox' framing is more popular-science than mechanism-accurate — NAC's strongest evidence is acetaminophen overdose (clinical), mucolytic use, and trichotillomania/OCD/addiction (moderate). Generic 'oxidation reduction' is the weakest of the supported claims.
Creatine Monohydrate
- Dose
- unspecified
- Mechanism
- Increases muscle and brain phosphocreatine stores, accelerating ATP regeneration during high-intensity work and supporting cognitive performance under metabolic stress.
- Take
- Dose not stated. Standard is 5 g/day, no loading needed. The most evidence-backed item on the list — strong for strength and lean mass, increasingly clear for cognition under sleep deprivation. Hard to mis-dose; hard to argue with.
Black seed oil
- Dose
- unspecified
- Mechanism
- Nigella sativa seed oil; thymoquinone is the principal active. Modest anti-inflammatory effects, with human trial data on blood pressure, fasting glucose, and lipid markers.
- Take
- Dose not stated. Trials use 1–3 g/day. Real but modest cardiometabolic effects — small BP and lipid improvements in meta-analyses, weaker on broad 'anti-inflammatory' claims. Reasonable inclusion at the right dose, but redundant with nattokinase and D3+K2 on the same axis.
Magnesium glycinate/chloride
- Dose
- unspecified
- Mechanism
- Cofactor for >300 enzymes including those in ATP utilization and neuromuscular transmission; modulates GABAergic tone supporting sleep architecture and HRV.
- Take
- Dose not stated. Glycinate is well-tolerated and doses of 200–400 mg elemental magnesium move sleep and recovery markers; chloride is more typical of transdermal use and harder to bioavailability-track. Author covers both without saying which one or how much, which is the only real ambiguity here.
Collagen peptides
- Dose
- unspecified
- Mechanism
- Hydrolyzed collagen contains bioactive di-/tripeptides (notably Pro-Hyp and Hyp-Gly) that signal fibroblasts and chondrocytes; most amino acids enter the general pool, but the signaling fragments are the proposed differentiator from generic protein.
- Take
- Dose not stated. Trials show benefit at 10–20 g/day (skin elasticity at the lower end, joint pain at the higher end). Below ~10 g/day this becomes expensive amino-acid powder. Worth disclosing the dose.
Vitamin D3
- Dose
- unspecified
- Mechanism
- Steroid hormone with receptors throughout the body; regulates calcium/phosphate, immune function, and Leydig cell T synthesis. Repleting deficiency has broad effects across many endpoints.
- Take
- Dose not stated. The 'optimizing vit D in winter' framing implies the author already knows what they're doing — winter is the right time and the right framing. 2,000–5,000 IU/day brings most adults into the 40–60 ng/mL target range; pairing with K2 is the right move at this dose.
Vitamin K2
- Dose
- unspecified
- Mechanism
- Activates osteocalcin and matrix Gla protein, directing calcium toward bone and away from arterial walls; pairs with high-dose D3 to mitigate vascular calcification risk.
- Take
- Dose not stated. Standard is 100–200 mcg MK-7. Sensible and well-paired with D3, especially during winter dosing. No standalone testosterone or longevity claim — this is correct insurance pairing.
Nattokinase
- Dose
- unspecified · Daily
- Mechanism
- Serine protease isolated from Bacillus subtilis natto fermentation; degrades fibrin, modestly reduces fibrinogen and blood pressure in human trials.
- Take
- Dose not stated. Standard is 2,000 FU/day. Real but small effects on BP and fibrinogen; some lipid signal. The 'plaque reversal' claim is overstatement — there's no human RCT demonstrating regression of atherosclerotic plaque from nattokinase. Sensible inclusion as a fibrinolytic adjunct, not a substitute for actual lipid management.
Risks & interactions
- 'Plaque reversal' claim on nattokinase is unsupportedmedium
Nattokinase has demonstrated fibrinolytic activity and small effects on systolic blood pressure and fibrinogen in meta-analyses. There is no human RCT showing it regresses atherosclerotic plaque burden — that claim is recurring in supplement marketing but not in the literature. A reader optimizing for actual cardiovascular risk should look at lipid management (statins, EPA, lifestyle) rather than expecting plaque regression from a fibrinolytic enzyme.
- Nattokinase + antiplatelets/anticoagulantsmedium
Nattokinase has additive effects with aspirin, warfarin, DOACs, and clopidogrel via fibrinolysis and platelet modulation. Stacking is plausible bleeding-risk territory, especially around surgery or dental procedures. Brett doesn't mention concurrent anticoagulants, but anyone reading and copying this stack who is on blood thinners should not add nattokinase without coordinating with their clinician.
- Doses unspecified across the entire stacklow
None of the seven items have doses listed. Most of these compounds have well-established standard doses (5 g creatine, 2,000 FU nattokinase, ~300 mg magnesium glycinate, 4,000 IU D3, 100–200 mcg MK-7, 10–20 g collagen, 600–1,800 mg NAC, 1–3 g black seed oil), so a reader with context can fill in the blanks. But explicit disclosure is good practice and avoids the assumption.
The biggest evidence gap here is omega-3. Black seed oil and nattokinase do small amounts of work on the same axes — BP, lipids, inflammation — that high-dose EPA/DHA does much more thoroughly, with cardiovascular outcome trials behind it (REDUCE-IT, JELIS) that none of the items currently on the list have. For a stack pitched as 'cheap, safe and high ROI' for cardiovascular healthspan, fish oil is the single most-supported addition the author isn't already taking.
Estimated cost
Retail commodity-supplement pricing across the seven items: collagen peptides and nattokinase carry the bulk of the cost; creatine, NAC, magnesium, and D3+K2 are inexpensive. Bulk or stack-bundle pricing can pull the low end down to ~$60.