Dave Asprey - 7 Brain Compounds I Take For Superhuman Focus
7 Brain Compounds YT video
Anybody feel like weighing in on this? Not heard of most of these.
Here is the list:
[1:42]Sulbutiamine [3:01]Sarcosine [4:15]Uridine [5:10]Thunbergia Lauriforia [6:40] (Thai Tea compound) Dileucine [8:09]Tudca [9:25] ACE-167 - Oral peptide.
In the video 7 Brain Compounds I Take For Superhuman Focus, biohacking advocate Dave Asprey outlines seven oral compounds intended to enhance cognitive performance, metabolic efficiency, hepatic protection, and endocrine output. Asprey’s central thesis posits that cognitive deficits, executive fatigue, and physical decline stem primarily from sub-optimal cellular bioenergetics, impaired neurotransmitter receptor sensitivity, and systemic inflammation rather than chronological aging. To address these vectors, he presents a heterogeneous stack of synthetic vitamin derivatives, amino acid metabolites, plant extracts, bile acid derivatives, and investigational peptides.
From a translational medicine perspective, the presentation mixes clinically validated interventions with severe translational leaps and unverified experimental compounds. The seven compounds discussed are:
While compounds such as di-leucine and TUDCA possess solid mechanistically backed human clinical trials (Paulussen et al., 2021; Kars et al., 2010), others rely on extrapolation from psychiatric disease models (sarcosine in schizophrenia/major depression) or animal models (Thunbergia laurifolia). Most critically, the assertion that ACE-167 serves as an established, safe oral hormone booster for healthy adults represents a major translational gap unsupported by published human clinical safety data.
| Claim from Video | Speaker’s Evidence | Scientific Reality (Current Data) | Evidence Grade | Verdict |
|---|---|---|---|---|
| Sulbutiamine enhances dopamine receptor sensitivity, brain energy, and focus in healthy individuals. | Cited 1960s research, memory/attention studies in cognitive decline, and biohacker use. | Synthetic lipophilic B1 prodrug that elevates central ThTP levels. Clinical efficacy is established for post-infectious asthenia (Starling-Soares et al., 2020) and as an adjunct in early Alzheimer’s (Ollat et al., 2007). Nootropic focus enhancement in healthy, thiamine-replete adults lacks rigorous human RCT proof. | Level C | Plausible |
| Sarcosine targets the glutamate/glycine system to eliminate anhedonia and boost cognitive performance. | Cited antidepressant trial additions and glutamate-glycine brain communication mechanism. | Sarcosine is a potent GlyT1 inhibitor that elevates synaptic glycine to co-activate NMDA receptors. Human RCTs show efficacy in schizophrenia negative symptoms and Major Depressive Disorder vs citalopram (Lane et al., 2008; PMC5652016). No trials exist for nootropic use in healthy cohorts. High doses carry theoretical excitotoxicity and oncogenic risks. | Level B | Plausible (In MDD/Psychiatric contexts) / Speculative (In healthy adults) |
| Uridine builds phospholipids and creates neural connections without stimulant side effects. | Cited animal studies on neural connections and presence in commercial nootropic stacks. | Uridine feeds the Kennedy pathway for phosphatidylcholine synthesis. In animal models, it increases dendritic spine density when paired with DHA/choline (PMC8139993). Human clinical data is limited to multinutrient medical foods (Souvenaid) in mild cognitive impairment (Soininen et al., 2017). Monotherapy in healthy humans is unproven. | Level D | Translational Gap |
| Thunbergia laurifolia reduces neuroinflammation, stress, and aging damage via natural dopamine pathways. | Cited traditional Thai herbal tea use and high polyphenol/antioxidant content. | In vitro and rodent studies confirm T. laurifolia contains rosmarinic/caffeic acid that attenuates hepatic fibrosis and ROS (PMC5749275; PMC12207397). Zero human clinical trials exist evaluating neuroprotection, dopamine modulation, or executive function. Standardized supplements do not exist. | Level D | Translational Gap |
| Di-leucine is 42% more effective than regular leucine at stimulating muscle protein synthesis (MPS). | Cited acute clinical trials comparing di-leucine to monomeric L-leucine. | Human tracer study (Paulussen et al., 2021) confirmed 2g oral di-leucine stimulated fractional synthetic rate (FSR) of muscle protein synthesis ~42% more than 2g free L-leucine at rest. Recent training trials (Hagele et al., 2024) confirm performance gains. | Level B | Strong Support |
| TUDCA daily supplementation (500–1000 mg) protects the liver and yields a “liver biological age of 10.” | Personal FibroScan diagnostic result and liver enzymatic processing capacity. | TUDCA acts as an ER chemical chaperone. Human RCT (Kars et al., 2010; 1,750 mg/day) showed a 30% increase in liver/muscle insulin sensitivity in obese adults. FibroScan measures tissue stiffness (kPa) and steatosis (CAP), not “biological age.” Claiming a “liver age of 10” is an unvalidated diagnostic interpretation. | Level B (for ER stress/insulin sensitivity) / Level E (for FibroScan “biological age”) | Strong Support(For metabolic mechanism) / Unsupported(For “liver age of 10”) |
| ACE-167 is an orally active peptide that restores LH sensitivity and naturally boosts testosterone. | Speaker assertion of upstream hormone promotion and natural TRT alternative. | ACE-167 is an early-stage investigational peptide targeting TSPO/steroidogenesis evaluated solely in preclinical animal/cell models (Acurx SEC Filing, 2023). Zero human peer-reviewed clinical trials exist regarding oral bioavailability, endocrine safety, or testosterone restoration. Source unverified in live search for human data. | Level D | Safety Warning(Safety Data Absent) |
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HUMAN CLINICAL EVIDENCE TIERING
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[ HIGH CONFIDENCE TIER ]
• Di-leucine: 2.0 g post-exercise or with meals to amplify mTORC1/MPS.
• TUDCA: 500–1,750 mg/day for ER stress & metabolic/insulin sensitivity.
[ EXPERIMENTAL TIER ]
• Sulbutiamine: 200–400 mg/day for post-infectious asthenia / thiamine deficit.
• Sarcosine: 1,000–2,000 mg/day (ONLY under psychiatric oversight for MDD).
• Uridine Monophosphate: 250–500 mg/day paired with Omega-3 (DHA) & Choline.
[ RED FLAG / SAFETY DATA ABSENT ZONE ]
• ACE-167: DO NOT USE. Pre-clinical peptide; 0 human clinical safety data.
• Thunbergia laurifolia: Lacks human standardization & clinical trials.
=======================================================
` BIOLOGICAL PATHWAY MAP
[ Sulbutiamine ] —> BBB Penetration —> ↑ Central ThTP/ThDP —> Choline Uptake
[ Sarcosine ] —> GlyT1 Blockade —> ↑ Synaptic Glycine —> NMDA Co-activation
[ Uridine ] —> CTP Catalysis —> Kennedy Pathway —> Phosphatidylcholine
[ Di-leucine ] —> Sestrin2 Binding —> mTORC1/p70S6K —> Translation Initiation
[ TUDCA ] —> ER Chaperoning —> UPR Suppression —> Insulin Receptor Signaling
[ ACE-167 ] —> TSPO Binding —> StAR Transport —> Cholesterol Steroidogenesis`
Sulbutiamine (O-isobutyrylthiamine disulfide) is formed by joining two modified thiamine molecules via a disulfide bridge. The addition of lipophilic isobutyrate moieties eliminates the positive quaternary nitrogen charge present in native thiamine, enabling rapid passive diffusion across the blood-brain barrier (BBB). Upon entering the central nervous system, intracellular thiamine pyrophosphokinase converts the molecule into active coenzymes: thiamine diphosphate (ThDP) and thiamine triphosphate (ThTP). ThDP is an essential cofactor for rate-limiting enzymes in glucose utilization, including pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase, and transketolase. ThTP directly modulates neuronal membrane permeability by phosphorylating voltage-gated sodium channels and upregulating high-affinity choline uptake (HACU) in hippocampal cholinergic terminals (Starling-Soares et al., 2020).
Glutamate-mediated neurotransmission requires obligatory co-agonist binding at the N-methyl-D-aspartate (NMDA) receptor complex. The NR1 subunit contains a specific glycine binding site (GlyB​) that must be occupied alongside glutamate binding on the NR2 subunit to open the ionotropic Ca2+ channel. Sarcosine (N-methylglycine) acts as a high-affinity competitive inhibitor of Glycine Transporter 1 (GlyT1), located on adjacent glial cells and presynaptic membranes. By inhibiting GlyT1, sarcosine prevents astrocytic reuptake of glycine, elevating extracellular glycine concentrations within the synaptic cleft from sub-saturating levels (~100 nM) to concentrations that fully occupy the GlyB​ site. This potentiates NMDA receptor-mediated long-term potentiation (LTP) in the prefrontal cortex and hippocampus, mitigating anhedonic symptoms (Lane et al., 2008).
Exogenous uridine monophosphate (UMP) is hydrolyzed in plasma to uridine, which crosses the BBB via equilibrative nucleoside transporters (ENT1/ENT2). Inside the neuronal cytoplasm, uridine is phosphorylated by uridine kinase to UTP. UTP is converted to cytidine triphosphate (CTP) by CTP synthetase. CTP reacts with phosphocholine via CTP:phosphocholine cytidylyltransferase—the rate-limiting step of the cytidine 5’-diphosphocholine (Kennedy) pathway—to generate CDP-choline. CDP-choline subsequently reacts with diacylglycerol (DAG) to form phosphatidylcholine, the major phospholipid component of neuronal cell membranes. Increased membrane phospholipid synthesis drives neurite outgrowth and dendritic spine formation when co-supplemented with polyunsaturated fatty acids (PMC8139993).
Di-leucine consists of two L-leucine residues linked by a peptide bond. Unlike monomeric amino acids that rely on sodium-independent L-type amino acid transporters (LAT1/SLC7A5), di-leucine is absorbed intact across enterocytes via the high-capacity H+/peptide cotransporter PepT1 (SLC15A1). This avoids competitive inhibition with other neutral amino acids at LAT1. Upon entry into skeletal myocytes, di-leucine binds with elevated affinity to Sestrin2, an intracellular leucine sensor. Binding to Sestrin2 causes its dissociation from GATOR2, relieving GATOR1-mediated inhibition of Rag GTPases. Activated Rag GTPases recruit Mechanistic Target of Rapamycin Complex 1 (mTORC1) to the lysosomal membrane, where Rheb stimulates mTORC1 kinase activity. This results in downstream hyper-phosphorylation of p70S6 kinase 1 (p70S6K) and eukaryotic initiation factor 4E-binding protein 1 (4E-BP1), triggering a ~42% increase in myofibrillar translation initiation compared to monomeric leucine (Paulussen et al., 2021).
Tauroursodeoxycholic acid (TUDCA) is a hydrophilic bile acid conjugate. Under conditions of metabolic overload or oxidative stress, misfolded proteins accumulate in the lumen of the endoplasmic reticulum (ER). TUDCA binds directly to hydrophobic regions of exposed, misfolded proteins, acting as a chemical chaperone that prevents toxic aggregation and facilitates proper refolding. This alleviates ER stress and attenuates the three canonical UPR stress sensors: PERK, IRE1-alpha, and ATF6. Suppression of PERK/IRE1-alpha prevents downstream activation of c-Jun N-terminal kinase (JNK) and IkappaB kinase (IKK), preserving insulin receptor substrate 1 (IRS-1) tyrosine phosphorylation. Consequently, downstream Akt/PKB phosphorylation is restored, improving hepatic and muscular insulin sensitivity by ~30% (Kars et al., 2010). Additionally, TUDCA acts as a agonist at the Farnesoid X Receptor (FXR) and G-protein coupled bile acid receptor 1 (TGR5), regulating bile acid synthesis via CYP7A1 downregulation and promoting GLP-1 secretion.
ACE-167 is an investigational peptide targeting Translocator Protein (TSPO) located on the outer mitochondrial membrane of testicular Leydig cells. In preclinical models, TSPO interacts with the Steroidogenic Acute Regulatory (StAR) protein to facilitate the rate-limiting import of free cholesterol from the outer to the inner mitochondrial membrane. Inside the inner membrane, cytochrome P450 side-chain cleavage enzyme (CYP11A1) converts cholesterol to pregnenolone, the obligate precursor for all downstream steroid hormones (including progesterone, dehydroepiandrosterone, and testosterone). While hypotheses suggest ACE-167 acts upstream to optimize Leydig cell response to luteinizing hormone (LH) stimulation, no published human clinical pharmacokinetic, pharmacodynamic, or safety data exist to confirm these preclinical observations (Acurx SEC Filing, 2023).
Produced by Gemini 2.5 Flash
Thanks to you and er…Mr/Ms Gemini 
Taking 7 supplements/drugs risks a non-trivial chance of a drug-drug interaction. The DDI risk could be checked with a frontier LLM, but I suspect that interaction data is missing for the less commonly used ones.
One way to have superhuman focus, or even maintain just human focus, is to avoid distractions. Listening to zero value added grifters like Dave Asprey is a distraction to avoid. Avoiding such distractions also allows you to have superhuman focus on legitimate health advice that adds to your QOL in addition to lifespan and healthspan. So avoid wasting time on frauds, and invest it in yourself by listening only to legitimate sources - Dave Asprey is the opposite of a legitimate source of health advice.
Unfortunately that does not work for me. I have been diagnosed with adult ADHD (actually really ADD). Plus my bout of Long Covid negatively affected my concentration and cognition.
I wouldn’t say Asprey is a fraud: he’s been at the forefront of biohacking for a long time, I think he’s veered off the path of sceptical inquiry by the lure of money - similar to Huberman and others.