Quick Comparison
| B-Complex | Creatine | |
|---|---|---|
| Half-Life | Water-soluble; excreted daily (except B12 which is stored) | 3 hours (plasma), but tissue stores persist for weeks |
| Typical Dosage | Standard: A quality B-complex providing 25-100 mg of B1, B2, B3, B5, B6, plus 400-800 mcg folate (as methylfolate) and 500-1000 mcg B12 (as methylcobalamin). Methylated forms preferred for B9 and B12 (folate → methylfolate, B12 → methylcobalamin). Take in the morning — B vitamins can be mildly energizing. | Standard: 3-5 g daily (no loading phase needed for cognitive effects). Loading (optional): 20 g daily for 5-7 days, then 3-5 g maintenance. Creatine monohydrate is the most studied form. |
| Administration | Oral (capsules, tablets, sublingual). Methylated forms preferred for B9 and B12. Take with breakfast. | Oral (powder, capsules). Creatine monohydrate is the gold standard form with the most research support. |
| Research Papers | 10 papers | 10 papers |
| Categories |
Mechanism of Action
B-Complex
Each B vitamin serves specific neurological functions: B1 (thiamine) — cofactor for transketolase (pentose phosphate pathway), pyruvate dehydrogenase, and alpha-ketoglutarate dehydrogenase; essential for glucose metabolism and ATP production in neurons. B2 (riboflavin) — precursor to FAD/FMN, cofactors for Complex I and II of the electron transport chain, and glutathione reductase. B3 (niacin/niacinamide) — precursor to NAD+/NADPH via the salvage pathway; NAD+ is substrate for sirtuins, PARP, and 400+ dehydrogenases. B5 (pantothenic acid) — component of coenzyme A, required for acetylcholine synthesis via choline acetyltransferase and for fatty acid oxidation. B6 (pyridoxine) — cofactor for AADC (5-HTP to serotonin, L-DOPA to dopamine), GABA synthesis (GAD), and homocysteine metabolism. B9 (folate) — tetrahydrofolate donates methyl groups for dTMP and purine synthesis, and for homocysteine remethylation. B12 (cobalamin) — cofactor for methionine synthase (myelin maintenance) and methylmalonyl-CoA mutase.
Creatine
Creatine is phosphorylated by mitochondrial creatine kinase (CK-Mt) to form phosphocreatine (PCr), which serves as a rapidly mobilizable high-energy phosphate reserve. When neuronal ATP is consumed during demanding tasks (synaptic vesicle cycling, ion pump activity, action potential propagation), cytosolic brain-type creatine kinase (CK-BB) catalyzes the transfer of the phosphoryl group from PCr to ADP, regenerating ATP within milliseconds — far faster than oxidative phosphorylation or glycolysis can respond. This PCr/CK shuttle also transports high-energy phosphates from mitochondria to distant synaptic sites. Creatine provides direct neuroprotection by stabilizing the mitochondrial permeability transition pore (mPTP), preventing cytochrome c release and downstream apoptotic cascades. It scavenges reactive oxygen species by acting as a direct antioxidant against superoxide and peroxynitrite. Creatine also increases GLUT4 expression in neurons, improving glucose uptake, and upregulates brain-derived neurotrophic factor (BDNF) expression in the hippocampus, supporting synaptic plasticity and memory consolidation.
Risks & Safety
B-Complex
Common
Bright yellow urine (harmless — riboflavin excretion), mild nausea.
Serious
Very safe at standard doses. B6 can cause peripheral neuropathy at >200 mg daily for extended periods.
Rare
Flushing from niacin (B3) if non-flush form is not used.
Creatine
Common
Water retention (mild weight gain), gastrointestinal discomfort at high doses.
Serious
Very safe — one of the most studied supplements in existence. No kidney damage in healthy individuals.
Rare
Muscle cramping, dehydration if water intake is insufficient.
Full Profiles
B-Complex →
The B vitamins (B1, B2, B3, B5, B6, B9, B12) are essential coenzymes in brain energy metabolism, neurotransmitter synthesis, and methylation reactions. Deficiency in any B vitamin impairs cognitive function. B12 and folate deficiency specifically cause irreversible neurological damage if untreated. A high-quality B-complex is foundational for any nootropic regimen, particularly for vegetarians, older adults, and those under chronic stress.
Creatine →
Best known as a sports supplement, creatine is increasingly recognized as one of the most effective cognitive enhancers available — particularly for vegetarians, the sleep-deprived, and older adults. It serves as a rapid energy buffer for neurons by recycling ATP, the cell's primary energy currency. The brain consumes enormous amounts of ATP, making creatine supplementation directly relevant to cognitive performance.