Comparison
Alpha-Lipoic Acid vs Spermidine
Side-by-side of Alpha-Lipoic Acid and Spermidine. Every row below is pulled from the compound schema and will update as our data grows. For deeper reads, follow through to each compound page.
Alpha-Lipoic Acid
Alpha lipoic acid supplement guide: 600 mg/day oral dosing, R-ALA vs racemic absorption, neuropathy trial data, antioxidant mechanism, interactions.
Spermidine
Spermidine supplement benefits cover autophagy induction, longevity signals, and cognition. Wheat germ extract data, doses, and human trials reviewed.
Effects at a glance
Alpha-Lipoic Acid
- •Approved Rx for diabetic neuropathy in Germany at 600 mg/day IV (Thioctacid) since 1960s
- •Improves neuropathy symptoms (TSS, NIS) at 600 mg/day IV across ALADIN and SYDNEY trials
- •R-ALA enantiomer absorbs 40-100% better than racemic mixtures
- •Activates AMPK; produces small HbA1c reductions in T2DM
- •Plasma half-life ~30 minutes; split dosing or sustained-release is standard
- •Hypoglycemia risk with insulin or sulfonylureas; medication adjustment may be required
Spermidine
- •Endogenous polyamine that induces autophagy via EP300 acetyltransferase inhibition and TFEB activation
- •Concentrated in wheat germ, soybeans, aged cheese, and mushrooms; ~10 to 15 mg/day in Mediterranean diets
- •Eisenberg 2016 reported dietary spermidine extended mouse lifespan and improved cardiac function
- •Wirth 2018 pilot (n=28) reported cognitive signal at 0.9 mg/day in older adults at risk for dementia
- •Larger Wirth 2019 follow-up (n=85) did not replicate the memory benefit at 12 months
- •Generally regarded as safe at supplemental doses; food-source position is reassuring
Side-by-side
| Attribute | Alpha-Lipoic Acid | Spermidine |
|---|---|---|
| Category | supplement | supplement |
| Also known as | ALA, thioctic acid, R-ALA, R-lipoic acid | spermidine trihydrochloride, wheat-germ-extract spermidine |
| Half-life (hr) ↗ | 0.5 | 6 |
| Typical dose (mg) ↗ | 600 | 1.2 |
| Dosing frequency | 1 to 3 times daily on empty stomach | daily, typically morning with food |
| Routes | oral, iv | oral |
| Onset (hr) | 0.5 | 2 |
| Peak (hr) | 1 | 4 |
| Molecular weight | 206.33 | 145.25 |
| Molecular formula | C8H14O2S2 | C7H19N3 |
| Mechanism | Dual lipid- and water-soluble antioxidant; redox cycles with dihydrolipoic acid (DHLA) to scavenge ROS, regenerate vitamin E and C, and chelate transition metals. Activates AMPK in liver and muscle; cofactor for pyruvate and alpha-ketoglutarate dehydrogenase complexes. | Induces macroautophagy via inhibition of EP300 histone acetyltransferase and activation of TFEB-mediated lysosomal biogenesis. Substrate for hypusination of eIF5A, required for translation of mitochondrial respiration proteins. |
| Legal status | Dietary supplement (US, UK, Canada, most EU); prescription drug for diabetic neuropathy in Germany | OTC dietary supplement (wheat-germ extract has GRAS status in US) |
| WADA status | allowed | allowed |
| DEA / Rx | Not scheduled | OTC supplement (not scheduled) |
| Pregnancy | Insufficient data; precautionary avoidance | Insufficient data; not routinely recommended at supplemental doses |
| CAS | 62-46-4 | 124-20-9 |
| PubChem CID | 864 | 1102 |
| Wikidata | Q161227 | Q411089 |
Safety profile
Alpha-Lipoic Acid
Common side effects
- nausea
- abdominal discomfort
- diarrhea
- sulfurous odor
- rash (rare)
Contraindications
- pregnancy and lactation (insufficient safety data)
- active insulin autoimmune syndrome predisposition
Interactions
- insulin and sulfonylureas: additive hypoglycemia; medication dose adjustment may be required(major)
- thyroid hormone: may reduce T4 to T3 conversion at high doses(moderate)
- biotin: ALA competes with biotin uptake; chronic use can induce biotin insufficiency(minor)
- iron supplements: ALA chelates iron and reduces absorption; separate dosing(moderate)
- chemotherapy (oxidative-stress-dependent agents): theoretical interference; coordinate with oncology team(moderate)
Spermidine
Common side effects
- mild GI upset (rare)
- headache (rare)
Contraindications
- wheat-germ allergy or celiac disease (for wheat-germ-extract products)
- active cancer (theoretical)
- pregnancy and lactation (insufficient data)
Interactions
- DFMO (difluoromethylornithine): competing polyamine metabolism; do not combine without oncology guidance(moderate)
Which Should You Take?
Alpha-Lipoic Acid and Spermidine score evenly on the criteria we weight (goal breadth, legal accessibility, evidence depth). The conditionals below should drive the decision more than any aggregate score.
- → If your priority is metabolic health and glucose control, pick Alpha-Lipoic Acid.
- → If your priority is long-term neuroprotection, pick Alpha-Lipoic Acid.
- → If your priority is focus or working memory, pick Spermidine.
Edge case: Half-lives differ materially (Alpha-Lipoic Acid ~0.5 hr vs Spermidine ~6 hr). Spermidine reaches steady state faster; Alpha-Lipoic Acid is easier to dial in if tolerability is uncertain.
Default choice: either is defensible. Alpha-Lipoic Acid edges out on goal breadth + legal accessibility; Spermidine is the right call if your priority sits in the goals listed above.
This verdict is generated from each compound's schema (goals, legal status, evidence outcomes, dosing route). It updates automatically as our compound data evolves; the deeper read sits on each individual compound page.
Common questions
What is the difference between Alpha-Lipoic Acid and Spermidine?
Alpha-Lipoic Acid and Spermidine differ in category (supplement vs supplement), mechanism, and typical dosing. See the side-by-side table for full details.
Which has a longer half-life, Alpha-Lipoic Acid or Spermidine?
Alpha-Lipoic Acid half-life is 0.5 hours; Spermidine half-life is 6 hours.
Can you stack Alpha-Lipoic Acid with Spermidine?
Stack compatibility depends on mechanism overlap, legal status, and individual response. Check each compound page for specific interactions and contraindications before combining.
Go deeper