Fisetin vs Tesofensine

Side-by-side comparison of mechanisms, dosing, interactions, and stacking potential.

FisetinTesofensine
CategoryPharmaceuticalsPharmaceuticals
Standard DoseResearch indicates 20 mg/kg/day for 2 consecutive days as an intermittent senolytic protocol (approximately 1400-2000 mg for a 70-100 kg individual).Research indicates 0.25-0.5 mg daily via oral administration.
TimingTake with fat-containing meal for improved bioavailability (fisetin is lipophilic with poor water solubility). Liposomal or lipophilic formulations preferred.Morning dosing only. Avoid afternoon/evening dosing due to stimulant properties and potential insomnia.
Cycle DurationIntermittent senolytic courses ongoing. Daily low-dose use for antioxidant/anti-inflammatory effects can be continuous.12-24 week cycles. Monitor cardiovascular parameters throughout.
Evidence Levelanimal_plus_anecdotalmoderate_human
A

Fisetin

Pharmaceuticals

Mechanism

Fisetin is a naturally occurring flavonol (3,7,3',4'-tetrahydroxyflavone) found in strawberries, apples, and persimmons that acts as a senolytic by inhibiting the PI3K/Akt/mTOR survival pathway and BCL-2 family anti-apoptotic proteins in senescent cells. It also activates sirtuin-mediated pathways (SIRT1), reduces NF-kB-driven inflammation, and scavenges free radicals as a direct antioxidant. Fisetin demonstrated the most potent senolytic activity among 10 flavonoids screened in a 2018 study, reducing senescent cell burden in aged mice and extending both healthspan and lifespan markers.

Standard Dosing

Research indicates 20 mg/kg/day for 2 consecutive days as an intermittent senolytic protocol (approximately 1400-2000 mg for a 70-100 kg individual).

Timing

Take with fat-containing meal for improved bioavailability (fisetin is lipophilic with poor water solubility). Liposomal or lipophilic formulations preferred.

Cycle Duration

Intermittent senolytic courses ongoing. Daily low-dose use for antioxidant/anti-inflammatory effects can be continuous.

Side Effects

  • GI discomfort at high senolytic doses
  • Diarrhea
  • Headache
  • Generally well-tolerated — no serious adverse events reported in clinical trials to date

Contraindications

  • Known hypersensitivity to fisetin or flavonoids
  • Pregnancy and breastfeeding (insufficient safety data)
  • Active chemotherapy without oncologist coordination

Best Stacking Partners

Dasatinib + Quercetin (complementary senolytic pathways)Spermidine (autophagy induction)Rapamycin (upstream senescence prevention)Omega-3 (anti-inflammatory synergy)
B

Tesofensine

Pharmaceuticals

Mechanism

Tesofensine (NS2330) is a triple monoamine reuptake inhibitor with affinity for dopamine (DAT), serotonin (SERT), and norepinephrine (NET) transporters. It suppresses appetite through indirect stimulation of alpha-1 adrenoceptor and dopamine D1 receptor pathways, reflecting additive effects of increased NE and DA activity. Tesofensine is a dual-action drug with both anorexigenic properties (appetite suppression) and metabolic properties (increased energy expenditure), silencing GABAergic hypothalamic neurons in the lateral hypothalamus.

Standard Dosing

Research indicates 0.25-0.5 mg daily via oral administration.

Timing

Morning dosing only. Avoid afternoon/evening dosing due to stimulant properties and potential insomnia.

Cycle Duration

12-24 week cycles. Monitor cardiovascular parameters throughout.

Side Effects

  • Increased heart rate
  • Elevated blood pressure
  • Dry mouth
  • Insomnia
  • Constipation
  • Nausea
  • Headache
  • Anxiety/restlessness

Contraindications

  • Uncontrolled hypertension
  • History of cardiovascular disease
  • Concurrent MAOI use
  • Glaucoma
  • Hyperthyroidism
  • Pregnancy and breastfeeding
  • History of seizures
  • Anorexia nervosa
  • Cardiovascular disease
  • Uncontrolled anxiety

Best Stacking Partners

AOD-96045-Amino-1MQ

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