Tongkat Ali

Pharmacological Actions and Time to Effect
Tongkat Ali, scientifically known as Eurycoma longifolia, is a traditional herbal medicine with a wide range of potential pharmacological effects, supported by both in vitro and in vivo studies. Below is a detailed breakdown, including the time it takes for each action to manifest, based on clinical and preclinical evidence:

Male Fertility Enhancement: This action includes enhancing semen volume, spermatozoa count, and motility, as well as increasing testosterone production and improving erectile function and sexual libido. Studies show sperm motility increased by 44.4% and semen volume by 18.2% after 12 weeks of supplementation, with testosterone increases of 30.2% in rat models (source).
Antimalarial Effect: Effective against Plasmodium falciparum, with IC50, IC90, and IC99 values for extract at 14.72, 139.65, and 874.15 μg/L respectively, compared to artemisinin at 4.30, 45.48, and 310.97 μg/L. Time to effect is not well-documented in humans, primarily studied in vitro (source).
Cytotoxic and Anti-Proliferative Effects: Demonstrates cytotoxicity against cancer cell lines like A-549, MCF-7, and HeLa, with IC50 values for NF-κB inhibitors <1 μM and cell viability ranging from 21.01%–66.9% at 100 μM for HeLa cells. These effects are typically measured in vitro, with no specific time to effect in humans (source).
Antimicrobial Effects: Active against Gram-positive (Staphylococcus aureus) and Gram-negative (Pseudomonas aeruginosa) bacteria, with inhibition zones of 7–25 mm and minimum inhibitory concentrations of 75 mg/mL for S. aureus and 25 mg/mL for P. aeruginosa. Time to effect is not specified, as it’s primarily an in vitro measure (source).
Anti-Inflammatory Effects: Inhibits NF-κB with IC50 values <1 μM, activates Nrf2 via ROS-dependent p38 MAPK pathway, and shows antioxidant activity at 10–250 µg/mL. Time to effect in humans is not well-documented, but animal studies suggest rapid onset (source).
Anti-Anxiolytic Effects: Reduces anxiety in mice, similar to diazepam, and improves stress hormone profiles in humans, with significant effects observed after 4 weeks in clinical trials (source).
Antidiabetic Effects: Decreases blood glucose by 38%–47% at 150 mg/kg in hyperglycemic rats and enhances glucose uptake >200% at 50 μg/mL. Time to effect in humans is not specified, but animal studies suggest weeks of supplementation (source).
Osteoporosis Preventive Effects: Prevents bone calcium loss, stimulates osteoblast proliferation, and enhances testosterone levels, with no specific time to effect documented in humans, likely requiring chronic use (source).
Miscellaneous Effects: Includes hormonal (anti-estrogenic), ergogenic (increases muscle strength), insecticidal, muscular, antiulcer, and anti-rheumatism effects. For ergogenic effects, benefits are seen after 5-8 weeks, with Cmax and Tmax for eurycomanone at 0.33 ± 0.03 mcg/mL and 4.40 ± 0.98 h, respectively (source).

Pharmacokinetics
The pharmacokinetics of Tongkat Ali, particularly for its active compounds like eurycomanone, are crucial for understanding its efficacy and safety. Below are the detailed parameters:

Half-life: For eurycomanone, studies report a half-life of 0.35 ± 0.04 h in one study and 1.00 ± 0.26 h in another, suggesting variability possibly due to formulation or species (source). For 13α(21)-epoxy-eurycomanone, the half-life is 0.75 ± 0.25 h, longer due to lower elimination rate.
Bioavailability: Oral bioavailability for eurycomanone is 10.5%, with Cmax at 0.33 ± 0.03 mcg/mL and Tmax at 4.40 ± 0.98 h. For 9-methoxycanthin-6-one, absorption is <1% orally, indicating poor bioavailability for some compounds (source).
Distribution and Excretion: Eurycomanone has a volume of distribution (V_d) of 0.68 ± 0.30 L/kg, well distributed in extravascular fluids, with an elimination rate constant (k_e) of 0.88 ± 0.19 h⁻¹ and clearance (CL) of 0.39 ± 0.08 L/h/kg (source).
CYP Inhibition: Eurycomanone shows IC50 >250 μg/mL for CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2C19, CYP2E1, and CYP3A4, indicating a low likelihood of drug-herb interactions (source).

Dosage and Safety
Dosage recommendations and safety profiles are critical for practical use. Below is a detailed table summarizing the dosage ranges, safety data, and toxicity information:

Aspect	Details
General Dosing Range	100 to 800 mg daily, with specific uses like male infertility at 200 mg twice daily up to 3 months. (source)
Safe Range	Possibly safe at 200 mg daily for up to 9 months or 400 mg daily for 3 months (source)
Minimum Effective Dose	Often 100 mg daily for testosterone and muscle effects, varying by condition (source)
Maximum Safe Dose	Not clearly defined, but exceeding 800 mg daily is not recommended due to potential risks (source)
LD50	In mice, LD50 for alcoholic extract is 1500-2000 mg/kg, and for aqueous extract >3000 mg/kg, indicating low acute toxicity (source)
Risks at High Doses	Potential for DNA damage and genotoxicity, with positive results in chromosome aberration tests at 500-2500 μg/mL and in vivo comet assays at 2000 mg/kg bw, particularly affecting stomach and duodenum (source)
Side Effects	Possible mercury or lead poisoning from contaminated supplements, presence of sildenafil in some products, and rare cases of liver injury, especially in bodybuilders (source)