What are the adverse effects and safety considerations of tongkat ali (Eurycoma longifolia) and fadogia agrestis?

Safety Profile of Tongkat Ali and Fadogia Agrestis

Both tongkat ali (Eurycoma longifolia) and fadogia agrestis have documented safety concerns, with tongkat ali showing a relatively favorable safety profile at standard doses while fadogia agrestis demonstrates clear testicular toxicity in animal studies that should raise significant caution for human use.

Tongkat Ali (Eurycoma longifolia) Safety Data

Acute Toxicity Profile

• The oral LD50 of alcoholic extract in mice is 1500-2000 mg/kg, while aqueous extract LD50 exceeds 3000 mg/kg 1
• At therapeutic doses (200 mg daily in humans), liver and renal function tests show no adverse changes with chronic use 1

Clinical Safety in Human Studies

• A study of 76 men with late-onset hypogonadism treated with 200 mg daily for 1 month showed no reported adverse effects 2
• The extract significantly improved testosterone levels and symptom scores without documented toxicity at this standard dose 2

Known Adverse Effects

• Allergic reactions: Tongkat ali can trigger allergic reactions in susceptible individuals and may be used in oral food challenge testing for spice allergies 3
• Skin reactions: Skin prick testing may be helpful in screening for allergic reactions to tongkat ali 3

Perioperative Safety

• Does not require discontinuation before surgery, unlike many supplements with antiplatelet effects or CNS depression properties, due to lack of significant bleeding risk or anesthetic interaction concerns 3

Traditional Use Side Effects

• Historically used for treating itches (topical leaf decoctions), suggesting potential for skin irritation in some individuals 1
• The plant has been used to treat various conditions including malaria, fever, and dysentery, but specific adverse effects from traditional use are not well-documented 1, 4

Fadogia Agrestis Safety Concerns

Testicular Toxicity (Animal Data)

• Significant testicular dysfunction documented in male rats at doses of 18,50, and 100 mg/kg body weight administered for 28 days 5
• Adverse effects include alterations in testicular cholesterol, sialic acid, glycogen, and multiple enzyme activities (acid phosphatase, gamma-glutamyl transferase, alkaline phosphatase, glutamate dehydrogenase) 5
• Decreased testicular protein concentrations observed at all tested doses 5

Dose-Dependent Recovery

• At the lowest dose (18 mg/kg), some testicular function indices showed recovery after 10 days of discontinuation 5
• Higher doses (50 and 100 mg/kg) showed less recovery potential, suggesting dose-dependent permanent damage 5
• The study authors concluded that fadogia agrestis "may adversely affect the functional capacities of the testes" 5

Critical Safety Gap

• No human safety studies exist for fadogia agrestis - all available data comes from animal models 5
• The testicular toxicity observed in rats raises serious concerns about reproductive safety in men, particularly given that many users take these supplements specifically for testosterone enhancement

Comparative Risk Assessment

Tongkat Ali: Lower Risk Profile

• Established human safety data at 200 mg daily doses 2, 1
• LD50 values suggest wide therapeutic window 1
• Primary concern is allergic reactions in susceptible individuals 3
• No documented reproductive toxicity in humans at therapeutic doses 6

Fadogia Agrestis: Higher Risk Profile

• Clear testicular toxicity in animal models at multiple dose levels 5
• No human safety studies to establish safe dosing 5
• Potential for permanent reproductive damage at higher doses 5
• The irony that a supplement marketed for testosterone enhancement causes testicular dysfunction in animal studies is particularly concerning

Clinical Recommendations

For Tongkat Ali Use

• Screen for spice allergies before initiating supplementation, particularly in patients with history of food allergies 3
• Standard therapeutic dose is 200 mg daily of standardized water-soluble extract 2
• Monitor for allergic reactions (skin rash, pruritus, urticaria) during initial weeks of use 3
• No need to discontinue before surgical procedures 3
• Liver and renal function monitoring is not required at standard doses based on available safety data 1

For Fadogia Agrestis Use

• Exercise extreme caution given documented testicular toxicity in animal models 5
• If patients insist on use despite counseling, recommend the lowest possible dose (equivalent to 18 mg/kg in rat studies showed some recovery potential) 5
• Strongly advise against use in men concerned about fertility given clear reproductive toxicity signals 5
• Consider baseline and follow-up testosterone levels, semen analysis if fertility is a concern, and testicular examination 5
• Counsel patients that no human safety data exists and animal data shows concerning reproductive toxicity 5

Critical Pitfalls to Avoid

• Do not assume "natural" equals "safe" - fadogia agrestis demonstrates clear toxicity despite being a traditional remedy 5
• Do not combine multiple testosterone-boosting supplements without understanding individual safety profiles and potential additive toxicities 5
• Do not ignore allergic symptoms with tongkat ali - these can progress from mild skin reactions to more serious hypersensitivity 3
• Do not recommend fadogia agrestis to patients trying to conceive given documented testicular dysfunction in animal models 5