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Bulbine Natalensis

Bulbine natalensis
Evidence Level
Preliminary
6 Clinical Trials
4 Documented Benefits
1/5 Evidence Score

Bulbine natalensis (now classified as Bulbine latifolia) is a South African plant whose stem has a traditional use for male sexual function and is now sold as an ingredient in testosterone boosters. Its best-characterized compounds are anthraquinones such as knipholone. The testosterone claims come from rat studies: a water extract of the stem raised testosterone and luteinizing hormone and increased mating behavior at 25 and 50 mg/kg, while 100 mg/kg did not show the same pattern. The same research group found raised liver enzymes, slight liver and kidney tissue changes and less favorable blood lipids in rats after 14 days. Human trials of its effect on testosterone, libido or strength are lacking. The only human study is a 28-day safety study in 36 healthy men, reported as a conference abstract, which did not measure testosterone.

Studied Dose 650 mg/day of a branded product (ProLensis, 325 mg twice daily) for 28 days in the only human study, a safety study that did not measure testosterone. Rat studies used 25 to 100 mg/kg/day of a stem water extract for 7 to 14 days.
Active Compound Anthraquinones, including knipholone, bulbine-knipholone and 6'-O-methylknipholone. A rat study's screen of the stem extract also found saponins, cardiac glycosides, tannins and alkaloids. Which compound, if any, drives the rat hormone effects is not known.

Benefits

Short-term tolerance in a 28-day study of healthy men

In a double-blind, placebo-controlled study of 36 healthy men, 650 mg a day of a branded Bulbine natalensis product for 28 days left 27 of 29 blood, liver, kidney and heart measures no different from placebo; alkaline phosphatase and creatinine shifted slightly but stayed within normal ranges. It did not measure testosterone or libido and was reported only as a conference abstract.

Supported by Trial 1

Testosterone and pituitary hormones in male rats (animal data)

In male rats given a water extract of the stem by mouth, 25 and 50 mg/kg a day raised serum testosterone, luteinizing hormone and follicle-stimulating hormone, with the largest effects at 50 mg/kg, and estradiol fell. Results at 100 mg/kg were inconsistent, and in one study testosterone fell at that dose. The one human study did not measure testosterone.

Supported by Trial 3, Trial 4

Sexual behavior in male rats (animal data)

Over 7 days, 25 and 50 mg/kg of the stem extract increased mount, intromission and ejaculation frequency and penile reflexes in male rats and shortened the time to first mount, while 100 mg/kg produced the opposite pattern. These are rat findings, not evidence of effects on libido or erections in people.

Supported by Trial 2, Trial 5

Mating and fertility measures in rats (animal data)

In a reproductive study, 7 days of 25 or 50 mg/kg raised mating and fertility success indices in male rats, while litter numbers, sperm count and sperm motility did not differ from controls. In pregnant rats, 25 and 50 mg/kg did not change reproductive measures, but 100 mg/kg raised the embryo resorption rate. These are rat results only.

Supported by Trial 4, Trial 6

Mechanism of action

1

Pituitary and testicular signaling (rat data)

In rats, the extract raised luteinizing and follicle-stimulating hormones along with testosterone, and increased testis weight and several testicular enzyme, protein and cholesterol measures, which points to stimulation through the pituitary and testes. This has been shown only in rats.

2

Anthraquinone compounds

The plant contains anthraquinones such as knipholone, and several new ones have been isolated from the rhizome. Their link to the rat hormone effects is unknown. In a test of nine supplements labeled as containing the plant, these compounds were detected in only five, at 11.3 to 90.4 mg per daily dose.

3

Drug-metabolizing enzymes in cell studies

In lab studies, extracts and knipholones activated the pregnane X receptor in human liver cells, raised CYP3A4, CYP2C9, CYP1A2 and CYP2B6 activity, and increased expression of the gene for the drug transporter P-glycoprotein; a methanol extract also strongly inhibited CYP2C9. These cell findings have not been tested in people.

Clinical trials

1
Bulbine natalensis Safety in Healthy Men: 28-Day Placebo-Controlled Study (conference abstract)
PubMed

Placebo-controlled, double-blind study (randomization not described) of the short-term safety of a branded Bulbine natalensis product (ProLensis), presented as a poster at a sports nutrition conference and supported in part by a grant from Sports Nutrition Research, LTD. (Hofheins et al. 2012, J Int Soc Sports Nutr)

36 apparently healthy men (mean age 29.4) taking 325 mg twice daily (650 mg/day) or a matched placebo for 28 days; group sizes were not reported.

In 27 of 29 blood, liver, kidney, blood count and heart measures there was no difference from placebo. Alkaline phosphatase rose 3% versus a 3.8% fall on placebo, and creatinine fell 7.4% versus no change on placebo; all values stayed within normal clinical ranges. Testosterone, libido and performance were not measured. Published only as a conference abstract.

2
Animal Study (Male Rats): Sexual Behavior and Testosterone over 7 Days
PubMed

Rat study of an oral water extract of Bulbine natalensis stem at 25, 50 and 100 mg/kg for 7 days, with a phytochemical screen of the extract. (Yakubu et al. 2009, Int J Androl)

Male rats; no human participants.

At 25 and 50 mg/kg, mount, intromission and ejaculation frequency, penile reflexes, serum testosterone and luteinizing hormone rose, and mount and intromission latency fell. The 100 mg/kg dose produced the opposite pattern on these measures. Rat findings only.

3
Animal Study (Male Rats): Testicular and Hormone Markers over 14 Days
PubMed

Rat study of an oral water extract of Bulbine natalensis stem at 25, 50 and 100 mg/kg for 14 days, measuring testicular markers and reproductive hormones. (Yakubu et al. 2010, Pharm Biol)

60 male Wistar rats in four groups of 15.

All doses raised the testis-to-body weight ratio and several testicular enzyme and content measures. Testicular and serum testosterone, luteinizing hormone and follicle-stimulating hormone rose, with the largest effects at 50 mg/kg; at 100 mg/kg the serum hormone rise appeared only after 7 daily doses. Rat findings only.

4
Animal Study (Rats): Reproductive Toxicology in Males and Pregnant Females
PubMed

Rat study of an oral water extract of Bulbine natalensis stem at 25, 50 and 100 mg/kg a day, assessing mating, fertility, hormones and testis histology in males and pregnancy outcomes in females. (Yakubu et al. 2009, Theriogenology)

Male and female Wistar rats; no human participants.

At 25 and 50 mg/kg, mating and fertility indices, testosterone, luteinizing hormone and follicle-stimulating hormone rose in males; estradiol fell at all doses. The 100 mg/kg dose lowered testosterone and progesterone in males and raised the resorption index in pregnant females. Sperm count, motility and testis histology were normal. Rat findings only.

5
Animal Study (Male Rats): Liver and Kidney Function and Histology over 14 Days
PubMed

Rat study of an oral water extract of Bulbine natalensis stem at 25, 50 and 100 mg/kg for 14 days, measuring liver and kidney function markers and tissue histology. (Afolayan et al. 2009, J Med Food)

Male Wistar rats; no human participants.

Serum ALT, AST, ALP and GGT, total bilirubin, globulin and urea rose, while albumin and conjugated bilirubin fell and serum creatinine and electrolytes did not change; liver and kidney weight relative to body weight fell at 50 and 100 mg/kg. Histology showed slight distortions of liver lobules and kidney tubules. The authors concluded the extract is not completely safe as an oral remedy. Rat findings only.

6
Animal Study (Male Rats): Blood Counts and Blood Lipids over 14 Days
PubMed

Rat study of an oral water extract of Bulbine natalensis stem at 25, 50 and 100 mg/kg for 14 days, measuring blood counts and serum lipids. (Yakubu et al. 2009, Indian J Exp Biol)

Male Wistar rats; no human participants.

Red blood cell measures did not change, but white blood cell counts rose. All doses raised serum cholesterol and triglycerides; HDL cholesterol fell and the atherogenic index rose, while LDL did not change. Rat findings only.

Side effects and drug interactions

Common Potential side effects

Liver and kidney (animal data): in male rats given 25 to 100 mg/kg of a stem water extract for 14 days, liver enzymes (ALT, AST, ALP, GGT) and bilirubin rose and tissue showed slight liver and kidney changes. Stop and see a doctor for yellowing skin or eyes, dark urine or unusual tiredness.
Human safety data come from one 28-day study of 36 healthy men at 650 mg a day, reported only as a conference abstract: most measures matched placebo, with small shifts in alkaline phosphatase and creatinine within normal ranges. Longer-term human safety is unknown.
Blood lipids and white cells (animal data): in rats, 14 days of the extract raised cholesterol and triglycerides, lowered HDL cholesterol and raised white blood cell counts.
Pregnancy and hormones: at 100 mg/kg the extract lowered testosterone in male rats and raised embryo resorption in pregnant rats. There are no human pregnancy or breastfeeding data, so avoid it then.
Product content varies: in a test of nine supplements labeled as containing Bulbine natalensis, its marker anthraquinones were detected in only five.

Important Drug interactions

Medicines cleared by CYP3A4 or CYP2C9: in cell studies the extract and its anthraquinones raised these enzymes, and it strongly inhibited CYP2C9 activity, which could change blood levels of such drugs. This has not been tested in people; ask a pharmacist before combining.
Medicines cleared by CYP1A2 or CYP2B6, or carried by P-glycoprotein: extracts raised these enzymes and the transporter gene in cell studies; the clinical relevance is unknown.
Testosterone therapy and other hormone treatments: the extract changed testosterone, luteinizing hormone, follicle-stimulating hormone and estradiol in rats, so tell your prescriber.
Drugs or supplements that can strain the liver or kidneys: avoid combining, given the liver enzyme and tissue changes seen in rats.

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Frequently asked questions about Bulbine Natalensis

Has Bulbine natalensis been tested in people?

Only in one small safety study: 36 healthy men took 650 mg a day of a branded product or placebo for 28 days, reported as a conference abstract. Most blood, liver, kidney and heart measures matched placebo. It did not measure testosterone, libido or strength, so there is no human evidence for those effects.

Does Bulbine natalensis raise testosterone?

In rats, a stem extract at 25 and 50 mg/kg raised testosterone and luteinizing hormone, but 100 mg/kg did not show the same pattern and lowered testosterone in one study. The one human study did not measure testosterone, so the rat results cannot be assumed to apply to people.

How do the rat doses compare with the dose used in people?

As our own rough calculation using the FDA body-surface-area method (rat dose divided by 6.2), and not a dose recommendation, the 25 to 100 mg/kg rat doses correspond to about 320 to 1,300 mg a day for an 80 kg adult. The 650 mg/day used in the human study falls inside that range, and in rats those doses raised liver enzymes and caused slight liver and kidney tissue changes over 14 days, although in the 28-day human study liver markers other than a small alkaline phosphatase rise did not differ from placebo. The branded product's extraction method was not reported, so the amounts may not be directly comparable.

Do products labeled with Bulbine natalensis match their labels?

Not reliably. When researchers tested nine supplements labeled as containing Bulbine natalensis, its marker anthraquinones were detected in only five, at 11.3 to 90.4 mg per daily dose. The plant's marker compounds were not detected in the other four.

What is Bulbine Natalensis?

Bulbine natalensis (now classified as Bulbine latifolia) is a South African plant whose stem has a traditional use for male sexual function and is now sold as an ingredient in testosterone boosters. Its best-characterized compounds are anthraquinones such as knipholone.

What is Bulbine Natalensis used for?

NutraSmarts does not list Bulbine Natalensis under a health category. What the research covers: In a double-blind, placebo-controlled study of 36 healthy men, 650 mg a day of a branded Bulbine natalensis product for 28 days left 27 of 29 blood, liver, kidney and heart measures no different from placebo; alkaline phosphatase and creati…

What is the recommended dosage of Bulbine Natalensis?

The clinically studied dose is 650 mg/day of a branded product (ProLensis, 325 mg twice daily) for 28 days in the only human study, a safety study that did not measure testosterone. Rat studies used 25 to 100 mg/kg/day of a stem water extract for 7 to 14 days. Always follow the product label and check with a healthcare provider for personal advice.

Is Bulbine Natalensis safe, and does it have side effects?

Side effects and cautions reported for Bulbine Natalensis include: Liver and kidney (animal data): in male rats given 25 to 100 mg/kg of a stem water extract for 14 days, liver enzymes (ALT, AST, ALP, GGT) and bilirubin rose and tissue showed slight liver and kidney changes. It may also interact with some medications. Bulbine Natalensis is not right for everyone, so check with a healthcare provider first if you are pregnant or breastfeeding, have a medical condition, or take prescription medication.

Does Bulbine Natalensis interact with any medications?

Possible interactions include: Medicines cleared by CYP3A4 or CYP2C9: in cell studies the extract and its anthraquinones raised these enzymes, and it strongly inhibited CYP2C9 activity, which could change blood levels of such drugs. This has not been tested in people; ask a pharmacist before combining. If you take prescription medication, check with a pharmacist or doctor before using it.

How strong is the scientific evidence for Bulbine Natalensis?

NutraSmarts rates the evidence for Bulbine Natalensis as Preliminary (1 out of 5). It is backed by 6 study summaries and 11 cited references summarized on this page. A higher rating reflects more, larger, and better-designed human studies.

References(11 citations)

Evidence ratings on NutraSmarts are based on the totality of human clinical research, with emphasis on randomized controlled trials, meta-analyses, and systematic reviews. The references below directly support claims made throughout this page.

  1. Hofheins JE, Habowski SM, Ziegenfuss TN, Lopez HL. Short term safety of bulbine natalensis supplementation in healthy men J Int Soc Sports Nutr. 2012;9(Suppl 1):P33. doi: 10.1186/1550-2783-9-S1-P33.SourceUsed to support: Not PubMed-indexed: a conference poster abstract (9th ISSN Conference, 2012) available in PubMed Central as PMC3500755. Placebo-controlled, double-blind study in 36 healthy men taking 650 mg/day of ProLensis or placebo for 28 days: 27 of 29 safety measures did not differ; alkaline phosphatase and creatinine shifted slightly within normal ranges. Testosterone was not measured. Supported in part by a grant from Sports Nutrition Research, LTD.
  2. Yakubu MT, Afolayan AJ. Effect of aqueous extract of Bulbine natalensis (Baker) stem on the sexual behaviour of male rats. Int J Androl. 2009;32(6):629-36. doi: 10.1111/j.1365-2605.2008.00910.x.PubMedUsed to support: Rat study: 7 days of 25 and 50 mg/kg of the stem water extract increased mount, intromission and ejaculation frequency, penile reflexes, serum testosterone and luteinizing hormone; 100 mg/kg produced the opposite pattern. The extract contained saponins, cardiac glycosides, tannins, alkaloids and anthraquinones. Animal data only.
  3. Yakubu MT, Afolayan AJ. Anabolic and androgenic activities of Bulbine natalensis stem in male Wistar rats. Pharm Biol. 2010;48(5):568-76. doi: 10.3109/13880200903207094.PubMedUsed to support: Rat study in 60 male Wistar rats: 14 days of 25, 50 or 100 mg/kg raised testis weight ratio, testicular markers, testicular and serum testosterone, luteinizing hormone and follicle-stimulating hormone, most at 50 mg/kg; at 100 mg/kg the serum hormone rise appeared only after 7 doses. Animal data only.
  4. Yakubu MT, Afolayan AJ. Reproductive toxicologic evaluations of Bulbine natalensis Baker stem extract in albino rats. Theriogenology. 2009;72(3):322-32. doi: 10.1016/j.theriogenology.2009.01.026.PubMedUsed to support: Rat study: 25 and 50 mg/kg raised mating and fertility indices and testosterone, luteinizing hormone and follicle-stimulating hormone in males, with no change in litter numbers or sperm measures; estradiol fell at all doses. 100 mg/kg lowered testosterone and progesterone in males and raised the resorption index in pregnant females. Animal data only.
  5. Afolayan AJ, Yakubu MT. Effect of Bulbine natalensis Baker stem extract on the functional indices and histology of the liver and kidney of male Wistar rats. J Med Food. 2009;12(4):814-20. doi: 10.1089/jmf.2008.0221.PubMedUsed to support: Rat study: 14 days of 25 to 100 mg/kg raised serum ALT, AST, ALP, GGT, total bilirubin, globulin and urea and caused slight distortions of liver lobules and kidney tubules; the authors concluded the extract is not completely safe as an oral remedy. Animal data only.
  6. Yakubu MT, Afolayan AJ. Effect of aqueous extract of Bulbine natalensis Baker stem on haematological and serum lipid profile of male Wistar rats. Indian J Exp Biol. 2009;47(4):283-8..PubMedUsed to support: Rat study: 14 days of 25 to 100 mg/kg did not change red blood cell measures but raised white blood cell counts, raised serum cholesterol and triglycerides, lowered HDL cholesterol and raised the atherogenic index. Animal data only.
  7. Husain I, Manda V, Alhusban M, Dale OR, Bae JY, Avula B, Gurley BJ, Chittiboyina AG, Khan IA, Khan SI. Modulation of CYP3A4 and CYP2C9 activity by Bulbine natalensis and its constituents: An assessment of HDI risk of B. natalensis containing supplements. Phytomedicine. 2021;81:153416. doi: 10.1016/j.phymed.2020.153416.PubMedUsed to support: Cell study: a methanol extract activated the pregnane X receptor in human liver (HepG2) cells and raised CYP3A4 and CYP2C9 expression and activity; knipholone was the most potent constituent. The extract and its anthraquinones strongly inhibited CYP2C9 and weakly inhibited CYP3A4. The authors call for studies of clinical relevance.
  8. Husain I, Dale OR, Manda V, Ali Z, Gurley BJ, Chittiboyina AG, Khan IA, Khan SI. Bulbine natalensis (currently Bulbine latifolia) and select bulbine knipholones modulate the activity of AhR, CYP1A2, CYP2B6, and P-gp. Planta Med. 2022;88(12):975-984. doi: 10.1055/a-1557-2113.PubMedUsed to support: Cell study: water and methanol extracts and knipholones raised CYP2B6 and CYP1A2 activity and expression of the P-glycoprotein gene (ABCB1) and activated the aryl hydrocarbon receptor; the methanol extract also inhibited CYP1A2 and CYP2B6. Notes the plant is currently classified as Bulbine latifolia.
  9. Bae JY, Avula B, Wang YH, Wang M, Ali Z, Viljeon AM, Khan IA. Development and Validation of a UHPLC-PDA-MS Method for the Quantitative Analysis of Anthraquinones in Bulbine natalensis Extracts and Dietary Supplements. Planta Med. 2020;86(2):144-150. doi: 10.1055/a-1037-4051.PubMedUsed to support: Analytical study: of nine dietary supplements labeled as containing Bulbine natalensis, anthraquinone-type marker compounds were detected in only five, at a total of 11.3 to 90.4 mg per daily dose.
  10. Bae JY, Ali Z, Wang YH, Chittiboyina AG, Zaki AA, Viljoen AM, Khan IA. Anthraquinone-Based Specialized Metabolites from Rhizomes of Bulbine natalensis. J Nat Prod. 2019;82(7):1893-1901. doi: 10.1021/acs.jnatprod.9b00187.PubMedUsed to support: Chemistry study: six previously unreported anthraquinone derivatives and eight known compounds were isolated from Bulbine natalensis rhizomes. Lab work only.
  11. Bodede O, Prinsloo G. Ethnobotany, phytochemistry and pharmacological significance of the genus Bulbine (Asphodelaceae). J Ethnopharmacol. 2020;260:112986. doi: 10.1016/j.jep.2020.112986.PubMedUsed to support: Review of the genus Bulbine: anthraquinones are its most abundant compounds, reported activities come from lab and animal bioassays, and the authors state that the therapeutic potential still needs confirmation in preclinical and clinical studies.