Home Ingredients Magnolol (Magnolia Bark Compound)

Magnolol (Magnolia Bark Compound)

Magnolia officinalis
Evidence Level
Preliminary
5 Clinical Trials
5 Documented Benefits
1/5 Evidence Score

Magnolol is a neolignan found in the bark of Magnolia officinalis, the tree behind the traditional herb hou po, and it sits alongside its close chemical relative honokiol in most magnolia bark extracts. In lab and animal work it boosts GABA-A receptor signaling, the brain's main calming system, and it slows the growth of several mouth bacteria. No published human trial has tested isolated magnolol taken as a supplement. The human studies that exist used magnolia bark extract in chewing gum or mints, held in the mouth rather than swallowed as capsules, or Relora, a magnolia plus phellodendron blend standardized to honokiol and berberine rather than magnolol. In rats, swallowed magnolol circulates mainly as glucuronide and sulfate conjugates. An extract that was about 94 percent magnolol was not genotoxic in bacterial and mouse tests and caused no treatment-related harm in rats fed it for 90 days.

Studied Dose No human trial has tested a dose of isolated magnolol taken as a supplement. Gum and mint studies used small amounts of magnolia bark extract (an EU-member assessment capped it at 3 mg per portion); Relora studies used 500 or 750 mg a day of a magnolia plus phellodendron blend.
Active Compound Magnolol (5,5'-diallyl-2,2'-biphenyldiol, also written 5,5'-di-2-propenyl-1,1'-biphenyl-2,2'-diol), a neolignan from Magnolia officinalis bark and a positional isomer of honokiol; high-purity magnolia bark extracts can be more than 90 percent magnolol.

Benefits

Breath freshness and mouth bacteria in gum and mint studies

In a nine-person study run by a gum maker, mints and gum containing magnolia bark extract lowered total saliva bacteria more than plain products for up to an hour, and in a 123-person trial a gum with the extract plus zinc cut breath sulfur compounds more than a plain gum for one hour. These products were held in the mouth, not swallowed as capsules.

Supported by Trial 1, Trial 3

Plaque acidity and gum bleeding scores in a 30-day chewing gum study

In a randomized double-blind study of 120 adults with high counts of cavity-linked bacteria, a sugar-free gum with magnolia bark extract, chewed daily for 30 days, lowered plaque acid production, salivary mutans streptococci and bleeding on probing compared with xylitol and control gums. The gum's magnolol content was not reported.

Supported by Trial 2

Stress and mood scores in magnolia plus phellodendron trials

Two small maker-funded trials of Relora, a magnolia plus phellodendron blend standardized to honokiol and berberine, reported lower short-term anxiety in 26 women and lower salivary cortisol and better mood scores in 56 stressed adults. Sleep, trait anxiety and cortisol did not differ from placebo in the first trial. Neither tested magnolol on its own.

Supported by Trial 5, Trial 4

Calming signals at GABA-A receptors in lab and animal studies

In brain neurons and in cells carrying recombinant GABA-A receptors, magnolol increased receptor responses, most strongly at a delta-containing subtype found outside synapses. In mice given magnolol by injection, its sleep effects were blocked by flumazenil, which points to the benzodiazepine site. None of this has been measured in people taking magnolol by mouth.

Supported by Trial 4

Sleep patterns in mouse studies

Mice injected with magnolol fell asleep sooner and spent more time in both non-REM and REM sleep over the next three hours, and the effect disappeared when the benzodiazepine-site blocker flumazenil was given. The magnolol was injected into the abdomen, not swallowed, and no human sleep study of magnolol exists.

Supported by Trial 4, Trial 3

Mechanism of action

1

Positive modulation of GABA-A receptors (lab and animal work)

In laboratory recordings, magnolol enhanced both fast synaptic and steady background GABA-A currents and modulated every receptor subunit combination tested, most strongly delta-containing receptors. In mice given magnolol by injection, flumazenil reversed its sleep effects, so at least part of its action runs through the benzodiazepine site. These findings come from animals and cells only.

2

Antibacterial action against mouth bacteria (lab data)

In test-tube work, magnolol, honokiol and magnolia bark extract stopped the growth of bacteria linked to breath odor and dental plaque (Porphyromonas gingivalis, Fusobacterium nucleatum and Streptococcus mutans) at about 8 to 31 micrograms per milliliter. These test-tube results, not infection studies in people, are the rationale for adding it to breath-freshening gum and mints.

3

Fast conjugation after swallowing

In rats given magnolol by mouth, sulfate and glucuronide conjugates dominated the bloodstream, while the free compound concentrated in tissues, highest in the liver. Human liver and intestine enzymes (mainly UGT2B7, plus UGT1A10 in the gut) glucuronidate magnolol, so much of a swallowed dose circulates in conjugated form.

Clinical trials

1
Magnolia Bark Extract Mints and Gum - Saliva Bacteria Study
PubMed

Laboratory testing plus a small in-mouth study of mints and chewing gum with magnolia bark extract, with Listerine mouthwash as a positive control, by authors at the Wm. Wrigley Jr. Company (Greenberg et al. 2007, J Agric Food Chem)

Nine healthy volunteers after lunch; saliva sampled before and after mints or gum with and without the extract.

Mints with the extract reduced total salivary bacteria by 61.6 percent at 30 minutes and 33.8 percent at 60 minutes, while flavorless mints reduced bacteria by 3.6 percent at 30 minutes and were followed by a 47.9 percent rise at 60 minutes. Gum with the extract lowered bacteria by 43.0 percent at 40 minutes versus 18.0 percent for placebo gum. Very small, short and maker-run; the extract was held in the mouth, not swallowed.

2
Magnolia Bark Extract Chewing Gum for 30 Days - RCT
PubMed

Randomized double-blind three-arm intervention comparing a sugar-free gum with magnolia bark extract, a xylitol gum and a control gum, chewed daily for 30 days (Campus et al. 2011, Caries Res)

120 healthy adults at high caries risk, with salivary mutans streptococci of at least 10^5 CFU/ml and bleeding on probing above 25 percent.

The magnolia gum significantly reduced plaque acidogenicity, salivary mutans streptococci and gingival bleeding compared with the xylitol and control gums. Within-group drops from baseline in mutans streptococci (p = 0.01) and plaque acidity (p = 0.01) were also seen. The abstract does not state the extract dose or its magnolol content.

3
Zinc Acetate Plus Magnolia Bark Extract Gum - Breath Sulfur RCT
PubMed

Controlled double-blind randomized study of a 2.23 g sugar-free gum with 0.012 percent zinc acetate and 0.15 percent magnolia bark extract versus a plain gum, measured over two hours (Porciani et al. 2012, J Clin Dent)

123 adults (67 men, 56 women, mean age 37) with oral volatile sulfur compounds of at least 75 ppb at baseline.

Sulfur compounds fell 50.9 percent after 10 minutes of chewing the test gum versus 31.2 percent for the plain gum, and 27.6 versus 6.9 percent after one hour; both between-group differences were significant, while the two-hour difference (13.6 versus 2.3 percent) was not reported as significant. The extract was combined with zinc, so its own share cannot be separated. No product problems were reported.

4
Relora (Magnolia Plus Phellodendron) Pilot in Women - RCT
PubMed

Randomized double-blind placebo-controlled pilot of Relora 250 mg three times daily for 6 weeks, funded by the maker Next Pharmaceuticals (Kalman et al. 2008, Nutr J)

40 overweight premenopausal women aged 20 to 50 with above-average anxiety scores; 26 completed.

Relora lowered state (short-term) anxiety versus placebo, but trait anxiety, salivary cortisol and amylase, appetite, body measures and sleep quality and latency did not differ. Three people left because of adverse events (two on Relora, one on placebo), with no serious events. The blend is standardized to honokiol and berberine, so the results cannot be credited to magnolol.

5
Relora for Cortisol and Mood in Stressed Adults - RCT
PubMed

Randomized double-blind placebo-controlled trial of Relora 250 mg twice daily (500 mg a day) for 4 weeks, funded by the maker Next Pharmaceuticals (Talbott et al. 2013, J Int Soc Sports Nutr)

56 adults (35 men, 21 women) screened for moderate stress.

Salivary cortisol exposure was 18 percent lower than placebo (p<0.05), and mood scores were better, including overall stress (11 percent lower), fatigue (31 percent lower) and vigor (18 percent higher). The product is a magnolia plus phellodendron blend standardized to honokiol and berberine; its magnolol content was not reported.

Side effects and drug interactions

Common Potential side effects

No human safety trial of isolated magnolol taken as a swallowed supplement has been published, so its tolerability at capsule doses is unknown.
Gum and mint studies with a few milligrams of magnolia bark extract per serving reported no product-related problems, but exposure was brief and mostly limited to the mouth.
In a 6-week trial of the magnolia plus phellodendron blend Relora, two people on the blend and one on placebo withdrew because of adverse events; no serious adverse events occurred.
Rat studies of a magnolia bark extract that was about 94 percent magnolol found no treatment-related harm at up to 240 mg/kg a day for 90 days, and the extract was not genotoxic in bacterial mutation and mouse micronucleus tests.
Magnolol enhances GABA-A receptor activity and promoted sleep in mice when injected, so drowsiness is plausible; avoid driving until you know how a product affects you.
In a 2010 second assessment under the EU novel food rules, the Dutch Novel Foods Unit (CBG-MEB) agreed with the UK's initial assessment that a gum maker's high-magnolol extract was safe as proposed, at up to 0.2 percent in breath-freshening gum and mints (no more than 3 mg per piece); supplement capsules were not assessed.
Pregnancy and breastfeeding: no human safety data; avoid.

Important Drug interactions

Sedatives, sleep medicines, benzodiazepines and alcohol: magnolol acts on GABA-A receptors, including the benzodiazepine site in mice, so added drowsiness is possible. No human interaction study exists.
In recombinant enzymes and human liver microsomes, magnolol selectively inhibited the glucuronidation enzymes UGT1A9 and UGT1A7, with inhibition constants in the nanomolar range, which could slow clearance of medicines handled by these enzymes.
In human and rat liver microsomes, magnolol inhibited CYP1A and CYP2C enzymes and weakly inhibited CYP3A; relevance at supplement doses is untested, so check with a pharmacist if you take prescription drugs.
Dutch and UK novel food assessors judged drug interactions unlikely at the low intakes from breath mints and gum; larger capsule doses were not assessed.

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Frequently asked questions about Magnolol (Magnolia Bark Compound)

How is magnolol different from magnolia bark and honokiol?

Magnolol is one compound from Magnolia officinalis bark. Honokiol is its close chemical relative, and magnolia bark extracts contain both in amounts that depend on the plant and the extraction method. Some purified extracts are more than 90 percent magnolol, while the stress blend Relora is standardized to honokiol and berberine instead.

Has magnolol been tested on its own in people?

Not as a swallowed supplement. Human studies have used magnolia bark extract in chewing gum and mints for breath and plaque measures, or the magnolia plus phellodendron blend Relora for stress. Magnolol has also been measured in urine after volunteers took a multi-herb Japanese remedy, but that was a measurement study, not an effect trial.

Why is magnolol added to chewing gum and mints?

In lab tests, magnolol and magnolia bark extract stop the growth of several mouth bacteria linked to breath odor and plaque. Small studies of gum and mints containing the extract found lower saliva bacteria counts and fewer breath sulfur compounds for about an hour. The effect is local, from contact in the mouth.

Does magnolol help with sleep?

That has only been shown in mice, which slept more after magnolol was injected, an effect blocked by a benzodiazepine-site blocker. No human sleep study of magnolol exists. The one magnolia plus phellodendron trial that measured sleep, in women, found no difference from placebo in sleep quality or time to fall asleep.

What is Magnolol?

Magnolol is a neolignan found in the bark of Magnolia officinalis, the tree behind the traditional herb hou po, and it sits alongside its close chemical relative honokiol in most magnolia bark extracts.

What is Magnolol used for?

NutraSmarts does not list Magnolol under a health category. What the research covers: In a nine-person study run by a gum maker, mints and gum containing magnolia bark extract lowered total saliva bacteria more than plain products for up to an hour, and in a 123-person trial a gum with the extract plus zinc cut breath sulfur…

What is the recommended dosage of Magnolol?

No human trial has tested a dose of isolated magnolol taken as a supplement. Gum and mint studies used small amounts of magnolia bark extract (an EU-member assessment capped it at 3 mg per portion); Relora studies used 500 or 750 mg a day of a magnolia plus ph… Always follow the product label and check with a healthcare provider for personal advice.

Is Magnolol safe, and does it have side effects?

Side effects and cautions reported for Magnolol include: No human safety trial of isolated magnolol taken as a swallowed supplement has been published, so its tolerability at capsule doses is unknown. It may also interact with some medications. Magnolol 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 Magnolol interact with any medications?

Possible interactions include: Sedatives, sleep medicines, benzodiazepines and alcohol: magnolol acts on GABA-A receptors, including the benzodiazepine site in mice, so added drowsiness is possible. No human interaction study exists. If you take prescription medication, check with a pharmacist or doctor before using it.

How strong is the scientific evidence for Magnolol?

NutraSmarts rates the evidence for Magnolol as Preliminary (1 out of 5). It is backed by 5 study summaries and 16 cited references summarized on this page. A higher rating reflects more, larger, and better-designed human studies.

References(16 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. Alexeev M, Grosenbaugh DK, Mott DD, Fisher JL. The natural products magnolol and honokiol are positive allosteric modulators of both synaptic and extra-synaptic GABA(A) receptors. Neuropharmacology. 2012;62(8):2507-14. doi: 10.1016/j.neuropharm.2012.03.002.PubMedUsed to support: Electrophysiology study in hippocampal neurons and recombinant GABA(A) receptors: magnolol and honokiol enhanced both phasic and tonic GABAergic transmission and modulated every alpha, beta and gamma subunit combination tested, with particularly high efficacy at delta-containing receptors. Laboratory work only; the authors note that side effects and drug interactions would also be expected.
  2. Chen CR, Zhou XZ, Luo YJ, Huang ZL, Urade Y, Qu WM. Magnolol, a major bioactive constituent of the bark of Magnolia officinalis, induces sleep via the benzodiazepine site of GABA(A) receptor in mice. Neuropharmacology. 2012;63(6):1191-9. doi: 10.1016/j.neuropharm.2012.06.031.PubMedUsed to support: Mouse EEG study: magnolol given by intraperitoneal injection at 5 or 25 mg/kg shortened sleep latency and increased non-REM and REM sleep for 3 hours; the effects were reversed by the benzodiazepine-site antagonist flumazenil. Animal study with injected, not oral, dosing.
  3. Lin SP, Tsai SY, Lee Chao PD, Chen YC, Hou YC. Pharmacokinetics, bioavailability, and tissue distribution of magnolol following single and repeated dosing of magnolol to rats. Planta Med. 2011;77(16):1800-5. doi: 10.1055/s-0030-1271159.PubMedUsed to support: Rat pharmacokinetic study (20 mg/kg intravenous; 50 mg/kg oral, single and seven doses): after oral dosing, magnolol sulfates and glucuronides predominated in the blood, whereas free magnolol predominated in liver, kidney, brain, lung and heart, with the highest levels in the liver.
  4. Homma M, Oka K, Kobayashi H, Niitsuma T, Yamamoto S, Itoh H, Takahashi N. Liquid chromatographic determination of magnolol in urine collected from volunteers after a single dose of saiboku-to, an oriental herbal medicine for bronchial asthma. J Pharm Pharmacol. 1993;45(9):839-41. doi: 10.1111/j.2042-7158.1993.tb05697.x.PubMedUsed to support: Developed a liquid chromatography method for magnolol in urine and used it to show urinary excretion profiles of magnolol in healthy and asthmatic volunteers after a single dose of Saiboku-to, a ten-herb remedy. A human measurement study of magnolol from a multi-herb product, not an effect trial.
  5. Zhu L, Ge G, Zhang H, Liu H, He G, Liang S, Zhang Y, Fang Z, Dong P, Finel M, Yang L. Characterization of hepatic and intestinal glucuronidation of magnolol: application of the relative activity factor approach to decipher the contributions of multiple UDP-glucuronosyltransferase isoforms. Drug Metab Dispos. 2012;40(3):529-38. doi: 10.1124/dmd.111.042192.PubMedUsed to support: In vitro study with human liver and intestine microsomes and recombinant enzymes: several UGT isoforms glucuronidate magnolol; UGT2B7 is mainly responsible in liver, and UGT2B7 and UGT1A10 in intestine. Notes that magnolol is used as a food additive in mints and gums.
  6. Zhu L, Ge G, Liu Y, He G, Liang S, Fang Z, Dong P, Cao Y, Yang L. Potent and selective inhibition of magnolol on catalytic activities of UGT1A7 and 1A9. Xenobiotica. 2012;42(10):1001-8. doi: 10.3109/00498254.2012.681814.PubMedUsed to support: In vitro study: magnolol at 10 microM selectively inhibited UGT1A9 and the extra-hepatic UGT1A7 in recombinant enzymes and human liver microsomes, with Ki values in the nanomolar range; the authors conclude in vivo inhibition is likely and raise a caution for magnolol-containing products.
  7. Kim SB, Kang HE, Cho HJ, Kim YS, Chung SJ, Yoon IS, Kim DD. Metabolic interactions of magnolol with cytochrome P450 enzymes: uncompetitive inhibition of CYP1A and competitive inhibition of CYP2C. Drug Dev Ind Pharm. 2016;42(2):263-9. doi: 10.3109/03639045.2015.1047846.PubMedUsed to support: Human and rat liver microsome study: CYP2C and CYP3A contribute to magnolol metabolism; magnolol inhibited CYP1A (IC50 1.62 microM) and CYP2C (IC50 5.56 microM) potently and CYP3A weakly (IC50 35.0 microM). The authors suggest possible CYP1A and 2C inhibition in rats; clinical relevance in people is untested.
  8. Li N, Song Y, Zhang W, Wang W, Chen J, Wong AW, Roberts A. Evaluation of the in vitro and in vivo genotoxicity of magnolia bark extract. Regul Toxicol Pharmacol. 2007;49(3):154-9. doi: 10.1016/j.yrtph.2007.06.005.PubMedUsed to support: Genotoxicity testing of a magnolia bark extract containing 94% magnolol and 1.5% honokiol: no mutagenic activity in Salmonella and E. coli reverse mutation assays with or without metabolic activation, and no increase in micronuclei in mice.
  9. Liu Z, Zhang X, Cui W, Zhang X, Li N, Chen J, Wong AW, Roberts A. Evaluation of short-term and subchronic toxicity of magnolia bark extract in rats. Regul Toxicol Pharmacol. 2007;49(3):160-71. doi: 10.1016/j.yrtph.2007.06.006.PubMedUsed to support: Rat feeding studies of magnolia bark extract: no treatment-related effects at up to 480 mg/kg/day for 21 days or up to 240 mg/kg/day for 90 days on clinical signs, blood measures, organ weights or tissue findings. The applicant's dossier summary within the Dutch assessment report records the test extract as 94% magnolol and 2.0% honokiol; the Dutch committee itself describes it as at least 90% magnolol plus honokiol.
  10. Sarrica A, Kirika N, Romeo M, Salmona M, Diomede L. Safety and Toxicology of Magnolol and Honokiol. Planta Med. 2018;84(16):1151-1164. doi: 10.1055/a-0642-1966.PubMedUsed to support: Review of magnolol and honokiol safety: concentrated magnolia bark extract showed no mutagenic or genotoxic potential; a 90-day study set a no-adverse-effect level above 240 mg/kg/day; interactions through glucuronidation cannot be excluded. Two authors are employees of the confectionery maker Perfetti Van Melle, which also paid consultancy fees to the other authors' department.
  11. Greenberg M, Urnezis P, Tian M. Compressed mints and chewing gum containing magnolia bark extract are effective against bacteria responsible for oral malodor. J Agric Food Chem. 2007;55(23):9465-9. doi: 10.1021/jf072122h.PubMedUsed to support: Wrigley-authored study: magnolia bark extract, magnolol and honokiol inhibited P. gingivalis, F. nucleatum and S. mutans at 8 to 31 microg/mL in vitro; in 9 volunteers, extract mints cut total salivary bacteria by 61.6% at 30 minutes and extract gum by 43.0% at 40 minutes, versus smaller changes with control products.
  12. Campus G, Cagetti MG, Cocco F, Sale S, Sacco G, Strohmenger L, Lingström P. Effect of a sugar-free chewing gum containing magnolia bark extract on different variables related to caries and gingivitis: a randomized controlled intervention trial. Caries Res. 2011;45(4):393-9. doi: 10.1159/000330234.PubMedUsed to support: Randomized double-blind trial in 120 adults at high caries risk: 30 days of sugar-free gum with magnolia bark extract reduced plaque acidogenicity, salivary mutans streptococci and bleeding on probing compared with xylitol and control gums.
  13. Porciani PF, Grandini S. The effect of zinc acetate and magnolia bark extract added to chewing gum on volatile sulfur-containing compounds in the oral cavity. J Clin Dent. 2012;23(3):76-9..PubMedUsed to support: Randomized double-blind trial in 123 adults: gum with 0.012% zinc acetate and 0.15% magnolia bark extract reduced oral volatile sulfur compounds more than a plain gum at the end of chewing (50.9% vs 31.2%) and at one hour (27.6% vs 6.9%); no product-related problems reported.
  14. Kalman DS, Feldman S, Feldman R, Schwartz HI, Krieger DR, Garrison R. Effect of a proprietary Magnolia and Phellodendron extract on stress levels in healthy women: a pilot, double-blind, placebo-controlled clinical trial. Nutr J. 2008;7:11. doi: 10.1186/1475-2891-7-11.PubMedUsed to support: Maker-funded pilot RCT of Relora (magnolia plus phellodendron, standardized to honokiol and berberine) 250 mg three times daily for 6 weeks in 40 overweight premenopausal women (26 completed): state anxiety improved versus placebo; trait anxiety, salivary cortisol and amylase, appetite, body measures and sleep quality and latency did not.
  15. Talbott SM, Talbott JA, Pugh M. Effect of Magnolia officinalis and Phellodendron amurense (Relora®) on cortisol and psychological mood state in moderately stressed subjects. J Int Soc Sports Nutr. 2013;10(1):37. doi: 10.1186/1550-2783-10-37.PubMedUsed to support: Maker-funded RCT of Relora 500 mg/day for 4 weeks in 56 moderately stressed adults: salivary cortisol exposure 18% lower than placebo and better mood-state scores. The blend is standardized to honokiol and berberine; magnolol content not reported.
  16. Medicines Evaluation Board (CBG-MEB), Novel Foods Unit; Committee on the Safety Assessment of Novel Foods (VNV). Magnolia bark extract: second opinion regarding consumer safety, in accordance with European Regulation 258/97 concerning novel foods and novel food ingredients. Netherlands novel food assessment report under Regulation (EC) No 258/97. 2010;Report No. 2010-04 BNV, The Hague, 25 September 2010, addressed to the Minister of Health, Welfare and Sport; 62 pages, including the applicant's dossier summary (Annex A) and the UK ACNFP initial assessment (Annex B)..SourceUsed to support: Not PubMed-indexed; official Dutch regulatory report. It is a member-state second opinion within the EU novel food procedure for the applicant William Wrigley Jr Company, concurring with the UK ACNFP initial assessment; it is not the EU authorization itself. The assessed extract was over 92.5% magnolol and at least 94% magnolol plus honokiol, for use at up to 0.2% in breath-freshening gum and mints (no more than 3 mg per portion). The committee agreed with the UK assessors that this use is unlikely to pose a risk, citing negative genotoxicity tests and a 90-day rat no-adverse-effect level of 240 mg/kg/day, and agreed drug interactions are unlikely at these intakes. The applicant's summary states there is no pharmacokinetic profile of magnolol in humans and that urinary magnolol after Saiboku-to was mostly glucuronidated.