IngredientesRelora® is a proprietary blend of a patented extract of the bark of Magnolia officinalis and an extract of the bark of Phellodendron amurense (U.S. Patent Nos. 6,582,735 and 6,814,987). The trademark is held by Next Pharmaceuticals, Inc. The formulation draws on two botanically and pharmacologically distinct plants, each with its own long history in traditional medicine, and combines standardized bark extracts of both into a single finished ingredient.
Magnolia officinalis (family Magnoliaceae) is known in Chinese pinyin as Houpo (厚朴). One type — Magnolia officinalis — is commonly called the houpo magnolia, and the tree is native to China, where it has been used for thousands of years as a supplement in traditional Chinese medicine. In Japan, the same species or the closely related M. obovata is called wakoboku. Traditionally in Asian medicine, Magnolia biondii, Magnolia obovata, and Magnolia officinalis are among the species most commonly used.
Phellodendron amurense (family Rutaceae) is the Amur cork tree. It is a major source of huáng bò (黄柏), one of the 50 fundamental herbs used in traditional Chinese medicine. The tree is native to eastern Asia: northern China, northeast China, Korea, Ussuri, Amur, and Japan. It is known as hwangbyeok in Korean and kihada in Japanese.
The product is standardized to "not less than 1.5% honokiol and 0.1% berberine." These are the marker compounds used to characterize the extract quality of the Magnolia officinalis and Phellodendron amurense fractions, respectively.
The Relora® blend can be taken on its own, as part of a supplement with energy-supporting B-vitamins, or as part of a comprehensive multivitamin formula. It is available primarily as vegetarian capsules. The proprietary blend per capsule is most commonly supplied at 250 mg, and products providing 300 mg per capsule also exist on the market. Dosing recommendations in published sources include taking a 300 mg capsule of Relora 2 to 3 times per day.
The bark of Magnolia officinalis, known under the pinyin name "Houpo," has been traditionally used in Chinese and Japanese medicines for the treatment of anxiety, asthma, depression, gastrointestinal disorders, headache, and more. Magnolia bark, particularly from Magnolia officinalis and Magnolia grandiflora, has been used in traditional Chinese medicine for over 2,000 years. Known as "Houpo," it was commonly used to treat digestive disorders, respiratory issues, anxiety, and inflammation.
A variety of traditional Japanese and Chinese herbal medicines are derived from Magnolia species and have long been used to treat anxiety and neurotic disorders. Such herbal formulas include Houpu Tang, Xiao Zhengai Tang, Ping Wei San, and Shenmi Tang from China, and Hange-koboku-to and Sai-boku-to from Japan. These formulas are traditionally prepared from the bark of species such as Magnolia officinalis and Magnolia obovata.
Magnolia flowers and bark have been used in Chinese medicine since at least 100 AD. Magnolias have also been cultivated in Chinese Buddhist temple gardens since 600 AD. Magnolia officinalis has long been used as a traditional Chinese and Japanese medicine for the treatment of gastrointestinal disorders, anxiety, and bronchial asthma.
Beyond anxiety and digestion, the range of traditional applications was broad. The bark of Magnolia officinalis is reportedly used as an antibacterial, antiseptic, antispasmodic, aphrodisiac, appetizer, digestive, diuretic, emmenagogue, expectorant, ophthalmic, stomachic, and tonic.
A particular aspect of traditional preparation involves the processing technique known as "sweating." In China, M. officinalis is usually processed after collection. According to the Chinese Pharmacopoeia (version 2015), the primary processing of Houpo enforces sweating treatment, called "Fahan," which is a special drying process considered an essential embodiment of high quality and genuine medicinal materials. The quality and clinical effect of Houpo are closely related to this process.
Huang Bai, commonly known as Huang Bo or Cortex Phellodendri, is the bark of Phellodendron chinense or Phellodendron amurense, a deciduous tree belonging to the family Rutaceae. It first appeared in the Shennong Ben Cao Jing in the late Western Han Dynasty (around 100 BCE). This makes it among the oldest documented herbal medicines in the Chinese pharmacopeia.
The earliest known writings about this preparation are found in the Shennong ben cao jing. The bark is categorized in the traditional Chinese medicine counterpart of humorism, Wu Xing, as bitter and cold, affecting the kidney, urinary bladder, and large intestine meridians.
Phellodendron amurense (Huang Bai or Amur cork tree) has been used in traditional Chinese medicine to eliminate dampness, reduce heat, and alleviate pain. It is often employed to treat conditions such as urinary tract infections, skin disorders, and rheumatoid arthritis. It has also been used as a Chinese traditional medicine for the treatment of meningitis, bacillary dysentery, pneumonia, tuberculosis, tumours, jaundice and liver cirrhosis, as well as to treat orally abdominal pain, diarrhea, gastroenteritis, and urinary tract infections.
The name "Huang" means yellow in Chinese, derived from the bright yellow color of the plant's inner bark. The bark is peeled from the tree and allowed to dry in the sun. The Chinese have used the herb for centuries to help repair tissues and bones, and the Ainu people of China use the plant as a painkiller.
The two major active principles identified in Magnolia bark extracts are magnolol and honokiol, which are positional isomers. Honokiol is 3′5-diallyl-2,4′-biphenyldiol (CAS [35354-74-6]) and magnolol is 5,5′-diallyl-2,2′-biphenyldiol (CAS [528-43-8]).
Honokiol belongs to a class of neolignan biphenols. As a polyphenol it is relatively small and can interact with cell membrane proteins through intermolecular interactions like hydrogen bonding, hydrophobic interactions, or aromatic pi orbital co-valency. It is hydrophobic and readily dissolved in lipids. Critically, because of its physical properties, honokiol can readily cross the blood–brain barrier and the blood–cerebrospinal fluid barrier. As a result, honokiol is a potentially potent therapy with high bioavailability.
The isomers magnolol (5,5′-diallyl-2,2′-dihydroxybiphenyl) and honokiol (3,5′-diallyl-4,2′-dihydroxybiphenyl) are the principal active components of magnolia bark extract, typically making up 1–10% of the dried bark, depending upon the species and the isolation methods.
More than 250 ingredients can be found in the bark, flowers, and leaves of the magnolia, but two of the main compounds used in dietary supplements are magnolol and honokiol.
Berberine is a protoberberine isoquinoline alkaloid found in Huangbai (Phellodendron amurense), and has been a cornerstone of Traditional Chinese Medicine for millennia, with emerging evidence supporting its multi-target pharmacology.
Phellodendron amurense bark (huangbo) has about 2–4% berberine content. Additional alkaloids present in Huang Bai include: berberine alkaloid, magnoflorine, phellodendrine, candicine, lumicaeruleic acid, campesterol, glycosides, phenolic compounds, and phytonutrients.
Much pharmacological activity has been reported for Magnolia officinalis and its major compounds, notably antioxidant, anti-inflammatory, antibiotic, and antispasmodic effects.
The anxiolytic and relaxant effects of the magnolia bark fraction are most extensively attributed to interactions with GABAA receptors. Magnolol and honokiol are positive allosteric modulators of GABAA receptors. They enhance both phasic and tonic neurotransmission in hippocampal neurons. Their activity shows little dependence upon GABAA receptor subunit composition, with the greatest enhancement seen at δ-containing receptors.
Magnolol and honokiol enhance both phasic and tonic GABAergic neurotransmission in hippocampal dentate granule neurons. All recombinant receptors examined were sensitive to modulation, regardless of the identity of the α, β, or γ subunit subtype, although the compounds showed particularly high efficacy at δ-containing receptors.
The biphenyl-type neolignans honokiol and magnolol are the main constituents of Magnolia bark extracts. In the central nervous system, Magnolia bark preparations that contain honokiol are thought to primarily interact with γ-aminobutyric acid A (GABAA) receptors.
Importantly, while honokiol and magnolol are positive allosteric modulators at GABAA receptors (comparable in target to benzodiazepines), numerous animal studies have demonstrated that honokiol and berberine act as anxiolytic agents. When compared to pharmaceutical agents such as Valium (diazepam), honokiol and berberine appear to be as effective in their anti-anxiety activity yet not nearly as powerful in their sedative ability.
The magnolia and phellodendron fractions may bind to key central nervous system receptors, including those for GABA and the serotonin transporter, which encourages feelings of satiety and relaxation. Research into the serotonin transporter interaction provides a potential additional mechanism for satiety and mood-related effects observed in human studies, though this mechanism remains less characterized than the GABAergic pathway.
The Relora combination has been proposed to modulate the hypothalamic-pituitary-adrenal (HPA) axis. One study measured the effects of Relora on salivary cortisol, finding benefits in reducing cortisol and increasing dehydroandrostenedione (DHEA) levels in stressed subjects. The exact upstream mechanism by which the plant extracts reduce cortisol secretion is not fully established in the published literature; proposed pathways involve central nervous system modulation leading secondarily to reduced HPA tone.
Stress responses inherently involve the noradrenergic system, which has been investigated in the pharmacological mechanism of honokiol. Research has examined interactions of honokiol and related biphenyl-type neolignans with the norepinephrine transporter (NET), which is responsible for the synaptic clearance of norepinephrine and is the target of many anxiolytics.
Note on evidence base: The published clinical trials on Relora® as a specific proprietary formulation are limited in number, generally small in sample size, and predominantly involve short treatment periods (4–6 weeks). The studies listed below represent the totality of identifiable peer-reviewed human trials on the Relora® blend. Where stated by original authors, findings should be characterized as preliminary.
Talbott et al. (2013) — Journal of the International Society of Sports Nutrition
This is the largest and most cited Relora-specific trial. The study assessed salivary cortisol exposure and psychological mood state in 56 subjects (35 men and 21 women) screened for moderate stress and supplemented with a standardized/patented Magnolia/Phellodendron combination (Relora®, Next Pharmaceuticals) or placebo for 4 weeks. The product was standardized to "not less than 1.5% honokiol and 0.1% berberine." Subjects ingested 500 mg/day at breakfast (250 mg) and dinner (250 mg) in white opaque capsules or a look-alike placebo.
Results: After 4 weeks of supplementation, salivary cortisol exposure was significantly (p<0.05) lower (−18%) in the Relora group compared to placebo. Compared to placebo, the Relora group had significantly better (p<0.05) mood state parameters, including lower indices of Overall Stress (−11%), Tension (−13%), Depression (−20%), Anger (−42%), Fatigue (−31%), and Confusion (−27%), and higher indices of Global Mood State (+11%) and Vigor (+18%). These results indicate that daily supplementation with the combination reduces cortisol exposure and perceived daily stress, while improving a variety of mood state parameters, including lower fatigue and higher vigor.
Limitations: The results suggest an effective natural approach to modulating the detrimental health effects of chronic stress in moderately stressed adults. Future studies should examine the possible performance and recovery benefits of Relora supplementation in athletes overstressed by the physical and psychological demands of training and competition. The study was relatively small, conducted over only 4 weeks, and involved sponsor-affiliated investigators.
Kalman et al. (2008) — Nutrition Journal
This study measured the effects of Relora® on anxiety, stress, and sleep in healthy premenopausal women. The randomized, parallel, placebo-controlled clinical study was conducted with healthy, overweight (BMI 25 to 34.9), premenopausal female adults, between the ages of 20 and 50 years, who typically eat more in response to stressful situations and scored above the national mean for women on self-reporting anxiety. The intervention was Relora (250 mg capsules) or identical placebo 3 times daily for 6 weeks. Anxiety as measured by the Spielberger STATE-TRAIT questionnaires, salivary amylase and cortisol levels, Likert Scales/Visual Analog Scores for sleep quality and latency, appetite, and clinical markers of safety.
Results: The intent-to-treat population consisted of 40 subjects with 26 participants completing the study. Relora was effective, in comparison to placebo, in reducing temporary, transitory anxiety as measured by the Spielberger STATE anxiety questionnaire. It was not effective in reducing long-standing feelings of anxiety or depression as measured using the Spielberger TRAIT questionnaire. Other assessments conducted in this study including salivary cortisol and amylase levels, appetite, body morphology, and sleep quality/latency were not significantly changed by Relora in comparison to placebo. This pilot study indicates that Relora may offer some relief for premenopausal women experiencing mild transitory anxiety. There were no safety concerns or significant adverse events observed in this study.
Limitations: High dropout rate (14 of 40 subjects did not complete), small total sample, short duration, female-only population, and involvement of the manufacturer's medical writing team in study preparation.
Kalman et al. (2006 FASEB abstract) — Randomized, Double-Blind, Placebo-Controlled Trial
This exploratory prospective randomized double-blind placebo-controlled clinical trial was conducted to assess the safety and efficacy of a proprietary blend of two plant extracts in reducing anxiety, salivary cortisol, and food intake. The study enrolled healthy overweight physically active, 25–50-year-old women with anxiety who reported eating more in response to stressful situations. Subjects were randomized (1:1) to receive either placebo or 750 mg of Relora™ (Magnolia officinalis/Phellodendron amurense extracts) for 6 weeks, with evaluations at baseline, mid- and end-study. Efficacy variables included: mood and stress scores, cortisol levels, macronutrient intake, appetite, dietary restraint, and sleep ratings.
Results: An intent-to-treat analysis indicated that the Spielberger Trait and Anxiety Index Total scores improved significantly, and by twice as much with Relora as with placebo (p=0.047). Both groups showed significant decreases in Cohen PSS and PANAS scores, with placebo showing more improvement than Relora. Cortisol levels decreased in both groups at all times of day, but not significantly. The Relora group had twice as much average reduction in sleep latency (11 min, p=0.012) as the placebo group (5 min, p=0.147). Both groups showed significant decreases in macronutrient/caloric intake. No significant safety concerns or serious adverse events were noted.
Garrison & Chambliss (2006) — Alternative Therapies in Health and Medicine
Garrison R and Chambliss WG conducted a randomized, double-blind, placebo-controlled pilot study published in Alternative Therapies in Health and Medicine (2006 Jan-Feb;12(1):50-4), in which subjects took Relora or placebo for six weeks. All subjects reported higher than usual levels of anxiety and a tendency to eat more in response to stress. Results: Subjects in the control group gained an average of 1.5 kg over the course of the study; however, subjects taking Relora did not gain any weight on average. The Relora group presented a trend toward lower cortisol levels at the end of the study, particularly in the evenings. In contrast, evening cortisol levels increased in the control group. Subjects in both groups improved on a number of psychological measures, and there was a correlation between self-reported stress and weight gain. The results indicate that obese subjects who eat in response to stress may benefit from taking a dietary supplement ingredient containing proprietary extracts of M. officinalis and P. amurense. The mechanism of action appears to be through reduction of cortisol levels and possibly perceived stress, thereby helping participants maintain body weight.
Limitations across weight/eating studies: All studies involve small, exclusively female, overweight cohorts. The weight maintenance finding (non-gaining versus control gaining) from Garrison & Chambliss has not been replicated in a larger independent trial. The cortisol changes did not consistently reach statistical significance across studies.
One study (unpublished sponsor in-house data at the time of publication) measured the effects of Relora on salivary cortisol and found that it had some effect on morning cortisol while also raising dehydroandrostenedione (DHEA) levels. The later published Talbott et al. (2013) trial confirmed a statistically significant 18% reduction in salivary cortisol versus placebo in a 4-week regimen at 500 mg/day, though this finding requires independent replication in larger cohorts before firm clinical conclusions can be drawn.
A registered randomized, double-blind, placebo-controlled crossover trial (NCT02734251, sponsored by InterHealth Nutraceuticals, Inc.) aimed to evaluate the effects of Relora supplementation on responses to induced stress produced by a combination of cognitive and physiologic stressors in healthy men and women. The effects of the supplement, compared with a placebo, were to be evaluated using measures to assess anxiety (STAI-Part 1), mood (Bond-Lader VAS), HPA axis activation (salivary cortisol), and cognitive function including cognitive flexibility, reaction time, processing speed, attention, sustained attention, working memory, and executive function. Published results from this trial have not been identified in the peer-reviewed literature at the time of this writing.
A substantial body of preclinical data underlies the proposed mechanisms of Relora's constituent compounds. Honokiol and magnolol have been identified as neurologically active agents, with anxiolytic, sedative, neuroprotective, and anti-convulsant actions in multiple animal models. Extracts from Magnolia bark have been shown in preclinical work to have anti-anxiety, anti-inflammatory, anti-microbial, anti-oxidant, anti-platelet, and neurotrophic properties. However, the mechanisms underlying many of these activities have not been fully elucidated, and only a very few clinical trials have been published. These animal and in vitro findings should not be directly extrapolated to confirmed human efficacy.
The dosages used in peer-reviewed human clinical trials are as follows:
Published dosing recommendations also include taking a 300 mg capsule of Relora 2 to 3 times per day.
The Kalman et al. (2008) pilot study indicates that Relora may offer some relief for premenopausal women experiencing mild transitory anxiety, with no safety concerns or significant adverse events observed. No significant safety concerns or serious adverse events were noted in the Kalman et al. FASEB 2006 trial. Most human studies on Relora showed no significant adverse effects, and the supplement is viewed as generally safe for healthy adults.
Relora is considered likely unsafe during pregnancy. Phellodendron contains a chemical called berberine, which can cross the placenta and might harm the fetus. As most berberine-containing plants are considered uterine stimulants, they should be used with care during pregnancy. Avoidance during pregnancy and lactation is advised because of limited clinical data.
Magnolol may interact with acetaminophen; one study documented reduced acetaminophen-induced liver damage in rats. Additive adverse reactions with antiplatelet medications may occur. MBE and honokiol may interact with benzodiazepines. Magnolol may stimulate corticosterone secretion or increase steroid medication concentrations.
This direct positive modulation of both synaptic and extra-synaptic populations of GABAA receptors suggests that supplements containing magnolol and/or honokiol would be effective anxiolytics, sedatives, and anti-convulsants; however, significant side effects and risk of drug interactions would also be expected. This is particularly relevant for concurrent use with CNS depressants, sedatives, anesthetics, and benzodiazepines.
Drug-herb interactions are documented in animals and in vitro. Based on these limited data, caution is advisable in patients self-medicating with magnolia bark extract.
The berberine fraction of the Phellodendron extract is associated with dose-dependent gastrointestinal effects at higher doses. Commonly reported adverse events associated with berberine include gastrointestinal effects (e.g., nausea, diarrhea, abdominal discomfort) and muscle-related adverse events (e.g., muscle pain, myopathy). No severe adverse effects and no significant changes in plasma kidney and liver parameters were observed in clinical studies of berberine. Mild to moderate constipation was seen in 3–8% of subjects in some trials. At the low berberine content of Relora (standardized to a minimum of only 0.1% berberine), the gastrointestinal risk is likely proportionally lower than in studies of isolated berberine at pharmacological doses, though this has not been directly studied.
Direct positive modulation of both synaptic and extra-synaptic populations of GABAA receptors suggests that supplements containing magnolol and/or honokiol would be effective anxiolytics, sedatives, and anti-convulsants; however, significant side effects and risk of drug interactions would also be expected. Although human studies characterize Relora as "relaxing but non-sedating" at the doses tested, this classification is relative to clinical sedatives and the low standardized doses used; the underlying pharmacological mechanism involves the same receptor family as benzodiazepines and barbiturates.
All published clinical trials of Relora® have been conducted in healthy adults (predominantly healthy, overweight, premenopausal women, or moderately stressed adults). No clinical safety data exist for children, the elderly, individuals with hepatic or renal impairment, or individuals with diagnosed psychiatric disorders taking psychoactive medications.
Relora® is a proprietary blend of a patented extract of the bark of Magnolia officinalis and an extract of the bark of Phellodendron amurense, protected under U.S. Patent Nos. 6,582,735 and 6,814,987. Relora® is a Lonza trademark, registered in the USA (having transitioned from the original rights holder, Next Pharmaceuticals, Inc.). The ingredient is licensed to numerous finished-product manufacturers who incorporate it into single-ingredient capsule products as well as combination stress-support formulas.
Condiciones de salud que relora® (propietario) puede ayudar a apoyar.
Relora® has clinical evidence specifically for stress-related food cravings, particularly for sugary snacks. Pilot RCT data and open-label follow-up studies showed Relora diminished stress-related sugary snack cravings and promoted more healthful eating habits. No clinical evidence pertains to addictions in the substance-dependence sense; evidence is limited to cortisol-driven food cravings.
Multiple placebo-controlled RCTs have tested Relora® directly for anxiety. A 2008 pilot RCT (Kalman et al., Nutrition Journal, n=40 overweight premenopausal women) found Relora reduced transitory state anxiety on the Spielberger STATE questionnaire versus placebo, though it did not reduce trait (long-standing) anxiety. A 2006 FASEB-reported RCT showed Spielberger Trait and Anxiety Index Total scores improved significantly and by twice as much with Relora as with placebo (p=0.047). Evidence is promising but limited to small pilot studies.
Relora® has been clinically studied for appetite and satiety, particularly in stress-related eating contexts. The magnolia and phellodendron fractions may bind to GABA receptors and serotonin transporters in the CNS, which are associated with feelings of satiety. A follow-up pilot RCT showed Relora may help diminish stress-related sugary snack cravings and promote healthier eating habits. Effects appear primarily mediated through stress and cortisol reduction rather than direct appetite suppression.
Burnout is characterized by chronic fatigue, reduced vigor, and elevated stress. Talbott et al. (2013) found that 4 weeks of Relora supplementation significantly reduced fatigue (−31%) and increased vigor (+18%) on the Profile of Mood States (POMS) in moderately stressed subjects versus placebo. Both Magnolia officinalis and Phellodendron amurense have documented traditional use in TCM for states of overwork and exhaustion.
An early open-label clinical study at the Living Longer Clinic (Cincinnati) in 50 chronically stressed adults given Relora 200 mg three times daily for 2 weeks found that 78% reported feeling more relaxed. Controlled RCT data (Talbott et al., 2013) showed significantly reduced tension and improved global mood in moderately stressed adults. Honokiol's GABA-A modulation provides a plausible non-sedating anxiolytic mechanism.
Relora® has been specifically studied in populations with stress-induced eating behaviors. Garrison & Chambliss (2006) enrolled only overweight women who reported eating more in response to stress and found significantly less weight gain in the Relora group versus controls. The cortisol-lowering effect is the proposed primary mechanism, as elevated cortisol promotes caloric cravings and overeating in stressed individuals.
Talbott et al. (2013) demonstrated significant improvements across multiple mood-state dimensions in moderately stressed adults taking Relora® versus placebo, including reduced anger (−42%), confusion (−27%), and improved global mood state (+11%) and vigor (+18%). These outcomes collectively reflect enhanced emotional resilience under stress conditions.
Clinical evidence supports a role for Relora® in attenuating stress-related weight gain. In Garrison & Chambliss (2006), stress-eating overweight women taking Relora did not gain weight on average over 6 weeks while control subjects gained 1.5 kg. An early pilot suggested Relora maintained healthy cortisol and DHEA levels, supporting body-fat distribution. Effects are primarily indirect, mediated through cortisol reduction.
Relora® is a proprietary blend of Magnolia officinalis and Phellodendron amurense bark extracts with clinical trial evidence for HPA axis and cortisol support. A double-blind RCT (Talbott et al., 2013, JISSN) found 500 mg/day for 4 weeks significantly reduced salivary cortisol by 18% and improved mood profiles in moderately stressed adults versus placebo.
Relora's active constituents modulate multiple neurotransmitter systems. Honokiol and magnolol are positive allosteric modulators of GABA-A receptors (PubMed 22445602), and Magnolia/Phellodendron fractions bind to the serotonin transporter. Berberine from Phellodendron inhibits monoamine oxidase-A, raising serotonin, dopamine, and norepinephrine in preclinical models. These actions collectively support a multi-system neurotransmitter-balancing profile.
Sleep quality is a direct endpoint in two Relora® clinical studies. Kalman (FASEB 2006) found Relora reduced sleep latency by twice as much as placebo (11 min vs. 5 min, p=0.012). An early open-label pilot found 74% of participants experienced more restful sleep on Relora. Mechanistically, honokiol's GABA-A and benzodiazepine-site activity promotes NREM sleep without heavy sedation.
A proprietary blend of Magnolia officinalis bark and Phellodendron amurense bark standardized to honokiol and berberine. A placebo-controlled pilot RCT demonstrated Relora reduced transient anxiety in premenopausal women. It is used specifically for stress-related cortisol management.
Sistemas corporales que relora® (propietario) puede ayudar a apoyar.
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