Relora with Bacopa [Discontinued] by DaVinci Laboratories

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Alzheimer disease. It is unclear if oral bacopa is beneficial in patients with Alzheimer disease. Details: A small clinical study in patients with Alzheimer disease or mild cognitive impairment shows that taking bacopa 300 mg daily for 12 months does not improve measures of cognitive function or memory when compared with donepezil or baseline measures (109623).
• Attention deficit-hyperactivity disorder (ADHD). It is unclear if oral bacopa is beneficial in children with ADHD. Details: A small clinical study in boys 6-14 years of age with symptoms consistent with ADHD but without an official diagnosis shows that taking a specific bacopa supplement (KeenMind - CDRI 08, Flordis) for 14 weeks does not improve symptoms of ADHD but improves some cognitive outcomes including error-making, cognitive flexibility, executive functioning, and sleep when compared with placebo. Bacopa 160 mg was given once daily in those weighing 20-35 kg and twice daily in those over 35 kg (109625). However, another small, open-label study in children aged 6-12 years with ADHD shows that taking a different bacopa supplement (BacoMind, Natural Remedies), 225 mg daily for 6 months, improves symptoms such as restlessness, impulsivity, learning problems, and attention deficit when compared to baseline (97603). The validity of these findings is limited by the lack of blinding or comparator group.
• Back pain. Although there is interest in using oral bacopa for back pain, there is insufficient reliable information about the clinical effects of bacopa for this condition.
• Cognitive function. Bacopa seems to improve some measures of cognitive function, but data are conflicting. Details: A meta-analysis of 9 small clinical studies, along with more recent clinical research, shows that taking bacopa 300-600 mg daily for at least 12 weeks is not associated with improved measures of cognition including working memory, learning rate, recognition of pictures and words, reaction time, or attention when compared with placebo. However, subgroup analysis of this meta-analysis and another small clinical study show some evidence of improved reaction times, verbal learning, total recall, retention, memory, and information processing in healthy adults when compared with placebo (10058,17946,33287,97605,109624,111520). In children aged 6-8 years old, a very small clinical study shows that taking a syrup containing bacopa extract 350 mg three times daily for 3 months improves visual motor function and immediate memory when compared to baseline (33304). The validity of this finding is limited by the lack of a statistical comparison to the placebo group. Bacopa has also been studied in combination with other ingredients. A study in healthy adults aged 18-60 years shows that taking a single dose of a combination of bacopa 300 mg, American ginseng 100 mg, and coffee fruit extract 100 mg (Bacognize) improves some measures of working memory and attention by a small amount at 45 minutes when compared with placebo (103375). It is unclear if these effects are due to bacopa, other ingredients, or the combination. In contrast, a moderate-sized study in healthy, middle-aged adults shows that taking a combination product containing whole plant bacopa 7.5 grams, gingko biloba, and group B vitamins for 12 weeks does not improve measures of memory, attention, cognition, mood, or stress reactivity when compared with placebo. Subgroup analysis shows a possible benefit of bacopa supplementation on measures of attention in those with an optimal diet at baseline (111334).
• Cognitive impairment. It is unclear if oral bacopa is beneficial in patients with cognitive impairment. Details: A small clinical study in patients with mild cognitive impairment or Alzheimer disease shows that taking bacopa 300 mg daily for 12 months does not improve measures of cognitive function or memory when compared with donepezil or baseline (109623).
• Congestive heart failure (CHF). Although there is interest in using oral bacopa for CHF, there is insufficient reliable information about the clinical effects of bacopa for this condition.
• Depression. It is unclear if oral bacopa is beneficial in patients with depression. Details: Preliminary clinical research in adults with depression who have not responded to citalopram 40 mg daily shows that adding bacopa extract 300 mg twice daily for 4 weeks improves scores on depression rating scales when compared with citalopram alone (103378).
• Hypertension. Although there is interest in using oral bacopa for hypertension, there is insufficient reliable information about the clinical effects of bacopa for this condition.
• Insomnia. Although there is interest in using oral bacopa for insomnia, there is insufficient reliable information about the clinical effects of bacopa for this condition.
• Irritable bowel syndrome (IBS). Bacopa has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with diarrhea-predominant IBS shows that taking a combination of bacopa and bael (Aegel marmalos) reduces symptoms in 65% of patients, compared with 78% of patients taking clidinium bromide, chlordiazepoxide, and blond psyllium, and 33% taking placebo. Neither treatment is more effective than placebo for preventing relapses (10059).
• Parkinson disease. It is unclear if oral bacopa is beneficial in patients with Parkinson disease. Details: A very small study in older adults with Parkinson disease taking levodopa shows that taking a specific bacopa extract (Cognitus, Herbarium) 225 mg or 450 mg daily for 90 days does not improve Parkinsonian or systemic symptoms, motor activity, emotional function, or social outcomes when compared with placebo (111523). The validity of these findings is limited by a small sample size and lack of randomization.
• Rheumatoid arthritis (RA). Although there is interest in using oral bacopa for RA, there is insufficient reliable information about the clinical effects of bacopa for this condition.
• Sexual dysfunction. Although there is interest in using oral bacopa for sexual dysfunction, there is insufficient reliable information about the clinical effects of bacopa for this condition.
• Smoking cessation. Oral bacopa has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A moderate-sized clinical study in adults with a history of smoking 5 or more cigarettes daily for at least 3 years shows that using a specific combination product containing bacopa 100 mg, ashwagandha, Indian gooseberry, tribulus, albizia lebbeck, licorice, clove, ginger, cowhage, holy basil, turmeric (Smotect , Smotect India) twice daily for 3 months reduces the number of cigarettes smoked daily and alveolar carbon monoxide and carboxyhemoglobin levels but does not improve lung capacity when compared with placebo (112115). It is unclear if these effects are due to bacopa, other ingredients, or the combination. More evidence is needed to rate bacopa for these uses.

(Read more about BACOPA)

POSSIBLY EFFECTIVE

• Gingivitis. Magnolia bark extract might modestly reduce gum bleeding and inflammation when added to gum or toothpaste. Details: One clinical study shows that chewing gum containing magnolia bark extract plus xylitol for 5 minutes three times daily for 30 days reduces gingival bleeding by 33%, compared with 24% after chewing gum containing xylitol alone (92459). Another clinical study in adults with gingivitis shows that using a fluoride toothpaste containing magnolia extract 0.3% twice daily reduces gingivitis severity by about 0.27 points on the gingival index after 3 months, compared to 0.15 points for patients using the toothpaste without magnolia extract (92464).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Aging skin. Although there is interest in using topical magnolia for aging skin, there is insufficient reliable information about the clinical effects of magnolia for this purpose.
• Allergic rhinitis (hay fever). Although there is interest in using oral magnolia for hay fever, there is insufficient reliable information about the clinical effects of magnolia for this condition.
• Anxiety. Oral magnolia has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in healthy females with mild anxiety shows that taking a proprietary blend of magnolia and phellodendron bark extract (Relora, Next Pharmaceuticals), standardized to 1.5% honokiol and 0.1% berberine, 250 mg three times daily for 6 weeks reduces temporary feelings of stress-induced anxiety almost 2-fold when compared with placebo. However, taking this product does not seem to improve long-standing feelings of stress-induced anxiety (34246). It is unclear if this effect is due to magnolia, other ingredients, or the combination. Additionally, this study was funded by the supplement manufacturer.
• Dental plaque. It is unclear if oral magnolia is beneficial in patients with dental plaque. Details: Clinical research in adults with gingivitis shows that using a toothpaste containing 0.3% magnolia extract twice daily modestly reduces plaque severity by about 0.41 points on the mean plaque index after 3 months, compared to a 0.27 point reduction for patients using the toothpaste without magnolia extract (92464). While statistically significant, this improvement might not be clinically meaningful.
• Diabetes. Although there is interest in using oral magnolia for diabetes, there is insufficient reliable information about the clinical effects of magnolia for this condition.
• Headache. Although there is interest in using oral magnolia for headache, there is insufficient reliable information about the clinical effects of magnolia for this condition.
• Menopausal symptoms. Oral magnolia has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A moderate-sized clinical study in postmenopausal patients shows that taking a specific combination of magnolia, Vitex agnus-castus, soy isoflavones, vitamin D, and lactobacillus (Estromineral Serena Plus, Meda Pharma SpA) daily for one year decreases the frequency and intensity of hot flashes and improves sleep quality and the ability to fall asleep when compared with soy isoflavones alone (95031). Additionally, a small clinical study shows that taking this same product daily for one year improves vasomotor symptoms, mood disorders, somatic symptoms, sleep disorders, blood pressure, and glycemic control when compared to baseline (110708). However, the validity of these findings is limited by a lack of control group. Overall, it is unclear if the effects of this magnolia-containing product in postmenopausal patients are due to magnolia, other ingredients, or the combination.
• Obesity. Oral magnolia has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in overweight females who report stress eating shows that taking a specific product containing a combination of bark extracts of magnolia plus phellodendron (Relora, Next Pharmaceuticals, Inc.) 250 mg three times daily for 6 weeks seems to prevent weight gain, compared with a 1.5 kg weight gain in those taking placebo (14349). This finding is limited because differences between groups were not statistically compared. Furthermore, it's unclear if this product induces weight loss.
• Postpartum depression. It is unclear if oral magnolia tea is beneficial for preventing postpartum depression. Details: A small clinical study in healthy postpartum patients shows that drinking 1 cup of magnolia tea daily for 3 weeks may improve depressive symptoms and sleep efficiency when compared with usual care alone. Magnolia tea (plant part unspecified) was steeped in 300 mL of hot water for 12 minutes prior to consumption (105089).
• Stress. Oral magnolia has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small low-quality clinical trial in moderately stressed healthy adults shows that taking a proprietary blend of magnolia and phellodendron bark extract (Relora, Next Pharmaceuticals) 250 mg twice daily for 4 weeks improves overall mood and decreases stress when compared with placebo (94904). It is unclear if this effect is due to magnolia, other ingredients, or the combination. Additionally, this study was funded by the supplement manufacturer. More evidence is needed to rate magnolia for these uses.

(Read more about MAGNOLIA)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acne. It is unclear if topical phellodendron is beneficial in patients with acne. Details: A small clinical study in patients with mild to moderate acne shows that applying a facial mask containing an unknown dose of phellodendron for 15-20 minutes daily for 3 days, then every other day for 8 weeks, reduces the number of acne lesions when compared to baseline. About 33% of patients showed a moderate improvement and 11% showed an excellent improvement in overall lesions at week 8. However, no significant difference in the total number of lesions was seen (97317).
• Benign prostatic hyperplasia (BPH). Oral phellodendron has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with BPH shows that taking five tablets of a specific traditional Chinese medicine product containing phellodendron bark, gardenia fruit, licorice root, safflower, Indian long pepper, and other ingredients three times daily with conventional therapy for 6 months improves storage-related lower urinary tract symptoms, such as urinary frequency, urinary urgency, and nocturia, when compared with placebo plus conventional therapy. However, this product did not appear to improve voiding-related symptoms (109450).
• Diabetes. Although there has been interest in using oral phellodendron for diabetes, there is insufficient reliable information about the clinical effects of phellodendron for this purpose.
• Diabetic foot ulcers. Topical phellodendron has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A large clinical study in adults with diabetic foot ulcers shows that applying gauze soaked in a Traditional Chinese Medicine (TCM) solution containing phellodendron, forsythia, honeysuckle, dandelion, and Scolopendra once daily for 4 weeks is associated with a higher rate of clinical efficacy and greater reduction in wound area when compared with applying gauze soaked with a Kangfuxin control solution (106438). Kangfuxin is an herbal TCM solution commonly used in the treatment of diabetic foot ulcers. The validity of these findings is limited by the unclear reporting of outcomes and discrepancies in the data. Additionally, it is unclear how these findings would compare with the use of standard care. A small clinical study in adults undergoing negative pressure wound aspiration therapy (NPWT) for diabetic foot ulcers shows that the addition of liquid compound phellodendron TCM irrigation to NPWT for 30 days improves wound symptom scores and wound healing and bacterial cultures compared with saline control (112389). A moderate size clinical study in adults undergoing ultrasonic debridement for diabetic foot ulcers shows that rinsing the wound with a liquid compound phellodendron TCM for 4 weeks reduces wound area and bacterial cultures and improves healing rate and efficacy compared with a Kangfuxin control solution (112390). The lack of blinding and randomization limits the validity of these findings. Additionally, in all three trials the phellodendron solution contained other TCM ingredients such as forsythia, honeysuckle, dandelion, golden cypress, and centipede (106438,112389,112390). Thus, it is unclear if the effects are due to phellodendron, other ingredients, or the combination.
• Obesity. Oral phellodendron has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small clinical study in overweight individuals shows that taking a specific blend of phellodendron and sweet orange extracts (Citrofen, Next Pharmaceuticals) 740 mg twice daily for 8 weeks reduces body weight by 3.7% when compared with placebo (94902,94903). This blend also seems to reduce levels of low-density lipoprotein (LDL) cholesterol by about 30% and triglycerides by about 14% when compared with placebo. It also appears to reduce systolic and diastolic blood pressure and fasting glucose (94902). Another specific combination product containing a combination of extracts of phellodendron plus magnolia (Relora, Next Pharmaceuticals) has been evaluated for weight loss in females who have a tendency to eat during stressful situations. One small clinical study in overweight, postmenopausal individuals shows that taking this product 250 mg three times daily for 6 weeks prevents weight gain when compared with placebo (14349). However, another small clinical study in overweight, postmenopausal individuals shows that taking this product at the same dose for 6 weeks does not decrease appetite, caloric intake, body weight, or waist or hip circumference when compared with placebo (94901).
• Osteoarthritis. Oral phellodendron has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with osteoarthritis of the knee shows that taking a specific blend of phellodendron and sweet orange extracts (Citrofen, Next Pharmaceuticals) 740 mg twice daily for 8 weeks improves functional measures of joint pain and movement by 16% to 41% when compared with placebo (94903).
• Peptic ulcers. Although there has been interest in using oral phellodendron for peptic ulcers, there is insufficient reliable information about the clinical effects of phellodendron for this purpose.
• Stress. Oral phellodendron has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with moderate stress shows that taking a specific product containing a combination of extracts of phellodendron plus magnolia (Relora, Next Pharmaceuticals) 250 mg twice daily for 4 weeks improves stress and mood by 11% when compared with placebo (94904).
• Tuberculosis. Although there has been interest in using oral phellodendron for tuberculosis, there is insufficient reliable information about the clinical effects of phellodendron for this purpose.
• Wound healing. Topical phellodendron has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A moderate sized clinical trial in adults recovering from anal fistulotomy shows that using 200 mL of compound phellodendron decoction in 1.8 liters of warm water for fumigation and sitting (sitz) bath for 7 days reduces pain, wound edema and exudation, and total wound healing time compared with fumigation and sitz bath with warm water alone (112391). Four other herbs were in the decoction, so it is unclear if the effects are due to phellodendron, other ingredients, or the combination. More evidence is needed to rate phellodendron for these uses.

(Read more about PHELLODENDRON)

POSSIBLY SAFE ...when used orally and appropriately, short-term. Bacopa has been used safely in clinical trials at a dose of up to 600 mg daily for up to 12 weeks (10058,10059,17946,97605).

CHILDREN: POSSIBLY SAFE
when used orally and appropriately, short-term. Clinical research suggests bacopa extract might be safe to use at a dose of 225 mg daily for up to 6 months or 320 mg daily for up to 14 weeks in children aged 6-14 years (33304,97603,109625).

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.

(Read more about BACOPA)

POSSIBLY SAFE ...when used orally and appropriately, short-term. A specific product containing magnolia extract and phellodendron extract (Relora, Next Pharmaceuticals, Inc.) has been used with apparent safety in clinical trials at a dose of 250 mg two to three times daily for up to 6 weeks (14349,34246,94904). ...when used topically in a toothpaste for up to 6 months (92464).

PREGNANCY: UNSAFE
when the magnolia flower bud is used orally due to reports of uterine stimulant activity (11953). There is insufficient reliable information available about the safety of using magnolia bark during pregnancy; avoid using.

LACTATION:
Insufficient reliable information available; avoid using.

(Read more about MAGNOLIA)

POSSIBLY SAFE ...when used orally and appropriately in combination with other ingredients, short-term. A specific product containing a combination of extracts of phellodendron plus magnolia (Relora, Next Pharmaceuticals) 250 mg 2-3 times daily has been used with apparent safety in clinical trials lasting up to 6 weeks (14349,94901,94904). Also, a specific product containing a combination of extracts of phellodendron plus sweet orange (Citrofen, Next Pharmaceuticals) 740 mg twice daily has been used with apparent safety for up to 8 weeks (94903). ...when used topically (97317). There is insufficient reliable information available about the safety of phellodendron when used orally as a single ingredient.

CHILDREN: LIKELY UNSAFE
when used orally in newborns. The berberine constituent of phellodendron can cause kernicterus in newborns, particularly preterm neonates with hyperbilirubinemia (2589).

PREGNANCY: LIKELY UNSAFE
when used orally. The berberine constituent of phellodendron is thought to cross the placenta and may cause harm to the fetus. Kernicterus has developed in newborn infants exposed to berberine (2589).

LACTATION: LIKELY UNSAFE
when used orally. The berberine constituent of phellodendron and other harmful constituents can be transferred to the infant through breast milk (2589).

(Read more about PHELLODENDRON)

ANTICHOLINERGIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, concurrent use might decrease the effectiveness of both agents.  Details Bacopa seems to inhibit acetylcholinesterase and might increase acetylcholine levels, which could counteract the effects of anticholinergic drugs (17946). Similarly, anticholinergic drugs might counteract the cholinergic effects of bacopa.

CEVIMELINE (Evoxac) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, bacopa might increase the effects and adverse effects of cevimeline.  Details In one case, a 58-year-old female taking cevimeline long-term for Sjogren syndrome experienced hyperhidrosis, malaise, nausea, and tachycardia shortly after taking a single dose of bacopa. Symptoms resolved after two days. Cevimeline is metabolized by cytochrome P450 (CYP) 2D6 and CYP3A4, and researchers theorize that bacopa may have inhibited these isoenzymes (109627). However, it is unclear if bacopa causes clinically significant inhibition of either CYP2D6 or CYP3A4.

CHOLINERGIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, concurrent use of bacopa with other cholinergic drugs might have additive effects.  Details Bacopa seems to inhibit acetylcholinesterase and might increase acetylcholine levels (17946). Theoretically, this could result in additive cholinergic effects when used with cholinergic drugs.

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, bacopa might increase the levels and adverse effects of CYP1A2 substrates.  Details Research on the effects of bacopa extracts on CYP1A2 enzymes is conflicting. Some in vitro evidence shows that bacopa extract can moderately and non-competitively inhibit CYP1A2, while other in vitro evidence suggests that any effect is unlikely to be clinically significant (97269,97606).

CYTOCHROME P450 2C19 (CYP2C19) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, bacopa might increase the levels and adverse effects of CYP2C19 substrates.  Details In vitro evidence suggests that bacopa extract can moderately and non-competitively inhibit CYP2C19 enzymes (97606). It is not known whether this is clinically significant.

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, bacopa might increase the levels and adverse effects of CYP2C9 substrates.  Details Research on the effect of bacopa extracts on CYP2C9 enzymes is conflicting. Some in vitro evidence suggests that bacopa extract can moderately and non-competitively inhibit CYP2C9, while other in vitro evidence suggests that any effect is unlikely to be clinically significant (97269,97606).

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, bacopa might increase the levels and adverse effects of CYP3A4 substrates.  Details Research on the effects of bacopa extracts on CYP3A4 enzymes is conflicting. Some in vitro evidence suggests that bacopa extract can moderately and competitively inhibit CYP3A4, while other in vitro evidence suggests that any effect is unlikely to be clinically significant (97269,97606).

THYROID HORMONE Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, bacopa might have additive effects when used with thyroid hormone.  Details Animal research suggests that bacopa increases thyroxine (T4) levels in mice by about 40% (33286).

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ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, magnolia might have additive effects and increase the risk of bleeding when used with anticoagulant or antiplatelet drugs.  Details In vitro research shows that the chemicals magnolol and honokiol, isolated from magnolia bark, inhibit platelet aggregation that is experimentally induced by collagen and arachidonic acid. However, they do not inhibit platelet aggregation that is induced by adenosine diphosphate, platelet-activating factor, or thrombin (18273). This interaction has not been reported in humans.

CNS DEPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use of large doses of magnolia bark and CNS depressants might have additive effects.  Details In vitro and animal research shows that constituents extracted from magnolia bark, especially honokiol and magnolol, have sedative effects. These effects may be due to the inhibition of catecholamine release and modulation of gamma-aminobutyric acid-A (GABA-A) receptors (11946,11952).

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ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, phellodendron might increase the risk of bleeding when used with anticoagulant or antiplatelet drugs.  Details Phellodendron contains berberine. In vitro and in vivo research suggest that berberine can inhibit platelet aggregation (33660,33694). Theoretically, phellodendron might also inhibit platelet aggregation.

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, phellodendron may increase the risk of hypoglycemia when taken with antidiabetes drugs.  Details Phellodendron contains berberine. Clinical research shows that berberine may lower blood glucose levels (20579,34247,34265,34282). Theoretically, phellodendron might also lower blood glucose levels.

ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, phellodendron might have additive effects with antihypertensive drugs.  Details Phellodendron contains berberine. Animal research suggests that berberine can have hypotensive effects (33692,34308). Also, a clinical study suggests that taking berberine in combination with amlodipine can lower systolic and diastolic blood pressure when compared with amlodipine alone (91956). Theoretically, phellodendron might also reduce blood pressure.

CNS DEPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, phellodendron might increase the sedative effects of CNS depressants.  Details Phellodendron contains berberine. Animal research suggests that berberine may have sedative effects (13519,33650,33664,33692). Theoretically, phellodendron might also have CNS depressants effects.

CYCLOSPORINE (Neoral, Sandimmune) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, phellodendron might increase blood levels of cyclosporine.  Details Phellodendron contains berberine. Preliminary clinical research shows that berberine can reduce metabolism of cyclosporine and increase serum levels, likely through inhibition of cytochrome P450 3A4 (CYP3A4), which metabolizes cyclosporine (13524). Theoretically, phellodendron might also reduce the metabolism of cyclosporine.

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, phellodendron might increase serum levels of drugs metabolized by CYP2C9.  Details Phellodendron contains berberine. Preliminary clinical research shows that berberine can inhibit CYP2C9 (34279). Theoretically, phellodendron might also inhibit CYP2C9.

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, phellodendron might increase serum levels of drugs metabolized by CYP2D6.  Details Phellodendron contains berberine. In vitro research and preliminary clinical evidence show that berberine can inhibit CYP2D6 (21117,34279,34297). Theoretically, phellodendron might also inhibit CYP2D6.

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, phellodendron might increase serum levels of drugs metabolized by CYP3A4.  Details Phellodendron contains berberine. In vitro research and preliminary clinical research show that berberine moderately inhibits CYP3A4 (13524,21114,34279,34297). Theoretically, phellodendron might also inhibit CYP3A4.

DEXTROMETHORPHAN (Robitussin DM, others) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, phellodendron may increase serum levels of dextromethorphan.  Details Phellodendron contains berberine. Preliminary clinical research shows that berberine can inhibit cytochrome P450 2D6 (CYP2D6) activity and reduce the metabolism of dextromethorphan (34279). Theoretically, phellodendron may also inhibit the metabolism of dextromethorphan.

LOSARTAN (Cozaar) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, phellodendron might reduce the therapeutic effects of losartan by decreasing its conversion to its active form.  Details Phellodendron contains berberine. Preliminary clinical research suggests that berberine can inhibit cytochrome P450 2C9 (CYP2C9) activity and reduce metabolism of losartan (34279). Theoretically, phellodendron might also inhibit the metabolism of losartan.

METFORMIN (Glucophage) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, phellodendron might increase the therapeutic and adverse effects of metformin.  Details Phellodendron contains berberine. In vitro and animal studies show that berberine can increase the systemic exposure and half-life of metformin, potentially increasing metformin's effects and side effects. This interaction seems to be most apparent when berberine is administered 2 hours prior to metformin. Taking berberine and metformin at the same time does not appear to increase systemic exposure to metformin (103195). It is unclear if phellodendron might have this same effect.

MIDAZOLAM (Versed) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, phellodendron might reduce metabolism of midazolam, which might increase the risk of severe adverse effects.  Details Phellodendron contains berberine. Preliminary clinical research shows that berberine can inhibit cytochrome P450 3A4 (CYP3A4) activity and reduce metabolism of midazolam (34279). Theoretically, phellodendron might also inhibit the metabolism of midazolam.

PENTOBARBITAL (Nembutal) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, phellodendron might increase the sedative effect of pentobarbital.  Details Phellodendron contains berberine. Animal research shows that berberine can prolong pentobarbital-induced sleeping time (13519). Theoretically, phellodendron might increase the sedative effects of pentobarbital.

TACROLIMUS (Prograf) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, phellodendron might increase blood levels of tacrolimus.  Details Phellodendron contains berberine. In a 16-year-old patient with idiopathic nephrotic syndrome who was being treated with tacrolimus 6.5 mg twice daily, intake of berberine 200 mg three times daily increased the blood concentration of tacrolimus from 8 to 22 ng/mL. Following a reduction of the tacrolimus dose to 3 mg daily, blood levels of tacrolimus decreased to 12 ng/mL (91954). It is unclear if phellodendron might have this same effect.

(Read more about PHELLODENDRON)

General ...Orally, bacopa is generally well tolerated.
Most Common Adverse Effects:
Orally: Abdominal cramps, diarrhea, dry mouth, headache, nausea.

Cardiovascular ...Orally, bacopa has been reported to cause palpitations (10058).

Gastrointestinal ...Orally, bacopa has been reported to cause abdominal cramps, abdominal pain, bloating, decreased appetite, diarrhea, dry mouth, excessive thirst, flatulence, indigestion, nausea, and increased stool frequency. Rates of adverse gastrointestinal events have ranged from 12% to 30% (10058,17946,33295,97605,109623,111520).

Musculoskeletal ...Orally, bacopa has been reported to cause arthralgia, muscle fatigue, and myopathy (10058,109623,111522). In one case, a 21-year-old male experienced progressive proximal weakness, muscle atrophy, weight loss, dark urine, and elevated serum markers of myopathy, with muscle biopsy showing immune-mediated necrotizing myopathy, after taking a supplement containing bacopa for 5 years (111522).

Neurologic/CNS ...Orally, bacopa has been reported to cause drowsiness, headache, insomnia, and vivid dreams (10058,10059,17946,109623).

Other ...Orally, bacopa has been reported to cause flu like symptoms and fatigue (10058,97605,111520).

(Read more about BACOPA)

General ...Orally, magnolia seems to be well tolerated.
Most Common Adverse Effects:
Topically: Contact dermatitis.

Dermatologic ...Topically, magnolia bark has been associated with reports of allergic contact dermatitis (92463,92468,95030,110709). In several cases, the use of anti-aging facial creams containing magnolia bark extract was associated with allergic contact dermatitis of the face (92463,92468,95030). In one case, the use of a vaginal gel containing magnolia bark extract was associated with allergic contact dermatitis of the vulva (110709). Symptoms typically resolve with the use of topical corticosteroids and discontinuation of magnolia bark extract (95030,110709). Patch testing suggests that the magnolia bark extract constituents magnolol and honokiol are responsible for this adverse effect (110709).

Endocrine ...In a clinical trial of an oral combination product containing extracts of magnolia and phellodendron, one patient reported thyroid dysfunction (14349). However, it's not known if this side effect is related to magnolia or some other factor.

Gastrointestinal ...In a clinical trial of an oral combination product containing extracts of magnolia and phellodendron, one patient reported heartburn (14349). However, it's not known if this side effect is related to magnolia or some other factor.

Neurologic/CNS ...In a clinical trial of an oral combination product containing extracts of magnolia and phellodendron, one patient reported shaking hands and perilabial numbness. Another patient reported fatigue and headache (14349). However, it's not known if these side effects are related to magnolia or some other factor.

Psychiatric ...In a clinical trial of an oral combination product containing extracts of magnolia and phellodendron, one patient reported sexual dysfunction (14349). However, it's not known if this side effect is related to magnolia or some other factor.

(Read more about MAGNOLIA)

General ...Orally, phellodendron seems to be well tolerated.

Endocrine ...Orally, a combination product containing extracts of phellodendron plus magnolia has been associated with one report of thyroid dysfunction in one clinical trial (14349,94901). However, it is unknown if this is related to phellodendron or some other factor.

Gastrointestinal ...Orally, a combination product containing extracts of phellodendron plus magnolia has been associated with one report of heartburn in one clinical trial (14349,94901). However, it is unknown if this is related to phellodendron or some other factor.

Genitourinary ...Orally, a combination product containing extracts of phellodendron plus magnolia has been associated with one report of sexual dysfunction in one clinical trial (14349,94901). However, it is unknown if this is related to phellodendron or some other factor.

Neurologic/CNS ...Orally, a combination product containing extracts of phellodendron plus magnolia has been associated with single reports of shaking hands, perilabial numbness, fatigue, and headache in clinical research (14349,94901). However, it is unknown if this is related to phellodendron or some other factor.

(Read more about PHELLODENDRON)