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INSUFFICIENT RELIABLE EVIDENCE to RATE

• Age-related cognitive decline. Oral fo-ti has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with mild age-related cognitive decline shows that taking a combination product containing fo-ti root and Panax ginseng as five capsules three times daily for 3 months improves memory when compared to baseline (50720). The validity of these findings is limited by a lack of placebo control group.
• Aging. Although there has been interest in using oral fo-ti for aging, there is insufficient reliable information about the clinical effects of fo-ti for this purpose.
• Alopecia areata. Although there has been interest in using oral fo-ti for alopecia areata, there is insufficient reliable information about the clinical effects of fo-ti for this purpose.
• Alzheimer disease. Although there has been interest in using oral fo-ti for Alzheimer disease, there is insufficient reliable information about the clinical effects of fo-ti for this purpose.
• Androgenic alopecia. Although there has been interest in using oral fo-ti for androgenic alopecia, there is insufficient reliable information about the clinical effects of fo-ti for this purpose.
• Cardiovascular disease (CVD). Although there has been interest in using oral fo-ti for CVD, there is insufficient reliable information about the clinical effects of fo-ti for this purpose.
• Dyslipidemia. Oral fo-ti has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in adults in China with dyslipidemia shows that taking four capsules of a specific combination product (Blood Fat Droplets, Vita Green Pharmaceutical Ltd.), containing extracts of fo-ti 43 mg, hawthorn 129 mg, Asian water plantain 86 mg, corn silk 86 mg, reishi mushroom 43 mg, and white mulberry 43 mg, twice daily for 12 weeks decreases low-density lipoprotein (LDL) cholesterol by 12 mg/dL, or around 9%, but does not improve total cholesterol, high-density lipoprotein (HDL) cholesterol, or triglyceride levels, when compared with placebo (99854).
• Insomnia. Although there has been interest in using oral fo-ti for insomnia, there is insufficient reliable information about the clinical effects of fo-ti for this purpose.
• Osteoarthritis. Although there has been interest in using oral fo-ti for osteoarthritis, there is insufficient reliable information about the clinical effects of fo-ti for this purpose.
• Osteoporosis. Although there has been interest in using oral fo-ti for osteoporosis, there is insufficient reliable information about the clinical effects of fo-ti for this purpose.
• Parkinson disease. Although there has been interest in using oral fo-ti for Parkinson disease, there is insufficient reliable information about the clinical effects of fo-ti for this purpose.
• Wrinkled skin. Although there has been interest in using topical fo-ti for wrinkled skin, there is insufficient reliable information about the clinical effects of fo-ti for this purpose. More evidence is needed to rate fo-ti for these uses.

(Read more about FO-TI)

There is insufficient reliable information available about the effectiveness of glossy privet.

(Read more about GLOSSY PRIVET)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Age-related macular degeneration (AMD). It is unclear if oral goji berry reduces the risk of developing AMD. Details: A small, unblinded clinical study in healthy adults aged 45 to 65 years shows that consuming goji berries 28 grams five times a week for 90 days improves macular pigment optical density, which is a marker for AMD, when compared to baseline (110767). The validity of this finding is limited by the lack of statistical comparison to the other study group that received a supplement containing lutein and zeaxanthin.
• Cancer. Although there is interest in using oral goji for cancer, there is insufficient reliable information about the clinical effects of goji for this condition.
• Cardiovascular disease (CVD). It is unclear if oral goji improves risk factors for CVD. Details: A meta-analysis of 6 mostly small clinical studies of adults in China shows that consuming goji as polysaccharide extract or juice for 1-3 months modestly improves triglycerides, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and fasting blood glucose but does not impact total cholesterol when compared with no treatment or placebo (110765). Another meta-analysis of 4 small clinical studies in adults also shows that consuming goji polysaccharide extract or goji berries for 1-4 months modestly improves triglycerides and HDL but does not impact total or LDL cholesterol when compared with placebo or healthy eating. Goji also had no impact on systolic or diastolic blood pressure, or markers of oxidative stress (110768). However, the interpretation of the findings from these meta-analyses is limited by the use of variable goji forms and doses, as well as inclusion of studies in heterogeneous patients, including healthy people, patients with diabetes, and patients with metabolic syndrome. Furthermore, most studies were conducted in China; it is unclear if these benefits can be extrapolated to other geographic locations.
• Cognitive function. It is unclear if oral goji berry improves cognition in healthy young individuals. Details: A small clinical crossover study in healthy participants 14-24 years of age shows that taking goji berry fruit water extract (BIOMIX Company) 3600 mg in 3 divided doses daily for 4 weeks might improve certain cognitive measures such as verbal learning, short-term memory, and attention when compared with baseline (105488). The validity of these findings are limited due to incomplete outcome reporting and a lack of statistical comparisons between the treatment and placebo groups.
• Cough. Although there is interest in using oral goji for cough, there is insufficient reliable information about the clinical effects of goji for this purpose.
• Depression. It is unclear if oral goji berry polysaccharide is beneficial for adolescents with subthreshold depression. Details: A small clinical study in adolescents aged approximately 15 years with subthreshold depression in China shows that taking goji berry polysaccharide extract 300 mg daily for 6 weeks modestly improves clinician-assessed depression scores (i.e. Hamilton Depression Scale, HAMD-24) but does not improve self-reported depression scores (i.e. Beck Depression Inventory) or scores assessing sleep quality, psychological distress, or anxiety when compared with placebo (110769). However, these results are from an interim analysis, which limits the interpretation of these findings. Furthermore, it is unclear if results can be extrapolated to patients in other geographic locations.
• Diabetes. It is unclear if oral goji berry polysaccharides improve glycemic control in patients with diabetes. Details: One small clinical study in patients with type 2 diabetes shows that taking goji fruit polysaccharide powder 150 mg twice daily for 3 months results in a slightly lower postprandial glucose area under the curve (AUC), but does not seem to affect insulin levels or insulin resistance, when compared with placebo. A subgroup of patients who were not taking antidiabetes medications had a greater reduction in postprandial blood glucose (92117).
• Dry eye. Although there is interest in using oral goji for dry eye, there is insufficient reliable information about the clinical effects of goji for this purpose.
• Erectile dysfunction (ED). Although there is interest in using oral goji for ED, there is insufficient reliable information about the clinical effects of goji for this condition.
• Hypertension. Although there is interest in using oral goji root bark for hypertension, there is insufficient reliable information about the clinical effects of goji for this condition.
• Obesity. It is unclear if oral goji berry juice improves weight loss. Details: Preliminary clinical research in healthy, overweight adults shows that drinking a specific goji fruit juice (GoChi, FreeLife International LLC) 120 mL daily for 14 days while following a weight loss diet and participating in an exercise program decreases waist circumference by about 4.7 cm more than exercise and diet alone. However, drinking goji berry juice along with diet and exercise does not improve body weight, body mass index, or body fat when compared with diet and exercise alone (52536).
• Quality of life. Small clinical studies suggest that oral goji berry juice may modestly improve quality of life in healthy adults. Details: Small clinical studies in healthy adults suggest that taking a specific standardized goji fruit juice (GoChi, FreeLife International LLC) 120 mL daily for 14-30 days improves subjective measures of energy levels, athletic performance, sleep quality, mental acuity, calmness, feelings of well-being, and gastrointestinal regularity when compared with placebo (17082,52532,52542). These studies were funded by the juice manufacturer.
• Sunburn. It is unclear if oral goji extract can prevent sunburn. Details: A small clinical study in healthy Japanese adults shows that taking goji extract 900 mg daily for 8 weeks reduces and accelerates resolution of erythema after exposure to a standard dose of UVB irradiation when compared with placebo (110770). All study participants were highly UV-sensitive; it is unclear whether these results can be extrapolated to individuals less sensitive to UV irradiation.
• Tinnitus. Although there is interest in using oral goji for tinnitus, there is insufficient reliable information about the clinical effects of goji for this purpose. More evidence is needed to rate goji for these uses.

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POSSIBLY EFFECTIVE

• Chronic kidney disease (CKD). Oral rehmannia acteosides might reduce proteinuria when used in conjunction with angiotensin II receptor blockers in patients with CKD. Details: A large clinical trial in adults with chronic glomerulonephritis shows that taking rehmannia acteosides extract 400 mg twice daily, in conjunction with irbesartan 150 mg daily, for 8 weeks decreases proteinuria by 36%, compared with a reduction of 28% with irbesartan alone (93662).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Aplastic anemia. It is unclear if oral rehmannia is beneficial in patients with aplastic anemia. Details: A small clinical study in adults with aplastic anemia shows that taking rehmannia polysaccharide (dose unknown), in conjunction with stanozolol, increases the incidence of symptom remission by 45% when compared with stanozolol alone (70704).
• Atopic disease. Although there has been interest in using oral rehmannia for atopic disease, there is insufficient reliable information about the clinical effects of rehmannia for this purpose.
• Diabetes. Although there has been interest in using oral rehmannia for diabetes, there is insufficient reliable information about the clinical effects of rehmannia for this purpose.
• Diabetic nephropathy. Oral rehmannia has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A large clinical study in adults with chronic kidney disease due to type 2 diabetes receiving standard care with an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker shows that taking a specific combination product (Rehmannia-6, PuraPharm) containing rehmannia, Japanese cornel dogwood, wild yam, poria mushroom, Asian water plantain, and peony root bark twice daily for 48 weeks modestly slows the decline in kidney function when compared with standard care alone (112821). It is unclear if this effect is due to rehmannia, other ingredients, or the combination.
• Metabolic syndrome. Although there has been interest in using oral rehmannia for metabolic syndrome, there is insufficient reliable information about the clinical effects of rehmannia for this purpose.
• Obesity. It is unclear if oral rehmannia root extract is beneficial in patients with obesity. Details: A very small clinical study in females with obesity shows that taking steamed rehmannia root extract 4 grams twice daily for 8 weeks decreases waist circumference by 2.6%, but does not affect body weight or body fat percentage, when compared to baseline (93660). The validity of these findings is limited by the lack of a control group.
• Osteoporosis. Although there has been interest in using oral rehmannia for osteoporosis, there is insufficient reliable information about the clinical effects of rehmannia for this purpose.
• Rheumatoid arthritis (RA). Although there has been interest in using oral rehmannia for RA, there is insufficient reliable information about the clinical effects of rehmannia for this purpose. More evidence is needed to rate rehmannia for these uses.

(Read more about REHMANNIA)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Androgenic alopecia. Although there has been interest in using oral white mulberry for androgenic alopecia, there is insufficient reliable evidence about the clinical effects of white mulberry for this purpose.
• Common cold. Although there has been interest in using oral white mulberry for symptoms of the common cold, including cough and sore throat, there is insufficient reliable evidence about the clinical effects of white mulberry for this purpose.
• Diabetes. While research is mixed, most small clinical studies suggest that oral white mulberry does not reduce fasting blood glucose or glycated hemoglobin (HbA1c) in patients with type 2 diabetes; however, it does seem to improve insulin resistance and postprandial blood glucose in these patients. Details: A meta-analysis of 4 small, mostly low-quality clinical studies in adults with impaired glucose tolerance or type 2 diabetes shows that taking white mulberry extract for 12 weeks does not reduce HbA1c when compared with placebo, dietary education, or no treatment. White mulberry extract also does not reduce fasting plasma glucose but may improve glucose intolerance (110480). However, studies utilized heterogeneous dosing regimens, with doses ranging from 500 mg twice daily to 4.6 grams three times daily and 1-deoxynojirimycin (DNJ) content in each dose ranging from 5-18 mg. Additionally, a small clinical study in adults with type 2 diabetes not included in the analysis above shows that taking white mulberry extract 300 mg twice daily for 12 weeks improves insulin resistance but does not reduce fasting blood glucose or HbA1c when compared with placebo (110481). Due to its small size, this study may have been inadequately powered to detect a difference between groups. One clinical study in adults with type 2 diabetes shows that taking powdered white mulberry leaf 1 gram three times daily for 4 weeks reduces fasting blood glucose levels by 27% compared with an 8% reduction with glyburide 5 mg daily. However, neither treatment significantly reduced HbA1c levels over the 4-week period (16494). The short study duration may explain the lack of significant HbA1c reduction. The effect of white mulberry on postprandial glucose levels has also been assessed. Taking a single 0.8-1.2 gram dose of powdered white mulberry leaf standardized to contain DNJ 1.5% or taking a single 250 mg dose of a specific white mulberry leaf extract (Reducose, Phynova Group) standardized to contain DNJ 4.5% to 5.5% reduces peak blood glucose levels after ingestion of 50-75 grams of sucrose when compared with placebo in adults with or without type 2 diabetes (16495,17051,105796).
• Hyperlipidemia. It is unclear if oral white mulberry is beneficial in patients with hyperlipidemia; the available research has mixed results. Details: A small clinical study in adults with type 2 diabetes shows that taking white mulberry extract 300 mg twice daily for 12 weeks does not decrease serum triglycerides, or levels of total, low-density lipoprotein (LDL), or very-low-density lipoprotein (VLDL) cholesterol when compared with placebo (110481). Due to its small size, this study may have been inadequately powered to detect a difference between groups. However, another small clinical study in adults with type 2 diabetes shows that taking white mulberry leaf 1 gram three times daily for 4 weeks reduces total cholesterol levels by 12%, triglycerides by 16%, LDL by 23%, and VLDL by 17% when compared to baseline. Plasma HDL was increased by 18% (16494). The validity of these findings is limited by the lack of a comparator group. White mulberry has also been studied in combination with other ingredients. In one small clinical study, taking a specific product (LopiGLIK, Akademy Pharma) containing white mulberry leaf extract 200 mg, berberine, and red yeast rice daily for 4 weeks reduced LDL cholesterol to less than 130 mg/dL in 57% of participants, compared with only 22% of those receiving a different combination product (Armolipid Plus, RottapharmSpA) that contains red yeast rice, berberine, and other ingredients, without white mulberry. Both products reduced triglycerides and total cholesterol to a similar extent (100624).
• Hypertension. Although there has been interest in using oral white mulberry for hypertension, there is insufficient reliable evidence about the clinical effects of white mulberry for this purpose.
• Impaired glucose tolerance (prediabetes). It is unclear if oral white mulberry is beneficial in patients with impaired glucose tolerance. Details: One small clinical study in obese patients with impaired glucose tolerance shows that taking white mulberry leaf powder 4.6 grams three times daily before meals for 12 weeks decreases fasting blood glucose by around 4 mg/dL and glycated hemoglobin (HbA1c) by 0.12% when compared to baseline. Neither measure was improved in the placebo group (103870). Although a statistically significant improvement in glycemic control was established, the observed reductions in fasting plasma glucose and HbA1c were modest and unlikely to be clinically meaningful.
• Joint pain. Although there has been interest in using oral white mulberry for joint pain, including joint pain associated with osteoarthritis and rheumatoid arthritis (RA), there is insufficient reliable information about the clinical effects of white mulberry for these conditions.
• Obesity. It is unclear if oral white mulberry can reduce body weight in patients who are obese or overweight. Details: A small clinical study in overweight and obese adults on a calorie-restricted diet shows that taking white mulberry extract 800 mg three times daily with meals for 90 days reduces body weight by about 10%, compared to a loss of about 3% with placebo (100627). However, a small clinical study in overweight and obese adults with type 2 diabetes shows that taking white mulberry extract 300 mg twice daily for 12 weeks does not decrease body weight when compared with placebo (110481).
• Osteoporosis. Although there has been interest in using oral white mulberry for osteoporosis, there is insufficient reliable evidence about the clinical effects of white mulberry for this purpose. More evidence is needed to rate white mulberry for these uses.

(Read more about WHITE MULBERRY)

POSSIBLY UNSAFE ...when used orally. Fo-ti has been linked to several cases of liver damage (7626,7627,14327,14347,14482,16459,17192,50711,50727,50729) (92892,92895,112231).

CHILDREN: POSSIBLY UNSAFE
when used orally. Fo-ti has been linked to several cases of liver damage in adults and at least one case in a 5-year-old child (14339,92895).

PREGNANCY: POSSIBLY UNSAFE
when used orally. Fo-ti contains anthraquinone constituents, which can exert a stimulant laxative effect. Bulk-forming or emollient laxatives are preferred in pregnancy (272). Fo-ti has also been linked to several cases of liver damage (7626,7627,14327). There is insufficient reliable information available about the safety of fo-ti when used topically during pregnancy.

LACTATION: POSSIBLY UNSAFE
when used orally. Anthraquinone constituents can cross into breast milk and might cause loose stools in some breast-fed infants (272). Fo-ti has also been linked to several cases of liver damage (7626,7627,14327). There is insufficient reliable information available about the safety of fo-ti when used topically during lactation.

(Read more about FO-TI)

POSSIBLY SAFE ...when used orally and appropriately (12).

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

(Read more about GLOSSY PRIVET)

POSSIBLY SAFE ...when goji fruit preparations are used orally and appropriately, short-term. Goji berry whole fruit, boiled or steamed, has been used with apparent safety at a dose of 15 grams daily for 16 weeks (105489). Other goji berry products have also been used with apparent safety in clinical research, including a specific goji fruit juice (GoChi, FreeLife International) 120 mL daily for 30 days (52532), a goji fruit polysaccharide 300 mg daily for 3 months (92117), and a specific milk-based formulation of goji berry (Lacto-Wolfberry, Nestlé Research Center) for 3 months (52539). There has been some concern about the atropine content of goji; however, most analyses show that levels of atropine in goji berries from China and Thailand are far below potentially toxic levels (52524,94667). There is insufficient reliable information available about the safety of oral use of other parts of the goji plant.

PREGNANCY AND LACTATION:
Insufficient reliable information available. Some animal research shows that goji fruit may stimulate the uterus (12). However, this has not been reported in humans. Until more is known, avoid using during pregnancy or lactation.

(Read more about GOJI)

POSSIBLY SAFE ...when used orally and appropriately, short term. Rehmannia root extract 4 grams daily or rehmannia leaf extract 800 mg daily has been used with apparent safety for 8 weeks in clinical studies (93660,93662).

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

(Read more about REHMANNIA)

POSSIBLY SAFE ...when used orally and appropriately. White mulberry powdered leaf or leaf extract has been used with apparent safety at doses of up to 4.6 grams three times daily for up to 12 weeks (16494,17051,100627,103870,105796,110480). There is insufficient reliable information available about the safety of white mulberry berries.

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

(Read more about WHITE MULBERRY)

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, fo-ti might increase the risk of hypoglycemia when taken with antidiabetes drugs.  Details Fo-ti reportedly has hypoglycemic effects (5,19).

CONTRACEPTIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, taking large amounts of fo-ti might interfere with contraceptive drugs due to competition for estrogen receptors.  Details In vitro research suggests that fo-ti extract has estrogenic activity (10143,16061,50710).

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, fo-ti might increase or decrease the levels and clinical effects of drugs metabolized by CYP1A2.  Details In vitro research suggests that fo-ti might inhibit CYP1A2 (12479,112351). Additionally, in vitro research suggests that the degree of CYP1A2 inhibition depends on the type of fo-ti extract (i.e., the raw plant leads to greater inhibition than extensively processed extracts) (112351). However, in an animal study, an aqueous extract of fo-ti inhibited CYP1A2 while an alcoholic extract of fo-ti induced CYP1A2 (92898). Induction or inhibition of CYP1A2 by fo-ti has not been reported in humans.

CYTOCHROME P450 2B6 (CYP2B6) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, fo-ti might increase the levels and clinical effects of drugs metabolized by CYP2B6.  Details Animal research suggests that fo-ti might inhibit CYP2B6 (92898). One in vitro study suggests that the degree of CYP2B6 inhibition may depend on the type of fo-ti extract (i.e., the raw plant leads to greater inhibition than extensively processed extracts) (112351). However, this interaction has not been reported in humans.

CYTOCHROME P450 2C19 (CYP2C19) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, fo-ti may increase the levels and clinical effects of drugs metabolized by CYP2C19.  Details Animal and in vitro research suggests that fo-ti may inhibit CYP2C19 (12479,92898,112351). An in vitro study suggests that the degree of CYP2C19 inhibition may depend on the type of fo-ti extract (i.e., the raw plant leads to greater inhibition than extensively processed extracts) (112351). However, this interaction has not been reported in humans.

CYTOCHROME P450 2C8 (CYP2C8) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, fo-ti might increase the levels and clinical effects of drugs metabolized by CYP2C8.  Details In vitro research suggests that fo-ti might inhibit CYP2C8 (112351). However, this interaction has not been reported in humans.

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, fo-ti may increase the levels and clinical effects of drugs metabolized by CYP2C9.  Details Animal and in vitro research suggests that fo-ti may inhibit CYP2C9 (12479,92898,112351). However, this interaction has not been reported in humans.

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, fo-ti may increase the levels and clinical effects of drugs metabolized by CYP2D6.  Details Animal research suggests that fo-ti might inhibit CYP2D6 (92898). Additionally, an in vitro study suggests that the degree of CYP2D6 inhibition may depend on the type of fo-ti extract (i.e., the raw plant leads to greater inhibition than extensively processed extracts) (112351). However, this interaction has not been reported in humans.

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, fo-ti might increase the levels and clinical effects of drugs metabolized by CYP3A4.  Details In vitro research suggests that fo-ti might inhibit CYP3A4 (12479,112351). One in vitro study suggests that the degree of CYP3A4 inhibition may depend on the type of fo-ti extract (i.e., the raw plant leads to greater inhibition than extensively processed extracts) (112351). However, this evidence conflicts with animal research suggesting that fo-ti does not inhibit CYP3A4 (92898). This interaction has not been reported in humans.

DIGOXIN (Lanoxin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, fo-ti, particularly raw fo-ti root, might increase the risk of hypokalemia and cardiotoxicity when taken with digoxin.  Details Raw fo-ti root contains anthraquinone derivatives, which might have stimulant laxative effects (5,16459). In vitro research shows that fermented and processed fo-ti root have reduced laxative effects compared with raw fo-ti root (99855).

DIURETIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, fo-ti, particularly raw fo-ti root, might increase the risk of hypokalemia when taken with diuretic drugs.  Details Raw fo-ti root contains anthraquinone derivatives, which might have stimulant laxative effects and compound diuretic-induced potassium loss (5,16459). In vitro research shows that fermented and processed fo-ti root have reduced laxative effects compared with raw fo-ti root (99855).

ESTROGENS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, taking large amounts of fo-ti might interfere with hormone replacement therapy through competition for estrogen receptors.  Details In vitro research suggests that fo-ti extract has estrogenic activity (10143,16061,50710).

HEPATOTOXIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, fo-ti might increase the risk of liver damage when taken with hepatotoxic drugs.  Details Fo-ti has been linked to liver damage in many reports (7626,7627,14327,14339,14347,14482,16459,17192,50711,50727,50729,92892,92895).

STIMULANT LAXATIVES Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, fo-ti, particularly raw fo-ti root, might increase the risk of fluid and electrolyte depletion when taken with stimulant laxatives.  Details Raw fo-ti root contains anthraquinone derivatives, which might have stimulant laxative effects (5,16459). However, in vitro research shows that fermented and processed fo-ti root have reduced laxative effects compared with raw fo-ti root (99855).

SULINDAC (Clinoril) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, fo-ti might increase or decrease the levels and clinical effects of sulindac.  Details Animal research suggests that the type of fo-ti extract might affect the levels of sulindac differently; the raw plant may increase levels, but processed parts may decrease levels (112351). Induction or inhibition of CYP1A2 by fo-ti has not been reported in humans.

WARFARIN (Coumadin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, fo-ti might increase the effects and adverse effects of warfarin.  Details Fo-ti may have stimulant laxative effects and cause diarrhea, especially when the raw or unprocessed fo-ti root is used (5,12,16459,50733,99855). Diarrhea can increase the effects of warfarin, increase international normalized ratio (INR), and increase the risk of bleeding. Also, fo-ti has been linked to cases of acute liver failure which can decrease clotting factor production and increase the effects of warfarin. In one case, a patient who had been stable on warfarin presented with acute hepatitis and an INR elevated to 14.98. The patient had been taking fo-ti for 90 days prior to admission. Discontinuation of warfarin and fo-ti lead to a decrease in the INR and full recovery (17192).

(Read more about FO-TI)

(Read more about GLOSSY PRIVET)

ANTIDIABETES DRUGS Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = B Theoretically, concomitant use of goji fruit polysaccharides or goji root bark with antidiabetes drugs might have additive effects.  Details Animal and in vitro research show that goji root bark and fruit polysaccharides might have hypoglycemic effects (7126,92118,94667). However, clinical research has only shown that taking goji fruit polysaccharides with or without antidiabetes drugs modestly reduces postprandial glucose when compared with control, with no reports of hypoglycemia (92117).

ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use of goji root bark, but not goji fruit, with antihypertensive drugs might have additive effects.  Details Animal and in vitro research suggest that goji root bark has hypotensive effects (7126,94667). However, goji fruit juice does not appear to reduce systolic or diastolic blood pressure in humans (17082).

CYTOCHROME P450 2C19 (CYP2C19) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, goji berry might inhibit CYP2C19 and reduce metabolism of CYP2C19 substrates.  Details In vitro research shows that goji berry tincture and juice inhibit CYP2C19 enzymes (105486). Concomitant use with goji may decrease metabolism and increase levels of CYP2C19 substrates. However, this has not been reported in humans.

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, goji berry might inhibit CYP2C9 and reduce metabolism of CYP2C9 substrates.  Details In vitro research shows that goji berry tincture and juice inhibit CYP2C9 enzymes (105486). Additionally, multiple case reports suggest that goji berry concentrated tea and juice inhibit the metabolism of warfarin, a CYP2C9 substrate (7158,105462). Concomitant use with goji may decrease metabolism and increase levels of CYP2C9 substrates.

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, goji berry might inhibit CYP2D6 and reduce metabolism of CYP2D6 substrates.  Details In vitro research shows that goji berry juice inhibits CYP2D6 enzymes (105486). Concomitant use with goji may decrease metabolism and increase levels of CYP2D6 substrates. However, this has not been reported in humans.

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, goji berry might inhibit CYP3A4 and reduce metabolism of CYP3A4 substrates.  Details In vitro research shows that goji berry juice inhibits CYP3A4 enzymes (105486). Concomitant use with goji may decrease metabolism and increase levels of CYP3A4 substrates. However, this has not been reported in humans.

FLECAINIDE (Tambocor) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, goji berry might increase the levels and clinical effects of flecainide.  Details In one case report, a 75-year-old patient stable on flecainide and warfarin presented to the emergency room with fainting and pleomorphic arrhythmia caused by flecainide toxicity. Flecainide toxicity was attributed to drinking 1-2 glasses of concentrated goji tea daily for 2 weeks. Theoretically, goji may have inhibited the cytochrome P450 2D6 (CYP2D6) metabolism of flecainide (105462).

WARFARIN (Coumadin) Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Probable •  Level of Evidence = D Goji can increase the effects of warfarin and possibly increase the risk of bleeding.  Details There are at least 5 case reports of increased international normalized ratio (INR) in patients stabilized on warfarin who began drinking goji juice, concentrated goji tea, or goji wine (7158,16529,23896,105462,105487). Goji may inhibit the metabolism of warfarin by cytochrome P450 2C9 (CYP2C9) (7158).

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ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, rehmannia might increase the risk of hypoglycemia when taken with antidiabetes drugs.  Details Animal research shows that rehmannia may have hypoglycemic effects (15061,93668).

ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, rehmannia might increase the risk of hypotension when taken with antihypertensive drugs.  Details Animal research shows that rehmannia may have hypotensive effects. Laboratory research shows that formulations of dried and processed rehmannia root inhibit angiotensin-converting enzyme (ACE) (104272).

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ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, white mulberry leaf might increase the risk of hypoglycemia when taken with antidiabetes drugs.  Details Clinical research shows that white mulberry leaf can lower blood glucose levels (16494,16495,17051,103870,105796). Advise patients to monitor glucose levels closely.

ORGANIC CATION TRANSPORTER 2 (OCT2) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, white mulberry leaf might slow the elimination and increase the adverse effects of drugs which are OCT2 substrates.  Details Animal research shows that coadministration of white mulberry leaf extract with metformin, an OCT2 substrate, slows the renal elimination of metformin via inhibition of OCT2 activity (103869). OCT2 is expressed in the kidneys and is responsible for transporting cationic drugs into tubular epithelial cells in order to be excreted in the urine.

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General ...Orally, fo-ti may be unsafe.
Most Common Adverse Effects:
Orally: Abdominal pain, diarrhea, nausea, and vomiting with use of unprocessed fo-ti.
Serious Adverse Effects (Rare):
Orally: Hepatotoxicity with processed or unprocessed fo-ti.

Dermatologic ...Orally, one case of a fine maculopapular rash was reported in a patient taking the herbal product known as Shen-Min, which contains fo-ti. Symptoms resolved within three weeks after discontinuing the product (14482). It is unclear if the rash was due to fo-ti or other ingredients in the herbal product.

Gastrointestinal ...Orally, unprocessed fo-ti may cause diarrhea, abdominal pain, nausea, and vomiting (12,50733).

Hematologic ...Orally, one case of mild eosinophilia was reported in a patient taking the herbal product known as Shen-Min, which contains fo-ti. Symptoms resolved within three weeks after discontinuing the product (14482). It is unclear if this reaction was due to fo-ti or other ingredients in the herbal product. A case of agranulocytosis was reported in a 65-year-old female taking fo-ti 30 grams/day for 17 days. The patient recovered gradually following a 15-day hospitalization, which included treatment with intravenous steroids and granulocyte colony-stimulating factor (112231).

Hepatic ...Orally, cases of liver damage due to both processed and unprocessed fo-ti have been well documented in the medical literature. (7626,7627,14327,14339,14347,14482,16459,17192,50711,50726)(50727,50729,92892,92895,112231).
In a systematic review, around 450 cases of hepatitis associated with fo-ti were identified. These cases occurred in patients 5-78 years of age. Liver damage occurred at a wide range of doses, formulations, and durations of intake. The type of liver injury ranged from hepatocellular, to cholestatic, or mixed. Outcomes ranged from full recovery to cirrhosis, liver transplantation, and/or death. The evidence suggests that when the daily fo-ti dose is less than 12 grams, the median time to occurrence of liver damage is 60 days. When the daily fo-ti dose is more than 12 grams, the median time to liver damage is 30 days (92895). Presenting signs and symptoms may include jaundice, abdominal pain, nausea, fatigue, loss of appetite, dark urine, myalgias, and elevations in liver function tests (LFTs), ferritin, transferrin, prothrombin time, and INR (17192,92892). Other manifestations may include fever, skin rash, thrombocytopenia, pancytopenia, and arthralgias. Symptoms and increased LFTs usually seem to resolve within a month after discontinuing fo-ti (7626,7627,14339,14347,14482,16459). In one case series, liver enzymes began to normalize 48 hours after discontinuation of fo-ti and treatment with S-adenosylmethionine, compound glycyrrhizin injection, polyene phosphatidylcholine, and reduced glutathione. All patients were eventually discharged home in stable condition (92892). Rechallenge with fo-ti should not be attempted. A patient who had recovered from hepatitis associated with fo-ti use presented with myalgias and markedly elevated LFTs after a single dose of the herb (17192).
It is thought that this idiosyncratic reaction leading to liver damage is at least partially related to genetic polymorphisms. Cytochrome P450 1A2 (CYP1A2) is the predominant enzyme involved in biotransformation of emodin, a constituent of fo-ti thought to play a role in liver damage. In one genetic study, the frequency of CYP1A2*1C mutation in fo-ti induced drug-induced liver injury patients was 46.5%, which is significantly higher than the 27.9% frequency of liver injury reported in healthy patients without the mutation. Patients with a CYP1A2*1C mutation may have decreased activity of the CYP1A2 enzyme, which could inhibit the metabolism of fo-ti, causing an accumulation of toxic substances (92897).

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General ...None reported. However, respiratory allergies (allergic rhinitis, asthma) and cross-allergenicity have been reported with the pollen of other Oleaceae species including common privet (Ligustrum vulgare), olive, ash, and lilac (416,417).

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General ...Orally, goji fruit seems to be well tolerated.
Serious Adverse Effects (Rare):
Orally: Allergic reactions including anaphylaxis.

Dermatologic ...A case of photosensitivity secondary to consumption of goji berries has been reported. The patient presented with a pruriginous eruption that had lasted for 2 weeks. The patient had been taking goji berries for 5 months and cat's claw for 3 months. Upon testing, it was revealed that the patient tested positive to goji berries in a photoprovocation test, but not to cat's claw (40263).

Hepatic ...Orally, consumption of goji berries has been associated with a single case report of autoimmune hepatitis (52541). A case of acute hepatitis has also been reported in a female who consumed 2 ounces of a specific combination product (Euforia, Nuverus International) containing goji berry, pomegranate, curcumin, green tea, noni, acai berry, aloe vera, blueberry, resveratrol, mangosteen, and black seed, daily for one month. It is unclear whether the liver injury was caused by goji berry, other ingredients, or the combination (90125).

Immunologic ...Several cases of allergic reactions secondary to consumption of goji berries have been reported. Symptoms included facial angioedema with dyspnea, pharyngeal itching, itching in the mouth, ears, and axilla, labial angioedema, and perioral skin rash (92116). Anaphylaxis has also been reported (52538).

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

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General ...Orally, white mulberry leaf seems to be well tolerated.
Most Common Adverse Effects:
Orally: Transient bloating, constipation, flatulence, and loose stools.

Gastrointestinal ...Orally, white mulberry leaf powder 4. 6 grams three times daily for 4 weeks was associated with bloating and flatulence in 50% of patients, loose stools in 25% of patients, and constipation in 21% of patients in one clinical study. However, reports of these adverse effects decreased over the course of the 12-week study, suggesting that for some patients the adverse effects may be transient in nature (103870).

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