Raspberry Ketone Plus by Herbadiet

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Aging skin. Although there is interest in using oral or topical acai to prevent aging skin, there is insufficient reliable information about the clinical effects of acai for this purpose.
• Athletic performance. It is unclear if oral acai is beneficial for improving athletic performance. Details: Preliminary clinical research in amateur cyclists shows that consuming 400 grams of pasteurized acai pulp daily for 15 days prevents oxidative damage and decreases levels of blood lactate during exercise by 28% when compared with placebo. Consuming acai pulp also seems to increase anaerobic threshold intensity, but does not improve maximum workload or measures of exertion, when compared to baseline (102860).
• Erectile dysfunction (ED). Although there is interest in using oral acai for ED, there is insufficient reliable information about the clinical effects of acai for this condition.
• Hypercholesterolemia. Although there is interest in using oral acai for hypercholesterolemia, there is insufficient reliable information about the clinical effects of acai for this condition.
• Metabolic syndrome. Although there is interest in using oral acai for metabolic syndrome, there is insufficient reliable information about the clinical effects of acai for this condition.
• Obesity. It is unclear if oral black seed is beneficial for improving metabolic indices in overweight individuals. Details: In overweight individuals, preliminary clinical research shows that consuming 100 mg of acai pulp (Sambazon Acai Smoothie Pack, Sambazon Inc.) twice daily for one month reduces fasting glucose and total cholesterol levels when compared with baseline. However, no effect was seen on levels of low density lipoprotein (LDL) cholesterol, triglycerides, high density lipoprotein (HDL) cholesterol, or blood pressure (17731). The validity of these findings is limited by the lack of a comparator group.
• Osteoarthritis. Although there is interest in using oral acai for osteoarthritis, there is insufficient reliable information about the clinical effects of acai for this condition.
• Tinnitus. It is unclear if oral acai is beneficial for chronic tinnitus. Details: A small clinical study in adults with unilateral or bilateral chronic tinnitus, with either normal hearing or mild hearing loss, shows that taking dried acai pulp extract 100 mg daily for 3 months decreases tinnitus discomfort when compared with baseline (107846). However, the validity of this finding is limited by the lack of statistical comparison to the placebo group, which reported a numerically similar improvement in tinnitus discomfort. More evidence is needed to rate acai for these uses.

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INSUFFICIENT RELIABLE EVIDENCE to RATE

• Athletic performance. It is unclear if oral garcinia is beneficial for improving athletic performance. Details: Two very small, exploratory studies in untrained females and in elite athletes show that taking hydroxycitric acid (HCA), the active ingredient of garcinia, 250 mg daily for 5 days increases time to exhaustion and lowers the respiratory exchange ratio when compared with taking placebo (19151,26858).
• Hyperlipidemia. It is unclear if oral garcinia is beneficial in patients with hyperlipidemia. Details: A small open-label study of adults with obesity shows that taking garcinia 600 mg twice daily for 3 months may reduce total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides when compared to baseline (111243). The validity of these findings is limited by a lack of a comparator group and blinding.
• Nonalcoholic fatty liver disease (NAFLD). It is unclear if oral garcinia is beneficial in patients with NAFLD. Details: A small clinical study in females with obesity and NAFLD shows that taking a specific product containing garcinia bark leaf extract (HCA Garcinia Vita Plus, Vitamin House) 312.5 mg daily for 8 weeks in combination with a calorie-restricted diet improves body weight, body mass index (BMI), triglycerides, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol when compared to baseline. However, liver enzyme levels increased slightly (111240). While a calorie-restricted control group was included, a lack of appropriate statistical comparison limits the validity of any between-group findings. Thus, it is unclear if these results are due to garcinia, the calorie-restricted diet, or the combination.
• Obesity. Despite contradictory evidence, oral garcinia seems to produce a very modest weight reduction in some people who are obese or overweight. Details: A meta-analysis of 8 small clinical trials shows that taking garcinia for 8-12 weeks seems to reduce weight by about 1.3 kg and body mass index (BMI) by about 1 kg/m2 when compared with control (104432). This analysis is limited by prominent heterogeneity in the included studies and a lack of sensitivity analyses. Most studies included in the analyses used garcinia 1000-4667 mg (standardized to 50% or 60% hydroxycitric acid) in divided doses daily as non-branded extracts or as specific branded supplements (Super CitriMax, InterHealth Nutraceuticals; Citrin, Sabinsa Corporation) (728,19152,19153,88158,104432). It is unclear which dose, if any, may be most beneficial. More recently, a small, open-label trial in adults with obesity shows that taking garcinia 600 mg twice daily for 3 months reduces body weight and BMI by 1.7 kg and 0.7 kg/m^2 when compared to baseline (111243). The validity of these findings is limited by a lack of a comparator group and blinding. Limited research has also studied garcinia in combination with glucomannan for 6 months, with evidence of moderate benefit for weight loss (96536). More evidence is needed to rate garcinia for these uses.

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INSUFFICIENT RELIABLE EVIDENCE to RATE

• Alzheimer disease. Although there has been interest in using oral green coffee for Alzheimer disease, there is insufficient reliable information about the clinical effects of green coffee for this condition.
• Diabetes. Although there has been interest in using oral green coffee for diabetes, there is insufficient reliable information about the clinical effects of green coffee for this condition.
• Hypercholesterolemia. It is unclear if oral green coffee is beneficial for hypercholesterolemia. Details: A meta-analysis of small clinical trials shows that taking green coffee extract modestly reduces levels of total and low-density lipoprotein (LDL) cholesterol, and increases levels of high-density lipoprotein (HDL), when compared to placebo. There was no effect on triglyceride levels (111048). These changes are unlikely to be clinically significant. In addition, this analysis is limited by the significant heterogeneity of the patient populations and any effect of green coffee extract in patients with hyperlipidemia is unclear. A small preliminary clinical study included in this meta-analysis in patients with hypercholesterolemia shows that drinking a beverage containing soluble green coffee 0.7 grams and soluble roasted coffee 1.3 grams (containing chlorogenic acids 148.4 mg per serving) three times daily for 8 weeks reduces LDL cholesterol, total cholesterol, and triglycerides when compared with baseline (103957). The validity of this finding is limited by the lack of a comparator group. Furthermore, it is unclear if the benefits are due to green coffee, roasted coffee, or the combination.
• Hypertension. It is unclear if oral green coffee extract is beneficial for lowering blood pressure. Details: Two small clinical studies in Japanese adults with mild, untreated hypertension show that taking green coffee extracts providing 50-140 mg chlorogenic acids daily for 4-12 weeks reduces systolic blood pressure by 5-10 mmHg and diastolic blood pressure by 3-7 mmHg when compared with placebo (17971,17972).
• Metabolic syndrome. Oral green coffee extract seems to improve some, but not all, measures of metabolic syndrome. Details: In patients with metabolic syndrome, clinical research shows that taking green coffee extract (Arjuna Natural Extracts Ltd) 400 mg twice daily for 8 weeks improves some measures of metabolic syndrome when compared with placebo. Systolic blood pressure, fasting blood glucose, insulin resistance, and waist circumference were reduced by a small amount, but there was no effect on glycated hemoglobin, lipid profile, or diastolic blood pressure (104831).
• Obesity. Oral green coffee extract may have a small effect on weight loss. Details: A meta-analysis of 13 clinical studies in patients with overweight or obesity shows that taking either green coffee extract 90-1000 mg, containing chlorogenic acids 30-500 mg, or pure chlorogenic acid 1200 mg daily for 8-12 weeks reduces weight by about 2 kg and body mass index (BMI) by 0.56 kg/m2 when compared with placebo (103954). Individual clinical studies have used a specific green coffee extract (Svetol, Naturex) (17982,17983). In the meta-analysis, there was no clear dose-response relationship (103954). This weight loss is unlikely to be clinically significant. In addition, this analysis is limited by the significant heterogeneity of the included studies and patient populations. In 2014 a trial reporting efficacy of a green coffee extract for treatment of obesity was determined to be "seriously flawed" by the Federal Trade Commission (FTC), resulting in its retraction by the authors and payment of a significant fine by the sponsoring company (Applied Food Sciences, Inc.) (88168,88169). This flawed study was not included in the 2020 meta-analysis (103954). In contrast to these findings, some clinical research has shown that taking green coffee does not reduce body weight. In one study, taking polyphenols 300 mg twice daily alone or in combination with oat-derived beta-glucans does not affect body weight or body composition when compared to baseline (109208). Also, in overweight or obese patients with breast cancer, a small clinical trial shows that taking green coffee extract (Arjuna Natural Extracts Ltd) 400 mg twice daily for 12 weeks does not affect body weight, body composition, or glycemic indices, when compared with placebo (111046).
• Polycystic ovary syndrome (PCOS). It is unclear if oral green coffee extract is beneficial for PCOS. Details: A small clinical trial in patients with PCOS shows that taking green coffee extract (Bonyan Salamat Kasra Company, Iran) 400 mg daily for 6 weeks modestly decreases total cholesterol and triglyceride levels when compared with taking placebo. However, there was no effect on glycemic indices, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, or body weight (111047). More evidence is needed to rate green coffee for these uses.

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INSUFFICIENT RELIABLE EVIDENCE to RATE

• Alopecia areata. It is unclear if raspberry ketone is beneficial for alopecia areata. Details: Preliminary clinical research shows that applying a raspberry ketone 0.01% solution to the scalp once daily for 5 months increases hair growth in 50% of patients with androgenic alopecia or alopecia areata when compared with baseline (17955). The validity of this finding is limited by the lack of a comparator group.
• Androgenic alopecia. It is unclear if raspberry ketone is beneficial for androgenic alopecia. Details: Preliminary clinical research shows that applying a raspberry ketone 0.01% solution to the scalp once daily for 5 months increases hair growth in 50% of patients with androgenic alopecia or alopecia areata when compared with baseline (17955). The validity of this finding is limited by the lack of a comparator group.
• Obesity. Raspberry ketone has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small, uncontrolled clinical trial in healthy adults suggests that taking raspberry ketone 200 mg with vitamin C 1200 mg daily for four weeks reduces body weight and body fat mass (19065). Another clinical study in overweight adults shows that taking a specific product (Prograde Metabolism, Ultimate Wellness Systems) containing 1000 mg of a proprietary blend of raspberry ketone, capsicum extract, caffeine, garlic root, ginger root, bitter orange, L-theanine, and black pepper twice daily for 8 weeks, in conjunction with dieting, reduces body weight, fat mass, and waist and hip circumference when compared with dieting alone (40802). More evidence is needed to rate raspberry ketone for these uses.

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POSSIBLY SAFE ...when used orally and appropriately, short-term. Acai pulp, in a dose of up to 162.5 grams daily, has been used with apparent safety for up to 3 months in clinical research (17731,99400). There is insufficient reliable information available about the safety of acai when used topically.

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

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There is insufficient reliable information available about the safety of garcinia extract when used orally. However, there is some concern about liver toxicity. There are numerous case reports of elevated liver enzymes and symptoms of liver toxicity in patients who have taken garcinia alone or in combination with other ingredients for as little as one week. In at least two reports, hepatotoxicity occurred in patients who were taking garcinia alone. Most other reports occurred in patients taking multi-ingredient products (13037,53511,93380,93381,93384,93385,93392,93393,93394,96535)(102544,102545,111241).

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

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POSSIBLY SAFE ...when used orally and appropriately. Green coffee extracts taken in doses up to 1000 mg daily, providing up to 500 mg chlorogenic acid, have been used with apparent safety for up to 12 weeks in clinical research (17971,17972,103954). A specific green coffee extract (Svetol, Naturex) has been used with apparent safety in doses up to 200 mg five times daily for up to 12 weeks (17981,17982,17983). Green coffee also contains caffeine, although in lower amounts than regular coffee. One cup of green coffee contains about 20-50 mg of caffeine, compared with about 100 mg in one cup of regular coffee. According to a review by Health Canada, and a subsequent large meta-analysis conducted in the US, doses of caffeine up to 400 mg daily are not associated with significant adverse cardiovascular, bone, behavioral, or reproductive effects in healthy adults (11733,98806). The US Dietary Guidelines Advisory Committee states that there is strong and consistent evidence that consumption of caffeine 400 mg daily is not associated with increased risk of major chronic diseases, such as cardiovascular disease or cancer, in healthy adults (98806). Keep in mind that only the amount of ADDED caffeine must be stated on product labels. The amount of caffeine found in ingredients such as green coffee, which naturally contains caffeine, does not need to be provided. This can make it difficult to determine the total amount of caffeine in a given product.

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

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LIKELY SAFE ...when used orally in food amounts. Raspberry ketone has Generally Recognized as Safe (GRAS) status for use as a food additive (102356,102358). There is insufficient reliable information available about the safety of raspberry ketone when used in medicinal amounts. However, raspberry ketone is structurally similar to synephrine, a known stimulant agent. Orally, cases of heart palpitations, tachycardia, elevated blood pressure, coronary vasospasm, sweating, feelings of shakiness, and diarrhea are reported after taking raspberry ketone (17961,112386,112400). In one case report, pulseless electrical activity arrest followed by resistant polymorphic ventricular tachycardia occurred in a patient taking raspberry ketone (112386).

PREGNANCY AND LACTATION:
There is insufficient reliable information available about the safety of raspberry ketone; avoid using.

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ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking acai with antidiabetes drugs might interfere with glycemic control.  Details Preliminary clinical research in healthy adults has shown that taking acai may increase or decrease levels of fasting blood glucose (17731,105321).

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ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, hydroxycitric acid (HCA), the main active ingredient in garcinia, might increase the risk of bleeding when used with antiplatelet or anticoagulant drugs.  Details HCA inhibits platelet aggregation in vitro. The inhibitory effect seems to be greater in platelets extracted from diabetic subjects than non-diabetic subjects (26862).

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, hydroxycitric acid (HCA), the main active ingredient in garcinia, might have additive effects with antidiabetes drugs and increase the risk of hypoglycemia.  Details HCA reduces fasting and postprandial blood glucose levels in animal models, theoretically by delaying glucose absorption (26863,26867,26868). This effect has not been reported in humans.

HEPATOTOXIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use with other potentially hepatotoxic drugs might increase the risk of developing liver damage.  Details There have been reports of acute hepatitis with elevated liver enzymes associated with garcinia, when taken alone or in combination with other ingredients (13037,53511,93380,93381,93384,93392,93393,93394,102544,102545). Case reports collected from the Drug Induced Liver Injury Network suggest this risk may be greater in people who carry the HLA B*35:01 allele (108401).

SEROTONERGIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, combining garcinia with other serotonergic drugs might increase the risk of serotonergic side effects, including serotonin syndrome.  Details In one report, a patient experienced serotonin syndrome after taking garcinia extract (60% hydroxycitric acid) 1000 mg daily in combination with escitalopram 20 mg, which had been taken for a year. The patient was switched to sertraline 50 mg daily and again experienced serotonin syndrome (23545).

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ADENOSINE (Adenocard) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, green coffee might decrease the vasodilatory effects of adenosine and interfere with its use prior to stress testing.  Details Green coffee can contain caffeine. Caffeine is a competitive inhibitor of adenosine at the cellular level. However, caffeine does not seem to affect supplemental adenosine because high interstitial levels of adenosine overcome the antagonistic effects of caffeine (11771). It is recommended that methylxanthines such as caffeine, as well as methylxanthine-containing products, be stopped 24 hours prior to pharmacological stress tests (11770). However, methylxanthines appear more likely to interfere with dipyridamole (Persantine) than adenosine-induced stress testing (11771).

ALCOHOL (Ethanol) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, alcohol might increase the levels and adverse effects of caffeine.  Details Green coffee can contain caffeine. Concomitant use of alcohol can increase caffeine serum concentrations and the risk of caffeine adverse effects. Alcohol reduces caffeine metabolism (6370,24693).

ALENDRONATE (Fosamax) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, green coffee may decrease the levels and effects of alendronate.  Details In human research, drinking coffee with alendronate reduces the bioavailability of alendronate by 60% (11735). Whether green coffee reduces the bioavailability of alendronate has not been investigated. Separate green coffee ingestion and alendronate administration by two hours.

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Unlikely •  Level of Evidence = D Theoretically, green coffee may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.  Details Green coffee can contain caffeine. Caffeine is reported to have antiplatelet activity (8028,8029). Theoretically, caffeine in green coffee might increase the risk of bleeding when used concomitantly with these agents. However, this interaction has not been reported in humans. There is some evidence that caffeinated coffee might increase the fibrinolytic activity in blood (8030).

ANTIDIABETES DRUGS Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = B Theoretically, taking green coffee and antidiabetes drugs might interfere with blood glucose control.  Details In clinical research, green coffee extract results in modest reductions in blood glucose levels in various populations (17982,19327,111049). However, other reports claim that caffeine might increase or decrease blood sugar levels (6024,8646,19329,19330,19331,19332).

ANTIHYPERTENSIVE DRUGS Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = B Theoretically, taking green coffee with antihypertensive drugs might increase the risk of hypotension.  Details Clinical studies have shown that green coffee extract decreases blood pressure (17971,17972). When used with antihypertensive drugs, green coffee might have additive blood pressure-lowering effects. However, this has not been shown in clinical research.

BETA-ADRENERGIC AGONISTS Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Probable •  Level of Evidence = D Theoretically, concomitant use of large amounts of green coffee might increase cardiac inotropic effects of beta-agonists.  Details Green coffee can contain caffeine. Caffeine can increase cardiac inotropic effects of beta-agonists (15).

CIMETIDINE (Tagamet) Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Likely •  Level of Evidence = B Theoretically, cimetidine might increase the effects and adverse effects of caffeine in green coffee.  Details Green coffee can contain caffeine. Cimetidine can reduce caffeine clearance by 31% to 42% (11736,24700).

CLOZAPINE (Clozaril) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = B Theoretically, green coffee might increase the levels and adverse effects of clozapine and acutely exacerbate psychotic symptoms.  Details Green coffee can contain caffeine. Caffeine can increase the effects and toxicity of clozapine. Caffeine doses of 400-1000 mg daily inhibit clozapine metabolism (5051). Clozapine is metabolized by cytochrome P450 1A2 (CYP1A2). Researchers speculate that caffeine might inhibit CYP1A2. However, there is no reliable evidence that caffeine affects CYP1A2. There is also speculation that genetic factors might make some patients more sensitive to an interaction between clozapine and caffeine (13741).

CONTRACEPTIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Probable •  Level of Evidence = B Theoretically, concomitant use might increase the effects and adverse effects of caffeine found in green coffee.  Details Green coffee can contain caffeine. Oral contraceptives decrease the rate of caffeine clearance by 40% to 65% (2714,11737).

DIPYRIDAMOLE (Persantine) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Theoretically, green coffee might decrease the vasodilatory effects of dipyridamole and interfere with its use prior to stress testing.  Details Green coffee can contain caffeine. Caffeine is a methylxanthine that may inhibit dipyridamole-induced vasodilation (11770,11772,24974,37985,53795). It is recommended that methylxanthines such as caffeine, as well as methylxanthine-containing products such as green coffee, be stopped 24 hours prior to pharmacological stress tests (11770). Methylxanthines appear more likely to interfere with dipyridamole (Persantine) than adenosine-induced stress testing (11771).

DISULFIRAM (Antabuse) Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Probable •  Level of Evidence = B Theoretically, disulfiram might increase the levels and adverse effects of caffeine.  Details Green coffee can contain caffeine. In human research, disulfiram decreases the clearance and increases the half-life of caffeine (11840).

DIURETIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use might increase the risk of hypokalemia.  Details Green coffee can contain caffeine. Caffeine, especially in excessive amounts, can reduce potassium levels due to stimulation of the sodium-potassium pump (23579,37905,37953,38003,38034). Diuretics can also cause lower potassium levels.

EPHEDRINE Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Probable •  Level of Evidence = D Theoretically, concomitant use might increase the risk of stimulant adverse effects.  Details Green coffee can contain caffeine. There is evidence that using ephedrine with caffeine might increase the risk of serious life-threatening or debilitating adverse effects such as hypertension, myocardial infarction, stroke, seizures, and death (1275,6486,9740,10307). Tell patients to avoid taking caffeine with ephedrine and other stimulants.

ESTROGENS Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Probable •  Level of Evidence = B Theoretically, estrogens might increase the levels and adverse effects of caffeine.  Details Green coffee can contain caffeine. Estrogen inhibits caffeine metabolism (2714).

FLUCONAZOLE (Diflucan) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = B Theoretically, fluconazole might increase the levels and adverse effects of caffeine.  Details Green coffee can contain caffeine. Fluconazole decreases caffeine clearance by approximately 25% (11022,24978).

FLUVOXAMINE (Luvox) Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Probable •  Level of Evidence = B Theoretically, fluvoxamine might increase the levels and adverse effects of caffeine.  Details Green coffee can contain caffeine. Fluvoxamine reduces caffeine metabolism (6370,38287).

LITHIUM Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, abrupt green coffee withdrawal might increase the levels and adverse effects of lithium.  Details Green coffee can contain caffeine. Abrupt caffeine withdrawal can increase serum lithium levels (609). Two cases of lithium tremor that worsened with abrupt coffee withdrawal have been reported (609,610).

MEXILETINE (Mexitil) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = B Theoretically, mexiletine might increase the levels and adverse effects of caffeine.  Details Green coffee can contain caffeine. Mexiletine can decrease caffeine elimination by 50% (1260,11741,24981).

MONOAMINE OXIDASE INHIBITORS (MAOIs) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use might increase the risk of a hypertensive crisis.  Details Green coffee can contain caffeine. Caffeine has been shown to inhibit monoamine oxidase (MAO) A and B in laboratory studies (37724,37877,37912,38108). Concomitant intake of large amounts of caffeine with MAOIs might precipitate a hypertensive crisis (15).

NICOTINE Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Theoretically, concomitant use might increase the risk of hypertension.  Details Green coffee can contain caffeine. Concomitant use of caffeine and nicotine has been shown to have additive cardiovascular effects, including increased heart rate and blood pressure. Blood pressure was increased by 10.8/12.4 mmHg when the agents were used concomitantly (36549).

PENTOBARBITAL (Nembutal) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, green coffee might reduce the effects of pentobarbital.  Details Green coffee can contain caffeine. Theoretically, caffeine might negate the hypnotic effects of pentobarbital (13742).

PHENOTHIAZINES Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, phenothiazines might increase the levels and adverse effects of caffeine.  Details Green coffee can contain caffeine. Phenothiazines can reduce the metabolism of caffeine by inhibiting cytochrome P450 1A2 (CYP1A2) (23573,23574).

PHENYLPROPANOLAMINE Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Theoretically, phenylpropanolamine might increase the risk of hypertension, as well as the levels and adverse effects of caffeine.  Details Green coffee can contain caffeine. Concomitant use of phenylpropanolamine and caffeine might cause an additive increase in blood pressure (11738). Phenylpropanolamine also seems to increase caffeine serum levels (13743).

PIOGLITAZONE (Actos) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, caffeine might increase the levels and clinical effects of pioglitazone.  Details Green coffee contains caffeine. Animal research suggests that caffeine can modestly increase the maximum concentration, area under the curve, and half-life of pioglitazone, and also reduce its clearance. This increased the antidiabetic effects of pioglitazone (108812). However, the exact mechanism of this interaction is unclear.

QUINOLONE ANTIBIOTICS Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = B Theoretically, quinolone antibiotics might increase the levels and adverse effects of caffeine.  Details Green coffee can contain caffeine. Concomitant use of quinolones can decrease caffeine clearance and increase effects and risk of adverse effects (606,607,608,23554,23555,23556,24695,24696,24697).

RILUZOLE (Rilutek) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use might increase the levels and adverse effects of both caffeine and riluzole.  Details Green coffee can contain caffeine. Caffeine and riluzole are both metabolized by cytochrome P450 1A2 (CYP1A2), and concomitant use might reduce metabolism of one or both agents (11739).

STIMULANT DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = C Theoretically, concomitant use might increase stimulant adverse effects.  Details Green coffee can contain caffeine. Due to the central nervous system (CNS) stimulant effects of caffeine, concomitant use with stimulant drugs can increase the risk of adverse effects (11832).

TERBINAFINE (Lamisil) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = B Theoretically, terbinafine might increase the levels and adverse effects of caffeine.  Details Green coffee can contain caffeine. Terbinafine decreases the clearance of intravenous caffeine by 19% (11740).

THEOPHYLLINE Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Probable •  Level of Evidence = B Theoretically, green coffee might increase the levels and adverse effects of theophylline.  Details Green coffee can contain caffeine. Large amounts of caffeine might inhibit theophylline metabolism (11741).

VERAPAMIL (Calan, others) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use might increase the levels and adverse effects of caffeine.  Details Green coffee can contain caffeine. Verapamil increases plasma caffeine concentrations by 25% (11741).

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STIMULANT DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, raspberry ketone might increase the risk of adverse cardiovascular effects with stimulant drugs.  Details Structurally, raspberry ketone resembles synephrine, a known stimulant agent. Heart palpitations, elevated blood pressure, coronary vasospasm, pulseless electrical activity arrest, and resistant polymorphic ventricular tachycardia have been reported in patients taking raspberry ketone (17961,112386,112400).

WARFARIN (Coumadin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, raspberry ketone might increase warfarin dose requirements.  Details In one case report, a patient taking warfarin 55 mg per week had a decrease in INR over a period of one month while taking raspberry ketone 250 mg daily. A warfarin dose increase to 70 mg per week was necessary to maintain a therapeutic INR while taking raspberry ketone (17962). The mechanism for this potential interaction is not known.

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

Other ...Raw acai fruit and juice can be contaminated with a parasitic protozoan called Trypanosoma cruzi, which causes American trypanosomiasis or Chagas Disease. A Brazilian outbreak of this disease in 2006 was linked to consumption of acai juice (17194,30245).

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General ...Orally, garcinia and its constituent, hydroxycitric acid (HCA), seem to be generally well tolerated in clinical research.
Most Common Adverse Effects:
Orally: Diarrhea, gastrointestinal discomfort, headache, and nausea.
Serious Adverse Effects (Rare):
Orally: Garcinia has been linked with cases of hepatotoxicity and liver failure. There have also been rare cases of mania and pancreatitis.

Cardiovascular ...There is a case report of a 48-year-old female who developed acute necrotizing eosinophilic myocarditis (ANEM) after using a garcinia supplement orally for 2. 5 weeks. On admission to hospital, she was hypotensive and had an elevated serum troponin level, progressing to fulminant heart failure, acute kidney failure, and sustained ventricular arrhythmias. She recovered after treatment with extra-corporeal membrane oxygenation (ECMO) and high-dose corticosteroids (88160). Although the patient had no prior medical history and was not taking any medications, this cannot conclusively be attributed to garcinia.
When taken orally, a specific formulation of the multi-ingredient product Hydroxycut (Iovate Health Sciences Inc.), which was available until 2009, has been associated with malignant hypertension and hypertensive retinopathy. Hydroxycut contains caffeine, garcinia, gymnema, green tea, glucomannan, guarana extract, and willow bark. The suspected causal agent is caffeine, which is dosed at 600 mg daily if Hydroxycut is taken as recommended; however, the responsibility of the other ingredients cannot be ruled out (16527).

Endocrine ...In one case report, a 56-year-old female with pre-existing diabetes, hepatitis C, and hypertension developed diabetic ketoacidosis (DKA) and pancreatitis after taking an unknown amount of garcinia and African mango for one month. Upon admission, she presented with altered mental status, elevated serum glucose and lipase, and high anion gap metabolic acidosis. After 3 days of intensive supportive care, the DKA and pancreatitis resolved. The suspected probable causal agent was garcinia; however, African mango cannot be ruled out (97341). There have been at least 3 other cases of acute pancreatitis associated with use of garcinia (unknown dose) for 2 weeks and up to 7 months in adults ages 36-82 years (105056,105058,105071).

Gastrointestinal ...Orally, garcinia and its active constituent hydroxycitric acid (HCA) have caused mild and infrequent nausea, diarrhea, and other gastrointestinal symptoms (728,11977,19153,88158,88159).

Hepatic ...Orally, garcinia and its constituent hydroxycitric acid (HCA) might cause liver toxicity. Several cases of acute liver toxicity have been reported in patients taking garcinia supplements (93392,93393,93394,95573,102544,102545,104431,111241). Reported doses of garcinia extract range from 480-1800 mg daily, providing up to 900 mg HCA daily (93392,93394,95573,102544,104431). However, not all experts agree that HCA plays a causal role in the hepatotoxicity associated with garcinia supplements; some suggest other mechanisms may be in play, such as immune-mediated processes (95576,108401). In most cases, patients presented with a hepatocellular pattern of toxicity and symptoms of abdominal pain, coagulopathy, jaundice, and elevated transaminases after taking garcinia for several weeks to several months (93393,93394,95573,102544,102545,104431,108401,111241). In most of these cases, there was no evidence of other natural causes of liver disease, such as viral hepatitis. Some of these patients used acetaminophen at recommended doses for limited durations, suggesting that a potential synergistic effect may occur when multiple hepatotoxic agents are used concomitantly.
The Drug-Induced Liver Injury Network has identified 22 cases (11 moderate; 7 severe) of liver injury from garcinia, with 5 cases occurring with garcinia alone, 16 cases occurring in combination with green tea, and 1 case occurring in combination with ashwagandha. Clinical presentations of liver injury related to garcinia closely resemble green tea-related liver injury. Most patients (82%) presented with a hepatocellular pattern of enzyme elevations. The median age of these case reports was 35 years, 41% identified as Hispanic, and most patients were overweight but not obese. In case reports involving garcinia alone, the carrier frequency on HLAB*35:01 was 60%, which is higher than the carrier frequency found in reports of liver injury due to other supplements (19%) and in population controls (11%). Within 3 months of injury onset, 1 patient required liver transplantation and 1 patient died from liver injury (108401).
There have been at least four cases of liver failure requiring transplantation associated with garcinia supplements (93392,95573,98425,104431). In one case related specifically to garcinia, a 52-year-old female had been taking a combination product (USA Nutra Labs) providing garcinia 1000 mg daily, standardized to 60% HCA. The supplement also provided calcium 50 mg, chromium 200 mcg, and potassium 50 mg. Symptoms started within a few weeks of initiation of the product (93392). In another case, a 34-year-old Hispanic male experienced acute liver failure requiring transplant after taking a specific garcinia product (Garcinia Cambogia 5:1 Extract, Swanson Vitamins) 160 mg three times daily before meals for 5 months (95573). In other reports, one 26-year-old male and one female presented to the emergency room with liver failure after 2-7 months of taking a supplement containing garcinia and green tea, with or without whey protein, Veldt raisin, and coffea arabica (98425,104431).
There have also been numerous cases of acute liver toxicity associated with combination products containing garcinia, such as Hydroxycut (Iovate Health Sciences Inc) (13037,53511,93380,93381,93384,93385,96535,98425,104431). Available until 2009, Hydroxycut contained garcinia, green tea, chromium, caffeine, calcium, potassium, and gymnema. A currently available garcinia-containing combination product called Seryburn Day Triple has also been associated with supplement-induced liver injury. (13037,93380,93381,95570,95572,95575,111241). In most of these cases, patients had elevated levels of liver enzymes without evidence of chronic liver disease. Patients usually developed symptoms within 1-12 weeks of taking the product. The clinical pattern of liver damage was often hepatocellular. Most cases reported altered liver enzyme values including ALT, AST, bilirubin, alkaline phosphatase, and international normalized ratio. In most cases, symptoms resolved with near normalization of enzyme levels once the garcinia-containing combination product was discontinued (13037,53511,93380,93381,93384,95567,95572,95575,111241).
However, there is one report of transplant related to Hydroxycut use (93381). As the suspected causal agents, garcinia and green tea were removed from the product during reformulation in 2009 (13037,53511,93380,93381,93384). Hepatotoxicity has been reported in at least one new formulation of Hydroxycut not containing garcinia (93394). Consequently, some experts believe that there is not enough information to attribute hepatotoxicity from this product to garcinia or HCA (95576). Also, in some cases, causality of hepatotoxicity was less clear because patients were taking many other supplements and drugs (95570).There is also a report of fatal liver failure in an obese female taking montelukast while also taking two dietary supplements containing multiple ingredients, including garcinia, gymnema, chromium, bitter orange, and many others. The authors speculated that the combination of montelukast with one or more ingredients in these dietary supplements may have resulted in liver failure (93385).

Musculoskeletal ...Orally, garcinia-containing products have been associated with rhabdomyolysis. There is a case report of a patient who developed rhabdomyolysis 3 hours after ingestion of an herbal product containing ephedra, guarana, chitosan, gymnema, garcinia, and chromium (19154). Since there were multiple ingredients, the effect cannot be conclusively attributed to garcinia. Another case of rhabdomyolysis has been reported for a patient taking an undetermined formulation of Hydroxycut at a dose of 4 caplets daily, naproxen sodium 220 mg as needed for pain, dextroamphetamine daily for 5 days, and hydrocodone-acetaminophen and cyclobenzaprine for pain. Two weeks later, after stopping Hydroxycut and receiving supportive care, the rhabdomyolysis resolved. Hydroxycut was determined to be possibly associated with the rhabdomyolysis (95566). Since Hydroxycut contains multiple ingredients and garcinia content was possible but not confirmed, a causal relationship with garcinia could not be determined.

Neurologic/CNS ...Orally, garcinia and its active constituent hydroxycitric acid (HCA) may cause headache and dizziness (11977). A 35-year-old female reported ocular complications, headache, dizziness, and nausea after taking garcinia extract, providing more than 500 mg of HCA, three times daily for one week. The patient's neurologic symptoms resolved one day after discontinuing the garcinia extract (102546). It is unclear if these neurologic adverse effects were separate from or related to the patient's visual disturbances.

Ocular/Otic ...In one case, a 35-year-old female presented with ocular pain in both eyes, decreased vision in the left eye, headache, dizziness, and nausea after taking garcinia extract orally for one week. Ophthalmologic testing was consistent with adverse ocular effects, showing myopic shift with anterior chamber shallowing and swelling of retinal nerve fiber and macula. The patient reported taking a garcinia product containing hydroxycitric acid 500 mg three times daily, which was more than double the recommended dose per the product label. Symptoms resolved upon discontinuation of the garcinia extract and treatment with oral and topical steroids (102546).

Psychiatric ...Orally, garcinia supplements have been linked to several cases of mania. Typically, symptoms develop 1-8 weeks after starting garcinia. In a report of three patients, symptoms included reduced need for sleep, increased activities and spending, delusions of grandiosity, pressured speech, and agitation. Two of the patients were previously diagnosed with bipolar disorder, and use of garcinia was believed to precipitate episodes during stable phases of the disease. The third patient had no history of bipolar disorder, and use of garcinia was thought to possibly have unmasked previously undiagnosed primary bipolar disorder. In all three cases, recovery included discontinuation of garcinia (95568). In a separate case report, a 23-year-old male taking a specific combination product containing garcinia (Hydroxycut) 1-2 capsules daily for 1 month presented to the emergency room with mania. The patient had no history of bipolar disorder. Although the patient was started on risperidone and clonazepam, symptoms resolved following discontinuation of the supplement. Treatment was discontinued within 4 days of initiation, and the patient remained asymptomatic (95574). A 22-year-old female with no history of bipolar disorder developed mania and psychosis, presenting 10 days after starting Garcinia Cambogia Plus (Apex Vitality Health) 500-1500 mg daily, and Cleanse and Detox (Apex Vitality Health). The latter supplement contains raspberry ketones, licorice root, pumpkin seed, buckthorn root, Cascara sagrada, Irvingia gabonensis, rhubarb, pectin, Lactobacillus acidophilus, and aloe. Symptoms improved upon stopping the supplements and starting lithium and quetiapine (99421).

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General ...Orally, green coffee appears to be well-tolerated. Although green coffee contains caffeine, it is present in small quantities which are less likely to cause adverse effects. Green coffee contains about 20-50 mg caffeine per cup, compared with about 100 mg caffeine per cup of brewed coffee.

Cardiovascular ...Although acute administration of caffeine, a constituent of green coffee, can cause increased blood pressure, regular consumption does not seem to increase either blood pressure or pulse, even in mildly hypertensive patients (1451,1452,2722,13739). Drinking one or more cups daily of caffeinated coffee, such as green coffee, also doesn't seem to increase the risk of developing hypertension in habitual coffee drinkers (8033,13739).
Chlorogenic acids found in green coffee extracts may adversely affect plasma homocysteine levels. In one randomized controlled trial, 2 grams of chlorogenic acids (the amount found in about 1.5 L of strong coffee) daily for one week resulted in a 12% increase in plasma homocysteine levels (8035). However, in another trial of green coffee extract in a dose equivalent to 140 mg of chlorogenic acids daily for 4 months, there was a slight decrease in plasma homocysteine levels from baseline, but this did not differ significantly from placebo treatment (17970).
The diterpenes cafestol and kahweol found in green coffee beans have been implicated in the hypercholesterolemic effects of unfiltered coffee (19336,53599). However, these compounds are removed from some green coffee extracts. For instance, Svetol (Naturex, South Hackensack, NJ) is reported to contain less than 4 ppm of cafestol and kahweol (88171).

Dermatologic ...Positive skin tests and symptoms of contact allergy have been reported in workers exposed to green coffee bean dust (53568,53653).

Endocrine ...Some evidence shows that caffeine, a constituent of green coffee, is associated with fibrocystic breast disease, breast cancer, and endometriosis in females; however, this is controversial since findings are conflicting (8043). Restricting caffeine in females with fibrocystic breast conditions doesn't seem to affect breast nodularity, swelling, or pain (8996). A population analysis of the Women's Health Initiative observational study has found no association between consumption of caffeine-containing beverages and the incidence of invasive breast cancer in models adjusted for demographic, lifestyle, and reproductive factors (108806). Also, a dose-response analysis of 2 low-quality observational studies has found that high consumption of caffeine is not associated with an increased risk of breast cancer (108807).
Clinical research in healthy adults shows that increased consumption of caffeine results in increased insulin resistance (91023).

Gastrointestinal ...Orally, stomach irritation was reported by one person in a clinical trial of green coffee extract (104831).

Musculoskeletal ...Epidemiological evidence regarding the relationship between caffeine, which is found in green coffee, and the risk of osteoporosis is contradictory. Caffeine can increase urinary excretion of calcium (2669,10202,11317). Females identified with a genetic variant of the vitamin D receptor appear to be at an increased risk of the detrimental effect of caffeine on bone mass (2669). However, moderate caffeine intake, less than 300 mg per day, does not seem to significantly increase osteoporosis risk in most postmenopausal adults with normal calcium intake (2669,6025,10202,11317).

Neurologic/CNS ...Orally, dizziness was reported by one person in a clinical trial of green coffee extract (104831).

Ocular/Otic ...Conjunctivitis caused by green coffee bean dust in coffee workers has been described in case reports (53657,53589).

Psychiatric ...Chronic use of caffeine, especially in large amounts, may produce tolerance, habituation, and psychological dependence (3719). Abrupt discontinuation of caffeine may result in physical withdrawal symptoms, including headache, fatigue, drowsiness, decreased physical energy, difficulty concentrating, depression, anxiety, irritability, and reduced alertness (13738). Certain populations such as children and the elderly may be more susceptible to the adverse effects of caffeine (13736).

Pulmonary/Respiratory ...Occupational exposure to green coffee beans has been documented to cause numerous adverse respiratory reactions, including bronchial reactivity, asthma, and rhinitis (53589,53641,53644,53648,53650,53665). Healthy subjects exposed experimentally to green coffee dust displayed acute decreases in expiratory flow rates (53653). In one study, green coffee workers displayed numerous acute respiratory symptoms when exposed to dust; these included coughing, increased sputum, sneezing, difficulty in breathing, running nose, and wheezing; these symptoms resolved after leaving work (53647).

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General ...Orally, a thorough evaluation of safety outcomes for raspberry ketone has not been conducted. Structurally, raspberry ketone resembles synephrine, a known stimulant agent.

Cardiovascular ...Structurally, raspberry ketone resembles synephrine, a known stimulant agent. Although not well studied in humans, stimulant-related side effects are possible. Orally, cases of heart palpitations, tachycardia, elevated blood pressure, coronary vasospasm are reported after taking raspberry ketone (17961,112386,112400). In one case report, pulseless electrical activity arrest followed by resistant polymorphic ventricular tachycardia occurred in a patient taking raspberry ketone. The arrhythmia resolved after numerous defibrillation shocks and placement of a temporary transvenous pacemaker with overdrive pacing (112386). In another case report, 5 episodes of ST elevation occurred over 2 days following ingestion of raspberry ketone (112400).

Neurologic/CNS ...Structurally, raspberry ketone resembles synephrine, a known stimulant agent. Although not well studied in humans, stimulant-related side effects are possible. Two case reports describe symptoms of sweating, diarrhea, and feelings of shakiness after oral use of raspberry ketone (17961,112400).

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