Prune & Senna by Wonder Laboratories

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Diabetes. Preliminary clinical research shows that drinking jambolan tea 2 grams, prepared with jambolan leaves in one liter of water, does not improve fasting blood glucose in patients with type 2 diabetes when compared with placebo (13092). More evidence is needed to rate jambolan for this use.

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POSSIBLY EFFECTIVE

• Constipation. Consuming whole dried plums (prunes), plum juice, or plum puree seems to improve symptoms of constipation at least as effectively as psyllium. Details: Clinical research in patients with chronic constipation shows that taking dried plum juice 54 grams daily for 8 weeks modestly reduces the rate of hard and lumpy stools and increases the rate of normal stools at about 3 weeks when compared with placebo. Subjective improvements in constipation and hard stools also occurred by 8 weeks. However, there was no effect on flatulence, loose stools, or feelings of urgent or incomplete defecation (109233). Another small clinical study in patients with certain gastrointestinal symptoms shows that consuming a drink containing dried plum puree and plum juice 125 mL twice daily for 2 weeks increases fecal frequency by 0.6 times per week when compared to baseline (95293). However, the validity of the finding in this study is limited by the lack of a comparator group. Research has also compared dried plums with psyllium. One small clinical study in adults shows that taking dried plums 50 grams twice daily for 3 weeks improves straining and consistency and modestly increases the number of weekly bowel movements when compared with taking an equivalent dose of fiber in the form of psyllium 11 grams daily (95280). Another small clinical study in adults with constipation shows that drinking a specific type of plum juice (PlumSmart, Sunsweet Growers) 240 mL daily 15-30 minutes prior to the main meal for 2 weeks results in a 4.7-fold greater likelihood of relief from constipation within 24 hours when compared with drinking apple juice. Drinking plum juice is equally effective to drinking apple juice containing psyllium. Plum juice also improves stool softness, although it does not increase the weekly number of bowel movements, when compared with apple juice (95294). Clinical research also shows that taking a specific plum-derived mixed fiber supplement (SupraFiber, Sunsweet Growers Inc.) 5 grams dissolved in liquid twice daily after meals for 4 weeks improves symptoms of constipation as effectively as psyllium 5 grams daily. An increase of at least one complete bowel movement per week for at least 2 weeks occurred in 75% of patients in both groups (95275).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Dyslipidemia. It is unclear if oral dried plums (prunes) are beneficial in the treatment of dyslipidemia. Details: A meta-analysis of 9 small clinical studies shows that taking plum as either dried plum 11.5-100 grams daily or prune and plum juice 50-250 mL daily for 2 to 12 weeks reduces low-density lipoprotein cholesterol but does not improve total cholesterol, high-density lipoprotein cholesterol, or triglycerides when compared with placebo (112401). The interpretation of these results is limited by poor quality of evidence and heterogeneity due to differences in study populations, design, and amounts and types of plum used. In addition, it is unclear whether patients in all studies had dyslipidemia at baseline.
• Hepatitis. Although there has been interest in using oral plum for hepatitis, there is insufficient reliable information about the clinical effects of plum for this purpose.
• Hypertension. It is unclear if oral plum is beneficial for hypertension. Details: A meta-analysis of 5 small to moderate-sized clinical trials in adults shows that taking dried plum 11.5-23 grams daily for 8 weeks, prune juice 57 grams daily for 2 weeks, or plum juice 200-250 mL daily for 8-12 weeks does not reduce systolic or diastolic blood pressure when compared with placebo (112402). The validity of these findings is limited by low quality of evidence and substantial heterogeneity of the included studies, which enrolled individuals of varying health status and studied different types and regimens of plum. In addition, some studies were in healthy or normotensive patients.
• Obesity. It is unclear if oral plum is beneficial for overweight or obesity. Details: Meta-analysis of 7 small to moderate-sized, moderate-quality clinical trials in adults with normal weight, or overweight and obesity shows that taking dried plum 75-84 grams daily for 8 to 12 weeks or prune or plum juice 50 to 250 mL daily for 4 to 24 weeks does not reduce body weight (112402). Additionally, meta-analysis of 5 of these clinical trialsstudies also shows plum does not reduce body fat percentage (112402).
• Osteopenia. Some preliminary clinical research shows that oral dried plums (prunes) are beneficial for preventing loss of bone mineral density (BMD) in postmenopausal adults. It is unclear if prunes can increase BMD or if they are beneficial for preventing loss of BMD in other populations. Details: Preliminary clinical research in postmenopausal adults aged 55-75 years shows that eating dried plums 50 grams daily for 12 months preserves hip BMD, compared with a modest reduction in hip BMD in adults eating no dried plums. However, there was no benefit on other body sites or on total body BMD. The greatest benefit occurred in individuals with the lowest BMD at baseline. Calcium carbonate and vitamin D3 were supplemented as needed to provide a total intake of calcium 1200 mg and vitamin D3 800 IU from diet plus supplements. This study also evaluated a dose of 100 grams daily; however, there was a high dropout rate in this study arm (109236). The validity of the findings from this study are limited by the mixed population, of which 68% had osteopenia and the remainder had osteoporosis or normal BMD. Other preliminary clinical research in osteopenic postmenopausal adults shows that eating dried plum 100 grams, in addition to taking calcium 500 mg and vitamin D 400 IU, daily for 12 months improves BMD in the ulna by a moderate amount and in the spine by a small amount when compared with consuming dried apple (95276,95278). In the same population also receiving calcium and vitamin D supplementation, consumption of dried plums 50 grams or 100 grams daily for 6 months modestly attenuates total body, but not total hip, lumbar spine, or forearm, losses in BMD when compared with control (95284). Some very preliminary clinical research suggests that this increase in BMD might be maintained for up to 5 years after dried plum consumption (95279). However, research in other populations has not shown benefit. A clinical study in postmenopausal breast cancer survivors shows that consuming dried plums 90 grams daily for 6 months does not improve BMD, muscular strength, or body composition when compared with participating in resistance training and taking calcium 450 mg and vitamin D 800 IU daily (95277). Also, in middle aged and older males, preliminary clinical research shows that eating dried plum 100 grams, in addition to taking calcium 500 mg and vitamin D 300 IU, daily for 12 months does not improve most measures of BMD when compared with not eating plum (109235). However, only some of the patients in this study had osteopenia or osteoporosis.
• Postoperative ileus. It is unclear if oral dried plums (prunes) are beneficial for improving gastrointestinal function after surgery. Details: A small clinical study in females taking docusate sodium 100 grams twice daily after gynecological surgery shows that adding up to 12 dried plums (4 ounces) daily for three days does not reduce the time to first bowel movement when compared with docusate sodium alone. There was also no effect on pain severity with a bowel movement, the need for laxatives, or time to discharge. However, consuming dried plums increased the likelihood of having a bowel movement during the first three days after surgery (109237). The validity of this study is limited by the lack of blinding and its small size. More evidence is needed to rate plum for these uses.

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LIKELY EFFECTIVE

• Constipation. Taking senna orally is effective for the short-term treatment of constipation. Details: Senna is an FDA-approved nonprescription drug marketed for the short-term treatment of constipation in adults and children ages 2 years and older (15429,15433,15436,15441,15442,74545,74607,74609,74613,74615). Senna usually produces a laxative effect 6-10 hours after oral administration (15429,96559). However, in children ages 3-15 years, mineral oil and lactulose might be more effective (15434,15435). Taking senna with psyllium is also effective for the short-term treatment of constipation (8424,74593), with the combination increasing stool moisture to a greater degree than psyllium alone (8424). In patients with opioid or loperamide-induced constipation, taking senna appears to be as effective as lactulose, psyllium, and docusate for relieving constipation (15432,74586,74644,74650). Some population research has found that senna may be more effective than docusate, polyethylene glycol, and lactulose for preventing problematic constipation, the need for an enema, and abdominal imaging in pediatric cancer patients receiving opioids (92710). Senna also seems to be beneficial in chronic constipation. Clinical guidelines published by the American Gastroenterology Association and American College of Gastroenterology in 2023 give a conditional recommendation suggesting the use of senna over managing chronic idiopathic constipation without senna based on low-quality of evidence conducted over 4 weeks (112859). In geriatric patients, senna plus psyllium is more effective than lactulose for treating chronic constipation (15438,15439,15440). Also, a small study in middle-aged adults with chronic idiopathic constipation shows that taking senna (ALOSENN granules) 500 mg twice daily for 4 weeks seems to be similarly effective to taking magnesium oxide 500 mg three times daily (105959).

POSSIBLY EFFECTIVE

• Bowel preparation. Taking oral senna might be effective for bowel cleansing before colonoscopy. Details: A meta-analysis of 10 clinical trials in adults shows that taking senna alone or with other bowel preparations does not improve bowel cleansing before elective colonoscopy when compared with non-senna bowel preparations. However, in a subgroup analysis of 3 clinical studies, taking senna solution alone is about 2.5 times more likely to result in a clean bowel when compared with polyethylene glycol alone (112893). The interpretation of these findings is limited by varied senna dosages and regimens. Additionally, 2 clinical studies that were not included in this meta-analysis show that senna is as effective or more effective than polyethylene glycol for improving bowel cleanse quality (15431,40088). Conversely, other studies show that polyethylene glycol is superior to senna (40086,74587,74606,74636). It is also unclear if taking senna with polyethylene glycol improves bowel cleansing when compared with polyethylene glycol alone (74583,74585). Some clinical studies show that senna is as effective as castor oil and bisacodyl for bowel cleansing (74548,74603,74624). Although taking senna alone is less effective than sodium phosphate (15431,74567,74570,74653,92712), some evidence suggests that taking a combination of senna, sodium picosulfate, and polyethylene glycol is more effective than sodium phosphate for bowel cleansing prior to colonoscopy (74538). Limited research has also assessed the benefit of adding senna to a preparation regimen for small bowel capsule endoscopy; however, it is unclear whether the addition of senna improves endoscopy outcomes when compared with the preparation regimen alone (96557). There is insufficient reliable information available about the effectiveness of senna for its other uses.

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POSSIBLY SAFE ...when used orally and appropriately, short-term. Jambolan tea prepared from 2 grams of jambolan leaves per liter of water has been consumed in place of water with apparent safety in clinical research (13092).

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

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LIKELY SAFE ...when used orally in the amounts typically found in food.

POSSIBLY SAFE ...when dried plums are used orally as a medicine. Dried plums have been used with apparent safety at doses of up to 100 grams daily for up to 12 months (95271,95272,95280,95281,95295,112402,112403). ...when plum juice or dried plum essence is used orally as a medicine. Plum juice has been consumed with apparent safety at a dose of up to 250 mL daily for up to 12 weeks and up to 90 grams daily for 24 weeks (95293,95294,112402). Dried plum essence has been consumed with apparent safety at a dose of up to 100 mL daily for up to 4 weeks (95274,112402).

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using amounts greater than those found in food.

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LIKELY SAFE ...when used orally and appropriately, short-term. Senna is an FDA-approved nonprescription drug (8424,15429,15431,15442,40086,40088,74535,74545,74548,74562)(74567,74570,74583,74585,74586,74587,74593,74603,74606,74607)(74609,74613,74615,74624,74636,74639,74644,74650,74653,92711)(92712).

POSSIBLY UNSAFE ...when used orally long-term or in high doses. Long-term, frequent use, or use of high doses has been linked to serious side effects including laxative dependence and liver toxicity (13057,13095).

CHILDREN: LIKELY SAFE
when used orally and appropriately, short-term. Senna is an FDA-approved nonprescription drug for use in children 2 years and older. (15429,15434,15435).

CHILDREN: POSSIBLY UNSAFE
when used orally long-term or in high doses. Long-term, frequent use, or use of high doses has been linked to serious side effects including laxative dependence and liver toxicity (13057,13095,105956).

PREGNANCY: POSSIBLY SAFE
when used orally and appropriately, short-term (15429,24480). POSSIBLY UNSAFE...when used orally long-term or in high doses. Long-term, frequent use, or use of high doses has been linked to serious side effects including laxative dependence and liver toxicity (13057,13095).

LACTATION: POSSIBLY SAFE
when used orally and appropriately, short term. Although small amounts of constituents of senna cross into breast milk, senna has been taken while breast-feeding with apparent safety. Senna does not cause changes in the frequency or consistency of infants' stools. (6026,15429,15436,15437,24482,24484,24485,24486,24487,74545).

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CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D There is some in vitro evidence that jambolan can inhibit CYP2C9 (99067). Theoretically, concomitant use of jambolan with CYP2C9 substrates may increase levels of drugs metabolized by CYP2C9.  Details Some drugs metabolized by CYP2C9 include amitriptyline (Elavil), diazepam (Valium), zileuton (Zyflo), celecoxib (Celebrex), diclofenac (Voltaren), fluvastatin (Lescol), glipizide (Glucotrol), ibuprofen (Advil, Motrin), irbesartan (Avapro), losartan (Cozaar), phenytoin (Dilantin), piroxicam (Feldene), tamoxifen (Nolvadex), tolbutamide (Tolinase), torsemide (Demadex), warfarin (Coumadin), and others.

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ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, plum juice might have antiplatelet effects.  Details Consuming plum juice while taking anticoagulant or antiplatelet drugs might increase the risk of bruising and bleeding. In healthy volunteers, drinking plum juice 200 mL daily for 28 days prolonged clotting time and inhibited platelet aggregation (95304,101248).

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DIGOXIN (Lanoxin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, senna might increase the risk of adverse effects when taken with digoxin.  Details Overuse/abuse of senna increases the risk of adverse effects from cardiac glycosides, such as digoxin, due to potassium depletion (15425).

DIURETIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, senna might increase the risk of hypokalemia when taken with diuretic drugs.  Details Overuse of senna might compound diuretic-induced potassium loss and increase the risk for hypokalemia (15425).

ESTROGENS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, taking senna may interfere with the absorption of exogenous estrogens.  Details Some preliminary clinical evidence suggests that senna reduces the absorption of estradiol and decreases serum concentrations of estrone and estrone sulfate by decreasing intestinal transit time (74647,74651).

STIMULANT LAXATIVES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, senna might increase the risk for fluid and electrolyte loss when taken with other stimulant laxatives.  Details Senna is a stimulant laxative; concomitant use with other stimulant laxatives might compound fluid and electrolyte loss (19,15425).

WARFARIN (Coumadin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, excessive use of senna might increase the effects of warfarin.  Details Senna has stimulant laxative effects and can cause diarrhea. Diarrhea can increase the effects of warfarin, increase international normalized ratio (INR), and increase the risk of bleeding. In one case report, excessive use of senna for 3 weeks resulted in diarrhea, bloody stools, and an elevated INR of 11.9 (16530).

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General ...No adverse effects have been reported; however, a thorough evaluation of safety outcomes has not been conducted.

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General ...Orally, plum seems to be well tolerated.
Most Common Adverse Effects:
Orally: Gastrointestinal effects, including flatulence and diarrhea.
Serious Adverse Effects (Rare):
Orally: Allergic reactions. Consumption of dried plums or plum pits has been reported to cause bowel obstruction and esophageal perforation.

Gastrointestinal ...Orally, plum has been reported to cause gastrointestinal issues (95272,95276,95285), including flatulence (95293) and diarrhea (95300).
In one case report, small bowel obstruction with impaction in the terminal ileum occurred in a 10-month old infant who consumed a dried plum. This was likely due to the infant being unable to properly chew the plum (95296).
Consumption of plum pits has also caused serious gastrointestinal adverse effects. Ileal obstruction occurred in a 71-year-old female who swallowed a plum pit (101250). In a young male, ileostomy obstruction due to plum pits has occurred (95298). Swallowing a plum pit has also caused an esophageal perforation in a 75-year-old male (95285).

Immunologic ...Orally, plum has been reported to cause allergic reaction in sensitive individuals (95286,95297).

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General ...Orally, senna is generally well-tolerated when used short-term in appropriate doses.
Most Common Adverse Effects:
Orally: Abdominal pain and discomfort, cramps, diarrhea, flatulence, nausea, fecal urgency, and urine discoloration.
Serious Adverse Effects (Rare):
Orally: Skin eruptions.

Cardiovascular ...Excessive use can cause potassium depletion and other electrolyte abnormalities (15425). In theory, this could cause potentially dangerous changes in heart rhythm. A small decrease in heart rate was seen in one clinical study (74587).

Dermatologic ...In adults, there are rare case reports of skin eruptions associated with senna, including erythema multiforme, fixed drug eruption, lichenoid reaction, toxic epidermal necrolysis, urticaria, photosensitivity, and contact dermatitis (96558). Infants and young children given senna products have experienced contact reactions on the buttocks due to prolonged exposure to stool while wearing a diaper overnight. These reactions range from erythema with small blisters, to large fluid-filled blisters with skin sloughing, as occurs with second degree burns (96559). In a case series of children treated with senna for chronic constipation, burn-like reactions occurred in 2.2%, typically with higher doses (mean 60 mg/day, range 35.2 to 150 mg/day) (96558,96559). These reactions can be avoided by giving senna early in the day, so that bowel movements occur at a time when diapers can be changed quickly (96559).

Gastrointestinal ...Orally, senna can cause abdominal pain and discomfort, cramps, bloating, flatulence, nausea, fecal urgency, and diarrhea (15427,15434,15435,15436,15439,15440,15441,105955). Chronic use has also been associated with "cathartic colon," radiographically diagnosed anatomical changes to the colon such as benign narrowing, colonic dilation, and loss of colonic folds (15428). The clinical relevance of these findings is unclear. Chronic use can also cause pseudomelanosis coli (pigment spots in intestinal mucosa) which is harmless, usually reverses with discontinuation, and is not associated with an increased risk of developing colorectal adenoma or carcinoma (6138). The cathartic properties of senna leaf are greater than the fruit (15430). Thus, the American Herbal Products Association only warns against long-term use of senna leaf (12).

Hepatic ...Chronic liver damage, portal vein thrombosis, and hepatitis have been reported following oral use of senna alkaloids, such as in tea made from senna leaves (13057,13095,41431,74560,74564,74584,105956). There is a case report of hepatitis in a female who consumed moderate amounts of senna tea. The patient was a poor metabolizer of cytochrome P450 2D6 (CYP2D6). It's thought that moderate doses of senna in this patient led to toxic hepatitis due to the patient's reduced ability to metabolize and eliminate the rhein anthrone metabolites of senna, which are thought to cause systemic toxicity (13057). There is also a case of liver failure, encephalopathy, and renal insufficiency in a female who consumed 1 liter/day of senna tea, prepared from 70 grams of dried senna fruit, over 3 years (13095). In another case report, a 3-year-old female presented with hepatitis that led to pancytopenia after drinking tea made from 2-3 grams dry senna leaves three times or more weekly for over one year (105956).

Immunologic ...In one case report, a 19-year-old male developed anaphylaxis with dyspnea, facial edema, and hives. This reaction was determined to be caused by the senna content in a specific combination product (Delgaxan Plus, Pompadour Ibérica) that the patient ingested (105957).

Musculoskeletal ...Hypertrophic osteoarthropathy, finger clubbing, cachexia, and tetany have been reported from excessive oral senna use in humans (15426,74580,74582,74620,74625).

Renal ...Nephrocalcinosis has been reported as a result of oral senna overuse (74582).

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