Pomegranate

Generic name: Punica Granatum L.
Brand names: Pomegranate, Seeded Apple

Usage of Pomegranate

Antioxidant effects

Clinical data

The effect of pomegranate juice or extract on oxidative stress was investigated via a systematic review and meta-analysis of 11 randomized controlled trials of adult subjects, either healthy or with various health conditions (eg, rheumatoid arthritis, obesity, hemodialysis, osteoarthritis, type 2 diabetes) (N=484). Duration of interventions ranged from 2 to 72 weeks. Pooled data revealed no overall significant effect on measures of oxidative stress (ie, malondialdehyde [MDA], total antioxidant capacity, glutathione peroxidase, paraoxonase).(Morvaridzadeh 2020)

Cardiovascular risk factors

Clinical data

In a systematic review and meta-analysis of randomized controlled trials that investigated the effect of fruit consumption (whole, freeze-dried, powdered, or juice) on cardiovascular disease risk, no significant overall effects of pomegranate juice (dosage range, 100 to 400 mL/day for 28 to 90 days) on systolic or diastolic blood pressure (3 studies; n=167 and n=168, respectively) or pulse wave velocity (1 study; n=48) were observed; no other forms of pomegranate were studied.(Wang 2021) In contrast, results from a 2017 systematic review and meta-analysis of 8 randomized controlled trials (N=574) identified statistically significant reductions in both systolic (weighted mean difference, −4.96 mm Hg; P<0.001) and diastolic blood pressure (−2.01 mm Hg; P=0.021) with pomegranate juice when administered for less than 12 weeks (study dosages ranged from 50 to 500 mL/day; treatment durations ranged from 2 weeks to 18 months). Systolic, but not diastolic, measures were also significant for supplementation durations of more than 12 weeks and for doses above and below 240 mL/day.(Sahebkar 2017)

Another systematic review and meta-analysis of patients with type 2 diabetes (7 randomized controlled trials [N=350]) reported no significant changes in lipid parameters (ie, total cholesterol, triglycerides, low-density lipoprotein [LDL], high-density lipoprotein [HDL]) with pomegranate supplementation (juice, seed oil, peel extract, extract at various dosages and durations [6 to 12 weeks]).(Jandari 2020) Similar results were reported in another meta-analysis of 12 randomized controlled trials (N=545) that enrolled both healthy subjects and subjects with various conditions (eg, hypertension, hyperlipidemia, obesity) consuming pomegranate preparations (juice, seed oil, fruit, extract) at various dosage and durations (10 days to 1 year). No significant changes were observed in total cholesterol, LDL, HDL, or triglycerides, and results remained consistent among all subgroup analyses.(Sahebkar 2016)

In a placebo-controlled trial in 66 obese women with knee osteoarthritis, a pomegranate peel extract dosage of 500 mg twice daily for 8 weeks reduced total cholesterol, triglycerides, and body mass index (BMI), but not LDL. Markers of oxidative stress were also significantly improved versus placebo (P<0.05).(Haghighian 2021)

Although pooled data from a meta-analysis of 14 randomized controlled trials of both healthy participants and those with various health conditions (N=572) reflected significant improvements in the inflammatory biomarkers high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor alpha, and interleukin 6 (P=0 for each) with pomegranate supplementation, specific markers of endothelial dysfunction (ie, E-selectin, intracellular adhesion molecules, vascular cell adhesion molecules) were not significantly affected. Additionally, no significant effect was found on CRP or MDA levels. Pomegranate was administered predominantly as juice (50 to 750 mL/day), but also as an extract (500 to 1,000 mg/day) and oil (480 mg/day) for durations ranging from 48 hours to 12 weeks.(Wang 2020)

Diabetes and glucose metabolism

Clinical data

Pooled data from a meta-analysis of 16 randomized controlled trials (N=627) demonstrated no effect of pomegranate intake (juice, seed oil, or extract at various dosages and for various durations [1 to 12 weeks]) on fasting blood glucose (15 studies [n=582]) or fasting insulin (8 studies [n=361]) overall or when evaluated by subgroup analysis (patients with cardiovascular disease risks vs healthy patients, receipt of pomegranate juice vs extract/seed oil, duration of intervention, dose, study design, or baseline parameters [ie, glucose, insulin, BMI]). A similar lack of effect was observed on insulin resistance and HbA1c.(Huang 2017) In another systematic review and meta-analysis of patients with type 2 diabetes (7 randomized controlled trials [N=350]), no changes in fasting blood glucose (6 trials [n=312]), nor in insulin resistance, HbA1c, or insulin (5 studies [n=252] for each of the last 3 parameters) were observed with pomegranate supplementation (juice, seed oil, peel extract, extract at various dosages and durations [6 to 12 weeks]). The pooled estimate from a random-effects model (4 studies [n=159]) and the pooled mean difference (5 datasets [n=219]) also showed no significant effect of pomegranate on body weight or BMI. In contrast, 2 studies reported statistically significant improvements in waist circumference with pomegranate supplementation (P<0.001 and P=0.01).(Jandari 2020) In a prospective randomized, double-blind, placebo-controlled trial, pomegranate seed powder 5 g twice daily for 8 weeks in 60 patients with type 2 diabetes demonstrated statistically significant reductions in fasting blood glucose and HbA1c compared with placebo (P<0.05), but no significant difference in total cholesterol or triglycerides.(Seyed Hashemi 2021)

Exercise endurance performance

Clinical data

In a double-blind, randomized, placebo-controlled, crossover trial in 30 amateur endurance-trained male athletes, consumption of pomegranate extract 750 mg containing 30% punicalagins (Pomanox P30) for 15 days produced a statistically significant increase in total time to exhaustion (P<0.02) as well as in time to reach ventilatory threshold 2 (P<0.001) compared with placebo. In contrast, no differences between treatments were observed for the rate of perceived exertion, maximal oxygen consumption, oxygen consumption at ventilatory threshold 2, lactate, strength tests, or muscle damage and inflammation markers (creatine kinase, C-reactive protein).(Torregrosa-Garcia 2019)

Hemodialysis

Clinical data

In an open-label, randomized, crossover trial in 24 end-stage renal disease patients receiving hemodialysis, both pomegranate juice and juice extract were found to be safe and well tolerated. Patients were assigned to either 4 weeks of pomegranate juice (100 mL administered immediately before each dialysis treatment) followed by 4 weeks of pomegranate juice extract (1,050 mg tablet administered once daily), or to 4 weeks of pomegranate juice extract followed by 4 weeks of pomegranate juice, with a 4-week washout between the 2 treatment periods. No treatment-related adverse events occurred. No significant effects of the juice or juice extract were found on predialysis blood pressure measurements or on posttreatment cytokine production, serum lipids, or biomarkers of systemic inflammation or oxidative stress.(Rivara 2015)

Intrauterine growth restriction

Clinical data

A placebo-controlled trial investigating the impact of maternal dietary supplementation with pomegranate juice on intrauterine growth restriction pregnancies diagnosed at 24 to 34 weeks' gestation (N=99) found no differences in fetal brain volume between treatment groups; however, risk of brain injury was lower in the pomegranate juice group.(Ross 2021)

Kidney stones

Animal data

Levels of oxalates, calcium, and phosphates were regulated subsequent to dose-dependent anti-inflammatory activity of a pomegranate methanolic extract in a rat model of urolithiasis. A chloroform extract was less protective than the methanolic form. Other animal studies have demonstrated inhibition of hyperoxaluria-induced oxidative renal tubular damage via reductions in reactive oxygen species, inducible nitric oxide synthase, nuclear factor-kappaB, and p38-mitogen-activated protein kinase with pomegranate juice and extracts.(Nirumand 2018)

Clinical data

In a study of 23 adults with recurrent stone formation, daily supplementation with pomegranate extract (1,000 mg for 90 days) decreased supersaturation of calcium oxalate via significant down-regulation of paraoxonase/arylesterase activity.(Nirumand 2018)

Multiple sclerosis

Clinical data

The effects of a nano-emulsion formulation of pomegranate seed oil (GranaGard) were examined in a crossover trial with an active extension in 30 patients with multiple sclerosis. Though clinical disability scores were not significantly affected, significant benefit or trends toward benefit in cognitive function were observed (average z-score of cognitive performance tests was significantly improved at 3 months with pomegranate seed oil treatment versus baseline [P=0.034]), with a lingering effect observed in the following 3 months after patients were switched to placebo.(Petrou 2021)

Prostate-specific antigen

Clinical data

In a phase 2, multicenter, double-blind, randomized, dose-exploring study conducted in 104 men with rising PSA following initial therapy for localized prostate cancer, pomegranate extract was administered as 1 g or 3 g daily, with 36% of men completing the full 18-month treatment; each capsule contained polyphenol 1,000 mg (comparable to about 8 ounces of pomegranate juice). Results showed a significant increase in median doubling time of PSA, from approximately 12 months to almost 19 months, with administration of pomegranate extract (P<0.001). No significant difference in PSA doubling time was found between the 2 doses. However, only 1 patient in each dose group met objective PSA decline response criterion. The most common treatment-related adverse events were GI in nature and included diarrhea, reflux disease, nausea, abdominal pain, constipation, frequent bowel movements, stomach discomfort, and vomiting.(Paller 2013)

Weight

Clinical data

A systematic review and meta-analysis of 13 randomized controlled trials (N=532) assessed the nonacute effect of pomegranate consumption on body weight and body composition (ie, waist circumference, fat percentage) in adults. Interventions included pomegranate extract, juice, and vinegar. No significant effect was observed on weight reduction (11 studies [n=422]) and subgroup analyses revealed that this effect was not impacted by formulation, duration of intervention, healthy versus unhealthy participant baseline status, or baseline BMI. Similar results were observed for BMI (10 studies [n=424]), waist circumference (6 studies [n=213]), and body fat percentage (5 studies [n=122]).(Gheflati 2019)

Pomegranate side effects

Three cases of priapism lasting up to 8 hours have been reported subsequent to concomitant use of sildenafil 50 mg and pomegranate juice.(Senthilkumaran 2012)

Fecal impaction as a result of pomegranate seed bezoars has been reported in more than 30 cases. In one case, the impaction was successfully removed via manual disimpaction; however, a secondary traumatic rectal ulcer was observed. In a second case, surgical management was required.(El-Majzoub 2014, Martinez-Pascual 2012)

A case of transient hyperphosphatasemia was reported in a 20-month-old who presented to the emergency department with a 2-month history of hyporexia and feeding difficulties following a daily diet of cereal porridge and pomegranate juice. Alkaline phosphatase levels were pathologically elevated (1,510 units/L) but normalized within 1 month of discontinuing the pomegranate juice.(Molina Gutierrez 2021)

Before taking Pomegranate

Avoid use. Information regarding safety and efficacy in pregnancy and lactation is lacking.

How to use Pomegranate

Various pomegranate dosages, formulations, and durations of treatment have been studied.

Cardiovascular disease risk factors

Pomegranate juice in amounts ranging from 50 to 750 mL/day for various durations have been used in studies evaluating effects on cardiovascular disease risk factors.(Sahebkar 2017, Wang 2020)

Exercise endurance performance

Pomegranate extract 750 mg/day (as two 375 mg capsules of Pomanox P30 [containing 30% punicalagins]) for 15 days has been used in a study evaluating effects on exercise endurance performance.(Torregrosa-Garcia 2019)

Prostate-specific antigen

Pomegranate extract 1 g/day or 3 g/day (ie, 1 or 3 capsules, with each capsule containing 1,000 mg of polyphenol extract, comparable to 240 mL or 720 mL of pomegranate juice, respectively) for up to 18 months was used in a trial evaluating effects on rising PSA levels in men with recurrent prostate cancer.(Paller 2013)

Warnings

No data.

What other drugs will affect Pomegranate

Pomegranate juice can increase the effects of sildenafil. Prolonged and painful priapism has occurred; avoid concomitant use.(Senthilkumaran 2012)

Panobinostat: Pomegranate may increase the serum concentration of panobinostat. Avoid combination.(Abdlekawy 2017, Farkas 2007, Farydak February 2015, Hidaka 2005, Kim 2006, Misaka 2011, Park 2016, Shravan Kumar 2011, Voruganti 2012a, Voruganti 2012b)

Ribociclib: Pomegranate may increase the serum concentration of ribociclib. Avoid combination.(Abdlekawy 2017, Farkas 2007, Hidaka 2005, Kim 2006, Kisqali July 2020, Misaka 2011, Park 2016, Shravan Kumar 2011, Voruganti 2012a, Voruganti 2012b)

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