Written by Karen Pilkington and the CAM-Cancer Consortium.
Updated March 1, 2017

Pomegranate (Punica granatum)

Does it work?

Systematic reviews, meta-analyses

Two reviews described as systematic have been published. The first included ‘one systematic review of the effectiveness of pomegranate products in the treatment of cancer and another on their safety’ 30. Four clinical studies were found on the effectiveness of three pomegranate products. Two controlled studies, 31,32 one dose comparison study 33 and an uncontrolled open study 22 were identified (see Table 1 for further details). These were assessed against a set of criteria derived from previous reviews and judged to be poor quality.

The total number of studies included in the review that related to safety is not entirely clear but included animal studies, clinical studies and case reports which were described narratively. The conclusions were that there is evidence of an anticancer effect in prostate cancer and that pomegranate can safely be used in high doses. There appears to be a contradiction regarding its effects on liver enzymes: in the abstract, this is stated as induction but, in the discussion, inhibition is described.  The authors also reported that commercial pomegranate products vary greatly in their content of coactive ingredients. The limitations of the search (PubMed only, limited search terms) suggests that relevant studies may not have been located and so the comprehensiveness of this review is uncertain.

A second review focused on pomegranate juice on plasma C-reactive protein concentrations, a marker of inflammation 36. SCOPUS, Medline and two Iranian bibliographic databases were searched for prospective trials. The review methods appear rigorous: data extraction was carried out by two independent reviewers who also assessed the risk of bias of each trial. Five RCTs with a total of 432 participants were included and a meta-analysis conducted. Evidence of a significant effect on plasma C-reactive protein was not found.

Narrative reviews

A detailed review of the phytochemistry and pharmacological actions of all pomegranate components was published in 2007 1. The authors concluded that ‘the actions ofPunica granatumcomponents suggest a wide range of clinical applications for the treatment and prevention of cancer…’ However, this conclusion was based on the results of pre-clinical studies and only one clinical trial was mentioned.

Subsequently, a review summarised the research relating to the effects of pomegranate in prevention of various cancers, including breast, colon, lung, prostate and skin cancers 21. Research showing inhibition of the growth of cancer cells in culture and in preclinical animal studies was described but, again, only one clinical trial was mentioned.

The most recent narrative review aimed to provide a ‘comprehensive analysis of known targets and mechanisms’ and an evaluation of the potential of pomegranate polyphenols as anticancer agents 35. Evidence on prostate cancer was considered the strongest with some indications of a beneficial effect on PSA doubling time. However, a risk of genotoxicity was also highlighted based on results of two studies: a study of high doses of whole fruit extract in mice and a study of the fruit skin extract on breast cancer cells (the latter being a beneficial effect). The authors recommend an accurate assessment of risk-benefit before any recommendations could be made on its potential in cancer treatment.

Clinical trials

A further three randomized clinical trials have been published since the publication of the above reviews and are not included in those.

Prostate cancer

No statistically significant differences were seen in the most recent RCT which compared pomegranate juice and placebo on PSA levels 34. In this trial, the initial intention was to compare placebo, pomegranate extract and standard pomegranate juice but, due to slow recruitment, the study was converted to a two arm (pomegranate extract versus placebo) 1 year after the study was started. The power of the study was reported to be unaltered by this change as the sample size of 183 was sufficient for the 2 way comparison.  Most participants were Caucasian, had surgery or radiation therapy as primary treatment, and were initially staged as T2c or less, Groups were well-matched at baseline and although only 128 completed the 12 months of treatment, rates and reasons for early termination were similar across the groups. Most adverse events were judged not to be related to the pomegranate product except for 3 cases of gastrointestinal events such as nausea, constipation and decreased appetite (definitely related) and, teeth discoloration and abdominal bloating (posibly related). A preplanned subgroup analysis of men with the MnSOD AA genotype suggested that these may be a group more sensitive to the effects of antioxidants

Another recent RCT investigated the effects on specific biomarkers 37. Interpretation of the results was complicated by the effects of surgery.

Breast cancer

No trials in patients with breast cancer were located although one RCT assessed the  effect of consumption of pomegranate juice on breast cancer risk 38.  Sixty-four postmenopausal women were assigned to either a commercial pomegranate juice or to apple juice for 3 weeks. Serum levels of estradiol, estrone, testosterone, androstenedione, and sex hormone binding globulin serum were measured and no significant differences between groups found. The study was small and it is not clear if it was of sufficient size to detect differences. A further analysis indicated a significant reduction in estrone and testosterone in normal weight as compared with overweight women taking pomegranate. However, estrone levels in this group were higher than the control group at baseline so the relevance of this finding is unclear.

Citation

Karen Pilkington, CAM-Cancer Consortium. Pomegranate (Punica granatum) [online document]. http://cam-cancer.org/The-Summaries/Herbal-products/Pomegranate-Punica-granatum. March 1, 2017.

Document history

Fully revised and updated in March 2017 by Karen Pilkington.

First published in January 2013, authored by Karen Pilkington.

References

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