Evidence from pomegranate study not firm

“A daily glass of pomegranate juice could help to beat male impotence” The Daily Telegraph said today. The newspaper heralds the fruit juice as a drug-free alternative to Viagra, based on a study that looked at the effect of pomegranate juice on erectile dysfunction.

The Sun, also covering the story, claimed that in a study in American men, nearly half reported an improvement in erections as the juice - thought to be rich in antioxidants - increases blood supply.

The research underlying the story was funded by POM Juice, a pomegranate juice manufacturer. It tested the effect of pomegranate juice on erectile dysfunction, and found that some of the men who drank the juice believed that it improved their erectile activity.

However, the actual differences between this group and the placebo group were small and the significance of the findings was overstated. Of the two questionnaires used to measure erectile dysfunction, only one of them found that pomegranate juice had more of an effect than the placebo, and this positive result was not statistically significant. This means the observed difference could well have occurred by chance. It is also likely that the men in the trial could tell the difference between pomegranate and placebo juice, which means the trial may not have been properly ‘blinded’ – that is some of the effect may have occurred because the men expected an effect from the pomegranate juice.

Results from larger, better studies are needed to determine whether or not the small differences can be plausibly attributed to the effects of pomegranate juice. In the meantime, a glass of pomegranate juice can be regarded as part of a healthy diet. Proven treatment for erectile dysfunction is available through a visit to the GP.

Where did the story come from?

Dr CP Forest and colleagues from the Male Clinic in Beverly Hills and the David Geffen School of Medicine at the University of California carried out the research. The study was funded by POM Wonderful, a manufacturer of pomegranate juice. The study was published in the peer-reviewed medical journal: International Journal of Impotence Research.

What kind of scientific study was this?

The study was a double-blind randomised crossover trial comparing the effects of pomegranate juice (manufactured by POM Wonderful) with placebo juice.

Sixty one sexually active males aged 21 to 70 years participated in the study. All were in stable monogamous relationships and were likely to attempt to have sexual intercourse with their partner at least once a week. All the men had mild to moderate erectile dysfunction for at least three months before the study (as indicated by an erectile function domain score of 17-25 on the International Index of Erectile Dysfunction (IIEF) questionnaire. Men with significant health problems (including untreated endocrine disease, liver, kidney or neurological disease, diabetes, and prostate cancer) were not included and neither were men who drank three or more alcoholic drinks per day. Any medication (herbal, over-the-counter or prescription) was discontinued before the study began.

The researchers performed a crossover trial, which means that the same men eventually had both the pomegranate juice and the placebo juice. The researchers randomly allocated the men to either receiving pomegranate juice or the placebo juice first, and performed an initial (baseline) evaluation of them.

Those men starting with the pomegranate juice were advised to drink eight ounces of juice – a medium sized glass - every day either with or just after their evening meal. This continued for 28 days. At the end of this period, the men were assessed using the IIEF and a questionnaire called the Global Assessment Questionnaire (GAQ) where they self-evaluated the effect of the juice on their erectile activity.

During the next two weeks, the men did not take any juice (this is called the ‘washout’ period, which allows the previous treatment to be cleared from the body). They were then swapped to the opposite treatment for 28 days, and at the end of this period, were reassessed using the IIEF and GAQ.

What were the results of the study?

The study found that overall 25 of the 53 men (47%) taking pomegranate juice reported an improvement in erectile function compared to 17 of the 55 men (31%) taking placebo juice. At the end of the study, data were not available for six men who were lost to follow-up.

The researchers go on to report that the GAQ scores showed the ‘men were more likely to have improved scores if they drank pomegranate juice’, though this result was not statistically significant. There was no difference between the groups in scores on the IIEF, which is considered to be a more objective measure of erectile dysfunction.

What interpretations did the researchers draw from these results?

The researchers concluded that they demonstrated a trend towards improved erectile function with pomegranate juice. They say that larger studies with longer treatment periods may clarify the issue and might ‘achieve statistical significance’.

What does the NHS Knowledge Service make of this study?

The study has some weaknesses, some of which the researchers themselves discuss. It is difficult to say exactly how these will have affected the results:

• The overall difference in GAQ scores between the pomegranate and placebo groups was not statistically significant. The researchers have acknowledged this and say that the study “observed a trend toward increased erectile function”, which means very little scientifically in a study of this size. They suggest that larger studies may show significance.
• Placebo juice also seemed to improve erectile function with 31% of men taking the placebo demonstrating improved scores on the GAQ. This result highlights the complexity of the causes of erectile dysfunction in healthy young males. A high rate of response to placebo 30% or more is not unusual in studies of this type and reinforces the need to ensure the participants did not know which juice they were getting.
• Although the authors claim that the placebo juice was similar in colour and taste to the pomegranate juice, they did not report testing if the men could actually taste the difference. Considering the unique taste of pomegranates, it is unlikely that the two were exactly matched. Because of this, participants may have known what “treatment” they were having at what time, i.e. they would not be “blinded”. This would have biased the measures of treatment effect if participants had some expectation (conscious or subconscious) of how the juice might affect them.
• The men in this study did not always drink their juice as they were asked to. The researchers report that “at least 87% of subjects in each cohort consumed the study beverage a minimum of 21 days during each 28-day study period”.
• There was no difference between groups in scores on the IIEF. The IIEF is a questionnaire that determines the severity of erectile dysfunction in a more objective way than the GAQ (which rates what effect men felt the drink had on their erectile function). The researchers say that the pomegranate juice may have taken up to two weeks to show any effects and so scores on the IIEF, which rated sexual activity over the whole of the 28 days of “treatment” may not have been sensitive enough to detect any differences.

Fruit juices can be a good contribution to a healthy diet and there are good reasons, such as their vitamin C content, to drink them. Until there is more information from larger studies with longer treatment times and more effective blinding it is impossible to be sure that improvement in erectile function is a benefit of drinking this juice. The researchers say as much by concluding that “further studies are warranted to clarify the efficacy and clinical role of pomegranate juice on male erectile dysfunction”. The large effect on erectile dysfunction of placebo recorded in this study is notable, and has implications for all erectile dysfunction treatments.

Sir Muir Gray adds...

There is evidence that research funded by an industry is more likely to produce a positive result than research funded by a disinterested source; therefore it is essential to wait to see if other studies produce the same result.

Just one more point, my wife bought pomegranates and made juice (which I did not like). She assures me it was just by chance.