The activity of cyclooxygenase enzymes associated with inflammation, COX-1 and COX-2, was inhibited in animals fed a polyphenol-rich extract of pomegranate fruit, according to results published in the open-access Journal of Inflammation.

If the study can be repeated in humans it offers promise for preventing chronic inflammation, brought about by an over-expression or lack of control of the normal protective mechanism. Chronic inflammation has been linked to range of conditions linked to heart disease, osteoporosis, cognitive decline and Alzheimer’s, type-2 diabetes, and arthritis.

It is in terms of arthritis that the researchers focus their study, and indicate that pomegranate extracts could provide an alternative to use of non-steroidal anti-inflammatory drugs (NSAIDs), especially in light of mounting concerns about the adverse effects of NSAID use. 

Some of these drugs, which are among the most frequently prescribed medications worldwide, have been linked with gastrointestinal toxicity, increased blood pressure, and increased risk of cardiovascular disease.

“Consumption of pomegranate fruit extract may be of value in inhibiting inflammatory stimuli-induced cartilage breakdown and production of inflammatory mediators in arthritis,” wrote the researchers, led by Tariq Haqqi from Case Western Reserve University in Cleveland, Ohio.

Pomegranate, a rich source of antioxidants, has been linked to improved heart health, but a growing body of science indicates the fruit protect against prostate cancer. Studies have also reported a role in joint health by slowing cartilage loss in arthritis.

It is these antioxidants, and particularly ellagitannin compounds like punicalagins and punicalins, which accounts for about half of the fruit’s antioxidant ability, that are reportedly behind the proposed health benefits.

Study details

Haqqi and co-workers fed four rabbits the pomegranate extract, equivalent of 175 ml of pomegranate juice, while two rabbits given water instead acted as the controls. Blood samples were taken to measure inflammatory biomarkers and antioxidant levels.

The data showed that blood antioxidant levels were significantly higher after ingestion of the pomegranate extract, indicating the bioavailability of the antioxidants.

Moreover, COX-1 and COX-2 activity was significantly reduced in the pomegranate-fed animals, compared to control, particularly for COX-2. Indeed, COX-1 activity was reduced by about seven per cent following ingestion of the extract, while COX-2 activity decreased by about 26 per cent.

“Although direct inhibitory effect of plant extracts or components on COX enzyme activity have been reported by several investigators, inhibition of COX enzyme activity by polyphenols that become bioavailable after consumption of pomegranate fruit or extract has not been reported,” wrote the researchers.

While the results are promising for pomegranates, the researchers rightfully stated that additional animal studies are required, “followed by controlled clinical trials.”

Two studies, both in overweight subjects, confirmed the safety of the ellagitannin-rich pomegranate extract, with no adverse effects reports, and showed a significant reduction in thiobarbituric acid reactive substances (TBARS) in the blood linked with cardiovascular disease risk.

The findings were published in the Journal of Agricultural and Food Chemistry.

According to the authors, formulations containing pomegranate extracts are commercially available in dietary supplements, but, until now, no studies have reported the safety of such extracts in human subjects.

Pomegranate, a rich source of antioxidants, has been linked to improved heart health, but a growing body of science indicates the fruit protect against prostate cancer and slowing cartilage loss in arthritis.

It is these antioxidants, and particularly ellagitannin compounds like punicalagins and punicalins, which accounts for about half of the fruit’s antioxidant ability, that are reportedly behind the proposed health benefits.

Lead author David Heber from the University of California, Los Angeles (UCLA), in collaboration with researchers from the University of Colorado and Pom Wonderful, recruited  64 overweight individuals with increased waist size to take part in the safety study, and a further 22 overweight subjects for the study to measure the effects on TBARS.

Overweight, but otherwise healthy, subjects were chosen because excess abdominal fat has been associated with increased inflammation and oxidative stress, said the researchers.

The first of the two pilot clinical studies assigned the 64 to receive either one or two capsules per day giving daily extract doses of 710 mg (435 mg of gallic acid equivalents, GAEs) or 1420 mg (870 mg of GAEs), respectively, and placebo. The commercially available POMx supplement was used (Pom Wonderful, California).

No major adverse effects were reported during the 30 days. Some minor adverse events were reported but none deemed related to the supplement. Moreover, no significant changes occurred in measures of complete blood count (CBC), chemistry, and urinalysis.

In the second trial, 22 subjects received two POMx capsules providing 1000 mg of extracts per day (610 mg of GAEs). Heber and co-workers report

The researchers did note an increase in body weight among the subjects, however. This could be attributed to the timing of the study, which coincided with end of autumn and several important US holidays.

A significant decrease of 0.13 micromoles in TBARS was observed in these subjects, they report. TBARS is considered an important biomarker for oxidative stress, and is strongly linked to cardiovascular events.

“Further studies are underway to document the effects of this supplement in subjects with type 2 diabetes, known to have a more marked increase in oxidant stress,” wrote the authors.

“This research was part of POMx’s new dietary ingredient (NDI) safety submission, which to the best of our knowledge is currently the only pomegranate dietary supplement to be submitted to the U.S. Food and Drug Administration (FDA),” They added.

Source: Journal of Agricultural and Food Chemistry