Researchers find pomegranate juice exacerbates Parkinson's in rat model

A study using POM Wonderful’s pomegranate juice has found it exacerbated neurodegeneration in a rat/rotenone model of Parkinson’s disease.  The finding ran counter to the researchers’ expectations.

The study, published online and set for the May print issue of Neurobiology of Aging, used a widely accepted model of Parkinson’s disease in which rats are exposed to rotenone, a naturally-derived toxin that is used as a pesticide.  Exposure to rotenone mimics the neurodegeneration observed in Parkinson’s. Other studies have shown that polyphenols can attenuate or block the neuronal death in animal models of neurodegeneration so the researchers from the University of Pittsburgh, the University of Purdue and the Pittsburgh Veterans Administration health care system theorized that pomegranate juice, rich in various classes of polyphenols, would have similar effects.  Other polyphenols that in studies have shown neuroprotective effects in the face of neurodegenerative models have included curcumin, quercitin and fisten. Pomegranate juice contains a suite of polyphenols such as ellagic acid and gallic acid and flavonoids such as hydrolyzable tannins [ellagitannins, gallotannins, punicalagin], and anthocyanins and their glycosides [pelargonidin, cyaniding, delphinidin]. But instead of a protective effect, in this model the researchers found just the opposite.

Study details

The rats were divided into four groups, one group that received sugar water only, two groups that received sugar water and either rotenone or pomegranate juice and a fourth group that received both the juice and rotenone. The animals were evaluated on their motor skills including rearing behavior (an exploratory movement in which rats stand more or less erect and touch surfaces with their forelimbs) and a postural instability test. After the tests, the rats’ brain tissue was harvested and evaluated for nigrosriatal degradation. The nigrostriatal pathway is one of the avenues for dopamine activity in the brain and is in particular assocation with motion. Degradation of this pathway is one of the hallmarks of Parkinson’s.

The researchers were surpised by their results. “Contrary to our expectation, [pomegranate juice] failed to provide neuroprotection resulting in an exacerbation of rotenone-induced nigrostriatal degeneration,” they wrote.

Why this might be the case is something that stumped the researchers, but they postulated that it might have something to do with the full spectrum of polyphenols present in the juice. “The reasons for this discrepancy between our results and previous studies are not known. Nonetheless, a crucial difference between our present work and the aforementioned studies is the use of a polyphenol mixture . . . instead of individual phytochemicals at high concentrations,” they wrote.

They continued: “A possible answer could be related to misconceptions about the antioxidant properties of [pomegranate juice]; polyphenolic phytochemicals are considered double-edged swords in cellular redox status. Experimental evidence in cell models supports the pro-oxidant nature of a large number of polyphenol compounds.”

Occasional foods consumed year round

Alexander Schauss, PhD, senior director of scientific and regulatory consultancy AIBMR Life Sciences, said the researchers had good reason to postulate at the outset that pomegranate juice might show a protective effect in this case.

“Researchers had found that pomegranate juice had some evidence that it would delay the development of Alzheimer’s,” Schauss told NutraIngedients-USA.  But the results of the recent study illustrated a reservation Schauss said he has had about pomegranate and other polyphenol-rich foods that in the past have been consumed only occasionally while they were in season.  Could consuming such traditionally seasonal foods prove to be too much of a good thing?

Schauss said he likens the situation to work that he did years ago on soursop (Annona muricata L.), a tree fruit widely cultivated throughout the tropics. Schauss found that cases of atypical Parkinson’s disease observed on the island of Guam were linked to individuals who preserved the fruit and consumed it year-round. Soursop in its fresh state is a fruit with a very short shelf life, Schauss wrote in a chapter on the fruit for the book Bioactive Foods in Promoting Health: Fruits and Vegetables

 Soursop has developed natural pesticides to help it withstand insect attack, Schauss said. “Chemistry is the only way that plants have to protect themselves,” he said.

Schauss said this issue has entirely to do with the nature of the particular plant source, and not all polyphenol-rich tropical fruits might be similarly implicated. “I’ve done 18 years of work on acai, but the difference there is that there are four harvest periods for acai in its native Brazil.  More than 60% of the diet of the people in those regions has consisted of acai and tapioca, and they have consumed it year round for many years without problems,” he said.

Schauss said this most recent study on pomegranate juice calls for additional studies to see if the results can be replicated and, if so, to further quantify any possible toxicity concerns for long-term pomegranate juice consumption.

“This result for pomegranate is something I would take pretty seriously. This isn’t something I’d write off,” he said.

Source: Neurobiology of Aging

Published online ahead of print, doi: 10.1016/j.neurobiolaging.2013.10.077

“Pomegranate juice exacerbates oxidative stress and nigrostriatal degeneration in Parkinson's disease”

Authors: V. Tapias, J.R. Cannon and J.T. Greenamyre