Pomegranate's link with learning may not be far from truth

Jewish New Year fruit may hold seeds of hope for brain disease sufferers

Israeli neurologist, nanotech expert make pomegranate oil capsules that send antioxidants where they can have the most effect

Shoshanna Solomon is The Times of Israel's Startups and Business reporter

Pomegranates at the Mahane Yehuda market in Jerusalem on August 25, 2016. (Nati Shohat/Flash90)
Pomegranates at the Mahane Yehuda market in Jerusalem on August 25, 2016. (Nati Shohat/Flash90)

As Jewish families across the world reach for the pomegranate that they customarily eat on Rosh Hashanah, they may not realize that the fruit, with its juicy red seeds and crown-like crest, could hold a key to graceful aging.

King Solomon is said to have designed his crown based on that of the pomegranate, and the image of the fruit often appears on ancient coins of Judea. The pomegranate is said to have 613 seeds, which correspond with the 613 Jewish precepts or commandments set out by the Torah regulating the Jewish way of life. For this reason, and because it represents fruitfulness, knowledge, learning and wisdom, and is seasonal in Israel, it customarily appears on Jewish New Year dinner tables.

The association of the pomegranate with knowledge, learning and wisdom may not be far from the truth. Pomegranate seed oil (PSO) contains high concentrations of punicic acid, or omega 5 as it is also called, which is believed to be one of the most powerful antioxidants in nature.

“Oxidation of proteins and lipids play an important role in aging and neuro degeneration in the brain in general,” said Prof. Ruth Gabizon, a researcher of degenerative brain diseases at the Neurology Department of Hadassah University Hospital in Jerusalem. “Brain cells die over time, from when we are teenagers, and they are not replaced.”

Prof. Ruth Gabizon, a researcher of degenerative brain diseases at the Neurology Department of Hadassah University Hospital in Jerusalem (Courtesy)

Common daily activities, such as digesting food and breathing, create free radicals that result in oxidation and damage to human cells, in particular to brain cells. Unlike blood or skin cells, brain cells do not get replaced by new ones. So free radicals are harmful to our health and end up impairing our thinking, memory, orientation and alertness, among others.

Degenerative brain disease and brain atrophy are typical of debilitating illnesses such as Alzheimer’s, Parkinson’s, and Creutzfeldt-Jakob disease in which brain cells are destroyed, followed by rapid functional and behavioral deterioration and eventual death.

The number of people worldwide living with dementia, for example, is expected to almost double every 20 years, reaching 75 million in 2010 and 131.5 million in 2050, according to Alzheimers’ Disease International.

Fighting fire with food

Aging and brain degeneration are a natural and unavoidable process, explained Gabizon, but they can be accelerated or slowed down depending on our lifestyles.

Antioxidants are known for their ability to protect against the destruction of brain and body cells. They can be found in foods such as cranberries, blueberries, beans, artichokes, pecans and foods containing Vitamin E.

GranaGard is a food supplement that contains pomegranate seed oil (Courtesy Efrat Eshel)

“If we are able to control the levels of free radicals, maybe our cells will work better and live longer,” Gabizon said. “Our approach is that even if we cannot cure the severely affected patients with diseases such as Alzheimer’s, since they are diagnosed at a stage when large numbers of brain cells are already dead, perhaps we can delay the disease’s advance at early stages or even prevent disease outbreak in healthy people at risk of developing neurodegeneration, which is actually most of us.

“This, by extending the life span of brain cells, and improving their functioning even under dire conditions in which the body is filled with ‘biological garbage’ like the destructive oxidizing free radicals.”

Antioxidants, as they are present in many vegetables and fruits, may in principle protect against the destruction of brain and body cells. And this is the case for pomegranate seed oil.

Unfortunately, antioxidants that we consume through food and supplements do not always have the desired impact because they are consumed in too low of a concentration or broken down in the digestive system, and thus never make it to the brain or other cells.

The challenge, said Gabizon, is to make sure the pomegranate oil that we eat, which generally is filtered out by the liver, gets to the parts of our body which can benefit from it.

So Gabizon teamed up with Prof. Shlomo Magdassi — an expert in the field of nanotechnology from the Casali Institute for Applied Chemistry at the Hebrew University of Jerusalem — and together devised a way to break down the oil into tiny particles that can slip through the liver undetected and make their way to the brain.

The product they have developed, called GranaGard, has a high concentration of antioxidants that have a good chance of reaching the brain.

Prof. Shlomo Magdassi of the Institute of Chemistry at the Faculty of Science, February 02, 2012. (Nati Shohat/Flash90)

A study of GranaGard performed by Gabizon and Magdassi found that consumption by lab mice with multiple sclerosis delayed the spread of the disease and considerably reduced its intensity. An additional experiment with lab mice who suffered from Creutzfeldt-Jakob showed that the use of GranaGard “considerably delayed the spread of the disease and lowered the intensity of the accompanying degenerative-dementing processes,” Gabizon said.

The two studies were published in the international Journal of Nanomedicine in November 2015 and in the International Journal of Nanomedicine in 2014.

Gabizon and Magdassi patented the product and formed the firm Granalix Biotechnologies Ltd. They are now hoping to undertake clinical trials to test the effect of their formulation in humans with Creutzfeldt-Jakob, Alzheimer’s and multiple sclerosis, Gabizon said.

GranaGard is already on sale as a dietary supplement at  and is being used by patients with degenerative brain diseases, their family members and others, Gabizon said. The recommended dose is two capsules with breakfast.

Seeds of hope

M is a Jerusalem-based 50-year old medical professional who was diagnosed a year and a half ago with brain atrophy. He has been using GranaGard for a year and three months, after a friend recommended the supplement and after he met with Gabizon to find out more about it.

“One of the ways to deal with atrophy is via fighting free radicals,” M said, preferring not to make his identity known. Since his diagnosis, he has started an antioxidant diet, which includes taking GranaGard and his regular medications along with exercise. Since his diagnosis, he said, there has been no deterioration in his condition.

He would “absolutely” recommend taking the supplement, M said. “I cannot substantially say this (GranaGard) absolutely benefited me, but I have incorporated it as an important piece of my regime. The end result is that I am still functioning.”

Prof. Tamir Ben-Hur, the chairman of the Department of Neurology at the Hadassah Medical Center, knows the supplement and also knows Gabizon, but has no stake in the firm or the technology, he said.

“Oxidation is one of the important mechanisms of tissue injury in many diseases, including neurodegenerative diseases like Alzheimer’s,” he said in a phone interview. “To use antioxidants to stall the process has been around for a while but efforts have generally failed, because either the anti-oxidants were too weak or the active ingredient did not reach the brain.”

The concept behind GranaGard is not new, he said, but the way it is used makes it more powerful than other antioxidants available, such as Vitamin E.

Products that consumers find in health stores – either creams or products to be taken orally — are sometimes inconsistent in their dosages and don’t get effectively absorbed. “These capsules help the formulation surpass the liver, and this is the true advantage of this product versus other products in the stores.”

“There is no clinical proof that GranaGard can slow down Alzheimer’s, and I hope a clinical trial will prove that. But there is good biological research data that it is well absorbed by the gut, reaches the brain and has an antioxidant effect on the brain. We believe it may work with humans but we need to prove it,” he said.

Elderly men play backgammon at a country club in northern Tel Aviv, illustrative (Tomer Neuberg/Flash90)

“I would certainly recommend it to people who are aging and prone to degenerative diseases,” he added. “When you have a pre-Alzheimer’s condition there is nothing to prevent the disease from developing and nothing to stop it. There is no clinical proof of efficacy, but I suggest people take it, because there is good biological rationale, and good data in animals, so why not?”

Gabizon is cautious about raising hopes of patients who are suffering from these debilitating afflictions. At the moment, the only product her company has on the market is an over-the-counter food supplement. Most likely, to actually defeat these illnesses, a cocktail of various compounds will have to be developed, she said.

But each step forward is a victory, she added. Their component has shown a way antioxidants can be broken down to go undetected by the liver and has shown a “definite effect” on the pathology of mice.

“We have not yet proven the formulation’s effect on the human brain,” she said, “But the effect on mice has been proven and we hope to show the same effect with humans during the clinical trials. Even if we don’t find a cure for these diseases, if we are able to delay the degeneration process by a few years, we have done our job.”

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