The pomegranate potential
Pomegranates are known to contain powerful antioxidants that fight the oxygen free radicals that cause inflammation, accelerated aging of the tissues, the activation of harmful genes within DNA and an overloaded immune system. Various herbs, spices such as turmeric and teas, as well as dark chocolate, pecans, fruits like blueberries, goji berries, elderberries, cranberries, blackberries and vegetables and pulses like sweet potatoes, broccoli, artichoke and kidney beans also reduce the effects of oxidative damage in the body.
The leading health problems facing us today – including conditions like heart disease, cancer, dementia and other neurological diseases – have been linked to increased levels of oxidative damage.
But until now, there has been no natural, powerful antioxidant capable of crossing the “blood-brain barrier” (BBB) – the semi-permeable, highly selective membrane of endothelial cells that separates the circulating blood from the brain and extracellular fluid in the central nervous system. While the BBB is a vital mechanism for protecting the brain from fluctuations in plasma composition and from substances that can upset neural function, it also keeps out those that can benefit the brain.
Punicic acid (Omega 5) found in oil made from pomegranate seeds (not the red fruit but the small, hard seeds inside) is among the most powerful natural antioxidants, but to breach the BBB, it had to be turned into a submicron self-emulsion formulation.
Researchers headed by experimental neurology Prof. Ruth Gabizon at the neurology department at Hadassah University Medical Center in Jerusalem’s Ein Kerem, along with Prof. Shlomo Magdassi of the Hebrew University’s Nanotechnology and the Casali Center for Applied Chemistry, have developed a food supplement called GranaGard with high concentrations of punicic acid. This substance converts in the body into conjugated linoleic acid, an established neuroprotector. Hadassit, the Hadassah Medical Organization’s research and development arm, and Yissum, the R&D company of the university, established Granalix. This company markets the supplement (it is made by the SupHerb company in Nazareth), which has been approved by the US Food and Drug Administration (FDA). The supplement (NIS 120 for 60 capsules, a month’s supply, and sold via the company’s website and at some stores) is aimed at preventing or slowing the development of neurological disorders from multiple sclerosis to dementia and even reducing symptoms in patients who suffer from them. As GranaGard is a food supplement, it cannot legally make therapeutic claims, but it can provide data on mice studies in which the rodents showed significant improvement in neurological conditions and benefits shown in patients who have taken the supplement over time.
GABIZON, WHO was born in Argentina and came on aliya with her family at the age of 11, is married to Prof. Alberto Gabizon, chief of the oncology institute at Jerusalem’s Shaare Zedek Medical Center, and they have four grown children.
“We met at the Weizmann Institute of Science. I am not a physician, but a neurology researcher,” she said in an interview with The Jerusalem Post. She did a post-doctoral fellowship at the University of California at San Francisco with Prof. Stanley Prusiner, an American neurologist and biochemist who discovered prions – a class of infectious self-reproducing pathogens primarily or solely composed of protein – for which he received the Nobel Prize in Physiology or Medicine in 1997.
“It was very serendipitous, as I had read Prusiner’s articles on prions and then met somebody by chance who was on sabbatical at the university. I sent a letter to Prof. Prusiner, and I was accepted to work at his lab. I was in the right place at the right time, as he was doing totally pioneering work.”
When she returned to Israel in 1988 and continued her research on prion-caused diseases in the lab she built at Hadassah’s neurology department, she did not work on theoretical research detached from the physical disease. “I was part of the clinical department, exposed to patients and their families.”
GABIZON HAS devoted most of her career to the study of neurodegenerataive and prion disorders, including Creutzfeldt-Jakob disease (CJD), a genetic disease among Jews of Libyan and Tunisian origin that was identified in Israel in the 1980s. The incidence of the disease in this ethnic group is about 100 times more than in the worldwide population, and there are some 50,000 carrier families in Israel and 15 actually suffering from the disease. Its effects were similar to the “mad-cow disease” (bovine spongiform encephalopathy) that affected cows whose brain and spinal cord had been contaminated in Britain and killed its first victim there in 1995.
Genetic CJD is vertically transmitted from parent to child in autosomal dominant inheritance. Gabizon noted that there have also been some sporadic cases among Jewish of Ashkenazi origin.
“A young man or woman in their 30s, at the beginning of their life, have just finished their studies and started on a career, got married, and are raising kids. In the midst of this intensive endeavor – a mother or father, perhaps an uncle, becomes ill. The patient is not particularly old, in his 50s or 60s, and is still very much active – with future plans and unattained goals. Yet the disease is progressing at an alarming rate. At first, the patient doesn’t remember small details or his speech slurs. He gets lost in a familiar neighborhood, loses balance. Something is happening; something is festering. He visits his family doctor and then a neurologist, undergoing CT or MRI; his condition continues to deteriorate relentlessly. And then the patient is no longer really with us, even if he or she still lives a bit longer. This is of course shocking and very sad. But it is just the beginning of the story.”
In the midst of all this mayhem, “the specialist asks: ‘Are you from Libya or Tunis?’ Then there are genetic examinations. Thus our man or woman, still in their 30s, and their entire family, find out that their family member is afflicted with a hereditary disease.”
There is a mutation that causes an important protein in the brain to change its form, so that instead of breaking down when it has completed its role, it oxidizes and is stored in brain cells in clusters called amyloids. As a result of the accumulation of clusters of faulty protein, destructive free radicals are created, damaging the quality of the cells. Ultimately, a process of accelerated destruction of the cells is created by this combined co-dependent process, in which protein does not break down, but rather accumulates in clusters, thus creating free radicals that harm the quality of the brain cells.
“Most people who are CJD carriers don’t want to know because the symptoms show up after the age of 40, and there is nothing to do for them. They become confused, very nervous and then paralyzed. They usually die within three months of diagnosis. There is no approved blood test for it,” she said. “But if a couple suspected of being carriers plan to have a baby, they usually want to test embryos by in-vitro fertilization and then use preimplantation genetic diagnosis (PGD) to find unaffected embryos that could be implanted.”
“In view of the dead end reached by all researchers in treating the disease, we decided at the lab to tackle the problem from a totally different direction. If we cannot ‘clean’ the brain cells of destructive faulty protein clusters, thereby curing the patients, perhaps we can strengthen their durability, extend the life span of brain cells, and improve their functioning even under dire conditions such as these, with all of the ‘biological garbage’ and the destructive oxidizing free radicals.”
To this end, “we decided to research the influence of antioxidization on the brain cells, through lab mice in which we planted the Libyan mutation of the PRP protein. The research hypothesis was that if we treat them with sufficiently strong antioxidization that can reach the brain, this may protect the cells and compensate for the damage already incurred. We further stipulated that the treatment should be completely safe of side effects, in order to offer it to young carriers before the disease erupts, as a preventive measure used over many years with no risk involved.”
Her prion research led Gabizon to look for antioxidants connected to lipids that could cross the BBB and reach the brain. “By chance, I bought face cream from the Israeli cosmetics company Lavido that was made from pomegranate oil. People said how young I looked. The Chinese, by the way, discovered long ago that pomegranate seeds were good to eat.”
She called the head of the company and asked for a sample of the oil. “We gave it to mice with the Libyan mutation. We saw that it postponed the mice’s death somewhat, but not enough.” So Gabizon went to Magdassi, who prepared a nano formula with tiny particles and two emulsants. When mixed with water, it turns white. The emulsion isn’t destroyed in the stomach and liver; it goes directly to the blood and breaches the BBB. We started to give it to multiple sclerosis patients after it was effective in slowing the animal model of the disease in mice. We also gave it to mice models with Alzheimer’s disease and to healthy mice that we caused to get a stroke.” It is also being tested on Parkinson’s disease.
“We can’t cure these neurodegenerative diseases, because when neurons die, they can’t be restored. But the supplement can help prevent the disease in people at risk. I have two capsules a day for two years, and so has my husband. I find the supplement improves my sharpness of thinking and gives me much more energy. There are no known side effects or harmful interactions with drugs. The supplement is comprised of 90% pucinic acid in a form that can enter the brain.”
GRANALIX, JUST at the beginning of its marketing effort, sells some 5,000 containers a month, mostly through the Internet. “It costs NIS 10 to manufacture and sells for NIS 120; most of the income goes towards manufacture, salaries and other expenses. We also redirect profits into expanding our research,” said Gabizon, who does not yet profit from the patent held by Yissum and Hadassit registered three years ago. “We don’t want it to be expensive and prohibitive to most people who can benefit from it.”
To register GranaGard as a pharmaceutical drug, the company would have to spend a fortune on large, time-consuming clinical trials and fees for applications to the FDA. “We could do this at some point,” but it is very complicated. In the meantime, since GranaGard is a safe food supplement, we ask patients taking it how they feel. Some report improvement in a month or even a week of taking the supplement.”
The food supplement’s efficacy in the form of nanodrops taken by rodents with a multiple sclerosis model, CJD and metabolic disorders was proven in three articles in scientific journals, the International Journal of Nanomedicine, Nanomedicine and Neurobiology in Disease. GranaGard was shown to delay disease onset in a mouse model of genetic prion disease, which presents neurodegenerative features reminiscent of Alzheimer’s disease. It also was shown to reduce the disease burden in a mouse model of multiple sclerosis. “There are many other studies on the way,” she said.
“Alzheimer’s and Parkinson’s disease seem to be prion-like diseases with aggregation and oxidation, so punicic acid with this delivery system could be effective, without being destroyed in the stomach and liver,” she added.
Neuropaths recommend pomegranate oil to people, but they don’t take into account that it can’t help against neurodegenerative diseases because it doesn’t reach the brain in the form or ordinary supplements.”
IF THE formulation can delay Alzheimer’s disease, it would bring about a revolution, she declared. The International Alzheimer’s Association has reported that by 2030, the number of dementia patients will double, reaching about 70 million worldwide. Global expenditure on treatment has now reached $600 billion, 70% from Western Europe and North America alone.
In Israel, there are now some 120,000 dementia patients, including 1% of the population in their 60s. This percentage is doubled every five years, reaching 30% for ages 85 to 90 and 66% of those over 90.
This data is even more alarming in view of solutions offered by medicine (nowadays appearing quite ordinary – such as nutrition, cholesterol, diabetes, blood pressure issues and hygiene) that have increased life expectancy and created a new demography, she added. ‘The various degenerative brain diseases harm half of the population over 80 and cause significant mental and physical suffering. A cure has yet to be found for the disease, but our nutritional supplement may prevent it.”
The common cause of all degenerative brain diseases is pathological oxidization of components in the nerve cells, which is the precise point of departure of GranaGard. “Since there is no reversal for highly faulty nerve cells, the treatment focuses on maintaining the existing ones, that is, maintaining our brain cells for as long as possible,” she concluded.