Life Extension Magazine May 2010
Is Conventional Pomegranate Extract Enough?
By Julius Goepp, MD
An abundance of clinical data has established pomegranate as a broad-spectrum, multi-modal defense against the leading causes of death in the Western world, from atherosclerosis to cancer and diabetes.1
In the last decade alone, more than seven times as many studies have been published validating pomegranate than in all the preceding years combined.2
The bulk of this research has focused on the benefits of pomegranate juice and fruit extracts. Now scientists are discovering a novel source of pomegranate’s myriad benefits: the various botanical components of the pomegranate tree, particularly its seeds and flowers.
The latest scientific evidence indicates that pomegranate flower extract and seed oil uniquely complement conventional pomegranate fruit extract’s capacity to combat multiple diseases of aging.1
For example, a 2009 pre-clinical model found that extracts from pomegranate flowers reduced hardening of the arteries by 70%, while juice alone reduced it by only 40% compared to controls.3 In addition, flower extracts were found to significantly decrease blood lipid and glucose levels.
In this article, you will learn the latest scientific evidence of pomegranate’s life-saving effects, along with new studies exploring various constituents of the plant and their power to combat a host of degenerative diseases through distinct physiological pathways.
Conventional Pomegranate Extracts: Polyphenols Provide Degenerative Disease Defense
The polyphenolic content of pomegranate juice and pulp have historically aroused the greatest scientific interest. In particular, the formidable antioxidant capacity of their ellagitannin content has been credited with much of pomegranate’s health-promoting power.4,5
Recent analysis has further clarified pomegranate’s underlying mechanisms of action, most notably in the area of beneficial gene expression—inhibiting pro-inflammatory nuclear factor-kappaB (NF-kB)4 and downregulating production of cancer-stimulating androgen receptors in prostate cells.5 Pomegranate’s unique role in upregulating expression of paraoxonase-1 (PON-1), an enzyme required for artery-cleansing high-density lipoprotein (HDL) to function optimally, has also generated substantial scientific interest.6,7 (See Innovative Strategies to Combat Kidney Disease)
Pomegranate’s clinically validated cardioprotective effects have prompted some to label it the “heart-healthy” juice.8 Its flavonoid content inhibits oxidative damage to low-density lipoprotein (LDL), helping to protect blood vessels against atherosclerosis.9 Pomegranate polyphenols exert anti-inflammatory effects that further protect blood vessels from damage, reduce the size and number of atherosclerotic lesions, prevent thickening of arterial walls, and lower blood pressure.8
Polyphenols and other components in pomegranate juice exert beneficial effects that extend beyond the cardiovascular system. Numerous phytochemicals in pomegranate juice—ellagic acid in particular—have been shown to disrupt cancer development at multiple stages.2,10,11 Another polyphenol unique to pomegranate is punicalagin, which converts into molecules known to slow prostate cancer cell growth.4 These act by inhibiting pro-inflammatory NF-kB, a cytokine implicated in the development of numerous forms of cancer.4,12-14
Scientists have also focused on pomegranate’s antimicrobial potential. Polyphenols contained in the juice inhibit the growth of a number of pathogenic (disease-causing) bacteria, fungi, and parasites.15-17
Pomegranate Flower Extract: Preventing Metabolic Syndrome
The global epidemic of metabolic syndrome and its associated pathologies—obesity, type 2 diabetes, and cardiovascular disease—has lent new urgency to the discovery of anti-diabetic agents with low toxicity suitable for long-term use.18 New research points to extract of the pomegranate flower as an attractive, safe, low-cost intervention.
In 2006, Chinese scientists discovered a previously unknown polyphenol in pomegranate flower extract that combats weight gain, impaired glucose control, and systemic inflammation. They gave it the name pomegranatate.19
Indian researchers have demonstrated the capability of flowers from male pomegranate plants to influence blood sugar in normal and experimentally diabetic rats.20
In 2005, researchers in Australia demonstrated that 6 weeks of supplementing obese diabetic rats with pomegranate flower extracts prevented blood sugar increases following a glucose-laden meal—but had no such effect in normal rats.21
Yet another profound anti-diabetic activity emerged: pomegranate flower extract enhanced gene expression of the vital transcription factor PPAR-gamma, which regulates cellular responses to energy intake. (See Innovative Strategies to Combat Kidney Disease) It also normalized expression of a glucose-transporting protein in heart muscle, enabling the diabetic animals’ hearts to better utilize energy from sugar. 21 Together these effects suggest a viable molecular pathway for improved insulin sensitivity—an important step in preventing diabetic complications (and slowing aging).
The same researchers convincingly demonstrated that extracts of pomegranate flower reduce cardiac muscle triglyceride content in diabetic rats, simultaneously lowering triglyceride and total cholesterol levels in the blood.22 Normalization of these vital lipid parameters occurred through upregulated expression of PPAR-alpha, the gene transcription factor that controls how cells take up and utilize fatty acids. These twin findings have profound implications: drug companies have spent millions in the effort to find a pharmaceutical that could induce these effects. As a dual PPAR-alpha and PPAR–gamma activator, pomegranate flower extract offers potential realization of that effort through a safe, low-cost, natural intervention.23
The same team of researchers reported that pomegranate flower extract significantly reduced heart muscle fibrosis (thickening and stiffening) in obese diabetic rats.24 Cardiac fibrosis ranks among the more deadly complications of diabetes, resulting in gradually diminishing cardiac output and heart failure. Six weeks of oral treatment with the flower extract reduced the amount of inflexible collagen protein in the animals’ left ventricles and around their coronary arteries.
These results were attained via alterations in gene expression, in this case through downregulation of genes that produce the stiffening proteins collagen and fibronectin. Pomegranate flower extract also reduced heart muscle signaling of endothelin-1, a vasoconstrictor (blood vessel-narrowing) peptide implicated in cardiac fibrosis. Additionally, the extract reduced gene expression of the inflammatory regulatory molecule NF-kB,24 which plays an important role in controlling the inflammation and metabolic alterations associated with obesity.25
Inflammation is the target of another newly discovered component of pomegranate flowers—punicanolic acid, a member of the triterpene family of beneficial essential oil molecules. In laboratory studies, punicanolic acid inhibits production of the potent inflammatory mediator TNF-alpha,26 which is found at increased levels in overweight and obese people and contributes to insulin resistance.27
The inflammation observed in obese and overweight people not only adds to insulin resistance. It also underlies the increased risk of cardiovascular disease seen in obese individuals and in animal models of type 2 diabetes. The condition is characterized by substantially elevated blood sugar levels, LDL, very low-density lipoprotein (VLDL), triglycerides, and oxidized fats. At the same time, beneficial HDL and cellular antioxidant systems are found to be depressed in such individuals.
Oral administration of pomegranate flower extract reversed all of these conditions in a laboratory rat model of type 2 diabetes, highlighting its potential utility for aging individuals at risk for diabetes and its cardiovascular complications.28 The extract also helps ameliorate fatty liver disease,29 the most common cause of liver function abnormalities in people with obesity and type 2 diabetes.
Pomegranate flower extract is a potent inhibitor of the digestive enzyme alpha-glucosidase.30 Alpha-glucosidase breaks complex carbohydrates into their simple sugar components for absorption into the blood. Inhibiting its action slows the rate at which free sugar is absorbed into the bloodstream.
The practical effect of this beneficial action was apparent in an animal model: in diabetic rats fed a carbohydrate-rich meal, oral administration of the flower extract markedly lowered plasma glucose levels during the postprandial (after-meal) period.30 This is a vitally important finding, because postprandial blood sugar elevations contribute greatly to the tissue damage caused by high glucose levels (glycation). Postprandial sugar spikes are also responsible for excessive insulin release that can cause a subsequent drop in glucose levels, triggering inappropriate hunger and further eating.
Additional multi-targeted effects of pomegranate flower extract are emerging rapidly: phenolic compounds from the flowers exhibit numerous anti-atherosclerotic effects even in non-diabetic animal models, reducing the size and number of atherosclerotic plaques by up to 70%.3