Ingredient Spotlight: Pomegranate

Biomedical research over the past few years has yielded quite a few nutritional interventions, each the subject of dozens of human trials. As fruits go, pomegranate (Punica granatum) is near the top of the list, with strong supporting clinical data for a number of applications. If the recent past is any indication, the work on pomegranate is set to continue.

The bulk of clinical trials on pomegranate utilize juice or extracts from the ripe fruit. Pomegranate extracts standardized for water-soluble polyphenols called punicalagins (pronounced PYOO-nee-ka-LAH-jins) typically possess the same or similar activity as pomegranate juice. In fact, the activity of the juice is attributed mainly to an abundance of punicalagins in the husk and rind. These ellagitannin compounds are extracted to a large degree during the commercial juicing process.

Ellagitannins, OPC Cousins

Chemically speaking, punicalagins are twin isomers within a class of polyphenols known as ellagitannins (ETs). ETs are also known as hydrolysable tannins because they hydrolyze and convert into other polyphenols, such as ellagic acid.

Nearly all phenolics act as antioxidants by lending and accepting charged particles. They stabilize more reactive compounds that are prone to oxidation, while remaining relatively stable themselves. This unique attribute enables polyphenolics to stabilize and neutralize reactive molecules that can cause harm to the body, such as free radicals and oxidized proteins and lipids. Tannins are a little different from a lot of other phenolic compounds because they typically possess several phenolic groups on each molecule. Likewise, it’s the tannins’ diversity and number of charged, stable functional groups that explain their interesting ability to stabilize and interact with different shapes and sizes of other molecules. Think of it as a kind of molecular jigsaw puzzle.

Punicalagins from pomegranate have reversed oxidative DNA damage, upregulated cell signaling proteins, protected collagen while inhibiting collagenase, and exerted antioxidant effects via a number of different, biologically relevant mechanisms, such as inhibition of lipid peroxidation that reduces cell membrane integrity.

On the molecular level, tannins’ diverse stabilizing activities explain their historical use in stabilizing and preserving skins to make leather. This mechanism also at least partially explains why some of the major dietary sources of tannins-chemical cousins of ET, including green tea, cocoa, grape seed, and pine bark oligomeric proanthocyanidins (OPCs)-appear to offer nutritional support in a number of areas. Both ETs and OPCs may support cardiovascular health, and a key mechanism for this action is thought to be tannins’ stabilization of circulating blood proteins and lipids.

There is one key chemical distinction between ETs (e.g. pomegranate) and condensed tannins (e.g. cocoa and OPC). ETs are more readily converted, as part of an antioxidant cascade, into other active phenolic metabolites, such as ellagic acid and gallic acid. In fact, key innovations for producing pomegranate extract in recent years have resulted in the preservation of natural levels of punicalagins, so that their resulting cascades occur inside of the body as opposed to during the manufacturing process.

It is difficult to compare and contrast different sources of tannins-and, really, who can argue with the researched benefits on dietary sources of OPC? The data indicates that, while most tannins have a lot of activities in common, not all tannins exert the same activity at physiological concentrations on the same pathways. For example, compared to cocoa flavanols, pomegranate punicalagins exhibited different binding activity on amylase and glucoamylase enzymes in vitro related to metabolic function.¹ The research also suggests a certain likelihood that different sources of tannins, when combined together, can exert a synergistic effect on biological systems. Synergistic activities of the natural spectrum of pomegranate polyphenols found in many juices and extracts (as opposed to the fruit’s major isolated compounds) have been systematically measured and described in the literature. The data, consistent with much of that on other medicinal and food plants, suggests that a balance should be struck between rigorous purification and retaining the phytochemical profile as it is found in nature.

Pomegranate for the Young and the Restless

Research continues on pomegranate fruit and its effect on cardiovascular health, but new clinical findings suggest the benefits of pomegranate may span different age populations. Recent trials have observed positive effects with pomegranate in at least three different demographics: healthy young adults, prediabetic teenagers, and older diabetic adults.²

In one 2012 study performed at Sheffield Hallam University in the United Kingdom, four weeks of pomegranate consumption lowered blood pressure in 51 healthy adults ages 30–50.³ This study is the second to observe blood pressure lowering from pomegranate juice over placebo.

The cardio-supportive effects of pomegranate have translated into some interesting benefits for athletes of different ages. Several research groups have shown that pomegranate, specifically its punicalagins, exert a positive impact on nitric oxide synthesis in blood vessel endothelial cells. This mechanism is thought to be especially useful for vasodilation, thus offering a higher volume of blood and oxygen flow to muscles during exercise, which is necessary for muscle performance and recovery. At the same time, a single dose of punicalagins has demonstrated increased plasma antioxidant status. This may be clinically important because increased levels of nitric oxide are not likely to help without a simultaneous reduction in the oxidative stress caused by intense exercise.

To evaluate the hypothesis that a nitric oxide–boosting antioxidant can help athletes, two recent clinical trials show that consumption of pomegranate polyphenols improved exercise performance and recovery in young athletes. One study, published in 2011, found that resistance-trained young men recovered faster from intense training after two days of pomegranate juice consumption, compared to men in a placebo group.⁴

Clinicals on pomegranate have also investigated effects in metabolically challenged teenagers, as well as in women just before giving birth. A study on 30 teens with pre-metabolic syndrome found that pomegranate and grape juice improved markers of metabolic syndrome and vascular inflammation.⁵

In a 2012 study performed at Washington University in St. Louis, consumption of pomegranate juice (but not apple juice) during the last few days of pregnancy reduced placenta levels of oxidative stress.⁶ In the mechanistic part of this study, punicalagins-but not ellagic acid-reduced oxidative stress in placental tissue in vitro, demonstrating that there may exist potential differences in bioactivity between punicalagin and its daughter molecule, ellagic acid.

New Trials on Special Populations

In the past year, pomegranate has also been studied in semi-healthy populations where results show improvement in a number of relevant clinical markers. A 2012 study on people on long-term kidney dialysis found pomegranate juice intake to improve a number of kidney health markers, while no improvements were observed in a placebo group.⁷ Subjects consuming pomegranate juice also experienced a significantly lower rate of hospitalization due to infection, and a tenfold lower rate in atherosclerotic plaque.

The combined anti-inflammatory, antioxidant, and antibacterial effects exerted by pomegranate ETs have also contributed to positive findings revealing potential application for oral care and gastrointestinal health. A handful of other clinical trials suggest that pomegranate may be a strong selection for gender-specific applications.

Pomegranate Seed Oil

The seeds from pomegranate fruit are a great snack. A little smaller than sunflower seeds, pomegranate seeds are rich in punicic acid, a conjugated linoleic acid (CLA) that is considered an omega-5 fatty acid. Several studies on the seed oil suggest potential benefits for weight management and lipid metabolism. A recent clinical trial, performed in Austria and published in the journal Menopause, found that a daily dose of just 60 mg of pomegranate seed oil improved sleep quality versus placebo, along with a trend for improvement in the Menopause Rating Scale II.⁸

Fruits From Flower

Researchers continue to evaluate and discover new active compounds from various parts of the pomegranate tree. For example, punicatannins A and B are new compounds recently isolated from pomegranate flowers by Navindra Seeram, PhD, and colleagues at the Bioactive Botanical Research Laboratory at the University of Rhode Island. Punicatannins exhibit a very rare functional group: a 3-oxo-1,3,3a,8b-tetrahydrofuro[3,4-b]benzofuran attached to a (¹C₄)-glucopyranose core. To our knowledge, this functional group has been found in only one other species on the planet. Punicatannins also possess some very interesting antidiabetic activities that could be related to their unique molecular structure.

In any case, we are thankful to live in a relative golden age for scientific research on nutritional interventions. The research oeuvre on pomegranate serves as a strong example of the advances we have made in understanding what forms of pomegranate are the best, and why. The hope is to keep building on the strong scientific foundation already established, so that the market permits (and consumers demand) access to dietary supplement ingredients that reliably maintain optimal health.

References

1. A Barrett et al., “Inhibition of α-amylase and glucoamylase by tannins extracted from cocoa, pomegranates, cranberries, and grapes,” Journal of Agricultural and Food Chemistry,  vol. 61, no. 7 (February 2013): 1477–1486.
2. M Aviram et al., “Pomegranate protection against cardiovascular diseases,” Evidence-Based Complementary and Alternative Medicine, published online November 18, 2012.
3. A Lynn et al., “Effects of pomegranate juice supplementation on pulse wave velocity and blood pressure in healthy young and middle-aged men and women,” Plant Foods for Human Nutrition, vol. 67, no. 3 (September 2012): 309–314.
4. JR Trombold et al., “The effect of pomegranate juice supplementation on strength and soreness after eccentric exercise,” Journal of Strength and Conditioning Research, vol. 25, no. 7 (July 2011): 1782–1788.
5. M Hashemi et al., “Acute and long-term effects of grape and pomegranate juice consumption on vascular reactivity in paediatric metabolic syndrome,” Cardiology in the Young, vol. 20, no. 1 (February 2010): 73–77.
6. B Chen et al., “Pomegranate juice and punicalagin attenuate oxidative stress and apoptosis in human placenta and in human placental trophoblasts,” American Journal of Physiology, Endocrinology, and Metabolism, vol. 302, no. 9 (May 2012): E1142–E1152.
7. L Shema-Didi et al., “One year of pomegranate juice intake decreases oxidative stress, inflammation, and incidence of infections in hemodialysis patients: a randomized placebo-controlled trial,” Free Radical Biology & Medicine, vol. 53, no. 2 (July 2012): 297–304.
8. L Auerbach et al., “Pomegranate seed oil in women with menopausal symptoms: a prospective randomized, placebo-controlled, double-blinded trial,” Menopause, vol. 19, no. 4 (April 2012): 426–432.