Cardiovascular Support

Research collaborators from both Israel and Los Angeles, California conducted a three-year human trial on the effects of pomegranate juice consumption by atherosclerotic patients with carotid artery stenosis (CAS) on the progression of carotid lesions and changes in oxidative stress and blood pressure. Cholesterol, fat, and other substances stick to the inner lining of an artery and cause plaque formation. The narrowing of blood vessels leads to several cardiovascular diseases such as atherosclerosis, CAS, and several other myopathies of the heart and blood vessels. In CAS, a blood clot occurs in the carotid artery resulting in an ischemic stroke. The researchers reported that consumption of pomegranate juice significantly reduced plaque formation in these CAS patients. Moreover, a decrease in systolic pressure was shown. Lipid analyses revealed that a significant reduction in LDL oxidation occurred in these patients as well.

Aviram, M., Rosenblat, M., Gaitin, D., Nitecki, S., Hoffman, A., Dornfeld, L., Volkova, N., Presser, D., Attias, J., Liker, H., Hayek, T. 2004. Pomegranate juice consumption for 3 years by patients with carotid intima-media thickness, blood pressure and LDL oxidation. Clinical Nutrition. 23: 423-433.

In the vascular system, endothelial nitric oxide synthase (eNOS) produces nitric oxide and plays an important role in maintaining blood pressure homeostasis. High nitric oxide levels aid in relaxing the blood vessels and serve as a good indicator of overall vascular integrity. Researchers in Japan showed that the anthocyanin cyanidin-3-glucoside from purple corn increased eNOS production in bovine artery endothelial cells (BAECs) in vitro. This, in turn, relaxes vascular endothelial cells and indirectly affects blood pressure and may be able to prevent atherosclerosis as a long-term benefit.

Xu, JW., Ikeda, K.,Yamori, Y. 2004. Upregulation of endothelial nitric oxide synthase by cyanidin-3-glucoside, a typical anthocyanin pigment. Hypertension. 44: 217-222.

A small uncontrolled study in 2013 recruited 11 healthy Japanese women with high peripheral cold (thermal) constitution who were given three tablets daily containing 50 mg chokeberry extract (anthocyanin content equivalent to 35% w/w). The subjects were instructed to take all three tablets daily with water, after breakfast for four weeks. At the end of the study, the subjects’ body surface temperature after 20 minutes of acclimatization in an air-conditioned room was significantly higher than at the beginning. Psychological tests showed that factors related to cold were improved significantly and plasma noradrenaline concentration was elevated significantly (which would elevate thermogenesis) by chokeberry intake. However, peripheral blood flow was not affected. The authors concluded that chokeberry supplementation improves body temperature maintenance in healthy women with cold constitution, but that further research in placebo-controlled studies are needed to further investigate these findings.

Sonoda K, Aoi W, Iwata T, Li Y. 2013. Anthocyanin-rich Aronia melanocarpa extract improves body temperature maintenance in healthy women with cold constitution. Springerplus. 2:626. Doi: 10.1186/2193-1801-626. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3843504/pdf/40064_2013_Article_664.pdf. Accessed January 1, 2014.

One randomized, placebo-controlled human clinical study in 2005 found that rowers who supplemented their diets with chokeberry juice experienced less exercise-induced oxidative damage to red blood cells. Members of the Polish rowing team (19 males) comprised the study population. The treatment group (n=9) received 50 mL of chokeberry juice (23 mg/mL anthocyanin content) three times daily for four weeks. The placebo group (n=10) received 50 mL juice three times daily which was identical in taste and appearance to the chokeberry juice. At the end of four weeks of supplementation, the rowers performed an incremental rowing ergometer exercise as a control. The following day they performed another incremental rowing exercise at which time blood samples were taken prior to starting, one minute after completion, and after a 24 hour recovery period. Concentrations of thiobarbituric acid reactive substances (TBARS) were assessed as a measure of red blood cell oxidative damage. TBARS concentrations were significantly lower in the chokeberry group than in the placebo group. The chokeberry group also experienced lower creatine kinase activity after the rowing exercise suggesting a reduction in muscle damage associated with hard exercise.

Pilacyzynska-Szczesniak L. Skarpanska-Steinborn A, Deskur E, Basta P, Horoszkiewicz-Hassan M. The influence of chokeberry juice supplementation on the reduction of oxidative stress resulting from an incremental rowing ergometer exercise. Int J Sport Nutr Exerc Metab. 2005;14:48-58.

Protection Against Gastric Diseases

Researchers in Japan conducted studies on the antioxidant properties of a chokeberry extract and the effects on gastric mucosal damage. When chokeberry was administered to rats with gastric hemorrages, the gastric mucosal protection was proportional to the increased anthocyanin levels from the chokeberry extract. They suggested that the cyanidins in chokeberry scavenge the radicals generated during gastric mucosal damage.

Matsumoto, M., Hara, H., Chiji H., Kasai T. Gastroprotective effect of red pigments in black chokeberry fruit (Aronia melanocarpa Elliot) on acute gastric hemorrhagic lesions in rats. Journal of Agric. And Food Chem. 2004.

Protection Against UV Radiation Damage

Excessive exposure to solar ultraviolet (UV) radiation, particularly its UV-B component, can cause many adverse effects in humans that include erythema (redness of the skin), hyperplasia (increase in number of cells), hyperpigmentation (uneven dark patches), immunosuppression, photoaging and skin cancer. Researchers in Madison, Wisconsin examined the effect of a pomegranate extract on human epidermal keratinocyte (NHEK) cells in vitro. When skin is exposed to excess sunlight, a cascade of adverse chemical changes take place. For example, a series of key proteins crucial to cell regulation (p38, c-Jun-N-terminal kinase [JNK], extracellular signal-regulated kinases [ERK]) are chemically phosphorylated and skin cells are damaged. In addition, other nuclear factors such as the NF-кB pathways are modified, producing detrimental results. The researchers showed that when NHEK UV-induced cells were treated with pomegranate extracts, NF-кB modification was prevented and harmful protein alterations were inhibited. Thus, pomegranate extract could be used to prevent UV damage and possibly skin cancer.

Afaq, F., Malik, A., Syed, D., Maes, D., Matsui, M.S., Mukhtar, H. 2005. Pomegranate fruit extract modulates UV-B mediated phosphorylation of imtogen activated protein kinases and activation of nuclear factor kappa B in normal human epidermal keratinocytes paragraph sign. Photochem. Photobiol. 81(1): 38-45.

Structure-Function Relationships

The antioxidant activities of a series of commonly consumed and biogenetically related plant phenolics, namely, anthocyanidins, anthocyanins, and catechins, in a liposomal model system were investigated. Distinct structure-activity relationships were revealed for the antioxidant abilities of these structurally related compounds. Whereas antioxidant activity increased with an increasing number of hydroxyl substituents present on the B-ring for anthocyanidins, the converse was observed for catechins. However, substitution by methoxyl groups diminished the antioxidant activity of the anthocyanidins. Substitution at position 3 of ring C played a major role in determining the antioxidant activity of these classes of compounds. The anthocyanidins, which possess a hydroxyl group at position 3, demonstrated potent antioxidant activities. For the cyanidins, an increasing number of glycosyl units at position 3 resulted in decreased antioxidant activity. Similarly, the substitution of a galloyl group at position 3 of the flavonoid moiety resulted in significantly decreased antioxidant activity for the catechins. Among catechins, cis-trans isomerism, epimerization, and racemization did not play a role in overall antioxidant activity

Seeram, N.P., Nair, M.G. 2002. Inhibition of lipid peroxidation and structure-activity-related studies of the dietary constituents anthocyanins, anthocyanidins, and catechins. J. Agric Food Chem. 50:5308-5312

Researchers from the HortResearch Institute of New Zealand presented some interesting findings highlighting how compounds may act as poor “chemical” antioxidants while still effectively protecting cells from cytotoxicity. Methylating polyphenolic compounds, including flavonoids, typically eliminated their “chemical” antioxidant capacity—as determined by tests such as FRAP and ORAC. Methylation, however, only moderately reduced protection of human Jurkat cells in culture from hydrogen peroxide-induced cytotoxicity. Interestingly, the methylated compounds appeared to be somewhat less available to the cells, suggesting absorption by the cells may not necessarily be required for phenolic compounds to protect them from hydrogen peroxide. These observations provide insight that while polyphenolics almost certainly do have chemical antioxidant effects in vivo, their overall beneficial effect on the body is much more complicated and much of their benefit may come from unrelated mechanisms.

Deng, D., Zhang, J., Cooney, J.M., Skinner, M.A., Adaim, A., Jensen, D.J., Stevenson, D.E. 2006. Methylated polyphenols are poor “chemical” antioxidants but can still effectively protect cells from hydrogen peroxide-induced cytotoxicity. FEBS Letters 580: 5247-5250.

Then, in a 2007 review paper from the HortResearch Institute of New Zealand, the researchers discuss how many of the potential benefits from polyphenolic antioxidant compounds occur via regulation of cellular processes and there are more “indirect” antioxidant activities. There is much discussion on whether or not there are high enough circulating concentrations of intact anthocyanins to be bioavailable and exhibit in vivo activity. However, protection from oxidative stress may occur at much lower concentrations than what would be required for chemical antioxidant protection (as detected by tests like ORAC). Also, metabolites with rearranged chemical structures may have greater activity than the native forms. Some studies indicate that polyphenols may induce the upregulation of endogenous antioxidant enzymes in vivo and the protection may occur at the gene transcription level.

Stevenson, D.E., Hurst, R.D. 2007. Review: Polyphenolic phytochemicals-just antioxidants or much more? Cell. Mol. Life Sci:1-17.