Friday, October 3, 2008

Blood Orange Health Benefit Summary for Doctors

Written by Marianne Trevorrow, MA ND

There is an increasing prevalence in Western societies of diseases commonly associated with oxidative stress; cardiovascular disease, diabetes, and cancers being the most well known of these so-called ‘diseases of affluence’. Increased production of oxygen free radicals from such causes as chronic stress, poor diet and environmental pollutants are often at the core of progressive cellular damage from lipid oxidation, which in turn can cause breaking of DNA strands and the release of inflammatory blood chemicals known as cytokines. This chronic release of pro-inflammatory chemical signals is believed to play an important role in the initiation and promotion of pre-disease conditions such as atherosclerosis or metabolic syndrome (Esposito & Giuliano, 2006).

Consumption of a diet rich in fruits, juice and vegetables, along with whole grains and omega-3 fats, commonly known as the ‘Mediterranean diet’, has been demonstrated to decrease risk factors for both metabolic syndrome and coronary heart disease (de Logeril et al; 1999; Espositio et al. 2004). These protective qualities are believed to be promoted in large part by antioxidant phytonutrients such as flavonoids, which are believed to be the largest source of antioxidant compounds in the human diet (Scalbert et al. 2005). Flavonoids such as the one that cna be found in teh VioVi blood orange juice are effective antioxidants because of their free radical scavenging abilities; by reducing free radical activity, they can help protect the body’s tissues against the progressive effects of oxidative stress lowering the incidence of many chronic diseases (Knekt et al. 2002).

The red color makes the difference
Numerous studies have demonstrated that flavonoid compounds are particularly high in fruits such as blood oranges . These oranges are native to the volcanic soils around Mount Etna on the island of Sicily, in Italy. Due to the large fluctuations of temperature characteristic of this region, Red Oranges have much higher levels of antioxidant compounds such as Vitamin C, flavonoids and carotenoids than regular oranges. Their distinctive red color, in fact, is due to the presence of one particular flavonoid family known as anthocyanins, which are present in both the peel and the juice portion of the orange. This is the same red pigment found in blueberry and pomegranate juices, but is unique in richnes the cocktail of antiooxidant in red oranges among citrus fruits.

Up until the past decade, most of the studies on the health-promoting benefits of red oranges, similar to other citrus fruit, focused almost exclusively on their high vitamin C content. More recently, however, improvements in chemical analysis methods such as High pressure liquid chromatography (HPLC), and tests of anti-oxidant capacity such as Oxygen Radical Absorbance Capacity (ORAC) and a vitamin E based assay known as Trolox Equivalent Antioxidant Capacity (TEAC), have allowed researchers to determine specific constituents and to quantify the relative effect of these constituents individually, as well as any synergistic effects that can be measured in whole food compounds.

As indicated in Figure 1, Anthocyanins, abundant in Blood Orange varieties are almost not present in the traditional ornage juice sold in the US stores shelves. Vitamin C content in freshly squeezed red oranges is approximately 2 times higher than non-pigmented oranges, while the flavonoids hesperidin and nairirutin are approximately 2-3 times greater. (Proteggente et al. 2003).

A 1999 study argued that the antioxidant activity of red orange juice is mainly related to its total flavonoid content, including the anthocyanins and also hesperidin and nairirutin. Oranges with higher levels of these compounds were demonstrated to be better antioxidants (Rapisarda et al, 1999). More recent studies have given more importance to the Vitamin C components (Arena E. et al. 2001; Proteggente et al. 2003), but what does seem clear is that in addition to the anti-oxidant properties of Vitamin C, which are well known, the abundant flavonoids present in red orange juice are themselves a significant source of dietary antioxidants.

Studies on anthocyanins found in red oranges have shown protective effects on heart muscle and red blood cells from oxygen mediated damage (Amorini et al, 2003), against LDL oxidation (Amorini et al. 2001) and against free radical associated DNA damage (Aquaviva et al. 2003). Cyandin-3-glycoside (C3G), the most common anthocyanin present in red orange juice, has been shown in one study to have antioxidant activity higher than either Vitamin C or resveratrol, an anti-oxidant component of red wine (Amorini et al., 2001).

Hesperidin and nairirutin, the other main flavonoids in red orange juice, are metabolized by the human gut to form the compounds hesperitin and naringenin, which have also been shown to have many health-promoting effects. A hesperitin metabolite, for example, has been shown to protect human skin fibroblast cells from ultra violet A-induced oxidative stress (Proteggente et al., 2003). Hesperitin and naringenin together were shown to lower cholesterol levels by inhibiting cholesterol ester synthesis in human liver cells (Borradaile et al. 1999). Hesperitin and naringenin have also been shown in vitro to have antiplatelet (Jin YR et al., 2007), anti-inflammatory (Hirata et al. 2005), neuroprotective (Heo et al. 2004), anticarcinogenic (Shen et al. 2004), and anti-inflammatory (Rotelli et al. 2003) activity.

Ironically however, these same free radical scavenging qualities that make flavonoids such effective anti-oxidants also make them unstable to high temperatures or UV light for long periods. A recent study by Fiore et al., showed that red orange juices that were both flash pasteurized and refrigerated maintained a high level of both anthocyanins and antioxidant ability for up to four months—values comparable to freshly squeezed juice (Fiore et al. 2005). On the other hand, high temperature processing and long shelf-storage were both shown to degrade anthocyanins to the point where they were almost negligible, according to the authors.

This is a unique benefit of Blood Orasnge juice against companies that are selling products with less amounts of juice or with juice that has been sterilized etc. This, I think, is your products greatest leverage against the ‘multi-nationals’—as Fiore points out on p. 1133 (I’ve attached the article)—there is huge difference between the cold pasteurized and sterilized juices—that might be good to put into a graphic.

Also: Rapisarda’s articles (attached) points out that anthocyanin levels can vary significantly according to variety, environmental conditions, fruit maturity and cold storage (for example, he reports a 500% increase in C3G over 120 days’ storage at 8°C).

In addition to in vitro evidence for the anti-oxidant abilities of red orange juice, several human trials have also demonstrated that the red orange juice flavonoids can increase the antioxidant capacity in plasma or in specific types of blood cells after they are ingested. Citrus flavonoids such as hesperidin and nairirutin are present in red oranges as glycosides—that is bound to sugar molecules. In the human digestive tract, enzymes remove the sugar molecules, creating what are known as aglycones (molecules ‘without sugars’). The anthocyanins such as C3G, interestingly, as also present in red orange juice as glycosides, but appear to be absorbed with their sugar molecules intact (Cao et al. 2001; Prior, 2003). In both forms, flavonoids then enter the bloodstream and become biologically active as free radical scavenging anti-oxidants.

This was demonstrated in a 2005 study with human subjects found a significant increase in plasma vitamin C and the anthocyanin C3G after consuming red orange juice for a period of 21 days (Riso et al. 2005). They also found increased white blood cell DNA resistance to oxidative stress in the group consuming the red orange juice over the control group. Another more recent group found decreased DNA damage in one type of white blood cell for 24 hours following a single serving of red orange juice given to volunteers. Interestingly, this effect was not seen after volunteers were given a drink supplemented with the same amount of vitamin C (Guarnieri et al. 2007).

Extracts taken from blood orange juice have also been shown to have some beneficial therapeutic effects in human studies in physical stress recovery. One group found a marked decrease in levels of serum free radicals and other markers of oxidative stress in diabetic patients given the extract daily for 2 months (Bonina et al. 2002). This free radical-lowering effect was also found in professional handball players also given the extract daily for a 2 month period (Bonina et al. 2005).


Daily consumption of Blood Orange juice has been an integral part of the Mediterranean diet for generations. As part of this healthy diet, daily intake of red orange juice provides high levels of flavonoids, including anthocyanins, hesperidin and nairirutin, as well as vitamin C, beta-carotene and dietary fiber. Taken together, all of these compounds have important health benefits, but as a whole food, red orange juice has synergistic benefits greater than those of the individual phytonutrients and vitamins, ones that we are only just beginning to truly understand. This is why a daily glass of red orange juice may just prove to be an economical way not only to maintain good health but also to protect against many of the common diseases of aging, including atherosclerosis, stroke, diabetes, and many cancers.

1. Amorini AM et al. Activity and mechanism of the antioxidant properties of cyanidin-3-O-glucopyranoside. Free Radical Research 2001, 35, 953-66.
2. Amorini AM et al. Cyanidin-3-O-glucopyranoside protects myocardium and erythrocytes from oxygen radical-mediated damages. Free Radical Research, 2003, 37(4): 453-460.
3. Aquaviva R et al. Cyanindin and cyanidin-3-O-β-D-glucoside as DNA cleavage protectors and antioxidants. Cell Biology and Toxicology 2003; 19, 243-252.
4. Arena E. et al. Evaluation of antioxidant capacity of blood orange juices as influenced by constituents, concentration process and storage. Food Chemistry 2001, 74, 423-427.
5. Bonina F. et al. Evaluation of oxidative stress in diabetic patients after supplementation with a standardized red orange extract. Diabetes Nutrition Metabolism, 2002 Feb, 15(1), 14-19.
6. Bonina F. et al. Oxidative stress in handball players: effect of supplementation with a red orange extract. Nutrition Research, 2005, 25, 917-924.
7. Borradaile NM, et al. Regulation of HepG2 cell apolipoprotein B metabolism by the citrus flavonones hesperitin and naringenin. Lipids , 1999, 34, 591-598.
8. Cao G., et al. Anthocyanins are absorbed in glycated forms in elderly women: A pharmacokinetic study. American Journal of Clinical Nutrition 2001, 73, 920-926.
9. Esposito K et al. Effect of a Mediterranean-style diet on endothelial dysfunction and markets of vascular inflammation in the metabolic syndrome: a randomized trial. JAMA 2004; 292: 1440-1446.
10. Esposito K, Giuliano D., Diet and inflammation: a link to metabolic and cardiovascular diseases. Eur Heart Journal 2006 Jan 27(1): 15-20.
11. Fiore A., et al. Antioxidant activity of pasteurized and sterilized commercial red orange juices. Molecular Nutrition Food Research, 2005, 49, 1129-1135.
12. Galvano F et al. Journal of Nutritional Biochemistry, 2004, 15, 2-11.
13. Guarnieri et al. Orange juice vs. vitamin C: effect on hydrogen peroxide-induced DNA damage in mononuclear blood cells British Journal of Nutrition, 2007, 97, 639-643.
14. Heo HJ et al. Effect of antioxidant flavonone, naringenin, from Citrus junos on neuroprotection. Journal of Agricultural and Food Chemistry, 2004, 52, 1520-1525.
15. Hertog MGL et al. Dietary antioxidant flavonoids and risk of coronary heart disease: the Zutphen Elderly Study. Lancet 1993, 342, 1007-11.
16. Hertog, MGL et al. Flavonoid intake and long-term risk of coronary heart disease and cancer in the seven countries study. Archives of Internal Medicine, 1995, 155, 381-386.
17. Hirata A et al., Kinetics of radical-scavenging activity of hesperetin and hesperidin and their inhibitory activity on COX-2 expression. Anticancer Research, 2005, 25, 3367-3374.
18. Knekt P et al. Flavonoid intake and risk of chronic diseases. American Journal of Clinical Nutrition, 2002, 76, 560-568.
19. Jin YR et al. Antiplatelet activity of hesperitin, a bioflavonoid, is mainly mediated by inhibition of PLC-gamme2 phosphorylation and cyccloxigenase-1 activity. Atherosclerosis, 2007, 194 (1), 144-152.
20. Prior RL. Fruits and vegetables in the preventional of cellular oxidative damage. American Journal of Clinical Nutrition, 2003, 78, 570A-578S.
21. Proteggente AR, et al. Hesperetin glucuronide, a photoprotective agent arising from flavonoid metabolism in human skin fibroblasts. Photochemistry Photobiology 2003 Sep; 78 (3), 256-61.
22. Proteggente AR, et al. The compositional characterization and antioxidant activity of free juices from Sicilian sweet orange (citrus sinensis L. osbeck) varieties. Free Radical Research, 2003, 37(6), 681-687.
23. Rapisarda P, et al. Antioxidant effectiveness as influenced by phenolic content of fresh orange juices. Journal of Agricultural and Food Chemistry, 1999, 47, 4718-4723.
24. Rapisarda P et al. Storage temperature effects on blood orange fruit quality. Journal of Agricultural and Food Chemistry, 2001, 49, 3230-3235.
25. Riso P et al. Effects of blood orange juice intake on antioxidant bioavailability and on different markers related to oxidative stress. Journal of Agricultural and Food Chemistry, 2005, 53, 941-947.
26. Scalbert A et al. Dietary polyphenols and the prevention of disease. Critical Reviews in Food Science and Nutrition, 2005, 45:1-20.
27. Rotelli et al. Comparative study of flavonoids in experimental models of inflammation Pharmacology Research, (2003), 48, 601-606.
28. Shen SC et al. Structurally related antitumor effects of flavonones in vitro and in vivo: involvement of caspase 3 activation, p21 gene expression, and reactive oxygen species production. Toxicology App Pharm, 2004, 197, 84-95.
Steinmetz KA, & Potter JD., Vegetables, fruit and cancer prevention: a review. Journal of the American Dietetic Association. 1996, 96, 1027-1039.


cirospat said...

where is possible to buy this orange juice in city of Palermo ?
I had the opportunity to try it and taste is great, good quality, completely different from other artificial orange juices.

I'm interested in buying this product in Palermo, if i knew shops.

Thanks and regards

Bruce said...

Citrus fruits are really rich in vitamins. Most doctors and (Hilton Head) dentists advice their patients to eat lots of fruits and veggies because of the health benefits that it can give to our body. Vitamins that we get in fruits serve as protector against bad bacteria.

I remember when I had canker sore. My dentist, Hilton Head based, prescribed me medicine and advised me to drink plenty of water and eat fruits so I am protected against bad bacteria and also to boost my immune system.