Life Extension Magazine®
System-wide free radical damage to healthy cells is an age accelerator. In experimental models, when genes are inserted that boost internal defenses against free radicals, life span can be extended by nearly 100%.1-3 The good news is that natural compounds found in certain plants (polyphenols) can exert similar effects in aging humans. They have been shown to favorably modulate gene expression that blunts free radical injury at the molecular level. Among the most powerful of these are anthocyanins. Anthocyanins are pigmentary compounds that lend fruits like grapes, blueberries, and black currants their dark color. Scientists are increasingly focusing on the benefits of one anthocyanin in particular: cyanidin-3-glucoside or C3G.1 Scores of studies in the past two years have established its potent combination of antioxidant, anti-inflammatory, DNA-protective, and gene-regulating effects. In this article, you will learn how C3G’s multimodal mechanisms reduce free radical activity. You will find the latest research on its ability to combat numerous age-related conditions, including cancer, heart disease, and metabolic syndrome. You will also discover its newly identified, singular power to enhance night vision. An Exceptional Multitargeted NutrientPlants are relentlessly exposed to ultraviolet sunrays. To survive this daily onslaught, certain plants produce compounds that specifically reduce free radical damage. These compounds are known as polyphenols, a large class of biologically active molecules.4-6 Polyphenols are chemicals that, by their intrinsic structure, diminish the effects of free radicals on surrounding tissue.5,7
The anthocyanin class of polyphenols is especially effective in blunting this form of damage. And C3G is the most common of the anthocyanins found in dark fruits—which come from plants that thrive best in direct sunlight, where free radicals are generated in abundance.8,9 It’s no accident, then, that C3G has recently been shown to provide animal and human tissues optimal defense from free radical attack, both by preventing their formation and by scavenging those already formed.7,9-12 What has researchers so interested in C3G, however, is that it also protects from the “downstream” consequences of free radicals at the genetic level. Perhaps the most subtle and intriguing effect of C3G on human tissue is its ability to directly influence gene expression.13 While we carry genes for every protein and structure in our bodies, only a few of those thousands of genes are active at any given moment. C3G selectively upregulates genes that confer protection on aging tissues, while downregulating those that cause damage (such as pro-inflammatory cytokines).14,15 C3G is well-absorbed from the intestinal tract in both animals and humans, and it readily reaches therapeutic levels in the bloodstream.16,17 Anti-Cancer PowerHigh intake of fruits and vegetables is associated with protection from most forms of cancer. One unique mechanism is attributed to the polyphenols in the anthocyanin family.7 These brightly colored molecules, including C3G, afford protection against most of the events in the cascade of cancer formation.18,19 Antioxidant activity supplied by anthocyanins, including C3G, protects DNA from the damage that can initiate cancers.20 Activation of so-called oncogenes (genes that induce cancer-cell reproduction) is another early step in cancer development. C3G potently inhibits a common oncogene called ras in human cells transplanted into rats.21 Suppression of the inflammatory “master switch” that links inflammation to cancer causation (NF-kB) can prevent many of the “second hits” that promote cancer development.22,23 C3G potently inhibits NF-kB in many tumor types.7,24 Once a cancer gets started, it can invade local tissue and/or metastasize into other areas of the body. C3G and other anthocyanins can prevent expression of the proteins that cancer cells produce to help them invade.25,26 The body’s own natural defense against cancer is programmed cell death (apoptosis). Anthocyanins such as C3G can upregulate so-called “suicide pathways” that trigger apoptosis in cancer cells, while sparing normal tissue.21,27-31 This can be a key fact that can delay or even eliminate tumor growth. Tumor cells, like all mammalian cells, go through a cycle of changes as they replicate. Anthocyanins can block the cell cycle, causing what amounts to a microscopic traffic jam and preventing cancer cells from proliferating in a coordinated fashion.32 C3G has also been shown to take the “bite” out of cancer cells. Scientists tell us that cancer cells exist in a state known as “undifferentiated.” That means that they don’t form cohesive and functional structures such as a lung or a liver. C3G has been found to induce normal differentiation of certain cancers, particularly dangerous melanoma cells.33 When cancer cells differentiate, their potential to cause damage is gravely impaired. By all of these different mechanisms, C3G has been shown to impair cancer cell growth, development, and spread in a variety of human cancers in laboratory and animal studies. C3G shows promise in mitigating breast, colon, lung, esophageal, and skin cancers.7,8,24,34,35 System-Wide Cardiovascular DefenseCardiovascular disease continues to be the leading cause of preventable death in older adults. C3G offers protection at several vital levels in the chain of events leading to heart attacks and stroke. Anthocyanins such as C3G inhibit nitrogen free radicals that trigger endothelial dysfunction.36,37 At the same time, C3G promotes healthy endothelial cells, where it contributes to vascular integrity and the ability to respond to blood pressure changes.38 C3G helps reduce cholesterol levels in laboratory studies, thus lowering the risk of lipid oxidation, which triggers inflammation and atherosclerosis.39 Antioxidant benefits of C3G and other anthocyanins help prevent that lipid oxidation, while also preventing the inflammation itself.40 Once atherosclerotic plaques form, C3G can stabilize them and reduce the risk that they’ll rupture and cause a catastrophic heart attack or stroke.41 Remarkably, C3G also inhibits the blood pressure-boosting hormone called angiotensin-converting enzyme (ACE), which may help keep blood pressure under control.42
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Combating Diabesity and the Metabolic SyndromeThe combination of obesity and diabetes has been referred to as “diabesity,” and is widely recognized as a precursor to metabolic syndrome.43 Scientists have convincingly demonstrated that C3G suppresses body weight gain in animals given a high fat diet.44 Astonishingly, the supplementation also completely normalized blood sugar and insulin elevations, and blocked elevation of the fat-associated cytokine leptin. These researchers also showed that C3G enhances secretion of beneficial cytokines such as adiponectin, which can help prevent progression to diabetes.45 These effects are produced by beneficial changes in expression of hundreds of genes.15 C3G also lowers blood sugar and enhances insulin sensitivity by downregulating a fat-related cytokine that contributes to insulin resistance.14 An astonishing and yet-to-be fully explored benefit of the anthocyanins is their ability to inhibit intestinal enzymes that break down starch for absorption. By blocking those enzymes, calories contained in starch remain in the intestinal tract and can’t contribute to weight gain. C3G and others in its family offer potent suppression of intestinal alpha-glucosidase and pancreatic alpha-amylase, two enzymes that can cause excess glucose absorption to occur.46-48
C3G Restores Night VisionThe ability to see well in low-light conditions deteriorates rapidly with age, placing maturing individuals in greater danger of accidental falls, car accidents, and other preventable, injurious hazards. A primary cause of this so-called “night blindness” is light damage and oxidative stress in the retina. The retina is constantly exposed to highly focused beams of light, which include dangerous ultraviolet radiation. C3G offers protection at several vital levels in the chain of events leading to heart attacks and stroke. C3G plays a unique role in protecting retinal tissue from damage. It works by multiple mechanisms at several sites in the retina. Most importantly, C3G stimulates regeneration of the retinal pigment called rhodopsin.56 Rhodopsin is vital to vision in dim light. When depleted, rhodopsin takes longer to return to its normal, light-sensitive state. C3G increases the restoration of rhodopsin levels.57,58 C3G also serves to protect retinal cells against the harmful oxidation that is triggered by light.59 It accomplishes this by reducing the accumulation of a fluorescent pigment called A2E that amasses with age and interferes with normal retinal function. C3G’s ability to quench oxygen free radicals is credited with this effect.59 Retinal cells are nerve cells that are capable of transmitting electrical signals. C3G and other cyanidin components of berries have neuroprotective effects on retinal cells.60 SummaryPlant-based nutrients known as anthocyanins and their major component, C3G, afford aging humans multimodal protection against a broad spectrum of degenerative diseases. C3G offers comprehensive antioxidant protection, powerful control of inflammation at multiple levels, marked reduction in DNA damage, and beneficial regulatory effects on hundreds of vital genes. It confers real-world protection against age-related conditions ranging from night blindness to cardiovascular disease, cancer, diabetes, and obesity.
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