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Introduction
According to the US Department of Agriculture, starch consumption per capita in the United States is approximately 150 pounds/year, of which the majority of that is wheat. The debilitating effects of consuming gluten proteins from wheat in individuals with a genetic predisposition to gluten intolerance (celiac disease) have been well documented and include: malabsorption (leading to diarrhea, flatulence, and bloating), inflammation, loss of intestinal villi and intestinal lesions, anemia, neuropathy, infertility, and fatigue (Mubarak et al., 2012). Over the past four decades wheat has been genetically modified via the crossing wheat with non-wheat grasses, and irradiation of wheat seeds and embryos with chemicals, gamma rays, and high-dose X-rays to produce more resilient plants with larger seeds. While these genetic variants have improved crop yield, they also altered wheat protein such that gluten and gliadin (a major wheat allergin) concentrations increased significantly (van den Broeck et al., 2010). This altered protein content in genetically modified wheat has been suggested to play a significant role in the increased prevalence of celiac disease document over the past decade (Lohi et al., 2007).
While the negative effects of wheat gluten consumption in celiac disease are well established, the potential negative effects of industrialized wheat consumption in otherwise healthy individuals are less clear. A quick google.com search for “gluten non-celiac” turns up over 100 pages of information related to the adverse health effects of gluten consumption and gluten-free living; however, most are blogs and popular opinion pages with little scientific value (i.e.: Oprah.com). Can gluten consumption by non-celiac individuals adversely affect the body as many of these self-proclaimed experts claim? Though research is currently in its preliminary stages, the answer is trending towards yes.
Biesiekierski et al. (2011) investigated the effects of gluten consumption on gastrointestinal symptoms in inflammatory bowel disease patients without celiac disease. Subjects were screened for celiac disease, followed a gluten-free diet, and only those whose symptoms improved were included in the study. Subjects were then randomly placed into two groups, one of which received gluten-free bakery items and who whose bakery items were spiked with 16g gluten for 6 weeks. The subjects consuming the gluten diet experienced a significant increase in symptoms including pain, bloating, and diarrhea. The largest difference in symptoms between groups was reported for fatigue, suggesting that gluten consumption may have negative implications systemically. Although there were no observed increases in colonic inflammation, Biesiekierski et al. was unable to rule out low-grade small-intestinal inflammation as a cause of the fatigue.
Although Biesiekierski et al. did not report increases in colonic inflammation, the effects of gluten induced low-grade small intestinal inflammation on fatigue development cannot be disqualified. Activated intestinal immune cells and their subsequent secretion of inflammatory cytokines have been found to both stimulate the enteric nervous system (Ohman et al., 2009) and interact with the central nervous system (Collins & Bercik, 2009), and gut inflammation has been linked with chronic fatigue (Lakhan & Kirchgessner, 2010). Evidence from in vitro research lends support to the hypothesis that gluten induced inflammation may increase fatigue in non-celiac patients. Gliadin has been shown to increase epithelial permeability (Sander et al., 2005), induce apoptosis (Giovani et al., 2000), increase oxidative stress (Rivabene et al., 1999), and induce inflammation (Laparra Llopis et al., 2010) in human intestinal epithelial cells via the NF-kappaB/TNF-α pathway.
Given that gluten may increase inflammation and oxidative stress, consuming a reduced gluten diet in conjunction with antioxidant-rich foods may positively affect health. GlycoMyx is a gluten free starch comprised of purple potato flower, and is a viable alternative to wheat flour. Perhaps most intriguing about purple potato starch is not that it is naturally gluten free, but rather the high anthocyanin concentration.
Anthocyanins are a polyphenol belonging to the family of plant flavanoids. Specifically, they are a water soluble pigment that is responsible for the blue, purple, and red colors of many fruits, vegetables, and flowers (Takeoka & Dao, 2002). The reports from a number of investigations in cell cultures, animal models, and humans demonstrate that anthocyanins posses a variety of protective effects. This review has been compiled to educate the consumer on the health promoting and therapeutic properties of anthocyanin consumption.
Antioxidant Properties
Reactive oxygen species are generated during regular metabolism and at low concentrations play a significant role in cellular signaling, immune response, and gene regulation. In contrast, the over production of reactive oxygen species damages intracellular organelles and cellular membranes, and has been implicated as a major factor in a number of diseases such as aging, cardiovascular disease, cancer, and diabetes (Allen & Tresini, 2000). Consequently, a number of organizations recommend consuming antioxidant-rich foods to promote health.
The antioxidant capacity of anthocyanins has been studied in vitro and in human models. Steed and Truong (2008) measured the anthocyanin composition and antioxidant capacity of purple potatoes. Whole potatoes were reported to contain approximately 400 mg phenols per 100g, of which approximately 100 mg were cynadin. The oxygen radical absorbance capacity (ORAC) was reported to be 5,800, which is similar to that of a granny smith apple. Wang et al. (1997) reported that the antioxidant capacity of cynadin was 3.5-fold greater than vitamin E. Anthocyanins have been shown to protect erythrocytes and hepatocytes from peroxide and ischemic damage (Tedesco et al., 2001; Tsuda et al., 2000). Ramirez-Tortosa et al. (2001) reported that anthocyanin supplementation in vitamin-E deficient rats increased blood antioxidant capacity, and reduced lipid peroxidation and DNA damage.
Anthocyanins also appear to offer cognitive and neuroprotective effects. The stress placed on mitochondria via reactive oxygen species has been implicated as a major factor in many neurodegenerative diseases. Anthocyanins have been shown to protect neural mitochondria from oxidative stress and to suppress oxidative-induced neural apoptosis in rat brains (Kelsey et al., 2011). According to Lu et al. (2012), anthocyanins may not only protect neural tissue against oxidative damage, but may also stimulate mitochondrial biogenesis. The authors reported that anthocyanin treatment in rats prevented neuron loss in the hippocampus and increased cognitive performance.
Although research involving the antioxidant capacities of anthocyanin consumption in humans is in early stages, preliminary results show high potential. Vinson et al. (2012) investigated the effects of purple potato starch and commercial potato starch on antioxidant capacity in hypertensive humans. Purple potato starch consumption increased antioxidant capacity whereas commercial potato consumption resulted in a pro-oxidant state. Accordingly, much of the health promoting effects of anthocyanins have been suggested to be due to their antioxidant activity (He & Giusi, 2010).
Anti-Inflammatory Properties
Inflammation occurs in response to tissue injury, and chronic inflammation is present in nearly every metabolic and auto-immune disease. Further, inflammation has been indicated as a mediator of cancer as inflammatory cells have been shown to promote tumor growth (Grivennikov et al., 2010). Anthocyanins have been shown to possess anti-inflammatory properties in part by inhibiting the conversion of arachidonic acid to inflammatory stimulating prostaglandins via COX enzymes. Wang et al. (1999) reported that cynadin was a stronger anti-inflammatory than aspirin. Seeram et al. (2001) demonstrated that anthocyanin fractions showed anti-inflammatory properties similar to those of ibuprofen and naproxen.
Rossi et al. (2003) investigated the therapeutic effects of cynadin therapy in rats with carrageenan-induced lung inflammation. Anthocyanin administration reduced inflammatory cell infiltration, lipid peroxidation, and prostaglandin E2 in a dose dependent manner. Anthocyanin administration has also been found to suppress inflammatory genes in adipocytes, hepatocytes, and endothelial cells (Hasselund et al., 2012; Hwang et al., 2011; Ju et al., 2011). Given the potential for gastric bleeding and liver toxicity, anthocyanins may provide a natural alternative to chronic aspirin and ibuprofen administration.
Anti-Carcinogenic Properties
In addition to indirectly reducing the risk of cancer via anti-oxidant and anti-inflammatory mechanisms, anthocyanins may also directly suppress carcinoma growth. Kamei et al. (1995) reported that anthocyanins inhibited the growth of malignant intestinal carcinoma cells. In a follow up study, Kamei et al. (1998) found that anthocyanins derived from red wine inhibited the growth of gastric carcinoma cells. More recently, anthocyanins have been found to suppress oral, colon, and prostate cancer cell growth via cell cycle arrest (Zhang et al., 2008).
Cardiovascular Benefits
Some of the biggest contributors to coronary heart disease appear to be hypertension, hypercholesterolemia, and inflammation. Endothelial damage via hypertension and the oxidation of low density lipoprotein (LDL) result in the infiltration of inflammatory cells, leading to vascular lipid accumulation, atherosclerotic plaques, and upon rupture or occlusion, myocardial infarction (Badimon and Vilahur, 2012). Anthocyanins may promote cardiovascular health by protecting against LDL oxidation, increasing high density lipoprotein (HDL), reducing blood pressure, and modulating prostaglandin metabolism (Mazza, 2007).
Investigations regarding the French Paradox found that red wine consumption increased serum antioxidant capacity. Early investigations found that the cardio-protective effects of red wine were attributed to increased antioxidant capacity, and later research showed that the anthocyanin content in red wine was in large part responsible for the increased antioxidant capacities (Whitehead et al., 1995). Shortly after, a number of investigations demonstrated that anthocyanin consumption protects LDL against peroxyl and copper-induced oxidation (Abuja et al., 1998; Matsumoto et al., 2002). Anthocyanins may also be cardio-protective by positively influencing HDL cholesterol, such as those seen in studies involving red wine consumption (Giziano et al., 1993). Indeed, Zhu et al. (2011) reported improved HDL concentrations in human subjects supplemented with 320 mg of anthocyanin extract per day.
Anthocyanins may be an effective nutrient in the treatment of hypertension. Vinson et al. (2012) reported significant decreases in systolic and diastolic blood pressure in hypertensive patients following high-anthocyanin purple potato consumption. These reductions occurred above and beyond the effects of anti-hypertensive drugs in 14 of the 18 subjects. Anthocyanins are effectively taken up by endothelial cells (Lu et al., 2012) and may in part improve hypertension via promoting vasodilation by activating the nitric oxide – cGMP pathway (Zhu et al., 2011). Further, anthocyanins may also directly reduce inflammation in vascular tissue: Zhu et al. demonstrated decreases in inflammatory cell infiltration via reductions in vascular adhesion molecule-1. Thus, anthocyanins may improve heart health by improving the lipid profile, protecting against inflammation-induced vascular injury, and reducing hypertension.
Diabetes Prevention
The secretion of insulin from pancreatic β-cells stimulates the uptake of blood glucose by muscle, nervous, hepatic, and neural tissue. Diabetes mellitus type II (DMII) is highly associated with insulin resistance, a condition whereby the cellular response to insulin is inadequate resulting in the inability of tissues to take up blood glucose combined with a lack of hepatic glucose production (Samuel & Shulman, 2012). As a result, chronic hyperglycemia ensues and can result in vascular, neural, renal, hepatic, and vision complications.
Although drugs have been developed to stimulate additional β-cell insulin release, these drugs are ineffective at controlling blood glucose, adversely affect β-cell function, and can cause weight gain (Pfeiffer, 2003). In contrast, anthocyanins have been shown to improve function and protect β-cells against glucose-induced oxidative stress (Al-Awwadi et al., 2005). Daniel et al. (2003) demonstrated that anthocyanins extracted from banyan bark had significant hypoglycemic, hypolipidemic, and serum insulin elevating effects in diabetic rats, possibly by improving β-cell function. Anthocyanins may indeed improve β-cell function via anti-inflammatory and antioxidative mechanisms. Zhang et al. (2004) reported that anthocyanins enhanced insulin secretion while selectively inhibiting COX-2 enzymes. Anthocyanins have been shown to inhibit alpha-glucosidase, thus resulting in reduced post-prandial blood glucose (Matsui et al., 2001). Given the effects of anthocyanins on β-cell performance and post-prandial blood glucose, consuming a diet of anthocyanin-rich foods may help in the treatment/prevention of DMII and protect against the deleterious effects hyperglycemia.
Obesity Control
Obesity is associated with a variety of metabolic disorders such as diabetes, hypertension, cancer, and cardiovascular disease. Adipocytes synthesize and release a number of signaling cytokines that play a role in energy homeostasis. Adiponectin, in particular, has been shown to improve insulin action, fatty acid oxidation, lipid deposits in skeletal muscle, and promote weight loss, in part via PPARƴ activation (Yamauchi et al., 2001), whereas adipocyte dysfunction has been implicated as a major factor in the development of diabetes and obesity (Funahashi et al., 1999).
Given that adiponectin gene expression and plasma concentrations are reduced in the obese state, a number of drug therapies have been developed to improve adiponectin production. Anthocyanins have also been shown to improve adiponectin secretion and PPARƴ activation in adipocytes (Tsuda et al., 2003), and thus may help treat obesity and improve insulin sensitivity. Tsuda et al. (2006) investigated the human adipocyte response to the anthocyanin cyanidin. Anthocyanins were found to significantly increase adiponectin production while reducing plasminogen activated inhibitor-1 (a pro-thrombic factor) and the inflammatory cytokine interlukin-6. Further, anthocyanins increased PPARƴ and lipolytic gene expression while reducing lipogenic gene expression. Ju et al. (2011) reported findings similar to Tsuda et al., and also demonstrated that anthocyanins may prevent adipocyte dysfunction by protecting adipocytes against inflammation and oxidation. The results reported by Tsuda and Ju et al. support the use of anthocyanins as an obesity therapy.
Non-alcoholic fatty liver disease (NAFLD) is a major complication associated with insulin resistance that can accelerate the development of obesity. NAFLD increases oxidative stress, resulting in lipid peroxidation, inflammation, nonalcoholic steatohepatitis (NASH), and when left untreated may progress to liver failure Choudhury & Sanyal, 2004). Anthocyanins from purple potatoes may improve NAFLD via a variety of mechanisms. The antioxidant and anti-inflammatory properties of anthocyanins have been shown to protect hepatocytes against COX-2 and iNOS-induced liver injury via an up regulation of hepatic antioxidant enzymes (Hwang et al., 2010).
Of even more interest, anthocyanins may improve NAFLD by activating adenosine monophosphate-activated protein kinase (AMPK) in human hepatocytes. AMPK regulates hepatic energy metabolism by affecting glucose transport, gluconeogenesis, and lipolysis (Zhang & Zhou, 2009), and has also been shown to inhibit hepatic lipid accumulation (Kim et al., 2010). Hwang et al. (2011) demonstrated that anthocyanins from purple potatoes decreased lipid peroxidation and attenuated hepatic lipid accumulation by activating AMPK. Anthocyanins reduced fatty acid synthase and increased AMPK activation in cells exposed to high glucose concentrations, suggesting that anthocyanins may be especially hepatoprotective to individuals with hyperglycemia.
Digestion and Absorption
When assessing the potential of a nutrient or dietary supplement based upon predominantly animal and in vitro studies (as in the case of this review) one must consider the stability and bioavialability of the substrate in humans. Purple potato starch was chosen for GlycoMyx in part because the anthocyanin pigments found in purple potatoes have been shown to be significantly more stable than those found in berries and other plants (Goda et al., 1997). Research from the early 2000’s has shown low levels of anthocyanins in the plasma and urine following consumption (He & Guisti, 2010); however, improved analytical techniques have shown that anthocyanins are absorbed in the methylated, sulfated, and glucoronidated states (Felgines et al., 2007), and that these metabolites may have greater bioactivities (Setchell et al., 2002). Talavera et al. (2003) demonstrated that about 25% of anthocyanins are effectively absorbed in the stomach. In a follow up study, Talavera et al. (2004) reported that the small intestine absorbs approximately another 10-20% of anthocyanins, with the greatest absorption rates occurring with cyanadin. These results suggest that anthocyanins are well absorbed by the gastrointestinal tract.
To play a role in organ health, anthocyanins must next be available to the various tissues in question. Although research in humans is limited, animal research suggests that anthocyanins are indeed bioavailable to various tissues. Talavera et al. (2005) reported that following consumption, high anthocyanin concentrations were found in the liver, kidneys, GI tract, and brain of rats. In pigs, Kalt et al. (2008) reported high levels in the liver, kidney, eyes, and brain. Thus, anthocyanins may provide protection for the digestive organs, and also the brain and eyes via their ability to cross the blood to brain barrier.
Conclusions
Excessive gluten consumption appears to affect a wide variety of people without a genetic predisposition to glucose intolerance (celiac disease). Gluten has been shown to irritate the small intestine causing low grade inflammation that results in bloating, diarrhea, flatulence, pain and fatigue. Anecdotal evidence suggests that reducing gluten consumption may improve health and longevity. GlycoMyx is a gluten free potato starch that is also high in anthocyanins, specifically cyanidin. Cyanidin and other anthocyanins have been shown to have a host of health benefits, including anti-inflammatory and antioxidant capabilities that protect tissues against damage and may be preventative or therapeutic to cancer, heart disease, diabetes, and obesity. Additionally, anthocyanins have been shown to reduce hypertension, and improve dysfunctional adipocytes and hepatic steaosis. Given the beneficial effects of reduced gluten and increased anthocyanin consumption, GlycoMyx appears to be a viable food in the promotion of health and wellness, and a possible therapeutic agent for metabolic diseases.
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According to the US Department of Agriculture, starch consumption per capita in the United States is approximately 150 pounds/year, of which the majority of that is wheat. The debilitating effects of consuming gluten proteins from wheat in individuals with a genetic predisposition to gluten intolerance (celiac disease) have been well documented and include: malabsorption (leading to diarrhea, flatulence, and bloating), inflammation, loss of intestinal villi and intestinal lesions, anemia, neuropathy, infertility, and fatigue (Mubarak et al., 2012). Over the past four decades wheat has been genetically modified via the crossing wheat with non-wheat grasses, and irradiation of wheat seeds and embryos with chemicals, gamma rays, and high-dose X-rays to produce more resilient plants with larger seeds. While these genetic variants have improved crop yield, they also altered wheat protein such that gluten and gliadin (a major wheat allergin) concentrations increased significantly (van den Broeck et al., 2010). This altered protein content in genetically modified wheat has been suggested to play a significant role in the increased prevalence of celiac disease document over the past decade (Lohi et al., 2007).
While the negative effects of wheat gluten consumption in celiac disease are well established, the potential negative effects of industrialized wheat consumption in otherwise healthy individuals are less clear. A quick google.com search for “gluten non-celiac” turns up over 100 pages of information related to the adverse health effects of gluten consumption and gluten-free living; however, most are blogs and popular opinion pages with little scientific value (i.e.: Oprah.com). Can gluten consumption by non-celiac individuals adversely affect the body as many of these self-proclaimed experts claim? Though research is currently in its preliminary stages, the answer is trending towards yes.
Biesiekierski et al. (2011) investigated the effects of gluten consumption on gastrointestinal symptoms in inflammatory bowel disease patients without celiac disease. Subjects were screened for celiac disease, followed a gluten-free diet, and only those whose symptoms improved were included in the study. Subjects were then randomly placed into two groups, one of which received gluten-free bakery items and who whose bakery items were spiked with 16g gluten for 6 weeks. The subjects consuming the gluten diet experienced a significant increase in symptoms including pain, bloating, and diarrhea. The largest difference in symptoms between groups was reported for fatigue, suggesting that gluten consumption may have negative implications systemically. Although there were no observed increases in colonic inflammation, Biesiekierski et al. was unable to rule out low-grade small-intestinal inflammation as a cause of the fatigue.
Although Biesiekierski et al. did not report increases in colonic inflammation, the effects of gluten induced low-grade small intestinal inflammation on fatigue development cannot be disqualified. Activated intestinal immune cells and their subsequent secretion of inflammatory cytokines have been found to both stimulate the enteric nervous system (Ohman et al., 2009) and interact with the central nervous system (Collins & Bercik, 2009), and gut inflammation has been linked with chronic fatigue (Lakhan & Kirchgessner, 2010). Evidence from in vitro research lends support to the hypothesis that gluten induced inflammation may increase fatigue in non-celiac patients. Gliadin has been shown to increase epithelial permeability (Sander et al., 2005), induce apoptosis (Giovani et al., 2000), increase oxidative stress (Rivabene et al., 1999), and induce inflammation (Laparra Llopis et al., 2010) in human intestinal epithelial cells via the NF-kappaB/TNF-α pathway.
Given that gluten may increase inflammation and oxidative stress, consuming a reduced gluten diet in conjunction with antioxidant-rich foods may positively affect health. GlycoMyx is a gluten free starch comprised of purple potato flower, and is a viable alternative to wheat flour. Perhaps most intriguing about purple potato starch is not that it is naturally gluten free, but rather the high anthocyanin concentration.
Anthocyanins are a polyphenol belonging to the family of plant flavanoids. Specifically, they are a water soluble pigment that is responsible for the blue, purple, and red colors of many fruits, vegetables, and flowers (Takeoka & Dao, 2002). The reports from a number of investigations in cell cultures, animal models, and humans demonstrate that anthocyanins posses a variety of protective effects. This review has been compiled to educate the consumer on the health promoting and therapeutic properties of anthocyanin consumption.
Antioxidant Properties
Reactive oxygen species are generated during regular metabolism and at low concentrations play a significant role in cellular signaling, immune response, and gene regulation. In contrast, the over production of reactive oxygen species damages intracellular organelles and cellular membranes, and has been implicated as a major factor in a number of diseases such as aging, cardiovascular disease, cancer, and diabetes (Allen & Tresini, 2000). Consequently, a number of organizations recommend consuming antioxidant-rich foods to promote health.
The antioxidant capacity of anthocyanins has been studied in vitro and in human models. Steed and Truong (2008) measured the anthocyanin composition and antioxidant capacity of purple potatoes. Whole potatoes were reported to contain approximately 400 mg phenols per 100g, of which approximately 100 mg were cynadin. The oxygen radical absorbance capacity (ORAC) was reported to be 5,800, which is similar to that of a granny smith apple. Wang et al. (1997) reported that the antioxidant capacity of cynadin was 3.5-fold greater than vitamin E. Anthocyanins have been shown to protect erythrocytes and hepatocytes from peroxide and ischemic damage (Tedesco et al., 2001; Tsuda et al., 2000). Ramirez-Tortosa et al. (2001) reported that anthocyanin supplementation in vitamin-E deficient rats increased blood antioxidant capacity, and reduced lipid peroxidation and DNA damage.
Anthocyanins also appear to offer cognitive and neuroprotective effects. The stress placed on mitochondria via reactive oxygen species has been implicated as a major factor in many neurodegenerative diseases. Anthocyanins have been shown to protect neural mitochondria from oxidative stress and to suppress oxidative-induced neural apoptosis in rat brains (Kelsey et al., 2011). According to Lu et al. (2012), anthocyanins may not only protect neural tissue against oxidative damage, but may also stimulate mitochondrial biogenesis. The authors reported that anthocyanin treatment in rats prevented neuron loss in the hippocampus and increased cognitive performance.
Although research involving the antioxidant capacities of anthocyanin consumption in humans is in early stages, preliminary results show high potential. Vinson et al. (2012) investigated the effects of purple potato starch and commercial potato starch on antioxidant capacity in hypertensive humans. Purple potato starch consumption increased antioxidant capacity whereas commercial potato consumption resulted in a pro-oxidant state. Accordingly, much of the health promoting effects of anthocyanins have been suggested to be due to their antioxidant activity (He & Giusi, 2010).
Anti-Inflammatory Properties
Inflammation occurs in response to tissue injury, and chronic inflammation is present in nearly every metabolic and auto-immune disease. Further, inflammation has been indicated as a mediator of cancer as inflammatory cells have been shown to promote tumor growth (Grivennikov et al., 2010). Anthocyanins have been shown to possess anti-inflammatory properties in part by inhibiting the conversion of arachidonic acid to inflammatory stimulating prostaglandins via COX enzymes. Wang et al. (1999) reported that cynadin was a stronger anti-inflammatory than aspirin. Seeram et al. (2001) demonstrated that anthocyanin fractions showed anti-inflammatory properties similar to those of ibuprofen and naproxen.
Rossi et al. (2003) investigated the therapeutic effects of cynadin therapy in rats with carrageenan-induced lung inflammation. Anthocyanin administration reduced inflammatory cell infiltration, lipid peroxidation, and prostaglandin E2 in a dose dependent manner. Anthocyanin administration has also been found to suppress inflammatory genes in adipocytes, hepatocytes, and endothelial cells (Hasselund et al., 2012; Hwang et al., 2011; Ju et al., 2011). Given the potential for gastric bleeding and liver toxicity, anthocyanins may provide a natural alternative to chronic aspirin and ibuprofen administration.
Anti-Carcinogenic Properties
In addition to indirectly reducing the risk of cancer via anti-oxidant and anti-inflammatory mechanisms, anthocyanins may also directly suppress carcinoma growth. Kamei et al. (1995) reported that anthocyanins inhibited the growth of malignant intestinal carcinoma cells. In a follow up study, Kamei et al. (1998) found that anthocyanins derived from red wine inhibited the growth of gastric carcinoma cells. More recently, anthocyanins have been found to suppress oral, colon, and prostate cancer cell growth via cell cycle arrest (Zhang et al., 2008).
Cardiovascular Benefits
Some of the biggest contributors to coronary heart disease appear to be hypertension, hypercholesterolemia, and inflammation. Endothelial damage via hypertension and the oxidation of low density lipoprotein (LDL) result in the infiltration of inflammatory cells, leading to vascular lipid accumulation, atherosclerotic plaques, and upon rupture or occlusion, myocardial infarction (Badimon and Vilahur, 2012). Anthocyanins may promote cardiovascular health by protecting against LDL oxidation, increasing high density lipoprotein (HDL), reducing blood pressure, and modulating prostaglandin metabolism (Mazza, 2007).
Investigations regarding the French Paradox found that red wine consumption increased serum antioxidant capacity. Early investigations found that the cardio-protective effects of red wine were attributed to increased antioxidant capacity, and later research showed that the anthocyanin content in red wine was in large part responsible for the increased antioxidant capacities (Whitehead et al., 1995). Shortly after, a number of investigations demonstrated that anthocyanin consumption protects LDL against peroxyl and copper-induced oxidation (Abuja et al., 1998; Matsumoto et al., 2002). Anthocyanins may also be cardio-protective by positively influencing HDL cholesterol, such as those seen in studies involving red wine consumption (Giziano et al., 1993). Indeed, Zhu et al. (2011) reported improved HDL concentrations in human subjects supplemented with 320 mg of anthocyanin extract per day.
Anthocyanins may be an effective nutrient in the treatment of hypertension. Vinson et al. (2012) reported significant decreases in systolic and diastolic blood pressure in hypertensive patients following high-anthocyanin purple potato consumption. These reductions occurred above and beyond the effects of anti-hypertensive drugs in 14 of the 18 subjects. Anthocyanins are effectively taken up by endothelial cells (Lu et al., 2012) and may in part improve hypertension via promoting vasodilation by activating the nitric oxide – cGMP pathway (Zhu et al., 2011). Further, anthocyanins may also directly reduce inflammation in vascular tissue: Zhu et al. demonstrated decreases in inflammatory cell infiltration via reductions in vascular adhesion molecule-1. Thus, anthocyanins may improve heart health by improving the lipid profile, protecting against inflammation-induced vascular injury, and reducing hypertension.
Diabetes Prevention
The secretion of insulin from pancreatic β-cells stimulates the uptake of blood glucose by muscle, nervous, hepatic, and neural tissue. Diabetes mellitus type II (DMII) is highly associated with insulin resistance, a condition whereby the cellular response to insulin is inadequate resulting in the inability of tissues to take up blood glucose combined with a lack of hepatic glucose production (Samuel & Shulman, 2012). As a result, chronic hyperglycemia ensues and can result in vascular, neural, renal, hepatic, and vision complications.
Although drugs have been developed to stimulate additional β-cell insulin release, these drugs are ineffective at controlling blood glucose, adversely affect β-cell function, and can cause weight gain (Pfeiffer, 2003). In contrast, anthocyanins have been shown to improve function and protect β-cells against glucose-induced oxidative stress (Al-Awwadi et al., 2005). Daniel et al. (2003) demonstrated that anthocyanins extracted from banyan bark had significant hypoglycemic, hypolipidemic, and serum insulin elevating effects in diabetic rats, possibly by improving β-cell function. Anthocyanins may indeed improve β-cell function via anti-inflammatory and antioxidative mechanisms. Zhang et al. (2004) reported that anthocyanins enhanced insulin secretion while selectively inhibiting COX-2 enzymes. Anthocyanins have been shown to inhibit alpha-glucosidase, thus resulting in reduced post-prandial blood glucose (Matsui et al., 2001). Given the effects of anthocyanins on β-cell performance and post-prandial blood glucose, consuming a diet of anthocyanin-rich foods may help in the treatment/prevention of DMII and protect against the deleterious effects hyperglycemia.
Obesity Control
Obesity is associated with a variety of metabolic disorders such as diabetes, hypertension, cancer, and cardiovascular disease. Adipocytes synthesize and release a number of signaling cytokines that play a role in energy homeostasis. Adiponectin, in particular, has been shown to improve insulin action, fatty acid oxidation, lipid deposits in skeletal muscle, and promote weight loss, in part via PPARƴ activation (Yamauchi et al., 2001), whereas adipocyte dysfunction has been implicated as a major factor in the development of diabetes and obesity (Funahashi et al., 1999).
Given that adiponectin gene expression and plasma concentrations are reduced in the obese state, a number of drug therapies have been developed to improve adiponectin production. Anthocyanins have also been shown to improve adiponectin secretion and PPARƴ activation in adipocytes (Tsuda et al., 2003), and thus may help treat obesity and improve insulin sensitivity. Tsuda et al. (2006) investigated the human adipocyte response to the anthocyanin cyanidin. Anthocyanins were found to significantly increase adiponectin production while reducing plasminogen activated inhibitor-1 (a pro-thrombic factor) and the inflammatory cytokine interlukin-6. Further, anthocyanins increased PPARƴ and lipolytic gene expression while reducing lipogenic gene expression. Ju et al. (2011) reported findings similar to Tsuda et al., and also demonstrated that anthocyanins may prevent adipocyte dysfunction by protecting adipocytes against inflammation and oxidation. The results reported by Tsuda and Ju et al. support the use of anthocyanins as an obesity therapy.
Non-alcoholic fatty liver disease (NAFLD) is a major complication associated with insulin resistance that can accelerate the development of obesity. NAFLD increases oxidative stress, resulting in lipid peroxidation, inflammation, nonalcoholic steatohepatitis (NASH), and when left untreated may progress to liver failure Choudhury & Sanyal, 2004). Anthocyanins from purple potatoes may improve NAFLD via a variety of mechanisms. The antioxidant and anti-inflammatory properties of anthocyanins have been shown to protect hepatocytes against COX-2 and iNOS-induced liver injury via an up regulation of hepatic antioxidant enzymes (Hwang et al., 2010).
Of even more interest, anthocyanins may improve NAFLD by activating adenosine monophosphate-activated protein kinase (AMPK) in human hepatocytes. AMPK regulates hepatic energy metabolism by affecting glucose transport, gluconeogenesis, and lipolysis (Zhang & Zhou, 2009), and has also been shown to inhibit hepatic lipid accumulation (Kim et al., 2010). Hwang et al. (2011) demonstrated that anthocyanins from purple potatoes decreased lipid peroxidation and attenuated hepatic lipid accumulation by activating AMPK. Anthocyanins reduced fatty acid synthase and increased AMPK activation in cells exposed to high glucose concentrations, suggesting that anthocyanins may be especially hepatoprotective to individuals with hyperglycemia.
Digestion and Absorption
When assessing the potential of a nutrient or dietary supplement based upon predominantly animal and in vitro studies (as in the case of this review) one must consider the stability and bioavialability of the substrate in humans. Purple potato starch was chosen for GlycoMyx in part because the anthocyanin pigments found in purple potatoes have been shown to be significantly more stable than those found in berries and other plants (Goda et al., 1997). Research from the early 2000’s has shown low levels of anthocyanins in the plasma and urine following consumption (He & Guisti, 2010); however, improved analytical techniques have shown that anthocyanins are absorbed in the methylated, sulfated, and glucoronidated states (Felgines et al., 2007), and that these metabolites may have greater bioactivities (Setchell et al., 2002). Talavera et al. (2003) demonstrated that about 25% of anthocyanins are effectively absorbed in the stomach. In a follow up study, Talavera et al. (2004) reported that the small intestine absorbs approximately another 10-20% of anthocyanins, with the greatest absorption rates occurring with cyanadin. These results suggest that anthocyanins are well absorbed by the gastrointestinal tract.
To play a role in organ health, anthocyanins must next be available to the various tissues in question. Although research in humans is limited, animal research suggests that anthocyanins are indeed bioavailable to various tissues. Talavera et al. (2005) reported that following consumption, high anthocyanin concentrations were found in the liver, kidneys, GI tract, and brain of rats. In pigs, Kalt et al. (2008) reported high levels in the liver, kidney, eyes, and brain. Thus, anthocyanins may provide protection for the digestive organs, and also the brain and eyes via their ability to cross the blood to brain barrier.
Conclusions
Excessive gluten consumption appears to affect a wide variety of people without a genetic predisposition to glucose intolerance (celiac disease). Gluten has been shown to irritate the small intestine causing low grade inflammation that results in bloating, diarrhea, flatulence, pain and fatigue. Anecdotal evidence suggests that reducing gluten consumption may improve health and longevity. GlycoMyx is a gluten free potato starch that is also high in anthocyanins, specifically cyanidin. Cyanidin and other anthocyanins have been shown to have a host of health benefits, including anti-inflammatory and antioxidant capabilities that protect tissues against damage and may be preventative or therapeutic to cancer, heart disease, diabetes, and obesity. Additionally, anthocyanins have been shown to reduce hypertension, and improve dysfunctional adipocytes and hepatic steaosis. Given the beneficial effects of reduced gluten and increased anthocyanin consumption, GlycoMyx appears to be a viable food in the promotion of health and wellness, and a possible therapeutic agent for metabolic diseases.
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