C3G Benefits: The Complete Guide A Nutrient Partitioning Powerhouse

[01dragonslayer]

C3G (cyanidin 3-glucoside) is a naturally occurring anthocyanin (flavonoid) found in blueberries, blackberries, acai berries, and all kinds of other dark-colored fruits and vegetables under God's sun. This potent nutrient has so many health and physique-enhancing riches it's almost embarrassing, potentially confusing people, or worse yet, causing a certain degree of skepticism. Anyway, here's my best attempt at a shortlist of C3G benefits:

1. C3G increases insulin sensitivity enhancing glucose uptake by myotubes, causing muscle fibers to preferentially calories instead of being stored as fat.*
2. C3G, taken before a workout, helps shuttle energy from pre-workout nutrition directly to muscle cells.*
3. C3G raises levels of adiponectin, which regulates glucose levels and increases fatty acid breakdown.*
4. C3G compares favorably to a pharmaceutical glucose-disposal agent.*
5. C3G shrinks fat cells and limits fat gain and abdominal obesity.*
6. C3G improves endurance by increasing the production of chemical intermediates involved in the production of ATP, the cell's energy source.*
7. C3G reduces blood sugar, triglycerides, and cholesterol.*
8. C3G increases mitochondrial number and function.*
9. C3G increases and enhances the activity of brown adipose tissue, which is metabolically active and calorie-burning).*
10. C3G reduces systemic inflammation.*
11. C3G promotes stomach and intestinal-lining health.*
12. C3G improves night vision and helps prevent eye fatigue.*
13. C3G promotes heart and liver health.*
14. C3G mimics the life-extending benefits seen in calorie restriction diets.*
15. C3G's actual biochemical pathways that allow it to do all these actions are diverse. Here's my briefest outline of the facts. Check them out, and let me know if you're as impressed as me.

C3G and the Cellular Master Switch
First and perhaps foremost, C3G has profound effects on a chemical called adenosine monophosphate kinase, or AMPK. AMPK is found in every cell in the body and serves as the body's master regulating switch, determining in large part how fat you are, how muscular you are, and even how long you'll live.

According to at least one study involving humans, ingesting C3G increases the production of AMPK by a factor of 2.88. In turn, these increased levels of AMPK cause a massive up-regulation of a "transcriptional activator" known as PGC-1 alpha, which then increases exercise capacity, fatigue resistance, and oxygen uptake, which all contribute to additional muscle mass (assuming all other factors are copacetic).

C3G Mimics the Actions of the Most Powerful Hormone
Insulin is the most powerful hormone our bodies make. C3G has insulin-like properties in that it activates insulin receptor substrates, which in turn activate insulin-signaling proteins. These signaling proteins then stimulate glucose uptake by skeletal muscle tissue instead of fat cells.

The take-home point is – assuming you've got your exercise and lifestyle ducks in order – you could eat more food than maintenance amounts and any weight gain would go to muscle instead of fat. But C3G's insulin-like properties don't stop there. One of several laboratory experiments involving C3G showed two dosage-related drops in blood sugar of 33% and 51%, prompting the authors of the study to remark how favorably it compared with a powerful pharmaceutical glucose-disposal agent.

C3G Sends Fat Cells to Fat Camp
C3G also activates adiponectin, causing fat cells to function as another endocrine organ (like the thyroid or adrenals), regulating insulin sensitivity, lipid metabolism, and inflammation. When the C3G-related increase of adiponectin occurs, insulin sensitivity increases, inflammation decreases, and fat cells disgorge fatty acids into the bloodstream, causing them (and you) to get slimmer.

The increased adiponectin also helps produce more cellular engines known as mitochondria. In theory, if you control mitochondrial health and growth, you could at least double your lifespan without any of the diseases typically associated with aging. And from an athletic perspective, controlling the vitality and number of mitochondria in your muscle cells could lead to huge strength and endurance improvements that don't decline with the passing of years.

This increase in mitochondria, in some cases, causes the metabolically sluggish white fat to turn into the more metabolically active, calorie-burning brown fat. It also induces palmitate oxidation and citrate synthase activity, both of which are intermediates in the production of ATP, making cells chug along faster and longer.

So Why Can't I Just Eat a Mess of Blueberries?
All of this makes it seem logical to increase your intake of C3G by just adding more blueberries to your diet. It's a nice thought, but C3G has terrible bioavailability. You'd have to eat bushels of dark berries to get the muscle-building, fat-burning, life-extending, and heart-protective C3G benefits.

Maybe you think you're already eating enough blueberries to be fortified by C3G. Excuse me for being crass; if your morning stool isn't at leaser some shade of purple, you probably didn't eat enough blueberries to benefit from C3G.

The Ultimate Supplement?
There are several great supplements out there. Some work by manipulating your anabolic/androgenic hormones. Some address a specific muscle-building pathway, while others are powerful anti-inflammatories, but there's no other substance that appears to do as many things, from so many biochemical angles, as cyanidin 3-glucoside.

The difficulty in extracting the substance from natural sources makes the Indigo-3G® supplement a bit pricey, but it's worth it.


Research:

1. Guo H et al. Cyanidin-3-O-β-glucoside regulates fatty acid metabolism via an AMP-activated protein kinase-dependent signaling pathway in human HepG2 cells. Lipids Health Dis. 2012 Jan 13;11:10. doi: 10.1186/1476-511X-11-10. ABSTRACT: Background: Hepatic metabolic derangements are key components in the development of fatty liver disease. AMP-activated protein kinase (AMPK) plays a central role in controlling hepatic lipid metabolism through modulating the downstream acetyl CoA carboxylase (ACC) and carnitine palmitoyl transferase 1 (CPT-1) pathway. In this study, cyanidin-3-O-β-glucoside (Cy-3-g), a typical anthocyanin pigment was used to examine its effects on AMPK activation and fatty acid metabolism in human HepG2 hepatocytes. Results: Anthocyanin Cy-3-g increased cellular AMPK activity in a calmodulin kinase kinase dependent manner. Furthermore, Cy-3-g substantially induced AMPK downstream target ACC phosphorylation and inactivation, and then decreased malonyl CoA contents, leading to stimulation of CPT-1 expression and significant increase of fatty acid oxidation in HepG2 cells. These effects of Cy-3-g are largely abolished by pharmacological and genetic inhibition of AMPK. Conclusion: This study demonstrates that Cy-3-g regulates hepatic lipid homeostasis via an AMPK-dependent signaling pathway. Targeting AMPK activation by anthocyanin may represent a promising approach for the prevention and treatment of obesity-related nonalcoholic fatty liver disease.
2. Wei X et al. Cyanidin-3-O-β-glucoside improves obesity and triglyceride metabolism in KK-Ay mice by regulating lipoprotein lipase activity. J Sci Food Agric. 2011 Apr;91(6):1006-13. doi: 10.1002/jsfa.4275. ABSTRACT: Background: Cyanidin-3-O-β-glucoside (Cy-3-g)-rich foods have been reported to inhibit the onset of obesity, but whether the pure anthocyanin supplementation affects obesity remains uncertain. Results: Cy-3-g supplementation significantly reduced obesity, accumulation of fat in visceral adipose and liver tissues, and plasma triglyceride levels. Furthermore, adenosine monophosphate (AMP)-activated protein kinase phosphorylation (pAMPK) in the skeletal muscle and visceral adipose were significantly increased by Cy-3-g consumption. This was followed by the activation of lipoprotein lipase (LPL) in plasma and skeletal muscle but the suppression of this enzyme in visceral adipose. LPL activation in skeletal muscle cells and its suppression in adipocytes by Cy-3-g were blocked by inhibition of pAMPK. Conclusion: Our present data thus demonstrate that Cy-3-g improves obesity and triglyceride metabolism in KK-Ay mice. The underlying mechanism is found to be partly related to the activation of LPL in plasma and skeletal muscle, and inhibition of LPL in adipose tissue following the activation of pAMPK.
3. Guo H et al. Cyanidin 3-glucoside attenuates obesity-associated insulin resistance and hepatic steatosis in high-fat diet-fed and db/db mice via the transcription factor FoxO1. J Nutr Biochem. 2012 Apr;23(4):349-60. doi: 10.1016/j.jnutbio.2010.12.013. ABSTRACT: Obesity is a major risk factor for the development of type 2 diabetes, and both conditions are now recognized to possess significant inflammatory components underlying their pathophysiologies. Here, we hypothesized that cyanidin 3-glucoside (C3G), a typical anthocyanin reported to possess potent anti-inflammatory properties, would ameliorate obesity-associated inflammation and metabolic disorders, such as insulin resistance and hepatic steatosis in mouse models of diabesity. Male C57BL/6J obese mice fed a high-fat diet for 12 weeks and genetically diabetic db/db mice at an age of 6 weeks received dietary C3G supplementation (0.2%) for 5 weeks. We found that dietary C3G lowered fasting glucose levels and markedly improved the insulin sensitivity in both high-fat diet fed and db/db mice as compared with unsupplemented controls. White adipose tissue messenger RNA levels and serum concentrations of inflammatory cytokines (tumor necrosis factor-α, interleukin-6, and monocyte chemoattractant protein-1) were reduced by C3G, as did macrophage infiltration in adipose tissue. Concomitantly, hepatic triglyceride content and steatosis were alleviated by C3G. Moreover, C3G treatment decreased c-Jun N-terminal kinase activation and promoted phosphorylation and nuclear exclusion of forkhead box O1 after refeeding. These findings clearly indicate that C3G has significant potency in antidiabetic effects by modulating the c-Jun N-terminal kinase/forkhead box O1 signaling pathway and the related inflammatory adipocytokines.
4. Sasaki R et al. Cyanidin 3-glucoside ameliorates hyperglycemia and insulin sensitivity due to downregulation of retinol binding protein 4 expression in diabetic mice. Biochem Pharmacol. 2007 Dec 3;74(11):1619-27. doi: 10.1016/j.bcp.2007.08.008. ABSTRACT: Adipocyte dysfunction is strongly associated with the development of obesity and insulin resistance. It is accepted that the regulation of adipocytokine expression is one of the most important targets for the prevention of obesity and improvement of insulin sensitivity. In this study, we have demonstrated that anthocyanin (cyanidin 3-glucoside; C3G) which is a pigment widespread in the plant kingdom, ameliorates hyperglycemia and insulin sensitivity due to the reduction of retinol binding protein 4 (RBP4) expression in type 2 diabetic mice. KK-A(y) mice were fed control or control +0.2% of a C3G diet for 5 weeks. Dietary C3G significantly reduced blood glucose concentration and enhanced insulin sensitivity. The adiponectin and its receptors expression were not responsible for this amelioration. C3G significantly upregulated the glucose transporter 4 (Glut4) and downregulated RBP4 in the white adipose tissue, which is accompanied by downregulation of the inflammatory adipocytokines (monocyte chemoattractant protein-1 and tumor necrosis factor-alpha) in the white adipose tissue of the C3G group. These findings indicate that C3G has significant potency in an anti-diabetic effect through the regulation of Glut4-RBP4 system and the related inflammatory adipocytokines.
5. Takanori T et al. Anthocyanin enhances adipocytokine secretion and adipocyte-specific gene expression in isolated rat adipocytes. Biochem Biophys Res Commun. 2004 Mar 26;316(1):149-57. doi: 10.1016/j.bbrc.2004.02.031. ABSTRACT: Adipocyte dysfunction is strongly associated with the development of obesity and insulin resistance. It is accepted that the regulation of adipocytokine secretion or the adipocyte-specific gene expression is one of the most important targets for the prevention of obesity and amelioration of insulin sensitivity. In this study, we demonstrated that anthocyanins (cyanidin or cyanidin 3-glucoside) have the potency of a unique pharmacological function in isolated rat adipocytes. Treated adipocytes with anthocyanins enhanced adipocytokine (adiponectin and leptin) secretion and up-regulated the adipocyte specific gene expression without activation of PPARgamma in isolated rat adipocytes. The gene expression of adiponectin was also up-regulated in white adipose tissue in mice fed an anthocyanin supplemented diet. As one of the possible mechanisms, AMP-activated protein kinase activation would be associated with these changes, nevertheless, the AMP:ATP ratio was significantly decreased by administration of the anthocyanins. These data suggest that anthocyanins have a potency of unique therapeutic advantage and also have important implications for preventing obesity and diabetes.
6. Guo H et al. Cyanidin 3-glucoside protects 3T3-L1 adipocytes against H2O2- or TNF-alpha-induced insulin resistance by inhibiting c-Jun NH2-terminal kinase activation. Biochem Pharmacol. 2008 Mar 15;75(6):1393-401. doi: 10.1016/j.bcp.2007.11.016. ABSTRACT: Anthocyanins are naturally occurring plant pigments and exhibit an array of pharmacological properties. Our previous study showed that black rice pigment extract rich in anthocyanin prevents and ameliorates high-fructose-induced insulin resistance in rats. In present study, cyanidin 3-glucoside (Cy-3-G), a typical anthocyanin most abundant in black rice was used to examine its protective effect on insulin sensitivity in 3T3-L1 adipocytes exposed to H(2)O(2) (generated by adding glucose oxidase to the medium) or tumor necrosis factor alpha (TNF-alpha). Twelve-hour exposure of 3T3-L1 adipocytes to H(2)O(2) or TNF-alpha resulted in the increase of c-Jun NH(2)-terminal kinase (JNK) activation and insulin receptor substrate 1 (IRS1) serine 307 phosphorylation, concomitantly with the decrease in insulin-stimulated IRS1 tyrosine phosphorylation and cellular glucose uptake. Blocking JNK expression using RNA interference efficiently prevented the H(2)O(2)- or TNF-alpha-induced defects in insulin action. Pretreatment of cells with Cy-3-G reduced the intracellular production of reactive oxygen species, the activation of JNK, and attenuated H(2)O(2)- or TNF-alpha-induced insulin resistance in a dose-dependent manner. In parallel, N-acetyl-cysteine, an antioxidant compound, did not exhibit an attenuation of TNF-alpha-induced insulin resistance. Taken together, these results indicated that Cy-3-G exerts a protective role against H(2)O(2)- or TNF-alpha-induced insulin resistance in 3T3-L1 adipocytes by inhibiting the JNK signal pathway.
7. Tsuda T et al. Microarray profiling of gene expression in human adipocytes in response to anthocyanins. Biochem Pharmacol. Biochem Pharmacol. 2006 Apr 14;71(8):1184-97. doi: 10.1016/j.bcp.2005.12.042. ABSTRACT: Adipocyte dysfunction is strongly associated with the development of obesity and insulin resistance. It is accepted that the regulation of adipocytokine secretion or the adipocyte specific gene expression is one of the most important targets for the prevention of obesity and amelioration of insulin sensitivity. Recently, we demonstrated that anthocyanins, which are pigments widespread in the plant kingdom, have the potency of anti-obesity in mice and the enhancement adipocytokine secretion and its gene expression in adipocytes. In this study, we have shown the gene expression profile in human adipocytes treated with anthocyanins (cyanidin 3-glucoside; C3G or cyanidin; Cy). The human adipocytes were treated with 100 microM C3G, Cy or vehicle for 24 h. The total RNA from the adipocytes was isolated and carried out GeneChip microarray analysis. Based on the gene expression profile, we demonstrated the significant changes of adipocytokine expression (up-regulation of adiponectin and down-regulation of plasminogen activator inhibitor-1 and interleukin-6). Some of lipid metabolism related genes (uncoupling protein2, acylCoA oxidase1 and perilipin) also significantly induced in both common the C3G or Cy treatment groups. These studies have provided an overview of the gene expression profiles in human adipocytes treated with anthocyanins and demonstrated that anthocyanins can regulate adipocytokine gene expression to ameliorate adipocyte function related with obesity and diabetes that merit further investigation.
8. Tsuda T et al. Gene expression profile of isolated rat adipocytes treated with anthocyanins. Biochim Biophys Acta. 2005 Apr 15;1733(2-3):137-47. doi: 10.1016/j.bbalip.2004.12.014. ABSTRACT: Adipocyte dysfunction is strongly associated with the development of obesity and insulin resistance. It is accepted that the regulation of adipocytokine secretion or the adipocyte specific gene expression is one of the most important targets for the prevention of obesity and amelioration of insulin sensitivity. Recently, we demonstrated that anthocyanins, which are pigments widespread in the plant kingdom, have the potency of anti-obesity in mice and the enhancement adipocytokine secretion and adipocyte gene expression in adipocytes. In this study, we have shown for the first time the gene expression profile in isolated rat adipocytes treated with anthocyanins (cyanidin 3-glucoside; C3G or cyanidin; Cy). The rat adipocytes were treated with 100 muM C3G, Cy or vehicle for 24 h. The total RNA from the adipocytes was isolated and carried out GeneChip microarray analysis. A total of 633 or 427 genes was up-regulated (> 1.5-fold) by the treatment of adipocytes with C3G or Cy, respectively. The up-regulated genes include lipid metabolism and signal transduction-related genes, however, the altered genes were partly different between the C3G- and Cy-treated groups. Based on the gene expression profile, we demonstrated the up-regulation of hormone sensitive lipase and enhancement of the lipolytic activity by the treatment of adipocytes with C3G or Cy. These data have provided an overview of the gene expression profiles in adipocytes treated with anthocyanins and identified new responsive genes with potentially important functions in adipocytes related with obesity and diabetes that merit further investigation.
9. Grace M et al. Hypoglycemic activity of a novel anthocyanin-rich formulation from lowbush blueberry, Vaccinium angustifolium Aiton. Phytomedicine. 2009 May;16(5):406-15. doi: 10.1016/j.phymed.2009.02.018. ABSTRACT: Blueberry fruits are known as a rich source of anthocyanin components. In this study we demonstrate that anthocyanins from blueberry have the potency to alleviate symptoms of hyperglycemia in diabetic C57b1/6J mice. The anti-diabetic activity of different anthocyanin-related extracts was evaluated using the pharmaceutically acceptable self-microemulsifying drug delivery system: Labrasol. Treatment by gavage (500 mg/kg body wt) with a phenolic-rich extract and an anthocyanin-enriched fraction formulated with Labrasol lowered elevated blood glucose levels by 33 and 51%, respectively. The hypoglycemic activities of these formulae were comparable to that of the known anti-diabetic drug metformin (27% at 300 mg/kg). The extracts were not significantly hypoglycemic when administered without Labrasol, demonstrating its bio-enhancing effect, most likely due to increasing the bioavailability of the administered preparations. The phenolic-rich extract contained 287.0+/-9.7 mg/g anthocyanins, while the anthocyanin-enriched fraction contained 595+/-20.0 mg/g (cyanidin-3-glucoside equivalents), as measured by HPLC and pH differential analysis methods. The greater hypoglycemic activity of the anthocyanin-enriched fraction compared to the initial phenolic-rich extract suggested that the activity was due to the anthocyanin components. Treatment by gavage (300 mg/kg) with the pure anthocyanins, delphinidin-3-O-glucoside and malvidin-3-O-glucoside, formulated with Labrasol, showed that malvidin-3-O-glucoside was significantly hypoglycemic while delphinidin-3-O-glucoside was not.
10. Tsuda T et al. Dietary cyanidin 3-O-beta-D-glucoside-rich purple corn color prevents obesity and ameliorates hyperglycemia in mice. J Nutr. 2003 Jul;133(7):2125-30. doi: 10.1093/jn/133.7.2125. ABSTRACT: Anthocyanins, which are used as a food coloring, are widely distributed in human diets, suggesting that we ingest large amounts of anthocyanins from plant-based foods. Mice were fed control, cyanidin 3-glucoside-rich purple corn color (PCC), high fat (HF) or HF + PCC diet for 12 wk. Dietary PCC significantly suppressed the HF diet-induced increase in body weight gain, and white and brown adipose tissue weights. Feeding the HF diet markedly induced hypertrophy of the adipocytes in the epididymal white adipose tissue compared with the control group. In contrast, the induction did not occur in the HF + PCC group. The HF diet induced hyperglycemia, hyperinsulinemia and hyperleptinemia. These perturbations were completely normalized in rats fed HF + PCC. An increase in the tumor necrosis factor (TNF)-alpha mRNA level occurred in the HF group and was normalized by dietary PCC. These results suggest that dietary PCC may ameliorate HF diet-induced insulin resistance in mice. PCC suppressed the mRNA levels of enzymes involved in fatty acid and triacylglycerol synthesis and lowered the sterol regulatory element binding protein-1 mRNA level in white adipose tissue. These down-regulations may contribute to triacylglycerol accumulation in white adipose tissue. Our findings provide a biochemical and nutritional basis for the use of PCC or anthocyanins as a functional food factor that may have benefits for the prevention of obesity and diabetes.
11. Guo H et al. Cyanidin 3-glucoside attenuates high-fat and high-fructose diet-induced obesity by promoting the thermogenic capacity of brown adipose tissue. J Nutr Biochem. 2012 Apr;23(4):349-60. doi: 10.1016/j.jnutbio.2010.12.013.
12. Shi M et al. The effect of cyanidin-3-O-β-glucoside and peptides extracted from yoghurt on glucose uptake and gene expression in human primary skeletal muscle myotubes from obese and obese diabetic participants. Journal of Functional Foods. 2018 Dec 51:55-64. DOI:10.1016/j.jff.2018.10.012
13. Grace M et al. Hypoglycemic activity of a novel anthocyanin-rich formulation from lowbush blueberry, Vaccinium angustifolium Aiton. Phytomedicine. 2009 May;16(5):406-15. doi: 10.1016/j.phymed.2009.02.018.

 

[R2D2]

Eat your berries, friends. so many health benefits

 

[01dragonslayer]

Eat your berries, friends. so many health benefits

Always throw some strawberries and blueberries in my oatmeal.

 

[Thor]

Nice read 01DS, very interesting.