Durk Pearson & Sandy Shaw’s®
Life Extension NewsTM
Volume 16 No. 2 • February 2013

To trace something unknown back to something known is alleviating, soothing, gratifying, and gives moreover a feeling of power. Danger, disquiet, anxiety attend the unknown —the first instinct is to eliminate these distressing states. First principle: any explanation is better than none ... The cause-creating drive is thus conditioned and excited by the feeling of fear.
— Friedrich Nietzsche

Anthocyanins to Prevent Obesity and Diabetes Anthocyanins Enhance Secretion of the Adipocytokines Leptin and Adiponectin Without Activating PPARgamma-induced Lipogenesis

Thiazolidinedione drugs used to treat diabetes (example: pioglitazone) are powerful activators of PPARgamma, which can potently increase insulin sensitivity, but unfortunately also activate PPARgamma target genes that increase lipogenesis (fat synthesis), thereby inducing weight gain as an undesirable side effect. A 2004 paper1 reported that anthocyanins (colored molecules such as cyanidin or cyanidin 3-glucoside found in blueberries and many other blue or purple fruits and vegetables but not beets) are able to increase the release of adipocytokines (specifically adiponectin and leptin) from rat adipocytes (fat cells) that enhance insulin sensitivity without activating PPARgamma induced lipogenesis, by a mechanism that may be different from that of thiazolidinediones. As the authors summarize: “[t]hese data suggest that anthocyanins have a potency of unique therapeutic advantage and also have important implications for preventing obesity and diabetes.”1

The researchers also report that in another study, the gene expression of adiponectin was upregulated in white adipose tissue in mice fed an anthocyanin supplemented diet. As we mentioned in the article just above, leptin acts as a signal that reduces food intake and increases energy expenditure. In an earlier study,2 some of the same researchers that published paper #1 found that purple corn color, enriched with the anthocyanin cyanidin 3-O-beta-D-glucoside, prevented obesity and ameliorated hyperglycemia in mice fed a high fat diet. In that paper, the scientists also reported that dietary anthocyanin normalized hypertrophy of the adipocytes in the epididymal white adipose tissues. Hypertrophy of adipocytes, an increase in the size of fat cells, results in larger, more insulin resistant cells.

Anthocyanins Effective at Nanomolar Quantities

In a different paper,3 scientists found that anthocyanins were protective against oxidative stress induced by high doses of glucose in pancreatic mouse beta-cells despite their very low bioavailability because they are bioactive at NANOMOLAR quantities. Thus, very small amounts were required and could be effective intracellularly even at their low bioavailability. “Mouse pancreatic beta-cells (TC-3) were treated with chokeberry anthocyanins [chokeberries are purple/dark blue colored like blueberries or bilberries] at concentrations between 0 and 3 nM, expressed as cyanidin 3-galactoside. ... the viability and proliferation of TC-3 cells is stimulated by all tested anthocyanin concentrations.” “Our data shows that the oxidative stress induced by 100 mM glucose determined a significant decrease (50%) of GSH [glutathione]. The intracellular GSH level increased significantly (25%) in cells preincubated with 0.2 nM chokeberry anthocyanins compared to glucose (100 mM) treated cells, but remain under the normal GSH levels in untreated pancreatic beta-cells. The GSH level in cells treated with the highest concentration of chokeberry anthocyanins (1.0 nM) and 100 mM glucose was restored, being even HIGHER than for untreated cells.”3 (emphasis added)

These protective effects of chokeberry anthocyanins at such low concentrations are remarkable and, although this paper did not report changes induced by the anthocyanins in inflammatory cytokines, oxidative stress induced by high levels of glucose is known to be associated with increased inflammation. Hence, anthocyanins would likely have anti-diabetic effects, as has been reported in other studies (cited in paper #3).

In paper #1, the researchers explain that “[a]nthocyanins are the largest group of water-soluble pigments in the plant kingdom. They are widely distributed in the human diet through crops, beans, fruits, vegetables, and red wine, suggesting that we ingest significant amounts of anthocyanins from plant-based daily diets.” The authors reported that in four of their earlier papers (citations provided in paper #1), they showed that in addition to antioxidant properties, cyanidin 3-O-beta-D-glucoside, a typical anthocyanin, also had anti-inflammatory properties based on in vitro and in vivo studies.


1. Tsuda et al. Anthocyanin enhances adipocytokine secretion and adipocyte-specific gene expression in isolated rat adipocytes. Biochem Biophys Res Commun. 316:149-157 (2004).
2. Tsuda et al. Dietary cyanidin 3-O-beta-D-glucoside-rich purple corn color prevents obesity and ameliorates hyperglycemia in mice. J Nutr. 133:2125-30 (2003).
3. Rugina et al. Protective effect of chokeberry anthocyanin-rich fraction at nanomolar concentrations against oxidative stress induced by high doses of glucose in pancreatic beta-cells. Bul UASVM, Vet Med. 68(1):313-9 (2011).

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