Study shows green tea and cocoa protecting against complications of diabetes

In tests performed with experimental models and cultured cells, green tea and cocoa have been found capable of preventing or reversing damage to kidneys and retinas in diabetics.

By José Tadeu Arantes  |  Agência FAPESP – The beneficial effects of green tea and cocoa, and especially their antioxidant and anti-inflammatory properties, have been widely publicized. The Thematic Project “Effects of green tea (Camellia sinensis), cocoa and nitric oxide donor on diabetic nephropathy and retinopathy: contribution of the reduction of oxidative stress and inflammation and elevation of nitric oxide”, supported by FAPESP, has shown that green tea and cocoa can also act as coadjuvants in the prevention or treatment of renal and retinal complications of diabetes.

“We started with the hypothesis that these products might be beneficial because they reduce oxidative stress and inflammation, as well as increase levels of nitric oxide, a vasodilator with a diminished presence in diabetics. So we separately studied the effects of green tea, cocoa and a nitric oxide donor, finding real benefits from both green tea and cocoa. The project produced ten articles in scientific journals,” said Jose Butori Lopes de Faria, Full Professor of Nephrology at the University of Campinas (UNICAMP) in São Paulo State, Brazil, and principal investigator for the project.

Studies relating to the retina were coordinated by UNICAMP researcher and ophthalmologist Jacqueline Mendonça Lopes de Faria.

The researchers used experimental models (mice and rats) in which diabetes was induced, as well as cultured cells from mice and humans exposed to high glucose levels as a way of mimicking diabetes. They described various mechanisms that lead to renal and retinal injury and how these were reversed using green tea or cocoa.

“Besides the well-known antioxidative and anti-inflammatory action of green tea, we showed that it [green tea] reduces apoptosis, or programmed death, of podocytes. These cells are essential to the maintenance of the glomerular barrier, which restricts the passage of proteins from blood to urine. The passage of albumin into urine is the main renal alteration in diabetics,” Lopes de Faria told Agência FAPESP.

The beneficial effects of both green tea and cocoa are attributed to the presence of polyphenols: epigallocatechin gallate in the case of green tea and epicatechin in cocoa. In collaboration with Marcelo Ganzarolli de Oliveira, Full Professor at UNICAMP’s Chemistry Institute, the researchers characterized the chemistry of these two products, confirming the presence of the aforementioned polyphenols using high-performance liquid chromatography and mass spectrometry.

However, they were surprised to find that cocoa acted positively even when the polyphenol was removed. “To investigate the effect of epicatechin, we used two kinds of cocoa: one rich in epicatechin and the other with none at all. Contrary to expectations, the latter type also had an effect that would protect a patient from complications associated with diabetes. This had never before been described in the scientific literature. So we wrote a paper suggesting that theobromine, which is a methylxanthine, might be responsible for the effect. Later publications corroborated our opinion,” Lopes de Faria said.

There are already a great many studies in the scientific literature on the beneficial effects of green tea and cocoa. Two recent studies should be noted, according to Lopes de Faria. The first is a meta-analysis, published in the British Journal of Nutrition, covering a sample that comprised hundreds of thousands of individuals and showing that green tea affords protection against multiple causes of death and cardiovascular disease.

The second, published in The Journal of the American Medical Association (JAMA), shows that even daily consumption of a small piece of chocolate with a high concentration of cocoa causes a significant reduction in systolic blood pressure.

Publications resulting from the project

1. Peixoto EB, et al. “Reduced LRP6 expression and increase in the interaction of GSK3β with p53 contribute to podocyte apoptosis in diabetes mellitus and are prevented by green tea”. J Nutr Biochem, 2015 Apr;26(4):416-30. doi:10.1016/j.jnutbio.2014.11.012.
2. Duarte DA, et al. “Polyphenol-enriched cocoa protects the diabetic retina from glial reaction through the sirtuin pathway”. J Nutr Biochem, 2015 Jan;26(1):64-74. doi:10.1016/j.jnutbio.2014.09.003.
3. Papadimitriou A, et al. “Theobromine increases NAD+/Sirt-1 activity and protects the kidney under diabetic conditions.” Am J Physiol Renal Physiol, 2015 Feb 1;308(3):F209-25. doi:10.1152/ajprenal.00252.2014.
4. Rosales MA, et al. “Endocytosis of tight junctions caveolin nitrosylation dependent is improved by cocoa via opioid receptor on RPE cells in diabetic conditions”. Invest Ophthalmol Vis Sci. 2014 Sep 4;55(9):6090-100. doi:10.1167/iovs.1414234.
5. Papadimitriou A, et al. “Increase in AMPK brought about by cocoa is renoprotective in experimental diabetes mellitus by reducing NOX4/TGFβ-1 signaling”. J Nutr Biochem, 2014 Jul;25(7):773-84. doi:10.1016/j.jnutbio.2014.03.010.
6. Rosales MA, et al. “S-nitrosoglutathione inhibits inducible nitric oxide synthase upregulation by redox posttranslational modification in experimental diabetic retinopathy”. Invest Ophthalmol Vis Sci, 2014 May 2;55(5):2921-32. doi:10.1167/iovs.13-13762.
7. Silva KC, et al. “Green tea is neuroprotective in diabetic retinopathy”. Invest Ophthalmol Vis Sci, 2013 Feb 15;54 (2):1325-36. doi:10.1167/iovs.12-10647.
8. Faria AM, et al. “Uncoupling endothelial nitric oxide synthase is ameliorated by green tea in experimental diabetes by re-establishing tetrahydrobiopterin levels”. Diabetes, 2012 Jul;61(7):1838-47. doi:10.2337/db11-1241.
9. Ribaldo PD, et al. “Green tea (Camellia sinensis) attenuates nephropathy by downregulating Nox4 NADPH oxidase in diabetic spontaneously hypertensive rats”. J Nutr, 2009 Jan;139(1):96-100. doi:10.3945/jn.108.095018.
10. Tata A, et al. “Spatial distribution of theobromine–a low MW drug–in tissues via matrix-free NALDI-MS imaging”. Drug Test Anal, 2014 Sep;6(9):949-52. doi:10.1002/dta.1691.