Pancreatic Wellbeing

Curcumin

Curcumin, an extract from the Indian spice turmeric, has been used in many pancreatic cancer trials [1].
Studies have found that populations with the highest curcumin consumption have a lower incidence and risk of various types of cancers, including pancreatic cancer [2-4]. Curcumin can halt the growth of pancreatic cancer cells in vitro [5].
Three published human clinical trials have used 8g curcumin a day:
A trial of curcumin in 25 patients with advanced pancreatic cancer, demonstrated biological activity in two patients. One had ongoing stable disease for >18 months; one additional patient had brief, but marked, tumour regression (73%) accompanied by significant increases in serum cytokine levels [6].
Curcumin has also been used in combination with gemcitabine in locally advanced pancreatic cancer which could not be surgically removed [7]. However the trial used patients of poor nutritional status and had high drop-out rates from gastrointestinal symptoms [7].
A phase I clinical trial used 19 patients with pancreatic cancer who were resistant to gemcitabine-based chemotherapy. Four patients continued for >6 months. The average survival time was 161 days and there was a one-year survival rate of 19% [8], much higher than the average.

References

1.Aggarwal BB, Kumar A, Bharti AC et al. Anticancer potential of curcumin:Preclinical and clinical studies. Anticancer Research 2003;23(1A):363-398.
2.Sinha R, Anderson DE, McDonald SS, Greenwald P. Cancer risk and diet in India. J Postgrad Med. 2003;49:222–8.
3.Goel A, Kunnumakkara AB, Aggarwal BB. Curcumin as “Curecumin”: from kitchen to clinic. Biochem Pharmacol. 2008;75:787–809.
4.Stan SD, Singh SV, Brand RE. Chemoprevention strategies for pancreatic cancer. Nat Rev Gastroenterol Hepatol. 2010;7:347–56.
5.Youns M, Fathy G. Upregulation of extrinsic apoptotic pathway in curcumin-mediated antiproliferative effect on human pancreatic carcinogenesis. J Cell Biochem 2013; [Epub ahead of print].
6.Dhillon N, Aggarwal BB, Newman RA et al. Phase II trial of curcumin in patients with advanced pancreatic cancer. Clinical Cancer Research 2008;14(14):4491-4499.
7.Epelbaum R, Schaffer M, Vizel B et al. Curcumin and gemcitabine in patients with advanced pancreatic cancer. Nutr Cancer. 2010;62:1137–1141.
8.Kanai M, Yoshimura K, Asada M et al. A phase I/II study of gemcitabine-based chemotherapy plus curcumin for patients with gemcitabine-resistant pancreatic cancer. Cancer Chemother Pharmacol 2011;68(1):157-164.

Curcumin and Pancreatitis

A human randomised controlled trial using 500mg curcumin per day and 5mg piperine per day (a compound in black pepper) may reverse lipid peroxidation, a sign of stress on the pancreas, in patients with tropical pancreatitis [1]. Curcumin has also been shown to prevent [2] and help treat [3,4] acute pancreatitis in animal models.

Curcumin and Type 2 Diabetes

Curcumin has been shown to protect human pancreatic islets cells from oxidative stress [5]. A randomised placebo controlled trial was undertaken on 240 glucose-intolerant patients for nine months. Patients took 6 x 250mg curcumin capsules a day. Curcumin treatment lowered HbA1c and slowed the deterioration to T2DM [6].
In diabetic animals, curcumin improves high blood sugar and high blood lipids [7-9].

References

1. Durgaprasad S, Pai CG, Vasanthkumar et al. A pilot study of the antioxidant effect of curcumin in tropical pancreatitis. Indian J Med Res. 2005;122(4):315–318.
2. Yu WG, Xu G, Ren GJ et al. Preventive action of curcumin in experimental acute pancreatitis in mouse. Indian J Med Res. 2011;134(5):717-24.
3. Zhong K. Curcumin Mediates a Protective Effect Via TLR-4/NF-κB Signaling Pathway in Rat Model of Severe Acute Pancreatitis. Cell Biochem Biophys. 2015 epub ahead of print..
4. Gulcubuk A, Haktanir D, Cakiris A et al. Effects of curcumin on proinflammatory cytokines and tissue injury in the early and late phases of experimental acute pancreatitis. Pancreatology. 2013;13(4):347-54.
5. Balamurugan AN, Akhov L, Selvaraj G & Pugazhenthi S. Induction of antioxidant enzymes by curcumin and its analogues in human islets: implications in transplantation. Pancreas 2009; 159 85–93.
6. Chuengsamarn S, Rattanamongkolgul S, Luechapudiporn R et al. Curcumin extract for prevention of type 2 diabetes. Diabetes Care 2012;35 2121–2127.
7. Hussain HE. Hypoglycemic, hypolipidemic, and antioxidant properties of combination of curcumin from Curcuma longa, Linn, and partially purified product from Abroma augusta, Linn. in streptozotocin induced diabetes. Indian Journal of Clinical Biochemistry 2002; 17 33–43.
8. Arun N & Nalini . Efficacy of turmeric on blood sugar and polyol pathway in diabetic albino rats. Plant Foods for Human Nutrition 2002; 57 41–52.
9. Pari L, Murugan P. Effect of tetrahydrocurcumin on blood glucose, plasma insulin and hepatic key enzymes in streptozotocin induced diabetic rats. Journal of Basic and Clinical Physiology and Pharmacology 2005;16 257–274.

Green Tea

Green tea extract contains antioxidant compounds such as epigallocatechin-3-gallate (EGCG).
Compounds such as EGCG have been found to have anti-proliferative properties and induce cell death in pancreatic cancer cells, in both in vitro and in vivo studies [1-4]. A study in mice suggests EGCG blocks the pancreatic cancer pathways and it may be useful in both the prevention and treatment of pancreatic cancer [5].

References

1. Vu, HA, Beppu Y, Chi HT et al. Green tea epigallocatechin gallate exhibits anticancer effect in human pancreatic carcinoma cells via the inhibition of both focal adhesion kinase and insulin-like growth factor-I receptor. J Biomed Biotechnol 2010: 290516.
2. Shankar, S, Suthakar G, Srivastava RK. et al. Epigallocatechin-3-gallate inhibits cell cycle and induces apoptosis in pancreatic cancer. Front Biosci 2007;12:5039-5051.
3. Shankar, S, Ganapathy S, et al. EGCG inhibits growth, invasion, angiogenesis and metastasis of pancreatic cancer. Front Biosci 2008;13:440-452.
4. Li, Y, Zhang T, Jiang Y, et al. (-)-Epigallocatechin-3-gallate inhibits Hsp90 function by impairing Hsp90 association with cochaperones in pancreatic cancer cell line Mia Paca-2. Mol Pharm 2009;6(4):1152-1159.
5. Shankar S, Marsh L, Srivastava RK. EGCG inhibits growth of human pancreatic tumors orthotopically implanted in Balb C nude mice through modulation of FKHRL1/FOXO3a and neuropilin. Mol Cell Biochem. 2013;372(1-2):83-94.

Green Tea in Pancreatic conditions

An in vitro study showed that the green tea polyphenol EGCG could prevent pancreatic fibrosis through the antioxidant effect [1]. The same ingredient could also help prevent pancreatitis [2-4] and septic shock [5] in animal models.

Green Tea in Type 2 Diabetes and Obesity

Studies of EGCG in animals show that it may inhibit the pathways that lead to glucose intolerance caused by obesity [6-9] and may even have a direct anti-obesity effect [10]. In humans, gallated catechin (GC) from the green tea polyphenol EGCG may reduce blood glucose levels through blocking normal glucose uptake in the food pipe [11].

References

1. Asaumi H, Watanabe S, Taguchi M et al. Green tea polyphenol (-)-epigallocatechin-3-gallate inhibits ethanol-induced activation of pancreatic stellate cells. Eur J Clin Invest. 2006;36(2):113-22.
2. Takabayashi F, Harada N, Hara Y. The effects of green tea catechins (Polyphenon) on DL-ethionine-induce acute pancreatitis. Pancreas. 1995;11(2):127-31.
3. Takabayashi F, Harada N. Effects of green tea catechins (Polyphenon 100) on cerulein-induced acute pancreatitis in rats. Pancreas. 1997;14(3):276-9.
4. Babu BI, Malleo G, Genovese T et al. Green tea polyphenols ameliorate pancreatic injury in cerulein-induced murine acute pancreatitis. Pancreas. 2009;38(8):954-67.
5. Di Paola R, Mazzon E, Muià C. Green tea polyphenol extract attenuates zymosan-induced non-septic shock in mice. Shock. 2006;26(4):402-9.
6. Furuyashiki T, Nagayasu H, Aoki Y, et al. Tea catechin suppresses adipocyte differentiation accompanied by down-regulation of PPARgamma2 and C/EBPalpha in 3T3-L1 cells. Biosci Biotechnol Biochem. 2004;68:2353–2359. [
7. Klaus S, Pultz S, Thone-Reineke C, Wolfram S. Epigallocatechin gallate attenuates diet-induced obesity in mice by decreasing energy absorption and increasing fat oxidation. Int J Obes (Lond) 2005;29:615–623.
8. Wu LY, Juan CC, Hwang LS, Hsu YP, Ho PH, Ho LT. Green tea supplementation ameliorates insulin resistance and increases glucose transporter IV content in a fructose-fed rat model. Eur J Nutr. 2004;43:116–124.
9. Han MK. Epigallocatechin gallate, a constituent of green tea, suppresses cytokine-induced pancreatic beta-cell damage. Exp Mol Med. 2003;35:136–139. [
10. Tian C, Ye X, Zhang R, Long J, Ren W, Ding S, Liao D, Jin X, Wu H, Xu S, Ying C. Green tea polyphenols reduced fat deposits in high fat-fed rats via erk1/2-PPARgamma-adiponectin pathway. PLoS One. 2013;8:e53796.
11. Park JH, Jin JY, Baek WK, Park SH, Sung HY, Kim YK, Lee J, Song DK. Ambivalent role of gallated catechins in glucose tolerance in humans: a novel insight into non-absorbable gallated catechin-derived inhibitors of glucose absorption. J Physiol Pharmacol. 2009;60:101–109.

Selenium

The recent Vitamins and Lifestyle (VITAL) study looked at the association between some known antioxidant agents (selenium β-carotene, lutein plus zeaxanthine, lycopene, vitamin C, vitamin E and zinc) and the risk of pancreatic cancer. There was no strong evidence of a link with the intake of antioxidants other than with selenium [1].
A recent UK study of the EPIC cohort indicated that high intake of selenium was associated with a reduced risk of pancreatic cancer [2].
The same conclusion has been confirmed by two other studies, which have stated that higher blood markers of selenium are connected with a lower risk of pancreatic cancer [3,4].
Apart from those at risk of prostate cancer, selenium could be taken as a way of reducing pancreatic cancer risk, but it is important to note that only people with low levels of selenium in their blood should take selenium supplements or it may do more harm than good [5].

Selenium and Type 2 diabetes

Studies also indicate that selenium may improve glucose metabolism. But supplementation could increase the risk of diabetes if a person already has normal levels of selenium in their blood [6-8]. It is therefore important that only patients with proven selenium deficiency take high dose selenium supplements.

References

1. Han X, Li J, Brasky TM, et al. Antioxidant intake and pancreatic cancer risk: The Vitamins and Lifestyle (VITAL) Study. Cancer 2013; 119: 1314- 1320.
2. Banim PJ, Luben R, McTaggart A et al. Dietary antioxidants and the aetiology of pancreatic cancer: a cohort study using data from food diaries and biomarkers. Gut 2013 ;62(10):1489-96.
3. Amaral AF, Porta M, Silverman DT et al. Pancreatic cancer risk and levels of trace elements. Gut 2012 61: 1583-1588.
4. Burney PG, Comstock GW and Morris JS. Serologic precursors of cancer: serum micronutrients and the subsequent risk of pancreatic cancer. Am J Clin Nutr 1989; 49: 895-900.
5. Rayman MP. Selenium and human health. Lancet 2012; 379 (9822): 1256-68.
6. Stranges S, Marshall JR, Natarajan R, et al. Effects of Long-Term Selenium Supplementation on the Incidence of Type 2 Diabetes: A Randomized Trial. Ann Intern Med 2007;147(4):217-23.
7. Lippman SM, Klein EA, Goodman PJ, et al. Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA 2009;301(1):39-51.
8. Rayman MP. Selenium and human health. Lancet 2012; 379(9822):1256-68.

For extended reading, you can download examinations of the relationship between diet, food supplements and health conditions here