Cancer and the Glutathione

In this page, I will look into the relationship between low gluthathione and cancer (Section A) and show that simple holistic interventions like broccoli therapy can help lots (Section B)

Section A

Cancer and Glutathione

Low glutathione is commonly observed in wasting and negative nitrogen balance, as seen in cancer, HIV/AIDS, sepsis, trauma, burns, and athletic overtraining. Low levels are also observed in periods of starvation. These effects are hypothesized to be influenced by the higher glycolytic activity associated with cachexia, which result from reduced levels of oxidative phosphorylation. (1)

A recent intervention study demonstrated that cruciferous vegetables could increase the detoxification of carcinogens and other xenobiotics in humans. In this 12-week randomized controlled trial in 391 healthy Chinese adults exposed to high levels of air pollution, daily consumption of a broccoli sprout-rich beverage (providing 600 µmol/day of glucoraphanin and 40 µmol/day of sulforaphane) significantly increased the urinary excretion of a known carcinogen, benzene, and a toxicant, acrolein, compared to placebo (2).

The biological activities of glucosinolate derivatives, isothiocyanates and indole-3-carbinol, which include modulation of xenobiotic metabolism, but also antioxidant and anti-inflammatory properties, induction of cell cycle arrest and apoptosis, and inhibition of angiogenesis, likely contribute to the potential benefits of cruciferous vegetables in the prevention of cancer (see the MIC articles on Isothiocyanates and Indole-3-Carbinol) (3).

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Evidence from observational studies

Numerous observational ( ) studies have examined the relationship between cruciferous vegetable intake and cancer risk.

 

Hu et al. (2015) (42)

Pancreatic cancer

4 prospective cohort and 5 case-control studies

Liu et al. (2013) (34)

Colorectal cancer

Genes

In the past decades, some observational studies have examined the effect of individuals’ genetic variations on the relationship between cruciferous vegetable intake and the risk of different cancer types. For example, a pooled analysis of two prospective cohort studies and six case-control studies found an inverse association between cruciferous vegetable consumption and risk of colorectal neoplasm in carriers of the GSTT1 null variant but not in individuals with the GSTM1 null variant or those with both the GSTT1and GSTM1 null variants (-/-) (36).

Limitations: Nutrient Interactions

Iodine and thyroid function

Very high intakes of cruciferous vegetables, such as cabbage and turnips, have been found to cause hypothyroidism (insufficient production of thyroid hormones) in animals (54). Two mechanisms can potentially explain this effect. The hydrolysis of progoitrin, found in cruciferous vegetables (see Figure 1), may yield a compound known as goitrin, which may interfere with thyroid hormone synthesis.

Chemo and GSH

However, once a tumor has been established, elevated levels of glutathione may act to protect cancerous cells by conferring resistance to chemotherapeutic drugs. The antineoplastic mustard drug canfosfamide was modelled on the structure of glutathione. (2)

Limitation of Retrospective case-control  studies

Most meta-analyses found inverse associations between cruciferous vegetable intake and risk of bladder, breast, colorectal, endometrial, gastric, lung, ovarian, pancreatic, prostate, and renal cancer. Subgroup analyses showed that inverse associations remained significant in pooled analyses of case-control studies but not in pooled analyses of prospective cohort studies. Retrospective case-control studies are susceptible to bias in the selection of participants (cases and controls) and prone to dietary recall bias compared to prospective cohort studies, which collect dietary information from participants before they are diagnosed with cancer (47). The method of cooking cruciferous vegetables, which strongly affects the bioavailability and potential anticancer benefits of isothiocyanates (see Metabolism and Bioavailability of Glucosinolates) may be a source of bias and explain variation in the results of the studies (heterogeneity among studies). The lack of information regarding cooking methods prevented data adjustment to reduce bias.

Reference and Precision Notes

(1).  Dröge W, Holm E (November 1997). “Role of cysteine and glutathione in HIV infection and other diseases associated with muscle wasting and immunological dysfunction”FASEB Journal11 (13): 1077–89. PMID 9367343. AND: Tateishi N, Higashi T, Shinya S, Naruse A, Sakamoto Y (January 1974). “Studies on the regulation of glutathione level in rat liver”Journal of Biochemistry75 (1): 93–103. doi:10.1093/oxfordjournals.jbchem.a130387PMID 4151174.
2.  Egner PA, Chen JG, Zarth AT, et al. Rapid and sustainable detoxication of airborne pollutants by broccoli sprout beverage: results of a randomized clinical trial in China. Cancer Prev Res (Phila). 2014;7(8):813-823.  (PubMed)

3.  Traka MH. Chapter nine – Health benefits of glucosinolates. Advances in Botanical Research. 2016;80:247-279.

 

a study in which no experimental intervention or treatment is applied. Participants are simply observed over time.nal Studies  case control…cohort studies prospective cohort studies

24 case-control and 11 prospective cohort studies

21.  Sergentanis TN, Economopoulos KP. GSTT1 and GSTP1 polymorphisms and breast cancer risk: a meta-analysis. Breast Cancer Res Treat. 2010;121(1):195-202.  (PubMed)

22.  Bryan HK, Olayanju A, Goldring CE, Park BK. The Nrf2 cell defence pathway: Keap1-dependent and -independent mechanisms of regulation. Biochem Pharmacol. 2013;85(6):705-717.  (PubMed)

 

34.  Liu X, Lv K. Cruciferous vegetables intake is inversely associated with risk of breast cancer: a meta-analysis. Breast. 2013;22(3):309-313.  (PubMed)

42.  Hu J, Hu Y, Hu Y, Zheng S. Intake of cruciferous vegetables is associated with reduced risk of ovarian cancer: a meta-analysis. Asia Pac J Clin Nutr. 2015;24(1):101-109.  (PubMed)

43.  Li LY, Luo Y, Lu MD, Xu XW, Lin HD, Zheng ZQ. Cruciferous vegetable consumption and the risk of pancreatic cancer: a meta-analysis. World J Surg Oncol. 2015;13:44.  (PubMed)

 

(2). Balendiran GK, Dabur R, Fraser D (2004). “The role of glutathione in cancer”. Cell Biochemistry and Function22 (6): 343–52. doi:10.1002/cbf.1149PMID15386533.

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