Life Extension Magazine®

Couple toasting with wine that their bodies can convert to acetaldehyde

Link Between Alcohol and Cancer Death

A 2011 European study found that alcohol intake accounted for one in ten cancer cases for men and one in thirty for women, even in moderate amounts. The reason? Alcohol is metabolized by the body into a DNA-mutating compound called acetaldehyde. Fortunately, a number of nutrients have been shown to neutralize acetaldehyde, ideally taken before you drink or before going to sleep if excessive alcohol is consumed.

Scientifically reviewed by Dr. Gary Gonzalez, MD, in October 2024. Written by: Michelle Flagg.

Link Between Alcohol and Cancer Death

Those who consume no alcohol are at higher risk of heart attack and ischemic stroke. Yet many of us drink more alcoholic beverages than is safe.

Problem drinking is defined as 12-15 drinks a week by the National Institutes of Health.1

Yet according to the latest research, alcohol in more moderate amounts can be deadly.

In one of the largest analyses of its kind, a 2011 epidemiological study of eight Western European countries revealed that drinking alcohol accounted for 1 out of 10 cancer cases in men and 1 in 30 for women, who tend to drink less.2

These included colorectal and breast cancer, along with cancers of the upper gastrointestinal tract and liver. Cancer incidence was not confined to heavy drinkers. Even those who had one to two drinks a day were at risk.

How could this happen?

You won't hear this from most doctors, but the body converts alcohol into a DNA-destroying metabolite called acetaldehyde. It is a compound sufficiently dangerous to be officially classified as a carcinogen by the International Agency for Research on Cancer.3-8 The good news is that specific nutrients many Life Extension® members already take have been shown to neutralize the cancer-causing effects of acetaldehyde before they take hold.

In this article, a scientifically validated, comprehensive anti-alcohol nutritional regimen is detailed. You will discover how acetaldehyde interferes with biological and cellular processes to induce functional and metabolic abnormalities that lead to cancer.

You will also learn nutrient interventions that operate via multiple pathways to protect against alcohol's most dangerous effects when taken before or after you drink.

When you drink alcohol, some of it converts to a metabolite called acetaldehyde, which is a highly reactive molecule that causes cancer through a variety of mechanisms. Acetaldehyde is also a primary factor involved in unpleasant next-day aftereffects of excess ethanol ingestion.9

Acetaldehyde binds to DNA, causing mutations that can initiate cancer development.5,10.11 It produces reactive oxygen species (ROS) that lead to inflammation, promoting tumor development once a cancerous cell has formed.7,8 Acetaldehyde impairs cells' natural antioxidant defense systems, making them still more vulnerable to cancer-causing oxidant damage.8 It depletes cells of vitamin B6, further impairing cells' abilities to battle oxidation.12 And acetaldehyde interferes with folic acid, blocking cells' natural DNA repair mechanisms and further promoting cancer growth.13

The most effective strategy for reducing alcohol-related cancer risk is to cut back alcohol consumption.14

Antioxidant Vitamins

But alcohol occupies a complicated place in today's health consciousness. It provides some definite benefits to cardiovascular health when used in small to moderate amounts.15 And, for many, alcohol produces both psychological and biological dependency, making it difficult to simply quit drinking.16 In addition, much of our social interaction occurs with some levels of alcohol.

Fortunately, there are proven nutrients that afford powerful antioxidant protection, while others directly interfere with acetaldehyde production in liver cells. Still others can restore the body's waning stores of essential nutrients.

Together these effects can help you lower your cancer risk if you choose to consume alcohol.

Antioxidant Vitamins

Table 1. Oral Cancer Risk Reduction from Antioxidant Vitamins and Nutrients17
Vitamin Percent Reduction in
Cancer Risk
Vitamin B6 41%
Carotene 39%
Folic Acid 39%
Niacin 38%
Vitamin C 37%
Vitamin E 26%
Thiamine 18%
Vitamin D 17%
Riboflavin 13%
Zinc 11%
Lycopene 9%

One of the best and most general ways to fight the acetaldehyde-induced oxidative stress that follows alcohol consumption is to assure that one has an adequate regular intake of key antioxidant vitamins.17 (See Table 1) In general, the higher the intake of these vitamins, the lower the risk of most cancers.18,19 Alcohol drinkers are especially vulnerable to this effect: the combination of high alcohol intake and low antioxidant vitamin intake increases the risk of colon cancer more than 6-fold.20,21

Treatment with antioxidant nutrients and vitamins can protect delicate DNA from cancer-inducing damage and reduce the inflammation that promotes cancer development in people who use alcohol chronically.22,23 A 2010 Harvard study demonstrated that intakes of vitamins A, C, and E from food alone did not reduce colon cancer risk.24 When intakes from supplements were included, the risk dropped by 19% for vitamin C intake and by 22% from vitamin E.24 The same study demonstrated a 12% decrease in cancer risk from multivitamin and folate supplementation. Similar effects have been demonstrated for other cancer types, including a variety of brain tumors.25

Selenium

Selenium is an essential dietary component for human life, and it has been shown to be protective against cancer.26 It is a vital constituent of the so-called selenoproteins that are necessary for proper antioxidant and DNA repair function of several important intracellular systems.26 Selenium deficiency leads to increased DNA damage and increased likelihood of cancer in laboratory animals, whereas dietary selenium reduces formation of pre-cancerous tissue.27,28

In humans, low selenium status is associated with increased risk of colon cancer.29 Selenium levels tend to be reduced in people who drink alcohol regularly.30 That is especially concerning because selenium deficiency is a major risk factor for liver cancer; conversely, people with the highest levels of selenium in their tissues have a 50% reduction in their risk of this cancer.31

Glutathione and N-Acetyl Cysteine (NAC)

Oxidative stress combined with acetaldehyde causes a profound impairment of the body's natural antioxidant systems, by depleting stores of a compound called glutathione.32 Restoring cellular healthy glutathione levels, therefore, seems to be a natural strategy to prevent alcohol-related cancers.

N-acetyl cysteine (NAC) powerfully replenishes glutathione levels in tissues, helping to fend off the consequences of acute oxidative stress.33,34 It is widely used in conventional medicine to fight the impact of toxic ingestions, such as acetaminophen (Tylenol®) overdose.35 Rats supplemented with NAC prior to treatment with acetaldehyde are potently protected against toxicity and death; the effect is even more powerful when combined with vitamin C and thiamine.36 Independently, NAC binds acetaldehyde directly, further preventing its damaging effects.37

Alcohol and Cancer Death
  • A landmark 2011 study revealed that drinking alcohol may account for 1 out of 10 cancer cases in men, and 1 in 30 for women.
  • Even modest alcohol consumption was found to increase risk for most forms of cancer. This occurs owing to a little-known process in which your body converts alcohol into acetaldehyde, a known carcinogen.
  • You can help your body battle the cancer-causing effects of alcohol by choosing a regimen of nutrients and phytonutrients that effectively neutralizes alcohol's toxic effects, including silymarin from milk thistle extract, resveratrol, grape seed extract, and barley grass.
  • Other compounds can help you restore nutrients and minerals depleted from your body as a result of alcohol consumption, including selenium and benfotiamine.

Benfotiamine

Alcohol and Cancer Death

Benfotiamine is a fat-soluble form of thiamine (vitamin B1).38 It is best known for its protective effects against formation of advanced glycation end products (AGEs) in people with diabetes or the metabolic syndrome.39 Since AGEs are known to play a major role in cancer formation (by promoting oxidative damage and inflammation),40 benfotiamine is finding a role in cancer prevention as well. By a separate mechanism, benfotiamine also directly prevents cell damage arising from alcohol use.41 And benfotiamine has significant antioxidant effects, preventing induction of cancer-causing DNA damage in laboratory studies.39,42

Folic Acid and SAMe

In addition to toxic acetaldehyde production, alcohol consumption depletes the body of certain important nutrients. Deficiencies of folic acid, zinc, and the sulfur-containing amino acid methionine are frequent among drinkers.6,43,44 Cells that lack these nutrients cannot suppress cancer genes called proto-oncogenes, often resulting in the initiation of a cancer.10,45 Compared with non-drinkers, men who consume more than two alcohol drinks daily have a 64% increased risk of colon cancer, while women have an 84% increase.11 But those with the highest folic acid and methionine intakes have an approximately one-third lower risk of colon cancer.11

Supplementation with folic acid, zinc, and S-adenosylmethionine (SAMe) is an effective way of preventing these widespread alcohol-related deficiencies and potentially lowering cancer risk.46-49 SAMe has additional value because, like NAC, it helps restore depleted glutathione in alcohol-damaged cells, providing additional antioxidant protection.50,51

Chlorophyllin

Chlorophyllin is a water-soluble form of the green plant pigment chlorophyll.52,53 It has been evaluated as a chemopreventive agent in populations at high risk for liver cancer, one of the most common tumors known, and one that is frequently caused by ingested toxins.52-54 Chlorophyllin is a large molecule thought to bind to many carcinogens and toxins, enhancing their excretion from the body before they damage DNA.54,55 Binding to toxins in the intestine prevents their uptake, further reducing their cancer-producing effects.54 Chlorophyllin also induces important enzymes that protect against oxidants arising from toxins such as acetaldehyde, while also reducing expression of inflammatory mediators.56,57

Grape Seed Extracts

Grape Seed Extracts

Extracts of grape seeds are known to be powerful antioxidants with health benefits on many tissues. In both animal and human studies, these extracts reduce markers of oxidative damage and enhance natural antioxidant mechanisms to protect cells and DNA from injury.58-62 Grape seed extracts have been shown to prevent alcohol-induced oxidative damage in all tissues examined in animal studies.63,64 These extracts are highly bioavailable in humans, making them especially appealing in combating the cancer-causing effects of alcohol.65,66

Silymarin (from Milk Thistle)

Table 2. Smoking- and Alcohol-Related Cancer Risk: 1965-2008
Smoking prevalence in US, 1965 40%86
Smoking prevalence in US, 1987 29%86
Percent of cancers preventable by elimination of cigarette smoking 30%86
Percent of mouth, esophagus, and lung cancer preventable by not smoking 90%86
Reduction in deaths from smoking, cholesterol, blood pressure, and physical inactivity, 2000 vs. 1980 308,90087
Life-years gained through reduction in smoking, cholesterol, blood pressure, and physical inactivity 2,770,500 life-years87
Reduction in smoking-attributable cancer deaths, 1979-2005 8.9%88
Reduction in smoking-attributable cancer deaths in California (state-sponsored tobacco control program), 1979-2005 25.7%88
Percent of cancers related to alcohol consumption, 2008 Up to 44%88
Despite plummeting rates of smoking-related cancers, alcohol-related cancer rates remain high.

Silymarin is a compound extracted from the milk thistle plant. It has long been used to improve liver health and enhance excretion of toxins, particularly those that are related to alcohol toxicity. Silymarin is a powerful antioxidant and protects DNA from cancer-inducing damage, especially in alcohol-induced liver disease.22,67 It inhibits conversion of ethanol to acetaldehyde and reduces cell proliferation in laboratory models of liver cancer.68

Silymarin also stabilizes cell membranes and promotes normal liver cell regeneration.67,69 It reduces inflammatory mediators that otherwise help to promote cancer growth.67,69,70 Long-term administration of silymarin significantly increases survival time of patients with liver cirrhosis, a frequent precursor of liver cancer.69 Laboratory studies reveal that silymarin reduces tumor cell proliferation and new blood vessel growth, helping to starve tumors of vital nutrients and oxygen.69 Finally, silymarin has been shown to inhibit development of tumor metastases, helping limit spread of cancer.69

Picrorhiza

Picrorhiza kurroa is a member of the figwort family, with a long history of use in traditional south Asian medical systems.71 Picrorhiza extracts given to laboratory animals following chronic alcohol ingestion reverse most of the deleterious biochemical changes induced by alcohol.72,73 A powerful antioxidant,71 picrorhiza also has specific anti-cancer effects, inhibiting toxin-induced cancer generation and increasing life span of tumor-afflicted animals.74,75 Picrorhiza also very specifically modifies the inflammatory "master molecule" called nuclear factor-kappaB, reducing production of inflammatory cytokines that can promote tumor growth.76 That mechanism, along with others, also promotes cancer cell death by apoptosis.71,76

Barley Grass

Barley Grass

Barley is a fiber- and antioxidant-rich grain with a number of chemopreventive properties of particular interest in the context of cancer.77 Toxin-induced gastrointestinal tumors in mice can be prevented using extracts of barley grain or bran.77,78 A powerful cancer-suppressing protein called lunasin, first identified in soy protein, has now been discovered to be abundant in barley as well.79,80 Barley lunasin suppresses formation of tumor cell colonies and protects DNA from cancer-inducing changes.79,80 Barley grass extracts also serve a prebiotic function, modifying the intestinal environment to prevent toxin-induced colon cancers.81

Resveratrol

Resveratrol is a versatile polyphenol derived from grapes and other plants. Like most polyphenols, resveratrol is also a powerful antioxidant and protector of DNA and mitochondria against alcohol's toxic effects.64,82,83 Even after DNA damage has occurred, resveratrol switches on essential DNA repair mechanisms to heal the injury before it can trigger cancerous change.83

But resveratrol has other unrelated beneficial health effects attained through its positive regulation of a control molecule called SIRT1. Resveratrol activates SIRT1 in vitro and produces changes that mimic caloric restriction—the best-studied mechanism to maximize life span in living organisms.84 SIRT1 switches off production of many inflammatory cytokines that contribute to cancer promotion.85 When cells are co-cultured with resveratrol before exposure to alcohol metabolites, they produce many fewer inflammatory cytokines—the result of SIRT1 activation.85 Together all of these mechanisms contribute to resveratrol's potent anticancer effects.

Summary

A landmark 2011 study revealed that drinking alcohol may account for 1 out of 10 cancer cases in men and 1 in 30 for women. Even modest alcohol consumption was found to increase risk for most forms of cancer. This occurs owing to a little-known process in which your body converts alcohol into acetaldehyde, an officially classified carcinogen.

Acetaldehyde boosts cancer risk by inflicting oxidative stress that damages DNA, prevents DNA repair, and triggers a pro-inflammatory cascade.

You can help neutralize these cancer-inducing effects through a comprehensive nutritional regimen. These include plant-based compounds like silymarin from milk thistle extract, resveratrol, grape seed extract, and barley grass. Increasing intake of specific vitamins and minerals can help you restore those depleted from your body as a result of alcohol consumption, including selenium, vitamin B6 and folic acid.

It is especially important to take nutrients like benfotiamine, N-acetyl cysteine (NAC), vitamin C and SAMe before or while ingesting alcohol. If you forget, take these nutrients immediately after alcohol ingestion.

Table 3. Impact of Alcohol Drinking on Cancer Rates, 201188
  Men Women
Cancer Incidence Attributable to Alcohol Consumption (Total) 10% 3%
For Oral, Esophageal, and Tracheal Cancers 44% 25%
For Liver Cancer 33% 18%
For Colorectal Cancer 17% 4%
Female Breast Cancer 5%
Percentage of Total Alcohol-Related Cancers Attributable to Alcohol Consumption Greater than Recommended Upper Limit 19% 4%

If you have any questions on the scientific content of this article, please call a Life Extension® Health Advisor at 1-866-864-3027.

References

1. Available at: http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001940/ Accessed August 21, 2011.

2. Schutze M, Boeing H, Pischon T, et al. Alcohol attributable burden of incidence of cancer in eight European countries based on results from prospective cohort study. BMJ. 2011;342:d1584.

3. Druesne-Pecollo N, Tehard B, Mallet Y, et al. Alcohol and genetic polymorphisms: effect on risk of alcohol-related cancer. Lancet Oncol. 2009 Feb;10(2):173-80.

4. Juliano C, Cossu M, Rota MT, Satta D, Poggi P, Giunchedi P. Buccal tablets containing cysteine and chlorhexidine for the reduction of acetaldehyde levels in the oral cavity. Drug Dev Ind Pharm. 2011 Mar 31.

5. Brooks PJ, Theruvathu JA. DNA adducts from acetaldehyde: implications for alcohol-related carcinogenesis. Alcohol. 2005 Apr;35(3):187-93.

6. Poschl G, Seitz HK. Alcohol and cancer. Alcohol Alcohol. 2004 May-Jun;39(3):155-65.

7. Seitz HK, Homann N. The role of acetaldehyde in alcohol-associated cancer of the gastrointestinal tract. Novartis Found Symp. 2007;285:110-9; discussion 119-4, 198-9.

8. Seitz HK, Stickel F. Risk factors and mechanisms of hepatocarcinogenesis with special emphasis on alcohol and oxidative stress. Biol Chem. 2006 Apr;387(4):349-60.

9. Penning R, van Nuland M, Fliervoet LA, Olivier B, Verster JC. The pathology of alcohol hangover. Curr Drug Abuse Rev. 2010 Jun;3(2):68-75.

10. Yu HS, Oyama T, Isse T, et al. Formation of acetaldehyde-derived DNA adducts due to alcohol exposure. Chem Biol Interact. 2010 Dec 5;188(3):367-75.

11. Giovannucci E, Stampfer MJ, Colditz GA, et al. Folate, methionine, and alcohol intake and risk of colorectal adenoma. J Natl Cancer Inst. 1993 Jun 2;85(11):875-84.

12. Vasdev S, Wadhawan S, Ford CA, Parai S, Longerich L, Gadag V. Dietary vitamin B6 supplementation prevents ethanol-induced hypertension in rats. Nutr Metab Cardiovasc Dis. 1999 Apr;9(2):55-63.

13. Sellers TA, Kushi LH, Cerhan JR, et al. Dietary folate intake, alcohol, and risk of breast cancer in a prospective study of postmenopausal women. Epidemiology. 2001 Jul;12(4):420-8.

14. Winstanley MH, Pratt IS, Chapman K, et al. Alcohol and cancer: a position statement from Cancer Council Australia. Med J Aust. 2011 May 2;194(9):479-82.

15. Brien SE, Ronksley PE, Turner BJ, Mukamal KJ, Ghali WA. Effect of alcohol consumption on biological markers associated with risk of coronary heart disease: systematic review and meta-analysis of interventional studies. BMJ. 2011 Feb 22;342:d636.

16. Hendler RA, Ramchandani VA, Gilman J, Hommer DW. Stimulant and sedative effects of alcohol. Curr Top Behav Neurosci. 2011 May 11.

17. Negri E, Franceschi S, Bosetti C, et al. Selected micronutrients and oral and pharyngeal cancer. Int J Cancer. 2000 Apr 1;86(1):122-7.

18. Bulger EM, Helton WS. Nutrient antioxidants in gastrointestinal diseases. Gastroenterol Clin North Am. 1998 Jun;27(2):403-19

19. Alabaster O, Tang Z, Shivapurkar N. Dietary fiber and the chemopreventive modelation of colon carcinogenesis. Mutat Res. 1996 Feb 19;350(1):185-97.

20. Jedrychowski W, Steindorf K, Popiela T, et al. Risk of colorectal cancer from alcohol consumption at lower vitamin intakes. A hospital-based case-control study in Poland. Rev Environ Health. 2001 Jul-Sep;16(3):213-22.

21. Jedrychowski W, Steindorf K, Popiela T, et al. Alcohol consumption and the risk of colorectal cancer at low levels of micronutrient intake. Med Sci Monit. 2002 May;8(5):CR357-63.

22. Ha HL, Shin HJ, Feitelson MA, Yu DY. Oxidative stress and antioxidants in hepatic pathogenesis. World J Gastroenterol. 2010 Dec 28;16(48):6035-43.

23. Yang CS, Lu G, Ju J, Li GX. Inhibition of inflammation and carcinogenesis in the lung and colon by tocopherols. Ann N Y Acad Sci. 2010 Aug;1203:29-34.

24. Park Y, Spiegelman D, Hunter DJ, et al. Intakes of vitamins A, C, and E and use of multiple vitamin supplements and risk of colon cancer: a pooled analysis of prospective cohort studies. Cancer Causes Control. 2010 Nov;21(11):1745-57.

25. Sheweita SA, Sheikh BY. Can dietary antioxidants reduce the incidence of brain tumors? Curr Drug Metab. 2011 Mar 25.

26. Brozmanova J, Manikova D, Vlckova V, Chovanec M. Selenium: a double-edged sword for defense and offence in cancer. Arch Toxicol. 2010 Dec;84(12):919-38.

27. Kautiainen A, Tornqvist M, Olsson U. Effects of selenium deficiency on the formation and detoxification of endogenous electrophiles in rats. J Nutr Biochem. 2000 Sep;11(9):425-30.

28. Feng Y, Finley JW, Davis CD, Becker WK, Fretland AJ, Hein DW. Dietary selenium reduces the formation of aberrant crypts in rats administered 3,2'-dimethyl-4-aminobiphenyl. Toxicol Appl Pharmacol. 1999 May 15;157(1):36-42.

29. Ferguson LR, Karunasinghe N, Philpott M. Epigenetic events and protection from colon cancer in New Zealand. Environ Mol Mutagen. 2004;44(1):36-43.

30. Dey Sarkar P, Ramprasad N, Dey Sarkar I, Shivaprakash TM. Study of oxidative stress and trace element levels in patients with alcoholic and non-alcoholic coronary artery disease. Indian J Physiol Pharmacol. 2007 Apr-Jun;51(2):141-6.

31. Sakoda LC, Graubard BI, Evans AA, et al. Toenail selenium and risk of hepatocellular carcinoma mortality in Haimen City, China. Int J Cancer. 2005 Jul 1;115(4):618-24.

32. McKillop IH, Schrum LW. Alcohol and liver cancer. Alcohol. 2005 Apr;35(3):195-203.

33. Pascale R, Daino L, Garcea R, et al. Inhibition by ethanol of rat liver plasma membrane (Na+,K+)ATPase: protective effect of S-adenosyl-L-methionine, L-methionine, and N-acetylcysteine. Toxicol Appl Pharmacol. 1989 Feb;97(2):216-29.

34. Novitskiy G, Traore K, Wang L, Trush MA, Mezey E. Effects of ethanol and acetaldehyde on reactive oxygen species production in rat hepatic stellate cells. Alcohol Clin Exp Res. 2006 Aug;30(8):1429-35.

35. Klein-Schwartz W, Doyon S. Intravenous acetylcysteine for the treatment of acetaminophen overdose. Expert Opin Pharmacother. 2011 Jan;12(1):119-30.

36. Sprince H, Parker CM, Smith GG, Gonzales LJ. Protective action of ascorbic acid and sulfur compounds against acetaldehyde toxicity: implications in alcoholism and smoking. Agents Actions. 1975 May;5(2):164-73.

37. Vasdev S, Mian T, Longerich L, Prabhakaran V, Parai S. N-acetyl cysteine attenuates ethanol induced hypertension in rats. Artery. 1995;21(6):312-6.

38. Balakumar P, Rohilla A, Krishan P, Solairaj P, Thangathirupathi A. The multifaceted therapeutic potential of benfotiamine. Pharmacol Res. 2010 Jun;61(6):482-8.

39. Schmid U, Stopper H, Heidland A, Schupp N. Benfotiamine exhibits direct antioxidative capacity and prevents induction of DNA damage in vitro. Diabetes Metab Res Rev. 2008 Jul-Aug;24(5):371-7.

40. Ansari NA, Rasheed Z. Non-enzymatic glycation of proteins: from diabetes to cancer. Biomed Khim. 2010 Mar-Apr;56(2):168-78.

41. Ayazpoor U. Chronic alcohol abuse. Benfotiamine in alcohol damage is a must. MMW Fortschr Med. 2001 Apr 19;143(16):53.

42. Schupp N, Dette EM, Schmid U, et al. Benfotiamine reduces genomic damage in peripheral lymphocytes of hemodialysis patients. Naunyn Schmiedebergs Arch Pharmacol. 2008 Sep;378(3):283-91.

43. Folate, alcohol, methionine, and colon cancer risk: is there a unifying theme? Nutr Rev. 1994 Jan;52(1):18-20.

44. Dinsmore WW, McMaster D, Callender ME, Buchanan KD, Love AH. Trace elements and alcohol. Sci Total Environ. 1985 Mar 15;42(1-2):109-19.

45. Purohit V, Khalsa J, Serrano J. Mechanisms of alcohol-associated cancers: introduction and summary of the symposium. Alcohol. 2005 Apr;35(3):155-60.

46. Potter JD. Methyl supply, methyl metabolizing enzymes and colorectal neoplasia. J Nutr. 2002 Aug;132(8 Suppl):2410S-12S.

47. Hermann S, Rohrmann S, Linseisen J. Lifestyle factors, obesity and the risk of colorectal adenomas in EPIC-Heidelberg. Cancer Causes Control. 2009 Oct;20(8):1397-408.

48. Lu SC, Mato JM. Role of methionine adenosyltransferase and S-adenosylmethionine in alcohol-associated liver cancer. Alcohol. 2005 Apr;35(3):227-34.

49. Prasad AS, Beck FW, Snell DC, Kucuk O. Zinc in cancer prevention. Nutr Cancer. 2009;61(6):879-87.

50. Holguin F, Moss I, Brown LA, Guidot DM. Chronic ethanol ingestion impairs alveolar type II cell glutathione homeostasis and function and predisposes to endotoxin-mediated acute edematous lung injury in rats. J Clin Invest. 1998 Feb 15;101(4):761-8.

51. Powell CL, Bradford BU, Craig CP, et al. Mechanism for prevention of alcohol-induced liver injury by dietary methyl donors. Toxicol Sci. 2010 May;115(1):131-9.

52. Egner PA, Munoz A, Kensler TW. Chemoprevention with chlorophyllin in individuals exposed to dietary aflatoxin. Mutat Res. 2003 Feb-Mar;523-524:209-16.

53. Egner PA, Wang JB, Zhu YR, et al. Chlorophyllin intervention reduces aflatoxin-DNA adducts in individuals at high risk for liver cancer. Proc Natl Acad Sci U S A. 2001 Dec 4;98(25):14601-6.

54. Kensler TW, Egner PA, Wang JB, et al. Chemoprevention of hepatocellular carcinoma in aflatoxin endemic areas. Gastroenterology. 2004 Nov;127(5 Suppl 1):S310-8.

55. Ferguson LR, Philpott M, Karunasinghe N. Dietary cancer and prevention using antimutagens. Toxicology. 2004 May 20;198(1-3):147-59.

56. Fahey JW, Stephenson KK, Dinkova-Kostova AT, Egner PA, Kensler TW, Talalay P. Chlorophyll, chlorophyllin and related tetrapyrroles are significant inducers of mammalian phase 2 cytoprotective genes. Carcinogenesis. 2005 Jul;26(7):1247-55.

57. Yun CH, Son CG, Chung DK, Han SH. Chlorophyllin attenuates IFN-gamma expression in lipopolysaccharide-stimulated murine splenic mononuclear cells via suppressing IL-12 production. Int Immunopharmacol. 2005 Dec;5(13-14):1926-35.

58. Simonetti P, Ciappellano S, Gardana C, Bramati L, Pietta P. Procyanidins from Vitis vinifera seeds: in vivo effects on oxidative stress. J Agric Food Chem. 2002 Oct 9;50(21):6217-21.

59. Fan P, Lou H. Effects of polyphenols from grape seeds on oxidative damage to cellular DNA. Mol Cell Biochem. 2004 Dec;267(1-2):67-74.

60. Llopiz N, Puiggros F, Cespedes E, et al. Antigenotoxic effect of grape seed procyanidin extract in Fao cells submitted to oxidative stress. J Agric Food Chem. 2004 Mar 10;52(5):1083-7.

61. Lu Y, Zhao WZ, Chang Z, Chen WX, Li L. Procyanidins from grape seeds protect against phorbol ester-induced oxidative cellular and genotoxic damage. Acta Pharmacol Sin. 2004 Aug;25(8):1083-9.

62. Busserolles J, Gueux E, Balasinska B, et al. In vivo antioxidant activity of procyanidin-rich extracts from grape seed and pine (Pinus maritima) bark in rats. Int J Vitam Nutr Res. 2006 Jan;76(1):22-7.

63. El-Ashmawy IM, Saleh A, Salama OM. Effects of marjoram volatile oil and grape seed extract on ethanol toxicity in male rats. Basic Clin Pharmacol Toxicol. 2007 Nov;101(5):320-7.

64. Guo L, Wang LH, Sun B, et al. Direct in vivo evidence of protective effects of grape seed procyanidin fractions and other antioxidants against ethanol-induced oxidative DNA damage in mouse brain cells. J Agric Food Chem. 2007 Jul 11;55(14):5881-91.

65. Sano A, Yamakoshi J, Tokutake S, Tobe K, Kubota Y, Kikuchi M. Procyanidin B1 is detected in human serum after intake of proanthocyanidin-rich grape seed extract. Biosci Biotechnol Biochem. 2003 May;67(5):1140-3.

66. Ward NC, Croft KD, Puddey IB, Hodgson JM. Supplementation with grape seed polyphenols results in increased urinary excretion of 3-hydroxyphenylpropionic Acid, an important metabolite of proanthocyanidins in humans. J Agric Food Chem. 2004 Aug 25;52(17):5545-9.

67. Feher J, Lengyel G. Silymarin in the treatment of chronic liver diseases: past and future. Orv Hetil. 2008 Dec 21;149(51):2413-8.

68. Brandon-Warner E, Sugg JA, Schrum LW, McKillop IH. Silibinin inhibits ethanol metabolism and ethanol-dependent cell proliferation in an in vitro model of hepatocellular carcinoma. Cancer Lett. 2010 May 1;291(1):120-9.

69. Feher J, Lengyel G. Silymarin in the prevention and treatment of liver diseases and primary liver cancer. Curr Pharm Biotechnol. 2011 Apr 5.

70. Ralhan R, Pandey MK, Aggarwal BB. Nuclear factor-kappa B links carcinogenic and chemopreventive agents. Front Biosci (Schol Ed). 2009;1:45-60.

71. Rajkumar V, Guha G, Kumar RA. Antioxidant and anti-neoplastic activities of Picrorhiza kurroa extracts. Food Chem Toxicol. 2011 Feb;49(2):363-9.

72. Rastogi R, Saksena S, Garg NK, Kapoor NK, Agarwal DP, Dhawan BN. Picroliv protects against alcohol-induced chronic hepatotoxicity in rats. Planta Med. 1996 Jun;62(3):283-5.

73. Saraswat B, Visen PK, Patnaik GK, Dhawan BN. Ex vivo and in vivo investigations of picroliv from Picrorhiza kurroa in an alcohol intoxication model in rats. J Ethnopharmacol. 1999 Sep;66(3):263-9.

74. Rajeshkumar NV, Kuttan R. Inhibition of N-nitrosodiethylamine-induced hepatocarcinogenesis by Picroliv. J Exp Clin Cancer Res. 2000 Dec;19(4):459-65.

75. Rajeshkumar NV, Kuttan R. Protective effect of Picroliv, the active constituent of Picrorhiza kurroa, against chemical carcinogenesis in mice. Teratog Carcinog Mutagen. 2001;21(4):303-13.

76. Anand P, Kunnumakkara AB, Harikumar KB, Ahn KS, Badmaev V, Aggarwal BB. Modification of cysteine residue in p65 subunit of nuclear factor-kappaB (NF-kappaB) by picroliv suppresses NF-kappaB-regulated gene products and potentiates apoptosis. Cancer Res. 2008 Nov 1;68(21):8861-70.

77. McIntosh GH, Jorgensen L, Royle P. The potential of an insoluble dietary fiber-rich source from barley to protect from DMH-induced intestinal tumors in rats. Nutr Cancer. 1993;19(2):213-21.

78. McIntosh GH, Le Leu RK, Royle PJ, Young GP. A comparative study of the influence of differing barley brans on DMH-induced intestinal tumours in male Sprague-Dawley rats. J Gastroenterol Hepatol. 1996 Feb;11(2):113-9.

79. Jeong HJ, Jeong JB, Hsieh CC, Hernandez-Ledesma B, de Lumen BO. Lunasin is prevalent in barley and is bioavailable and bioactive in in vivo and in vitro studies. Nutr Cancer. 2010;62(8):1113-9.

80. Jeong HJ, Lam Y, de Lumen BO. Barley lunasin suppresses ras-induced colony formation and inhibits core histone acetylation in mammalian cells. J Agric Food Chem. 2002 Oct 9;50(21):5903-8.

81. Kanauchi O, Mitsuyama K, Andoh A, Iwanaga T. Modulation of intestinal environment by prebiotic germinated barley foodstuff prevents chemo-induced colonic carcinogenesis in rats. Oncol Rep. 2008 Oct;20(4):793-801.

82. Manzo-Avalos S, Saavedra-Molina A. Cellular and mitochondrial effects of alcohol consumption. Int J Environ Res Public Health. 2010 Dec;7(12):4281-304.

83. Yan Y, Yang J, Chen G, et al. Protection of resveratrol and its analogues against ethanol-induced oxidative DNA damage in human peripheral lymphocytes. Mutat Res. 2011 Apr 3;721(2):171-7.

84. Agarwal B, Baur JA. Resveratrol and life extension. Ann N Y Acad Sci. 2011 Jan;1215:138-43.

85. Shen Z, Ajmo JM, Rogers CQ, et al. Role of SIRT1 in regulation of LPS- or two ethanol metabolites-induced TNF-alpha production in cultured macrophage cell lines. Am J Physiol Gastrointest Liver Physiol. 2009 May;296(5):G1047-53.

86. Newcomb PA, Carbone PP. The health consequences of smoking. Cancer. Med Clin North Am. 1992 Mar;76(2):305-31.

87. Capewell S, Hayes DK, Ford ES, et al. Life-years gained among US adults from modern treatments and changes in the prevalence of 6 coronary heart disease risk factors between 1980 and 2000. Am J Epidemiol. 2009 Jul 15;170(2):229-36.

88. Cowling DW, Yang J. Smoking-attributable cancer mortality in California, 1979-2005. Tob Control. 2010 Apr;19 Suppl 1:i62-7.