For detailed information on the studies summarised above, continue reading.
Please note this describes published clinical studies and therefore contains information of a scientific nature.
Ascorbic acid is a essential nutrient found primarily in fruits and vegetables and is a potent antioxidant. In a recent study it was shown trigger apoptosis (pre-programmed cell death) in cultured gastric cancer cells (Ha, et al. 2009). It is also thought to help in the prevention of gastric cancer by decreasing gastric oxidative stress which prevents DNA damage that can lead to the formation of cancerous cells (Oliveira, et al. 2003); by helping to eradicate Helicobacter pylori, the bacteria that causes gastric ulcers which can lead to cancer (Sezikli, et al. 2009; Zojaji, et al. 2009); and by modulating the immune system to prevent chronic inflammation (Sun, et al. 2005; Ernst 1999).
Alpha tocopherol is a fat-soluble antioxidant found in some vegetables, eggs, milk, and some nuts. Tocopherols have been shown to significantly inhibit behaviours in cultured gastric cancer cells that result in the development of metastasis and the invasion of these cells into tissues in the body (Liu, et al. 2009), as well as trigger their death directly (Sun, et al. 2009). Alpha tocopherol has also been shown in animal models (Sugimoto, et al. 2006) to significantly protect against gastric damage and ease inflammation as a result of Helicobacter pylori infection. In addition, alpha tocopherol has the ability in animal models to directly trigger gastric cell death and inhibit cellular proliferation (Olguín-Martínez, et al. 2006).
Beta-carotene is a precursor to vitamin A, and found in high concentrations in orange vegetables, some green leafy vegetables, and some oils. It is known trigger apoptosis and DNA damage in cultured gastric cancer cells (Jang, et al. 2009). It can also protect against gastrointestinal damage (Mózsik, et al. 1998). Beta-carotene combined with antioxidants including ascorbic acid and alpha tocopherol also significantly protects against infection with Helicobacter pylori and gastritis (Sjunnesson, et al. 2001).
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Clinical Studies Relevant To This Nutraceutical
Treatment of Gastric Cancer
In a one study (Correa, et al. 2000), 852 individuals, many with precursors of gastric cancer and all at high risk of developing new stomach tumours, were given either anti-Helicobacter therapy (the standard 14-day treatment used to kill Helicobacter pylori, the bacteria that causes the gastric ulcers which lead to cancer), or ascorbic acid daily, or beta-carotene daily, or combinations of all three. After six years, patients in this study taking any one of these three treatments were on average 3 times more likely to have had "histologic regression" (when cancerous cells or tissues in the stomach return to a more normal, non-cancerous appearance) than those patients taking a placebo, and patients taking a combination of these three treatments were three to five times more likely to have histologic regression (however it is important to note that some of the combinations were not statistically significant despite the strong trend towards increased rates of regression). Likewise in a similar study (Mannick, et al. 1996) which included 103 patients, daily ascorbic acid and beta-carotene for 4-12 months augmented the effect of the anti-Helicobacter therapy, increasing the percentage of patients able to clear the infection, and also significantly decreasing the oxidative damage which leads to the formation of new cancer cells.
Two other large studies have shown less clear effects. While one study (Plummer, et al. 2007) suggested that beta-carotene and ascorbic acid tended to have a beneficial effect on the regression and progression of pre-cancerous gastric lesions (with the 1383 patients taking beta-carotene, ascorbic acid, and alpha tocopherol daily having an average 25% decrease in progression, and a 30% increase in regression of their pre-cancerous lesions and also a small decrease in the rates of Helicobacter infection), in this case these outcomes did not reach statistical significance. Likewise, a large study including 29,584 participants (Blot, et al. 1993) over >5 years, showed that there were 24.7% less cancer deaths in individuals taking ascorbic acid, beta-carotene, and alpha tocopherol daily (in addition to molybdenum and selenium) compared to those taking a placebo. However, only the supplement containing beta-carotene showed a significantly beneficial effect on mortality from gastric cancer specifically - with a 23% decrease in death from gastric cancer in patients taking the supplement for at least one year.
Finally, two studies (Omenn, et al. 1996; ATBC Group 1994) presented evidence that very high doses of beta-carotene increase the risk of lung cancer specifically in regular cigarette smokers. It is thought that cigarette smoke increases the asymmetric cleavage of beta-carotene, which in turn decreases the level of the oxidised form of Vitamin A (retinoic acid), which can promote lung cancer cell proliferation. Although a later study (Hennekens, et al. 1996) disputed these findings, in the interests of caution we would strongly recommend that current smokers do not take any supplement containing beta-carotene.
Prevention of Gastric Cancer
A number of clinical trials have been undertaken to determine whether ascorbic acid, beta-carotene, and alpha-tocopherol have protective effects against gastric cancer. Combining 10 of these independent clinical studies into a single analysis which included 1057 patients with oesophageal cancer and 644 patients with gastric cancer (Kubo, et al. 2007), it was shown that individuals with a high intake of ascorbic acid were 26% less likely to develop gastric cancer and 51% less likely to develop oesophageal cancer than those who had a low intake. Likewise, those with a high intake of beta-carotene were 43% less likely to get gastric cancer and 54% less likely to get oesophageal cancer than those who had a low intake. A similar recent independent study (Pelucchi, et al. 2009) which in addition looked at the effects of alpha tocopherol on 230 gastric cancer patients and 547 matched controls showed similar results, demonstrating that beta-carotene and alpha tocopherol both significantly protected against gastric cancer, whereas the 17 other micronutrients analysed in the same study had no significant effect. In contrast to the previously mentioned meta-analysis of 10 studies however, in this case the protective effect of ascorbic acid did not reach statistical significance, although there did remain a trend towards protection against gastric cancer in patients consuming the highest rates of ascorbic acid consumption, with these individuals having on average a 33% lower risk of gastric cancer than control patients who had a lower intake.
Other Known Effects
Ascorbic acid, beta-carotene, and alpha tocopherol are important micronutrients for humans and have a range of other important roles in the body.
Ascorbic acid is required for a range of essential metabolic reactions, and is a strong antioxidant. Antioxidants neutralize free radicals, thereby preventing oxidative stress which can cause cardiovascular diseases, hypertension, chronic inflammatory diseases and diabetes, among other things. Some scientific evidence also suggests it has a beneficial role on the immune system, asthma, ischemic heart disease, and stroke prevention, however further work is ongoing to determine this conclusively.
Beta-carotene is also an antioxidant and is a precursor of Vitamin A. Vitamin A is required for normal bone development, functioning of the reproductive system, and cellular growth and proliferation. In addition there is some weak scientific evidence to suggest that beta-carotene is also beneficial for increasing cognitive performance and memory, immune system enhancement, and decreasing the severity of osteoarthritis.
Alpha tocopherol is also an important antioxidant with many functions within the body. Deficiency of alpha tocopherol can lead to neurological problems and anaemia. There is some limited evidence that alpha tocopherol may protect against Parkinson's disease, glaucoma, and blood clots, and when combined with other antioxidants such as ascorbic acid, may be protective against age-related macular degeneration.
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We would highly recommend that anyone interested in researching these nutritional supplements or prostate cancer further look at the main database of scientific and clinical studies, PubMed. It is free to search and view abstracts from millions of scientific studies published in peer-reviewed scientific journals over the past several decades. Full tutorials and help using PubMed can be found here. While they are generally of a technical nature and intended for a scientific/medical professional audience, non-specialists should also find them extremely useful.
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Ha YM, Park MK, Kim HJ, Seo HG, Lee JH, Chang KC. Cancer Lett. 2009 May 8;277(1):48-54. High concentrations of ascorbic acid induces apoptosis of human gastric cancer cell by p38-MAP kinase-dependent up-regulation of transferrin receptor.
Poulter JM, White WF, Dickerson JW. Acta Vitaminol Enzymol. 1984;6(3):175-82. Ascorbic acid supplementation and five year survival rates in women with early breast cancer.
Oliveira CP, Kassab P, Lopasso FP, Souza HP, Janiszewski M, Laurindo FR, Iriya K, Laudanna AA. World J Gastroenterol. 2003 Mar;9(3):446-8. Protective effect of ascorbic acid in experimental gastric cancer: reduction of oxidative stress.
Sun YQ, Girgensone I, Leanderson P, Petersson F, Borch K. Helicobacter. 2005 Feb;10(1):33-42. Effects of antioxidant vitamin supplements on Helicobacter pylori-induced gastritis in Mongolian gerbils.
Sezikli M, Cetinkaya ZA, Sezikli H, Güzelbulut F, Tiftikçi A, Ince AT, Gökden Y, Yaşar B, Atalay S, Kurdaş OO. Helicobacter. 2009 Aug;14(4):280-5. Oxidative stress in Helicobacter pylori infection: does supplementation with vitamins C and E increase the eradication rate
Zojaji H, Talaie R, Mirsattari D, Haghazali M, Molaei M, Mohsenian N, Derakhshan F, Zali MR. Dig Liver Dis. 2009 Sep;41(9):644-7. The efficacy of Helicobacter pylori eradication regimen with and without vitamin C supplementation.
Mannick EE, Bravo LE, Zarama G, Realpe JL, Zhang XJ, Ruiz B, Fontham ET, Mera R, Miller MJ, Correa P. Cancer Res. 1996 Jul 15;56(14):3238-43. Inducible nitric oxide synthase, nitrotyrosine, and apoptosis in Helicobacter pylori gastritis: effect of antibiotics and antioxidants.
Ernst P. Aliment Pharmacol Ther. 1999 Mar;13 Suppl 1:13-8. Review article: the role of inflammation in the pathogenesis of gastric cancer.
Plummer M, Vivas J, Lopez G, Bravo JC, Peraza S, Carillo E, Cano E, Castro D, Andrade O, Sánchez V, Garcia R, Buiatti E, Aebischer C, Franceschi S, Oliver W, Muñoz N. J Natl Cancer Inst. 2007 Jan 17;99(2):137-46. Chemoprevention of precancerous gastric lesions with antioxidant vitamin supplementation: a randomized trial in a high-risk population.
Blot WJ, Li JY, Taylor PR, Guo W, Dawsey S, Wang GQ, Yang CS, Zheng SF, Gail M, Li GY, et al. J Natl Cancer Inst. 1993 Sep 15;85(18):1483-92. Nutrition intervention trials in Linxian, China: supplementation with specific vitamin/mineral combinations, cancer incidence, and disease-specific mortality in the general population.
Correa P, Fontham ET, Bravo JC, Bravo LE, Ruiz B, Zarama G, Realpe JL, Malcom GT, Li D, Johnson WD, Mera R. J Natl Cancer Inst. 2000 Dec 6;92(23):1881-8. Chemoprevention of gastric dysplasia: randomized trial of antioxidant supplements and anti-Helicobacter pylori therapy.
Liu HK, Wang Q, Li Y, Sun WG, Liu JR, Yang YM, Xu WL, Sun XR, Chen BQ. J Nutr Biochem. 2009 Feb 4. Inhibitory effects of gamma-tocotrienol on invasion and metastasis of human gastric adenocarcinoma SGC-7901 cells.
Pelucchi C, Tramacere I, Bertuccio P, Tavani A, Negri E, La Vecchia C. Ann Oncol. 2009 Jan;20(1):160-5. Dietary intake of selected micronutrients and gastric cancer risk: an Italian case-control study.
Sun W, Xu W, Liu H, Liu J, Wang Q, Zhou J, Dong F, Chen B. J Nutr Biochem. 2009 Apr;20(4):276-84. gamma-Tocotrienol induces mitochondria-mediated apoptosis in human gastric adenocarcinoma SGC-7901 cells.
Jang SH, Lim JW, Kim H. Ann N Y Acad Sci. 2009 Aug;1171:156-62. Mechanism of beta-carotene-induced apoptosis of gastric cancer cells: involvement of ataxia-telangiectasia-mutated.
Kubo A, Corley DA. Am J Gastroenterol. 2007 Oct;102(10):2323-30; quiz 2331. Epub 2007 Jun 20. Meta-analysis of antioxidant intake and the risk of esophageal and gastric cardia adenocarcinoma.
Omenn GS, Goodman GE, Thornquist MD, Balmes J, Cullen MR, Glass A, Keogh JP, Meyskens FL, Valanis B, Williams JH, Barnhart S, Hammar S. N Engl J Med. 1996 May 2;334(18):1150-5. Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease.
The Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group. N Engl J Med. 1994 Apr 14;330(15):1029-35. The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers.
Hennekens CH, Buring JE, Manson JE, Stampfer M, Rosner B, Cook NR, Belanger C, LaMotte F, Gaziano JM, Ridker PM, Willett W, Peto R. N Engl J Med. 1996 May 2;334(18):1145-9. Lack of effect of long-term supplementation with beta carotene on the incidence of malignant neoplasms and cardiovascular disease.
Sugimoto N, Yoshida N, Nakamura Y, Ichikawa H, Naito Y, Okanoue T, Yoshikawa T. Biofactors. 2006;28(1):9-19. Influence of vitamin E on gastric mucosal injury induced by Helicobacter pylori infection.
Olguín-Martínez M, Mendieta-Condado E, Contreras-Zentella M, Escamilla JE, Aranda-Fraustro A, El-Hafidi M, Hernández-Muñoz R. Free Radic Biol Med. 2006 Oct 15;41(8):1325-37. Rate of oxidant stress regulates balance between rat gastric mucosa proliferation and apoptosis.
Mózsik G, Bódis B, Karádi O, Király A, Nagy L, Rumi G, Süto G, Szabó I, Vincze A. Inflammopharmacology. 1998;6(1):27-40. Cellular mechanisms of beta-carotene-induced gastric cytoprotection in indomethacin-treated rats.
Sjunnesson H, Sturegård E, Willén R, Wadström T. Comp Med. 2001 Oct;51(5):418-23. High intake of selenium, beta-carotene, and vitamins A, C, and E reduces growth of Helicobacter pylori in the guinea pig.