Cancer prevention through your diet
Association of Art And Science, Roma June 2000
Epidemiological data has shown that diet can significantly affect your chances of getting cancer. The American Institute of Cancer Research has released some general guidelines for cancer prevention:
1. Choose a diet rich in a variety of plant-based foods.
2. Eat plenty of vegetables and fruits.
3. Maintain a healthy weight and be physically active.
4. Drink alcohol in moderation, if at all.
5. Select foods low in fat and salt.
6. Prepare and store foods safely.
And, of course - Do not smoke or use tobacco in any form. Between 25 and 30% of all cancer deaths in Europe are due to tobacco smoking.
About 50% of cancer incidence and 35% of cancer mortality in the U.S. is represented by cancers of the breast, prostate, pancreas, ovary, endometrium, and colon, which are associated with Western dietary habits. Cancer of the stomach, is also currently a major disease in the Far East, and is related to distinct, specific nutritional elements such as excessive salt intake. To achieve reduction in risk of certain cancers, diet must be optimized, primarily to reduce caloric intake and the fat component. The latter should be 20% or less of total caloric intake and fiber should be increased to 25-35 g per day for adults. One approach to achieving these goals is a diet designed around adequate fiber intake from grains, especially cereals, vegetables, legumes, and fruits, which thereby reduces both calorie and fat intake.
A variety of external factors interacting with genetic susceptibility influence the carcinogenesis process (process whereby a normal cell loses ability to stop dividing, and thereby keeps dividing into a tumour) (Fig 1).
Figure 1. The pathway whereby a normal cell (primary cell) can become cancerous.
External factors including oxidative compounds, electrophilic agents, and chronic infections may enhance genetic damage .Approximately 40 micronutrients are required in the human diet.
Deficiency of vitamins B12, folic acid, B6, niacin, C, or E, or iron, or zinc, appears to mimic radiation in damaging DNA by causing single- and double-strand breaks, oxidative lesions, or both. For example, 2 to 20 percent of the US population has a low intake (< 50% of the RDA) for each of these eight micronutrients ranges and upto 50% may be deficient in at least one of these micronutrients.
Folate deficiency occurs in approximately 10% of the US population, and in a much higher percentage of the poor. Folate deficiency causes extensive incorporation of uracil into human DNA (4 million/cell), leading to chromosomal breaks. This mechanism is the likely cause of the increased cancer risk, and perhaps the cognitive defects associated with low folate intake. Some evidence, and mechanistic considerations, suggest that vitamin B12 and B6 deficiencies also cause high uracil and chromosome breaks. Maintaining adequate levels of serum folate or moderately increasing folate intakes from dietary sources and vitamin supplements can significantly reduce the risk of pancreatic and breast cancer, respectively, especially in smokers and people consuming alcohol.
Vitamin D has been linked to reduction of certain types of cancer. Epidemiological data suggest that intake of 800 IU/day of vitamin D may be associated with enhanced survival rates among breast cancer cases as well as to reduction of incidence and mortality rates from colon cancer.
Diets rich in whole and unrefined foods, like whole grains, dark green and yellow/orange-fleshed vegetables and fruits, legumes, nuts and seeds, contain high concentrations of antioxidant phenolics, fibers and numerous other phytochemicals that provide protection against chronic diseases as well as colon cancer.
Micronutrient deficiency may explain, in good part, why the quarter of the population that eats the fewest fruits and vegetables (five portions a day is advised) has approximately double the cancer rate for most types of cancer when compared to the quarter with the highest intake. Eighty percent of American children and adolescents and 68% of adults do not eat five portions a day.
Polyunsaturated fatty acids
A number of nutritional compounds are being shown to have anti-cancer properties. For example omega 3 fatty acids EPA and DHA (found in fish oil for example) are in this group. An inverse association between prostate cancer and serum n-3 PUFAs levels appears to exist.
Example of typical experimental data for anti-cancer effects
Cancer researchers have developed a number of experimental strategies to search for compounds that might fight cancer. These experimental models have to show if a compound can increase death of cancerous cells (apoptosis) or limit their proliferation.
Researchers use tumoural cells (cell lines) incubated and kept alive in artificial mediums to test these drugs and once there is a potential anti-cancer substance experiments are repeated in small animals, like mice and rats.
The effect of dietary fish oil on colonic crypt cell apoptosis and proliferation was examined in experiments with male rats, 24 and 48 h after administration of 1,2-dimethylhydrazine (DMH), influence of DMH on the induction of aberrant crypt foci (ACF) in the distal colon was assessed. Rats fed a high-fat semi-synthetic diet containing corn oil (CO) were given DMH (30 mg/kg body wt) or a sham (placebo) injection of EDTA/NaCl. Animals were then fed either the CO diet or a diet in which fish oil (EPA 18.7%; DHA 8%) was substituted for corn oil. Consumption of the fish oil diet was associated with increased apoptotic cell death (p < 0.001) and suppression of proliferation (p < 0.05) in colonic crypts both 24 and 48 h after DMH. In a second experiment, animals were given three injections of DMH or sham injections of carrier at weekly intervals. For 48 h after each injection animals were fed either the CO or FO diet, but otherwise maintained on the CO throughout. The number and crypt multiplicity of ACF in the distal colon were determined after 18 weeks, and animals given the FO diet for the 48 h period following carcinogen administration were found to have significantly fewer ACF than rats fed the CO diet (p < 0.05).
The data demonstrate that the fatty acid composition of the diet is an important determinant in the induction of carcinogenesis by DMH. The proliferative and apoptotic response of the colonic crypt to carcinogen and fish oil, coupled with the reduced incidence of ACF, suggest n-3 PUFA can protect against the carcinogenic effects of DMH by mediating changes in the balance proliferation and cell death.
An increased ratio of n-3 to n-6 polyunsaturated fatty acids (PUFAs) in the diet has also been shown to inhibits the growth of the rat mammary cancer model. There is also evidence that members of the n-3 PUFA series can inhibit the growth of human breast cancer cells both in vitro and in explants. Clinical trials of supplementary n-3 PUFAs in conjunction with a reduced fat intake have been proposed for breast cancer prevention. It is postulated that further dietary supplementation with vitamin E and a retinoid is likely to increase the effectiveness of such a diet.
In addition, various hormonal factors which influence growth and differentiation are critically important in the carcinogenic process. Diet and nutrition can influence these processes directly in the gastrointestinal tract by providing bioactive compounds to specific tissues via the circulatory system, or by modulating hormone levels. Differences in certain dietary patterns among populations explain a substantial proportion of cancers of the colon, prostate and breast. These malignancies are largely influenced by a combination of factors related to diet and nutrition. Their causes are multifactorial and complex, but a major influence is the widespread availability of energy-dense, highly processed and refined foods that are also deplete in fiber. These dietary patterns in combination with physical inactivity contribute to obesity and metabolic consequences such as increased levels of IGF-1, insulin, estrogen, and possibly testosterone. These hormones tend to promote cellular growth. For prostate cancer, epidemiological studies consistently show a positive association with high consumption of milk, dairy products, and meats. These dietary factors tend to decrease 1.25(OH)2 vitamin D, a cell differentiator, and low levels of this hormone may enhance prostate carcinogenesis. While the nutritional modulation of growth-enhancing and differentiating hormones is likely to contribute to the high prevalence of breast, colorectal, prostate, and several other cancers in the Western world, these cancers are relatively rare in less economically developed countries, where malignancies of the upper gastrointestinal tract are quite common. The major causes of upper gastrointestinal tract cancers are likely related to various food practices or preservation methods other than refrigeration, which increase mucosal exposure to irritants or carcinogens.
Role of free radicals from intracellular energy producing organelles called mitochondria in cell damage
Common micronutrient deficiencies are likely to damage cellular DNA by the same mechanism as radiation and many carcinogenic chemicals, and appear to be orders of magnitude more important, and should be taken into account. Remedying micronutrient deficiencies is likely to lead to a major improvement in health and an increase in longevity at low cost. The process of aging appears to be due, in good part, to the oxidants (free radicals) produced by mitochondria as by-products of normal metabolism. In old rats mitochondrial membrane potential, cardiolipin levels, respiratory control ratio, and overall cellular O2 consumption are lower than in young rats, and the level of oxidants (per unit O2) is higher. The level of mutagenic aldehydes from lipid peroxidation is also increased. Ambulatory activity declines markedly in old rats. Feeding old rats the normal mitochondrial metabolites acetyl carnitine and lipoic acid for a few weeks, restores mitochondrial function, lowers oxidants to the level of a young rat, and increases ambulatory activity. Thus, these two metabolites can be considered necessary for health in old age and are therefore conditional micronutrients. This restoration suggests a plausible mechanism: with age-increased oxidative damage to proteins and lipid membranes causes a deformation of structure of key enzymes, with a consequent lessening of affinity (Km) for the enzyme substrate; an increased level of the substrate restores the velocity of the reaction, and thus restores function.
Malnutrition is also common during treatment or due to cancer itself e.g. gastroesophageal cancer. For example, malnutrition is common in patients with esophageal and esophagogastric cancer. Compared to patients with other digestive and extradigestive neoplasia, the highest incidence (about 80%) is found in those with esophageal cancer. Malnutrition is associated with postoperative complications, increased morbidity, and prolonged hospital stays.
Nitrosamines have been suspected in the etiology of esophageal/gastric cardia cancer in the high incidence area of Linxian of the Henan Province in northern China, but marginal deficiencies in riboflavin, vitamins A and C, and other micronutrients may also be involved. A joint U.S.-China nutritional intervention study with investigators from the Cancer Institute of the Chinese Academy of Medical Sciences and the U.S. National Cancer Institute tested the effects of the following four combinations of nutrients on 29,584 subjects in an eight-group design: 1) retinol and zinc; 2) riboflavin and niacin; 3) vitamin C and molybdenum; and 4) vitamin E, beta-carotene and selenium. Supplementation with Group 4 nutrients significantly decreased mortality rate from stomach cancer, primarily due to the decrease in deaths resulting from adenocarcinomas of the gastric cardia; it lowered the total mortality rate and showed signs of other beneficial effects. Another study of nutrition and gastric cancer in a high incidence area of Linqu of the Shangdong province in northern China (in collaboration with the Beijing Institute for Cancer Research and the U. S. National Institutes of Health) found significantly lower serum concentrations of vitamin C and beta-carotene among individuals with intestinal metaplasia; an intervention trial with vitamins C and E and selenium (combined) is ongoing in Linqu.
In order to improve clinical outcomes and the quality of life for patients with esophageal and esophagogastric cancers, the extent of malnutrition must be identified and treated.
A diet that contains less than the normal daily calories has been found to delay the effects of aging and to increase the life span of experimental animals. Such restrictions in food intake has also been shown to reduce the initiation and formation of tumours in animals. The mechanism for these protective effects on aging and cancer of calorie restriction are not known but current research is focusing in on this phenomenon as another potential way of fighting cancer and the ill-effects of aging.
Overall a healthy nutrition with additional micronutrients keeps the immune system strong and prevents free radical damage, factors that limit possibility of cancer.
Nutrition as therapy - Importance of Proper diet
Vitamins, Minerals and Other Supplements
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http://www.uicc.org/nutrition/ Cancer and nutrition
Cancer Research Institute - offers an excellent introduction to cancer immunotherapy including history, causes, treatments, and statistics.
Coley's Toxins/Issel's Fever Therapy - gives a brief history behind the early use of William Coley's immunotherapy for cancer patients. For more information on the connection between Coley, the Rockefellers, and cancer research, see chapter 1 of A Commotion in the Blood by Stephen Hall.
Immune Attack on Cancer - a detailed account of how researchers are helping the immune system to rout malignancies. From Science News Online.
Oncolink - a rich source of information on many aspects of the genetics of cancer. Maintained by the University of Pennsylvania Cancer Center.
National Cancer Institute - a prime jumping-off point for information. NCI also runs CancerNet, a site updated monthly that provides information geared to three categories of the curious: patients and the public; health professionals; and basic researchers.
http://cancer.med.upenn.edu/cancer_news/cutting_edge.html highlight various emerging cancer technologies that are not ready for public use but hold promise for the future
http://www.fda.gov/cder/cancer/index.htm FDA Oncology Tools web site! Oncology Tools contains a variety of information related to cancer and approved cancer drug therapies