Processed Foods and Health (includes food additives)
FOOD PROCESSING INVOLVES THE USE OF TECHNIQUES AND SYNTHETIC ADDITIVES that help to prolong product shelf life, lower manufacturing costs, and create new products not found in nature.
Preservation of foods using salt and smoking or sun drying had been used for thousands of years, but in the nineteenth century, the technology of processing emerged in the form of tinning and canning food to serve the needs of large standing armies. Product success in this arena led to wider consumer acceptance of substituting processed goods for fresh, natural foods. Because processed foods reduce or remove many nutrients essential to human health, the products are often referred to in this day and age as “empty” calories.
Typical food additives in processed products include artificial colorings and preservatives; sweeteners (such as aspartame); flavor enhancers (such as MSG); chemical fat substitutes (such as olestra); and synthetic substitutes for natural oils (such as partially hydrogenated oil, added to at least forty thousand food products, which contains high levels of trans fats that contribute to heart disease by elevating “bad” cholesterol and reducing “good” cholesterol). Another entire category of processed foods is the refined grains typified by white bread and sugary low-fiber cereals.
As you can see from the studies below, processed foods and their additives cause a wide range of documented health problems for humans, everything from allergic reactions, asthma, anxiety, hyperactivity, and fatigue, to more serious ailments like cancer, heart disease, and diabetes.
Cancer and non-cancer health effects from food contaminant exposures for children and adults in California: a risk assessment. Vogt R, et al. Environ Health. 2012 Nov 9;11:83. Key Finding: “We estimated exposure to multiple food contaminants based on dietary data from 207 preschool-age children (2-4 years), 157 school-age children (5-7 years), and 466 parents of young children, and 149 older adults. We compared exposure estimates for eleven toxic compounds based on food frequency data by age group. Cancer benchmark levels were exceeded by all children (100%) for arsenic, dieldrin, DDE, and dioxins. Non-cancer benchmarks were exceeded by >95% of preschool-age children for acrylamide. Preschoolage children had significantly higher estimated intakes of 6 of 11 compounds compared to school-age children. Strategies to reduce risk include consuming less animal foods (meat, dairy and fish) and lower quantities of chips, crackers and other processed carbohydrate foods to reduce acrylamide intake.”
Association of Western and traditional diets with depression and anxiety in women. Jacka FN, et al. Am J Psychiatry. 2010 Mar;167(3):305-11. Key Finding: “Key biological factors that influence the development of depression are modified by diet This study examined the extent to which the high-prevalence mental disorders are related to habitual diet in 1,046 women ages 20-93 years randomly selected from the population. A “western” diet of processed or fried foods, refined grains, sugary products, and beer was associated with higher odds for major depression and anxiety disorders. These results demonstrate an association between habitual diet quality and the high-prevalence mental disorders.”
Meat consumption and prospective weight change in participants of the EPIC-PANACEA study. Vergnaud AC, et al. Am J Clin Nutr. 2010 Aug;92(2):398-407. Key Finding: “A total of 103,455 men and 270,348 women aged 25-70 y were recruited in 10 European countries. Diet was assessed at baseline with the use of a country-specific validated questionnaire. Total meat consumption was positively associated with weight gain in men and women, in normal-weight and overweight subjects, and in smokers and nonsmokers. Positive associations were observed for red meat, poultry, and processed meat.”
Correlates of dietary energy sources with cardiovascular disease risk markers in Mexican school-age children. Perichart-Perera O, et al. J Am Diet Assoc. 2010 Feb;110(2):253-60. Key Finding: “A positive association was observed between glucose and diastolic blood pressure with the intake of soft drinks/sweetened beverages, insulin concentrations and the intake of white (processed) bread, and triglyceride concentrations with the intake of added fats.”
High processed meat consumption is a risk factor of type 2 diabetes in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention study. Mannisto S. Kontto J, et al. Br J Nutr. 2010 Jun;103(12):1817-22. Key Finding: “Up to 12 years of followup, 1,098 incident cases of diabetes were diagnosed from 24,845 participants. High total meat consumption was a risk factor of type 2 diabetes, as was processed meat.”
The association of general and central obesity with major dietary patterns of adult women living in Tehran, Iran. Rezazadeh A, Rashidkhani B. J Nutr Sci Vitaminol (Tokyo) 2010;56(2):132-8. Key Finding: “A cross-sectional study was conducted in Tehran, Iran, with 460 women aged 20-50 y. Dietary intake in the previous year was collected by a semi-quantitative food frequency questionnaire. Our data showed that a dietary pattern high in processed meats, soft drinks, sweets, refined grains, snacks and processed juice might be positively associated with obesity.”
Dietary factors and the risks of oesophageal adenocarcinoma and Barrett’s oesophagus. Kubo A, et al. Nutr Res Rev. 2010 Jul 13: 1-17. Key Finding: “Patients at higher risk for Barrett’s oesophagus and oesophageal adenocarcinoma may benefit by reducing their intake of red meat and other processed food items.”
Red and processed meat consumption and risk of incident coronary heart disease, stroke, and diabetes mellitus: a systematic review and meta-analysis. Micha R, et al. Circulation. 2010 Jun 1;121(21):2271-83. Key Finding: “We performed a systematic review of 20 studies that met inclusion criteria, including 17 prospective cohorts and 3 case-control studies. Processed meat intake was associated with 42% higher risk of coronary heart disease, a 19% higher risk of diabetes mellitus. Consumption of red and processed meat were not associated with stroke, but only 3 studies evaluated these relationships.”
Does consumption of processed foods explain disparities in the body weight of individuals? The case of Guatemala. Asfaw A. Health Econ. 2009 Dec 22 {Epub ahead of print}. Key Finding: “This study examines the contribution of processed foods consumption to the prevalence of overweight/obesity in Guatemala. These findings suggest that increasing shares of partially and highly processed foods from the total consumption expenditure could be one of the major risk factors for the high prevalence of overweight/obesity in the country.”
Consumption and health effects of trans fatty acids: a review. Teegala SM, et al. J AOAC Int. 2009 Sep-Oct;92(5):1250-7. Key Finding: “Consumption of industrially produced trans fatty acids remains high in many populations, particularly in developing nations where partially hydrogenated vegetable oils are frequently used for home cooking and among individuals in developed countries having high intakes of bakery or processed foods. Well-controlled observational studies and randomized trials indicate that trans fatty acids consumption adversely affects multiple risk factor for chronic diseases, including numerous blood lipids and lipoproteins, systemic inflammation, endothelial dysfunction, and possibly insulin resistance, diabetes, and adiposity. Consistent evidence from prospective observational studies of habitual trans fatty acid consumption and retrospective observational studies using trans fatty acid biomarkers indicates that trans fatty acid consumption increases risk of clinical coronary heart disease.”
Trans fatty acids – effects on systemic inflammation and endothelial function. Mozaffarian D. Atheroscler Suppl. 2006 May;7(2):29-32. Key Finding: “Consumption of trans fatty acids predicts higher risk of coronary heart disease, sudden death, and possibly diabetes mellitus. These associations are greater than would be predicted by effects of trans fatty acids on serum lipoproteins alone. Systemic inflammation and endothelial dysfunction may be involved. Activation of inflammatory responses and endothelial dysfunction may represent important mediating pathways between trans fatty acids consumption and risk of coronary heart disease, sudden death, and diabetes.”
Intake of trans fatty acids and risk of coronary heart disease among women. Willett WC. Stampfer MJ, et al. Lancet 1993 Mar 6;34(8845):581-5. Key Finding: “Trans isomers of fatty acids, formed by the partial hydrogenation of vegetable oils to produce margarine and vegetable shortening, increase the ratio of plasma low-density-lipoprotein to high-density-lipoprotein cholesterol, so it is possible that they adversely influence risk of coronary heart disease (CHD). To investigate this possibility, we studied dietary data from 85,095 participants in the Nurses’ Health Study. During 8 years of follow-up, there were 431 new CHD. Intake of trans isomers was directly related to risk of CHD. Intakes of foods that are major sources of trans isomers (margarine, cookies, biscuits, cake and white bread) were each significantly associated with higher risks of CHD.”
Diet index-based and empirically derived dietary patterns are associated with colorectal cancer risk. Miller PE, Lazarus P, et al. J Nutr. 2010 Jul;140(7):1267-73. Key Finding: “The study included 431 incident colorectal cancer cases and 726 healthy controls. A meat, potatoes, and refined grains dietary pattern was positively associated with colorectal cancer risk in women and there was a suggestion of a positive association among men.”
Chronic intake of potato chips in humans increases the production of reactive oxygen radicals by leukocytes and increases plasma C-reactive protein: a pilot study. Naruszewicz M, et al. Am J Clin Nutr. 2009 Mar;89(3):773-7. Key Finding: “Relatively high concentrations of acrylamide in commonly ingested food products, such as French fries, potato chips, or cereals, may constitute a potential risk of human health. The objective of this pilot study was to investigate the possible connection between chronic ingestion of acrylamide-containing potato chips and oxidative stress or inflammation. Fourteen healthy volunteers were given 160 g of potato chips daily for 4 wk. An increase in acrylamide-hemoglobin adducts in blood was found in all the study subjects. These novel findings seem to indicate that chronic ingestion of acrylamide-containing products induces a proinflammatory state, a risk factor for progression of atherosclerosis.”
Food groups and renal cell carcinoma: results from a case-control study. Grieb SM, et al. J Am Diet Assoc. 2009 Apr;109(4):656-67. Key Finding: “This study used 335 incident cases identified from hospital records and the Florida cancer registry, and 337 population controls matched by age, sex and race. Eating habits were assessed through the use of the 70-item Block food frequency questionnaire. Increased risk of renal cell carcinoma was observed among all subjects and among women with increased consumption of red meat. White bread consumption increased renal cell carcinoma risk among women only, as did total dairy consumption.”
Food intake patterns associated with incident type 2 diabetes: the Insulin Resistance Atherosclerosis Study. Liese AD, et al. Diabetes Care. 2009 Feb;32(2):263-8. Key Finding: “The cohort included 880 middle-aged adults initially free of diabetes. At the 5-year follow-up, 144 individuals had developed diabetes. High intake of the food groups red meat, low-fiber bread and cereal, fried potatoes, eggs, cheese and cottage cheese was positively associated with both biomarkers of type 2 diabetes.”
Dietary patterns and risk of mortality from cardiovascular disease, cancer, and all causes in a prospective cohort of women. Heidemann C, et al. Circulation. 2008 Jul 15;118(3):230-7. Key Finding: “We prospectively evaluated the relation between dietary patterns and risk among 72,113 women and were followed up from 1984 to 2002. A Western pattern diet reflected high intakes of red meat, processed meat, refined grains, French fries, and sweets/desserts, was associated with a higher risk of mortality from cardiovascular disease (22%), cancer (16%) and all causes (21%) than a prudent diet with high intakes of vegetables and fruit, fish, poultry, and whole grains.”
Dietary patterns and risk of incident type 2 diabetes in the Multi-Ethnic Study of Atherosclerosis (MESA). Nettleton JA, et al. Diabetes Care. 2008 Sep;31(9):1777-82. Key Finding: “We characterized dietary patterns and their relation to incident type 2 diabetes in 5,011 participants from the Multi-Ethnic Study of Atherosclerosis. High intake of refined grains, high-fat dairy and red meat was associated with an 18% greater risk of type 2 diabetes.”
Dietary patterns and 15-y risks of major coronary events, diabetes, and mortality. Brunner EJ. Mosdol A, et al. Am J Clin Nutr. 2008 May;87(5):1414-21. Key Finding: “We analyzed the prospective relation of dietary patterns with incident chronic disease and mortality during 15 y of follow-up of 106,633 person-years at risk among men and women with a mean age of 50 y at the time of dietary assessment. The unhealthy dietary pattern of white bread, processed meat, fries and full-cream milk, compared to the healthy pattern of fruit vegetables, whole-meal bread, low-fat dairy and little alcohol, was associated with increased risk for coronary death or nonfatal myocardial infarction and diabetes.”
Epidemiological association between some dietary habits and the increasing incidence of type 1 diabetes worldwide. Muntoni S. Ann Nutr Metab. 2006;50(1):11-9. Key Finding: “We did an ecological study in the 37 world areas where a 3% yearly increase in type 1 diabetes incidence had been reported, and we calculated through the FAQs Food Balance Sheets the per capita daily supply of milk, meat and cereals from 1961 to 2000. A significant positive correlation with supply of milk was present from 1961 to 2000, while that with meat and cereals became significant in 1983 and 2000.”
Comparisons of prostate cancer mortality rates with dietary practices in the United States. Colli JL, Colli A. Urol Oncol. 2005 Nov-Dec;23(6):390-8. Key Finding: “This study found strong positive correlations between prostate cancer mortality and the consumption of total meat; added fats and oils; ice cream; salad/cooking oils; margarine, and vegetable shortening. The link between salad/cooking oil consumption and prostate cancer risk may be consistent with past studies which suggest that mu-linolenic acid (a component of salad/cooking oils) is a suspected risk factor for prostate cancer.”
Major dietary patterns are related to plasma concentrations of markers of inflammation and endothelial dysfunction. Lopez-Garcia E, et al. Am J Clin Nutr. 2004 Oct;80(4):1029-35. Key Finding: “Endothelial dysfunction is one of the mechanisms linking diet and the risk of cardiovascular disease. Markers of inflammation and endothelial dysfunction include C-reactive protein, interleukin 6, E-selectin, sVCAM and SICAM. We conducted a cross-sectional study of 732 women from the Nurses’ Health Study I cohort who were 43-69 y of age and free of cardiovascular disease, cancer, and diabetes mellitus. Dietary intake was documented by using a validated food-frequency questionnaire in 1986 and 1990. A Western pattern diet characterized by higher intakes of red and processed meats, sweets, desserts, French fries, and refined grains showed a positive relation with CRP, interleukin, E-selectin, sICAM and sVCAM. This study suggests a mechanism for the role of dietary patterns in the pathogenesis of cardiovascular disease.”
Prudent diet and the risk of insulin resistance. Villegas R, et al. Nutr Metab Cardiovasc Dis. 2004 Dec;14(6):334-43. Key Finding: “We performed a cross sectional study involving a group of 1,018 men and women sampled in the south of Ireland. Participants completed a detailed health and lifestyle questionnaire and provided fasting blood samples for analysis. A lower intake of meat (red meat), meat products, sweets, high fat dairy and white bread (white bread and unrefined cereal) may be associated with enhanced insulin sensitivity and a lower risk of type 2 diabetes.”
Dietary patterns and risk for type 2 diabetes mellitus in U.S. men. Van Dam RM, et al. Ann Intern Med. 2002 Feb 5;136(3):201-9. Key Finding: “Participants were 42,504 male health professionals, 40 to 75 years of age, without diagnosed diabetes at baseline. Using a food frequency questionnaire analysis, a ‘western’ diet characterized by higher consumption of red meat, processed meat, French fries, high-fat dairy products, refined grains, and sweets and desserts is associated with a substantially increased risk for type 2 diabetes in men.”
Prospective study of major dietary patterns and risk of coronary heart disease in men. Hu FB, et al. Am J Clin Nutr. 2000 Oct;72(4):912-21. Key Finding: “This was a prospective cohort of 44,875 men aged 40-75 y without diagnosed cardiovascular disease or cancer at baseline. During 8 y of follow-up, we documented 1,089 cases of CHD. The Western dietary pattern characterized by higher intake of red meat, processed meat, refined grains, sweets and dessert, French fries and high-fat dairy products predict the risk of coronary heart disease independent of other lifestyle variables.”
Trans fatty acid isomers in human health and in the food industry. Valenzuela A, Morgado N. Biol Res. 1999;32(4):273-87. Key Finding: “Trans fatty acids are unsaturated fatty acids that occur naturally in dairy and other natural fats. However, industrial hydrogenation of vegetable or marine oils is largely the main sources of trans fatty acids in our diet The ingestion of trans fatty acids increases low density lipoprotein (LDL) to a degree similar to that of saturated fats, but it also reduces high density lipoproteins (HDL), therefore trans isomers are considered more atherogenic than saturated fatty acids, increasing the risk of atherogenesis.”
Foods as risk factors for colorectal cancer: a case-control study in Burgundy (France). Boutron-Ruault MC, et al. Eur J Cancer Prev. 1999 Jul;8(3):229-35. Key Finding: “In men, the most significant risk factors were refined cereal products, seasoning animal fats, chocolate and coffee, whereas risk factors were delicatessen fat meat, pasta, rice, and chocolate in women. The strong association with refined cereal products is consistent with the hypothesis of a role of hyperinsulinism in colorectal carcinogenesis. The association with processed but not fresh meat suggests the importance of exogenous carcinogenesis in that area.”
Food groups and colorectal cancer risk. Levi F, et al. Br J Cancer. 1999 Mar;79(7-8):1283-7. Key Finding: “We examined data from a case-control study conducted between 1992 and 1997 in the Swiss canton of Vaud. Cases were 223 patients with incident, histologically confirmed colon cancer. Controls were 491 subjects. Significant associations were observed for refined grain and red meat, pork and processed meat.”
Dietary patterns and metabolic syndrome—a review of epidemiologic evidence. Baxter AJ, et al. Asia Pac J Clin Nutr. 2006;15(2):134-42. Key Finding: “Diet patterns with high meat intake were frequently associated with components of metabolic syndrome, particularly impaired glucose tolerance. High dairy intake was generally associated with reduced risk for components of metabolic syndrome with some inconsistency in the literature regarding risk of obesity. Minimally processed cereals appeared to be associated with decreased risk of metabolic syndrome, while highly processed cereals with high glycaemic index are associated with higher risk.”
Interactive effects of neonatal exposure to monosodium glutamate and aspartame on glucose homeostasis. Collison KS, et al. Nutr Metab. 2012 Jun 14;9(1):58. Key Finding: Certain food additives may be synergistic or additive. Aspartame and Monosodium Glutamate was investigated in mice. Aspartame exposure may promote hyperglycemia and insulin intolerance, and MSG may interact with aspartame to further impair glucose homeostasis.”
Consumption of artificial sweetener and sugar-containing soda and risk of lymphoma and leukemia in men and women. Schernhammer ES, et al. 2012 Dec;96(6):1419-28. Key Finding: “We repeatedly assessed diet in the Nurses’ Health Study and Health Professionals Follow-up Study. In men we found a daily serving of diet soda increased risks of multiple myeloma in comparison with men who did not consume diet soda. We also observed an unexpected elevated risk of non-Hodgkin lymphoma with a higher consumption of sugar-sweetened soda in men. When data for men and women were combined we saw an increased risk of leukemia.”
Studies on the effects of aspartame on memory and oxidative stress in brain of mice. Abdel-Salam OM, et al. Eur Rev Med Pharmacol Sci. 2012 Dec;16(15):2092-101. Key Finding: “These findings suggest impaired memory performance and increased brain oxidative stress by repeated aspartame administration in mice. Aspartame caused dose-dependent inhibition of brain serotonin, noradrenaline and dopamine.”
Gender dimorphism in aspartame-induced impairment of spatial cognition and insulin sensitivity. Collison KS, et al. PLoS One. 2012;7(4):e31570. Key Finding: “These data suggest that lifetime exposure to aspartame, commencing in utero, may affect spatial cognition and glucose homeostasis in C57BL/6J mice, particularly in males.”
Effect of long term intake of aspartame on antioxidant defense status in liver. Abhilash M, et al. Food Chem Toxicol. 2011 Jun;49(6):1203-7. Key Finding: “It can be concluded from these observations that long term consumption of aspartame leads to hepatocellular injury and alterations in liver antioxidant status maily through glutathione dependent system.”
Soft drinks consumption and nonalcoholic fatty liver disease. Nseir W, Nassar F. Assy N. World J Gastroenterol. 2010 Jun 7;16(21):2579-88. Key Finding: “Soft drinks are the leading source of added sugar worldwide and have been linked to obesity, diabetes and metabolic syndrome. The consumption of soft drinks can increase the prevalence of nonalcoholic fatty liver disease. During regular soft drinks consumption, fat accumulates in the liver by the primary effect of fructose and increases lipogenesis, and in the case of diet soft drinks, by the additional contribution of aspartame sweetener and caramel colorant which are rich in advanced glycation end products that potential increase insulin resistance and inflammation.”
Artificial sweeteners and the risk of gastric, pancreatic, and endometrial cancers in Italy. Bosetti C, et al. Cancer Epidemiol Biomarkers Prev. 2009 Aug;18(8):2235-8. Key Finding: “The present study adds further evidence on the absence of any adverse effect of low-calorie sweetener (including aspartame) consumption on the risk of common neoplasms in the Italian population.”
Nutrition, total fluid and bladder cancer. Brinkman M, Zeegers MP. Scand J Urol Nephtrol Suppl. 2008 Sep;(218):25-36. Key Finding: “A search of computerized databases was conducted to identify all epidemiological studies published between 1966 and October 2007 on the association between nutrition and bladder cancer. Possible risk factors identified are salted and barbecued meat, pork, total fat, pickled vegetables, salt, soy products, spices and artificial sweeteners.”
Genotoxicity testing of low-calorie sweeteners: aspartame, acesulfame-K, and saccharin. Bandyopadhyay A, et al. Drug Chem Toxicol. 2008;31(4):447-57. Key Finding: “Low-calorie sweeteners are chemicals that off the sweetness of sugar without the calories. Consumers are increasingly concerned about the quality and safety of many products present in the diet, in particular, the use of low-calorie sweeteners, flavoring, colorings, preservatives, and dietary supplements. In the present study, we evaluated the mutagenicity of the three low-calorie sweeteners in the Ames/Salmonella/microsome test and their genotoxic potential by comet assay in the bone marrow cells of mice. Sweeteners used were aspartame, acesulfame-K, and saccharin. The comet parameters of DNA were increased in the bone marrow cells due to sweetener-induced DNA strand breaks. Acesulfame-K and saccharin were found to induce greater DNA damage than aspartame. However, none could act as a potential mutagen in the Ames/Salmonella/microsome test. These findings are important since they represent a potential health risk associated with exposure to these agents.”
Life-span exposure to low doses of aspartame beginning during prenatal life increases cancer effects in rats. Soffritti, M, et al. Environ Health Perspect. 2007 Sep;115(9):1293-7. Key Finding: “We studied groups of 70-95 male and female Sprague-Dawley rats administered aspartame (2,000, 400, or O ppm) with feed from the 12 day of fetal life until natural death. Our results show a significant dose-related increase of malignant tumor-bearing animals, a significant increase in incidence of lymphomas/leukemias in males treated with 2,000 ppm, and a significant dose-related increase in incidence of lymphomas in females, and a significant dose-related increase in incidence of mammary cancer in females. The results of this carcinogenicity bioassay confirm and reinforce the first experimental demonstration of aspartame’s multipotential carcinogenicity at a dose level close to the acceptable daily intake for humans. Furthermore, the study demonstrates that when life-span exposure to aspartame begins during fetal life, its carcinogenic effects are increased.”
Artificial sweeteners and cancer risk in a network of case-control studies. Gallus S. Scotti L. Negri E, et al. Ann Oncol. 2007 Jan;18(1):40-4. Key Finding: “Cases were 598 patients with incident, histologically confirmed cancers of the oral cavity and pharynx, 304 of the oesophagus, 1,225 of the colon, 728 of the rectum, 460 of the larynx, 2,569 of the breast, 1,031 of the ovary, 1,294 of the prostate and 767 of the kidney (renal cell carcinoma). Controls were 7,028 patients admitted to the same hospitals as cases for acute, non-neoplastic disorders. The present work indicates a lack of association between saccharin, aspartame and other sweeteners and the risk of several common neoplasms.”
Synergistic interactions between commonly used food additives in a developmental neurotoxicity test. Lau K, et al. Toxicol Sct. 2006 Mar;90(1):178-87. Key Finding: “Exposure to non-nutritional food additives during the critical development window has been implicated in the induction and severity of behavioral disorders such as attention deficit hyperactivity disorder. Although the use of single food additives at their regulated concentrations is believed to be relatively safe in terms of neuronal development, their combined effects remain unclear. We therefore examined the neurotoxic effects of four common food additives in combinations (Brilliant Blue, L-glutamic acid, Quinoline Yellow, and aspartame) to assess potential interactions. Two independent models were used to analyze combination effects. Significant synergy was observed between combinations of Brilliant Blue with L-glutamic acid, and Quinoline Yellow with aspartame. Inhibition of neurite outgrowth was found at concentrations of additives theoretically achievable in plasma by ingestion of a typical snack and drink. Both combinations had a straightforward additive effect on cell cytotoxicity.”
First experimental demonstration of the multipotential carcinogenic effects of aspartame administered in the feed to Sprague-Dawley rats. Soffritti M. et al. Environ Health Perspect. 2006 Mar;114(3):379-85. Key Finding: “Aspartame was administered with feed to 8-week-old Sprague-Dawley rats (100-150/sex/group.) The treatment lasted until natural death, at which time all deceased animals underwent complete necropsy. The results of this study show for the first time that aspartame causes an increased incidence of malignant-tumor-bearing animals, an increase in lymphomas and leukemias, a statistically significant increased incidence of transitional cell carcinomas of the renal pelvis and ureter in females, and an increased incidence of malignant schwannomas of peripheral nerves in males. The results of this mega-experiment indicate that aspartame is a multipotential carcinogenic agent, even at a daily dose of 20 mg/kg body weight, much less than the current acceptable daily intake. On the basis of these results, a reevaluation of the present guidelines on the use and consumption of aspartame is urgent and cannot be delayed.”
NTP report on the toxicology studies of aspartame (CAS No. 22839-47-0) in genetically modified (FVB Tg.AC hemizygous) and B6.129-Cdkn2ata1Rdp (N2) deficient mice and carcinogenicity studies of aspartame in genetically modified {B6.129-Trp53tm1Brd(N5) haploinsufficient} mice (feed studies). National Toxicology Program. Natl Toxicol Program Genet Modif Model Rep. 2005 Oct;(1):1-222. Key Finding: “Under the conditions of this feed study, there was no evidence of carcinogenic of aspartame in male and female p53 haploinsufficient mice. Because this is a new model, there is uncertainty whether the study possessed sufficient sensitivity to detect a carcinogenic effect.”
Artificial sweeteners—do they bear a carcinogenic risk? Weilrauch MR, Diehl V. Ann Oncol. 2004 Oct;15(10):1460-5. Key Finding: “We performed searches for articles in English about artificial sweeteners. These articles included ‘first generation’ sweeteners such as saccharin, cyclamate and aspartame, as well as ‘new generation’ sweeteners such as acesulfame-K, sucralose, alitame and neotame. Epidemiological studies in humans did not find the bladder cancer-inducing effects of saccharin and cyclamate that had been reported from animal studies in rats. There is no evidence that aspartame is carcinogenic. Case-control studies showed an elevated relative risk for heavy artificial sweetener use. For new generation sweeteners, it is too early to establish any epidemiological evidence about possible carcinogenic risk. As many artificial sweeteners are combined in today’s products, the carcinogenic risk of a single substance is difficult to assess. However, according to the current literature, the possible risk of artificial sweeteners to induce cancer seems to be negligible.”
Interactive effects of neonatal exposure to monosodium glutamate and aspartame on glucose homeostasis. Collison KS, et al. Nutr Metab. 2012 Jun 14;9(1):58. Key Finding: Certain food additives may be synergistic or additive. Aspartame and Monosodium Glutamate was investigated in mice. Aspartame exposure may promote hyperglycemia and insulin intolerance, and MSG may interact with aspartame to further impair glucose homeostasis.”
Monosodium glutamate (MSG) intake is associated with the prevalence of metabolic syndrome in a rural Thai population. Insawang T, et al. Nutr Metab. 2012 Jun 8;9(1):50. Key Finding: 324 families from a rural area of Thailand were provided MSG for use in meals for 10 days. They were evaluated for energy and nutrient intake, and physical activity. The prevalence of metabolic syndrome was significantly higher in those with the highest MSG intake.”
The effect of dietary glutamate on fibromyalgia and irritable bowel symptoms. Holton KF, et al. Clin Exp Rheumatol. 2012 Nov-Dec;30(6 Suppl 74):10-7. Key Finding: “Dietary glutamate may be a contributor to fibromyalgia symptoms in some patients.”
Long term effect of monosodium glutamate in liver of albino mice after neo-natal exposure. Bhattacharya T, et al. Nepal Med Coll J. 2011 Mar;13(1):11-6. Key Finding: “Monosodium Glutamate is a naturally occurring excitatory neurotransmitter extensively used as a food additive and flavoring agent and is being implication in obesity, gonadal dysfunction, learning difficulty, etc. It produces oxygen derived free radicals metabolized in liver. Present work was undertaken to study the long term effects of histology of liver following MSG injection in neonate mice. Livers of 75 day old mice showed variable changes. Areas around central vein were most affects. Liver cords were disrupted. There were inflammatory cells around central vein.”
Dietary trans-fat combined with monosodium glutamate induces dyslipidemia and impairs spatial memory. Collison KS, et al. Physiol Behav. 2010 Mar 3;99(3):334-42. Key Finding: “Recent evidence suggests that intake of excessive dietary fat, particularly saturated fat and trans-hydrogenated oils can impair learning and memory. Central obesity, which can be induced by neonatal injections of monosodium glutamate, also impairs learning and memory. We treated mice with either a trans-fatty acids enriched diet, dietary MSG, or a combination of both and examined serum lipid profile and spatial memory compared to mice fed a standard diet Dietary trans-fat combined with MSG increased central adiposity, promoted dyslipidemia and impaired spatial learning.”
Monosodium glutamate neonatal treatment as a seizure and excitotoxic model. Lopez-Perez SJ., et al. Brain Res. 2010 Mar 4;1317:246-56. Key Finding: “Monosodium glutamate (MSG) subcutaneously administered to neonatal rats induces several neurochemical alterations in the brain. Rat pups were injected with a MSG solution at 1, 3, 5 and 7 postnatal days. Biochemical modifications were accompanied with behavioral alterations characterized by: screeching, tail stiffness, head nodding, and generalized convulsions, which were associated with electroencephalographic pattern alterations. Altered behavior found in animals treated with MSG suggests an initial seizure situation.”
Monosodium glutamate is not associated with obesity or a greater prevalence of weight gain over 5 years: findings from the Jiangsu Nutrition Study of Chinese adults. Shi Z, et al. Br J Nutr. 2010 Aug;104(3):457-63. Key Finding: “Animal studies and one large cross-sectional study of 752 healthy Chinese men and women suggest that monosodium glutamate may be associated with overweight/obesity and these findings raise public concern over the use of MSG as a flavor enhancer in many commercial foods. In this study data was analysed from 1,282 Chinese men and women. MSG intake was not associated with significant weight gain.”
Damage and plasticity in adult rat hippocampal trisynaptic circuit neurons after neonatal exposure to glutamate excitotoxicty. Gonzalez-Burgos I, et al. Int J Dev Neurosci. 2009 Dec;27(8):741-5. Key Finding: “Hippocampal vulnerability to excitotoxicity has been widely studied along with its implications to learning and memory. Neonatal glutamate excitotoxicity induces loss of CA1 pyramidal neurons in adult rats concomitantly with some plastic changes in the dendritic spines of surviving neurons. These may underlie the learning impairments seen in previous studies. Our results strongly suggest a long-term induction of plastic changes in the cytoarchitecture of the hippocampal trisynaptic circuit neurons after cell death provoked by the monosodium glutamate-induced excitotoxicity.”
Diltiazem prevention of toxic effects of monosodium glutamate on ovaries in rats. Bojanic V, et al. Gen Physiol Biphys. 2009;28 Spec No:149-54. Key Finding: “The female reproductive systems if very sensitive to different harmful environmental factors. A great danger is hidden in an increased use of food additives like monosodium glutamate (MSG0. Numerous studies have shown that application of high doses of MSG to different kinds of animals during the neonatal period may cause lesion of neural structures and the retina. Later in adulthood animals exhibit a series of neuroendocrine disorders: a stunted growth, obesity and infertility. Our results suggest that calcium overloading play an important role in mechanisms of MSG toxicity.”
Dose dependent development of diabetes mellitus and non-alcoholic steatohepatitis in monosodium glutamate-induced obese mice. Sasaki Y, et al. Life Sci. 2009 Sep 23;85(13-14):490-8. Key Finding: “A single 4 mg/g dose of MSG is the most suitable as the obese model and induces not only severe obesity and diabetes mellitus in neonatal mice, but also liver changes resembling human NAFLD/NASH.”
Dietary patterns and risk of oral cancer: a factor analysis study of a population in Jakarta, Indonesia. Amtha R. Zain R, et al. Oral Oncol. 2009 Aug;45(8):e49-53. Key Finding: “A matched case-control hospital-based study of oral cancer was conducted; the sample included 81 cases and 162 controls. A dietary pattern labeled ‘chemical’ related was loaded by processed food and monosodium glutamate. This pattern showed a threefold higher risk of oral cancer.”
Association of monosodium glutamate intake with overweight in Chinese adults: the INTERMAP Study. He K, et al. Obesity. 2008 Aug;16(8):1875-80. Key Finding: “This study examines the association between MSG intake and overweight in humans. We conducted a cross-sectional study involving 752 healthy Chinese aged 40-59 years, randomly sampled from three rural villages in north and south China. Prevalence of overweight was significantly higher in MSG users than nonusers.”
Long-term effect of neonatal monosodium glutamate (MSG) treatment on reproductive system of the female rat. Miskowiak B, et al. Folia Morphol (Warsz). 1999;58(2):105-13. Key Finding: “The study aimed at determining effects of monosodium glutamate introduced in the perinatal period on the reproductive system of sexually mature female rats. The perinatal injection of MSG was found to decrease relative weights of ovaries and uteri. Serum estradiol level in MSG injected females was lower than controls at the age of 12 and 18 months. In 12 and 18 month old females the alterations were accompanied by obesity and a decreased body length.”
The modifying influence of aging on behavior in mice neonatally injected with monosodium glutamate. Goldman M, Stowe GE. Psychopharmacology (Berl). 1985;86(3):359-64. Key Finding: “Newborn mice were injected with monosodium glutamate and behavioral testing and physical development in neonatal, juvenile, adult, and aged mice were observed by means of a battery of appropriate tests. Early exposure to MSG resulted in altered behavioral performances postnatally, which were transitory and reflected the neurotoxicity of the chemical. Although behavioral deficits were not observed in mice neonatally treated with MSG at 1 month of age, a definite decline was manifested at 12 months and 34 months of age.”
Pattern of intake of food additives associated with hyperactivity in Irish children and teenagers. Connolly A, et al. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2010 Apr;27(4):447-56. Key Finding: “No child or teenager in this study achieved the overall intakes of food additives used in the previous study linking food additives with hyperactivity, though in the case of the preservative sodium benzoate, it exceeded the previously used dose in both children and teenagers.”
‘Junk food’ diet and childhood behavioural problems: results from the ALSPAC cohort. Wiles NJ, et al. Eur J Clin Nutr. 2009 Apr;63(4):491-8. Key Finding: “Data on approximately 4,000 children participating in the Avon Longitudinal Study of Parents and Children in the UK was used. Behavioural problems were measured at age 7 using the Strengths and Difficulties Questionnaire. Children eating a diet high in junk food in early childhood were more likely to be in the top 33% on the hyperactivity sub-scale at age 7.”
Evaluation of the butter flavoring chemical diacetyl and a fluorochemical paper additive for mutagencity and toxicity using the mammalian cell gene mutation assay in L5178Y mouse lymphoma cells. Whittaker P, et al. Food Chem Toxicol. 2008 Aug;46(8):2928-33. Key Finding: “Diacetyl is a yellowish liquid that is usually mixed with other ingredients to produce butter flavor or other flavors in a variety of food products. Recent findings have shown irreversible obstructive lung disease among workers not only in the microwave popcorn industry, but also in flavoring manufacture, and in chemical synthesis of diacetyl, a predominant chemical for butter flavoring. It has been reported that perfluorochemicals utilized in food packaging are migrating into foods and may be sources of oral exposure.. Relatively small quantities of perfluorochemicals are used in the manufacturing of paper or paperboard that is in direct contact with food to repel oil or grease and water. Because of recent concerns about perfluorchemicals such as those found on microwave popcorn bags and diacetyl in foods, we evaluated both compounds for mutagenicity using the mammalian cell gene mutation assway in L5178Y mouse lymphoma cells. Diacetyl induced a highly mutagenic response in mouse lymphoma.”
Food additives and hyperactive behavior in 3-year-old and 8/9-year-old children in the community: a randomized, double-blinded, placebo-controlled trial. McCann D, et al. Lancet 2007 Nov 3;370(9598):1560-7. Key Finding: “Children included in the study were 153 3-year-olds and 144 8/9-year-olds. We found that artificial colours or a sodium benzoate preservative (or both) in the diet result in increased hyperactivity in 3-year-old and 8/9-year-old children.”
Synergistic interactions between commonly used food additives in a developmental neurotoxicity test. Lau K, et al. Toxicol Sci. 2006 Mar;90(1):178-87. Key Finding: “Exposure to non-nutritional food additives during the critical development window has been implicated in the induction and severity of behavioral disorders such as attention deficit hyperactivity disorder. Although the use of single food additives at their regulated concentrations is believed to be relatively safe in terms of neuronal development, their combined effects remain unclear. We therefore examined the neurotoxic effects of four common food additives in combinations (Brilliant Blue, L-glutamic acid, Quinoline Yellow, and aspartame) to assess potential interactions. Two independent models were used to analyze combination effects. Significant synergy was observed between combinations of Brilliant Blue with L-glutamic acid, and Quinoline Yellow with aspartame. Inhibition of neurite outgrowth was found at concentrations of additives theoretically achievable in plasma by ingestion of a typical snack and drink. Both combinations had a straightforward additive effect on cell cytotoxicity.”
Do artificial food colors promote hyperactivity in children with hyperactive syndromes? A meta-analysis of double-blind placebo-controlled trials. Schab DW, et al. Behav Pediatr. 2004 Dec;25(6):423-34. Key Finding: “We seek to assess whether artificial food colorings contribute to the behavioral symptomatology of hyperactive syndrome. We searched databases for double-blind placebo-controlled trials evaluating the effects of artificial food colorings. Fifteen trials met the primary inclusion criteria. Our findings are consistent with accumulating evidence that neurobehavioral toxicity may characterize a variety of widely distributed chemicals.”
The effects of a double blind, placebo controlled, artificial food colourings and benzoate preservative challenge on hyperactivity in a general population sample of preschool children. Bateman B, et al. Arch Dis Child. 2004 Jun;89(6):506-11. Key Finding: “A sample of 1,873 children were screened in their fourth year for the presence of hyperactivity. Children were selected to form four groups. Children were subjected to a diet eliminating artificial colourings and benzoate preservatives for one week. Behaviour was assessed by a tester blind to dietary status and by parents ratings. There is a general adverse effect of artificial food colouring and benzoate preservatives on the behavior of 3 year old children which is detectable by parents.”
Attention deficit and infantile hyperactivity. Berdonces JL. Rev Enferm (Spanish). 2001 Jan;24(1):11-4. Key Finding: “Hyperactivity is a very common disorder in children, especially males. Chocolate, sugar, sweeteners, additives, preservatives, dyes, can enhance an incidence of this syndrome.”
Food habits and pancreatic cancer: a case-control study of the Francophone community in Montreal, Canada. Ghadirian P, et al. Cancer Epidemiol Biomarkers Prev. 1995 Dec;4(8):895-9. Key Finding: “A total of 179 cases and 239 controls matched for age, sex, and language (French) were interviewed. Data on food habits, methods of food preparation and preservation, and related information was obtained through a questionnaire. The study found an increased risk of pancreatic cancer associated with a high consumption of salt, smoked meat, dehydrated food, fried food, and refined sugar. An inverse association was found with the consumption of food with no preservatives or additives, raw food, and food prepared by presto or high-pressure cooking.”
Foods and additives are common causes of the attention deficit hyperactive disorder in children. Boris M, Mandel FS. Ann Allergy. 1994 May;72(5):462-8. Key Finding: “This investigation evaluated 26 children who meet the criteria for attention deficit hyperactive disorder. Treatment with a multiple item elimination diet showed 19 children (73%) responded favorably. All 19 children reacted to many food dyes and/or preservatives. This study demonstrates a beneficial effect of eliminating reactive foods and artificial colors in children with ADHD.”