Food Additive Intake and Impact on Health!

Food Additive Intake and Health Effects: A Comprehensive Review.
By: Deborah A. Klein, MS, RD

ABSTRACT
This review examines the health ramifications of consuming food additives in regards to toxicity effects to organ tissues, stimulation of hyperactive syndromes in children, carcinogenic repercussions, reproduction adversities, and possible effects related to obesity. The specific additives researched include, but are not limited to: artificial food colors (e.g., E100, amaranth-food red No. 2, FDC Red no 3, Sunset Yellow FCF, cochineal extract (also called carmine), metanil yellow, orange II, and caramel color III), preservatives (e.g., sodium benzoate, nitrites, sulfites and monosodium glutamate), ‘first generation’ sweeteners (e.g., saccharin, cyclamate and aspartame) and ‘new generation’ sweeteners (e.g., acesulfame-K, alitame, neotame, and sucralose). Food additives, researchers have stated, have “possible noxious effects on health” and are still continuously used within various food products (14). Regulations to avoid early exposures to particular food additives, especially during pregnancy and lactation may have a significantly positive contribution to the health of humankind.

INTRODUCTION
Food additives are not all harmful. The majority are safe and an effective way to preserve, fortify and add flavor to pre-packaged foods. Food additives include the basic components, such as salt, sugar, vinegar, baking powder and soda, vitamins and minerals, thickening agents (gums), flavorings and natural colorings. Additives are classified as “direct additives,” which are directly added to the food during its preparation, and “indirect additives,” which are substances that may be leached into the food from the packaging materials. Judiciously used, food additives are very helpful to maintain food safety, maintain food quality in regards to taste and consistency, and provide vitamins and minerals (increasing nutrient density). However, some ill effects from food additives can occur, such as inducing gastrointestinal discomfort, headaches, allergenic responses, carcinogenic effects, hyperactivity and effects on pregnancy and lactation.
Concerns about the neurotoxic effects of food additives have become a prominent public health issue and has resulted in demands for an increased level of assurance that efforts are being made to minimize the risk of neurotoxicity from human exposure to food additives (18). The FDA has addressed these concerns by revising the toxicity testing guidelines for food additives (18). To protect one’s overall health and prevent ill consequences from specific foods, the most important element is awareness. Thus, the purpose of this research review is to provide an overview of the research regarding food additives, enlightening the public on what to look for on food labels and know the possible consequences of eating foods with particular food additives.

ARTIFICIAL FOOD COLORS:
An extensive list of artificial colors has been added to foods and researchers continue to assess the impact these colors have on one’s health. Human studies indicate that food colors (natural and synthetic) can induce a vast range of allergic reactions especially in sensitive or atopic individuals (8). An exorbitant amount of reports have been made on the significant impact artificial colors have in relation to hyperactivity. Researchers, who conducted studies of 3 year old children, concluded that artificial food colorings do indeed show adverse effects on their behavior (4). Artificial colors in the diet, researchers report result in increased hyperactivity in children within the general population (12, 13). Studies demonstrate that eliminating artificial colors from the diet in children with attention deficit hyperactive disorder (ADHD) can be extremely beneficial in behavior in regards to helping them have a higher response rate (6).
In addition, consuming particular food colorings/additives have been reported as extremely detrimental and considered unsafe during pregnancy and breastfeeding. Current evidence suggests that food additives “induce alterations of the differentiation of several cell-types,” during pregnancy (16). For instance, E100 color additive, “is suspected to be embryotossic,” amaranth (food red No. 2) can result in reducing “olfactory orientation in F1 generation mice and beta-cyclodextrin produces a transient neonatal growth retardation in rodents” (16). Another food additive, methylmercury can cause neurotoxicity in breastfed babies from being excreted into the milk, while nursing (16). The genotoxicity of some synthetic red tar dyes, which are used as food color additives in many countries have been researched extensively and an association has been reported with inducing DNA damage (17). Amaranth (food red No. 2) and allura red (food red No. 40) assays in pregnant mice was shown to be positive in inducing DNA damage in the colon (17). Acid red (food red No. 106) did not induce any DNA damage in the test samples. The 3 dyes (amaranth, allura red, and new coccine-food red No. 18) induced DNA damage in the colon starting at 10 mg/kg in male mice (17). In addition, 1 mg/kg of N-nitrosodimethylamine induced DNA damage in the liver and bladder; it did not induce colon DNA damage. When F1 generation mice were given the color additive amaranth within their diet, their reproductive, developmental and behavioral parameters were influenced significantly (23).
The color additive Sunset Yellow FCF in the diet was measured in mice and assessed for reproductive and neurobehavioral parameters (19). Research data does demonstrate that Sunset Yellow FCF produces some adverse effects in reproductive and neurobehavioral parameters in male and female offspring during the early lactation period (19). Furthermore, the natural color additive cochineal extract (also called carmine) in food can produce some adverse effects in reproductive and neurobehavioral parameters in mice (21). Also, consuming “the color additive caramel color III (AC), may cause a reduction in total white blood cell counts in rats due to reduced lymphocyte counts” (22). The carmel color III suppressed thymus-dependent immunity, as demonstrated by “a decreased natural cell-mediated cytotoxicity in the spleen” (22). Other commonly used food colors, metanil yellow and orange II induced cell mutation at low concentrations (24).
PRESERVATIVES/OTHER ADDITIVES:
Extensive preservatives are added into a multitude of food products, several of them have been reported as resulting in increasing hyperactivity, contributing to cancer, and have ill effects during pregnancy and breastfeeding. With this knowledge in mind, these carcinogens and ill inducing additives are still being incorporated into the food supply. Specifically, diazoaminobenzene, which is “used as an intermediate, complexing agent, and polymer additive”, is “metabolized into known carcinogens benzene and aniline” (15). Sodium benzoate preservative contributes, similar to artificial colors, in increasing hyperactivity in children (13). Henceforth, researchers have predicted that diazoaminobenzene is a carcinogen (13).
Animal studies indicate that the food additive, monosodium glutamate (MSG) may be correlated with increasing one’s risk in becoming overweight, in regards to influencing energy balance, by inducing hypothalamic lesions and leptin resistance (26). Studies examining the relationship of MSG and excess body weight in humans showed a positive correlation. The prevalence of being overweight was significantly higher in MSG users compared to nonusers, independent of physical activity and total energy intake (26). In neonatal mice, MSG induced severe obesity with diabetes mellitus and/or non-alcoholic fatty liver disease (27). During pregnancy and development in rats, MSG administered orally, significantly affected hypothalamic control of various hormones, which in turn, increased appetite (10). High concentrations of MSG have demonstrated to “induce neuronal necrosis and damage in the retina and circumventricular organs” (9).
An additive in cosmetics that penetrates into the skin, butylated hydroxytoluene (BHT) has been shown to be tumor promoting. BHT is metabolized into carboxylic acid and glucuronide, which has been demonstrated in rat studies to result in renal and hepatic damage (11). BHT also when applied to the skin was associated with toxic effects in lung tissue (11).
ARTIFICIAL SWEETENERS:
Since the introduction of artificial sweeteners being added to a variety of foods and drinks, the public has been concerned about their effects on one’s health. Specifically, the mass media reports on the correlation of artificial sweeteners and possible increased risk for various types of cancer. Through extensive research via PubMed searches from the National Library of Medicine on articles about artificial sweeteners, the overall risk of inducing cancer seems to be negligible; however researchers are still reporting some ill consequences from artificial sweeteners. Epidemiological studies in humans showed no induction of bladder cancer from saccharin and cyclamate as reported in animal studies in rats (2). Case control studies showed an elevated risk of 1.3 from excessive artificial sweetener consumption (no specific substances were specified) equating to greater than 1.7 grams per day. New generation sweeteners have not been around long enough to establish any epidemiological evidence about possible carcinogenic effects. Animal bioassay results predict human cancer risks, and a recent animal study confirms that there is a potential carcinogenic effect from consuming aspartame (28).
However, human studies of both men and woman consuming aspartame daily from beverages for a year and over 5 years of follow-up showed that higher levels of aspartame intake were not associated with increased risk of overall hematopoietic cancer nor brain cancer (29) Overall research through 2004 showed that aspartame does not seem to pose a threat to promoting cancer, based on the acceptable daily intake of 40 mg/kg/day in Europe and 50 mg/kg in the United States, which equates to 10 cans of a drink fully sweetened with aspartame (1). “Intakes of over 1 g/day were needed to alter brain neurotransmitters and provoke seizures in monkeys” and randomized controlled trials of high doses in humans did not show any behavioral influence (1). However, other studies in 2006, suggest that “aspartame is a multipotential carcinogenic compound whose carcinogenic effects are evident at a daily dose of 20 mg/kg”, which is significantly less than the acceptable daily intake for humans (30).
Researchers speculate that an increase in lymphomas and leukemias may be related to one of the metabolites in aspartame, specifically methanol, which is metabolized in both rats and humans into formaldehyde. In long-term experiments both methanol and formaldehyde have demonstrated an increase in lymphomas and leukemias (30). As another perspective, artificial sweeteners can be beneficial in reducing body weight, for people who often drink regular sodas. “Drinking large volumes of aspartame sweetened soda, reduces sugar intake and thus may facilitate the control of calorie intake and body weight” (5). Please see Table 1 below for an extensive list of food additives and the negative influences on overall health.

Table 1: Specific Food Additives listed with their possible health effects.

Artificial colors/flavors– Yellow #5, Red #3, Blue #1, Green #3, etc. = some are suspected of being cancer causing, and may exacerbate hyperactivity (Journal Dev. Behav. Pediatrics 2004 Dec;25(6):423-34; Ann. Allergy 1994 May;72(5):462-8).
Artificial or processed sweeteners- Acesulfame potassium, Aspartame, Saccharin, Stevia, Splenda, sucralose, sorbitol, acesulfame, xylitol = may increase risk for cancer and stimulate appetite (Am J Clin Nutr 2003;78(suppl):843S-9S, Annals of Oncology 15(10):1460-1465, Oct 2004).
BHT - butylated hydroxytoluene (BHT) preservative= hepatotoxicity (liver toxicity) induced by the anti-oxidant food additive, may increase risk of cancer, and when BHT was applied to the skin, it was associated with toxic effects in lung tissue (Int. J. Toxicology 2002; 21 Suppl 2:19-94).
Caffeine = increases blood pressure, may cause insomnia if ingested late in the day, may affect the developing fetus, mildly addictive, can cause excess energy or hyperactivity in some people (Pediatrics 1989 Jan;83(1):7-17).
Carmine or cochineal extract - both are derived from female cochineal beetles, which are raised in Peru, the Canary Islands, and elsewhere. They provide a pink, red, or purple color to foods = may be declared as artificial color or color added on food labels and may be allergenic (www.cspinet.org/new/carmine).
Cocoa processed with alkali = processes out the benefits of cocoa, the antioxidants (catechins) are leached.
Dough conditioners – additives to help improve the quality of the finished dough= may include carcinogenic agents, for example, potassium bromate and may include emulsifiers such as mono-and diglycerides which include saturated fats.
Enriched, bleached flour = processed bread, destroys some of the nutrients originally present in the whole grains, enriched with some vitamins but not all those present in the original grain.
Flaxseed (whole not grounded), flaxseed oil = when the flax is whole, it goes right through, the body does not get the benefits of the omega-3’s; flaxseed oil may increase cancer risk due to high levels of alpha-linolenic acid (ALA) (Baillieres Clin Endocrinol Metab. 1998;12:691-705).
Ginseng (Panax ginseng) = Panax ginseng's most common side-effects is the inability to sleep. Other side-effects include nausea, diarrhea, euphoria, headaches, epistaxis, high blood pressure, low blood pressure, mastalgia, and vaginal bleeding.
Glycerol ester of wood resin = possible allergen, largely unabsorbed, some components are metabolized by the liver.
High fructose corn syrup, corn syrup solids = excess fructose can increase LDL (bad cholesterol level, clogs the arteries), is more readily converted to fat by the liver, increases the levels of fat in the bloodstream in the form of triglycerides (Am J Clin Nutr 1990;51:963-9).
Mono and diglycerides = those containing long-chain saturated fatty acids, especially stearic acid, increases blood cholesterol.
Monosodium glutamate (MSG) – flavor enhancer = may cause migraine headaches, chest tightness, wheezing, asthma attacks in those vulnerable, and increase appetite (Biomed Pharmacother 2006 Feb;60(2):86-91, An R Acad Nac Med (Madr) 2005;122(2):341-55).
Olestra- fat replacement = may cause diarrhea, loss of important fat-soluble vitamins.
Palm oil, palm kernel oil, fractionated palm kernel oil = saturated fat, increases LDL cholesterol.
Partially Hydrogenated and hydrogenated oils, trans fat = increases cholesterol level and is carcinogenic.
Polysorbate 60, 65- derived from sorbitol - an artificial sweetener = side effects include: Nausea, gas, diarrhea, stomach cramps or anal irritation.
Potassium bromate – may increase risk of cancer (www.cfsan.fda.gov).
Sodium nitrite, nitrites – meat preservatives = may increase risk of stomach cancer (Middleton’s Allergy: Principles and Practices. 5th ed. Mosby-Year Book, Inc.; 1998:1183-1186).
Sodium stearoyl lactylate- Sodium stearoyl lactate (and the similar calcium stearoyl lactate) - an emulsifier used as a dough strengthener in baked goods, is made by combining lactic acid and stearic acid, and then reacting the result with sodium
hydroxide or calcium hydroxide to make the sodium or calcium salt = stearic acid is a saturated fat (Baker’s Journal:November 2000).
Sodium sulfite, sulfites – provokes asthma attacks in those vulnerable, may increase risk for cancer.
Sorbitan ester of fatty acids - Mono-, di- and trisorbitan esters of palmitic, stearic, oleic, isostearic and sesquioleic acid = saturated fats.
Soy Protein Isolate, soy protein concentrate, isolated soy protein –isoflavones are weak estrogens = eating too much (more than 100 mg a day) could possibly increase risk of cancer (J. Nutrition 134:1229S-1233S, 2004).
Sucrose syrup = concentrated sugar
TBHQ (TERT-BUTYLHYDROQUINONE) = may induce free radical formation and erythrocyte membrane alterations (cell damage).
FUTURE RESEARCH
The emphasis of this review has been on isolated food additives. Since food additives are so vast, more research is needed on the effects of other food additives that were not included in this review. The development of standardized diagnostic criteria for hyperactivity would be helpful in identifying whether artificial colors and other additives indeed have a cause/effect relationship. More longitudinal prospective studies need to be done on food additives and influences on health (3). Further dietary research is needed that includes attention to adequate sample size, well designed criteria for subject selection, assurance of dietary compliance measures and consideration of synergistic effects of other dietary factors (3). More long-term studies relating to the effects of food additives would be useful information for the public. Any increased awareness on the consequences of consuming specific ingredients within food products, can have significant positive ramifications on human health and longevity. Rest assured, the food supply has never been better or safer, thank you to the regulatory agencies and public health authorities who are setting high standards for overall food safety (25).
REFERENCES
1. Lean, ME, Hankey, CR. Aspartame and its effects on health. BMJ 2004; 329:755-6.
2. Weihrauch, MR, Diehl, V. Artificial sweeteners-do they bear a carcinogenic risk? Annals of Oncology 2004; 15:1460-5.
3. National Institutes of Health Consensus Development Panel. National Institutes of Health consensus development conference statement: defined diets and childhood hyperactivity. Am J Clin Nutr 1983; 37:161-5.
4. Bateman, B, Warner, JO, Hutchinson, E, Dean, T, Rowlandson, P, Gant, C, Grundy, J, Fitzgerald, C, Stevenson, J. The effects of a double blind, placebo controlled, artificial food colorings and benzoate preservative challenge on hyperactivity in a general population sample of preschool children. Arch.Dis.Child. 2004; 89:506-11.
5. Tordoff, MG, Alleva, AM. Effect of drinking soda sweetened with aspartame or high-fructose corn syrup on food intake and body weight. Am J Clin Nutr 1990; 51:963-9.
6. Boris, M, Mandel, FS. Foods and additives are common causes of the attention deficit hyperactive disorder in children. Ann Allergy 1994; 72(5):462-8.
7. Epstein, SS. The chemical jungle: today’s beef industry. Int J Health Serv. 1990; 20(2):277-80.
8. Babu, S, Shenolikar, IS. Health & nutritional implications of food colors. Indian J Med Res. 1995; 102:245-9.
9. Ortiz, GG, Bitzer-Quintero OK, Zarate, CB, Rodriguez-Reynoso, S, Larios-Arceo F, Velzquez-Brizuela, IE, Pacheco-Moises F, Rosales-Corral SA. Monosodium glutamate-induced damage in liver and kidney: a morphological and biochemical approach. Biomed Pharmacother. 2006; 60(2):86-91.
10. Fernandez-Tresguerres, Hernandez, JA. Effect of monosodium glutamate given orally on appetite control (a new theory for the obesity epidemic). An R Acad Nac Med. 2005; 122(2):341-55.
11. Lanigan, RS, Yamarik, TA. Final report of the safety assessment of BHT(1). Int J Toxicol. 2002;21:19-24.
12. Schab, DW, Trinh, NH. Do artificial food colors promote hyperactivity in children with hyperactive syndromes? A meta-analysis of double-blind placebo-controlled trials. J Dev Behav Pediatr. 2004; 25(6):423-34.
13. McCann, D, Barrett, A, Cooper, A, Crumpler, D, Dalen, L, Grimshaw, K, Kitchin, E, Lok, K, Porteous, L, Prince, E, Sonuga-Barke, E, Warner, JO, Stevenson, J. 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. Lancet 2007; 370(9598):1524-5.
14. Petrescu, C, Aslau, DA, Doroftei, S, Vlaicu, B, Indrei, LL. Frequency of food additives in mass-consumed food products. Rev Med Chir Soc Med Nat Iasi 2003; 107(4):856-62.
15. Ress, NB. NTP Technical Report on the metabolism, toxicity and predicted carcinogenicity of diazoaminobenzene. Toxic Rep Ser 2002; 73:1-23.
16. Banderali, G, Carmine, V, Rossi, S, Giovannini, M. Food additives: effects on pregnancy and lactation. Acta Biomed Ateneo Parmense 2000; 71(Suppl 1):589-92.
17. Tsuda, S, Murakami, M, Matsusaka, N., Kano, K, Taniguchi, K, Sasaki, YF. DNA damage induced by red food dyes orally administered to pregnant and male mice. Toxicol Sci 2001; 61(1):92-9.
18. Sobotka, TJ, Ekelman, KB, Slikker W Jr, Raffaele, K, Hattan, DG. Food and Drug Administration Proposed Guidelines for Neurotoxicological Testing of Food Chemicals. Neurotoxicology 1996; 17(3-4):825-36.
19. Tanaka, T. Reproductive and neurobehavioral effects of Sunset yellow FCF administered to mice in the diet. Toxicol Ind Health 1996; 12(1):69-79.
20. Tanaka, T. Reproductive and neurobehavioral effects of cochineal administered to mice in the diet. Toxicol Ind Health 1995; 11(1):1-12.
21. Houben, GF, Penninks, AH, Seinen, W, Vos JG, Van Loveren, H. Immunotoxic effects of the color additive caramel color III: immune function studies in rats. Fundam Appl Toxicol 1993; 20(1):30-7.
22. Tanaka, T. Effects of amaranth on F1 generation mice. Toxicol Lett. 1992; 60(3):315-24.
23. Rastogi, PB, Thilly WG, Shirname-More L. Long-term low-dose mutation studies in human cells: metanil yellow and orange II. Mutat Res. 1991; 249(1): 265-73.
24. Newberne, PM, Conner, MW. Food additives and contaminants. An update. Cancer 1986; 58 (Suppl 8):1851-62.
25. HE, K, Zhao, L, Daviglus, ML, Dyer, AR, Van Horn, L, Garside D, Zhu, L, Guo D, Wu Y, Zhou, B, Stamler, J. Association of monosodium glutamate intake with overweight in Chinese adults: the INTERMAP Study. Obesity (Silver Spring) 2008; 16(8):1875-80.
26. Sasaki, Y, Suzuki, W, Shimada, T, Iizuka, S, Nakamura, S, Nagata, M, Fujimoto, M, Tsuneyama, K, Hokao, R, Miyamoto, KI, Aburada, M. Dose dependent development of diabetes mellitus and non-alcoholic steatohepatitis in monosodium glutamate-induced obese mice. Life Sci. 2009 Aug. 12.
27. Huff, J, LaDou, J. Aspartame bioassay findings portend human cancer hazards. Int J Occup Environ Health 2007; 13(4):446-8.
28. Lim, U, Subar, AF, Mouw T, Hartge, P, Morton, LM, Stolzenberg-Solomon, R, Campbell, D, Hollenbeck, AR, Schatzkin, A. Consumption of aspartame-containing beverages and incidence of hematopoietic and brain malignancies. Cancer Epidemiol Biomarkers Prev.2006;15(9):1654-9.
29. Environmental Health Perspectives, February 13, 2006.