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Artificial Sweeteners: How Safe Are They?

Rosalinda Mercedes E. Castillo, M.A.

Taste has always been associated with a particular property. Sweet denotes potential source of energy, salty as a source of minerals (i.e. sodium), bitter could be potentially dangerous or toxic. It is therefore expected that humans would prefer sweet food and will tend to add sweet substances to what they eat. The first recorded sweetener was honey, which was used in ancient cultures of Greece and China (Bright, 1999). It was later replaced by cane sugar, or the common table sugar as it is known today. Recent clinical manifestations of diseases apparently resulting from excessive use of sugar (i.e. obesity, diabetes) made it imperative to provide a substitute for sugar without the calories that go with it. Since the body makes use of carbohydrates as primary source of energy, followed by fats, and then, in cases of starvation, proteins, the most logical source would be a non carbohydrate substitute so that it will not serve as energy source, hence zero calorie. Sugar Substitutes Several artificial sweeteners have been synthesized with the primary aim of providing the taste without increasing blood sugar which is bad for diabetics, or caloric intake for obese individuals or simply those who want to maintain their weight. Saccharin. The first artificial sweetener was saccharin, which was synthesized in 1879 by Remsen and Fahlberg. It was well accepted during World Wars I and II because of its low production costs and the shortcoming of regular sugar (Bright, 1999). After the wars and the economy has recovered, sugar became more affordable, hence, the shift to cane sugar. But with increased availability of sugar, obesity increased in Western societies creating a need to shift, again, to sugar substitutes or artificial sweeteners as they are called today. Saccharin, in spite of its
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extreme sweetness, is also known for its bitter aftertaste. The need for new improved taste, calorie-reduced sweetener is inevitable. Cyclamate. By the 1950s, cyclamate was introduced. It tasted better than saccharin and blended well with the latter. Both substances were mixed together with other additives to produce better tasting food products, i.e. softdrinks, cakes. Aspartame. In 1981, another artificial sweetener, aspartame, was introduced as Nutra Sweet. It was used in dairy products as yogurt which was labeled low-calorie, light or diet. These three, saccharin, cyclamate and aspartame, constitute the first generation sweeteners. These are followed by new or second generation sweeteners such as acesulfame-K, alitame, neohesperidine, neotame, stevioside, sucralose and thaumatin which have different market areas as shown in Table 1. Their taste is often accompanied by a metallic and bitter aftertaste much unlike cane sugar. By combining any of these, the desired taste for the intended consumer is achieved. For example, a particular brand of softdrink in the United States contains aspartame only. The same brand of softdrinks sold in Germany contains cyclamate and acesulfame-K (Weihrauch & Diehl, 2004). Scientific Studies to Determine Possible Presence of Adverse Effects Most previous epidemiological studies of sweeteners and cancer risk in humans refer to bladder and brain cancers. Information with reference to other cancer sites are very scant. Saccharin has been linked to risk of bladder cancer in rats (Weihrauch & Diehl, 2004).and humans (Armstrong, 1975; Howe, 1977) although recent studies in humans failed to reproduce these findings (Cartwright, Adib, Glashan & Gray, 1981; Wynder & Stellman, 1980) and that saccharin did not lead to the formation of either urinary tract stones or epithelial lesions in humans (Capen, Dybing, Rice & Wilbourn, 1999).

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Table 1 Key artificial sweeteners and their key market areas. Sweetener Acesulfame-K Alitame Aspartame Cyclamate Neohesperidine Neotame Saccharin Stevioside Sucralose Thaumatin
Source: Lindley, 1999

Key Market Areas North America, Europe and Asia Oceania, South/Central America North America, Europe and Asia Europe and Asia DC Europe and Japan USA Asia, Europe and USA Asia North America Europe and Asia

Aspartame, on the other hand, initially exhibited apparent excess of lymphatic neoplasms in females but not in males, though a linear trend in risk is absent, indicating that the effect is not dose dependent (Soffriti et al., 2006). There seems to be major variations in results by geographical locations. In the United Kingdom, there is a 60% increased risk for bladder cancer in men than in women who used artificial sweeteners (Howe et al., 1977), and a slight excess risk in nonsmokers only (Weihbrauch & Diehl, 2004). In the US, there is no significant association with sweetener use and bladder or low urinary tract cancers (Hoover & Strasser, 1980; Wynder & Stellman, 1980). Except for the toxicological animal data required for Food and Drug Administration (FDA) approval, there are no larger studies that investigate the potentially hazardous effects of second
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generation sweeteners. None of the substances such as acesulfame-K, neohisperidine, alitame or sucralose has been suspected to cause cancer or to be genotoxic (Weihrauch & Diel, 2004). Owing to the fact that these were introduced only recently, larger epidemiological studies as those done on first generation sweeteners could not possibly be done. Conclusion Saccharin was shown to be safe for human consumption as this does not increase the risk of cancer at several common sites in humans (Gallus et al., 2007). A study by Soffriti et al. (2006) showed that aspartame is a multipotential carcinogenic compound whose carcinogenic effects are evident even at a daily dose of 20 mg/kg bw, much less than the current allowable dietary intake (ADI) for humans in Europe (40 mg/kg bw) and in the United States (50 mg/kg bw) contrary to an earlier study by Weihrauch and Diehl (2004) that the same artificial sweetener does not pose any risk of inducing cancer in humans. It is still too early to assess the second generation sweeteners epidemiologically although they were not suspected to cause any harmful effects. References Armstrong, B., & Doll, R. (1975). Bladder cancer mortality in diabetics in relation to saccharin consumption and smoking habits. British Journal of Preventive & Social Medicine, 29, 73 81. Bright, G. (1999). Low-calorie sweeteners - From molecules to mass markets. World Review of Nutrition and Dietetics, 85, 3 9. Capen, C. C., Dybing, E., Rice, J. M. & Wilbourn, J. D. (1999). Species difference in thyroid, kidney and urinary bladder carcinogenesis. IARC Scientific Publications, 147. Cartwright, R. A., Adib, R., Glashan, R., & Gray, B. K. (1981). The epidemiology of bladder cancer in West Yorkshire: A

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preliminary report on non-occupational aetiologies. Carcinogenesis, 2, 343 347. Gallus, S., Scotti, L., Negri, E, Talamini, R., Francheschi, S., Montella, M., et al. (2007). Artificial sweeteners and cancer risk in a network of case-control studies. Annals of Oncology, 18, 40 44. Howe, G. R., Burch, J. D., Miller, A. B., Morrison, B., Gordon, P., Weldon, L., et al. (1977). Artificial sweeteners and human bladder cancer. Lancet, 2, 578-581. Lindley, M. G. (1999). New developments in low-calorie sweeteners. World Review of Nutrition and Dietetics, 85, 44 51. Soffritti, M., Belpoggi, F., Degli Esposti, D., Lambertini, L., Tibaldi, E., & Rigano, A. (2006). First experimental demonstration of the multipotential carcinogenic effects of aspartame administered in the feed to Sprague-Dawley rats. Environmental Health Perspectives, 114(3), 379 385. Tavani, A., Giordano, L., Gallus, S., Talamini, R., Franceschi, S., Giacosa, A., et al. (2006). Consumption of sweet foods and breast cancer risk in Italy. Annals of Oncology, 17, 341-345. Weihrauch, M. R. & Diehl, V. (2004). Artificial sweeteners Do they bear a carcinogenic risk? Annals of Oncology, 15, 14601465. Wynder, E. L., & Stellman, S. D. (1980). Artificial sweetener use and bladder cancer: A case control study. Science, 207, 1214-1216.

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