HEALTH IMPLICATIONS OF ARTIFICIAL SWEETENERS Acesulfam May 1, 2008 Department of Nutrition Faculty of Public Health Al Arab Medical Sciences University Benghazi Presented by: Diwa Pandey

Sweeteners A type of food additive First recorded sweetener: Honey (ancient Greece and China) Later: Sugar (from cane or beet sugar) Replaced by The food industry: high fructose and glucose syrup etc Contain calories and are sources of energy Demand for low energy sweeteners By people Who wished to regulate their body weight such as the obese With diabetes mellitus: control the amount and type of carbohydrates Who preferred a reduced level of simple sugars in their food

Development of food additives Without the calories of sugar Sweet in perception = Palatable “Artificial sweeteners” 1 Synonymous terms 2 “Intense sweeteners” “Non-nutritive sweeteners” “High-intensity sugar alternatives” “Low-calorie or alternative sweeteners” “First generation artificial sweeteners” 3 Saccharine, Cyclamate & Aspartame “Second generation artificial sweeteners” 3 Acesulfame K, Sucralose, Neotame etc

Historical background Saccharine: Earliest Artificial Sweetener synthesised in 1879 Gained more acceptances during the two world wars Shortcoming in the supply of regular sugar + Low production cost By the 1950s the reason for its use shifted from that of being cost effective to that for calorie reduction The fast growing food industry + Increase in obesity in the western world = Profitable market for the calorie reduced “diet products Sugar partially or totally replaced by Artificial Sweeteners

Adverse effects 3,4 Public or consumers The role of artificial sweeteners on cancer risk has been widely debated over the past few decades Public or consumers Mixed feelings because they associate news about possible cancer risk with the use of these substances Reports on their potential carcinogenic effects News articles in public press Scientific publications in reliable medical journals

First Generation Artificial Sweeteners Saccharine 200 to 700 times sweeter than sugar: Has no calories Used in tabletop sweeteners, baked goods, soft drinks, jams, and chewing gum Was considered “Generally Recognized As Safe” (GRAS) until 1972, when it was removed from the GRAS list by the FDA 1 By definition in the law, a GRAS substance has a long history of safe use in foods, or is determined to be safe based on proven science. But if new evidence suggests that a GRAS substance may no longer be safe, the Food and Drug Administration (FDA) can prohibit its use or require further safety studies.

Concerns that rats developed bladder cancer after receiving high doses of saccharin 1 1977: The Food and Drug Administration (FDA) proposed a ban on saccharin The US Congress passed the Saccharin Study and Labeling Act This legislation put a moratorium on the ban while more safety studies were under way Foods containing it were required to carry a label warning: It could be a health hazard It was found to cause cancer in laboratory animals

Saccharine: Safety studies 1,3 Oldest and the most researched of the Artificial Sweeteners Animal studies Rodents Single generation studies: Only 1 out of 20 was positive Later rejected Found that the rats were infected with a bladder parasite which may have increased their susceptibility towards saccharine induced bladder cancer Later multigenerational studies: Link a higher incidence of bladder cancer with a high dose of saccharine But National Institute of Environmental Health Sciences National Cancer Institute Removed it as potential carcinogen because it could be shown that the cancer causing mechanism in rats does not apply to humans

Saccharine: Safety studies Research on monkeys Non-human primates were considered more suitable models than rats to study potential hazards of artificial sweeteners for humans 5 Subsequent studies on monkeys3 Administered saccharine for 24 years None of them developed bladder cancer Human studies1 National Cancer Institute 30 human studies where saccharin was not found to cause cancer 2000: National Toxicology Program determined that saccharin should no longer be listed as a potential cancer-causing agent 2001: Federal legislation removed the requirement for the warning label

Cyclamate 3 1951: Approval by FDA for use in food industry 1970 Higher incidence of bladder carcinoma in rats prohibited in several countries including the USA and UK. Studies Long term toxicity and a higher incidence of malignancies among non-human primates 2000 Dismissed by critics on the grounds that the results lacked adequate scientific interpretation Cancer Assessment Committee of the Centre for Food Safety and Applied Nutrition (FDA) Scientific Committee for Foods (European Union) WHO Cyclamate is not a carcinogen and re-admitted it to the food industry

Aspartame FDA approval 1,5 Synthesised : 1965 ; Sweetness (Vs Sugar): x 200 Almost two decades of exhaustive animal studies show that it does not have any cancer inducing effects even in large doses 5 FDA approval 1,5 Between 1981 and 1996: General-purpose sweetener in all foods and drinks Reputed journals3 1996 1999 Journal of Neuropathology and Experimental Neurology Western Journal of Medicine Increasing incidence of breast cancer Increasing brain tumour rates among rats Dismissed on the grounds that they were based on correlations not admissible in epidemiology, termed as “Ecological fallacy” Also not be confirmed by later human trials No risk to child by maternal consumption during pregnancy & lactation

Chemical structure of Aspartame: Aspartate (ASP), Phenylalanine (PHE) And Methanol (MET-OH) Because of the phenylalanine component It carries a risk for people with phenylketonuria (A rare genetic disorder) 1 Aspartame Regulation 1 Requires that a statement be placed on the label of all products containing aspartame cautioning such persons with phenylketonuria

Second Generation Artificial Sweeteners 1 FDA: OK 90 Studies FDA 1986-2003 Acesulfame-K [x 200] (FAO/WHO) Joint Expert Committee on Food Additives Neotame 100 Animal + Human Studies 2002 FDA [x 7000 +] Sucralose FDA 110 Animal + Human Studies 1998-1999 [x 500] No adverse effects at levels used in foods Latest finding: Annals of Oncology (2007) 4 Lack of association between the use of artificial sweeteners and the risk of several common neoplasm in human subjects

FDA Regulations: Artificial Sweeteners WHAT DO THEY IMPLY? Are approved by the FDA only after they undergo rigorous scrutiny Are not allowed into the market unless they are demonstrated to be safe for the public to consume The science of toxicology is based on the assumption that all compounds (including sugar and salt) are toxic at some levels 5 For all food additives, including artificial sweeteners the FDA determines an Acceptable Daily Intake (ADI) 2 What is an “ADI” ? 2 Defined as the amount of food additive that can be safely consumed on a daily basis over a person’s life time without risk

Accepted Daily Intake (ADI) levels of non-nutritive sweeteners 2 Eg For each of the approved sweeteners, the typical amount used by U.S. consumers is well within designated "acceptable daily intake (ADI) levels," or levels that can be consumed safely every day over a lifetime Eg Aspartame 2-3 mg/kg: Average consumption at the 90th Percentile

Beneficial role of artificial sweeteners as diet food Diets high in added sugars have been implicated with various health problems6 Obesity Dental caries, Dyslipidemias Overall poor diet quality American Dietetic Association (ADA) Artificial Sweeteners can help consumers 2 Cut down on calories and control weight Help to manage chronic conditions such as diabetes Potentially prevent cavities BUT Their use as a weight control measure seem to be effective only if used with concurrent energy restriction 7 and more rewarding if combined with healthy eating,physical activity and behavioural changes 8

Artificial Sweeteners “Appetite stimulants??” Another controversy of a relatively lower magnitude 9 During the 1980s There have been suggestions in popular press that not only are artificial sweeteners of no benefit in calorie control they may in fact increase appetite However a review of numerous short term studies found no association of artificial sweeteners with increased hunger rating and food intake

Conclusion: Artificial Sweeteners Despite unscientific articles in the mass media and the scientific press there seems to be no evidence at present that artificial sweeteners bear a carcinogenic risk, at least not if they are consumed within the permissible amounts Aspartame is the only artificial sweetener associated with adverse effects but only for persons with phenylketonuria, a rare metabolic disorder ADA: They may help to manage chronic conditions such as diabetes and potentially prevent cavities Their use as a weight control measure seem to be effective only if used with concurrent energy restriction and more rewarding if combined with healthy eating, physical activity and behavioural changes Declaration by the presenter: No conflict of interest

Major References: 1 Food and Drug Administration. Artificial Sweeteners: No calories…..Sweet! FDA Consumer Magazine 2006;40(4):27-28. 2 American Diabetes Association: Evidence-based nutrition principles and recommendations for the treatment and prevention of diabetes and related complications (Position statement). Diabetes Care 2002;25(1): 148-198. 3 Weinrauch MR, Diehl V. Artificial sweeteners- do they bear a carcinogenic risk. Annals Oncology 2004;15: 1460-1465. 4 Gallus S, Scotti L, Negri E, Talamini R, Frenchesci S, Montella M et al. Artificial sweeteners and cancer risk in a network of case control studies. Annals Oncology 2007;18: 40-44. 5 Stegnik LD. The aspartame story: a model for the clinical testing of a food additive. Am J Clin Nutr 1987;46:204-215. 6 Johnson RK, Frary C. Symposium: Carbohydrate-Friend or Foe. Choose beverages and foods to moderate your intake of sugars: The 2000 Dietary Guidelines for Americans-what’s all the fuss about. J Nutr 2001;131:2766s-2771s. 7 Sugar substitutes [Editorial] CMA J 1979;120:633-634. 8 International Food Information Council Foundation. Low calorie sweeteners: Their role in healthful eating [Pamphlet]. 9 Rolls BJ. Effect of intense sweeteners on hunger, food intake and body weight: a review. Am J Clin Nutr 1991;53:872-878.