1. 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

2. 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

3. 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

4. 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

5. 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

6. 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.

7. 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

8. 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

9. 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

10. 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

11. 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

12. 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

13. Second Generation Artificial Sweeteners 1
FDA: OK
90 Studies
FDA
Acesulfame-K
[x 200]
(FAO/WHO) Joint Expert Committee on Food Additives
Neotame
100 Animal + Human Studies
2002
FDA
[x ]
Sucralose
FDA
110 Animal + Human Studies
[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

14. 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

15. 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

16. 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

17. 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

18. 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

19. 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):
3 Weinrauch MR, Diehl V. Artificial sweeteners- do they bear a carcinogenic risk.
Annals Oncology 2004;15:
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:
5 Stegnik LD. The aspartame story: a model for the clinical testing of a food
additive. Am J Clin Nutr 1987;46:
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:
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: