- Click here for explanation of classification scheme.

To review if artificial sweeteners bear a carcinogenic risk.

• Relevant pre-clincal, clinical and epidemiological studies on artificial sweeteners and possible health risks were identified
• English language journals only
• Not limited to a certain period of time
• Key word used artificial sweetener, cancer, carcinogenic as well as all artificial names.

Non-English journals.

Several PubMed searches of the National Library of Medicine were performed. Relevant pre-clinical, clinical and epidemiological studies on artificial sweeteners and possible health risks were identified. All searches focused on English language journals only, but were not limited to a certain period of time. Where appropriate, cited references of articles were reviewed.

Compared animal and human studies for cancer.

Data sample varied, based on studies.

Saccharin

The first studies about the cancerogenous risk of saccharin in humans were only of descriptive design.

• Armstrong et al, 1974, a UK longitudinal study, did not show an increase in bladder cancer incidence during World War II, when saccharin consumption was high
• Armstrong et al, 1975, analyzed 19,709 death certificates from the UK between 1966 and 1972 and compared the bladder cancer mortality between diabetics, who used artificial sweeteners more frequently and non-diabetics. They did not find any significant differences between the groups.
• Jenson et al, 1982, a Danish study could not detect an increase of bladder cancer mortality in people aged 30 years or younger, who were born between 1941 and 1945, when saccharin use was higher than in the years before and after. The authors concluded that exposure to saccharin in utero does not increase bladder cancer incidence during the first three decades of life.
• Yu Y et al, 1998, a case-control study in China, analyzed different risk factors in 254 bladder cancer patients and 254 controls. They reported an odd ratio of 3.9 for bladder cancer in patients with frequent saccharin use of at least 15 years. This study has to be critically assessed as to its worth, because it was unable to identify the elevated risk of bladder cancer in smokers, which was proven by other larger trials.

Cyclamate

• There are no descriptive or case-control studies of cyclamate in humans, because it was approved after saccharin and products contained mixtures of both artificial sweeteners
• It was assumed that most consumers have used both saccharin and cyclamate since the introduction of cyclamate.

Aspartame

• Gurney JG et al, 1997: A case-controlled study on aspartame consumption was conducted in children with brain tumors. The study group compared 56 patients with 94 controls in terms of aspartame use and other known and suspected risk factors, such as maternal vitamin consumption, cured meat intake, passive smoke exposure, X-ray exposure and family history of brain history. They observed no elevated brain tumor risk to the child from maternal consumption of aspartame during pregnacy nor did they find elevated risks during any trimester of preganancy during breast-feeding.
• Epidemiological studies in humans: Many of these trials were conducted with small patient groups of up to 350 bladder cancer patients in the years 1965 to 1986. Wynder et al, 1980; Morrsion AS et al, 1980; Piper et al, 1986, showed no significantly increased risk of bladder carcinaoma for artificial sweetener use.
• Cartwright et al, 1981, a UK study, included 622 existing and 219 new cases of bladder cancer and matched them to hospital-based controls for age and sex. The study group found an increased relative risk (RR) for non-smoking males (RR=2.2; confidence interval (CI)=1.3-3.8) and non-smoking females (RR=1.6; 95% CI=0.8-3.2), but not for smokers. Sweetener use was defined as regular use for over one year at least five years to diagnosis.
• The most recent case-control study, Sturgeon et al, 1994, had 1,860 bladder cancer patients and 3,934 controls. They examined different factors, among which were smoking, urinary tract infection, coffee consumption, history of cystolithiasis and genetic pre-dispostion for the risk of inducing bladder cancer. Artificial sweetener consumption was classified as "low" (less than 1,680mg per day) or "heavy" (greater than 1,680mg per day). The risk of bladder cancer was not associated with low sweetener use in 966 patients and 3,410 controls. Heavy sweetener consumption (31 patients, 78 controls) led to a significantly increased RR of 1.3 (95% CI=0.9-2.1). High coffee consumption (greater than 50 cups per week) was associated with an RR of 1.4 and was comparable to heavy artificial sweetener use or the history of one or two urinary tract infections (RR=1.3). Authors felt, through scrutiny of the bladder cancer histologies, that heavy artificial sweetener use was asscoiated with higher grade, poorly differentiated tumors.

Human Data

• Heavy artificial sweetener use (greater than 1,680mg per day) leads to an increased relative risk of 1.3 for bladder cancer in humans. A more precise determination of the exact agents is not possible, because many artificial sweeteners are combined in current food products.
• Despite unscientific articles in the mass media and scientific press, there is no evidence that the artificial sweetener aspartame bears a carcinogenic risk. The approvals of new generation sweeteners (acesulfame-k, sucralose, alitame and neotame) are too recent to establish any epidemiological evidence about possible carcinogenic risks.

University/Hospital:

University of Cologne (Germany)

Review of actual studies.

• Armstrong B, Doll R. Bladder cancer mortality in England and Wales in relation to cigarette smoking and saccharin consumption. Br J Prev Soc Med. 1974; 28: 233-240.
• Armstong B, Doll R. Bladder cancer mortality in diabetics in relation to saccharin consumption and smoking habits. Br J Pre Soc Med. 1975; 29: 73-81.
• Jenson OM, Kamby C. Intra-uterine exposure to saccharin and risk of bladder cancer in man. Int J Cancer. 1982; 29: 507-509.
• Yu Y, Hu J, Wang PP et al. Risk factor for bladder cancer: a case-control study in noirtheast China. Eur J Cancer Prev. 1997; 6Z: 363-369.
• Gurney JG, Pogoda JM, Holly EA. Aspatame consumption in relation to childhood brain tumor risk: results froma case-control study. Natl Cancer Inst. 1997; 89: 1072-1074.
• Wynder EL, Stellman SD. Artificail sweetener use and bladder cancer; a case-control study. Science, 1980; 207:1214-1216.
• Morrison AS, Buring JE. Artificial sweeteners and cancer of the lower urinary tract. N Engl J Med. 1980; 302: 537-541.
• Cartwright RA, Adib R et al. The epidimilogy of bladder cancer in West Yorkshire. A preliminary report on non-occupational aetiologies. Carcinogenesis, 1981; 2: 343-347.
• Sturgeon SR, Hartge P, Silverman DT et al. Associations between bladder cancer risk factors and tumor stage and grade at diagnosis. Epidemiology, 1994; 5: 218-225.
• Piper JM et al. Bladder cancer in young women. Am J Epidemiol. 1986; 123: 1,033-1,042