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Monday, March 15, 2010

Saccharin's Turbulent History

Saccharin, first synthesized in 1879 by fellows at JHU, eventually became a popular sugar substitute.

Superficially, saccharin resembles sucrose in that it is composed of 2 organic rings.

Although the "sweetness triangle" theory is too simple to fully explain sweet-tasting molecules, it does provide a model that explains many, including saccharin - with its three hydrogen bonding oxygens and a hydrophobic base. (1)

In 1968 two studies linked cyclamate, a related sweetener, to bladder cancer. (2) Cyclamate was banned shortly afterward. (3) It remains banned in the United States, possibly because it has been found to have a broader range of toxic effects than saccharin (4, 5), but more probably, in my opinion, because there are enough acceptable alternatives.

Saccharin was, then, the only sweetener left on the market, and, in the wake of the ban, it was a highly suspicious substance - especially considering it's chemical and structural similarity. Implication in bladder cancer was repeatedly found, however, the dosage levels were so high that application to humans seemed unlikely (6, 7, 8). There was an attempt to ban saccharin in 1972 that failed. At that point there had been several studies that seemed to clear saccharin as a carcinogen, and that the mechanisms of it's action in mouse bladder cancer are not applicable to humans. (9, 10, 11).

Nevertheless, in 1977 the "Saccharin Study and Labeling Act" required a mandatory warning label. The response to this labelling was, paradoxically, highly increased usage. (3)

Saccharin has been found to inhibit digestive enzymes (12), cause ulcers (13), and cause some blood abnormalities (14). In at least two studies, saccharin use has been correlated with weight gain and, in 2008, a causative behavioral model was shown in rats. (15, 16)

Despite industry sponsorship of the molecule, it has never been shown that saccharin reduced mortality, obesity or weight gain among diabetics. One can only imagine, given the magnitude of the industry, how many unpublished studies there must be failing to conclude this relationship. The few published studies that there are seem to find the opposite.

Given that the benefits (unproven, possibly inverse) don't outweigh the risks (many), I would not recommend the use of saccharin to a diabetic. It is my opinion that, given the research, it is highly unlikely that saccharin is a carcinogen, however.

(1) "Computer Simulation of Chemical and Biological Properties of Saccharides" (1995) Dr. S. Immel
(2) "Production of Mouse Urinary Bladder Carcinomas by Sodium Cyclamate" (1970) George T. Bryan and Erdogan Ertürk
(3) "The Pursuit of Sweet: A History of Saccharin"
(4) Long-Term Toxicity and Carcinogenicity Study of Cyclamate in Nonhuman Primates (2000) S. Takayama, A. G. Renwick, S. L. Johansso
(5) "Effects of Sodium Cyclamate on the Rat Placenta: A Morphometric Study" (2006) Marcelo Alexandre de Matos; Alex Tadeu Martins & Reinaldo Azoubel, DOI: 10.4067/S0717-95022006000300001
(6) "Production of Urinary Bladder Carcinomas in Mice by Sodium Saccharin" (1970) George T. Bryan, Erdogbrevean Ertürk, and Osamu Yoshida
(7) "Evaluation of a new model to detect bladder carcinogens or co-carcinogens" (1975) Hicks RM, Wakefield J, Chowaniec J.
(8) "Response of the rat to saccharin with particular reference to the urinary bladder." J. Chowaniec and R. M. Hicks
(9) "Cancer Mortality and saccharin consumptionin diabetics" (1976) Bruce Armstrong
(10) "Feeding studies on sodium cyclamate, saccharin and sucrose for carcinogenic and tumour-promoting activity " (1970) F.J.C. Roe, L.S. Levy and R.L. Carter
(11) "A chronic study of artificial sweeteners in Syrian golden hamsters" (1975) J. Althoff, A. Cardesa, P. Pour and P. Shubik
(12) "The inhibition of urease and proteases by sodium saccharin." (1982) Lok E, Iverson F, Clayson DB.
(13) "Glandular stomach hemorrhage induced by high dose saccharin in young rodents" T. Okamura, E.M. Garlanda and S.M. Cohen
(14) "Haematological abnormalities induced by feeding a common artificial sweetener, saccharin, in ICR swiss mice" Om Prasada and Gulshan Raia
(15) "Artificial sweetener use and one-year weight change among women" (1986) Steven D. Stellman Ph.D. and Lawrence Garfinkel M.A.
(16) "A role for sweet taste: Calorie predictive relations in energy regulation by rats."(2008) Swithers, Davidson

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