Does aspartame cause cancer?

This post was chosen as an Editor's Selection for ResearchBlogging.org
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Aspartame and other artificial sweeteners have long been a source of controversy and debate regarding whether or not it has adverse health effects. Among the effects claimed, perhaps the most serious is potential carcinogenicity. However, industry and regulators generally maintain there is no evidence of carcinogenicity. Is the risk real?

To answer this question, I’ll look at two papers. On the “yes” side, the primary evidence of carcinogenicity comes from a bioassay conducted by the Ramazzini Foundation (Soffritti et al., 2007), which concluded that aspartame caused multiple forms of cancer in experimental animals at doses close to the human acceptable daily intake, with increased effects when exposure begins early in life. However, several agencies and researchers have been critical of the methodology and interpretation in this paper. I also did a quick independent look at several other carcinogenicity studies conducted by the Ramazzini Foundation, and every study I looked at had a positive result, which raises a bit of a flag.

On the “no” side, I’ll look at a safety evaluation published by Magnuson et al. (2007). This evaluation looked at animal bioassays (including the Ramazzini Foundation study) and human epidemiological data, and concluded that the data indicate aspartame is safe and that the Soffritti et al. 2007 study does not provide convincing evidence of aspartame carcinogenicity. However, this study was sponsored by Ajinomoto Company, Inc., the major producer of aspartame, and as a result the potential for bias has been raised. I do not believe that a study should be automatically discredited just because it was sponsored by a company with a financial stake in the outcome, but it does mean the conclusions should be examined carefully in case of any bias, whether intentional or not.

When there are two studies with conflicting positions, both of which of questions about their quality and/or potential biases, then instead of relying on the conclusions of the authors we need to look closer at the actual data.

The Soffriti et al. study involved feeding rats a diet with aspartame added at concentrations of 0, 400 ppm or 2000 ppm. They began feeding aspartame to the mothers of the study rats starting on the 12th day of pregnancy, then fed the study rats from weaning until their natural death. This differs from normal cancer bioassays for rats, in which exposure doesn’t normally start until after weaning, and the study is normally ended after 24 months. The authors reported a significant increase in total malignant tumours in male rats at 2000 ppm. The occurrence of lymphomas/leukemias was significantly increased in males and females at 2000 ppm, and showed a dose-related trend in females; a significant increase in mammary carcinomas was also observed in females.

Several concerns have been raised about this study. In particular, Magnuson et al. noted that the study did not reliably estimate early life exposure, and was missing quite a bit of key information. Also, perhaps more importantly, the elevated cancer rates reported in the rats exposed to 2000 ppm were actually generally consistent with normal rates of these cancers shown in unexposed rats; the control and low exposure rats in this study actually appeared to have lower rates of the cancers than normal. Also, the lymphomas/leukemias in the study were often in the lung, and the rat population used has a history of chronic lung infections which can cause lymphoma/leukemia in the lung.

Interestingly, the rats exposed to 2000 ppm aspartame actually seemed to live longer than the unexposed control rats in the study (causes of death were not reported). Since cancer rates increase with age, this alone could explain the increased cancer rates, and is a flaw in the study approach of running the experiment until all animals die a natural death rather than sacrificing animals at a fixed point after most of their lifespan has passed. An evaluation of a previous Ramazzini Foundation study by the European Food Safety Authority found that different dose groups were kept in separate rooms, resulting in different rates of disease in the populations; it is not clear whether this applies to the 2007 study. Overall, I’m inclined to agree with Magnuson et al. that the Soffritti et al study does not provide convincing evidence of carcinogenicity due to significant flaws in the methodology.

So what about the other carcinogenicity studies summarized by Magnuson et al.? Several other chronic rodent studies have been conducted; one of these initially showed borderline evidence of increased brain tumours at high doses, but further evaluation of the data from this study, including more detailed examination of the rat brains, found that this was not the case. The other studies were negative. There were also some more recent studies conducted by the US National Toxicology Program using mice with genetic modifications expected to make them more sensitive to various cancers; these studies did not show any evidence of carcinogenicity despite using doses up to 50,000 ppm.

There were some epidemiological studies that showed increases in rates of brain tumours and breast cancer starting around the time aspartame was introduced to the market. However, several flaws were identified in these studies by several scientists, including failure to account for changes in diagnosis at the same time, misleading presentation of data, and failure to account for the lag time between exposure and cancer development. Also, we have to remember that correlation does not automatically mean causation. Another more recent epidemiological study conducted by the National Cancer Institute did not show any evidence of an association between aspartame consumption and brain or blood cancers. Several case control studies also showed no significant relationships, although two found non-significant increased rates of certain brain cancers. Magnuson et al. concluded based on the combined results that there was no evidence of aspartame carcinogenicity.

Overall I agree that the available data do not provide any convincing evidence of aspartame causing cancer. However, there are enough question marks that I don’t think we can completely exclude it. Multiple studies have shown non-significant increases in certain brain cancers; while these studies have limitations and the results are not significant, given the widespread consumption of aspartame I believe it is worth continuing to study this. I’d also like to see another animal bioassay that includes the prenatal exposures used in the Ramazinni Foundation study without the methodological flaws to confirm whether there could be any associations between prenatal exposure and cancers.

Proving that a substance does not cause cancer is pretty much impossible; all we can do is collect more and more data until the weight of evidence becomes fairly convincing. Overall I think there is no clear evidence of carcinogenicity, but I’m not convinced the data are adequate yet to completely close the book.

Magnuson, B., Burdock, G., Doull, J., Kroes, R., Marsh, G., Pariza, M., Spencer, P., Waddell, W., Walker, R., & Williams, G. (2007). Aspartame: A Safety Evaluation Based on Current Use Levels, Regulations, and Toxicological and Epidemiological Studies Critical Reviews in Toxicology, 37 (8), 629-727 DOI: 10.1080/10408440701516184

Soffritti, M., Belpoggi, F., Tibaldi, E., Esposti, D., & Lauriola, M. (2007). Life-Span Exposure to Low Doses of Aspartame Beginning during Prenatal Life Increases Cancer Effects in Rats Environmental Health Perspectives, 115 (9), 1293-1297 DOI: 10.1289/ehp.10271

2 Responses to Does aspartame cause cancer?

  1. […] always been a bit uneasy about non-calorie sweeteners. And I really can’t get over the taste. Ashartus of cause/effect asks whether Aspartame is carcinogenic, and further fuels my […]

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