Study: Do artificial sweeteners increase the risk of cancer?

IN-DEPTH REVIEW OF RESEARCH

Study background

Artificial sweeteners are low- and no-calorie food additives with high sweetening power: 200 to 600 times sweeter than table sugar (sucrose). Artificial sweeteners are used as an alternative to added sugars in a wide range of food and beverages. Studies looking at links between artificial sweeteners and cancer have had conflicting results. Some animal studies suggest that certain artificial sweeteners potentially cause cancer, while others do not. Most human studies have focused only on the use of artificially sweetened beverages to estimate a person’s total intake of artificial sweeteners. This may have underestimated total exposure due to the wide use of artificial sweeteners in processed foods. This prospective, cohort study looked at more precise measurements of artificial sweetener intake from all dietary sources to determine if long-term exposure is linked with an increase in cancer risk in men and women.

Researchers of this study wanted to know

The researchers wanted to know if certain artificial sweeteners increase the risk of cancer.

Populations looked at in this study

This research looked at 102,865 adults from the French population-based NutriNet-Santé study—a large, ongoing effort looking at the links between nutrition and health. The average age at the beginning of the study was 42.5 years; about 80 percent of participants were women. Participants who had cancer at the beginning of the study were excluded.

Study design

Researchers collected information about the participants for an average of 7.8 years. They collected data about participants' diet every six months using online, 24-hour dietary records that were randomly assigned over 15 days. The average number of 24-hour diet records per participant was 5.6. Researchers also asked for detailed information each year about health status, physical activity, lifestyle and demographic choices. To verify cancer cases, participants provided medical records and pathology reports. Medical information was obtained from more than 90 percent of cancer cases; 95 percent of these were verified. The researchers used statistical tests to adjust for multiple factors, including age, sex, BMI, weight gain during follow-up, physical activity, smoking status, alcohol use, educational level, family history of cancer, prevalent diabetes and diet. Breast cancer models were adjusted for age at menarche, number of children, menopausal status and contraceptive use. These approaches (adjusting for different factors) were an attempt to understand whether artificial sweeteners or these other factors accounted for any changes in the rate of cancer.

Study findings

Among the participants:

• Artificial sweeteners were used by 37% of the participants.
• The most common artificial sweeteners used were NutraSweet/Equal (aspartame), which contributed to ~60% of the participants’ total intake of artificial sweeteners; Sunett/SweetOne (acesulfmame-K), which made up ~30% of total intake; and Splenda (sucralose) which made up ~10% of total artificial sweetener intake.
• The most common foods or drinks with artificial sweeteners were artificially sweetened beverages, table-top sweeteners and yogurt/cottage cheese.

By the end of the study, 3,358 cases (3.3%) of cancer were diagnosed among participants: 982 cases of breast cancer and 403 cases of prostate cancer. The results showed:

• a higher total intake of artificial sweeteners was linked to a 13% increase in risk for overall cancer when compared to participants who had no intake of artificial sweeteners. Over several years of follow-up, about 3 in 100 people who consumed no artificial sweeteners were diagnosed with cancer compared to 3 to 4 in 100 people who consumed artificial sweeteners.
• a higher intake of NutraSweet/Equal (aspartame) was linked to a 22% increase in risk for breast cancer when compared to participants who had no intake of artificial sweeteners. During the study, about 1 in 100 women who consumed no artificial sweeteners developed breast cancer compared to 1 to 2 in 100 women who consumed artificial sweeteners.
• no link between intake of Splenda (sucralose) and any type of cancer.
• no link between any artificial sweeteners and prostate cancer.
• no interaction between artificial sweetener intake and body mass index (BMI) for any type of cancer.
• that the link between intake of artificial sweeteners and breast cancer risk did not differ in premenopausal and postmenopausal women.

Strengths and Limitations

Strengths

• This prospective cohort study included over 102,000 participants and followed them for a median of nearly eight years, allowing researchers to determine how long-term intake of specific artificial sweeteners may impact overall cancer risk and by most the common site for women (breast) and men (prostate).
• The participants provided detailed diet records, including names/brands of specific products. Portion sizes were validated via photographs or serving container size. Researchers examined the effect of each type of artificial sweetener individually and combined sweeteners. This design is an improvement on past studies that have primarily relied on the use of artificially sweetened beverages to estimate total intake of artificial sweeteners.
• The researchers attempted to adjust for several factors (e.g., age, sex, BMI, physical activity, smoking, etc.) to help better determine the specific impact of artificial sweeteners on cancer risk.
• The study was funded by academic research institutions and European cancer institutes rather than companies that might have had a potential conflict of interest.

Limitations

• The participants were limited to French adults, the majority of whom were white. Most (~80%) of the participants were women. The results of the study may not apply as well to broader populations such as men or people from different racial or ethnic backgrounds or different countries. The study factored in a family history of cancer but did not look at whether participants had a hereditary genetic mutation that increases cancer risk.
• The study relied on participant-reported diet records, which can be prone to error. Nearly 15% of the participants were excluded due to being “energy under-reporters,” meaning their reports of total caloric intake were abnormally low when accounting for sex, age, height, weight and physical activity level.
• The potential for selection bias exists because participants in volunteer-based longitudinal cohort studies (including this one) are more likely to be women who have a higher educational and socioeconomic status.
• The researchers acknowledged the potential for “reverse causality” in which participants may change their diet (perhaps increasing their intake of sweeteners) before their cancer diagnosis.
• Too few cases of several types of cancer (e.g., pancreatic, kidney, liver, bladder) were diagnosed to evaluate the impact of artificial sweeteners.
• Although multiple adjustments were made to the data to better understand whether artificial sweeteners or other factors account for any changes in the rate of cancer, this type of observational study does not prove a direct link between artificial sweeteners and cancer. That requires a controlled, prospective study in which some people get artificial sweeteners and others do not over many years. These types of studies are difficult to conduct because it is hard, if not impossible, to control people’s diets.

Context

The results of prior studies looking at the effects of artificial sweeteners on cancer risk have been conflicting. Some animal studies suggest that artificial sweeteners may be linked to increased cancer rates but the results remain controversial as the levels of artificial sweeteners in these studies often exceed normal limits. In human studies, the results are mixed but the majority have not found evidence that artificial sweeteners contribute to cancer risk when used within established acceptable daily intakes (ADIs). A recent systematic review and meta-analysis found that most health outcomes (including cancer) did not differ in a meaningful way between people who were exposed or unexposed to artificial sweeteners, though researchers note that additional studies are needed.

It is difficult to study whether a single item in a person’s diet can increase their risk of cancer. A recent study in this same group of participants (NutriNet-Santé study) found that a high intake of regular sugar was linked to a 17 percent increase in relative risk for overall cancer and a 50 percent increase in relative risk for breast cancer. The researchers interpret this as suggesting that intake of artificial sweeteners and excessive sugar may be equally linked with cancer risk. Although they have limitations, these types of large, prospective cohort studies provide valuable information for determining whether specific foods or food additives could be considered modifiable risk factors for cancer prevention.

Conclusions

This study found that artificial sweeteners were linked to a 13 percent increase in cancer risk. To illustrate how this affects real-world risk, in the US, the average person’s lifetime risk of developing any cancer is about 40 percent; using artificial sweeteners would increase that to about 45 percent. The study also found that NutraSweet/Equal (aspartame) increased breast cancer risk by 22%. In the US, the average woman’s lifetime risk of breast cancer is about 13%; using artificial sweeteners would increase that to about 16 percent.

Many people use artificial sweeteners to avoid excess sugar, which comes with its own health risks. Most data indicate that artificial sweeteners are unlikely to have a large effect on cancer risk. Other lifestyle factors (drinking alcohol, obesity, lack of exercise, smoking) have similar or greater effects on cancer risk. In addition, this study did not include stevia, a no-calorie natural sweetener made from the stevia plant. It is possible that stevia could be a safer way to reduce sugar intake without increasing cancer risk, but more studies are needed. Although not enough evidence suggests that people who stop using artificial sweeteners can reduce their cancer risk, talking with a nutritionist about your overall diet may be helpful.