artificial sweeteners and cancer risk

 A large French population-based nutrition study (NutriNet-Sante) found that artificial sweeteners (especially aspartame and acesulfame-K) were associated with increased cancer risk (see artificial sweeteners and cancer PLOS2022 in dropbox, or doi.org/10.1371/journal.pmed.1003950)

Details:

-- 102,865 adults in the NutriNet-Sante study were included, from 2009-2021, with a median of 7.8 years of follow-up, comprising 708,905 person-years. All needed internet access to be included

-- mean age 42, 79% female, BMI 24

-- family history of cancer 38%, diabetes 2%, >2 years after high school education 65%, current smoker 17%/former 32%/never 50%, physical activity level low 21%/moderate 37%/high 28%

-- alcohol intake 8 g/d, saturated fats 33 g/d, dietary fiber 19 g/d, added sugar 39 g/d, % of energy from sugar 8%, sugary drinks 48 ml/d, whole grain food 34 g/d, fruit and veges 405 g/d, dairy 196 g/d, ultra-processed foods 17 g/d, 

-- artificial sweetener was consumed by 37% of the population, with intake 16 mg/d, aspartame 9 mg/d, acesulfame-K 5 mg/d, sucralose 2 mg/d, and were consumed by 28%, 34%, and 4% of the population, respectively

    -- the main sources of artificial sweeteners were soft drinks with no added sugars (53%), table-top sweeteners (29%), and yogurt/cottage cheese (8%)

-- dietary intakes including consumption of the various sweeteners was assessed by repeated 24-hour dietary records every 6 months

    -- average number of 24-hour dietary records: 5.6/person

-- associations between dietary sweeteners and cancer incidence was adjusted for age, sex, education, physical activity, smoking, BMI, height, weight gain during follow-up, diabetes, family history of cancer, number of 24-hour dietary records, and baseline intakes of energy, alcohol, sodium, saturated fats, fiber, sugar, fruits and vegetables, whole-grain foods, and dairy products

 -- main outcome: association between dietary artificial sweeteners (AS) and cancer outcomes, stratified by type of AS

Results:

-- artificial sweetener consumption higher in women, younger people, smokers, less physically active, more educated, and more likely to have prevalent diabetes. 

-- for food items, more AS also in those with lower total energy consumed, and lower alcohol intake, saturated fats, fiber, fruits and vegetables, and whole-grain foods, and more sodium, total sugar, dairy products, sugary foods and drinks, and unsweetened non-alcoholic beverages

-- overall 3,358 incident cancers were identified: 982 breast, 403 prostate, 2,023 obesity-related cancers; obesity-related cancers as defined by the World Cancer Research Fund: colorectal, stomach, liver, mouth, pharynx, larynx, esophageal, breast (usually post-menopausal breast cancer assoc with obesity and decreased in pre-menopause, though some conflicting results), ovarian, endometrial, and prostate

 

-- overall cancer risk, comparing artificial sweetener consumers to non-consumers: 3358 cases

           -- low AS consumers: 14% higher, aHR 1.14 (1.05-1.25)

           -- high AS consumers: 13% higher, aHR 1.13 (1.03-1.25) , p-trend = 0.002

    -- aspartame:

           -- low AS consumers: 12% higher, aHR 1.12 (1.02-1.23)

           -- high AS consumers: 15% higher, aHR 1.15 (1.03-1.28), p-trend =0.002

    -- acesulfame-K:

            -- low AS consumers: 12% higher, aHR 1.12( 1.03-1.22)

            -- high AS consumers: 13% higher, aHR 1.13 (1.01-1.26), p-trend =0.007

 

-- Breast cancer risk: 979 cases (no difference found between pre- and post-menopausal women)

           -- low AS consumers: nearly significant trend of 11% higher, aHR 1.11 (0.95-1.30)

           -- high AS consumers: nearly significant trend of 16% higher, aHR 1.16 (0.97-1.38), p-trend = 0.064

    -- aspartame:

           -- low AS consumers: nearly significant trend of 9% higher, aHR 1.09 (0.92-1.29)

           -- high AS: 22% higher, aHR 1.22 (1.01-1.48), p-trend =0.036

    -- acesulfame-K:

            -- low AS consumers: nearly significant trend of 11% higher, aHR 1.11 (0.95-1.30)

            -- high AS consumers: nearly significant trend of 17% higher, aHR 1.17 (0.96-1.43), p-trend=0.086

 

--Prostate cancer risk: 403 cases

     -- none are close to being statistically significantly associated with AS

 

-- obesity-related cancer risk: 2,023 cases

           -- low AS consumers: nearly significant trend of 8% higher, aHR 1.08 (0.97-1.21)

           -- high AS consumers: 13% higher, aHR 1.13 (1.00-1.28), p-trend = 0.036

    -- aspartame:

           -- low AS consumers: nearly significant trend of 8% higher, aHR 1.08 (0.96-1.22)

           -- high AS: 15% higher, aHR 1.15 (1.01-1.32), p-trend =0.026

    -- acesulfame-K:

            -- low AS consumers: nearly significant trend 9% higher, aHR 1.09 (0.97-1.22)

            -- high AS consumers: nearly significant trend of 13% higher, aHR 1.13 (0.97-1.30), p-trend=0.064

 

-- those consuming more than one AS, or those combining AS with sugar, had similar findings

        

Commentary:

-- the World Health Organization recommends limiting sugar consumption to <10% of daily energy intake because of its well-known deleterious effects including weight gain, metabolic syndrome, dental caries, etc.

-- several artificial sweeteners have been developed in this light, including ones with zero or few calories, though all have extremely high sweetness power

-- aspartame has 200 times the sweetness of sugar and in France is found in 1400 food products, and more than 6000 worldwide

-- acesulfame-K (E950) and sucralose (E955) are respectively 200 and 600 times sweeter than sucrose, and are calorie-free; this is used in sodas, fruit juices, alcohol, dairy products, ice cream, desserts, jams, baked goods, toothpaste/mouth wash, and is approved by the FDA as being safe

-- prior epidemiologic studies have not supported artificial sweeteners in weight loss, glycemic control, or cardiovascular/kidney diseases; and several of found higher incidences of obesity, hypertension, metabolic syndrome, type II diabetes, and cardiovascular events

-- many of the prior studies on artificial sweeteners and cancer had been done on animals or in vitro; most to the previous epidemiologic studies have also not differentiated different brands of artificial sweeteners

-- this study found that AS (especially aspartame and acesulfame-K) were associated with increased cancer risk, and in particular aspartame was associated with increased breast and obesity-related cancers (one should not necessarily assume that aspartame is the worst actor here: there was less use of the others and therefore harder to have a statistically significant outcome)

-- other studies have found that high levels of sugar intake are associated with increased cancer risk

 

-- another NutriNet-Sante Study found that people drinking sugary drinks had more cardiovascular events, and those drinking artificially sweetened ones did even worse: http://gmodestmedblogs.blogspot.com/2020/11/cardiovasc-disease-inc-with-sweet.html

-- a European prospective study found that consuming soft drinks was associated with higher mortality and that artificially-sweetened ones were much worse: http://gmodestmedblogs.blogspot.com/2019/10/soft-drinks-increase-mortality.html

-- another blog reviewed the role of non-caloric artificial sweeteners on weight and diabetes (increases insulin secretion, insulin resistance and accelerated atherosclerosis in animal studies) as well as some human data; and AS really harms the microbiome (enrichment of Bacteroides and some Clostridiales and decreases in Lactobacilli and some other members of Clostridiales; several of these microbiota changes have been associated with type II diabetes in humans): see http://gmodestmedblogs.blogspot.com/2017/01/artificial-sweeteners-microbiome1.html

-- other studies have found links between both sugar and AS soda consumption and hypertension (see https://www.tandfonline.com/doi/abs/10.3109/10641963.2015.1026044 )

Limitations:

-- requiring internet access might have limited the diversity of people involved, perhaps because of not being tech-savvy, or not speaking french, etc

-- this study had a younger group of healthy people (eg 2% diabetic) with more education, exercise, and healthy eating than in many societies (eg the US); so, these results may not be generalizable

    -- one issue with trying to isolate a single factor (eg AS) is that this is fundamentally reductionist: people have lots and lots of behaviors that probably function together for health outcomes. Those using artificial sweeteners are also probably as a group more likely to be overweight. Or have diabetes/pre-diabetes. Or perhaps eat other non-so-healthy foods. Or not do as much exercise (perhaps looking to an easy fix of substituting AS for sugar, perhaps under the misconception that AS is healthier…)

-- this was an observational study, so unable to assert causality (ie was it really the artificial sweetener's fault that cancer developed? or some other foods or less healthy behaviors in those consuming more AS?). is there reverse causality (those with cancer, knowingly or not, ate differently? also perhaps thinking that it is better for them to use AS??)

-- not much data on sucralose since lower consumption. And no information on other artificial sweeteners

So, bottom line: artificial sweeteners are certainly artificial (they live up to that part, as well as being really, really sweet) but really bad for the body: they seem much worse than sugar itself (which is itself much too prominent in US diets: see https://www.cdc.gov/nutrition/data-statistics/sugar-sweetened-beverages-intake.html ). sort of like margarine actually being worse than butter (turns out that trans fats are much worse than saturated ones...). so much for our guesses on what is healthier..

One of my personal medical missions is to talk with patients about the misrepresentation of artificial sweeteners (“no calories, so you will lose weight and help your diabetes”), help them decrease overall sugar intake, and really promote water as the best thing to drink (of course, with unsweetened coffee as a close second….)

geoff

 

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