Food additive emulsifiers and cancer risk: Results from the French prospective NutriNet-Santé cohort

Abstract

Background: Emulsifiers are widely used food additives in industrially processed foods to improve texture and enhance shelf-life. Experimental research suggests deleterious effects of emulsifiers on the intestinal microbiota and the metabolome, leading to chronic inflammation and increasing susceptibility to carcinogenesis. However, human epidemiological evidence investigating their association with cancer is nonexistent. This study aimed to assess associations between food additive emulsifiers and cancer risk in a large population-based prospective cohort.

Methods and findings: This study included 92,000 adults of the French NutriNet-Santé cohort without prevalent cancer at enrolment (44.5 y [SD: 14.5], 78.8% female, 2009 to 2021). They were followed for an average of 6.7 years [SD: 2.2]. Food additive emulsifier intakes were estimated for participants who provided at least 3 repeated 24-h dietary records linked to comprehensive, brand-specific food composition databases on food additives. Multivariable Cox regressions were conducted to estimate associations between emulsifiers and cancer incidence. Overall, 2,604 incident cancer cases were diagnosed during follow-up (including 750 breast, 322 prostate, and 207 colorectal cancers). Higher intakes of mono- and diglycerides of fatty acids (FAs) (E471) were associated with higher risks of overall cancer (HR high vs. low category = 1.15; 95% CI [1.04, 1.27], p-trend = 0.01), breast cancer (HR = 1.24; 95% CI [1.03, 1.51], p-trend = 0.04), and prostate cancer (HR = 1.46; 95% CI [1.09, 1.97], p-trend = 0.02). In addition, associations with breast cancer risk were observed for higher intakes of total carrageenans (E407 and E407a) (HR = 1.32; 95% CI [1.09, 1.60], p-trend = 0.009) and carrageenan (E407) (HR = 1.28; 95% CI [1.06, 1.56], p-trend = 0.01). No association was detected between any of the emulsifiers and colorectal cancer risk. Several associations with other emulsifiers were observed but were not robust throughout sensitivity analyses. Main limitations include possible exposure measurement errors in emulsifiers intake and potential residual confounding linked to the observational design.

Conclusions: In this large prospective cohort, we observed associations between higher intakes of carrageenans and mono- and diglycerides of fatty acids with overall, breast and prostate cancer risk. These results need replication in other populations. They provide new epidemiological evidence on the role of emulsifiers in cancer risk.

Trial registration: ClinicalTrials.gov NCT03335644.

Fig 1. Flowchart of included participants from the NutriNet-Santé cohort, 2009–2021 (n = 92,000).

Fig 2. Dietary sources of total and groups of emulsifier intakes among study participants from the NutriNet-Santé cohort, 2009–2021 (N = 92,000).^a,b FAs, fatty acids.

^aGroups of emulsifiers were defined as follows (European codes): total phosphates (E339, E340, E341, E343, E450, E451, E452), total lactylates (E481, E482), total polyglycerol esters of FAs (E475, E476), total mono and diglycerides of FAs (E471, E472, E472a, E472b, E472c, E472e), total celluloses (E460, E461, E464, E466, E468), total carrageenans (E407, E407a), total alginates (E400, E401, E402, E404, E405), and total modified starches (E14xx). ^bDetailed % are presented in eTable A in S1 Appendix.

Fig 3. Contribution of individual emulsifiers to total emulsifier intakes (%) among study participants from the NutriNet-Santé cohort, 2009–2021 (N = 92,000).^a FAs, fatty acids^a.

Other emulsifiers included (ordered by descending contributions): triphosphates (E451), gum arabic (E414), polyphosphates (E452), carob bean gum (E410), cellulose (E460), tricalcium phosphate (E341), mono and diacetyl tartaric acid esters of mono- and diglycerides of FAs (E472e), hydroxypropyl methyl cellulose (E464), polyglycerol esters of FAs (E475), lactic acid esters of mono- and diglycerides of FAs (E472b), sodium stearoyl-2-lactylate (E481), sodium alginate (E401), ammonium salts of phosphatidic acid (E442), esters of mono- and diglycerides of FAs (E472), polyglycerol esters of interesterified ricinoleic acid (E476), citric acid esters of mono- and diglycerides of FAs (E472c), silicon dioxide (E551), tripotassium phosphate (E340), methyl cellulose (E461), carboxymethylcellulose (E466), trisodium phosphate (E339), acetic acid esters of mono- and diglycerides of FAs (E472a), agar (E406), sucrose esters of FAs (E473), propylene glycol esters of FAs (E477), gellan gum (E418), sorbitan tristearate (E492), processed Euchema seaweed (E407a), beeswax (E901), potassium alginate (E402), maltitol (E965), triethyl citrate (E1505), xylitol (E967), glycerol esters of rosin (E445), polyoxyethylene sorbitan monooleate (E433), potassium dihydrogen citrate (E332), calcium alginate (E404), calcium stearoyl-2-lactylate (E482), konjac flour (E425), cross-linked sodium carboxymethylcellulose (E468), sucrose acetate isobutyrate (E444), sodium tartarate (E335), polyoxyethylene sorbitan monostearate (E435), sorbitan monostearate (E491), alginic acid (E400), propylene glycol (E1520), quillaia extract (E999), sodium aluminium phosphate (E541), magnesium hydrogen phosphate (E343), propylene glycol alginate (E405), and dimethyl polysiloxane (E900).

Fig 4. Associations between selected emulsifier intakes and cancer risks among study participants from the NutriNet-Santé cohort, 2009–2021 (N = 92,000).^a,b DAG, diglyceride of fatty acid; FAs, fatty acids; HR, hazard ratio; MAG, monoglyceride of fatty acid.

^aEmulsifiers with at least 1 statistically significant association with cancer risk are represented here. The detail of all investigated associations between emulsifier intakes and cancer risk with corresponding HRs and 95% CIs is provided in eTable D, as well as cut-offs for categories of emulsifier intakes, and number of cancer cases per category of emulsifier intakes. Mean values for emulsifier intake within each category is presented in eTable B. Groups of emulsifiers were defined as follows (European codes): total carrageenans (E407, E407a). The following emulsifiers were coded as sex-specific tertiles: total carrageenans, E407, E412, E415, E440, E450, E471, and E500. Due to a higher proportion of non-consumers among the included participants, the following emulsifiers were coded as non-consumers (first category), low consumers (second category), and high consumers (third category), with low- and high-consumptions defined according to sex-specific median intakes among consumers: E340, E410, E414, E475, and E901. ^bMultivariable Cox proportional hazard models were adjusted for age (time-scale), sex, BMI (continuous, kg/m²), height (continuous, cm), physical activity (categorical IPAQ variable: high, moderate, low), smoking status (never smoked, former smoker, current smokers), number of smoked cigarettes in pack-years (continuous), educational level (less than high school degree, <2 y after high school degree, ≥2 y after high school degree), number of dietary records (continuous), family history of cancer (yes/no), energy intake without alcohol (continuous, kcal/d), daily intakes of alcohol (continuous, g/d), lipids (continuous, g/d), sugars (continuous, g/d), sodium (continuous, g/d), fibre (continuous, g/d), consumption levels of fruits and vegetables (continuous, g/d), red and processed meats (continuous, g/d), and dairy products (continuous, g/d). Breast cancer models were additionally adjusted for oral contraception (yes/no, in total and premenopausal models only), age at menarche (never, <12 y, ≥12 y), number of biological children (continuous), age at first biological child (no child, <30 y, ≥30 y), menopausal status at baseline (premenopausal, postmenopausal, in total models only), hormonal treatment for menopause (yes/no, in total and postmenopausal models only).