Lecithins (E322)

What it is

Lecithins are fatty substances, mainly from soya, that keep oil and water mixed in food ¹.

E322 (INS 322) comprises phosphatide mixtures; oil-free soya lecithin is 21% phosphatidylcholine ¹.

How often it is used

Lecithins are the second most common additive in French packaged food ².

13,102 of 126,556 products listed them in 2019 ². Of 106,489 adults, 86.57% consumed them, cohort mean 53.94 mg/day ³.

In the body

Choline is freed from lecithins in digestion ¹.

Phospholipases hydrolyse phosphatidylcholine, which is absorbed intact or as lysophosphatidylcholine or choline ¹. Gut bacteria convert choline to trimethylamine, which hepatic FMO3 oxidises to trimethylamine N-oxide (TMAO) ⁴⁵. A week of antibiotics nearly abolished TMAO formation from labelled phosphatidylcholine in 6 adults; withdrawal restored it ⁴.

Phosphatidylcholine to trimethylamine N-oxideIntestinal lumen and gut bacteria, then hepatocyte endoplasmic reticulum

Phosphatidylcholine
Pancreatic phospholipase A2 (PLA2G1B)Ca2+, H2OReleases the sn-2 fatty acid; much of the product is absorbed and reacylated
1-Acyl-lysophosphatidylcholine
LysophospholipaseH2OReleases the sn-1 fatty acid
sn-Glycero-3-phosphocholine
Glycerophosphocholine phosphodiesteraseH2OAlso yields sn-glycerol 3-phosphate
Choline
Choline trimethylamine-lyase CutC, activated by CutD (gut bacteria)Glycyl radical, generated by CutD from S-adenosylmethionineCleaves the C–N bond; also yields acetaldehyde
Trimethylamine
Flavin-containing monooxygenase 3 (FMO3)FAD, NADPH, O2Hepatic; TMAO is excreted in urine; FMO3 deficiency causes trimethylaminuria
Trimethylamine N-oxide

What studies show

Higher blood TMAO was linked to heart attacks, strokes and deaths ⁴⁶.

Of 4007 angiography patients, 513 died or had a myocardial infarction or stroke within 3 years; the top TMAO quartile against the bottom gave hazard ratios of 2.54 (95% CI 1.96 to 3.28) and, fully adjusted, 1.43 (1.05 to 1.94) ⁴. Across clinical cohorts over 1 to 8 years, relative risks for high TMAO were 1.62 (1.45 to 1.80) for 3315 cardiovascular events among 19,256 participants, and 1.63 (1.36 to 1.95) for death in 12 of the articles ⁶. In 95,442 French adults over a median 7.4 years, lecithin intake was not associated with cardiovascular disease ⁷.

In atherosclerosis-prone mice, 1% dietary choline nearly tripled aortic lesions, and the increase was absent under antibiotics ⁸. EFSA set no numerical acceptable daily intake ¹.

Regulation

Four jurisdictions permit lecithins ^1111213.

Jurisdiction	Rule
European Union	Quantum satis in most foods; 1,000 mg/L in infant formulae, no safety concern below 16 weeks ¹¹⁰
United States	Generally recognised as safe under good manufacturing practice ¹¹
Japan	Five lecithins listed as existing additives ¹²
China	Phospholipids, quantum satis outside listed foods such as milk and oils ¹³

References

Regulator
EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS), Mortensen A, Aguilar F, Crebelli R, Di Domenico A, Frutos MJ, et al. Re-evaluation of lecithins (E 322) as a food additive EFSA Journal, 2017.
doi:10.2903/j.efsa.2017.4742 PubMed 32625454
Funding and finding
Funding
European Food Safety Authority; requestor: European Commission.
Finding
Phosphatidylcholine is absorbed intact or as lysophosphatidylcholine or choline after intestinal hydrolysis; dietary lecithins are hydrolysed by phospholipases to liberate choline. No need for a numerical ADI and no safety concern at reported uses, including for choline from lecithins. Lecithins (E 322) are used as emulsifying and stabilising agents of water-oil/fat mixtures in a wide range of foods. Identity: lecithins (E 322) are mixtures or fractions of phosphatides obtained by physical procedures from animal or vegetable foodstuffs, including hydrolysed products; JECFA treats lecithin (INS 322i) and partially hydrolysed lecithin (INS 322ii) as separate additives with distinct specifications; the main source is soya bean oil, with cottonseed, maize, sunflower, rapeseed and egg yolk of minor importance; JECFA set no numerical ADI (ADI 'not limited') in 1974. Food-grade lecithin from soya or other sources contains about 60% phospholipids and 40% triglycerides, sterols and carbohydrates; the phospholipid composition of soya bean lecithin on an oil-free basis is 21% phosphatidylcholine, 22% phosphatidylethanolamine, 19% phosphatidylinositol, 10% phosphatidic acid, 1% phosphatidylserine and 12% glycolipids, while 31P-NMR data from the European Lecithin Manufacturers Association give 12.69 to 22.23% phosphatidylcholine for liquid and de-oiled soya lecithin. Choline that can theoretically be released is 13.2% for phosphatidylcholine with two linoleate groups and up to 3.38% for commercial lecithins. Authorisation: Group I additive at quantum satis in most food categories, among them cocoa and chocolate products, bread and rolls, and fine bakery wares; 30,000 mg/kg in fats and oils essentially free from water; 1,000 mg/L in infant and follow-on formulae and in the corresponding foods for special medical purposes; 10,000 mg/kg in processed cereal-based and baby foods and other foods for young children. Bread and rolls and fine bakery wares were the largest contributors to exposure in most surveys for all groups above infancy, and formulae in infants. Refined brand-loyal mean exposure ranged from 7 mg/kg body weight per day in adolescents to 82 mg/kg bw per day in children, with 95th percentiles of 15 to 187; dietary lecithin from the regular diet is about 1 to 5 g/day, 14 to 71 mg/kg bw per day for a 70 kg adult. On trimethylamine, the Panel states that high doses of choline cause a fishy body odour through excretion of trimethylamine formed by bacterial action, but that lecithin does not present that risk because intestinal bacteria in general cannot cleave the esters and hence do not form major amounts of trimethylamine from choline, citing Zeisel et al. (1983) as cited in IOM (1998). Toxicology: no concern for genotoxicity; no adverse effects in chronic or carcinogenicity studies in rats up to 3,750 mg/kg bw per day; no reproductive toxicity study available; indications of altered brain development at 5% soya lecithin and above in the diet during gestation, lactation and post-weaning, in studies of limited relevance, for which a study to OECD TG 426 was recommended. The opinion does not assess trimethylamine N-oxide and cites no study of lecithins with cardiovascular outcomes.
Independent research
Chazelas E, Deschasaux M, Srour B, Kesse-Guyot E, Julia C, Alles B, et al. Food additives: distribution and co-occurrence in 126,000 food products of the French market Scientific Reports, 2020.
doi:10.1038/s41598-020-60948-w PubMed 32132606
Funding and finding
Funding
PhD grant from Paris 13 University (E. Chazelas); post-doctoral fellowship from the Fondation pour la Recherche Médicale (ARF201809007046, M. Deschasaux); French Ministry of Health (DGS Arrêté 29 Novembre 2019); French National Cancer Institute (INCa_14059); European Research Council (ERC CoG ADDITIVES_864219). Researchers were independent from funders. Funders had no role in the study design, the collection, analysis, and interpretation of data, the writing of the report, and the decision to submit the article for publication. Open Food Facts is a non-profit association.
Finding
53.8% of products contained at least one additive and 11.3% five or more. Appendix 7, products containing each additive: citric acid E 330 18,302; lecithins E 322 13,102; E 14XX modified starches 10,100; sodium carbonates E 500 8587; ascorbic acid E 300 7919; xanthan gum E 415 7327; sodium nitrite E 250 7144; diphosphates E 450 6529; pectins E 440 6504; mono- and diglycerides of fatty acids E 471 6060. Specific starches: E 1442 209, E 1422 173, E 1414 55, E 1450 30, E 1412 27, E 1420 19, E 1404 18, E 1440 5, E 1410 1. The footnote and the Discussion state that the number of products containing each specific modified starch may be underestimated because packaging often states only 'modified starch'. E 500 had the highest squared loading (0.64) in cluster 3, 'stabilizers and emulsifiers mostly used in biscuits and cakes'; sodium carbonate (E 500), diphosphates (E 450) and lecithins (E 322) co-occurred in 1667 products, mostly biscuits. The authors describe E 500, E 450, E 503 and E 422 as widely used in biscuits and cakes as acidity regulators, stabilizers and emulsifiers. Additive doses were not available.
Independent research
Chazelas E, Druesne-Pecollo N, Esseddik Y, de Edelenyi FS, Agaesse C, De Sa A, et al. Exposure to food additive mixtures in 106,000 French adults from the NutriNet-Santé cohort Scientific Reports, 2021.
doi:10.1038/s41598-021-98496-6 PubMed 34608173
Funding and finding
Registration
NCT03335644
Participants
106,489
Funding
NutriNet-Santé: Ministère de la Santé, Santé Publique France, INSERM, INRAE, CNAM and University Sorbonne Paris Nord. E. Chazelas: doctoral funding from University Sorbonne Paris Nord; C. Debras: French National Cancer Institute. Project: European Research Council (Horizon 2020, grant agreement No 864219), French National Cancer Institute (INCa_14059), French Ministry of Health (arrêté 29.11.19) and IdEx Université de Paris (ANR-18-IDEX-0001). Researchers were independent from funders; funders had no role in the study design, the collection, analysis and interpretation of data, the writing of the report, and the decision to submit the article for publication.
In-kind support
Some of the 2677 ad hoc laboratory assays of additive doses were ordered by the consumers' association UFC Que Choisir.
Finding
Intakes of 90 additives were estimated from repeated 24-h records matched to brand-level composition data (OQALI, Open Food Facts, Mintel GNPD), with doses from 2677 laboratory assays, EFSA dose data by food category or Codex GSFA levels; descriptive analyses were weighted to the 2016 French census. Table 1, % consumers; median, 95th percentile and mean (SD) in mg/day; mean (SD) in mg/kg bw/day: modified starches E 14xx 91.48%; 1304.66, 4270.38, 1596.45 (1394.44); 24.33 (21.84). Citric acid E 330 91.15%; 1380.84, 6193.84, 1956.51 (2231.41); 29.84 (34.31). Lecithins E 322 86.57%; 35.36, 168.33, 53.94 (71.99); 0.83 (1.1). Xanthan gum E 415 79.74%; 303.60, 1401.31, 439.26 (508.65); 6.62 (7.62). Mono- and diglycerides of fatty acids E 471 78.07%; 101.90, 547.24, 160.8 (197.42); 2.44 (2.98). Sodium carbonates E 500 67.10%; 560.00, 4950.00, 1267.46 (1913.51); 19.62 (29.73), with median 8.51 and 95th percentile 76.73 mg/kg bw/day. The ADI column reads NA for all six. Diphosphates E 450 64.36%; 62.86, 715.67, 178.33 (308.05); 2.74 (4.67); ADI 40 mg/kg bw/day, exceeded by 0.02% of all participants and 0.03% of consumers. Additives without a specified ADI can be used quantum satis, that is with no limitations other than current good manufacturing practice. The authors state that information on the health impact of regular and cumulative intake of food additives in humans, and on effects of their mixtures, is still missing.
Independent research
Tang WH, Wang Z, Levison BS, Koeth RA, Britt EB, Fu X, et al. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk New England Journal of Medicine, 2013.
doi:10.1056/NEJMoa1109400 PubMed 23614584
Funding and finding
Participants
4,007
Follow-up
3 years
Funding
Supported by grants from the National Institutes of Health and its Office of Dietary Supplements (R01HL103866 and 1P20HL113452). The clinical study GeneBank was supported by grants from the National Institutes of Health (P01HL098055, P01HL076491, R01HL103931, and R01DK080732) and a Cleveland Clinic/Case Western Reserve University Clinical and Translational Science Award (UL1TR000439). Dr. Hazen was supported by a gift from the Leonard Krieger Fund. The two studies were funded by the National Institutes of Health.
In-kind support
Mass spectrometry instrumentation was housed within the Cleveland Clinic Mass Spectrometry Facility, with partial support through a Center of Innovation by AB SCIEX. In the ICMJE forms, all eight authors answered No to third-party provision of writing assistance, medicines, equipment or administrative support for the submitted work, and Hazen and Tang named only the National Institutes of Health as a grant source for it.
Finding
After the challenge, plasma TMAO and d9-TMAO rose over time; in the 6 participants given antibiotics, TMAO and d9-TMAO in plasma and urine were almost completely suppressed, and both were again readily detectable at least 1 month after withdrawal. In the outcome study, 513 of 4007 participants had a major adverse cardiovascular event (death from any cause, non-fatal myocardial infarction or non-fatal stroke) within 3 years. Highest (above 6.18 µM) against lowest (below 2.43 µM) TMAO quartile: unadjusted hazard ratio 2.54 (95% CI 1.96 to 3.28); adjusted for traditional risk factors and hs-CRP 1.88 (1.44 to 2.44); further adjusted for myeloperoxidase, eGFR, white-cell count, body-mass index and medications 1.49 (1.10 to 2.03); further adjusted for angiographic extent of coronary disease 1.43 (1.05 to 1.94). Per 1 SD of TMAO: unadjusted 1.40 (1.29 to 1.51), adjusted 1.30 (1.20 to 1.41). Event counts by quartile are not given in the text. Intestinal microbiota convert the choline moiety of dietary phosphatidylcholine into trimethylamine, which hepatic flavin-containing monooxygenases convert into TMAO, which is excreted in urine.
Textbook or database
UniProt Consortium. UniProt: the Universal Protein Knowledgebase in 2025 Nucleic Acids Research, 2025.
doi:10.1093/nar/gkae1010 PubMed 39552041
Funding and finding
Funding
National Human Genome Research Institute (NHGRI) [HG002273]; Office of the Director, NIH OD [U24HG007822]; National Institute of Allergy and Infectious Diseases (NIAID); National Institute on Aging (NIA); National Institute of General Medical Sciences (NIGMS) [R35GM141873]; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); National Eye Institute (NEI); National Cancer Institute (NCI); National Heart, Lung, and Blood Institute (NHLBI); Biotechnology and Biological Sciences Research Council (BBSRC) [BB/T015608/1]; National Science Foundation's Directorate for Biological Sciences [BB/X002179/1]; Open Targets; Horizon 2020 - Research and Innovation Framework Programme [825575]; State Secretariat for Education, Research and Innovation (SERI); European Molecular Biology Laboratory (EMBL) Australia. Funding for open access charge: National Institutes of Health.
Finding
Reviewed human entries, release 2026_03, read through rest.uniprot.org on 2026-10-21. MB (P02144), myoglobin: monomeric haem protein of the muscle sarcoplasm that stores oxygen and facilitates its diffusion within muscle; reversibly binds oxygen through a pentacoordinated haem iron; has nitrite reductase activity. FMO3 (P31513): hepatic enzyme of the endoplasmic reticulum and microsomal membrane, cofactor FAD; trimethylamine + NADPH + O2 = trimethylamine N-oxide + NADP+ + H2O (EC 1.14.13.148); TMA is generated by gut microbiota from dietary precursors including L-carnitine; deficiency of FMO-mediated N-oxidation causes trimethylaminuria. CYP1A2 (P05177): hepatic cytochrome P450 of the endoplasmic reticulum, haem cofactor, using O2 and electrons from NADPH via cytochrome P450 reductase; catalyses the N-hydroxylation of heterocyclic amines. NAT2 (P11245): cytoplasmic; an N-hydroxyarylamine + acetyl-CoA = an N-acetoxyarylamine + CoA (EC 2.3.1.118); bioactivates several known carcinogens. SULT1A1 (P50225): cytoplasmic sulfotransferase using 3'-phosphoadenylyl sulfate; mediates the metabolic activation of carcinogenic N-hydroxyarylamines to reactive intermediates that form DNA adducts.
Independent research
Heianza Y, Ma W, Manson JE, Rexrode KM, Qi L. Gut microbiota metabolites and risk of major adverse cardiovascular disease events and death: a systematic review and meta-analysis of prospective studies Journal of the American Heart Association, 2017.
doi:10.1161/JAHA.116.004947 PubMed 28663251
Funding and finding
Registration
CRD42016052185
Participants
19,256
Follow-up
1 to 8 years across the included studies
Funding
Supported by grants from the National Heart, Lung, and Blood Institute (HL071981, HL034594, HL126024), the National Institute of Diabetes and Digestive and Kidney Diseases (DK091718, DK100383, DK078616), the Boston Obesity Nutrition Research Center (DK46200) and United States-Israel Binational Science Foundation grant 2011036; Qi held an American Heart Association Scientist Development Award (0730094N) and Heianza a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science.
Finding
High against low blood TMAO: pooled relative risk 1.62 (95% CI 1.45 to 1.80) for major adverse cardiovascular events, fixed effects, P heterogeneity 0.2, I2 23.5%; 1.62 (1.43 to 1.85) with random effects; 1.70 (1.52 to 1.91) after removing the one analysis in black haemodialysis patients. For all-cause mortality alone, 15 analyses from 12 articles with 2498 deaths among 11,676 participants gave 1.63 (1.36 to 1.95), random effects, I2 45.9%. Per 1 µmol/L of TMAO, adjusted 1.02 (1.01 to 1.03); per 1 SD of log TMAO, adjusted 1.21 (1.14 to 1.29). Elevated TMAO precursors: 1.26 (1.10 to 1.44) for L-carnitine or choline and 1.43 (1.19 to 1.73) for betaine. Associations did not differ significantly by age, body-mass index, smoking, kidney function, diabetes, prior cardiovascular disease or follow-up duration. The authors state that no prospective data in populations at general risk were available, that residual confounding by unmeasured factors cannot be excluded, that TMAO was measured once, and that trials lowering TMAO are needed to inform causality.
Independent research
Sellem L, Srour B, Javaux G, Chazelas E, Chassaing B, Viennois E, et al. Food additive emulsifiers and risk of cardiovascular disease in the NutriNet-Santé cohort: prospective cohort study BMJ, 2023.
doi:10.1136/bmj-2023-076058 PubMed 37673430
Funding and finding
Registration
NCT03335644
Participants
95,442
Follow-up
median 7.4 years
Funding
NutriNet-Santé: Ministère de la Santé, Santé Publique France, INSERM, INRAE, Conservatoire National des Arts et Métiers and University Sorbonne Paris Nord. Project: European Research Council (grant agreement 864219), French National Cancer Institute (INCa_14059), French Ministry of Health, IdEx Université de Paris (ANR-18-IDEX-0001) and a Bettencourt-Schueller Foundation research prize 2021. Researchers were independent from funders. The funders had no role in the design; collection, analysis, and interpretation of data; writing of the report; and decision to submit the article for publication.
Finding
1995 cardiovascular events over 666,509 person-years. Hazard ratios per 1 SD of intake: total celluloses (E460-E468) 1.05 (95% CI 1.02 to 1.09) for cardiovascular disease and 1.07 (1.02 to 1.12) for coronary heart disease; carboxymethylcellulose (E466, SD 32.0 mg/day) 1.03 (1.01 to 1.05) and 1.04 (1.02 to 1.06); total mono- and diglycerides of fatty acids (E471 and E472) 1.07 (1.04 to 1.11) for cardiovascular disease. Supplementary eTable2: total mono- and diglycerides of fatty acids (E471, E472, E472a, E472b, E472c and E472e; SD 287.5 mg/day) 1.07 (1.04 to 1.11), 1.08 (1.03 to 1.14) for coronary heart disease and 1.07 (1.01 to 1.13) for cerebrovascular disease; E471 alone (SD 208.6 mg/day) 1.03 (0.98 to 1.09), P = 0.2, for cardiovascular disease, and 1.03 (0.96 to 1.11) for coronary heart disease and for cerebrovascular disease. E471 was consumed by 81.6%, mean 161.2 mg/day. Diphosphates (E450) were consumed by 72.6%, mean 244.5 (SD 338.2) mg/day; eTable2 hazard ratios per SD (349.7 mg/day) were 0.99 (0.93 to 1.04) for cardiovascular disease, 0.96 (0.89 to 1.04) for coronary heart disease and 1.01 (0.93 to 1.09) for cerebrovascular disease. Trisodium phosphate (E339) was associated with coronary heart disease, 1.06 (1.00 to 1.12) per SD (58.4 mg/day), P = 0.03, not significant after correction for multiple testing (adjusted P = 0.3). Carrageenans and lecithins were not associated. Mean E466 intake 3.8 mg/day, consumed by 10.8%; E433 consumed by 1.1% and not analysed individually. Absolute risks by intake level are not reported.
Independent research
Wang Z, Klipfell E, Bennett BJ, Koeth R, Levison BS, DuGar B, et al. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease Nature, 2011.
doi:10.1038/nature09922 PubMed 21475195
Funding and finding
Funding
This research was supported by National Institutes of Health grants R01 HL103866, P01 HL098055, P01HL087018-020001, P01 HL28481 and P01 HL30568; B.J.B. was supported by NIH training grant T32-DK07789. The clinical study GeneBank was supported in part by P01 HL076491-055328, R01 HL103931 and the Cleveland Clinic Foundation General Clinical Research Center of the Cleveland Clinic/Case Western Reserve University CTSA (1UL1RR024989).
In-kind support
Abbott Diagnostics provided supplies for some of the fasting lipid profile, glucose, creatinine, troponin I and hsCRP measurements in GeneBank; the haemoglobin A1c and fasting glucose assays were supported by R01 DK080732.
Finding
Untargeted metabolomics identified choline, trimethylamine N-oxide (TMAO) and betaine, three metabolites of phosphatidylcholine, as predictors of cardiovascular disease. Oral but not intraperitoneal labelled phosphatidylcholine or choline yielded d9-TMAO, and three weeks of broad-spectrum antibiotics, or germ-free status, abolished it; conventionalisation restored it, establishing the route phosphatidylcholine to choline to trimethylamine to TMAO. In C57BL/6J.Apoe-/- mice weaned onto chow with 1.0% choline, aortic root lesions were augmented nearly threefold in both sexes, and antibiotics completely inhibited the increase; plasma TMAO rose from 2.5 ± 0.1 to 28.3 ± 2.4 µM in males and from 4.0 ± 0.5 to 158.6 ± 32.9 µM in females, and fell below 100 nM on antibiotics. Dietary choline, TMAO or betaine raised macrophage scavenger receptors CD36 and SR-A1 and foam-cell formation, which antibiotics prevented; the choline analogue 3,3-dimethyl-1-butanol raised neither TMAO nor macrophage cholesterol. Hepatic expression of several flavin monooxygenases, FMO3 among them, correlated with lesion area, plasma TMAO and inversely with HDL cholesterol in mice, and a locus containing the FMO cluster on mouse chromosome 1 affected lesion size. The authors state that the participation of FMOs in human atherosclerosis and HDL cholesterol levels remains to be established.
Independent research
Jia J, Dou P, Gao M, Kong X, Li C, Liu Z, et al. Assessment of Causal Direction Between Gut Microbiota-Dependent Metabolites and Cardiometabolic Health: A Bidirectional Mendelian Randomization Analysis Diabetes, 2019.
doi:10.2337/db19-0153 PubMed 31167879
Funding and finding
Funding
The study was supported by Peking University Start-up grant BMU2018YJ002, High-performance Computing Platform of Peking University, and Beijing Technology and Business University grant 88442Y0033. The funding organizations had no role in the preparation of the manuscript.
Finding
Per 10 units of genetically predicted TMAO, odds ratios by inverse-variance weighting were 0.96 (95% CI 0.59 to 1.57) for type 2 diabetes, 1.00 (0.70 to 1.43) for coronary artery disease, 1.08 (0.73 to 1.60) for myocardial infarction, 0.94 (0.53 to 1.65) for stroke, 0.99 (0.79 to 1.26) for atrial fibrillation and 1.08 (0.59 to 1.99) for chronic kidney disease; genetically predicted carnitine was likewise unassociated. Genetically increased choline was suggestively associated with type 2 diabetes (1.84, 1.00 to 3.42, P = 0.05) and betaine inversely (0.68, 0.48 to 0.95, P = 0.023). In the reverse direction, type 2 diabetes (0.130 ± 0.036, P < 0.0001) and chronic kidney disease (0.483 ± 0.168, P = 0.004) were associated with higher TMAO per unit of log odds. Instruments were selected at a suggestive threshold of P < 5 × 10-5 and explained 9.6% of the variance in TMAO, 8.0% of choline, 15.4% of betaine and 17.1% of carnitine; MR-Egger intercepts gave no evidence of pleiotropy. The authors state that the observational evidence for cardiovascular disease may reflect confounding or reverse causality, that weak instrument bias cannot be excluded, and that a shared genetic basis rather than causation remains possible.
Regulator
EFSA Panel on Food Additives and Flavourings (FAF), Younes M, Aquilina G, Castle L, Engel KH, Fowler P, et al. Opinion on the re-evaluation of lecithins (E 322) as a food additive in foods for infants below 16 weeks of age and follow-up of its re-evaluation as food additive for uses in foods for all population groups EFSA Journal, 2020.
doi:10.2903/j.efsa.2020.6266 PubMed 33204307
Funding and finding
Funding
European Food Safety Authority; requestor: European Commission (question number EFSA-Q-2018-00094). Technical and toxicological data were submitted in response to a public call by the European Lecithin Manufacturers Association and Specialised Nutrition Europe.
Finding
Lecithins (E 322) are permitted at up to 1,000 mg/L in infant formulae (food category 13.1.1) and in dietary foods for infants for special medical purposes (13.1.5.1), and business operators reported use at up to that level. For infants below 16 weeks of age, mean exposure in the maximum level scenario was 200 mg/kg body weight per day and the high level 260 mg/kg bw per day; using mean reported levels, 62 mg/kg bw per day (95th percentile 81) for 13.1.1 and 180 mg/kg bw per day (234) for 13.1.5.1. Because choline is a precursor of acetylcholine and the 2017 opinion had found the neurodevelopmental data inadequate, the Panel compared choline in formula with that in human milk: mean total choline in formula was 225 mg/L, about 62% higher than the 138 mg/L in mature human milk, while choline released from lecithins contributed 12 mg/L, 8.7% of the human-milk content, and 21 mg/L at the maximum permitted level; nearly 75% of formula choline comes from added choline as a nutrient. The Panel concluded that intake of lecithins (E 322) in infant formula of category 13.1.1 or food for special medical purposes of 13.1.5.1 does not raise safety concerns up to the maximum permitted level, and recommended revised specifications: lower limits for arsenic, lead and mercury, a new limit for cadmium and microbiological criteria. Studies submitted did not address neurodevelopment, and post-marketing surveillance data did not allow firm conclusions. The exposure of infants to arsenic and lead from the additive left a very low margin of safety or exposure. The opinion does not mention trimethylamine, trimethylamine N-oxide or cardiovascular outcomes.
Regulator
US Food and Drug Administration. Lecithin, 21 CFR 184.1400, and enzyme-modified lecithin, 21 CFR 184.1063: direct food substances affirmed as generally recognized as safe Code of Federal Regulations, title 21, sections 184.1400 and 184.1063, read in the electronic Code of Federal Regulations, title 21 amended to 14 October 2026, 2026.
https://www.ecfr.gov/current/title-21/section-184.1400
Funding and finding
Funding
US Food and Drug Administration; the text is federal regulation codified by the Office of the Federal Register.
Finding
Section 184.1400: commercial lecithin is a naturally occurring mixture of the phosphatides of choline, ethanolamine and inositol, with smaller amounts of other lipids, isolated as a gum following hydration of solvent-extracted soy, safflower or corn oils, bleached if desired by hydrogen peroxide and benzoyl peroxide and dried by heating; it meets the specifications of the Food Chemicals Codex, 3rd edition (1981), pages 166 to 167; in accordance with 184.1(b)(1) the ingredient is used in food with no limitation other than current good manufacturing practice; prior sanctions different from the uses established in the section do not exist or have been waived. Source: 48 FR 51150, 7 November 1983. Section 184.1063: enzyme-modified lecithin is prepared by treating lecithin with phospholipase A2 (EC 3.1.1.4) or pancreatin; specifications include acetone-insoluble matter (phosphatides) not less than 50.0%, acid value not more than 40, lead not more than 1.0 part per million, hexane-insoluble matter not more than 0.3%, peroxide value not more than 20, water not more than 4.0% and lysolecithin 50 to 80 mole percent of total phosphatides; in accordance with 184.1(b)(1) the ingredient is used in food with no limitation other than current good manufacturing practice, the affirmation resting on use as an emulsifier as defined in 170.3(o)(8) at levels not exceeding current good manufacturing practice. Source: 61 FR 45889, 30 August 1996, as amended at 78 FR 14666, 81 FR 5595 and 88 FR 17724. Neither section sets a numerical limit on intake or use.
Textbook or database
Japan Food Chemical Research Foundation. List of existing food additives Japan Food Chemical Research Foundation, English translation of the Japanese list, revision of 25 August 2025, 2025.
https://www.ffcr.or.jp/en/tenka/list-of-existing-food-additives/list-of-existing-food-additives.html
Funding and finding
Funding
not stated. The page is published by the Japan Food Chemical Research Foundation and states that it translates the Japanese list first compiled by public notice of the Minister for Health and Welfare on 16 April 1996 and since revised, the latest revision announced by the Consumer Affairs Agency.
Finding
Existing food additives are substances of natural origin permitted for use and distribution in Japan as an exception to the designation system of the Food Sanitation Act, because of long use in Japan; the status was set by the 1995 amendment of the Act, which made all additives subject to designation. Entry 76 of the list is xanthan gum, described as a substance composed mainly of polysaccharides obtained from the cultured solution of bacteria belonging to Xanthomonas. Five entries are lecithins: 153 vegetable lecithin, mainly lecithin from rape seeds or soybeans; 312 yolk lecithin, from egg yolk; 251 fractionated lecithin, mainly sphingomyelin, phosphatidylinositol, phosphatidylethanolamine and phosphatidylcholine from vegetable or yolk lecithin; 119 enzymatically modified lecithin, mainly phosphatidylglycerol from either; and 122 enzymatically decomposed lecithin, mainly phosphatidic acid and lysolecithin from either. The revision announced by the Consumer Affairs Agency on 25 August 2025 removed 30 additives and left 327 on the list.
Regulator
National Health Commission of the People's Republic of China; State Administration for Market Regulation. 食品安全国家标准食品添加剂使用标准 (National food safety standard: Standard for uses of food additives), GB 2760—2024 National standard of the People's Republic of China, issued 8 February 2024, in force from 8 February 2025, replacing GB 2760—2014, 2024.
https://file.jgvogel.cn/134/upload/resources/file/595476.pdf
Funding and finding
Funding
Issued by the National Health Commission and the State Administration for Market Regulation; the standard carries no funding statement. The text was read in a copy hosted by a third party, as the issuing bodies' sites refused automated access; its title page, contents and Table A.1 are those of GB 2760—2024.
Finding
Table A.1, ascorbic acid (vitamin C), CNS 04.014, INS 300, functions flour treatment agent and antioxidant: used in various foods in appropriate amounts according to production needs (按生产需要适量使用), except the food categories numbered 1 to 5, 10 to 62 and 68 in Table A.2, which comprise milks, fermented milk, milk powder and cream, butter, fresh fruit, vegetables, fungi and algae, cereals, rice, flours and raw noodles, fresh meat, aquatic products, eggs, sugars, honey, salt, spices, infant formulae and complementary foods for infants, drinking waters, fruit and vegetable juices, tea and coffee; maximum 5.0 g/kg in peeled or pre-cut fresh fruit (04.01.01.03) and in peeled, cut or shredded vegetables (04.02.01.03), 0.2 g/kg in wheat flour (06.03.01) and 1.5 g/kg in fruit and vegetable juices (14.02.01), as ready to drink. Table A.1, sodium carbonate (碳酸钠, CNS 01.302, INS 500(i)), function acidity regulator: according to production needs in various foods except categories 1 to 30 and 33 to 68 in Table A.2, and in fermented rice products; categories 31 and 32 are raw wet and raw dry noodle products. Sodium hydrogen carbonate (碳酸氢钠, CNS 06.001, INS 500(ii)), functions raising agent, acidity regulator and stabiliser: according to production needs in various foods except categories 1 to 56 and 58 to 68 in Table A.2, and in fermented rice products; category 57 is cereal-based complementary foods for infants and young children. Sodium sesquicarbonate (碳酸氢三钠, also named 倍半碳酸钠, CNS 01.305, INS 500(iii)), function acidity regulator: according to production needs in dairy products other than listed exceptions, only goat milk, and in pastries (07.02) and biscuits (07.03). Table A.1, phospholipids (磷脂, CNS 04.010, INS 322), functions antioxidant and emulsifier: according to production needs in various foods, except the categories numbered 1 to 4, 6, 8 to 53 and 59 to 68 in Table A.2, which comprise pasteurised and sterilised milk, fermented milk, milk and cream powder, vegetable oil, animal fats, butter, fresh fruit, vegetables, fungi and algae, cereals, rice, flours and noodle products, fresh, chilled and frozen meat, aquatic products, eggs, sugars, honey, salt, spices, drinking waters, fruit and vegetable juices, wines, and tea and coffee; cream (category 5), hydrogenated vegetable oil (7) and infant formulae and complementary foods for infants (54 to 58) are not among the exceptions. Table A.1, mono- and diglycerides of fatty acids (单,双甘油脂肪酸酯, CNS 10.006, INS 471), functions emulsifier and coating agent (乳化剂、被膜剂): according to production needs in various foods, except the 59 categories numbered 1 to 4, 6 to 11, 13 to 14, 16 to 30, 32 to 53 and 59 to 68 in Table A.2; cream (5), surface-treated fresh fruit (12) and vegetables (15), raw wet noodle products (31) and infant formulae and complementary foods for infants (54 to 58) are not among the exceptions; maximum 20.0 g/kg in butter and concentrated butter (02.02.01.01), 30.0 g/kg in raw dry noodle products (06.03.02.02), 6.0 g/kg in brown sugar, raw sugar, other sugars and syrups (11.01.02) and 5.0 g/kg in spices (12.09). Table A.1, phosphoric acid and phosphates (磷酸及磷酸盐), a group entry that includes disodium dihydrogen pyrophosphate (焦磷酸二氢二钠), tetrasodium pyrophosphate (焦磷酸钠), tetrapotassium pyrophosphate (焦磷酸四钾), trisodium monohydrogen diphosphate (焦磷酸一氢三钠) and calcium acid pyrophosphate (酸式焦磷酸钙); its INS numbers include 450(i), 450(ii), 450(iii), 450(v) and 450(vii); functions water-retention agent, raising agent, acidity regulator, stabiliser, coagulant and anticaking agent (水分保持剂、膨松剂、酸度调节剂、稳定剂、凝固剂、抗结剂). Maximum levels apply singly or in combination, expressed as phosphate (PO4 3-), for example 5.0 g/kg in dairy products other than listed exceptions, 15.0 g/kg in bakery wares (07.0), 5.0 g/kg in prepared and cooked meat products, 20.0 g/kg in non-dairy creamer and compound seasonings and 80.0 g/kg in seasoning packets for instant wet noodles (12.10.01.03); in infant formulae (13.01.01, 13.01.02) and complementary foods for infants and young children (13.02), 1.0 g/kg using only calcium hydrogen phosphate and sodium dihydrogen phosphate.

Updated 2026-10-21