Citric acid (E330)

What it is

Citric acid occurs in many foods; lemon juice contains about 7% ¹.

It is 2-hydroxy-1,2,3-propanetricarboxylic acid, INS 330, used as an acidulant, antioxidant synergist, sequestrant and flavouring agent ². Commercial production includes fermentation with Aspergillus niger ³⁴.

How often it is used

Citric acid is the most frequent additive in French packaged foods ⁵.

In April 2019 it was listed in 18,302 of 126,556 products ⁵. Between 2009 and 2020, 91.15% of 106,489 NutriNet-Santé adults consumed it, at a weighted mean of 1956.51 mg/day ⁶.

In the body

Citrate is made in the body, and eaten citric acid is broken down to carbon dioxide and water ¹³.

The sodium-coupled transporter SLC13A2 moves divalent citrate into intestinal and renal proximal tubule cells ⁷. Citrate is an intermediate of the mitochondrial citric acid cycle ⁸.

Citric acid cycleMitochondrial matrix; succinate dehydrogenase in the inner membrane

OxaloacetateCitrateCitrate synthase (CS)Acetyl-CoA, H2OIrreversible entry of the acetyl group; releases CoA
CitrateIsocitrateAconitase 2 (ACO2)[4Fe-4S] clusterVia cis-aconitate
Isocitrate2-OxoglutarateIsocitrate dehydrogenase 3 (IDH3A, IDH3B, IDH3G)NAD+ to NADH, Mg2+ or Mn2+NADHATP (high concentrations)Releases CO2; ADP and citrate activate
2-OxoglutarateSuccinyl-CoA2-Oxoglutarate dehydrogenase complex (OGDH, DLST, DLD)Thiamine pyrophosphate, Lipoate, CoA, FAD, NAD+ to NADHNADHATPReleases CO2; Ca2+ and ADP stimulate
Succinyl-CoASuccinateSuccinyl-CoA synthetase (SUCLG1 with SUCLG2 or SUCLA2)GDP to GTP or ADP to ATP, PhosphateReleases CoA; the only substrate-level phosphorylation of the cycle
SuccinateFumarateSuccinate dehydrogenase, complex II (SDHA, SDHB, SDHC, SDHD)FAD, covalently bound, Ubiquinone to ubiquinolPasses electrons directly to the respiratory chain
FumarateMalateFumarate hydratase (FH)H2O
MalateOxaloacetateMalate dehydrogenase 2 (MDH2)NAD+ to NADHEndergonic; pulled forward when the cycle runs

What studies show

Teeth can be eroded by frequent or large intakes of citric acid ¹.

In a meta-analysis of nine paediatric studies, dental erosion was associated with soft drinks (odds ratio 2.41, 95% CI 2.03 to 2.85) and vitamin C (1.16, 1.10 to 1.22); citric acid itself was not analysed ¹⁰.

In NutriNet-Santé, a soft-drink additive mixture led by citric acid was associated with type 2 diabetes (hazard ratio 1.13, 1.08 to 1.18, per standard deviation of score) ¹¹. Over a mean 7.7 years, diabetes was diagnosed in 384 of 36,214 adults in the top third and 355 of 36,215 in the bottom third ¹¹.

In 1973 JECFA set a group acceptable daily intake “not limited” for citric acid and its calcium, potassium, sodium and ammonium salts ².

Regulation

Citric acid is permitted in food in all four jurisdictions below ^1441516.

Jurisdiction	Status
EU	E330, Group I, quantum satis ¹⁴³
US	Generally recognised as safe; no limit beyond good manufacturing practice ⁴
Japan	Designated additive ¹⁵
China	As production requires, except 61 categories such as pasteurised milk and raw meat ¹⁶

References

Regulator
Joint FAO/WHO Expert Committee on Food Additives. Citric acid and its calcium, potassium and sodium salts WHO Food Additives Series No. 5, Toxicological evaluation of some food additives including anticaking agents, antimicrobials, antioxidants, emulsifiers and thickening agents; 17th meeting of JECFA, Geneva, 25 June to 4 July 1973; World Health Organization, Geneva, 1974.
https://www.inchem.org/documents/jecfa/jecmono/v05je24.htm
Funding and finding
Funding
not stated; monograph of the Joint FAO/WHO Expert Committee on Food Additives, published by the World Health Organization.
Finding
Citric acid is an intermediary substance in oxidative metabolism, engaged in the tricarboxylic acid cycle; citric acid and citrates occur in many foods and are normal metabolites in the body. Ingestion of citric acid frequently or in large doses may cause erosion of teeth and local irritation, apparently because of the low pH; the effects also occur with lemon juice, which contains about 7% citric acid and has a pH below 3. In rats, diets with 1.2% citric acid had no harmful effect on growth or reproduction over two successive generations and 90 weeks, and dental attrition was slightly more marked than in controls; 1380 mg/kg bw per day given orally to three dogs for 112 to 120 days produced no symptoms or renal damage. Citric acid and its calcium, potassium and sodium salts do not constitute a significant toxicological hazard to man; acceptable daily intake not limited.
Regulator
Joint FAO/WHO Expert Committee on Food Additives. Citric acid: summary of evaluations performed by the Joint FAO/WHO Expert Committee on Food Additives IPCS INCHEM, JECFA evaluation summary, page dated 12 Nov 01, 2001.
https://www.inchem.org/documents/jecfa/jeceval/jec_436.htm
Funding and finding
Funding
not stated; summary of evaluations of the Joint FAO/WHO Expert Committee on Food Additives, published on IPCS INCHEM.
Finding
INS 330; JECFA No. 218. Chemical names: 2-hydroxy-1,2,3-propane-tricarboxylic acid and its monohydrate. Functional classes: acidulant, synergist for antioxidant, sequestrant, flavouring agent. Latest evaluation 1973 (17th meeting, TRS 539; toxicological monograph FAS 5): ADI not limited, a group ADI for citric acid and its calcium, potassium, sodium and ammonium salts. The 1966 evaluation also set an ADI not limited.
Regulator
EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP). Scientific Opinion on the safety and efficacy of citric acid when used as a technological additive (acidity regulator) for all animal species EFSA Journal 13(2):4010; version published on 22 March 2016, replacing that of 17 February 2015, 2015.
doi:10.2903/j.efsa.2015.4010
Funding and finding
Funding
European Food Safety Authority; on request from the European Commission, question EFSA-Q-2013-00612, adopted on 27 January 2015. The application was submitted by FEFANA asbl (companies Impextraco, Provimi and Selko), and the opinion is based in part on data from a consortium of three companies producing or distributing citric acid.
Finding
Citric acid occurs in all living organisms as an intermediate in the tricarboxylic acid cycle; it is a normal constituent of the diet of humans and animals and, when ingested, is rapidly and completely metabolised to carbon dioxide and water. pKa values 3.14, 4.77 and 6.39. Citric acid (E 330) is authorised as a food additive for general use following the quantum satis principle, with limits for some products such as juices and infant foods; JECFA (1974) allocated an ADI 'not limited' for citric acid and its calcium, potassium and sodium salts, a position retained by the Scientific Committee for Food in 1991. The three applicant companies produce citric acid by fermentation of carbohydrate-based substrates with non-genetically modified strains of Aspergillus niger, followed by removal of solids, purification, concentration and crystallisation; the dossier documented absence of viable cells of the production strain in the final product. Malformin C was below the limit of detection (1 µg/kg) in eight commercial batches from the three companies; aflatoxins B1, B2, G1 and G2 and ochratoxin A were below the limits of detection in 13 batches. Rumen microbes rapidly metabolise citric acid to carbon dioxide and acetic acid (Wright, 1971). The use of citric acid in animal nutrition is safe for the consumer.
Regulator
US Food and Drug Administration. Citric acid, 21 CFR 184.1033: direct food substances affirmed as generally recognized as safe Code of Federal Regulations, title 21, section 184.1033 (59 FR 63895, 12 December 1994), read in the electronic Code of Federal Regulations, up to date as of 20 October 2026, 2026.
https://www.ecfr.gov/current/title-21/section-184.1033
Funding and finding
Funding
US Food and Drug Administration; the text is federal regulation codified by the Office of the Federal Register.
Finding
Part 184 lists direct food substances affirmed as generally recognized as safe. Citric acid (C6H8O7, CAS 77-92-9) is 2-hydroxy-1,2,3-propanetricarboxylic acid, a naturally occurring constituent of plant and animal tissues. It may be produced by recovery from sources such as lemon or pineapple juice, by mycological fermentation using Candida spp. (21 CFR 173.160 and 173.165) and by the solvent extraction process of 21 CFR 173.280 for recovery from Aspergillus niger fermentation liquor. It meets Food Chemicals Codex specifications and, in accordance with 21 CFR 184.1(b)(1), is used in food with no limitations other than current good manufacturing practice.
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.
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 UniProtKB entries read through rest.uniprot.org on 2026-10-21 (annotation updates of 2 September 2026). SLC13A2 (Q13183): low-affinity sodium-dicarboxylate cotransporter of the apical cell membrane that mediates the entry of succinate, citrate, fumarate and 2-oxoglutarate into the small intestine and renal proximal tubule, with a probable stoichiometry of 3 Na+ per divalent dicarboxylate; citrate is transported in protonated form as a divalent anion rather than the trivalent form normally found in blood; expressed in kidney and intestine. SLC13A5 (Q86YT5): high-affinity sodium/citrate cotransporter of the cell membrane that recognises the trivalent form of citrate at physiological pH, probably with 4 Na+; expressed most predominantly in the liver, with moderate expression in brain and testis. SLC25A1 (P53007): electroneutral antiporter of the mitochondrial inner membrane that exports citrate from mitochondria into the cytosol in exchange for malate. ACO2 (Q99798): mitochondrial aconitase isomerises citrate to isocitrate via cis-aconitate.
Textbook or database
Ragueneau E, Gong C, Sinquin P, Sevilla C, Beavers D, Grentner A, et al. The Reactome Knowledgebase 2026 Nucleic Acids Research, 2026.
doi:10.1093/nar/gkaf1223 PubMed 41251150
Funding and finding
Funding
The development of Reactome is supported by grants from the National Institutes of Health (U24HG012198 and U24HG012198-02S1 for Core Trust Seal development; U24HG011851), European Bioinformatics Institute (EMBL-EBI), Open Targets (The Target Validation Platform), and Connected Minds Prototyping (York University). Funding to pay the Open Access publication charges for this article was provided by the National Institutes of Health (U24HG012198). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Finding
Human pathway and reaction summations of release 97, read through reactome.org/ContentService on 2026-10-21. Digestion of dietary carbohydrate (R-HSA-189085): salivary and intestinal amylases convert starch to maltotriose, maltose, limit dextrins and some glucose; enzymes on the luminal surface of enterocytes digest limit dextrins and disaccharides to glucose, galactose and fructose; lactose yields glucose and galactose, sucrose glucose and fructose. Intestinal hexose absorption (R-HSA-8981373): SGLT1 co-transports Na+ with glucose and galactose, and basolateral GLUT2 releases hexoses into the blood. Glycolysis (R-HSA-70171): entirely cytosolic; two NAD+ are reduced to NADH per glucose; under anaerobic conditions or in cells lacking mitochondria NAD+ is regenerated by reducing pyruvate to lactate. Hexokinase reaction (R-HSA-70420): glucokinase and the three hexokinases catalyse an irreversible reaction; glucokinase occurs only in hepatocytes and pancreatic beta cells, has a higher Km than the hexokinases, is less readily inhibited by its product and is thought to act as a glucose sensor coupled to insulin release; glucokinase mutations are associated with MODY2. Phosphofructokinase 1 (R-HSA-70467): irreversible under physiological conditions, allosterically regulated by ATP, citrate and fructose 2,6-bisphosphate. Fructose 2,6-bisphosphate (R-HSA-9634600): its levels rise with insulin and fall with glucagon signalling; PKA phosphorylates PFKFB1. Pyruvate kinase (R-HSA-71670): essentially irreversible; isozymes L (liver) and R (red cells) come from PKLR, and PKLR mutations are associated with haemolytic anaemias. Pyruvate metabolism (R-HSA-70268): when oxygen is limiting, as in exercising muscle, or mitochondria are absent, as in red blood cells, NADH is reoxidised by reducing pyruvate to lactate, which is released into the blood, taken up mainly by the liver, oxidised to pyruvate and used for gluconeogenesis. Gluconeogenesis (R-HSA-70263): glucose synthesis from pyruvate consumes six high-energy phosphates, four from ATP and two from GTP. PDH complex (R-HSA-9861559): the mitochondrial complex converts pyruvate, CoA and NAD+ to acetyl-CoA, CO2 and NADH. PDH regulation (R-HSA-204174): PDK1 to PDK4 inactivate the complex by phosphorylation and PDP1 and PDP2 reactivate it. Vitamin B1 metabolism (R-HSA-196819): Wernicke-Korsakoff syndrome is associated with thiamin deficiency in alcoholism. Citric acid cycle (R-HSA-71403): all reactions are mitochondrial; the acetyl group of acetyl-CoA is completely oxidised to CO2, yielding one GTP or ATP, three NADH and one FADH2. Citrate synthase (R-HSA-70975) and IDH3 (R-HSA-70967) are irreversible; IDH3 releases CO2, is activated by ADP and inhibited by NADH and high ATP; the OGDH reaction (R-HSA-71401) releases CO2; aconitase, succinyl-CoA ligase, fumarate hydratase and MDH2 are reversible, MDH2 being highly endergonic but pulled forward by the cycle; succinate dehydrogenase (R-HSA-70994) reduces ubiquinone, with FAD covalently bound to His-99 of SDHA. Respiratory electron transport (R-HSA-611105): energy is largely released in mitochondria; oxygen consumption depends on ADP availability; 2.5 ATP form per NADH electron pair and 1.5 per FADH2 pair; 10 NADH give 25 and 2 FADH2 give 3, 28 in all, plus 2 from the Krebs cycle and 2 from glycolysis, 32 per glucose in theory; the actual yield probably does not reach 32; the glycerol phosphate shuttle bypasses complex I, so 1.5 ATP form per cytosolic NADH, while malate-aspartate shuttle NADH enters at complex I. Statements not used, because they conflict with UniProt or with the arithmetic: R-HSA-611105 assigns 3 ATP to malate-aspartate shuttle NADH and swaps the overall equations of the two shuttles; R-HSA-71401 states that ATP and NADH enhance and Ca2+ and ADP decrease OGDH activity, the reverse of UniProt Q02218; R-HSA-204174 states that dichloroacetic acid inhibits PDH, whereas UniProt records it as an inhibitor of PDK1 to PDK3.
Funding unknown
Sakhaee K, Alpern R, Poindexter J, Pak CY. Citraturic response to oral citric acid load The Journal of Urology, 1992.
doi:10.1016/s0022-5347(17)37437-2 PubMed 1552616
Funding and finding
Participants
6
Follow-up
4 hours after a single oral load
Funding
Not read: the full text returned HTTP 403 from the publisher and the AUA journal pages, no archived copy was found, and the abstract carries no funding statement. PubMed lists NIH grants M01-RR00633 (NCRR) and P01-DK20543 (NIDDK).
Finding
From the PubMed abstract: single oral load of 40 mEq citric acid in 6 normal subjects, compared with a control phase without drug, with serum and urinary citrate measured for 4 hours. Serum citrate rose significantly (p < 0.05) 30 minutes after the load and remained raised for 3 hours; urinary citrate excretion peaked at 2 hours and fell over the next 2 hours; differences between phases were significant at 2 and 3 hours. Urinary pH, carbon dioxide pressure, bicarbonate, total carbon dioxide and ammonium, serum electrolytes, and arterialised venous pH and carbon dioxide pressure did not change. The authors conclude that the citratemic and citraturic effects are largely accountable by absorbed citrate that escaped degradation.
Independent research
Li H, Zou Y, Ding G. Dietary factors associated with dental erosion: a meta-analysis PLoS One, 2012.
doi:10.1371/journal.pone.0042626 PubMed 22952601
Funding and finding
Participants
8,877
Funding
These authors have no support or funding to report.
Finding
Pooled odds ratios (Mantel-Haenszel) for dental erosion: soft drinks 2.41 (95% CI 2.03 to 2.85; 9 studies, 8877 participants), vitamin C 1.16 (1.10 to 1.22; 4 studies, 3975), sports drinks 1.58 (0.88 to 2.85), juice 0.90 (0.25 to 3.24), milk 0.67 (0.11 to 4.01), yoghurt 1.05 (0.28 to 3.96). Multivariate estimates were used when available, otherwise unadjusted ones. Citric acid was not analysed as a separate exposure. A 2016 correction (PLoS One 11:e0161518) changed only the location of one study, from the UK to Brazil.
Independent research
Payen de la Garanderie M, Hasenbohler A, Dechamp N, Javaux G, Szabo de Edelenyi F, Agaësse C, et al. Food additive mixtures and type 2 diabetes incidence: Results from the NutriNet-Santé prospective cohort PLoS Medicine, 2025.
doi:10.1371/journal.pmed.1004570 PubMed 40198579
Funding and finding
Registration
NCT03335644
Participants
108,643
Follow-up
mean 7.7 years (SD 4.6)
Funding
NutriNet-Santé public institutions: Ministère de la Santé, Santé Publique France, INSERM, INRAE, Conservatoire National des Arts et Métiers and University Sorbonne Paris Nord; European Research Council (grant agreement 864219, ADDITIVES); French National Cancer Institute (INCa_14059); French Ministry of Health (arrêté 29.11.19); IdEx Université de Paris (ANR-18-IDEX-0001); Bettencourt-Schueller Foundation Research Prize 2021; the laboratory of one author is supported by a European Research Council Starting Grant (ERC-2018-StG-804135 INVADERS) and the INSERM programme Microbiote. Researchers were independent from funders. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Finding
1,131 participants were diagnosed with type 2 diabetes. Nonnegative matrix factorisation identified five additive mixtures. Mixture 2, characterised by modified starches, pectin, guar gum, carrageenan, polyphosphates, potassium sorbates, curcumin and xanthan gum (E415 loading 0.16), was associated with type 2 diabetes incidence: hazard ratio 1.08 (95% CI 1.02 to 1.15) per increment of one standard deviation of the mixture score (SD 8.0), p = 0.006. Mixture 5, dominated by additives of sweetened drinks, gave a hazard ratio of 1.13 (1.08 to 1.18), p < 0.001. Mixtures 1, 3 and 4 showed no association. Associations persisted after adjustment for each emblematic additive in turn, so no single additive drove them, and did not differ by overall diet quality. Of 28 two-by-two interactions among the eight additives of mixture 2, three suggested synergism and four antagonism at p < 0.1. Absolute risks are not reported, but S1 Appendix Table H gives cases by tertile of the mixture 2 score (column labelled participants / incident cases; the values, summing to 1,131, are cases / participants): 260 / 36,215, 406 / 36,214 and 465 / 36,214, hazard ratios 1.28 (1.09 to 1.49) and 1.26 (1.08 to 1.48) against the lowest tertile, p-trend 0.007. With the mixture 2 score residualised on modified-starch intake (Table J), the hazard ratio was 1.06 (1.00 to 1.12). The authors state that residual confounding and exposure or outcome misclassification cannot be excluded and that causality cannot be established from this single observational study.
Funding unknown
Slanina P, Frech W, Ekström LG, Lööf L, Slorach S, Cedergren A. Dietary citric acid enhances absorption of aluminum in antacids Clinical Chemistry, 1986.
doi:10.1093/clinchem/32.3.539 PubMed 3948402
Funding and finding
Participants
10
Follow-up
45 days: three 7-day supplementation periods in fixed order, separated by balance periods of 4 to 7 days
Funding
not stated. Affiliations: Food Research Department, Swedish National Food Administration; Department of Analytical Chemistry, University of Umeå; Department of Internal Medicine, Uppsala University Hospital.
In-kind support
Perkin-Elmer provided the Model AA 3030 spectrometer on consignment.
Finding
Twice daily between meals for 7 days each, in fixed order: (a) 200 mL of lemon juice diluted fivefold with tap water, containing 6 mg citric acid per mL; (b) 10 mL of Al(OH)3 antacid suspension (Novalucol, 23.2 mg Al per mL); (c) both together. Mean whole-blood Al (Table 1): 0.004 and 0.005 mg/L at the two control samplings, 0.009 mg/L after lemon juice (p < 0.05 against the preceding sample), 0.012 mg/L after Al(OH)3 alone (p < 0.001) and 0.023 mg/L after Al(OH)3 with lemon juice (p < 0.001); the abstract gives 5 (SD 3), 9 (SD 4), 12 (SD 3) and 23 (SD 2) µg/L. The individual values in Table 1 for the combined period give an SD of 5.5 µg/L and a standard error of 1.7 µg/L, against the printed SD of 2. Blood Al did not return fully to control values in the balance periods. Speciation calculations indicate Al-citrate complexes in the acidic stomach.
Funding unknown
Sweis IE, Cressey BC. Potential role of the common food additive manufactured citric acid in eliciting significant inflammatory reactions contributing to serious disease states: A series of four case reports Toxicology Reports, 2018.
doi:10.1016/j.toxrep.2018.08.002 PubMed 30128297
Funding and finding
Participants
4
Funding
not stated: the article carries a conflict-of-interest statement but no funding statement.
Finding
Four case reports of joint pain with swelling and stiffness, muscle pain, dyspnoea, abdominal cramping and enervation beginning 2 to 12 hours after foods, beverages or an effervescent vitamin C containing manufactured citric acid and resolving over 8 to 72 hours; none of the four reported such symptoms after lemons or limes. Identification rested on the patients' observations and ingredient lists; amounts ingested were not quantified. The authors hypothesise that proteins or by-products of Aspergillus niger, the production organism, remain in manufactured citric acid, state that they cannot conclusively affirm that it causes the symptoms, and call for double-blind studies.
Regulator
European Commission. Commission Regulation (EU) No 1129/2011 of 11 November 2011 amending Annex II to Regulation (EC) No 1333/2008 of the European Parliament and of the Council by establishing a Union list of food additives Official Journal of the European Union, L 295, 12 November 2011, p. 1, 2011.
https://eur-lex.europa.eu/eli/reg/2011/1129/oj
Funding and finding
Funding
European Commission.
Finding
Annex II, Part C, Group I lists E 500 sodium carbonates with the specific maximum level quantum satis. E 500 is also listed at quantum satis in individual food categories, including soured cream butter and salt, and 'only as rising agent' in processed cereal-based foods and baby foods for infants and young children.
Textbook or database
Japan Food Chemical Research Foundation. List of designated additives Japan Food Chemical Research Foundation, English translation of Appended Table 1 of the Enforcement Regulations under the Food Sanitation Act, list as of 1 March 2024, 2024.
https://www.ffcr.or.jp/en/tenka/lists-of-additives/list-of-designated-additives.html
Funding and finding
Funding
not stated. The page is published by the Japan Food Chemical Research Foundation; the Consumer Affairs Agency food additives page links the Foundation's Japanese version as the list of designated additives (Appended Table 1 of the Enforcement Regulations).
Finding
Designated additives are those designated by the Prime Minister (by the Minister of Health, Labour and Welfare until March 2024), based on Article 12 of the Food Sanitation Act, as substances unlikely to harm human health; the designation covers chemically synthesised and natural substances. Appended Table 1 of the Enforcement Regulations held 476 designated additives as of 1 March 2024. Citric acid is entry No. 113; calcium citrate, monopotassium and tripotassium citrate and trisodium citrate are also listed.
Regulator
FAS China Staff. Usage Standard for Food Additives Finalized USDA Foreign Agricultural Service, GAIN report CH2024-0059, Beijing; unofficial translation of National Food Safety Standard GB 2760-2024, announced on 12 March 2024 by the National Health Commission and the State Administration for Market Regulation, in force from 8 February 2025, 2024.
https://apps.fas.usda.gov/newgainapi/api/Report/DownloadReportByFileName?fileName=Usage%20Standard%20for%20Food%20Additives%20Finalized_Beijing_China%20-%20People%27s%20Republic%20of_CH2024-0059.pdf
Funding and finding
Funding
US Department of Agriculture, Foreign Agricultural Service; voluntary report for public distribution, dated 6 May 2024.
Finding
Table A.1 of GB 2760-2024: citric acid, CNS No. 01.101, INS No. 330, functions acidity regulator and antioxidant, permitted based on production necessity in all categories of food except food categories 1 to 15, 17 to 53, 59 to 62 and 64 to 68 of Table A.2, 61 categories that include pasteurised milk, raw and fresh meat, fresh eggs, honey and drinking waters. Table C.1 lists citric acid among processing aids permitted in processing of all kinds of foods without a residue limit. The report states that the translation is unofficial and that stakeholders should conduct their own review of the regulation.

Updated 2026-10-21