NutriDex

The Supplement Research Compendium
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Caramel Color (4-MEI)

E150d

The browning agent in cola, soy sauce and beer — safe as a colour, dogged by a trace by-product

Moderate evidence 🍬Sweeteners & Additives

✚ Updated · How we grade evidence

Evidence tier
Moderate
Research weight
Citations
9 verified / 9
Classification
Sweeteners & Additives
❝
What the evidence says. Several controlled trials; effects real but modest or context-dependent.

What is Caramel Color (4-MEI)?

Caramel Color (4-MEI) (E150d) is a sweetener or food additive used for imparts brown to amber color and visual consistency to foods and beverages (cola, beer, soy sauce, gravies, baked goods, vinegars). NutriDex grades the human evidence as Moderate. Caramel color is the most widely used food colorant in the world, made by controlled heating of carbohydrates and classified into four types (E150a-d); ammonia/ammonium-sulfite processes (Class III E150c and Class IV E150d) generate a trace by-product, 4-methylimidazole (4-MEI), during manufacture. The caramel colour itself is well-studied and considered safe: EFSA (2011) and JECFA set a group ADI of 300 mg/kg bw/day, and the additive is GRAS in the US. The principal health question concerns 4-MEI, which IARC classifies Group 2B ("possibly carcinogenic to humans") based on lung tumors in mice; however no human evidence of harm exists, and regulators including FDA and EFSA judge real-world exposure to pose no immediate risk at the trace levels found in foods.

Purported Benefits

✓Imparts brown to amber color and visual consistency to foods and beverages (cola, beer, soy sauce, gravies, baked goods, vinegars)
✓Heat- and light-stable, acid-stable and microbiologically stable colorant suitable for low-pH carbonated drinks
✓Class IV (E150d) is specifically formulated to stay soluble and stable in acidic soft drinks
✓Contributes negligible calories and no sweetness; used purely for appearance, not flavor or preservation
✓World's most-used food colorant by volume, valued for low cost and reliable shade-matching

Dosing & Compounds

Typical Dose
EFSA (2011) and JECFA set a group ADI of 300 mg/kg bw/day for caramel colours E150a, c, d (derived from a NOAEL of 30 g/kg/day with a 100x uncertainty factor); E150c (E150b group) carries a lower ADI of 100 mg/kg bw/day due to immune-effect uncertainty from its THI constituent. Caramel color is GRAS / approved in the US (21 CFR 73.85). 4-MEI itself has no federal limit, but California Proposition 65 sets a No Significant Risk Level of 29 micrograms/day (1-in-100,000 lifetime cancer risk), triggering warning labels above that threshold.
Active Compounds
E-numbers: E150a (plain/Class I), E150b (caustic-sulfite/Class II), E150c (ammonia/Class III), E150d (ammonium-sulfite/Class IV)4-MEI by-product is generated chiefly in the ammoniated Class III (E150c) and Class IV (E150d) processesFound in colas and other dark soft drinks, beer and dark spirits, soy and Worcestershire sauce, balsamic vinegar, gravies, dark breads, confectionery and some pet foodsClass IV (E150d) dominates the soft-drink market; Class I (E150a) contains essentially no 4-MEI or THI

Safety & Cautions

The caramel colour additive is considered safe at the ADI; the debate is confined to the trace by-product 4-MEI in Class III/IV caramels. NTP 2-year bioassays found "clear evidence" of lung (alveolar/bronchiolar) tumors in male and female B6C3F1 mice but not in rats; 4-MEI was negative in standard genotoxicity tests (Ames, micronucleus), suggesting a non-genotoxic, high-dose mechanism. On this basis IARC classified 4-MEI Group 2B (possibly carcinogenic) in 2011/2012. There is no human evidence of cancer from caramel color or 4-MEI. FDA states a person would need to drink over a thousand cans of soda a day to approach the rodent tumor doses and does not advise dietary change. Consumer Reports (2014) found some sodas (notably Pepsi One and Malta Goya) exceeded California's 29 microgram/day level per serving, and a Johns Hopkins quantitative risk assessment (Smith 2015) estimated a small avoidable excess cancer burden from high-4-MEI drinks, prompting industry reformulation to lower-4-MEI caramels. EFSA noted dietary exposure to E150a/c/d may exceed the ADI in high consumers (especially children), driven by the colour mass rather than 4-MEI. No specific intolerance population is established; people wishing to minimize 4-MEI can choose plain (E150a) products or beverages without ammonia-process caramel. Educational only — always check with your doctor or pharmacist before combining Caramel Color (4-MEI) with any medicine.

Key Studies

Systematic review Akbari et al. 2023 ✓ PubMed
Systematic review (144 articles screened, 15 extracted) found the highest 4-MEI levels in caramel color, coffee, and cola drinks, identifying coffee as a leading exposure source by per-capita consumption.
systematic review Mukherjee & Chakrabarti 2016 ✓ Full text
Weight-of-evidence review found 4-MEI consistently negative in Ames and in vivo micronucleus assays, supporting a non-genotoxic mode of action for the mouse lung tumors.
regulatory assessment EFSA ANS Panel 2011 ✓ Source
Re-evaluation established a group ADI of 300 mg/kg bw/day for E150a/c/d (100 mg/kg for E150b group); concluded 4-MEI levels were not of concern but that total colour exposure may exceed the ADI in children and adults.
regulatory assessment FDA Q&A on 4-MEI ✓ Source
FDA found no reason to believe 4-MEI poses immediate or short-term danger at levels in food and did not recommend consumers change their diets, while continuing to review exposure data.
regulatory standard California OEHHA Proposition 65 ✓ Source
Set a No Significant Risk Level for 4-MEI of 29 micrograms/day, corresponding to a 1-in-100,000 lifetime cancer risk and triggering warning labels above that exposure.
Review Marete et al. 2025 ✓ PubMed
Comprehensive 2025 toxicological review of 4-MEI reports a toxicokinetic profile of rapid absorption, minimal metabolism, and fast renal elimination (low bioaccumulation), while noting NTP 'clear evidence' of carcinogenicity in mice and the unresolved threshold-vs-genotoxic regulatory divergence.
risk assessment Smith / Nachman 2015 (PLOS ONE) ✓ PubMed
Quantitative risk assessment estimated wide variation in soda 4-MEI (Coca-Cola ~76 lifetime US cancer cases vs Malta Goya ~5,011) and judged the excess risk 'avoidable and unnecessary.'
animal bioassay NTP 2007 ✓ PubMed
2-year rodent bioassay found clear evidence of carcinogenic activity (lung alveolar/bronchiolar neoplasms) in male and female B6C3F1 mice, with no carcinogenic activity in F344 rats.
authoritative classification IARC Monograph Vol. 101 ✓ Full text
Classified 4-methylimidazole as Group 2B, 'possibly carcinogenic to humans,' based on sufficient animal evidence (mouse lung tumors) and inadequate human evidence.
9 sources cited · 9 verified Search all studies on PubMed ↗

Common questions about Caramel Color (4-MEI)

What is Caramel Color (4-MEI) used for?

Caramel Color (4-MEI) is most often taken for Imparts brown to amber color and visual consistency to foods and beverages (cola, beer, soy sauce, gravies, baked goods, vinegars), Heat- and light-stable, acid-stable and microbiologically stable colorant suitable for low-pH carbonated drinks, Class IV (E150d) is specifically formulated to stay soluble and stable in acidic soft drinks, Contributes negligible calories and no sweetness; used purely for appearance, not flavor or preservation. The browning agent in cola, soy sauce and beer — safe as a colour, dogged by a trace by-product

Does Caramel Color (4-MEI) work — what does the evidence say?

Moderate evidence. Several controlled trials; effects real but modest or context-dependent. Caramel color is the most widely used food colorant in the world, made by controlled heating of carbohydrates and classified into four types (E150a-d); ammonia/ammonium-sulfite processes (Class III E150c and Class IV E150d) generate a trace by-product, 4-methylimidazole (4-MEI), during manufacture. The caramel colour itself is well-studied and considered safe: EFSA (2011) and JECFA set a group ADI of 300 mg/kg bw/day, and the additive is GRAS in the US. The principal health question concerns 4-MEI, which IARC classifies Group 2B ("possibly carcinogenic to humans") based on lung tumors in mice; however no human evidence of harm exists, and regulators including FDA and EFSA judge real-world exposure to pose no immediate risk at the trace levels found in foods.

What is the typical dose of Caramel Color (4-MEI)?

EFSA (2011) and JECFA set a group ADI of 300 mg/kg bw/day for caramel colours E150a, c, d (derived from a NOAEL of 30 g/kg/day with a 100x uncertainty factor); E150c (E150b group) carries a lower ADI of 100 mg/kg bw/day due to immune-effect uncertainty from its THI constituent. Caramel color is GRAS / approved in the US (21 CFR 73.85). 4-MEI itself has no federal limit, but California Proposition 65 sets a No Significant Risk Level of 29 micrograms/day (1-in-100,000 lifetime cancer risk), triggering warning labels above that threshold.

Is Caramel Color (4-MEI) safe? Any cautions or side effects?

The caramel colour additive is considered safe at the ADI; the debate is confined to the trace by-product 4-MEI in Class III/IV caramels. NTP 2-year bioassays found "clear evidence" of lung (alveolar/bronchiolar) tumors in male and female B6C3F1 mice but not in rats; 4-MEI was negative in standard genotoxicity tests (Ames, micronucleus), suggesting a non-genotoxic, high-dose mechanism. On this basis IARC classified 4-MEI Group 2B (possibly carcinogenic) in 2011/2012. There is no human evidence of cancer from caramel color or 4-MEI. FDA states a person would need to drink over a thousand cans of soda a day to approach the rodent tumor doses and does not advise dietary change. Consumer Reports (2014) found some sodas (notably Pepsi One and Malta Goya) exceeded California's 29 microgram/day level per serving, and a Johns Hopkins quantitative risk assessment (Smith 2015) estimated a small avoidable excess cancer burden from high-4-MEI drinks, prompting industry reformulation to lower-4-MEI caramels. EFSA noted dietary exposure to E150a/c/d may exceed the ADI in high consumers (especially children), driven by the colour mass rather than 4-MEI. No specific intolerance population is established; people wishing to minimize 4-MEI can choose plain (E150a) products or beverages without ammonia-process caramel.

How many studies support Caramel Color (4-MEI)?

NutriDex cites 9 sources for Caramel Color (4-MEI), graded "Moderate".

Cite this page
APA

Peh, D. (2026). Caramel Color (4-MEI) (E150d): Benefits, Dosage, Side Effects & Evidence. NutriDex — The Supplement Research Compendium. Retrieved 26 Jun 2026, from https://nutridex.info/s/caramel-color

BibTeX
@misc{nutridex_caramel_color,
  author       = {Peh, Daryl},
  title        = {Caramel Color (4-MEI) (E150d): Benefits, Dosage, Side Effects \& Evidence},
  year         = {2026},
  howpublished = {NutriDex --- The Supplement Research Compendium},
  url          = {https://nutridex.info/s/caramel-color},
  note         = {Reviewed by Dr Daryl Peh, MBBS Singapore, MMed FM. Accessed 2026-06-26}
}

For medical claims, citing the underlying primary studies linked above is preferred. NutriDex is an educational reference, not medical advice.

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