Occurrence of azo food dyes and their effects on cellular inflammatory responses.

OBJECTIVES: The aim of this study was to examine the occurrence of five azo food dyes-tartrazine, sunset yellow, carmoisine, allura red, and ponceau 4 R-in the food supply chain of Singapore and their effects on the in vitro synthesis of leukotriene B4 (LTB4) and F2-isoprostanes. METHODS: Trained personnel recorded the names of foods and beverages sold in a local supermarket that contained at least one of the five azo dyes. The occurrence of the azo dyes in the local food supply was computed. The synthesis of LTB4 and F2-isoprostanes from freshly isolated blood neutrophils were measured using gas chromatography-mass spectrometry. RESULTS: Of the 1681 processed food items, 194 (11.54%) contained at least one of the five azo dyes. Tartrazine was most prevalent in food and beverage products sold in Singapore, followed by allura red, sunset yellow, ponceau 4 R, and carmoisine. The five azo dyes augmented the in vitro synthesis of LTB4 and F2-isoprostanes from blood neutrophils. Tartrazine was significantly more potent in increasing LTB4 synthesis than the other dyes, which exhibited similar potencies. The five food dyes increased the formation of F2-isoprostanes from blood neutrophils at all tested concentrations. CONCLUSION: The high prevalence of azo dyes in the food supply of Singapore and their ability to elicit proinflammatory responses in vitro suggest a potential health risk to the local population.

Curcumin protects against tartrazine-mediated oxidative stress and hepatotoxicity in male rats.

OBJECTIVE: Synthetic dyes have been reported to exert detrimental effects on the health of humans. This study evaluated the effects of a diet containing tartrazine (Tz) on rats which included: i) biochemical parameters including hepatic enzymes, kidney functions and profiles of lipids; ii) markers of oxidative stress in cells by measuring concentrations of malondialdehyde (MDA) and glutathione (GSH); iii) activities of selected, key hepatic antioxidant enzymes including catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx); iv) pathologies of liver. Also, protective effects of three doses of curcumin (CUR), a natural food coloring agent, on these parameters in rats that had been co-exposed to Tz. MATERIALS AND METHODS: Fifty Wistar male albino rats were randomly divided into five groups: Group I, control, where rats were fed a normal diet; Group II, rats were fed normal diets containing 7.5 mg Tz/kg diet, dry mass (dm); In Groups III, IV and V, rats were fed diets containing Tz plus 1.0, 2.0 or 4.0 g CUR/kg diet, dm, respectively. Whole blood was collected after 90 d of exposure, homogenates of liver were prepared and the above analyses were conducted. RESULTS: Exposure to Tz in the diet caused statistically significant (p<0.05) greater concentrations of lipids, hepatic enzymes, and kidney function parameters as well as the indicator of oxidative stress MDA. Alternatively, activities of several antioxidant enzymes (i.e. CAT, SOD and GPx) and concentration of the substrate GSH, an indicator of non-enzymatic antioxidant capability, were significantly (p<0.05) less than those in control rats not exposed to Tz. Tz caused various histopathological changes in livers of rats, which were characterized by hemorrhage and dilatation of the central vein and sinusoids, hepatocyte necrosis, intracellular vacuolization. Co-administration of 2.0 (Group IV) or 4.0 g CUR/kg diet (Group V) with Tz significantly mitigated effects on functions of liver and kidney and the profile of relative concentrations of lipids. CUR significantly (p<0.05), and almost completely, reversed effects on enzymatic and non-enzymatic antioxidant and indicators of oxidative stress about rats fed Tz (Group II) to values in control rats. However, co-administration of 1.0 g CUR with Tz (Group III) exhibited a negligible effect on those parameters. The results of this study suggest benefits of the use of CUR, as a promising natural food additive to counteract oxidative stress caused by dietary exposure to the synthetic dye Tz due to potent protective antioxidant activity. CONCLUSIONS: Blending some natural food additives, such as CUR with diets containing synthetic dyes, could moderate potential effects of these artificial dyes. Decreasing or removing toxins in food is an essential step for the amelioration of human health status and decreasing risk of onset or progression of degenerative diseases.

Exposure estimate for FD&C colour additives for the US population.

Dietary exposures to the seven food, drug, and cosmetic (FD&C) colour additives that are approved for general use in food in the United States were estimated for the US population (aged 2 years and older), children (aged 2-5 years) and teenage boys (aged 13-18 years) based on analytical levels of the FD&C colour additives in foods. Approximately 600 foods were chosen for analysis, based on a survey of product labels, for the levels of FD&C colour additives. Dietary exposure was estimated using both 2-day food consumption data from the combined 2007-10 National Health and Nutrition Examination Survey (NHANES) and 10-14-day food consumption data from the 2007-10 NPD Group, Inc. National Eating Trends - Nutrient Intake Database (NPD NET-NID). Dietary exposure was estimated at the mean and 90th percentile using three different exposure scenarios: low exposure, average exposure and high exposure, to account for the range in the amount of each FD&C colour additive for a given food. For all populations and all exposure scenarios, the highest cumulative eaters-only exposures in food were determined for FD&C Red No. 40, FD&C Yellow No. 5 and FD&C Yellow No. 6. In addition, the eaters-only exposure was estimated for individual food categories in order to determine which food categories contributed the most to the exposure for each FD&C colour additive. Breakfast Cereal, Juice Drinks, Soft Drinks, and Frozen Dairy Desserts/Sherbet (also referred to as Ice Cream, Frozen Yogurt, Sherbet (including Bars, Sticks, Sandwiches)) were the major contributing food categories to exposure for multiple FD&C colour additives for all three populations.

Effect of food azo dye tartrazine on learning and memory functions in mice and rats, and the possible mechanisms involved.

UNLABELLED: Tartrazine is an artificial azo dye commonly used in human food and pharmaceutical products. The present study was conducted to evaluate the toxic effect of tartrazine on the learning and memory functions in mice and rats. Animals were administered different doses of tartrazine for a period of 30 d and were evaluated by open-field test, step-through test, and Morris water maze test, respectively. Furthermore, the biomarkers of the oxidative stress and pathohistology were also measured to explore the possible mechanisms involved. The results indicated that tartrazine extract significantly enhanced active behavioral response to the open field, increased the escape latency in Morris water maze test and decreased the retention latency in step-through tests. The decline in the activities of catalase, glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) as well as a rise in the level of malonaldehyde (MDA) were observed in the brain of tartrazine-treated rats, and these changes were associated with the brain from oxidative damage. The dose levels of tartrazine in the present study produced a few adverse effects in learning and memory functions in animals. The mechanisms might be attributed to promoting lipid peroxidation products and reactive oxygen species, inhibiting endogenous antioxidant defense enzymes and the brain tissue damage. PRACTICAL APPLICATION: Tartrazine is an artificial azo dye commonly used in human food and pharmaceutical products. Since the last assessment carried out by the Joint FAO/WHO Expert Committee on Food Additives in 1964, many new studies have been conducted. However, there is a little information about the effects on learning and memory performance. The present study was conducted to evaluate the toxic effect of tartrazine on the learning and memory functions in animals and its possible mechanism involved. Based on our results, we believe that more extensive assessment of food additives in current use is warranted.

Safety of ingestion of yellow tartrazine by double-blind placebo controlled challenge in 26 atopic adults.

BACKGROUND: Yellow dye tartrazine is a potential cause of exacerbations of asthma, allergic rhinitis and urticaria in atopic patients. The Brazilian Sanitary Surveillance Agency (ANVISA) published a consultation about the possibility of issuing a label warning addressing these potential effects of food and drugs containing tartrazine. The present study aims to evaluate tartrazine dye safety in atopic subjects suffering from allergic rhinitis, asthma, urticaria or sensitivity to non-steroidal anti-inflammatory drugs (NSAIDs). METHODS: Atopic patients with allergic rhinitis, asthma, urticaria or pseudo-allergic reactions to non-steroidal anti-inflammatory drugs were studied (n=26). The gold standard, double-blind placebo controlled, crossed-over challenge was used RESULTS: There were no statistical differences between placebo and drug in cutaneous, respiratory or cardiovascular aspects. CONCLUSIONS: In a group of atopic subjects with allergic rhinitis, asthma, urticaria or pseudo-allergic reactions to non-steroidal anti-inflammatory drugs, the administration of 35 mg of the tartrazine dye did not precipitate any kind of significant cutaneous, respiratory or cardiovascular reactions when compared to placebo.

Pattern of intake of food additives associated with hyperactivity in Irish children and teenagers.

A double-blind randomized intervention study has previously shown that a significant relationship exists between the consumption of various mixes of seven target additives by children and the onset of hyperactive behaviour. The present study set out to ascertain the pattern of intake of two mixes (A and B) of these seven target additives in Irish children and teenagers using the Irish national food consumption databases for children (n = 594) and teenagers (n = 441) and the National Food Ingredient Database. The majority of additive-containing foods consumed by both the children and teenagers contained one of the target additives. No food consumed by either the children or teenagers contained all seven of the target food additives. For each additive intake, estimates for every individual were made assuming that the additive was present at the maximum legal permitted level in those foods identified as containing it. For both groups, mean intakes of the food additives among consumers only were far below the doses used in the previous study on hyperactivity. Intakes at the 97.5th percentile of all food colours fell below the doses used in Mix B, while intakes for four of the six food colours were also below the doses used in Mix A. However, in the case of the preservative sodium benzoate, it exceeded the previously used dose in both children and teenagers. No child or teenager achieved the overall intakes used in the study linking food additives with hyperactivity.

[Food additive hypersenisivity--near myth]. / Lisäaineyliherkkyys--melkein myytti.

There are over 200 food additives that have been approved in Finland. They are being used in order to improve preservability, flavor, appearance and texture. Some of them may cause hypersensitivity reactions, the most common being anaphylactic reactions, urticaria and exacerbation of asthma. Such reactions are, however, very rare. Anaphylactic reactions and other symptoms have resulted from carmine, lysozyme, acetic acid and acetates, gums of plant origin, sulfites and tartrazine.

Lactobacilli and tartrazine as causative agents of red-color spoilage in cucumber pickle products.

The cucumber pickling industry has sporadically experienced spoilage outbreaks in pickled cucumber products characterized by development of red color on the surface of the fruits. Lactobacillus casei and Lactobacillus paracasei were isolated from 2 outbreaks of this spoilage that occurred about 15 y apart during the last 3 decades. Both organisms were shown to produce this spoilage when inoculated into pickled cucumbers while concomitantly degrading the azo dye tartrazine (FD&C yellow nr 5). This food dye is used as a yellow coloring in the brine cover solutions of commercial pickled cucumber products. The red color does not occur in the absence of tartrazine, nor when turmeric is used as a yellow coloring in the pickles. Addition of sodium benzoate to the brine cover solutions of a pickled cucumber product, more specifically hamburger dill pickles, prevented growth of these lactic acid bacteria and the development of the red spoilage.

Estimates of dietary exposure of children to artificial food colours in Kuwait.

To assess the intake of artificial food colour additives by 5-14-year-old children in the State of Kuwait, a 24-h dietary recall was conducted twice on 3141 male and female Kuwaiti and non-Kuwaiti children from 58 schools. The determination of colour additives in 344 foods items consumed was performed using high-performance liquid chromatography with diode array detector. A comparison with the Food and Agriculture Organization and World Health Organization acceptable daily intakes (ADIs) was undertaken to evaluate the potential risk associated with the consumption of artificial colour additives by children in Kuwait. The results indicated that out of nine permitted colours, four exceeded their ADIs by factors of 2-8: tartrazine, sunset yellow, carmoisine and allura red. Further, follow-up studies to provide insight into potential adverse health effects associated with the high intakes of these artificial colour additives on the test population are warranted.

Urinary metabolites of histamine and leukotrienes before and after placebo-controlled challenge with ASA and food additives in chronic urticaria patients.

BACKGROUND: The recovery of mediator metabolites from urine has the potential to provide a rapid, safe, and easily available index of release of mediators. We aimed to determine urinary metabolites of both histamine and leukotrienes (LTs) in patients affected by chronic urticaria (CU). METHODS: Twenty patients with CU were studied. They were selected on the basis of double-blind placebo-controlled challenge (DBPC) with acetyl salicylic acid (ASA) and food additives. Ten patients (group B) were negative to both challenges. Ten patients (group C) presented urticaria and/or the appearance of angioedema during or 24 h after challenge, with reactions to ASA (five patients) or food additives (five patients). We recruited 15 healthy volunteers as controls (group A). During a second challenge, groups B and C were challenged double-blind with a single dose of ASA, or a specific food additive, or placebo. The healthy group was challenged only with a placebo (talc capsule). Patients in groups B and C were challenged twice: with placebo (as groups B1 and C1) and with ASA (groups B2 and C2) or food additives (C2). Four samples of urine were collected; one during the night before the specific or sham challenge (baseline), and three at 2, 6 and 24 h after the challenge. Urinary methylhistamine (N-MH) and LTE4 were analyzed and normalized for urinary creatinine. RESULTS: For urinary N-MH at baseline, there was a significant difference only between group A and groups B1, B2, C1 and C2 (A vs. B1, P < 0.0001; A vs. B2, P < 0.0001; A vs. C1, P < 0.0001; A vs. C2, P < 0.0001). We detected a significant variation in urinary methylhistamine excretion only in group C2 after 2 h, 6 h and 24 h (P < 0.0001). However, no variations were observed in N-MH excretion rate in the other groups (A, B1, C1) after challenge with placebo, and in B2 after challenge with ASA 20 mg. For urinary LTE4 at baseline no differences were found between the mean values for the different groups. After specific challenge, only C2 patients showed significantly increased excretion rates of urinary LTE4 compared with the other groups challenged with placebo (A, B1, C1), or ASA (B2) (P < 0.0001). No significant correlation was seen between urinary LTE4 and methylhistamine excretion rate in any patients. CONCLUSION: Our results show that urinary excretion of N-MH and LTE4 is different for CU patients without ASA or food hypersensitivity, compared to those with CU with ASA or food additive hypersensitivity after specific challenge.

Tartrazine exclusion for allergic asthma.

BACKGROUND: Tartrazine is the best known and one of the most commonly used food additives. Food colorants are also used in many medications as well as foods. There has been conflicting evidence as to whether tartrazine causes exacerbations of asthma with some studies finding a positive association especially in individuals with cross-sensitivity to aspirin. OBJECTIVES: To assess the overall effect of tartrazine (exclusion or challenge) in the management of asthma. SEARCH STRATEGY: A search was carried out using the Cochrane Airways Group specialised register. Bibliographies of each RCT was searched for additional papers. Authors of identified RCTs were contacted for further information for their trials and details of other studies. SELECTION CRITERIA: RCTs of oral administration of tartrazine (as a challenge) versus placebo or dietary avoidance of tartrazine versus normal diet were considered. Studies which focused upon allergic asthma, were also included. Studies of tartrazine exclusion for other allergic conditions such as hay fever, allergic rhinitis and eczema were only considered if the results for subjects with asthma were separately identified. Trials could be in either adults or children with asthma or allergic asthma (e.g. sensitivity to aspirin or food items known to contain tartrazine). DATA COLLECTION AND ANALYSIS: Study quality was assessed and data abstracted by two reviewers independently. Outcomes were analysed using RevMan 4.1.1. MAIN RESULTS: Ninety abstracts were found, of which 18 were potentially relevant. Six met the inclusion criteria, but only three presented results in a format that permitted analysis and none could be combined in a meta-analysis. In none of the studies did tartrazine challenge or avoidance in diet significantly alter asthma outcomes. REVIEWER'S CONCLUSIONS: Due to the paucity of available evidence, it is not possible to provide firm conclusions as to the effects of tartrazine on asthma control. However, the six RCTs that could be included in this review all arrived at the same conclusion. Routine tartrazine exclusion may not benefit most patients, except those very few individuals with proven sensitivity.

Allergy to tartrazine in psychotropic drugs.

BACKGROUND: High psychiatric morbidity has been reported among those who complain of food intolerance or allergy. Many cases of food allergy or intolerance to drugs are not due to allergy to the food or drugs themselves, but to the additives used for coloring, flavoring, preserving, thickening, emulsifying, or stabilizing the product. Of various coloring dyes used, tartrazine (FD & C yellow no. 5) is the color most frequently incriminated in producing allergic reactions. The exact epidemiology and pattern of allergic reactions to tartrazine in psychotropic drugs have not been frequently studied and reported. METHOD: The present study included consecutive outpatients (May 1996 to April 1998) who developed allergic reactions or intolerance to tartrazine in psychotropic drugs. Total patients exposed to tartrazine-containing drugs were also recorded. The subjects showing allergic reactions to tartrazine were then exposed to non-tartrazine-containing brands. RESULTS: Of 2210 patients exposed to tartrazine-containing drugs, 83 (3.8%) developed allergic reactions. The symptoms subsided within 24 to 48 hours of stopping the drug. None of the patients showed allergy to non-tartrazine-containing brands. History of allergy to tartrazine was present in 13.2%, and 15.7% of patients had a history of aspirin sensitivity. CONCLUSION: Tartrazine allergy should be considered in patients developing drug allergy, because it would require changing the brand rather than stopping treatment with that drug.

[Purpura pigmentosa progressiva in type III cryoglobulinemia and tartrazine intolerance. A follow-up over 20 years]. / Purpura pigmentosa progressiva bei Kryoglobulinämie Typ III und Tartrazinintoleranz. Ein Verlauf über 20 Jahre.

A 58 year old patient with hepatitis virus C (HCV) infection had a secondary polyclonal IgG-IgM cryoglobulinemia with a benign 20 year course. Clinically the patient suffered from progressive pigmented purpura (PPP). Histologic evaluation revealed a lymphocytic vasculitis. Food containing tartrazine triggered flares of the PPP, as demonstrated with controlled oral provocation testing. In most of the previously described cases of HCV and type III cryoglobulinemia, the typical cutaneous finding was palpable purpura with leukocytoclastic vasculitis.

Fixed drug eruption to tartrazine.

An 11-year-old girl with a recurrent fixed drug eruption to tartrazine on the dorsum of the left hand is presented. Oral provocation tests to both the suspected food, an artificially coloured cheese crisp, and to tartrazine were positive. This case highlights fire need to consider artificial flavours, colours and preservatives as potential culprits in classic drug eruptions.

[Effect of an oligo-antigen diet on the behavior of hyperkinetic children]. / Der Einfluss einer oligoantigenen Diät auf das Verhalten von hyperkinetischen Kindern.

The influence of an oligoantigenic diet on different dimensions of the behavior of 21 children diagnosed as having attention-deficit hyperactivity disorder (ADHD) was examined. Treatment effects were assessed with three subjective measures (two questionnaires and an interview) and three objective measures (two attention tests and actometer). The study was divided into three phases: baseline, diet and provocation, each lasting three weeks. A crossover design was used. A significant effect was found for the subjective measures, but not for the objective measures. The results are discussed in terms of possible types of effects, e. g. rater effects and environmental effects. It may be that the oligoantigenic diet influences only certain dimensions of hyperactivity.