The use of dyes as food additives is not a modern invention and dates back to ancient times. As early as 1500 B.C.E. the Romans and Egyptians colored wines, medicines, and various other everyday foods 
. It is estimated that until around the mid-19th century, most food colorings came from natural sources such as peppers, blueberries, leaf chlorophyll, turmeric, indigo, cochineal, saffron, and various flowers 
. In 1885, the first synthetic dye, fuchsine, was obtained, which began the era of synthetic dyes 
. It is worth noting that dyes from natural sources were very expensive and difficult to obtain. It is believed that the development of fuchsin synthesis technology has opened the way to obtaining various dyes for both food and textile applications on a large scale at relatively low costs. Officially, the beginning of the era of the industrial use of synthetic dyes is considered to be 1856, when William Henry Perkin, looking for a simple way to synthesize quinine, accidentally obtained an intense purple dye—mauveine—and patented his invention 
. Mauveine is considered to be the first organic synthetic dye to be used on an industrial scale. After this discovery, the use of expensive and unstable natural dyes was discontinued, replacing them with synthetic dyes. Due to chemical stability, low production costs, and a larger range of shades, synthetic dyes were willingly used. Initially, they were mainly used for dyeing textiles 
. It was noticed that synthetic dyes have very strong coloring properties, so obtaining intense colors requires the addition of small amounts of dye. Due to this property, they were also used for coloring food products. Unfortunately, the first dyes of this type were aniline derivatives, which is a toxic compound, and its consumption can have dangerous side effects 
2. Antioxidant Dyes as Functional Food Additives and Their Relationship with Allergy
In the past, attention was drawn to the fact that dyes added to food were primarily intended to improve the appearance of food, and not to harm consumers. Recently, the approach to food additives has changed. It is important not only that food additives fulfill their technological function and are safe for consumers, but the additional functionality of the added substances, which has become an added value to their main purpose, is also very important. According to current trends, food additives, in addition to improving the organoleptic properties of food, should also increase the nutritional value of food. Food colorings have, for example, antioxidant properties 
. Antioxidants are perceived as substances with significant health-promoting properties. Food supplementation with antioxidants, including antioxidant dyes, may increase the nutritional value of foods 
. In unprocessed food, the most valuable sources of antioxidants are blue, red, and yellow fruits and vegetables, rich in anthocyanins and carotenes. A less important source of antioxidants are the green parts of plants, which are rich in chlorophyll 
Dyes of natural origin, including antioxidants, the source of which is mainly plant material, usually do not raise health concerns. An analysis by Lucas et al. 
showed that adverse reactions, including allergies, to natural food dyes are rather rare. Interestingly, there are various, contradictory hypotheses as to the possible relationship of antioxidant dyes added to food with allergic diseases, according to which these additives can both sensitize and prevent sensitization. In addition, it is also considered that the increase in the incidence of allergic diseases may be a consequence of both low and, on the contrary, high consumption of antioxidants. Since antioxidants are biologically active substances, it cannot be ruled out that all these hypotheses are possible 
Anthocyanins are a group of glycosidic dyes belonging to flavonoids, i.e., polyphenolic organic compounds. Polyphenols are a large group of dyes included in the so-called natural non-nutritive substances of plant origin. They are soluble in water. Currently, several hundred natural anthocyanin dyes and over a hundred synthetically obtained ones are known. Anthocyanins are found in various parts of plants; in flowers, fruit pulp, skin, leaves, stems, roots, and wood. Plant tissues usually contain a few to a dozen different anthocyanins. These dyes are characterized by a very diverse color from orange through various shades of red and violet to blue. Anthocyanins are chemically unstable. In the aqueous environment, depending on the pH and the presence of metal ions, anthocyanins change color due to a change in the structure of their molecules. In an acidic environment (pH < 3) anthocyanins are red, in a neutral environment (pH 7) they are violet, and in an alkaline environment (pH > 11) they are blue. Anthocyanins have strong antioxidant, anti-inflammatory, and anticancer properties. For this reason, anthocyanins are used as an active ingredient in nutraceuticals 
Natural anthocyanin dyes are most often obtained from grape pomace, blackcurrant, blueberries, elderberry, chokeberry, and cranberry. Recently, an extremely popular source of intensely blue anthocyanins is Clitoria ternatea
L.)—a species of tropical plant from the Fabaceae family. Anthocyanins as food colors are mainly used for the production of desserts and drinks. Blue food is considered extravagant and playful. Most often, extracts that are a mixture of anthocyanins are used, not single compounds. It is a simpler and cheaper solution. An interesting fact is that anthocyanin dyes are also used as indicators to assess the quality of colored food. The assessment of the anthocyanin profile is used to assess the quality of fruit jams and to check the quality of wine. The aging of these products causes a characteristic color change. It is associated with changing pH which is associated with the aging process of food 
Anthocyanins and their metabolites (mainly monoglucuronides) are excreted by the kidneys. These dyes are detected in the urine up to 24 h after ingestion 
. In the available literature, there are few reports of allergic reactions associated with the consumption of anthocyanins, either naturally occurring in food or added to food for coloring. Gallo et al. 
observed that the purple anthocyanin from eggplant skin, nasunin, can cause local hypersensitivity reactions. In patch tests conducted by these researchers on healthy volunteers with nasunin-containing eggplant peel extract, 12% of subjects experienced moderate skin irritation and 3% experienced an allergic reaction. Positive reactions were observed at a concentration of the dye above 5%, while the concentration of this dye in food or cosmetics usually does not exceed 1%. It seems that nasunin is a safe dye for food, medicine, cosmetics, and textiles 
Anthocyanins are naturally occurring pigments in various fruits and vegetables. Therefore, it is possible that they may be the cause of allergic reactions associated with the consumption of naturally containing plant foods. Case reports of allergic reactions of various clinical manifestations after consumption of grapes, especially purple or red wine, often in the presence of various cofactors, are available. Sebastia et al. 
reviewed 30 publications (1999–2010) on grape allergy. They reported both cases of oral allergy syndrome (OAS) and systemic anaphylactic reactions, usually in the presence of a cofactor (exercise or alcohol). It is worth noting that, in the analyzed cases of allergy to grapes or red wine, anthocyanins were never considered as the cause of hypersensitivity. Grapes contain a wide variety of well-identified proteins with known allergenic potential, such as lipid transfer proteins (nsLTP; Vit v 1), thaumatin-like proteins (TLPs), endochitinase 4A (the main grape allergen mainly responsible for allergic reactions to red wine), and endochitinase B 
. Sensitization to any of these proteins may cause a strong systemic anaphylactic reaction after consumption of grapes or their products (e.g., red wine), regardless of the grapes’ natural anthocyanins. The anthocyanins naturally present in grapes are not considered allergens.
An interesting edible source of anthocyanins are the flowers of Clitoria ternatea
(butterfly pea). They are mainly available in the form of dried leaves, from which intense blue infusions are obtained, known as blue tea (butterfly pea tea) with a characteristic herbal, earthy-woody taste. Clitoria flower infusion is also used as a natural blue colorant for drinks and desserts. Clitoria flowers can also be used to produce infusions in colors other than blue, by modifying the pH of the extract (e.g., lemon juice added to blue tea changes its color to purple) 
is not only the source of the naturally rare blue dye, but also an important remedy in traditional Ayurvedic medicine in Asia 
. In traditional medicine, the anti-inflammatory and antidiabetic effects of Clitoria
root, seed, leaf, and flower extracts are mainly used. Both the color and the anti-inflammatory properties of C. ternatea
petals are due to the high content of anthocyanins, mainly teratins-polyacylated delphinidin derivatives 
. The healing properties of Clitori
aextracts used in traditional medicine have been confirmed by the results of current research. Nair et al. 
identified twelve phenolic metabolites (nine ternatin anthocyanins and three glycosylated quercetins) in Clitoria ternatea
blue flower extracts. All Clitoria ternatea
polyphenols exhibited anti-inflammatory properties in macrophage-mediated inflammation caused by lipopolysaccharides (LPS). It has been shown that Clitoria ternatea
flower extracts strongly inhibit the activity of cyclooxygenase-2 (COX-2), reduce the release of free oxygen radicals, and reduce the production of nitric oxide by reducing the expression of nitric oxide synthase (iNOS). The available research results 
of extracts from other plants rich in ternatins indicate that they are a very good source of natural antioxidants, thanks to which they have a strong anti-inflammatory and antianaphylactic effect 
The available data do not indicate that intense blue Clitoria ternatea
flower extracts cause hypersensitivity reactions, regardless of the route of exposure. There are no reports of allergies after consuming infusions of these flowers or any food colored with them. On the contrary, it seems that extracts from various parts of clitoria (flowers, roots, or seeds) may have antihistamine and antiasthmatic effects 
. Singh et al. 
observed in an animal model that an alcoholic extract of Clitoria ternatea
flowers reduces dyspnoea and bronchospasm provoked by asthma exacerbation and reduces the concentration of proinflammatory cytokines, i.e., interleukin 1 beta (IL-1 beta) and interleukin 6 (IL-6) in the bronchi and alveoli. Therefore, it seems that standardized Clitoria
flower extracts may be a potential supportive therapy in the treatment of allergic asthma.
In summary, anthocyanins present in food, both naturally and added to foods for color, appear to have antiallergenic rather than proallergenic properties. The GA²LEN study showed that regular consumption of foods rich in anthocyanins, proanthocyanidins, and flavonoids not only does not involve a significant risk of allergic reactions, but also has a positive effect on the respiratory system and improves respiratory parameters measured by spirometry 
Betanin, also called beetroot red, is an organic chemical compound (glycoside) from the group of betalains. It is a natural food coloring with a dark red to purple color. Betanin is obtained from beets. Betanin dissolves in water and is sensitive to light and high temperature. These properties significantly limit the possibilities of using betanin for food coloring. Betanin is usually used in the dairy industry, mainly to color ice cream and yogurt. It is considered a completely harmless substance that can be consumed without restrictions. Under physiological conditions, it is completely excreted from the body in the urine 
. The only case of hypersensitivity to betanin (beetroot red) was reported by Zenaidi et al. 
based on prospective studies. Moreover, according to studies by Li et al. 
, betanin from food may have a protective effect against the development of allergic asthma. Li et al. 
examined the effect of betanin on experimentally induced ovalbumin (OVA) allergic asthma in BALB/c mice. It was observed that daily dietary supplementation with batanin significantly reduced the laboratory and clinical markers of allergic asthma and had a beneficial effect on the intestinal microbiota profile in mice. Also, Wang et al. 
confirmed the immunomodulatory and anti-inflammatory properties of betanin. It seems, therefore, that a diet rich in betanin prevents the development of allergic asthma and may be an effective support in the treatment of this disease.
Chlorophylls are natural lipid pigments present, e.g., in parts of plants exposed to light, algae, and photosynthetic bacteria (e.g., cyanobacteria). These are the basic pigments that enable the conversion of light energy into high-energy compounds in the process of photosynthesis. Chlorophylls are typical metalloporphyrin compounds (similar to hemoglobin and myoglobin). They are responsible for the characteristic green color of the organisms in which they occur. There are many types of chlorophylls (denoted by the letters a through g). Chlorophyll a (blue-green) and chlorophyll b (yellow-green) are the most abundant in nature. Under natural conditions, chlorophylls a and b occur together in a ratio of about 3:1 in all photosynthetic plants 
Chlorophylls for industrial applications are obtained as a result of solvent extraction of natural varieties of edible plant materials, including grasses, alfalfa, and nettle. The main color components are pheophytins and magnesium chlorophylls. Phaeophytins are formed as a result of partial or complete removal of naturally occurring coordination magnesium from chlorophylls in the process of removing post-extraction solvents. It should be remembered that the chlorophyll obtained as a result of extraction also contains other dyes, such as carotenoids, oils, fats, and waxes derived from natural raw material. Due to the instability of coordinated magnesium in the chlorophyll molecule and the associated color change from olive green to dark green, the use of chlorophyll as a food coloring is very limited. Chlorophyllins are derivatives of chlorophylls. Chlorophyllins are obtained via alkaline hydrolysis and cleavage of phytol from the chlorophyll molecule. They are more stable than chlorophylls and less sensitive to changes in the pH of the environment. This makes them better dyes for industrial applications than chlorophylls 
. In addition to chlorophylls and chlorophyllins, their copper complexes are also used as food dyes 
Chlorophylls dissolve in fats and chlorophyllins dissolve in water 
. Chlorophylls and chlorophyllins and their copper complexes are used as color additives in pasta, flavored vegetable oils, ice cream, fruit jellies, beverages, candies, canned peas, and pharmaceuticals and cosmetics. Chlorophyll dyes are considered the least durable plant dyes. They retain their characteristic green color only in living, undamaged tissues. The rate and nature of changes occurring during the storage and processing of raw materials rich in chlorophylls depends on environmental conditions, including mainly temperature, acidity, oxygen availability, the presence of metals, and specific enzymes such as chlorophyllase and lipoxygenase. Chlorophyllins are less sensitive to environmental conditions and have more intense colors than chlorophyll. 
Chlorophyll and its derivatives and metabolites are believed to have antioxidant, anti-inflammatory, and antiviral properties. Eating foods with a high content of these dyes may have a beneficial effect on health 
. For example, the phyllobilins (e.g., phylloucobilin, dioxobilin-type phylloucobilin, and phylloxanthobilin) are natural products of chlorophyll degradation. These linear chlorophyll metabolites are strong antioxidants with interesting physiological properties, including immunomodulatory ones 
. Although the exact mechanisms of the immunomodulatory effects are yet unknown, Karg et al. 
experimentally demonstrated the dose-dependent ability of phytobilins to inhibit the catabolism of tryptophan to kynurenine, suggesting a suppressive effect on cellular immune activation pathways. It is also possible that chlorophylls in combination with other substances, including chemotherapeutics, may show a synergistic effect and enhance the therapeutic effect of these substances. The results of Lauritano et al.’s 
experiments also showed that the products of the metabolic degradation of chlorophyll can inhibit the secretion of tumor necrosis factor alpha (TNF-α) using lipopolysaccharide (LPS)-stimulated macrophages. Also, Lin et al. 
observed the anti-inflammatory effect of chlorophyll and its derivatives by reducing the synthesis of proinflammatory factors and reducing the adhesion of inflammatory cells to the aortic endothelium in a mechanism dependent on the secretion of TNF-α by monocytes. Wang et al. 
, based on the results of their own research, postulate that chlorophylls can be a natural means of increasing the effectiveness of chemotherapeutic agents in the case of multi-drug-resistant pathogens. It is also likely that chlorophylls play a key role in the anticancer properties of natural plant extracts. Uğuz et al. 
showed that the removal of chlorophylls from green tea and olive leaf extracts significantly reduced the toxic effect of these solutions on cancer cells. In the light of the available data, it seems that chlorophyll and its derivatives have a huge pro-health potential, both individually and by enhancing the effect of other active food substances.
Despite the expected benefits of coloring food with chlorophyll and its derivatives, it is worth asking whether this supplementation is not associated with the risk of allergic reactions in consumers. The small number of available reports of possible allergic reactions associated with the consumption of chlorophyll suggests that this dye does not pose a significant allergic risk. In fact, only Böhm et al. 
in 2001 reported a case of a 28-year-old woman with allergy symptoms (recurrent angioedema, rhinoconjunctivitis, asthma-like symptoms), which they linked to the consumption of green-colored jelly beans with copper complexes of chlorophyll and chlorophyllins. The patient underwent two challenge tests: one open (with green jelly beans) and one blinded, placebo-controlled (with copper chlorophyllin), during which an anaphylactoid reaction in the form of facial angioedema and a runny nose was observed. Symptoms appeared 10 min after ingestion of five green jelly beans or 1 mg of copper chlorophyllin. As recommended, the patient eliminated copper chlorophyllin-stained foods from her diet and no new episodes of angioedema were observed during the three-year follow-up.
The problem of allergy to chlorophyll is not only the hypersensitivity to food color additives, but also the possible allergenic properties of chlorophyll naturally occurring in plants. Valbuena et al. 
reported a clinical case of a 52-year-old housewife with a history of allergic rhinoconjunctivitis to grass pollen, who experienced two episodes of shortness of breath with wheezing and coughing within 8–10 h after preparing raw chard. She had never experienced symptoms after inhaling chard fumes or after touching or ingesting chard before. Both raw chard and chlorophyll provocation results were positive in the patient. According to the clinical history, specific IgE for birch profilin (Bet v 2) was measured, but the result of this test was negative. Finally, Valbuena et al. 
diagnosed the patient as cross-allergic to a plant allergen other than profilins, but did not clearly identify the causative allergen.
When analyzing the case described above 
, it should be taken into account that natural sources of chlorophyll may contain proteins other than profilins, which may also cause allergies. Another case of chard allergy was reported by Jara-Gutiérrez et al. 
. These authors described a severe allergic reaction (cough, conjunctivitis, and angioedema) that developed in a 54-year-old woman minutes after contact with raw chard. The patient underwent skin prick tests (SPT) with a series of common inhalant allergens, lipid transfer proteins (LTP), and profilins, and native prick tests with raw chard, spinach, sugar beet, lettuce, and onion. The results were positive for pollen from grasses, olives, cypresses, plantains, Swiss chard, and profilins. Specific IgE was measured for beetroot (0.84 kU/L) and spinach (<0.1 kU/L). The test results suggested an allergy to profilin, which was not consistent with the patient’s clinical symptoms (severe reaction after contact with chard and no symptoms of inhalant allergy). As a result of subsequent laboratory tests, including the inhibition reaction on blots from raw and cooked beetroot extracts, a diagnosis of sensitization to chlorophyll a/b binding protein in chloroplasts with a molecular weight of 28 kDa was given.
Chlorophyll-binding proteins in chloroplasts are recognized allergens. Although to date only one allergen belonging to this group of proteins (Api g 3, celery) has been well-characterized and registered, it is very likely that proteins binding chlorophyll from other plants may also have significant allergenic properties.
Chlorophylls and their metabolites present in food can theoretically also have an antiallergic effect due to the antioxidant properties of these compounds 
. Fujiwara et al. 
noted that chlorophyll c2 extracted from Sargassum horneri reduced allergic symptoms in an animal model of allergic rhinitis. These researchers also evaluated the effectiveness of chlorophyll c2 in the treatment of patients with seasonal allergic rhinitis. This was a single-center, randomized, double-blind, placebo-controlled study. Sixty-six patients (20–43 years) with a minimum of 2 years of clinical history of allergic rhinitis were randomized to receive a single daily dose (0.7 mg) of chlorophyll c2 or placebo for 12 weeks. Throughout the procedure (weeks 4, 8, and 12), patients’ need for antiallergy medications (H1 antihistamines and nasal corticosteroids) and disease-specific quality of life (Japan Rhinitis Quality of Life Questionnaire; JRQLQ) were monitored. The results were compared to the state from before the start of the procedure. Based on the results, Fujiwara et al. 
concluded that chlorophyll c2 appears to be an attractive alternative treatment for allergic rhinitis.