Tagetes (Marigold): A Comprehensive Encyclopedic Reference
1. Identity and Botanical Classification
1.1 Taxonomy and Nomenclature
The genus Tagetes belongs to the family Asteraceae (formerly Compositae) and encompasses a diverse group of flowering plants commonly known as marigolds. Tagetes (marigold) is native to America, and its cultivation currently extends to other countries in Africa, Asia, and Europe. Many species of this genus, such as T. minuta, T. erecta, T. patula, and T. tenuifolia, are cultivated as ornamental plants and studied for their medicinal properties on the basis of their use in folk medicine.
The four most pharmacologically and commercially significant species are:
- Tagetes erecta L. — Known as Aztec marigold, African marigold, or Mexican marigold (Spanish: cempasúchil or cempoalxóchitl). The marigold (Tagetes erecta), also known as the "Flower of the Dead" or "Cempaxóchitl," is an emblematic flower in Mexican culture. It is the primary commercial source of lutein for the dietary supplement and food-coloring industries.
- Tagetes patula L. — Known as French marigold. Notable for its high concentration of thiophene compounds and flavonoid patuletin, and widely studied for its antifungal and antimicrobial properties.
- Tagetes minuta L. — Known as wild marigold or muster-john-henry. Cultivated primarily for its essential oil, also studied for antimicrobial and anti-angiogenic activity.
- Tagetes lucida Cav. — Known as Mexican tarragon, sweet-scented marigold, or pericón. A native aromatic plant that was and remains one of the most important ritual plants used frequently in Mexico. Its common names include "pericón," "yauhtli" (Nahuatl), "hierba anís," or "hierba de Santa María"; in English it is called Mexican mint marigold.
1.2 Botanical Description
T. erecta is an herbaceous plant that may be annual or perennial, growing to a height of 12 to 43 inches (30–110 cm), and matures in 100 to 120 days with a short-day cycle. The word "tagetes" is derived from Etruscan mythology, specifically the figure Tages. The word "erecta" in Latin means 'upright.' Other names of this plant include Aztec marigold and cempaxochitl. The marigold is native to Mexico and Central America. Its name comes from the Nahuatl "cempohualxochitl," meaning "twenty flowers," in reference to the abundance of petals on each flower. This flower is believed to have been cultivated in Mexico for over 3,000 years.
1.3 Common Forms and Commercial Preparations
Tagetes species are available in a range of commercial and traditional preparations:
- Marigold oleoresin and saponified flower extract: Lutein from Tagetes erecta L. is a purified extract obtained from marigold oleoresin, which is extracted from the petals of marigold flowers with organic solvents. The final product, after saponification, contains, as a major component, lutein and a smaller proportion of zeaxanthin.
- Standardized lutein supplements: Soft-gel capsules, tablets, and powder concentrates standardized to a defined percentage of total carotenoids, primarily marketed for eye health.
- Essential oils: Obtained by hydro-distillation of aerial parts or flowers; used primarily in cosmetics and aromatherapy.
- Dried herb and infusions: Particularly of T. lucida, consumed as a tea (infusion of aerial parts) in traditional Mexican medicine.
- Poultry feed additive: Tagetes meal (dried, ground flowers) and extract are used as colorants and xanthophyll sources in animal feed.
- Food colorant: It is used as a food colouring agent and nutrient supplement (food additive) in a wide range of baked goods.
2. Traditional and Historical Use
2.1 Pre-Hispanic Mesoamerica
Tagetes holds one of the longest and most thoroughly documented pre-Hispanic ethnobotanical records in the Americas. Ancient Mesoamerican peoples, such as the Aztecs, Mayans, and Purépecha, used the marigold in various ceremonies and rituals. In pre-Hispanic times, the marigold had a profound symbolic meaning. The Aztecs used it to decorate tombs and altars in honor of the deceased. They also believed that the flowers' scent guided the souls of the dead back to Earth during the Day of the Dead.
Yauhtli (Tagetes lucida) and cempoalxochitl (Tagetes erecta) are integral to Aztec medicine and religion. The Aztecs viewed disease as a consequence of sin, intertwining medicine with religious practices. Yauhtli was reported to treat 25 ailments, highlighting its significance in Aztec medicinal practices.
Of central importance is the 1552 work compiled by the young Aztec physician baptized as Martin de la Cruz, which was originally in Nahuatl and then translated into Latin as Libellus de Medicinalis Indorum Herbis. What we call Tagetes lucida and Tagetes erecta were burned along with copal (aromatic resin from the copal tree) in the incense burners associated with the imposing Templo Mayor in Tenochtitlán. The musky scent was believed by the Aztecs to carry messages and prayers to the gods.
Mexican tarragon has a history dating back to the 12th-century Aztecs and ancient Mayans (2000 BCE–1627 CE), who used this anise-flavored herb to flavor their famous cocoa-based drink, chocolatl, and enhanced their tobacco products with its leaves.
Marigolds were also sacred to Mayan cultures, and in both Aztec and Mayan cultures, the plant was often used to honor gods and spirits. Mayan priests would wash themselves with a marigold brew before calling on spirits.
2.2 Medicinal Uses in Traditional Mexican and Mesoamerican Systems
Different parts of the Tagetes species are used as remedies to treat various health problems, including dental, stomach, intestinal, emotional, and nervous disorders, as well as muscular pain, across the world.
In Mexico, T. lucida has a particularly well-documented medicinal history. A previous review of Mexican medicinal plants showed that 89 common species are associated with sedative and anxiolytic-like effects. Traditional Mexican healers recommend these species for reassurance and for treating stress, "nervios," "susto," shock, nervousness, and nervous excitement. Additional conditions treated include rheumatic pain, asthma, varicose veins, inflammation, abortion, carminative activity, anthelmintic infection, musculoskeletal pain, and neurological and inflammatory diseases. Tagetes lucida has been used for the treatment of emotional and nervous disorders as part of a mixture with other anxiolytic plants.
In Mexico, marigold seeds, either raw or toasted, have been used for centuries to treat intestinal worms. The leaves and roots are also used to make a laxative tea, which also helps with fever and general stomach pains.
Tagetes lucida is often dried and used as incense during Day of the Dead rituals. An anise-flavored tea brewed from the leaves is served during the celebration.
2.3 Spread to Other Traditions
With the arrival of the Spanish conquistadors in the 16th century, indigenous traditions blended with Christian beliefs. This led to the fusion of the indigenous Day of the Dead festivities with All Saints' Day and All Souls' Day, Catholic holidays celebrated on November 1 and 2. This fusion gave rise to the holiday we know today as the Day of the Dead. Through this process, the cultural and botanical use of marigolds spread further across the Americas and eventually to Europe, Africa, and Asia, where the plant was naturalized. It is native to Mexico and Central America, where it has long been used as a medicinal herb and dye plant.
3. Key Constituents and Active Compounds
3.1 Carotenoids
Carotenoids are the most commercially and pharmacologically significant class of compounds in T. erecta. Marigold (Tagetes spp.) flower petals are the most vital sources of carotenoids, especially lutein esters, for the production of natural lutein to use for food, feed, and pharmaceutical industries.
The extract contains 93% utilizable pigments (detected at 450 nm), consisting of all-trans and cis isomers of zeaxanthin (5%), all-trans and cis isomers of lutein, and lutein esters (88%). Lutein (3R,3'R,6'R-βε-carotene-3,3'-diol) is a member of a group of pigments known as xanthophylls and has no provitamin A activity.
Supplements derived from Tagetes erecta L. also contain zeaxanthin and meso-zeaxanthin at lower concentrations. The human macula uniquely concentrates three carotenoids: lutein, zeaxanthin, and meso-zeaxanthin.
In the body, the absorption and distribution of lutein have been established following administration of free lutein or its diacylester(s) from Tagetes petals. Lutein esters are hydrolyzed in the intestinal tract and free lutein is absorbed at the duodenum and jejunum levels.
3.2 Flavonoids
Marigold extracts are characterized by the presence of diverse compounds with different properties, namely phenylpropanoids, carotenoids, flavonoids, thiophenes, and others. The principal flavonoids identified across Tagetes species include patuletin (a major flavonoid in T. patula), quercetin, kaempferol, and related glycosides. Quercetagetin and its glycosides have also been identified as important constituents of T. erecta flowers. The modulation of the release and reuptake of serotonin and antidepressant effects may also be due to quercetin, a compound found in T. lucida.
3.3 Thiophenes
The thiophene class of compounds constitutes one of the most structurally distinctive phytochemical features of the Tagetes genus. T. patula accumulates in its tissues high amounts of thiophenes, well known for their phototoxic activity towards bacteria, nematodes, and fungi. The most studied thiophene is alpha-terthienyl (α-T), a compound that exhibits potent photosensitizing activity upon ultraviolet-A irradiation. Acting as a phototoxic agent, α-T generates reactive oxygen species (ROS) under ultraviolet (UV) light, leading to nematode mortality through oxidative stress.
Additional thiophene compounds identified include 5-(3-buten-1-ynyl)-2,2'-bithienyl (BBT) and 5-(4-hydroxy-1-butynyl)-2,2'-bithienyl (BBTOH).
3.4 Essential Oil Constituents
Generally speaking, the oils are rich in monoterpene hydrocarbons (ocimenes, limonene, terpinene, myrcene, etc.) and in acyclic monoterpene ketones (tagetone, dihydrotagetone, and tagetenone), which are the primary odorants, in addition to lower amounts of sesquiterpene hydrocarbons and oxygenated compounds. The main chemical structures found across Tagetes essential oils include limonene, α-pinene, β-pinene, terpinolene, (E)-β-ocimene, dihydrotagetone, tagetone, tagetenone, β-caryophyllene, and eugenol. In T. lucida specifically, the main component of the essential oil was identified as methyl chavicol, which matched over 90% of the whole composition.
3.5 Coumarins
Tagetes lucida is additionally notable for its coumarin content. The anxiolytic and sedative-like properties of T. lucida may result from the effect of its coumarinic constituents on serotonergic neurotransmission, manifesting an antidepressant effect by the serotonergic system. Key coumarins identified include 6,7-dimethoxy-coumarin (herniarin), 7-methoxycoumarin (umbelliferone methyl ether), and 7-isoprenyloxycoumarin.
4. Mechanisms of Action
4.1 Antioxidant and Blue-Light Filtering (Xanthophylls)
The retina is one of the most metabolically active tissues in the body. The highest concentration of xanthophylls is found within the retina, and this selective presence has generated many theories regarding their role in supporting retinal function. Antioxidant and blue light-filtering properties of lutein/zeaxanthin for short wavelengths are hypothesized to protect the eye against AMD. The filtration of blue light reduces chromatic aberration, which can enhance visual acuity and sensitivity.
4.2 Serotonergic and GABAergic Modulation (Coumarins and Flavonoids of T. lucida)
A study by Pérez Ortega et al. in 2016 demonstrated that extracts of different polarities from T. lucida had a sedative effect by reducing the spontaneous motor behavior of mice and an anxiolytic effect by interacting with the serotonergic and GABAergic neurotransmission system, attributing the possible effect to compounds identified as coumarins and flavonoids. The anxiolytic activity is partially blocked by WAY100635 (a 5-HT1A receptor antagonist) and flumazenil (a GABA/benzodiazepine receptor antagonist), indicating dual serotonergic and GABAergic mechanisms.
4.3 Phototoxic Membrane Disruption (Thiophenes)
After UVA irradiation, the photoactive thiophene compound alpha-terthienyl caused damage to membranes of the nucleus, mitochondria, and endoplasmic reticulum. Plasmolytic and autolytic changes resulted in plasma membrane breakage and cell wall aberrations in target microorganisms.
4.4 Anti-Inflammatory Cytokine Suppression
In preclinical models, T. erecta extracts have been shown to modulate inflammatory mediators. Treatment with the dry hydroalcoholic extract decreased myeloperoxidase activity as well as tumor necrosis factor and interleukin-6 levels. The extract also increased reduced glutathione levels and catalase activity and normalized superoxide dismutase and glutathione-S-transferase activities.
4.5 Protein Kinase C Inhibition (Anti-angiogenic)
A study examining a thiophene derivative from T. minuta found that the results validated the inhibitory effect on protein kinase C (PKC) isozymes α and β2 as the main mechanism underlying its antiangiogenic activity. The compound also inhibited VEGF-induced tube formation with an IC50 of 2.7 ± 0.4 μM and significantly impaired the invasiveness of bovine aortic endothelial cells as well as of the highly aggressive breast cancer cells, MDA-MB-231, when tested at 10 μM.
5. Scientific Evidence by Area of Use
5.1 Ocular Health — Age-Related Macular Degeneration (AMD)
This is the area with the strongest and most extensively studied human clinical evidence associated with Tagetes-derived compounds. Known mostly for their role in eye health, consumption and serum levels of these xanthophylls have been investigated for their potential beneficial effects on supporting vision performance of healthy eyes, as well as in the context of ocular diseases, including age-related macular degeneration (AMD), cataracts, and diabetic retinopathy.
Observational studies have reported that increased dietary intake and higher serum levels of lutein and zeaxanthin are associated with lower risk of age-related macular degeneration (AMD), especially late AMD.
The landmark human trial in this field is the Age-Related Eye Disease Study 2 (AREDS2), conducted by the U.S. National Eye Institute. The AREDS2 trial, a multicenter, double-masked clinical trial, enrolled 4,203 participants, aged 50 to 85 years, at risk for progression to advanced age-related macular degeneration. Participants were randomly assigned to daily placebo; lutein/zeaxanthin, 10 mg/2 mg; omega-3 long-chain polyunsaturated fatty acids, 1 g; or a combination to evaluate the effects on the primary outcome of progression to advanced age-related macular degeneration.
In the AREDS2 trial, adding omega-3 fatty acids or lutein + zeaxanthin to the AREDS formula had no additional overall effect on the risk of advanced AMD. However, AREDS2 participants who took antioxidants minus beta-carotene but with lutein + zeaxanthin (AREDS2 formula) had an incremental increase in benefit, compared to those who took the AREDS formula.
In a secondary analysis of AREDS2, the participants who benefitted most from taking lutein + zeaxanthin were those who did not get much of these nutrients in their diet. Within this group, those who received lutein/zeaxanthin supplements had a 26% reduced risk of developing advanced AMD compared with those who did not receive the supplements.
A ten-year follow-up analysis of AREDS2 data confirmed durable benefit: the AREDS2 formula, which substituted antioxidants lutein and zeaxanthin for beta-carotene, not only reduces risk of lung cancer due to beta-carotene, but is also more effective at reducing risk of AMD progression compared to the original formula. Specifically, participants who took an AREDS formulation containing lutein + zeaxanthin lacking beta-carotene had an 18% lower risk of progressing to advanced AMD compared with those who took AREDS containing beta-carotene.
A meta-analysis of nine randomized controlled trials (920 eyes, 855 with AMD) found that lutein supplementation (10 or 20 mg per day) was associated with an increase in macular pigment optical density (MPOD) (mean difference 0.07; 95% CI 0.03 to 0.10), visual acuity (mean difference 0.28; 95% CI 0.06 to 0.50) and contrast sensitivity (mean difference 0.26; 95% CI 0.22 to 0.30). Stratified analyses showed the increase in MPOD to be faster and greater with higher dose and longer treatment.
A broader meta-analysis of 20 RCTs including 938 AMD patients and 826 healthy subjects found that xanthophyll carotenoids supplementation was associated with a significant increase in MPOD in AMD patients (WMD, 0.07; 95% CI, 0.03 to 0.11) and healthy subjects (WMD, 0.09; 95% CI, 0.05 to 0.14).
Evidence strength: Strong. Human clinical evidence (AREDS2 multicenter RCT, multiple meta-analyses of RCTs) consistently supports lutein and zeaxanthin from T. erecta supplementation in reducing AMD progression risk, particularly in individuals with low baseline dietary intake. This is among the best-supported areas in all of nutritional supplement research.
5.2 Ocular Health — Cataracts
The AREDS2 trial also examined cataract outcomes. A secondary outcome of AREDS2 was to evaluate the effects of lutein/zeaxanthin on the subsequent need for cataract surgery. AREDS2 was designed to test large doses of lutein/zeaxanthin, 10 mg/2 mg, against near dietary levels of intake. Adding omega-3 fatty acids or lutein + zeaxanthin to antioxidants plus zinc (AREDS formula) had no overall effect on the need for cataract surgery.
Evidence strength: Moderate to weak for cataract endpoints specifically. The AREDS2 did not demonstrate a significant effect on cataract surgery rates from supplementation. Epidemiological data suggest a potential association between dietary lutein/zeaxanthin intake and lower cataract risk, but this has not been confirmed in large-scale RCTs with a cataract-specific primary endpoint.
5.3 Anxiolytic and Sedative Activity (Tagetes lucida)
Pharmacological studies on the use of T. lucida have indicated antioxidant, antibacterial, and anti-inflammatory properties, and in addition to influencing the activity of the CNS, this species is useful as an antinociceptive, antidepressant, anxiolytic, antipsychotic, and sedative.
Species from the Tagetes genus are reported as useful in infusion to treat stomachache and intestinal diseases, but also as tranquilizers. In one study, medicinal uses of T. erecta including its depressant effect on the central nervous system (CNS) were explored by interviewing healers and merchants of local markets of Morelos State, and by investigation of the phytochemical and pharmacological tranquilizing properties. Specific anxiolytic and/or sedative-like responses of different doses of T. erecta (10, 30, and 100 or 300 mg/kg, i.p.) were investigated using experimental models in mice such as the open-field, exploration cylinder, hole-board, and the barbituric-induced hypnosis potentiation tests.
Results demonstrated that lower doses of T. erecta significantly reduced immobility without altering locomotion; thus, it can be stated that the antidepressant effect of T. erecta was masked by a sedative effect at higher doses. This study showed that pretreatment with fluoxetine and imipramine enhanced the antidepressant action of T. erecta, whereas pretreatment with PCPA reversed its antidepressant effect in the forced swim test.
The ethanol extract and a mixture of phenolic compounds (quercetagetin 7-O-glucoside and 6,7-dimethoxy-coumarin) from T. lucida provoked an antinociceptive response in the neurogenic (central) and inflammatory (peripheral) phases of the formalin test.
Evidence strength: Preliminary. All evidence remains in the domain of preclinical animal studies and in vitro mechanistic work. Herbal therapies continue to have poor support in preclinical and clinical studies for anxiety disorders specifically. No controlled human clinical trials of T. lucida or T. erecta extracts for anxiety or depression have been published. This area requires human clinical investigation before any therapeutic claims can be substantiated.
5.4 Gastrointestinal Effects
Despite its use in gastrointestinal complaints in traditional medicine, the only scientific study that supports its effectiveness in the intestinal smooth muscle was made with the chloroform extract of T. lucida leaves. Authors reported that the chloroform extract reduced the contractile activity in the jejunum of rabbits. However, although the aqueous infusion is popularly consumed, there is no evidence on the effect of the aqueous extract of T. lucida on the gastrointestinal system, let alone on the mechanism of action involved.
For T. erecta, preclinical work investigated gastrointestinal anti-inflammatory effects: given the role of oxidative stress in ulcerative colitis (UC) etiology, and the amount of lutein (a carotenoid with antioxidant properties) in the dry hydroalcoholic extract of Tagetes erecta flowers (DHETE), this study investigated the intestinal anti-inflammatory properties of DHETE in an animal model of UC. In vivo, DHETE (300 mg/kg) attenuated weight loss, disease activity index, colon shortening, and histopathological changes promoted by DSS intake. Moreover, DHETE increased mucin colonic staining. In conclusion, DHETE reduced colitis severity by attenuating inflammatory cytokine secretion and improved the endogenous antioxidant defense in DSS-induced UC in mice.
Evidence strength: Very preliminary. All available evidence is from animal and in vitro studies. No human clinical trials have been conducted for gastrointestinal indications of Tagetes extracts specifically.
5.5 Antimicrobial Activity
These plants are studied in the field of agriculture for their fungicidal, bactericidal, and insecticidal activities. The antimicrobial activity of Tagetes is attributed primarily to its thiophenes and essential oil constituents.
Regarding antifungal activity, alpha-terthienyl (αT), a thiophene compound isolated from Tagetes patula (Asteraceae), exhibits antifungal activity towards five strains of dermatophytes (Trichophyton mentagrophytes, T. rubrum, T. violaceum, Epidermophyton floccosum, Microsporum cookei). αT plus UVA irradiation for 90 minutes acted as a fungistatic at concentrations between 6 μM and 24 μM. Between 1 and 10 days after irradiation, the fungal growth was reduced or arrested, with marked responses for T. mentagrophytes, T. rubrum, and M. cookei.
Tagetes species are known as a rich source of natural thiophenes, biologically active compounds whose activity, including antifungal activity, is enhanced by irradiation with UVA, suggesting that their extracts could be used in photodynamic therapy (PDT).
Evidence strength: Preliminary (in vitro and some in vivo models only). While the thiophene-based photodynamic antifungal mechanism is well-characterized at the biochemical level, no human clinical trials of Tagetes extracts for antimicrobial indications have been reported in the reviewed literature.
5.6 Anti-angiogenic and Anticancer Activity
In vitro work on T. minuta has identified a thiophene derivative with potential anti-angiogenic properties. Among plants screened, T. minuta showed an outstanding effect with an IC50 of 33.6 ± 3.4 μg/ml. Bio-guided isolation yielded the terthiophene α-terthienylmethanol as its active metabolite. Additionally, cytotoxic activity of T. lucida aqueous extracts and ethanolic extracts has been assessed against cell lines, though this work remains in the in vitro domain.
Evidence strength: Very preliminary. All data are from in vitro cell-based and in silico studies. No clinical evidence exists, and the relevance of these findings to human cancer therapy or prevention cannot be established at present.
5.7 Metabolic Effects (Antidiabetic and Anti-obesity)
The edible flowers of T. erecta have shown in vitro antioxidant, anti-inflammatory, and anti-aging properties. It has been shown for the first time the in vitro and in vivo, in a C. elegans model, antidiabetic and anti-obesity effect of T. erecta whole flower extracts.
Evidence strength: Very early/preclinical. Results rely on in vitro assays and the C. elegans invertebrate model. No human or mammalian clinical data exist for these indications.
6. Body Systems and Health Areas Associated with Tagetes
- Visual/ocular system: The predominant clinically validated application — macular pigment density, AMD risk reduction, potential role in cataract prevention. Lutein and zeaxanthin from T. erecta are the primary agents.
- Central nervous system: Anxiolytic, sedative, antidepressant, and antinociceptive activity investigated preclinically for T. lucida and T. erecta, via serotonergic (5-HT1A, 5-HT2A) and GABAergic pathways.
- Gastrointestinal system: Traditional use for stomachache, intestinal worms, and diarrhea; preclinical anti-inflammatory effects in colitis models.
- Integumentary system (skin/mucous membranes): Thiophene-based photodynamic antifungal and antimicrobial activity studied in dermatophyte models.
- Metabolic system: Preclinical evidence for antioxidant, anti-inflammatory, antidiabetic, and anti-obesity effects via polyphenol content.
- Vascular/oncological: In vitro anti-angiogenic activity of thiophene derivatives studied in cell-based models.
7. Dosage Forms and Reported Dosages
Dosages reported in peer-reviewed studies vary substantially by species, extract type, indication, and experimental system. The following figures are reported as stated in the cited sources and refer only to the forms and populations described therein.
7.1 Lutein/Zeaxanthin Supplementation (Human Clinical Trials)
- AREDS2 protocol: Participants were randomly assigned to daily placebo; lutein/zeaxanthin, 10 mg/2 mg; omega-3 long-chain polyunsaturated fatty acids, 1 g; or a combination. This is the most robustly studied human dose for AMD prevention and represents the formulation used in the key multicenter RCT.
- Meta-analysis dose range: Lutein supplementation at 10 or 20 mg per day was associated with an increase in MPOD, visual acuity, and contrast sensitivity across the nine trials included in that meta-analysis.
- Dietary model reference values: Dietary models include examples of how suggested effective levels of lutein/zeaxanthin can be achieved through diet alone, with values of 5 mg and 10 mg per day described.
7.2 Animal Study Dosages (Preclinical Models — Not Directly Applicable to Humans)
- Anxiolytic/sedative (T. erecta extract, mice, i.p.): Doses of 10, 30, and 100 or 300 mg/kg, i.p. were investigated using experimental models in mice.
- Anti-inflammatory/colitis (T. erecta dry hydroalcoholic extract, mice, oral): Doses of DHETE ranging from 30 to 300 mg/kg, once a day for 7 days.
7.3 Animal Feed (Regulatory Reference, EFSA)
The maximum proposed use level of 80 mg total carotenoids from saponified Tagetes extract/kg complete feed for chickens for fattening and laying hens is safe for these animal categories.
8. Safety Considerations and Interactions
8.1 General Regulatory Status
Carotenoids such as lutein and zeaxanthin are generally recognized as safe (GRAS) for human consumption, which allows food manufacturers to use them as additives. 21 CFR 73.295 designates Tagetes (Aztec marigold) meal and extract as a color additive exempt from certification under U.S. FDA regulations.
8.2 Contact Dermatitis and Allergic Sensitization
Tagetes minuta (Mexican marigold) can have an irritant effect on intact skin and can cause severe and prolonged allergic contact dermatitis, with cross-sensitization to other Compositae plants.
In particular, sesquiterpene lactones (SLs) may cause sensitization resulting in skin irritation and inflammation across the Asteraceae family. The Asteraceae-related allergy symptoms involve eczema, hay fever, asthma, or even anaphylaxis. Individuals with pre-existing sensitivity to other members of the Asteraceae/Compositae family (e.g., ragweed, chrysanthemums, chamomile) face potential cross-reactivity.
8.3 Beta-Carotene and Nutrient Competition
A notable pharmacokinetic interaction was identified in the AREDS2 trial: beta-carotene was shown to compete with lutein and zeaxanthin, as individuals who took all three nutrients had lower levels of circulating lutein and zeaxanthin when compared to participants who took lutein and zeaxanthin without beta-carotene. This competitive absorption at the intestinal level has relevance for the formulation of multi-carotenoid supplements.
8.4 Lung Cancer Risk (Beta-Carotene Context)
This safety signal relates to beta-carotene, not to lutein or zeaxanthin directly, but is relevant in the context of combined supplement use. AREDS2 participants who were former smokers who took a formulation with beta-carotene had a higher incidence of lung cancer. By contrast, lutein and zeaxanthin have not been associated with increased cancer risk.
8.5 Phototoxicity of Thiophenes
The thiophene compounds alpha-terthienyl and related structures present in Tagetes roots and leaves are photodynamically active. In the dark, αT caused no important ultrastructural modifications. After UVA irradiation, the photoactive compound caused damage to membranes of the nucleus, mitochondria, and endoplasmic reticulum. This phototoxic property, while exploited for agricultural and antimicrobial applications, represents a potential concern with topical application of Tagetes preparations containing high thiophene levels under conditions of UV exposure.
8.6 Occupational and Handling Considerations
The active substance (saponified Tagetes extract as a viscous paste) may be irritant to skin and eyes; no exposure by inhalation is expected. The EFSA FEEDAP panel also noted that in the absence of data, the panel cannot conclude on the safety for the user of commercial preparations.
8.7 Reproductive Toxicology
Traditional use records document that some Tagetes preparations were historically employed to promote abortion, a use reflected in ethnobotanical compilations. High-dose or concentrated extracts of several species have not been fully characterized for reproductive toxicology in rigorous mammalian studies, and this traditional indication implies a potential uterotonic effect that warrants caution.
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