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International Journal of Tryptophan Research : IJTR logoLink to International Journal of Tryptophan Research : IJTR
. 2022 May 26;15:11786469221102098. doi: 10.1177/11786469221102098

Tryptophan and Biogenic Amines in the Differentiation and Quality of Honey

Cristine Vanz Borges 1, Aline Nunes 2, Vladimir Eliodoro Costa 3, Ricardo de Oliveira Orsi 4, Leticia Silva Pereira Basilio 5, Gean Charles Monteiro 5, Marcelo Maraschin 2, Giuseppina Pace Pereira Lima 5,✉
PMCID: PMC9152190  PMID: 35656455

Abstract

Honey is a natural product with beneficial properties to health and has different characteristics depending on the region of production and collection, flowering, and climate. The presence of precursor amino acids of- and biogenic amines can be important in metabolomic studies of differentiation and quality of honey. We analyzed 65 honeys from 11 distinct regions of the State of Santa Catarina (Brazil) as to the profile of amino acids and biogenic amines by HPLC. The highest L-tryptophan (Trp), 5-hydroxytryptophan (5-OH-Trp), and tryptamine (Tryp) levels were detected in Cfb climate and harvested in 2019. Although we have found high content of serotonin, dopamine, and L-dopa in Cfb climate, the highest values occurred in honey produced during the summer 2018 and at altitudes above 900 m. Results indicate that the amino acids and biogenic amine levels in honeys are good indicators of origin. These data warrant further investigation on the honey as source of amino acids precursor of serotonin, melatonin, and dopamine, what can guide the choice of food as source of neurotransmitters.

Keywords: L-tryptophan, serotonin, melatonin, L-dopa, dopamine

Graphical Abstract.

Graphical Abstract

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Introduction

Honey is known for its antimicrobial, anti-inflammatory, anticancer, antiatherogenic, antithrombotic, and antioxidant effects, in addition to its analgesic activity in the human body. 1 Conscious consumption and the search for foods with good nutritional quality, aiming at the prevention of diseases, has been a priority in the human diet. In addition, there is also an interest in eating foods that provide well-being, both physical and emotional. 2 Phenolic compounds seem to be the most important constituents of honey, responsible for its antioxidant activity. 3 However, bioactive amines, as well as their precursor amino acids, have been the subject of many studies, due to the great interest regarding the nutritional paradox and their possible action as an antioxidant/well-being agent. These substances are also related to regulation of the cell cycle and play a fundamental role in the synthesis route of important neurotransmitters, 4 such as serotonin and dopamine.

Some studies report the presence of biogenic amines in samples of honey and other bee-derived products (ie, propolis), which have biological properties and can be used beneficially in the food and pharmaceutical industry. The presence of free amino acids in bee products can lead to the formation of biogenic amines (BA), which may be desirable or undesirable in food products, 5 making further research essential.

The ingestion of L-tryptophan (L-Trp) and 5-hydroxytryptophan (5-OH-Trp), for example, is essential for the formation of serotonin in the brain. Serotonin, a neurotransmitter, does not cross the blood–brain barrier 6 and the synthesis and turnover of this monoamine depend on the intake of amino acids. In humans, due to its essentiality, the recommended daily dose of L-Trp is around 4 mg/kg body weight per day for adults and 12 mg/kg body weight for children. 7 Thus, foods containing higher levels of L-Trp and 5-OH-Trp can help balance serotonin levels. It is noteworthy that honey is a source not only of L-Trp, but also of other metabolites derived from this amino acid and important to human health, such as nicotinamide (vitamin B6), melatonin, tryptamine, kynurenine, 3-hydroxykynurenine, and quinolinic and xanthurenic acids. 8 Furthermore, among other parameters, amino acid content has also been proposed as a method to determine the botanical and/or geographic provenance of food products, and honey has often been the target of this approach. 9

Honey and its derivatives have been increasingly valued natural substances; however, their physicochemical and biological properties are determined by many factors, including bee species, the nectar donor plant (specific for each season), geographic area/origin, seasonal conditions, harvesting and storage processes, and climatic conditions. 10 Therefore, it is important to expand the information on chemical composition and explore the biological activity of honeys from different geographic regions and methods of extraction, among other things. Due to its high complexity, the chemical analysis of honey poses a considerable challenge. Therefore, this study aimed to identify compounds from the biogenic amine class, as well as their precursor amino acids (ie, Trp and 5-OH-Trp) in honeys from different agro-ecological regions.

Methods

Honey collection places

Samples of honey (65) harvested in 2018 to 2019 were kindly provided by beekeepers from 11 agroecological regions of Santa Catarina State (Brazil), namely: (1) Planalto Serrano de São Joaquim, (2) coast, Itajaí, and Tijucas River Valleys, (3) coast of Florianópolis and Laguna, (4) Alto Vale do Itajaí, (5) Carboniferous, Extreme South, and Colonial Serrana, (6) Uruguai River Valley, (7) Alto Vale do Rio do Peixe and Alto Irani, (8) Central Plateau, (9) Northern Santa Catarina Plateau, (10) Santa Catarina Northwest, and (11) Campos de Lages (Table 1). All honey samples are polyfloral, because, in addition to presenting the predominant flowering described by beekeepers, they all contain pollen from native species of the regions of origin.

Table 1.

Location and predominant flowering of honey from Santa Catarina (flowering year/collection and season).

Sample Region City Altitude (m) Climate (Koppen-Geiger) Predominant flowering Year of collection Season
1A1 Coast, Itajaí, and Tijucas river valleys Benedito Novo 683 Humid subtropical climate (Cfa) Cinnamon and Piptocarpha angustifolia 2019 Summer
1A2 Itapoá 457 Wild flowers 2018 Spring
1A3 Itapoá Wild flowers 2019 Summer
1A4 Nova Trento 156 Wild flowers 2018 Spring
1A5 Nova Trento Eucalyptus 2019 Autumn
1B1 Jaguaruna 92 Eucalyptus 2019 Autumn
1B2 Coast of Florianópolis and Laguna Balneário Gaivota 9 Humid subtropical climate (Cfa) Wild flowers 2019 Spring
1B3 Jaguaruna 92 Wild flowers 2018 Autumn
1B4 Jaguaruna Eucalyptus 2019 Spring
1B5 Major Gercino 42 Wild flowers 2018 Autumn
1B6 Major Gercino Eucalyptus 2019 Autumn
2A1 Alto Vale do Itajaí José Boiteux 726 Humid subtropical climate (Cfa) Baccharis dracunculifolia 2018 Spring
2A2 José Boiteux 491 Dracena frangans and Holvenia dulcis 2018 Spring
2A3 José Boiteux 717 Eucalyptus 2019 Autumn
2A4 Salete 593 Holvenia dulcis 2018 Spring
2A5 Vidal Ramos 763 Baccharis dracunculifolia 2019 Summer
2A6 Vidal Ramos 493 Holvenia dulcis 2019 Summer
2A7 Vidal Ramos 761 Baccharis dracunculifolia 2019 Summer
2B1 Carboníferous, Extreme South, and Colonial Serrana Anitápolis 760 Humid subtropical climate (Cfa) Baccharis dracunculifolia, Piptocarpha angustifolia, trimera and Holvenia dulcis 2018 Spring
2B2 Anitápolis Eugenia sp., Holvenia dulcis, Clethra scabra, and Dracena fragans 2019 Summer
2B3 Orleans 600 Wild flowers 2018 Spring
2C1 Uruguai River Valley Descanso 272 Humid subtropical climate (Cfa) Holvenia dulcis 2018 Spring
2C2 Descanso Eucalyptus 2019 Autumn
2C3 Itapiranga 300 Eucalyptus 2019 Autumn
2C4 Itapiranga Holvenia dulcis 2019
2C5 Saudades 364 Holvenia dulcis 2018 Spring
2C6 Saudades Eucalyptus 2019 Autumn
3A1 Alto Vale do Rio do Peixe and Central Plateau Curitibanos 995 Humid temperate climate (Cfb) Wild flowers 2019 Summer
3A2 Curitibanos Wild flowers 2019 Summer
3A3 Erval Velho 699 Native fruit tree 2018 Spring
3A4 Erval Velho Holvenia dulcis 2018 Spring
3A5 Erval Velho Baccharis dracunculifolia and Holvenia dulcis 2019 Summer
3A6 Luzerna 725 Cinnamomum verum 2018 Spring
3A7 Luzerna Holvenia dulcis 2018 Spring
3A8 Luzerna Wild flowers 2019 Summer
3B2 Northern Santa Catarina Plateau Bela Vista do Toldo 793 Humid temperate climate (Cfb) Sebastiania commersoniana and Campomanesia xanthocarpa 2018 Spring
3B3 Três Barras 766 Sebastiania commersoniana 2018 Spring
3B5 Rio Negrinho 982 Wild flowers 2018 Spring
3B6 Rio Negrinho 982 Wild flowers 2019 Summer
3B7 Santa Terezinha 625 Holvenia dulcis 2018 Spring
3C1 Santa Catarina Northwest Campo Erê 894 Humid temperate climate (Cfb) Holvenia dulcis 2019 Summer
3C2 Campo Erê 650 Eucalyptus 2019 Autumn
3C3 Dionísio Cerqueira 856 Holvenia dulcis 2018 Spring
3C4 Dionísio Cerqueira Eucalyptus 2019 Autumn
3C5 Xaxim 598 Holvenia dulcis 2018 Spring
4A1 Lages Field Bocaina do Sul 980 Humid temperate climate (Cfb) Campomanesia xanthocarpa, Piptocarpha angustifolia, Eugenia sp., and Vochysia tucanorum 2018 Spring
4A2 Bocaina do Sul Clethra scabra 2019 Summer
4A3 Bom Retiro 522 Holvenia dulcis 2019 Summer
4A4 Bom Retiro 944 Clethra scabra 2019 Summer
4A5 Capão Alto 1007 Native plants 2018 Spring
4A6 Capão Alto Wild flowers 2019 Summer
4B1 Alto Vale do Rio do Peixe and Alto Irani Água Doce 1203 Humid temperate climate (Cfb) Piptocarpha tomentosa 2018 Spring
4B2 Água Doce 1203 Ocotea porosa 2018 Spring
4B3 Água Doce 1203 Baccharis trimera 2019 Summer
4B4 Lebon Régis 1280 Cinnamon, Piptocarpha angustifolia, Clethra scabra, Baccharis uncinella, and Cupania vernalis 2018 Spring
4B5 Lebon Régis 1280 Vernonia polysphaera and Baccharis trimera 2019 Autumn
4B6 Matos Costa 973 Astronium fraxinifolium, Lithrea brasiliensis, and Ilex theezans 2018 Spring
4B7 Matos Costa 1156 Clethra scabra 2019 Autumn
5(1) Planalto Serrano de São Joaquim Bom Jardim da Serra 1272 Humid temperate climate (Cfb) Piptocarpha angustifolia, Lithraea molleoides, Astronium fraxinifolium, Baccharis trimera, and Brosimum gaudichaudii 2018 Spring
5(2) Bom Jardim da Serra 1247 Senna bicapsularis, Struthanthus flexicaulis, and Baccharis trimera 2019 Autumn
5(3) São Joaquim 1276 Piptocarpha angustifolia, Lithrea brasiliiensis, Astronium fraxinifolium, and Baccharis trimera 2018 Spring
5(4) São Joaquim 1309 Eupatorium sp., Struthanthus flexicaulis, Baccharis trimera, and Strychnos pseudoquina 2019 Autumn
5(5) São Joaquim 1148 Piptocarpha angustifolia and Mimosa scabrella 2018 Spring
5(6) São Joaquim 1051 Senna bicapsularis 2019 Summer
5(7) São Joaquim 1055 Wild flowers 2019 Summer
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Extraction and chromatographic analysis

Biogenic amines (serotonin—Ser, melatonin—Mel, dopamine—Dop, and tryptamine—Tryp), L-Trp, 5-OH-Trp, and L-dopa were extracted as described by Lima et al. 11 Honey samples (1 g) were mixed with 3 mL of perchloric acid (5%, v/v), homogenized (vortex, 1 minute) and incubated in a cold ultrasonic bath (30 minutes), followed by centrifugation (10 minutes, 6000g, 5°C). The supernatant containing the free amines and amino acids was collected and subjected to derivatization using supernatant, 4.5 mol/L Na2CO3 and 18.5 mmol/L dansyl-chloride in acetone. The solution was kept at 60°C for 1 hour and, in sequence, proline (1 mg/mL) was added and the mixture kept in the dark for 1 hour and homogenized by vortexing every 15 minutes. After this interval, toluene (HPLC grade) was added, the mixture was vortexed (1 minute) and the supernatant (hydrophobic part containing the target compounds) was dried in a nitrogen line.

The samples were resuspended in acetonitrile (HPLC grade), homogenized by vortexing and incubated (1 minute) in an ultrasonic bath, followed by filtration (0.25 μm) and injection in a high-performance liquid chromatograph (HPLC; Dionex UltiMate 3000; Thermo Fisher Scientific, Bremen, Germany), according to Dadáková et al 12 with modifications. Briefly, 20 μL of sample was injected into an ACE C18 reverse phase column (4.6 × 250 mm; 5 µm), thermostatted at 25°C, coupled to a quaternary automatic sampler 3000 pump and diode array detector (DAD-3000RS). Amines and amino acids were eluted in a gradient system, as follows: 0 to 2 minutes, 40% A + 60% B; 2 to 4 minutes, 60% A + 40% B; 4 to 8 minutes, 65% A + 35% B; 8 to 12 minutes, 85% A + 15% B; 12 to 15 minutes, 95% A + 5% B; 15 to 21 minutes, 85% A + 15% B; 21 to 22 minutes, 75% A + 25% B; 22 to 25 minutes, 40% A + 60% B. Identification of biogenic amine and amino acids of interest (eg, L-Trp, 5-OH-Trp, Tryp, L-dopa, Ser, Mel, and Dop) was based on the retention times of analytical standards (Sigma-Aldrich, MO, USA), with detection at λ = 225 nm. For the purposes of compound quantification (µg/100 g), the peak areas were integrated using Chromeleon 7 software (Thermo Fisher Scientific, Bremen, Germany). The limit of detection (LOD), limit of quantification (LOQ), linear regression, regression coefficient (R2), recovery, and repeatability values (n = 6) observed are shown in Table 2. Repeatability (below 5%) was determined using 6 replicates/honey samples chosen at random. Mean recovery (%, n = 6) was tested with 5 concentrations (12.5, 50, 100, 150, and 200 mg/L) of analytical standard (Table 2).

Table 2.

LOD, LOQ, linear regression calibration curves, regression coefficient (R2), recovery, and repeatability of biogenic amines, by the analytical method in samples of honey.

Aminoacids/biogenic amines LOD a (mg/L) LOQ (mg/L) Regression equation R2 Recovery b values (%) Repeatability c
Tryptophan 0.019 0.104 y = 0.3614x + 0.1297 .99 96.5 3.3
5-OH-tryptophan 0.026 0.102 y = 0.2574x + 0.0561 .99 97.3 3.1
Tryptamine 0.049 0.106 y = 4.232x + 42.342 .99 94.8 4.1
Serotonin 0.013 0.085 y = 4.0423x + 19.911 .99 96.7 3.2
Melatonin 0.013 0.102 y = 1.3749x + 0.9985 .99 92.3 3.9
L-dopa 0.018 0.110 y = 205.1x − 0.012 .99 91.9 3.5
Dopamine 0.029 0.099 y = 3.822x + 71.767 .98 101.2 4.1
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a

Range for amino acids and biogenic amines 12.5 to 200 mg/L.

b

n = 6.

c

n = 6.

Statistical analysis

Data on biogenic amines and their precursors found in honey samples were submitted to analysis of variance (ANOVA), and if the data were significant, they were submitted to the Scott Knott test (P < .05). The ANOVA and the mean comparison test were performed using SISVAR statistical software. 13 Principal component analysis (PCA; XLSTAT software, version 2020; Addinsoft, France) was applied to visualize the possible correlation between amino acid content and the different classes of biogenic amines and the agroecological regions where the samples were collected.

Results and discussion

Currently, honey and its products have been valued as natural foods. However, it and its physicochemical and biological properties are affected by several factors of (a)biotic nature. The results clearly reveal that the composition of floral honeys produced in southern Brazil is dependent on several factors, including the geographical area of production, that is, the agroecological region of production and collection, as well as the nectar donor plants (specific for each season), as also verified in other similar studies. 10

In an attempt to establish a descriptive model for the grouping of precursor amines and amino acids according to the different agroecological regions of collection, as well as flowers from which nectar is collected, it was decided to compare the results obtained by PCA. Honeys from the coast of Florianópolis and Laguna (1B2) (Cfa climate, humid subtropical climate – harvested in spring 2019), from the Northern Plateau of Santa Catarina (3B2, harvested in spring 2018), and from the agroecological region of the Planalto Serrano de São Joaquim (Cfb climate – temperate oceanic climate) (5.5 and 5.7, harvested in summer 2018 and 2019) stood out for their L-Trp content (PC1+ and PC2+). Honeys from Cfa climate (Alto Vale do Itajaí—2A6 and Uruguai River Valley—2C3) harvested in 2019 (summer and autumn, respectively) are distinguished from the others by having the highest tryptamine content (35.01 and 35.43 µg/100 g, respectively). Both L-Trp and Tryp are precursors of Ser and their presence may be important for the control of some physiological disorders, such as obsessive-compulsive disorder. 14 Ser and Dop (r = .89, P < .05), as well as the amino acid L-dopa with these amines, showed a significant and strong correlation (Ser: r = .76 and Dop: .79, P < .05). Honey from the agroecological regions Alto Vale do Rio do Peixe and Alto Irani (4B6), harvested in Spring 2018, showed the highest levels of these amines (Ser: 495.15 µg/100 g; Dop: 33.98 µg/100 g) and the amino acid L-dopa (0.72 µg/100 g) (PC1+ and PC2−) (Figures 1 and 2B; Table 3).

Figure 1.

Figure 1.

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Two-dimensional projection and scores of profile of precursor amino acids and biogenic amines of floral honeys from the agroecological regions of the State of Santa Catarina. Honey samples are represented by blue points (see Table 1) and amino acids and biogenic amines by red points.

Abbreviations: 5-OH-TRP, 5-hydroxy-tryptophan; L-DOPA, DOP, dopamine; L-TRP, L-tryptophan; MEL, melatonin; SER, serotonin; TRYP, tryptamine.

Figure 2.

Figure 2.

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Two-dimensional projection and scores of profile of precursor amino acids and biogenic amines of floral honeys from the agroecological regions of the State of Santa Catarina analyzed as to the time of harvest (A) and season (B). Honey samples are represented by blue points (see Table 1) and amino acids and biogenic amines by red points.

Abbreviations: 5-OH-TRP, 5-hydroxy-tryptophan; L-DOPA, DOP, dopamine; L-TRP, L-tryptophan; MEL, melatonin; SER, serotonin; TRYP, tryptamine.

Table 3.

Precursor amino acids and biogenic amines (µg/100 g) of floral honeys from the agroecological regions of the State of Santa Catarina (harvest 2018 and 2019).

Honey L-Trp 1 5-OH-Trp 2 Tryp 3 Ser 4 Mel 5 L-DOPA 6 Dop 7
1A1 749.08 ± 33.86p 1314.04 ± 1.36d 15.58 ± 2.47g 21.27 ± 1.93l 25.64 ± 3.23h 0.07 ± 0.04h 12.79 ± 0.60b
1A2 930.66 ± 7.18o nd 22.47 ± 0.20d 55.63 ± 0.79c nd 0.02 ± 0.00j 1.68 ± 0.22j
1A3 875.64 ± 0.45o nd 12.36 ± 0.14h 20.68 ± 0.51l nd nd 2.62 ± 0.17i
1A4 970.84 ± 9.24o nd 17.21 ± 0.19f 24.11 ± 0.52k 11.99 ± 0.74k 0.03 ± 0.00j 2.32 ± 0.09i
1A5 1612.14 ± 46.25j 989.14 ± 67.77g 15.26 ± 1.29g 26.32 ± 1.75i 24.54 ± 5.72i 0.05 ± 0.00h 3.93 ± 0.02g
1B1 1408.79 ± 19.32k 708.82 ± 3.43j 12.60 ± 0.18h 23.80 ± 0.14k nd 0.02 ± 0.00j 1.48 ± 0.05j
1B2 3358.65 ± 13.70a 764.09 ± 0.06i 18.24 ± 1.93f 29.10 ± 0.25h nd 0.04 ± 0.00i 1.66 ± 0.07j
1B3 387.66 ± 23.42r 1188.36 ± 53.31e 10.63 ± 0.18i 10.21 ± 0.16r 36.16 ± 8.71g 0.02 ± 0.00j 4.08 ± 0.14g
1B4 1113.56 ± 36.04n 864.93 ± 78.17h 13.83 ± 1.94h 18.83 ± 0.73m 93.26 ± 12.95a 0.09 ± 0.04g 3.86 ± 1.03g
1B5 1150.29 ± 19.44n 36.76 ± 0.86t 8.25 ± 0.07j 15.26 ± 0.23o 20.85 ± 3.97i 0.02 ± 0.01j 2.99 ± 0.21h
1B6 1224.87 ± 13.32m 749.16 ± 14.09i 10.88 ± 2.20i 12.01 ± 0.02q nd 0.01 ± 0.00j 1.96 ± 0.18j
2A1 1226.04 ± 11.92m 112.67 ± 0.06s 11.44 ± 0.00i 13.16 ± 0.21p nd 0.05 ± 0.00h 1.55 ± 0.00j
2A2 1316.26 ± 142.72l 79.55 ± 30.53s 18.00 ± 0.12f 2.75 ± 0.10v nd 0.09 ± 0.00g 1.12 ± 0.01k
2A3 1081.90 ± 86.28n 1210.13 ± 90.22e 22.51 ± 0.39d 17.73 ± 0.06n 34.23 ± 1.30g 0.03 ± 0.02i 1.10 ± 0.13k
2A4 263.31 ± 21.91s 22.99 ± 0.44t 6.24 ± 0.07k 7.62 ± 0.21s nd nd Nd
2A5 1032.62 ± 14.80o 90.07 ± 32.13s 21.26 ± 0.22d 6.76 ± 0.12t nd 0.02 ± 0.00j 1.60 ± 0.17j
2A6 1083.81 ± 35.33n 494.50 ± 102.30m 35.01 ± 0.92a 4.74 ± 0.07u 30.19 ± 4.83h 0.03 ± 0.00j 1.01 ± 0.08k
2A7 944.98 ± 21.23o 34.40 ± 0.82t 11.90 ± 0.06i 13.50 ± 0.05p 19.17 ± 0.63i 0.02 ± 0.00j 1.73 ± 0.09j
2B1 1504.82 ± 4.88k 98.67 ± 13.70s 23.57 ± 0.20c 7.80 ± 0.40s nd 0.07 ± 0.00h 1.03 ± 0.01k
2B2 576.57 ± 6.24q 48.96 ± 5.73t 20.51 ± 0.10e 2.22 ± 0.15v nd 0.03 ± 0.01j 0.63 ± 0.07k
2B3 627.68 ± 7.54q 57.28 ± 11.45t 14.58 ± 0.02g 26.92 ± 0.75i 21.19 ± 2.64i 0.01 ± 0.00k 1.90 ± 0.18j
2C1 602.91 ± 6.76q 337.50 ± 81.44o 16.95 ± 0.94f 12.58 ± 0.79p 16.33 ± 1.14j nd 0.84 ± 0.06k
2C2 1191.99 ± 28.47m 141.90 ± 27.21r 14.47 ± 2.67g 8.02 ± 0.07s 12.21 ± 2.42k 0.01 ± 0.00j 1.75 ± 0.06j
2C3 836.37 ± 11.59p 182.38 ± 80.60r 35.43 ± 0.81a 7.16 ± 0.57t nd 0.10 ± 0.03g 1.32 ± 0.13j
2C4 377.62 ± 5.99r 111.11 ± 3.78s 12.35 ± 0.15h 5.43 ± 0.07u 14.15 ± 1.56k nd 0.71 ± 0.22k
2C5 743.89 ± 32.08p 138.26 ± 3.26r 26.97 ± 0.41b 5.94 ± 1.48t 17.43 ± 0.67j nd 1.13 ± 0.02k
2C6 1764.97 ± 20.53i 1156.40 ± 2.59f 17.62 ± 1.83f 8.24 ± 0.30s 20.01 ± 0.72i 0.01 ± 0.00j 1.44 ± 0.30j
3A1 1666.18 ± 15.98j 343.50 ± 23.86o 11.77 ± 0.15i 15.27 ± 0.99o 17.87 ± 1.27j 0.02 ± 0.01j 0.90 ± 0.02k
3A2 967.73 ± 12.19o 423.85 ± 14.23n 15.39 ± 0.87g 10.84 ± 0.36r nd 0.06 ± 0.00h 1.23 ± 0.02j
3A3 1515.81 ± 16.03k 624.56 ± 21.23k 24.17 ± 1.99c 7.10 ± 0.61t nd 0.07 ± 0.00h 0.86 ± 0.02k
3A4 1096.43 ± 47.62n 173.39 ± 5.96r 13.59 ± 0.33h 8.09 ± 0.05s nd 0.07 ± 0.00h 3.20 ± 0.04h
3A5 1207.37 ± 14.26m 664.09 ± 4.33j 15.31 ± 0.05g 8.80 ± 0.04r nd 0.08 ± 0.00g 2.34 ± 0.12i
3A6 1381.80 ± 1.09k 156.42 ± 9.71r 17.69 ± 0.96f 11.28 ± 0.03r 27.75 ± 2.76h 0.02 ± 0.00j 1.24 ± 0.01j
3A7 1440.32 ± 17.23k 255.07 ± 16.63q 18.28 ± 0.01f 17.31 ± 0.20n 37.79 ± 0.35f 0.02 ± 0.00j 1.48 ± 0.10j
3A8 1466.00 ± 4.52k 973.13 ± 34.25g 18.31 ± 0.47f 12.98 ± 0.47p nd 0.05 ± 0.02h 4.86 ± 1.04f
3B2 3158.17 ± 32.94b 352.68 ± 9.56o 21.29 ± 0.26d 37.01 ± 0.09e nd 0.05 ± 0.00h 1.54 ± 0.19j
3B3 928.68 ± 1.88o 173.53 ± 9.38r 10.30 ± 0.01i 13.74 ± 0.01p 14.93 ± 2.44k 0.02 ± 0.00j 0.69 ± 0.04k
3B5 1729.82 ± 16.02i 777.89 ± 2.44i 20.38 ± 0.02e 13.97 ± 0.18p nd 0.06 ± 0.01h 9.84 ± 0.06c
3B6 1228.09 ± 12.22m 221.52 ± 15.86q 16.89 ± 0.15f 8.82 ± 0.01r nd 0.02 ± 0.00j 2.92 ± 0.03h
3B7 1075.95 ± 14.30n 287.19 ± 2.56p 17.75 ± 0.16f 9.61 ± 0.50r nd 0.02 ± 0.00j 1.10 ± 0.04k
3C1 934.12 ± 3.76o 567.29 ± 13.81l 21.67 ± 0.81d 4.97 ± 0.00u nd 0.01 ± 0.00k 0.93 ± 0.00k
3C2 1309.26 ± 25.95l 1547.30 ± 55.99c 17.76 ± 0.99f 21.38 ± 0.13l nd 0.02 ± 0.00j 2.39 ± 0.07i
3C3 1378.81 ± 13.15k 87.45 ± 9.45s 16.50 ± 2.51g 51.52 ± 1.57d 58.63 ± 0.31d 0.53 ± 0.01b 8.49 ± 1.48d
3C4 637.20 ± 8.88q 161.84 ± 3.21r 11.99 ± 5.05i 12.98 ± 0.35p 17.60 ± 0.45j 0.01 ± 0.00k 2.51 ± 0.17i
3C5 954.75 ± 2.01o 108.54 ± 0.48s 16.13 ± 1.05g 14.92 ± 0.41o 41.77 ± 0.88e nd 2.36 ± 0.62i
4A1 2250.72 ± 2.55f 119.28 ± 0.34s 15.59 ± 0.63g 31.31 ± 1.24g nd 0.04 ± 0.01i 3.33 ± 0.37h
4A2 944.05 ± 2.95o 109.71 ± 1.51s 27.22 ± 1.02b 11.40 ± 0.52r nd 0.32 ± 0.00c 4.68 ± 0.07f
4A3 1451.82 ± 59.95k 155.58 ± 33.77r 14.61 ± 0.47g 10.56 ± 2.09r 44.49 ± 6.87e 0.06 ± 0.00h 3.96 ± 0.07g
4A4 1452.47 ± 51.42k 76.18 ± 7.58s 12.37 ± 0.78h 24.81 ± 0.74j nd 0.03 ± 0.00i 1.54 ± 0.06j
4A5 826.83 ± 0.73p 71.95 ± 5.36s 10.85 ± 0.54i 24.71 ± 0.25j nd 0.01 ± 0.00k 1.23 ± 0.01j
4A6 1291.53 ± 36.42l 287.23 ± 11.21p 17.77 ± 0.40f 37.70 ± 0.44e nd 0.03 ± 0.00j 2.40 ± 0.12i
4B1 1455.32 ± 30.95k 98.47 ± 10.14s 17.07 ± 0.33f 33.04 ± 0.24f 22.05 ± 1.30i 0.00 ± 0.00k 0.00 ± 0.00l
4B2 2412.74 ± 59.28e 153.78 ± 2.29r 20.26 ± 0.41e 26.98 ± 0.54i nd 0.09 ± 0.01g 2.48 ± 1.61i
4B3 2141.29 ± 10.93g 2045.59 ± 72.26a 18.65 ± 0.50f 12.05 ± 0.05q 45.15 ± 0.23e 0.09 ± 0.00g Nd
4B4 1951.09 ± 17.79h 115.81 ± 7.38s 22.13 ± 1.20d 20.83 ± 1.09l nd 0.05 ± 0.01h 0.68 ± 0.02k
4B5 837.81 ± 9.78p 76.73 ± 2.56s 16.03 ± 0.34g 11.82 ± 1.30r nd 0.09 ± 0.02g 0.69 ± 0.36k
4B6 884.27 ± 25.97o 99.36 ± 29.06s 17.41 ± 0.86f 495.15 ± 0.14a nd 0.72 ± 0.00a 33.98 ± 0.20a
4B7 786.62 ± 8.64p 71.21 ± 1.31s 13.62 ± 0.25h 33.38 ± 0.44f nd 0.03 ± 0.00j 1.74 ± 0.07j
5.1 626.98 ± 7.19q 1714.61 ± 28.85b 14.83 ± 1.48g 33.11 ± 0.54f 30.03 ± 1.32h 0.05 ± 0.00h 2.69 ± 0.03i
5.2 662.25 ± 7.29q 1700.99 ± 10.37b 15.95 ± 0.02g 23.05 ± 0.24k 32.83 ± 0.22g 0.05 ± 0.00h 2.97 ± 0.10h
5.3 1122.22 ± 46.81n 80.16 ± 6.03s 19.63 ± 2.77e 34.02 ± 3.20f 88.08 ± 2.31b 0.02 ± 0.00j 4.02 ± 0.99g
5.4 2024.21 ± 31.36h 70.86 ± 0.20s 15.89 ± 0.20g 16.87 ± 1.19n 35.24 ± 3.00g 0.02 ± 0.01j 1.85 ± 0.01j
5.5 2569.65 ± 92.00d 87.26 ± 5.95s 25.13 ± 0.13c 64.13 ± 0.05b 44.29 ± 2.48e 0.16 ± 0.03e 5.02 ± 0.02f
5.6 750.03 ± 28.87p 115.33 ± 15.91s 16.01 ± 0.32g 25.57 ± 1.65j 66.25 ± 3.76c 0.02 ± 0.00j 3.67 ± 0.65g
5.7 2827.54 ± 41.19c 81.84 ± 15.31s 18.65 ± 0.09f 27.92 ± 0.08h 35.53 ± 7.00g 0.13 ± 0.03f 4.19 ± 0.93g
Minimum 263.31 nd 6.24 2.22 nd nd Nd
Maximum 3358.65 2045.59 35.43 495.15 93.26 0.72 33.98
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Results are given as means ± standard deviation. Means followed by the same letter in the column do not differ statistically from each other by Scott-Knott test (P ⩽ .05).

1 L-tryptophan.

2 5-Hydroxy-tryptophan.

3 Tryptamine.

4 Serotonin.

5 Melatonin.

6 L-DOPA.

7 Dopamine.

L-Trp levels ranged from 263.31 µg/100 g (2A4, Spring 2018) to 3358.65 µg/100 g (1B2, Spring 2019) (Figure 2A; Table 3). This difference is attributed to the plant species visited by the bees during nectar collection, as well as the honeys’ geographic origin and the time/season of harvest. Other studies highlight L-Trp values greater than 14 mg/kg in rosemary honeys, 15 while levels reached 1.9 mg/100 g in sunflower honeys 16 and 1.10 mg/100 g in lavender honey. 17 Among the samples analyzed, the lowest L-Trp content was found in honey whose main flowering was Hovenia dulcis (Japanese grape) (2A4), from the Atlantic Forest region, with a Köppen climate classification of Cfa and harvested in Spring 2018 and grouped in PC1− and PC2− (Figure 1). It is worth mentioning that, at the same time of harvest, Mel was not detected. These results also demonstrate that the year of harvest and season affects the levels of biogenic amines (Figure 2A and B). On the other hand, the honey with the highest L-Trp content (3358.65 µg/100 g) was produced in the coastal region of Santa Catarina, whose predominant bloom was composed of wild flowers (polyfloral honey) and harvested in spring 2019 (Table 1; Figure 2A and B). Some articles describe that L-Trp content varies depending on the predominant flora. Hermosín et al 17 detected L-Trp values of between 0.19 and 1.10 mg/100 g and the variation was dependent on the predominant flowering, that is, the lowest content was found in orange blossom honeys and the highest in lavender honeys. The authors claim that amino acid composition does not exactly distinguish the botanical origin of honeys, or their authenticity. In our study, the L-Trp content of most samples is very close to that found in the literature and sample harvested in spring showed the highest level of this amino acid; however, it is worth noting that the botanical origin, as well as the climate, region, and season, can affect the level of metabolites, including amino acids. The levels of metabolites formed from tryptophan are not correlated with the results of L-Trp content.

L-Trp found in honeys may come from plants (pollen, nectar, and resins) or from the metabolism of bees during honey production. In pollen, the contents of this aromatic amino acid are quite variable and may be very low, that is, 0.028 g/kg to 0.197 g/g18,19 or much higher, such as described in Rhododendron ponticum pollen (8053.00 µg/g). 20

L-Trp in honey has been the subject of several studies related to human health. For example, L-Trp supplementation appears to improve the social behavior of people suffering from disorders due to malfunctioning of the serotonergic system.21,22 Intake of L-Trp has been linked to decreased levels of psychosis in both animal and human studies and sleep deprivation. 22 Other studies have demonstrated that ingestion of honey with milk before bedtime may decrease hypoglycemic effects in diabetic patients, 23 or improve the sleep quality of healthy people or those with coronary heart problems. 24 Thus, L-Trp supplementation appears to improve control over social behavior in individuals who suffer from disorders or behaviors associated with dysfunctions in serotonergic functioning.

L-Trp is transported into the brain via the leucine-preferring L1 system and may compete with other amino acids (eg, tyrosine, phenylalanine, leucine, isoleucine, and valine) called “large neutral amino acids” (LNAA). 2 The L-Trp : :p : LNAA ratio determines the flux of this amino acid and, consequently, the biosynthesiSer in the brain. 25 Foods with a high content of L-Trp, such as honey, often also contain other amino acids in varying concentrations. Thus, the net effect of the L-Trp content in honeys is relevant, but it should be considered carefully with regard to possible increases in Ser synthesis, given the competition for a transporter system in the blood–brain barrier between this amino acid and the other LNAA. 2 Furthermore, excess L-Trp may cause adverse reactions, such as gastric problems and dizziness, among others. 21

The remainder of the L-Trp that is not used for protein synthesis may be converted to biomolecules such as kynurenine (KYN) (responsible for approximately 90% of L-Trp catabolism 26 ) or those related to neuroimmunological signaling, such as Ser and Mel. About 1% of dietary L-Trp is used for Ser synthesis,26,27 by the conversion of L-Trp to 5-OH-Trp or Tryp, depending on the metabolic pathway. KYN, derived from L-Trp catabolism, originates niacin, precursor of the coenzyme nicotinamide adenine dinucleotide (NAD+). 27 In this pathway, 60 mg of Trp produces 1 mg of nicotinic acid or niacin. 28 The usual intake of Trp is approximately 900 to 1000 mg per day, 26 and the recommended daily dose is around 4 mg/kg body weight per day for adults and 12 mg/kg body weight for children. 7 According to our results, the consumption of honey as a source of L-Trp may help in several metabolic processes, including psychiatric and neurological disorders and anticancer immunity. 27 In children and adolescents with autism spectrum disorder, the intake of L-Trp may decrease symptoms of irritability and mild depression due to increased Ser levels. 29

Although there is no consensus on the necessary amount of 5-OH-Trp or Tryp (Ser precursors) to be ingested daily, considerable levels were detected in some honeys as 5-OH-Trp (4B3-2045.59 µg/100 g) and Tryp (2A6-35.01 µg/100 g and 2C3-35.43 µg/100 g) (Table 3). Foods with higher levels of 5-OH-Trp and Tryp may favor the formation of Ser and Mel, due to the ease in crossing the brain–blood barrier (BBB), 27 since both the synthesis and the turnover of Ser depend on the intake of L-Trp and 5-OH-Trp. 30 In this study, we highlighted the maximum content of 5-OH-Trp (2045.59 µg/100 g) in the sample from Baccharis dracunculifolia DC (4B3), originating from an altitude of approximately 900 m. The same compound was detected at a lower level (22.99 µg/100 g) in 2A4, from a lower altitude (Alto Vale do Itajaí), that is, 593 m, which also showed a lower content of L-Trp (263.31 µg/100 g) and Tryp (6.24 µg/100 g) and no melatonin, L-dopa and dopamine (Table 3). Tryp has been used as a fermentation marker, along with other amines such as tyramine, cadaverine, putrescine, and histamine. This aromatic and heterocyclic biogenic amine can induce vasoactive or psychoactive effects on the human body. 31 According to the authors, the consumption of 25 to 30 mg/kg of Tryp can cause migraines; however, to reach these values, it would be necessary to consume approximately 900 g of honey from the samples that contain the highest levels.

Ser cannot cross the BBB and its intake contributes to a decrease in reactive oxygen species, as described in red blood cells of a mouse model, 32 mainly in the process of lipid peroxidation. 14 In the present study, Ser, Dop, and the amino acid L-dopa were all detected at higher levels in honeys from the mild Cfb climate. In the present study, Ser was detected in greater amounts (495.15 µg/100 g) in 4B6, a honey from an altitude of 1280 m, produced in spring 2018 and Cfb climate (Table 3). In this region, “aroeira” (Schinus sp.), “aroeira branca” (Lithraea molleoides), and “caúna” (Ilex theezans Mart. ex Reissek) are predominant (Table 1). The non-detection of Mel stands out in this sample. The lack of conversion of Ser into Mel could eventually contribute to an increase of Ser in the investigated honey samples. However, this was not observed in samples that did not show detectable levels of Mel. A low Ser content was verified in honeys from 2A2 and 2B2, both from a Cfa climate and from the Atlantic Forest ecosystem, but from different flowerings, regions, and altitudes (Table 3).

Higher levels of Mel, unlike Ser and Dop, were detected in honeys from coastal regions (agroecological regions coast of Florianópolis and Laguna, 1B4-93.26 µg/100 g) with a Cfa climate, low altitude (92 m), predominantly flowering of Eucalyptus and harvest in Spring 2019. Mel, Ser, and Dop were grouped in PC1− (Figure 2A) according to the year of harvest and in PC1+ in relation to the season (Figure 2B). In these figures and in Table 3 it is possible to verify that the levels of Mel varied between seasons, year, flowering, and climate and it is not possible to use this compound as a biochemical marker of honey quality. Mel, unlike Ser, crosses the BBB, in addition to having high antioxidant potential and not being able to be stored in the pineal gland, being released into the bloodstream and rapidly degraded in the liver. 33 Mel is an essential molecule related to the circadian rhythm; it has immunomodulatory and neuroprotective actions in tumor suppression, in addition to being related to oxidative stress. 34 Several studies were carried out during the Covid-19 pandemic using Mel and it has been recommended that the use of this substance may be related to a decrease in side effects due to its anti-inflammatory and antioxidant action.35,36 Thus, honeys with higher levels of Mel could be an interesting source of this amine, given its already demonstrated pharmacological effects.

In the studied honeys, the presence of L-dopa and Dop was also evidenced, the levels reaching 0.72 and 33.98 µg/100 g (4B6), respectively (Table 3), in honey from Vale do Rio do Peixe and Alto Irani with an altitude 973 m, Cfb climate and flowering of “aroeira” (Schinus sp.), “aroeira branca” (L. molleoides), and caúna (I. theezans Mart. ex Reissek) (Table 1). It is important to mention that the highest Ser content was also detected in these samples.

L-dopa levels in honeys are poorly described in the literature, which makes the data found in this work interesting. L-dopa occurs in plants as it is a precursor of several alkaloids, catecholamines, and melanin. 37 In honeys from Turkey, whose predominant flowering was fava beans (Vicia fava), Topal et al 39 reported an L-dopa content of 0.0321 mg/10 g, much higher than those found in honeys from Santa Catarina, Brazil. The L-dopa content may be due to the botanical source, as its presence at considerable levels in several plant species has already been described, including in fava bean genotypes, in flowers, leaves, and fruits. In humans, L-dopa has been used in the treatment of Parkinson’s disease, characterized by a deficiency in the synthesis of this catecholamine and as Dop cannot cross the BBB, while L-dopa does and is decarboxylated to form Dop in nerve cells. 39 In addition to acting as a neutrotransmitter, Dop may act as an immunomodulatory regulator, besides being indispensable for neuroimmune communication, i.e., its relationship with alterations in the functions of macrophages, lymphocytes, neutrophils and monocytes, showing that immune cells, in homeostatic and pathological conditions, interact with Dop centrally and peripherally. 40 Some studies have shown a relationship between Dop levels and Dop receptors and diseases such as glaucoma, diabetes and cardiovascular disease. 41 The analyzed honeys have been demonstrated to be a source of both substances and may be beneficial as adjuvants in therapies aimed at increasing the content of L-dopa and Dop.

Conclusion

The amino acid and biogenic amine content of floral honeys vary depending on several factors, including the agroecological region of production and collection, as well as the nectar donor plants and season. Ser and Dop, as well as the amino acid L-dopa, showed a significant and strong correlation and were detected in higher levels in honey from agroecological regions with a milder climate (Cfb), at higher altitudes and in Spring 2018. A higher content of 5-OH-Trp was also found in samples from a milder climate, harvest in 2019. On the other hand, L-Trp and Tryp, as well as Mel, were found at higher levels in honeys harvested in 2019 during the hottest seasons and in Cfa climate.

Footnotes

Funding: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the São Paulo Research Foundation (FAPESP) (grants 2016/22665-2 and 2019/27227-1); the Foundation for Research Support of Santa Catarina (2020TR1452); and the National Council for Scientific and Technological Development (CNPq) (grants 307571/2019-0, 304657/2019-0, and 304657/2019-0).

Declaration Of Conflicting Interests: The author declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Author Contributions: CVB: Formal analyses, statistical analysis, writing (draft preparation and review and editing). AN: Methodology and data curation, writing (data preparation). VEC: Methodology. ROO: Methodology and data curation. LSPB: Methodology, data curation and statistical analysis. GCM: Methodology and data curation. MM: Conceptualization, formal analysis, supervision, and project administration, writing (original draft preparation and review and editing), and funding acquisition. GPPL: Conceptualization, formal analysis, supervision and project administration, writing (original draft preparation and review and editing), and funding acquisition.

ORCID iDs: Vladimir Eliodoro Costa Inline graphic https://orcid.org/0000-0003-3889-7514

Gean Charles Monteiro Inline graphic https://orcid.org/0000-0001-6072-8018

Giuseppina Pace Pereira Lima Inline graphic https://orcid.org/0000-0002-1792-2605

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