WO2015011321A1 - Food composition for honey bees and method for controlling infections in bees using said food - Google Patents

Abstract

The invention relates to a sweetened food composition for honey bees, the formulation of which contains at least one food-quality phytoalexin, preferably trans-resveratrol, in a quantity of between 0.1 and 2.8 wt.-%, inclusive, of the total weight of the composition. The composition can take the form of, and be administered as, a liquid food in sweetened solution (syrup) or a semi-solid food in the form of sweetened paste with a low moisture content of less than 50% (candy). In addition, the invention relates to a method for controlling infections in colonies of honey bees, particularly Nosema apis and Nosema ceranae, (Nosemosis A and C), comprising supplying beehives with at least one dose of the food composition. The method can be used to treat a beehive using programmed applications of the food, guaranteeing effective levels for at least five weeks, without producing aversive effects in the bee colony.

Description

 DESCRIPTION

 FOOD COMPOSITION OF HONEY BEES AND PROCEDURE FOR CONTROLLING INFECTIONS IN SUCH BEES THROUGH SAID FOOD Technical Field of the Invention

 The invention is part of the technical sector of Agriculture, more specifically in the area of Beekeeping (bee breeding) and Veterinary (treatment of diseases in hives), although it is also related to the Food and Consumer Products sector from bee breeding.

Object of the invention

 The present invention relates to a food composition for honey bee colonies containing food grade phytoalexins, mainly resveratrol (and especially trans-resveratrol), compounds that are capable of promoting normal colony development, and especially combating nosemosis (A and C). Likewise, the invention is related to a method to combat infections of the colonies of said honey bees by programmed feeding of the bee colonies with said food composition containing phytoalexins. Background of the invention

Colonies of honey bees are susceptible to infections and infestations by agents such as viruses, mites, lepidoptera, fungi, bacteria, etc., which affect the health of bees and consequently decrease the productivity of beekeeping farms and pollinating actions of these insects, collaterally causing serious economic and environmental damage. One of the main infestations suffered in the last decade by bees worldwide is attributed to the action of microsporide Nosema ceranae, considered one of the key factors of the recent phenomenon of massive collapse of bee colonies. Indeed, Nosema ceranae is currently the most prevalent bees pathogen in Spain (Reviewed by Higes M., Meana A., Bartolomé C, Botías C, Martín-Hernández R. Nosema ceranae (Microsporidia), a controversial 21 st century honey bee pathogen Environmental Microbiology Reports 2013, 5 (1), 17-29) even surpassing the prevalence of the destructive Varroa (Garrido-Bailón, Doctoral Thesis, 2012) which suggests the sanitary importance it presents. In addition, this same situation has been detected in different European countries (Austria, France, Holland, Switzerland, Slovenia, Poland, Italy, Greece, Portugal, Germany, etc.) and the American continent (States United, Argentina, Chile, Uruguay). In all these areas, the central role of Nosema ceranae in what is known as Hives Depopulation Syndrome (SDC) or Colony Collapse Disorder (CCD) (Higes et al., 2008 Environmental Microbiology, Higes) et al, 2009 Environmental Microbiology Reports), hence the need to improve control strategies. We are undoubtedly faced with the main health problem of world beekeeping in the 21st century. The results of research carried out by the inventors also allow us to rule out as a priority factor agricultural pesticides, mainly neonicotinoids, as responsible for the widespread problem of depopulation of hives.

As indicated above, in recent years there has been a high mortality of bees in different beekeeping areas both in Spain and in neighboring countries with similar productive characteristics (Faucon et al., 2002; Chauzat et al., 2004; Marinelli et al., 2004; Higes et al., 2005; Stoktad, 2007; Plischuck et al., 2009) or in other geographical areas (Finley et al., 1996; Mangum 1999). In all cases, high mortalities of bee colonies were reported, especially during autumn and winter, although during 2005 they were also detected throughout the year.

One of the main problems raised by this finding is the fact that fumagillin, the current available treatment of choice for nosemosis caused by N. apis (Katznelson and Jamieson, 1952; Hartwig and Przelecka, 1971; Higes et al. , 2004), although it is effective after its application (Higes et al., 2008, 2009) is currently not authorized in beekeeping in most countries of the European Union, so it is essential to develop new molecules that successfully supplant the absence of fumagiline. Therefore, the search for effective compounds against N. ceranae should also be a priority objective taking into account the current situation.

On the other hand, and given that many antifungals are of limited clinical use since they frequently lead to various toxicities in patients, such as hemolytic effect against human erythrocytes, another option appears oriented towards the use of some natural products, which do not seem to have that drastic effect One of those currently considered is resveratrol, which among other properties shows a potential appeal as an antifungal in humans, although the actual mechanism of its action is still unknown (Jung, 2005). In this regard, Maistrello et al. (2008) and more recently Costa et al. (2010) demonstrated, in tests performed only in the laboratory and without contrasting these results with in situ tests, that the analytical standard resveratrol (not suitable for human consumption) added to food increased the longevity of bees and was effective in inhibiting the development of Nosema ceranae in infected bees. However, these data have not yet been correlated with field studies or with conventional hive feeding. This substance has also been successfully tested against other microsporidia of humans and mammals (Leiro et al., 2004; Jung et al., 2005; Didier et al., 2006). Resveratrol has been detected as the main bioactive component in plant extracts used since past centuries in traditional medicine for human diseases, in fact it has been shown to be as potent as amphotericin B against S. cerevisae. Recent studies have shown that it can inhibit the development of microsporide Encephalitazoon cunicoli in in vitro experiments (Leiro, 2004).

Trans-resveratrol is a phytoalexin produced by angiosperms in response to microbial infections, damage, UV radiation, cold, heat, attack of microorganisms, abiotic stress, etc. The trans (t-r) form of resveratrol appears in the skin of grapes, peanuts, pistachios, soybeans (Langcage, 1976; Dercks, 1989; Jeandet, 1993). The cis (c-r) isomer has not been found in Vitis vinifera although both usually appear in wines. Resveratrol is a precursor to viniferins, which are potent antifungal agents (Palomino, 2000; Loredana, 2004). Both isomers appear naturally as two geometric isomers, generally trans is more predominant (Filip, 2003) although their glycoxides, piceids, trans (t-p) and cis (c-p) also have similar properties. In Vitro, the trans form is more thermostable and photostable and the cis is more unstable, rapidly moving to the trans form (Goldberg, 1995) although the trans can also undergo photoisomerization, generating some cis (Hanzlikova, 2004), so that in experiences prolonged and intense can increase the amount of cis (Trela, 1996). Description of the invention

A first object of the present invention is constituted by a sugary honey bee food composition containing in its formulation at least one phytoalexin, which is commonly and more preferably resveratrol in its trans- form, in a amount between 0.1% and 2.8% by weight of the total composition, including both limits.

Phytoalexin is pharmaceutical grade. Pharmaceutical grade means a phytoalexin suitable for human use and consumption with food grade quality, which must comply with USFDA, EFSA or AEMPS standards {U.S. Food and Drug Administration, European Food Safety Authority and Spanish Agency for Medicines and Health Products, respectively), since this food will leave a trace on honey produced by bees and cannot be a phytoalexin, for example industrial resveratrol, such as those They know in the market. In short, not all commercialized phytoalexins, such as resveratrol, are pharmaceutical grade and suitable for human consumption, so the present invention represents an advance in the field by using optimal phytoalexins for feeding honey bees, pollen, Waxes and other products. In a preferred embodiment, the phytoalexin is specifically resveratrol, its form being more preferably still trans- (one of the isomers of resveratrol). Preferably, of the total of phytoalexins that comprise the food 99% is trans- resveratrol. More preferably, 99.95% of the amount of phytoalexin contained in the composition (0.1% -2.8% by weight of the total composition) is only trans-resveratrol.

Basically, the composition comprises a phytoalexin which is resveratrol in its majority trans-form, and at least a second phytoalexin, acting synergistically. Preferably, the second phytoalexin or phytoalexins are selected from cis-resveratrol, a piceid isomer and any combination thereof. Resomertrol isomer means any of its cis- and trans- forms (the latter being always present in this embodiment); likewise, by means of a peptide isomer, any of its cis- and trans- forms is understood. This alternative is the most preferred, since the commercial and food grade phytoalexin compositions used to prepare the bee food composition always have traces of these forms: cis-resveratrol and piceid isomers.

The food composition can be selected from (and administered as) a liquid food in sugar solution and a semi-solid food in the form of sugar paste with humidity less than 50%. In the first case, the liquid may preferably be a syrup. of bee feeding. In the second case, it may be preferably a paste of sugars or honey (-food made from honey, also called "candy", very dry and hard that is softened by the progressive absorption of moisture from the hive-). By "sugary" it is understood that the food composition is mainly constituted by sugars, specifically these being generally between 20% -85%, and more preferably between 40% and 80%, by weight of the total composition.

When the food composition is a bee feeding syrup, it must contain at least one phytoalexin in an amount between 0.4% and 2.8% by total composition weight, including both limits. For example, it can contain between 1 and 7 grams of phytoalexins per 250 grams of syrup. When the food composition is a paste of sugars or honey, it may preferably contain between 0.1% and 0.7% by total composition weight, including both limits, of phytoalexins. For example, it can contain between 1 and 7 grams of phytoalexin per 1000 g of pasta. In one case or another, the food composition most preferably comprises 0.6% by weight of the total phytoalexin composition.

In a more preferred particular case of the invention when the food composition is a syrup, in its most preferred form it contains between 1 and 2 grams, more preferably between 1.5 and 1.75 grams (0.6% -0.7%), of phytoalexins, every 250 ml. of sugar syrup. Said syrup may be 50% sugar syrup of water.

In another particular case of the invention when the food composition is a semi-solid sugar paste, in its most preferred form it contains between 5 and 7 grams to, more preferably 6 grams (0.6%), of phytoalexins, for every 1 kg of semi-solid sugar paste , which may preferably comprise in its formulation:

^■ 30% glucose

^■ 50% fructose

^■ 18% water; Y

 ■ 2% additional components.

Preferably, the food composition also contains, in any of its forms, vitamins and / or amino acids that complement the food. The described food composition, in any of its variants, can be prepared from the combination of a sugary food for bees, preferably in the form of a liquid composition (for example syrup, commonly prepared from the mixture of water and sugar in equal parts by weight) or semi-solid (for example candy, commonly prepared with honey and water, although it can also be prepared with glucose syrup and water) with a composition of phytoalexins for human consumption, that is to say food grade, according to the criteria specified above. This phytoalexin composition may be composed exclusively of resveratrol, specifically trans-resveratrol, which is the most common form, or it may contain other phytoalexins such as those mentioned above, which is the most widespread case since traces of other known phytoalexins usually exist.

Food compositions of honey bee colonies such as those described here, contribute significantly to infection control, keeping parasitization levels within limits that allow colonies to be productive thanks to the presence of phytoalexins, which are It shows as an effective, economically and environmentally more sustainable and healthy alternative for the consumer than other compounds currently used, such as fumagillin (see Examples) These food compositions are especially effective against nosemosis, and particularly type A and C nosemosis. Within the scope of the present specification it is understood as control of an infection to reduction in parasitization without completely eliminating the infection.

The present invention also relates to the use of the described food composition, in any of its variants for the control of infections by pathogenic microorganisms in honey bee hives, and especially of nosemosis infections, the nosemosis type A and C being even more preferable. .

Thus, a third object of the present invention is a method for controlling infections by pathogenic microorganisms in honey bee hives, which comprises administering to the hive the food composition described above in any of its variants, which contains in its formulation the less a phytoalexin in an amount between 0.1% and 2.8% by weight of the total composition, including both limits, in at least one dose. The infection to be treated is in the most preferred case nosemosis, with nosemosis type A and C being even more preferable.

As stated above in relation to the product, resveratrol and more preferably trans-resveratrol is the pharmaceutical grade phytoalexin of preferred choice, although it can also be combined with other phytoalexins, thus being normally present in consumer phytoalexin compositions. human or food grade that are used to prepare the composition. In addition, the food composition can be administered in the form of liquid food or semi-solid food as described in the above variants, which are preferred. In the first case, the sugary liquid may preferably be a bee feeding syrup. In the second case, it may preferably be a semi-solid sugar-fed bee-feeding paste. In both food presentation variants, the method can be carried out more preferably with the specific compositions described above for the syrup and for the semi-solid sugary paste.

Preferably, the food composition should be administered to the hive by dividing it between 1 and 4 doses (ie, the total dose of food composition is administered in one, two, three or four times). When the composition is a sugary liquid, it should preferably be administered in four doses, while when it is a semi-solid paste it is administered at once; This is because sugary liquid compositions, such as syrup, are consumed faster, and can not be administered in large quantities of product because if released by accident could kill bees. On the contrary, when the product is semi-solid, this problem does not occur and therefore the entire dose can be administered at once. Thus, for example, the food composition can be administered to a hive in liquid form (syrup) or in semi-solid form (candy), containing a quantity of 7 grams of phytoalexin, specifically trans-resveratrol. In the first case, four doses of 250 grams of syrup each containing 1.75 grams of phytoalexin (25% of the total dose of phytoalexins per hive) would be administered. In the second case, a single dose of candy would be given, being 1 kilogram of candy containing 7 grams of phytoalexins (100% of the dose of phytoalexins per hive, at once). In short, the amount to be administered of food composition and phytoalexins is dosed differently according to the method of administration and the dosage. Also preferably, when the composition is administered in more than one dose, each dose is administered with a 7-day interval between them.

It has been proven, after two years of testing in field trials, that it is more convenient for the administration of the food composition in spring to be carried out in the form of liquid food (syrup), while in autumn it is more effective to administer it as food semi-solid (candy).

Thus, there has been a significant effect of the method described in the control of the infection of bees infected by nosemosis, with a reduction in parasitization, that is, in the number of bees infected by hive, and in the production of spores in these infected bees after administration of the food composition.

Being able to be the food composition constituted by the combination of a common and known sugary bee food and a phytoalexin composition prepared for human use and food quality, the memory also covers a method of controlling infections by pathogenic microorganisms in hives of honey bees, and especially of infections by nosemosis, being even more preferable nosemosis type A and C, which comprises administering to the hive separately but simultaneously both components, sugary food of bees and composition of phytoalexins. Said simultaneous administration of food and phytoalexins can be performed following all the alternatives and specifications set forth herein for the food composition in terms of proportions, types of foods and phytoalexins, etc. and as for the method (forms of administration: quantities, vehicle, frequencies, forms of administration ...).

Brief Description of the Figures

 Figure 1. Comparison of the number of spores counted in beehives infected with N. ceranae treated with or without resveratrol according to Example 1. The light gray figure represents the R group, and the dark gray figure represents the NR group .

Figure 2. Results of the first test commented on in Example 2.2 of comparison of treated hives with the food composition object of the present invention and foods comprising fumagillin. RJ: resveratrol in syrup; RC: resveratrol in candy; AF: formic acid; SMOKE: fumagiline; CJ: control of syrup treatment; CC: control of candy treatment; NI: without intervention. Figure 3. Percentage of average parasitization in each group treated in the study (CR = test group with resveratrol added to candy; JR = test group with resveratrol added to syrup; FUM = positive control group to which fumagiline was administered; C = control group only candy; J = control group only syrup; ST = control group without intervention). M1: before treatment in autumn 201 1; M2: after treatment in autumn 201 1; M3: before treatment in spring 2012; M4: after treatment in spring 2012; M5: before treatment in autumn 2012; M2: after treatment in autumn 2012. Figure 4. Percentage of average viability in the groups studied in April 2013. CR = trial group with resveratrol added to candy; JR = test group with syrup added resveratrol; FUM = positive control group to which fumagiline was administered; C = witness group only candy; J = control group only syrup; ST = control group without intervention. Figure 5. Average honey production in each group in summer 2012. CR = test group with resveratrol added to candy; JR = test group with syrup added resveratrol; FUM = positive control group to which fumagiline was administered; C = witness group only candy; J = control group only syrup; ST = control group without intervention. Examples

 Example 1. Laboratory evaluation of resveratrol activity against Nosema spp

The evaluation of the efficacy of resveratrol required to previously carry out toxicity tests of the product in the laboratory, and for this, preliminary studies of solubility and acceptance assessment of resveratrol had to be carried out to determine the maximum concentration that can be administered to bees. Since the tests must be carried out with bees of controlled age, it was necessary to take pictures of the hives that were introduced in incubators in the laboratory until the bees were born. Therefore, these tests can only be carried out in the months from mid-spring to early fall.

The methodology was adapted following the recommendations of OECD 213 (GUIDELINES FOR THE TESTING OF CHEMICALS. Honeybees, Acute Oral Toxicity Test) for the determination of oral toxicity of resveratrol. This guide indicates that for substances of low expected toxicity (such as resveratrol), tests can be performed limits with 100 active ingredient / bee. If the toxicity is higher than that value, no additional toxicity tests are required.

After carrying out several tests, it was possible to determine that the LD50 of resveratrol is greater than 100 by subsequently addressing the efficacy tests in the laboratory. In these studies, 2 groups were established with 4 replicates per group using bees born in the laboratory. A first group (R) of individually infected bees with 160,000 spores of N. ceranae, using the methodology developed and tuned. At 7 days post-infection, they were administered a (oral) dose of 6mg / ml that was maintained ad limitum for 24 hours. The second group (NR), was formed by infected bees (at the same dose as the previous group) that were not given resveratrol but a solution of water and sugar. Five bees were taken per replicate on days 9, 10 and 1 1 days post-infection, which in group R corresponded 24, 48 and 72 hours after the administration of resveratrol. It was observed that 72 hours after administration there is a statistically significant reduction (p <0.05) in spore counts in bees infected with N. ceranae.

Table 1. Comparison of the number of spores counted in beehives infected by N. ceranae treated with or without resveratrol.

Example 2. Analysis and evaluation of the method of treatment of infestations (nosenoma) in colonies of honey bees.

2. 7 Development of analytical methodology for analysis of trans-resveratrol and related compounds in raw material, honey, pollen wax and food for bees

In order to be able to know both the composition of the raw material and correctly establish the amount of resveratrol that should be added to the food, the Analytical Chemistry group participating in the invention has developed methods based on the use of high efficiency liquid chromatography (HPLC ) with ultraviolet detection, fluorescence and mass spectrometry. The tests have been carried out on trans-resveratrol, minimum wealth of 99%, pharmaceutical grade of Megaresveratrol® (Danbury, CT, USA); It has also been tested with 50% pure transresveratrol from the same commercial firm. In order to know the richness of the commercial product issued as an FDA-approved food supplement as a source of trans-resveratrol and other phytoalexins, and since it was based on a minimum wealth labeling of 99%, liquid chromatography was applied with row and fluorescent diode detection (HPLC-DAD-FLD) and it was found that within the expected variation the product met the specification; using liquid chromatography with mass spectrometric detection (HPLC-MS) the presence of trans-piceid and traces of cis-resveratrol was detected.

Subsequently, analyzes were made of the different foods supplied to the bees, and prepared as is thought by beekeepers in the field, on various preparations following the recommended dose; values between 0, 17 and 0.32 mg / L of trans-piceido and between 7.94 and 8.55 mg / L were found for trans- resveratrol. In the case of syrup, the values ranged from 0.24 to 0.18 mg / L for t-piceid and 6.94 to 8.03 mg / L for trans-resveratrol.

Examined with the developed analytical methodology, the variation of the composition of the food preparations over time showed that they were stable for at least one month, which also facilitates their storage and use by beekeepers.

For the evaluation of the residual quantities, after the treatments have been carried out, the same instrumental system has been applied but incorporating a mass spectrometric detector which has not only confirmed the identity of the analytes but also significantly reduced the detection limits. The analytical methodology has been partially presented in a thesis carried out in the group (ME Soto Sarria, 2012) and published in Liquid chromatographic determination of resveratrol and piceid isomers in honey ME Soto, J. Bernal, M ^a . T. Martín, M. Higes, JL Bernal, MJ Nozal, Food Analytical Methods, 5 (201 1) 162-171, which complements the study on the use of fumagiline, on which efficacy the one of the present invention has been compared: The stability and efectiveness of fumagillin in controlling Nosema ceranae (Microsporidia) infection in honey bees (Apis Mellifera) under laboratory and field conditions. M. Higes, MJ Nozal, A. Alvaro, L. Barrios, A. Meana, R. Martín, JL Bernal, J. Bernal. Apidologie, 42 (2011) 364-377. In all samples, trans- and cis-resveratrol (tr and cr) as well as trans- and cis-piceido (tp and cp) have been evaluated.

The validity of the analytical methodology in the HPLC-MS analysis of the residues of the compounds in the honey samples, pollen samples was verified in the first tests carried out on experimental apiary with the maximum theoretical amount of 7 grams of trans-resveratrol per hive. and wax collected at different time intervals in the hives as well as at the time of harvest, the values found were very variable as is always the case in this type of preliminary tests, samples and sampling.

Table 2. Total content of the different isomers in honey according to the type of food in which resveratrol and sampling have been administered

Total concentration (mgkg)

 Sampling

tp cp ^a tr cr

Candy R 1 ^or 4.4 55.3 206.9 8.9

Candy R 2 ^or 1.6 50.2 209.2 4.5

Syrup R 1 ^or 2.9 10.5 200.4 4.1

Syrup R 2 ^or 1.7 36.0 362.3 41.2

Table 3. Concentrations (mgkg ^"1 ) found of the different isomers in beehive pollen samples treated with resveratrol added in candy or syrup

Sample treatment t-p c-p t-r c-r

Candy R TN-03 ND ND 0.44 ND

Candy R TN-09 ND ND 0.07 ND

Candy R TN-19 ND ND 5.38 0.1 1

Candy R TN-23 ND ND 0.91 ND

Candy R TN-27 ND ND 10.29 0.05

Syrup R TN-08 ND ND 0.43 ND

Syrup R TN-1 1 ND ND 0.23 ND

Syrup R TN-14 ND ND 0.03 ND

Syrup R TN-17 ND ND 1.91 0.05 Syrup R TN-29 ND ND 1.82 0.09

 Candy R: candy with resveratrol

 Syrup R: syrup with resveratrol

As for the action against nosemosis, they showed remarkable efficacy with a reduction in parasitization that kept the hives at viability and productive levels similar to the groups that received fumagiline and well above the control groups that received only placebo.

2.2. Field evaluation of activity against Nosema spp. of trans-resveratrol and its isomers. Determination of the appropriate dosage.

 It was always based on trans-resveratrol, either 99% or 50% of the firm Megaresveratrol®.

Trials were started in Autumn 2011 with 65 hives, divided into the following groups: RJ (Resveratrol in syrup, n = 10), RC (Resveratrol in candy, n = 10), AF (Formic acid, n = 5), FUMA ( Positive control group, treated with Fumagilina, n = 10), CJ (Control group with syrup only, n = 10), CC (Control group only with candy, n = 10), ST (Control group without intervention, n = 10) . The RJ group received 1.75g MegaResveratrol® in 250 ml of 50% sugar syrup (4 treatments, 1 per week, which is 6 g in total of the active product resveratrol) and the RC group received 7g MegaResveratrol® (6 g in total of the active product) in 1 kg of candy (30% glucose, 50% fructose, 18% water). These trials (except the AF and ST group) have been continued in 2012, with treatments in spring and autumn. In total, 6 samples have been carried out, collected before and after the interventions in autumn 2011, spring 2012 and autumn 2012. In this way, data are available from a large group of hives that have been maintained for a long period of time, thus being able to know the real effect of treatments (application of resveratrol in different formulations and doses as well as controls) in the long term, obtaining data on production, viability and evolution of hives. It also served to determine the most appropriate time to apply the treatments as well as to propose the best form of application.

The results of the first trial of autumn 201 1 showed that in the groups that received resveratrol there was a reduction in parasitization (reduction in the number of bees infected by hive) comparable to the group that received treatment with fumagiline (Figure 2). Continuing with the study of the hives for a later year (except the AF group that was removed from the study), it was observed that during the spring of 2012, the percentage of parasitization fell in all the hives as a result of the increase in the population that It occurs naturally in hives during this period. Due to this the effect of the treatments in this period could not be observed. On the contrary, in the sampling carried out before the treatments of autumn 2012, it was clearly observed that the percentages of parasitization are much higher in those groups that did not receive any treatment in spring (C, J) when compared with the groups treated with resveratrol or fumagiline (CR, JR and FUM). The effect of the treatments in autumn also produced a reduction in the percentage of parasitization. The acceptance of resveratrol in autumn is more suitable in candy than in syrup, although it is reduced in spring, when on the contrary bees consume syrup administration better. The administration of the CR is a comfortable system that does not require many visits to the apiary, facilitating the work of the beekeeper (Figure 3).

The viability of the colonies at the end of the study in the groups treated with resveratrol (JR and CR) was similar to that of the group treated with fumagiline (Figure 4). Although the honey production results were only significantly higher in the FUM group (Figure 5).

Therefore, resveratrol, included in food for honey bees, proves to be effective for the treatment and control of Nosemosis. Although the effect on reducing parasitization is more evident in autumn, administration of the product in spring makes it easier for hives to reach autumn in with lower levels of parasitization.

Regarding the residues, we can observe that honey can present resveratrol naturally since it has been detected in the untreated groups (C and J) although in much smaller quantities than in the treated groups (CR and JR). In the latter, trans-resveratrol can be found in amounts up to 1000 times higher. The other isomeric forms that are detected in greater proportion are trans-piceid and cis-resveratrol. Table 4: Microgram concentrations per kilogram, obtained by HPLC-MS, of the different isomers found in honeys from treated hives. First sampling (1) between 2-6 December 201 1. Second sampling (2) between 9-10 January 2012.

a: mg / kg Table 5. Detection limits (LOD) and Quantification (LOQ) in g / kg obtained in

 LC-MS for the different isomers

 LOD LOQ analyte LOD LOQ analyte t-p 0.51 1.71 c-r 0.98 3.25 c-p 0.98 3.25 t-r 1.84 6.13

Claims

1. A sugary honey bee food composition that contains in its formulation at least one phytoalexin in an amount between 0.1% and 2.8% by weight of the total composition, including both limits, where 99% of the total phytoalexins it contains is trans-resveratrol, said composition further containing at least a second phytoalexin selected from the group consisting of cis-resveratrol, a piceido isomer and any combination thereof. 2. The food composition of the previous claim, where 99.95% of the total phytoalexins it contains is trans-resveratrol. 3. The food composition according to any one of the preceding claims, which is formulated as a liquid composition in a sugar solution or a semi-solid composition in the form of a sugar paste with a humidity level of less than 50%. 4 The food composition of the preceding claim, wherein the liquid composition is a syrup and contains between 1.5 grams and 1.75 grams of phytoalexin per 250 ml of sugar syrup with 50% water. 5. The food composition of claim 3, wherein the semi-solid composition in the form of a sugary paste with a humidity level of less than 50% is a sugar or honey paste that contains between 5 and 7 grams of phytoalexin per 1 kg of paste. which includes in its formulation: ■ 30% glucose ^■ 50% fructose ^■ 18% water, and ^■ 2% of other components. 6. Food composition according to any one of the preceding claims, which also comprises a component selected from the group consisting of vitamins, amino acids and a combination of both. 7. A method to control in the field infections by pathogenic microorganisms of the type Nosema apis and/or Nosema ceranae, causing nosemosis type A and C, in hives of honey bees, which comprises administering to the hive the food composition described in any one of claims 1 to 6 to feed it, said composition being administered in a single dose when presented in the form of a semi-solid paste, and in 4 doses, with 7 days interval between them, when it is presented in the form of a sugary liquid. 8. The method according to claim 7, where in spring the food composition is administered in the form of a sugar solution, and in autumn it is administered in the form of a sugar paste with humidity of less than 50%. 9. Use of the food composition described in any one of claims 1 to 6 for the field control of infections by pathogenic microorganisms in honey bee hives, where the infection is due to Nosema apis and/or Nosema ceranae.