Abstract

Based on a critical synthesis of the scientific literature and the main international recommendations, this article analyzes the relationships between repeated exposure to bee venom, systemic allergic reactions, and mechanisms of immunological tolerance. It shows that the reduction in local reactions or the apparent tolerance observed in some beekeepers neither constitutes a guarantee of durable protection nor a reliable indicator of an individual’s future risk. Epidemiological data reveal wide variability in prevalence estimates, largely explained by methodological differences and selection biases, in particular the healthy beekeeper effect, as confirmed by a recent worldwide meta-analysis focusing on beekeepers (Carli et al., 2024).

The article clearly distinguishes immunological sensitization from actual clinical risk and emphasizes the limitations of biological markers in predicting severe reactions at the individual level. It highlights the fundamentally different nature of natural exposure versus desensitization through venom immunotherapy (VIT), the only strategy whose protective efficacy against severe systemic reactions is solidly demonstrated.

In addition, a critical analysis of apitherapy by injection of bee venom (Bee Venom Therapy, BVT) shows that, despite an abundant literature, the clinical evidence is largely affected by methodological biases and does not demonstrate robust, reproducible therapeutic effects comparable to those of venom immunotherapy.

Finally, a practice-transfer chapter proposes realistic and proportionate recommendations for beekeepers, based on clinical vigilance, medical evaluation when necessary, and preparedness for emergency situations, without dramatization or false reassurance. Overall, the article aims to integrate beekeeping experience with scientific knowledge in order to promote responsible and sustainable management of the allergic risk associated with bee stings.

 

1. From the myth of the “immune” beekeeper to clinical reality

1.1 A belief firmly rooted in beekeeping practice

In the beekeeping world, one assertion recurs with remarkable consistency: “With repeated stings, you get used to it.” This idea is often expressed in a reassuring way and sometimes transmitted as empirical knowledge: experienced beekeepers are thought to be at lower risk than beginners, and repeated stings are assumed to act as a form of “natural vaccination” (Müller et al., 2005 ; Bilò & Bonifazi, 2008).

 

This belief is neither marginal nor recent. It is based on real observations: many beekeepers report progressively milder local reactions over the years, a decrease in perceived pain, or even an apparent absence of systemic symptoms despite repeated exposure (Golden et al., 1989). In an activity where stings are frequent and sometimes unavoidable, this interpretation plays an important psychological role: it makes the risk acceptable, manageable, almost normal.

Figure 1: The myth of the immune beekeeper is dangerous

However, this logic rests on an implicit assimilation that deserves scrutiny: fewer visible reactions equate to a lower immunological risk. This equivalence is neither self-evident nor demonstrated (Bonifazi et al., 2005).

1.2 Why this myth is intuitively plausible

From a simplified immunological standpoint, the idea of tolerance acquired through repeated exposure appears coherent. In other fields (respiratory or food allergies), gradual exposure can, in strictly controlled contexts, lead to modulation of the immune response (Akdis & Akdis, 2015). It is therefore tempting to transpose this reasoning to bee stings.

Moreover, everyday observation reinforces this impression: the most active beekeepers are often those who seem least affected on a day-to-day basis. Conversely, severe reactions are sometimes reported in people with little exposure, or after a long period without stings (Rueff et al., 2009). This contrast fuels the idea of a protective effect of repetition, all the more appealing because it valorizes experience and endurance.

However, this plausibility rests on a fragile inductive inference: it confuses apparent correlation with causal mechanism, without accounting for selection bias, survival effects, or the individual variability of immune responses (Golden, 2010).

1.3 What clinical reality contradicts

When one moves from individual experience to clinical data, the picture becomes markedly more nuanced. Available studies show that repeated exposure is neither a reliable safeguard nor a guarantee against severe systemic reactions. Severe anaphylaxis is documented in highly experienced beekeepers, sometimes after years of practice without any major incident (Müller, 2005 ; Bilò et al., 2019).

 

A crucial point is often underestimated: the absence of reaction during previous stings does not reliably predict the absence of a future reaction. The immune response to Hymenoptera venom can change over time, independently of the affected person’s subjective experience (Golden et al., 2017). Periods of apparent tolerance can precede abrupt systemic reactions, without clear warning signs.

Figure 2: The absence of reaction during previous stings does not reliably predict the absence of a future reaction

 

In addition, the beekeeping populations studied show a major structural bias: those who develop severe reactions tend to reduce exposure or stop beekeeping altogether. This phenomenon, known as the “healthy beekeeper effect,” mechanically leads to an overrepresentation of tolerant individuals in observed cohorts, creating the illusion that the occupation itself is protective (Stoevesandt et al., 2012).

1.4 Lived experience and risk assessment: a frequent confusion

It would be wrong—and counterproductive—to set beekeepers’ experience against scientific evidence. Experience is real, valuable, and often coherent at the individual level. But it becomes misleading when generalized into an implicit rule (Bilò & Bonifazi, 2008).

The reduction in local reactions, habituation to pain, or the trivialization of stings largely reflect sensory and behavioral processes, not necessarily a durable and protective modification of the immune system (Golden, 2006). In other words, feeling less affected does not mean being biologically protected.

This is precisely where the danger lies: excessive confidence in “acquired immunity” can delay medical assessment, minimize warning signs, or lead to unnecessary risk-taking (Bilò et al., 2016).

This first chapter establishes a fundamental distinction that will structure the entire analysis: exposure is not protection, and habituation is not immunity (Bonifazi et al., 2005 ; Golden, 2010).

Understanding this difference is not about dramatizing beekeeping, but about placing it in a realistic framework where individual experience is acknowledged without being absolutized. This clarification provides the basis for addressing prevalence, immunological mechanisms, and, above all, practices that are genuinely protective for beekeepers.

2. How frequent are severe allergic reactions, really?

 2.1 Highly variable figures across studies

When it comes to bee venom allergy in beekeepers, reported figures vary in bewildering proportions. Depending on the publication, the prevalence of reported systemic reactions ranges from under 1% to over 30% (Müller et al., 2005 ; Bilò et al., 2012 ; Golden et al., 2017). This spread does not reflect extreme biological instability, but rather major methodological heterogeneity.

Some studies rely on self-administered questionnaires, others on specialized clinical records; some include any systemic reaction, others only severe anaphylaxis. Added to this are substantial differences in the very definition of what constitutes an “allergic reaction,” ranging from localized or even generalized cutaneous symptoms to potentially lethal cardiovascular or respiratory involvement (Bonifazi et al., 2005).

For non-specialist readers, this variability can give the impression of an unreliable scientific field. In reality, it mainly highlights the difficulty of measuring a rare, multifactorial phenomenon that is highly dependent on the observation context.

This wide variability is not limited to older studies. A recent meta-analysis focusing specifically on beekeepers worldwide confirms the dispersion of reported prevalences and emphasizes the decisive role of data collection methods, definitions used, and selection biases—particularly the “healthy beekeeper” effect (Carli et al., 2024).

2.2 Self-report versus clinical diagnosis

A key explanatory factor lies in the data source. Studies based on subjective reporting tend to yield higher prevalence estimates than those based on confirmed clinical diagnoses (Rueff et al., 2009 ; Bilò & Bonifazi, 2008). This difference does not necessarily reflect deliberate overestimation, but rather frequent confusion between large local reactions, vasovagal events, toxic reactions, and true IgE-mediated allergic reactions.

Conversely, data from specialized allergy centers suffer from the opposite bias: they mainly capture the most severe or problematic cases and underrepresent moderate or atypical forms. Thus, neither self-report nor specialized diagnosis alone provides an exhaustive picture of actual risk.

This discrepancy largely explains why two apparently comparable studies can reach radically different conclusions about the frequency of severe reactions in beekeepers.

2.3 The “healthy beekeeper effect”: a major structural bias

A crucial methodological element, often overlooked in non-specialist discussions, is the healthy beekeeper effect. This selection bias follows a simple mechanism: beekeepers who develop severe systemic reactions tend to reduce exposure, modify their practices, or stop beekeeping altogether (Stoevesandt et al., 2012 ; Golden, 2010).

 

As a result, cohorts of active beekeepers observed at a given time are mechanically enriched in tolerant or low-reactive individuals. This leads to an underestimation of the real risk when results are extrapolated to everyone who has practiced beekeeping over their lifetime. This bias is all the more powerful because it is silent: the most severe cases gradually disappear from the observation field, reinforcing the illusion that the population is broadly protected by repeated exposure.

Figure 3: There is no scientific basis for the “healthy beekeeper effect”

 

2.4 Immunological sensitization and clinical risk: two distinct realities

Another frequent source of confusion concerns the distinction between immunological sensitization and clinically relevant allergy. Many beekeepers have high levels of bee-venom–specific IgE without ever having developed a clinically relevant systemic reaction (Müller, 2005). Conversely, severe reactions can occur in individuals whose biological markers appeared moderate.

This dissociation explains why studies based solely on serological or skin testing tend to overestimate the number of people “at risk,” without reliably predicting future clinical events (Golden et al., 1989 ; Golden et al., 2017).

For beekeepers, this distinction is essential: a positive test is not a verdict, but one element among others in individual risk assessment.

2.5 What can reasonably be retained

Despite this variability, some robust conclusions emerge. First, severe systemic reactions to bee venom among beekeepers are overall relatively infrequent, but not exceptional. Second, their occurrence is unpredictable at the individual level, independently of the number of previous stings or years of beekeeping experience (Bilò et al., 2019).

Finally, the wide dispersion of published figures should not be interpreted as paralyzing uncertainty, but as a signal: the risk can only be properly understood by combining clinical data, individual history, and exposure context.

Method point – Why prevalence estimates vary so widely

The observed differences between studies are mainly due to:

• heterogeneous definitions of allergic reactions,
• different data sources (self-report vs. specialized diagnosis),
• selection biases, notably the healthy beekeeper effect,
• and frequent confusion between biological sensitization and actual clinical risk (Bonifazi et al., 2005 ; Bilò et al., 2012 ; Golden, 2010).

This overview shows that the key question is not only how many reactions occur, but under what conditions they occur. This leads directly to the following paradox, often misunderstood by beekeepers: Why do the most exposed individuals sometimes appear less reactive—without being protected?

3. Sting frequency: apparent protection or masked risk?

3.1 The paradox of repeated exposure

A recurring finding in observational studies and field accounts is that beekeepers receiving many stings each season report, on average, fewer systemic reactions than those exposed only occasionally (Müller et al., 2005 ; Bilò & Bonifazi, 2008). At first glance, this seems to confirm the idea of a protective effect of repeated exposure.

This reasoning, however, rests on an implicit causal inversion: low reaction frequency is interpreted as a direct consequence of exposure, whereas it may just as well be a precondition. In other words, it is not necessarily the stings that make people tolerant; it may be the tolerant individuals who remain highly exposed (Golden, 2010).

This reversal of perspective is essential. It reminds us that observed exposure is the result of a progressive selection process, not a controlled intervention comparable to a therapeutic approach.

3.2 Low exposure, higher relative risk

Conversely, several studies show that severe systemic reactions occur more frequently in individuals with intermittent or low exposure, notably after a long period without stings (Rueff et al., 2009 ; Bilò et al., 2019). This observation has sometimes been interpreted as indirect evidence for a protective effect of repeated stings.

 

Such an interpretation neglects a key factor: the temporal dynamics of the immune response. Prolonged absence of exposure may be accompanied by a loss of apparent tolerance, but this does not mean that continuous exposure constitutes a reliable protective strategy. It rather indicates that the immune system remains plastic and reversible, capable of evolving in both directions (Golden et al., 2017).

Figure 4: Prolonged absence of exposure may be accompanied by a loss of apparent tolerance, but this does not mean that continuous exposure constitutes a reliable protective strategy.

Thus, the increased risk observed among occasional beekeepers does not validate repeated stings as a preventive measure; it underscores the unpredictability of individual trajectories.

3.3 Seasonal effects and discontinuity of exposure

In beekeepers, venom exposure is not constant throughout the year. The first spring stings, after several months without contact, are often perceived as more painful or associated with more marked reactions. This subjective experience partly matches clinical observations: systemic reactions may occur preferentially after a prolonged break, even in individuals previously considered low-reactive (Golden et al., 1989).

This phenomenon sometimes reinforces the idea that regular exposure is necessary to “maintain” tolerance. However, no solid data allow the definition of a threshold, frequency, or intensity of exposure that guarantees durable protection. In the absence of a controlled framework, repeating stings is more of a biological gamble than a managed mechanism.

3.4 Why natural exposure is not immunotherapy

A frequent confusion, both in beekeeping discourse and in some simplified interpretations, is to equate repeated natural exposure with a form of venom immunotherapy. This analogy is misleading.

Venom immunotherapy (VIT) relies on strict protocols: precisely calibrated doses, gradual dose increases, medical supervision, and long-term follow-up (Bonifazi et al., 2005 ; Bilò et al., 2016). By contrast, natural stings are unpredictable in number, location, venom load, and physiological context. They may occur under stress, fatigue, or concomitant inflammation—factors that can modulate the immune response.

Equating these two forms of exposure ignores the fundamental difference between a controlled therapeutic intervention and a random, potentially dangerous exposure.

3.5 Apparent protection, but not transferable

One of the major traps of empirical interpretation lies in overgeneralization: what seems to “work” for one individual is extrapolated to all beekeepers. Yet the literature clearly shows that venom response profiles are highly individual and influenced by genetic, immunological, and environmental factors that are still imperfectly understood (Golden, 2006 ; Golden, 2010).

Thus, even if some beekeepers tolerate dozens of stings per season without incident, this observation is neither proof of universal protection nor a strategy transferable to others. It describes an individual trajectory, not a biological rule.

3.6 Key message for practice

The paradox of repeated exposure can be summarized as follows: observed low reactivity is not a guarantee of future safety, and high exposure is not a preventive measure.

For beekeepers, this implies a balanced stance: acknowledging that experience modifies the lived experience of stings, without inferring acquired immunity. Caution does not oppose competence; it is part of it.

Method point – What observational studies cannot prove

Studies linking sting frequency and allergic reactions:

• are non-interventional,
• highly subject to selection bias,
• unable to establish direct causality between exposure and protection,
• which limits any normative conclusion about the “right” number of stings (Golden, 2010 ; Bilò et al., 2019).

After showing that sting frequency does not predict risk, an unavoidable question remains: What is actually happening in the immune system—and why are biological markers so often misinterpreted?

4. What is actually happening in the immune system?

(Understanding venom immunity without getting lost in immunology)

4.1 IgE, IgG4, and regulatory cells: the essentials without overinterpretation

Bee venom allergy is classically described as an IgE-mediated immune reaction, capable—upon re-exposure—of triggering a rapid inflammatory cascade that can progress to anaphylaxis (Bonifazi et al., 2005 ; Golden, 2006). While correct, this description is often overinterpreted in practice.

In beekeepers, the situation is more complex. A substantial proportion have high levels of bee-venom–specific IgE without ever developing a clinically relevant systemic reaction (Müller, 2005). Conversely, severe reactions can occur in individuals whose IgE levels did not appear particularly high.

This dissociation illustrates a fundamental point: IgE are necessary for allergic reactions, but they are not sufficient to predict occurrence or severity (Golden et al., 1989 ; Golden et al., 2017).

At the same time, other immunological mechanisms are involved, notably the production of specific IgG4 and the activation of regulatory T cells, which may modulate inflammatory responses (Akdis & Akdis, 2015). These mechanisms are often invoked to explain “acquired tolerance,” but their presence does not guarantee stable clinical protection.

4.2 Why biological markers poorly predict individual risk

In practice, it is tempting to interpret allergy test results as indicators of safety or danger. A strongly positive test may be experienced as an imminent threat; a weakly positive test as an implicit green light. This binary reading is misleading.

Available data show that neither skin tests nor serum measurements of specific IgE alone can reliably predict future anaphylaxis risk (Golden, 2010 ; Bilò et al., 2019). They indicate immunological sensitization, not the probability of a given clinical event.

In beekeepers, this gap is particularly pronounced because repeated exposure changes immunological profiles without those changes necessarily translating into protection or immediate danger. In other words, the immune system adapts—but in heterogeneous and potentially unstable ways.

4.3 Immunological adaptation is not clinical tolerance

A frequent conceptual slippage is to equate any change in immune response with protective tolerance. The adaptation observed in some beekeepers often corresponds to a precarious balance that may break under contextual factors: intercurrent infection, fatigue, stress, inflammation, or changes in venom load and sting location (Golden, 2006 ; Golden, 2010).

This fragility helps explain why systemic reactions can occur after years of apparently well-tolerated stings, without any obvious change in measured biological parameters. Venom immunity does not follow a linear trajectory toward definitive tolerance; it remains dynamic and reversible (Golden et al., 2017).

4.4 Natural exposure and immunotherapy: two distinct logics

It is essential to clearly distinguish immunological adaptation observed under repeated natural exposure from the desensitization induced by venom immunotherapy (VIT). VIT aims to induce durable clinical tolerance by controlling relevant parameters: dose, timing, duration, and administration context (Bonifazi et al., 2005 ; Bilò et al., 2016).

By contrast, natural exposure in beekeepers is non-standardized, unpredictable, and unsupervised. It can produce similar biological changes while failing to confer the clinical stability observed under VIT. Equating the two confuses an intentional, supervised therapeutic process with a random exposure—a major conceptual error.

4.5 What immunology can—and cannot—conclude

Immunology provides powerful tools to understand the mechanisms underlying venom reactions. It does not, however, allow these mechanisms to be translated into simple rules for individual prediction.

In beekeepers, biological markers should be interpreted as clues, integrated into a global assessment including clinical history, the nature of previous reactions, and the exposure context (Bilò & Bonifazi, 2008 ; Golden, 2010). Overinterpretation can lead to either false reassurance or unjustified anxiety.

Method point – Why “understanding” does not mean “predicting”

Current knowledge shows that:

• immunological sensitization is frequent among beekeepers,
• biological tolerance is neither stable nor universal,
• no single biomarker reliably predicts a future reaction,
• which requires constant interpretive caution (Bonifazi et al., 2005 ; Golden et al., 2017).

If repeated exposure is not a reliable protective strategy, and immunological markers are insufficient for risk assessment, one question becomes unavoidable:

Is there a truly effective and validated way to prevent severe reactions in beekeepers?

5. Venom immunotherapy (VIT): evidence-based protection

5.1 What VIT is—and what it is not

Venom immunotherapy (VIT) is currently the only intervention whose efficacy in preventing severe systemic reactions to Hymenoptera venom has been robustly demonstrated (Bonifazi et al., 2005 ; Bilò et al., 2016). Unlike natural exposure, VIT relies on controlled, progressive, standardized administration of venom in a specialized medical setting.

 

Its goal is not to change a single biological marker, but to reduce—clinically meaningfully—the risk of anaphylaxis after a subsequent sting. This distinction is essential: VIT success is measured in clinical protection, not in normalization of allergy tests (Golden, 2010).

Figure 5: With VIT, the risk of a severe systemic reaction after a subsequent sting is reduced to very low levels, generally below 5%

 

It is equally important to clarify what VIT is not. It is neither empirical desensitization nor simply repeated low-dose stings. To assimilate VIT to “better organized exposure” is to misunderstand its therapeutic logic and safety requirements.

5.2 Demonstrated efficacy and magnitude of protection

Data from clinical trials and prospective cohorts show that VIT reduces the risk of severe systemic reactions after a subsequent sting to very low levels, generally below 5%, and often close to zero for potentially lethal reactions (Bonifazi et al., 2005 ; Bilò et al., 2019).

In beekeepers, this efficacy is particularly important given the high likelihood of future stings. Unlike avoidance strategies—which are often unrealistic in this context—VIT enables continuation of beekeeping activities with objectively improved safety (Müller, 2005).

It should be emphasized, however, that this protection is not instantaneous. It requires an induction phase followed by maintenance treatment over several years and presupposes rigorous adherence to the protocol.

5.3 Clear indications—and acknowledged limits

International recommendations converge on a central point: VIT is clearly indicated in individuals who have experienced a systemic reaction to Hymenoptera venom, particularly when repeated exposure is expected, as in beekeepers (Bonifazi et al., 2005 ; Bilò et al., 2016).

By contrast, VIT is not recommended solely on the basis of biological sensitization or local reactions, even if extensive. This restriction may seem counterintuitive, but it reflects a fundamental principle of evidence-based medicine: treatment targets demonstrated clinical risk, not an isolated marker (Golden, 2010).

Moreover, VIT does not eliminate risk entirely. Reactions can occur during treatment or, more rarely, after subsequent stings. This is why it must always be integrated into a broader strategy including information, follow-up, and emergency preparedness (Bilò et al., 2019).

5.4 Why VIT is qualitatively different from natural exposure

One of the major contributions of VIT is the stability of the protection achieved. Where natural exposure induces fluctuating and unpredictable immunological adaptations, VIT aims for reproducible clinical tolerance, validated through standardized protocols and explicit evaluation criteria (Bonifazi et al., 2005).

This difference explains why apparently similar immunological profiles can correspond to radically different safety levels depending on whether they result from VIT or from uncontrolled exposure. VIT protection does not rely on random “training” of the immune system by stings, but on intentional, supervised modulation of immune responses.

5.5 What VIT concretely changes for beekeepers

For beekeepers who have experienced a systemic reaction, VIT profoundly transforms risk management. It does not remove the need for vigilance or medical follow-up, but it drastically reduces the likelihood of a severe event, with direct consequences for quality of life, occupational safety, and continuity of beekeeping activity (Bilò et al., 2016 ; Bilò et al., 2019).

It is essential that this option be presented without false promises: VIT is a demanding medical approach requiring time, specialized infrastructure, and close collaboration between the patient and the care team. It is not a “light” solution, but a proportionate response to a proven risk.

Method point – Why VIT is the reference

VIT stands apart from other approaches through:

• demonstrated efficacy in controlled studies,
• documented reduction in anaphylaxis risk,
• clearly defined indications,
• and strict medical supervision,
• making it the only prevention strategy supported by solid evidence (Bonifazi et al., 2005 ; Bilò et al., 2016 ; Golden, 2010).

At this stage, one question remains essential for beekeepers, including those who are not candidates for VIT: What can be done concretely, day to day, to manage risk in a realistic and responsible way?

6. Practical recommendations for beekeepers: vigilance, preparedness, and the limits of experience

6.1 Why practice cannot rely on experience alone

Beekeeping experience is real knowledge built over seasons, colonies, and stings. It helps anticipate situations, adjust techniques, and develop a fine relationship with living systems. But when it comes to allergic risk, experience quickly reaches its limits.

As shown in previous chapters, the absence of past reactions is not a guarantee for the future, and the reduction in local reactions does not necessarily reflect durable, protective immune changes (Golden, 2010 ; Bilò et al., 2019). In practice, this means that the implicit reasoning “so far everything has been fine, so I’m safe” is biologically fragile.

The first essential transfer to practice is therefore to separate beekeeping competence from immunological safety. Being an experienced beekeeper reduces certain technical risks, but not allergic risk in a reliable way.

6.2 Warning signs that should not be trivialized

A central prevention issue lies in early recognition of clinically relevant signals. In practice, beekeepers tend to consider only spectacular reactions as problematic. This approach is too narrow.

In particular, the following should be taken seriously:

• systemic reactions even if moderate (generalized urticaria, malaise, dizziness),
• progression or duration of symptoms from one sting to the next,
• reactions occurring after a long period without stings,
• or any respiratory or cardiovascular involvement, even if transient (Bonifazi et al., 2005 ; Bilò & Bonifazi, 2008).

Trivializing these signs is one of the most frequent mechanisms behind delayed diagnosis among beekeepers.

6.3 Medical evaluation: when and why to consult

A fundamental practical transfer is to clarify when an allergological evaluation is relevant. It is indicated:

• after any systemic reaction,
• when there is doubt about the nature of a reaction,
• or when exposure is expected to continue regularly (Golden et al., 2017 ; Bilò et al., 2016).

Conversely, consulting does not mean stopping beekeeping immediately, nor does it automatically imply embarking on a heavy therapeutic pathway. The goal is risk assessment, not disqualification of the activity. Medically, the evaluation of anaphylaxis risk after a first systemic reaction (generalized urticaria, swelling of subcutaneous tissues of the face or extremities, or submucosal swelling of the lips or throat, cutaneous flushing, malaise, nausea, vomiting, diarrhea, abdominal pain, dizziness, etc.) should include a tryptase measurement, the elevation of which can indicate a disorder (mast cell activation syndrome or MCAS) involving white blood cells implicated in allergic reactions (mast cells), as well as testing for the c-KIT mutation; these two parameters are associated with an increased risk of anaphylactic shock upon renewed exposure to venom. Concomitantly, initiation of medical desensitization (venom immunotherapy (VIT)) is indispensable.

6.4 The central role of an emergency kit

For beekeepers with an identified risk—whether or not they are on VIT—having an emergency kit available is an essential safety measure. It is not an admission of weakness, but a matter of responsibility, comparable to other occupational safety devices.

The effectiveness of a kit depends on two conditions:

1. it is actually available during handling,
2. and its use is known and integrated into reflexes (Bilò et al., 2016 ; Golden, 2010).

An emergency kit that is not within reach, or is not mastered, has only symbolic value.

6.5 What is not recommended—despite its implicit popularity

Practical transfer also requires explicitly naming certain non-recommended practices, precisely because they are rarely stated as such:

• seeking to “toughen up” deliberately through repeated stings,
• interpreting a sting-free season as proof of acquired safety,
• relying exclusively on isolated biological test results,
• or postponing consultation after a systemic reaction on the grounds of experience (Golden, 2006 ; Golden, 2010 ; Bilò et al., 2019).

These strategies rest more on subjective adaptation logic than on evidence-based prevention.

6.6 Managing risk without giving up beekeeping

A key transfer point is to move beyond the implicit alternative “continue as before” versus “stop beekeeping.” In most cases, this opposition is artificial.

Realistic risk management rests on:

• clear information,
• proportionate medical evaluation,
• context-appropriate preparedness measures,
• and, when indicated, VIT (Bonifazi et al., 2005 ; Bilò et al., 2016).

This approach allows many beekeepers to continue their activity knowingly, without denying risk or overdramatizing it.

The essential takeaway of the entire article can be summarized as follows: Experience protects against imprudence, not against allergy. Prevention rests on lucidity, not on acquired confidence.

Recognizing the limits of experience does not weaken beekeeping practice; it makes it more sustainable, safer, and more responsible, both for the beekeeper and for those around them.

Method point – Transfer without abusive simplification

The recommendations proposed here:

• do not rely on empirical “rules,”
• do not claim to eliminate risk,
• but translate the current state of knowledge into applicable vigilance principles (Bonifazi et al., 2005 ; Bilò et al., 2016 ; Golden et al., 2017).

7 Apitherapy by injection of bee venom (BVT): methodological limits, biases, and clinical scope

Apitherapy by injection of bee venom (Bee Venom Therapy, BVT) is sometimes presented as a therapeutic option for various chronic conditions, notably autoimmune diseases and pain syndromes. In view of the available literature, however, a strict conceptual distinction is required between BVT and venom immunotherapy (VIT) used in allergology.

VIT relies on standardized protocols, progressive dose escalation in the microgram range, defined intervals, close medical supervision, and a clearly established objective: prevention of IgE-mediated systemic reactions after stings (Sturm et al., 2018).

 

 

By contrast, BVT is characterized by a lack of standardization (dose, frequency, route of administration), marked methodological heterogeneity, and frequent extrapolation of experimental mechanisms toward unproven clinical effects. As with the widely held idea of “natural immunization” through repeated stings, evaluation of BVT is particularly exposed to systematic biases likely to lead to overestimation of efficacy.

Figure 6: Numerous methodological biases falsely give the impression that BVT is effective.

 

Several recurring methodological mechanisms explain why the BVT literature may give the impression of greater clinical efficacy than robust data actually allow:

1) Selection and survivorship bias

People who experience early severe reactions, adverse effects, or lack of benefit more often discontinue BVT. The remaining cohorts then appear artificially more “tolerant” or “responsive,” a phenomenon analogous to the healthy beekeeper effect described among beekeepers (Carli et al., 2024 ; Carli et al., 2025).

2) Causality error (correlation ≠ therapeutic effect)

A low frequency of adverse effects or subjective improvement may be a precondition for continuing treatment, not its consequence. Observational studies and case series therefore cannot support reliable causal inference.

3) Unblinding and high susceptibility to placebo effects

Venom injections frequently cause noticeable local reactions (pain, edema, pruritus), which compromises blinding in randomized trials and strengthens expectancy effects, especially for subjective outcomes such as pain.

4) Protocol heterogeneity and lack of standardization

Under the label “BVT,” very different practices coexist (venom concentration, injected volume, injection points, frequency, combinations with other interventions). This variability prevents reliable comparison and strongly limits reproducibility, unlike VIT which is framed by clear recommendations (Sturm et al., 2018).

5) Outcome drift

Many studies use multiple endpoints, often secondary, short-term, and sometimes redefined a posteriori. This mechanically increases the likelihood of “statistically significant” findings without demonstrated clinical relevance.

6) Underreporting of adverse events

Systematic reviews show that side effects and discontinuations are incompletely reported in part of the BVT literature, biasing assessment of the benefit–risk balance (Jang & Kim, 2020 ; Park et al., 2015).

7) Geographic bias and proximity to promotion (marketing) logics

A substantial proportion of positive BVT studies comes from countries where apitherapy is culturally or institutionally integrated into complementary medicine. This context favors:

• publication bias (negative results published less often),
• selection of favorable endpoints,
• and sometimes confusion between scientific evaluation and the promotion of a practice.
• This pattern is well documented in other areas of complementary medicine (Vickers et al., 1998).

7.1 Lack of measurable clinical effects on targeted diseases

When considering the most methodologically rigorous studies and clinically relevant endpoints, results are remarkably consistent: for most conditions studied (e.g., rheumatoid arthritis, multiple sclerosis, neurodegenerative diseases, chronic pain), no specific, reproducible, clinically significant effect is demonstrated.

Reported positive effects are generally limited to short-term subjective improvements, without demonstrated impact on objective markers, disease progression, or prognosis (Wesselius et al., 2005 ; Hartmann et al., 2016).

Like the idea of “immunization through stings,” BVT relies on a fragile extrapolation from partial observations and plausible mechanisms to clinical conclusions that are not supported by robust data.

Apparent benefits are highly dependent on methodological biases, whereas risks—particularly allergic risks—are well documented.

In the current state of knowledge, BVT cannot be considered an evidence-based therapeutic approach, and it should not be assimilated to, or substituted for, validated strategies such as venom immunotherapy in allergology.

8. Conclusion — Between lived experience and evidence-based responsibility

Beekeeping confronts those who practice it with a singular reality: an activity deeply grounded in experience, yet involving a biological risk that largely escapes intuition and empirical learning. Bee stings are an emblematic example. They are part of the job, the gesture, and sometimes even of beekeeping identity. Yet their trivialization is precisely the point of tension between lived experience and clinical reality.

The analysis of scientific data consistently shows that repeated exposure is not a reliable protection strategy against severe allergic reactions. The individual trajectories observed among beekeepers—ranging from durable apparent tolerance to systemic reactions occurring late—reflect the intrinsic variability of the human immune response, not a universal protective mechanism (Golden, 2010 ; Bilò et al., 2019).

This finding does not invalidate the value of beekeeping experience. It clarifies its limits. Experience refines techniques, improves colony management, and reduces many technical risks. However, it does not reliably predict the evolution of allergic risk, nor can it replace medical evaluation when a warning signal appears (Bonifazi et al., 2005 ; Golden et al., 2017).

Confusion between subjective adaptation, biological modification, and clinical tolerance is one of the common threads of persistent misunderstandings around bee stings. This confusion is reinforced by highly variable prevalence figures, important selection biases, and the temptation to interpret isolated immunological markers as indicators of safety or danger. Yet none of these elements, taken alone, can ground a prudent decision (Bilò & Bonifazi, 2008 ; Golden, 2010).

In this context, venom immunotherapy (VIT) occupies a particular place. It is neither a universal solution nor a light response, but the only strategy whose protective efficacy has been robustly demonstrated for people who have experienced a systemic reaction (Bonifazi et al., 2005 ; Bilò et al., 2016). Its existence underscores a central principle: when protection is possible, it relies on controlled, evaluable, reproducible protocols—not on random exposure.

For beekeepers, the most realistic stance is therefore neither blind trust in habituation nor abandoning the practice, but lucid and proportionate risk management. This includes recognizing clinically relevant signals, accepting medical assessment when necessary, and integrating preparedness measures appropriate to the exposure context (Bilò et al., 2019).

Like the idea of “immunization through stings,” apitherapy by injection of bee venom rests on fragmentary observations and plausible mechanisms, but lacks sufficient clinical grounding to support a therapeutic recommendation. In the absence of measurable, reproducible clinical effects on defined diseases, and given documented allergic risks, BVT cannot be considered an evidence-based approach.

Ultimately, the issue is not to choose between experience and science, but to articulate them correctly. Experience illuminates daily practice; science sets the limits of what can reasonably be expected. It is within this demanding but fertile space that engaged, responsible, and sustainable beekeeping can be built.

Experience makes it possible to work better with bees. Scientific knowledge makes it possible to protect oneself better. Recognizing this complementarity does not weaken beekeeping practice or those who carry it. On the contrary, it constitutes one of its strongest foundations.

 

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