LAUREN TESSIER, ND
Healthcare accessibility and delivery is an important issue in our current conversation. The disparities between cohorts and their healthcare utilization have been deeply studied; various minority groups suffer at the hand of poor healthcare delivery; of this there is no debate.1,2 To add an extra layer of complication, the male sex, which accounts for approximately 50.4% of the global population,3 fail to seek care as often as the female sex.4 Researchers postulate that projected societal concepts of masculine roles and ideology have a profound effect on male healthcare utilization.5 This concerning paradigm of healthcare inequality does not exist in the vacuum of primary care and emergency services; take my mold and environmental medicine specialty practice, for example: men account for only 16% of my patient population. Consider for a moment this number, in conjunction with the claims that anywhere from 50%6 to 68%7 of homes in the United States present with some form or sign of dampness or water damage. Moreover, 85% of commercial buildings studied by the EPA demonstrated a history of water damage, while 45% demonstrated current water damage.8 Needless to say, when only 16% of care is delivered to men, we not only need to wonder why, but we also need to be at the ready to assist any man who may be struggling as a result of exposure. While men may suffer from the commonplace mold-illness symptoms of fatigue, brain fog, myalgia, GI distress, joint pain, and immune system dysregulation, etc, they may also experience complaints arising from the disruption of the male endocrine system.
Mycotoxins & the Endocrine System
While it is well known that mycotoxin exposure results in oxidative damage to tissues, one must be mindful of the other means by which mycotoxins can wreak havoc in the human system. Research has demonstrated disruptive effects of mycotoxins on the endocrine system, including aberrant functionality as a result of altered metabolism of endogenous hormones.9-11 Not only does this disruption occur via anabolism11; it also occurs in the catabolic process. Animal studies have demonstrated that mycotoxins are capable of altering components of both Phase 1,12-14 and Phase 2 detox pathways.15-23 As endogenous hormones are catabolized by such pathways, it is possible that mycotoxins are therefore able to alter their metabolism, resulting in elevated levels of hormones and/or partially metabolized hormonal products. While metabolism is important to consider, one should also be aware of aberrant hormonal signaling that may arise from mycotoxin exposure. Research has demonstrated the ability of mycotoxins to alter nuclear receptor transcription10,24 as well as receptor stimulation and blockade.25 Given the ubiquitous nature of mycotoxins – both in our food26 and the built environment27-30 – and with the possibility of systemic exposure as a result of consumption,31 inhalation,32-34 or transdermal exposure,35-36 clinicians should be at the ready to address mold illness in the general population.
Mycotoxins & Testosterone
As one-half of our population has a system that largely depends on proper testosterone balance, one needs to be mindful of the ways in which mold exposure can appear clinically in this cohort. Testosterone is responsible for numerous bodily functions, including sexual differentiation, muscle, bone and body mass, and other less obvious processes, such as erythropoiesis.37 Proper testosterone balance is clearly necessary for overall health, as evidenced by research demonstrating correlations between reduced testosterone levels and increased morbidity and mortality in men.38
Testosterone and androgen deficiency may manifest as complaints of low libido, decreased body hair, gonadal atrophy, infertility, decreased occurrence of spontaneous erections, sleep difficulties, failure to develop secondary sex characteristics, osteopenia or osteoporosis, fatigue, gynecomastia, muscle mass reduction, climacteric events, depressed mood, cognitive difficulties, anemia, obesity, and decreased stamina and strength.39 Testosterone is produced primarily by the testicular Leydig cells,40 with a smaller portion produced by the adrenal glands.41 Studies have demonstrated that some mycotoxins interfere with the functionality of the 17-beta-hydroxysteroid dehydrogenase class of enzymes,11 which are required for proper androgenic metabolism, including testosterone production. Moreover, animal research suggests that Leydig cell testosterone production is negatively impacted by mycotoxins such as enniatin b,42 zearalenone,43,44 ochratoxin A,44 citrinin,44-46 T-2,44,47 and cytochalasin B.48 Furthermore, animal ancillary adrenal testosterone production is reduced in the presence of enniatin b42 and zearalenone.10
While systemic testosterone levels are demonstrably reduced in animals exposed to zearalenone,43 and T-2,49-52 production and systemic levels of androgenic hormones are not the only factors complicated by mycotoxin exposure. Animal research has shown that mycotoxins such as beauvericin, deoxynivalenol, and zearalenone and their metabolites act antagonistically at androgen receptors.53,54 Moreover, as the United States slides slowly into the void of estrogen dominance as a result of xenoestrogen exposure, we should not turn a blind eye to the estrogenic effects of mycotoxins on the male system. One of the most well-known xenoestrogenic mycotoxins is zearalenone and its family of metabolites.53 Their ability to stimulate estrogen receptors55,56 is a result of their structural resemblance to 17-beta-estradiol.57 Similar to zearalenone and its metabolites, the deoxynivalenol metabolite, 3-acetyl-deoxynivalenol, also acts agnostically at the estrogen receptor.53 Further complicating the estrogen and testosterone balance, zearalenone and its metabolites are not only able to stimulate receptors, but may also promote an increase in adrenal cortical estradiol production.10
Mold Exposure & Male Fertility
It is estimated that approximately 2.5-12% of the male population is infertile, with the highest rates occurring in Europe and Africa.58 With infertility on the rise, one should be careful to consider the possible etiology, including environmental exposure. It has been suggested in the literature59 that mycotoxins could be the cause of infertility in some countries where foodborne exposure is elevated. In fact, 2 studies of infertile men have demonstrated elevated levels of aflatoxin in their semen, compared to fertile controls.60,61 Such suggestions are not unfounded, as we know that Leydig cells are impacted by mycotoxin exposure. As these cells are responsible for testosterone production, they are also imperative to spermatogenesis. Animal studies have confirmed altered functionality and even cytotoxic effects in Leydig cells as a result of exposure to the mycotoxins citrinin,45 deoxynivalenol,62 ochratoxin A,62 T-2,47,63-68 aflatoxin,40,69 and zearalenone.70-73 Also necessary for spermatogenesis are the Sertoli cells, which have been documented in animal studies to be negatively affected by citrinin,74 fumonisin B1,75 ochratoxin A,76 T-2,77 and zearalenone.78-82 Moreover, the animal literature clearly documents altered in-vivo spermatogenesis in animals exposed to zearalenone,83,84 T-2,85 ochratoxin A,86 patulin,87 fumonisin B1,88-90 deoxynivalenol,91 citrinin,46 and aflatoxin B1.92-93 Reductions in viable sperm count have also been documented in animals exposed to zearalenone,94 deoxynivalenol,91,95 and T-2.49,50,96 Decreased motility in the presence of ochratoxin A,82 zearalenone,43,94 T-2,49,51,85 and other trichothecenes97 – and, in some instances, even germ cell apoptosis96 – have also been documented. Many of these changes have been reported in conjunction with testicular atrophy in animals exposed to zearalenone,83,98 and T-2.96
Increased Susceptibility & Protection
Animal studies suggest that unique susceptibility to mycotoxicity should be considered in the male population. For example, male rodents have demonstrated a reduced ability to renally clear deoxynivalenol from the system.99,100 Studies have shown elevated plasma and organ concentrations of deoxynivalenol in male rodents,101 without clear correlation to any sex-related variances in the major mechanism of detoxification via glucuronidation.99 While it is unclear whether the same findings apply to male humans or to other mycotoxins, it is still a point that should be considered when navigating the clinical approach to and prognosis of male clients. That said, we are aware that there are sex-correlated dimorphic differences in the human expression of Phase 1 pathways such as CYP3A5,102 CYP3A4,103,104 and CYP1A2.103 This is an important consideration, as we are aware that many mycotoxins are metabolized by some of these same pathways (keeping in mind that some of these pathways also result in intermediates that increase cytotoxicity)105; examples include: aflatoxin B1, which in humans is metabolized by human CYP1A2,105 -3A4,105,106 -2B1,107 -2c11,107 -3A1,107 -3A2,107 and -2A1106; ochratoxin A, which is metabolized by CYP1A1, -1A2, -2C9, and -3A4108; ennantin B, which is metabolized by CYP3A4, -1A2, and -2C1912; and aflatoxin G1, which is metabolized by CYP1A2, -3A5, and -3A4.198,110
Some animal studies demonstrate the protective role of testosterone in response to mycotoxin-induced damage; this includes the hormone’s protective role in cases of T-2-toxin-induced adrenocortical necrosis111 and aflatoxin-induced RBC hemolysis.112 On the other hand, animal studies also demonstrate that testosterone may be related to an increased incidence of deoxynivalenol-induced IgA nephropathy113,114 and anorexia,115 and also ochratoxin-induced liver and kidney damage.116 These findings are not limited to animal studies, as a human cohort study demonstrated a correlation between plasma ochratoxin A levels and C-reactive protein and cardiovascular risk score in men, though not in women.117
While much of this information comes from animal research – as does most of the mycotoxin literature – it does raise some interesting considerations regarding the management of our male clients, especially those suffering from mycotoxin exposure.
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Lauren Tessier, ND, is a licensed naturopathic physician specializing in mold-related illness. She is a nationally known speaker and is the vice president of the International Society for Environmentally Acquired Illness (ISEAI) – a non-profit dedicated to educating physicians about the diagnosis and treatment of environmentally acquired illness. Dr Tessier’s practice, “Life After Mold,” in Waterbury, VT, draws clients from all around the world who suffer from chronic complex illness as a result of environmental exposure and chronic infections. Dr Tessier’s e-booklet, Mold Prevention: 101, has been widely circulated and its suggestions implemented by many worldwide. Facebook tagging: @lifeaftermold