glyphosate

Tampons With Glyphosate: Underpinnings of Modern Period Problems?

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Floating around the internet in recent weeks was an announcement from Argentinian researchers who, quite by accident, found that sterile women’s health products were anything but sterile. It turns out that cotton grown from genetically modified cotton seeds and sprayed with glyphosate across the growth cycle (RoundUp and other herbicides), retain, and likely leach, glyphosate from the products that the cotton is spun into. It should not be a surprise that those cotton-based products retain the chemicals from which they were grown or processed, but it was. Not because the idea is far-fetched, it isn’t. Indeed, it is biologically more likely that these chemicals are retained than it is that they somehow would magically disappear post processing. What was surprising is that we never thought about this before.

When we consider that 89% of cotton crops are now genetically modified to be glyphosate tolerant, the implications of glyphosate transfer from what are considered sterile medical and hygiene products directly into the bloodstream of the users should give us pause. Heck, it should have given us pause many years ago, but it didn’t and wouldn’t yet if it were not for some accidental finding in a lab studying something else entirely. This accident speaks volumes about how thoroughly we test, or rather, do not test, many of the products we have on the market. It is precisely this lack of testing and lack of understanding that leads to the preponderance of chronic health conditions from which so many in the Western world suffer.

Glyphosate and Women’s Health

If we look at women’s health in particular, I cannot help but wondering if glyphosate leaching tampons has something to do with the increase in menstrual related problems like fibroids, endometriosis, PCOS, and others. The female vagina and cervix are remarkably efficient vehicles for drug absorption. The vaginal epithelium provides a vast surface area that is richly vascularized and highly innervated. Drugs and other chemicals absorbed via this route directly enter the bloodstream and avoid detoxification via the liver, meaning lower dosages are required to reach the same effect as an orally ingested medication. Small concentrations, therefore, could induce large effects. And small, regular exposures to glyphosate is likely what we get from tampon use.

In addition to the ease with which certain chemical compounds can be absorbed through the vagina and the cervix, both also boast a very tightly regulated microcrobial environment that, when healthy, is capable of fending off all sorts of bacterial and viral threats on its own, absent medical intervention. Indeed, recent research shows that many medical interventions intended to promote health, destroy the vaginal bacterial balance, and ultimately, increase the risk of serious sexually transferred diseases, and viral, bacterial, and fungal infections.

In this context, one has to wonder, what could possibly go wrong when we directly and continuously expose a woman to a potent environmental toxicant for several days every month, month in and month out, year after year? If we look at the research from other modalities detailing damage by glyphosate, we see that quite a lot can go wrong and often does.

How Glyphosate Preparations Work

A little known fact that explains many of glyphosates ill-effects on plants, animals, and humans: before its life as the most commonly used herbicide on the planet, glyphosate was used as a commercial descaling agent. Yes, that is right, glyphosate is a powerful descalant able to attach to and remove the most tenaciously attached mineral buildup in pipes (calcium and magnesium, in particular). Consider how mineral deficiencies impact human health.

As an herbicide, the active ingredient of Roundup and many others, glyphosate is used with various chemical boosters called adjuvants. The chemical adjuvants added to glyphosate preparations boost the potency of glyphosate alone, allowing it to penetrate cell walls more easily. Glyphosate is never used in isolation, but always with an adjuvant. So when I refer to glyphosate within this document, I am referring to the glyphosate herbicides with associated boosters.

Glyphosate is toxic to all plant life – all, not just some, but all plant life. Glyphosate kills plants via the disruption of a particular enzyme (enolpyruvylshikimate-3-phosphate synthase –EPSPS) required to synthesize essential amino acids. Of note, these amino acids comprise approximately 30% plant dry mass and contribute largely to the dietary needs of the larger animals and humans (one of the many reasons GM foods are nutrient reduced compared to organic).

The EPSPS enzyme is present in all plants, fungi, and many bacteria (including the bacteria that populate human skin, lungs, gut and reproductive regions). When this enzyme is blocked, organismal death is imminent via necrosis, a very messy form of cell death.

In order for crops to survive glyphosate spraying, they are modified to include either two copies of EPSPS enzyme or a strain resistant to these chemicals. These modifications allow farmers to spray glyphosate liberally, killing the weeds and other pests while protecting the crop. The plants are modified to resist the glyphosate, but not metabolize it. That means that glyphosate residues remain in and on the plant that is destined to become food or, in this case, cotton; cotton that is used in all sorts of applications from clothing to medical and hygiene products. (Glyphosate also remains in the soil and leaches into the surface and ground water).

Just as the ramifications of ingesting glyphosate modified foods are vast and complicated (see here, here, here and here for background), so too are the likely consequences of direct exposure to glyphosate and its adjuvants via skin contact or via the vaginal epithelia. With both local and systemic changes at play, understanding the potential consequences of glyphosate leaching tampons is difficult at best.

Glyphosate’s Mechanisms of Destruction – CYP Enzymes

Top on the list of glyphosate’s most detrimental activities, is its ability to disrupt critical enzymes. Glyphosate alters the body’s innate metabolic enzymes – the CYP450 enzymes – through multiple mechanisms and in a variety of directions; some of these enzymes are upregulated, while others are downregulated. The CYP enzymes are the proteins responsible for ensuring the metabolism of steroids, some vitamins (vitamins A and D), drugs, and environmental chemicals. There are also CYP enzymes that regulate what is called hemostasis (blood clot formation and dissolution), particularly important topic for women who also utilize hormonal contraception. Mess with these proteins and all sorts of things go wrong; mess with them directly, in a tightly regulated local environment like the vagina and it is possible, if not probable, that many of the problems we see in women’s reproductive health can be tracked back to these exposures.

Glyphosate Is an Endocrine Disruptor

Glyphosate’s ability to alter steroidogenesis directly via upregulating or downregulating the CYP enzymes responsible for steroid synthesis makes it one of the more potent endocrine disruptors. Glyphosate, it seems, disturbs steroidogenic enzymes at every turn, from top to bottom of the pathway.

The first step involved in making steroid hormones requires that cholesterol be transported into the mitochondria and converted by an enzyme called StAR into the mother hormone of all steroids – pregnenolone. Pregnenolone becomes progesterone and from there, depending upon the tissue within which these processes are occurring, progesterone can be converted to a whole bunch of other steroid hormones. Glyphosate downregulates StAR, effectively throwing a wrench in the entire steroidogenic machine. And if it does this in vaginal, cervical, or uterine cavity, a region hugely dependent upon a symphony of steroid hormones, I’d imagine there would be some problems. StAR is not the only enzyme involved in steroid balance that glyphosate interrupts.

Glyphosate can increase or decrease aromatase (CYP19) depending upon cell type. Since aromatase metabolizes testosterone into estradiol, glyphosate dysregulates estradiol concentrations. In the Leydig cells (male testicular cells), glyphosate increases aromatase, effectively reducing testosterone while increasing estradiol concentrations – not a healthy balance for male reproductive capacity. Consider in utero development of a male offspring. In contrast, in placental cells, glyphosate decreases aromatase, effectively decreasing estradiol and the other estrogens needed to maintain a healthy placenta. Worse yet, glyphosate is toxic to human placental cells in culture.

These are just the tip of the hormone-disruption iceberg. Glyphosate alters enzymes throughout the steroidogenic pathways in patterns we are only beginning to understand. Imagine the possible hormone disruption evoked by a lifetime of direct exposure via tampons leaching glyphosate into the vaginal epithelium, a surface replete with a full complement of hormone receptors, local steroidogenic machinery, and a direct connection to an ample blood supply so that these chemicals can do systemic harm. It’s difficult to imagine that this would be good, and yet, that is exactly where we find ourselves with GM cotton used in the production of tampons.

But wait, there’s more.

Glyphosate Disrupts Vitamin A Metabolism

Vitamin A? What do vitamins have to do with the vaginal epithelium (or the epithelia of any other body surface)? A lot. Vitamins and minerals are important co-factors of every bodily enzyme and a whole bunch of other stuff. Without proper nutrients, the enzymes responsible for the machinery that keeps us alive and kicking slows to a crawl and all sorts of chronic and intractable disease processes arise. In the case of vitamin A (retinoic acid is the active form in the body), the proper balance is so critical that disruption evokes everything from blindness, tumors, and cancers, to reproductive difficulties and many gynecological conditions such as endometriosis and fibroids. If one can get pregnant, glyphosate exposure is linked to severe congenital malformations in the offspring. Vitamin A balance is not something to be messed with, and yet, we do.

I’ve written about the Vitamin A pathway before and am likely to do so again, as this particular set of mechanisms merits a much deeper dive. Glyphosate’s impact on the retinoic acid pathway are complicated and the effects of disruption are far-reaching and diverse.

Briefly, glyphosate interacts with the metabolism of vitamin A at multiple junctures within the cascade, changing everything from receptor activity, and signal transduction, to what proteins are transcribed and how, and whether or not damaged DNA can repair itself (too much glyphosate and it cannot). What makes this pathway particularly difficult to understand is that it is tightly and locally regulated. Moreover, it has complicated cascades of compensatory reactions to maintain proper vitamin A concentrations that vary by location (compartment in pharmacological parlance), and more specifically, by cell type. Too much or too little vitamin A in one tissue and cell type does not always produce the same reactions in different cells. Making matters worse yet, the enzymes that regulate vitamin A synthesis and metabolism are largely competitive with other compounds. Endogenous and synthetic hormones and alcohol compete with vitamin A for enzyme activity. That means too much or too little estradiol or synthetic estrogens (from oral contraceptives, HRT, environmental estrogens, even from glyphosate itself) change how retinoic acid is used within any given cell by altering enzyme activity. Ditto for alcohol use.

With regard to women’s health, there is a growing body of evidence linking low vitamin A synthesis and activity within leiomyomas – fibroid tumors and in endometriosis cells. There is also evidence that chronic low level exposures to glyphosate initiates fibroid tissue growth in rodents. Similarly, from cancer research, we know that within many tumor types the machinery for vitamin A is disrupted and ultimately decreased such that local administration decreases tumor size. Together this suggests that certain types of aberrant cell growth and death may be linked to impaired vitamin A machinery, perhaps mediated by toxicant exposure.

To summarize, glyphosate disrupts hormone and vitamin balance and, in doing so, risks creating an environment of tumorogenesis and carcinogenesis both locally, systemically, and likely generationally, with a range of detrimental effects to us and our offspring.

But wait, there’s more.

Glyphosate Is an Anti-Microbial

Remember when I mentioned that the vagina, the cervix, and indeed, the entire uterine cavity contain a unique and highly efficient ecosystem of microbes that are capable of eradicating a wide range of pathogens independent of medical intervention? Well, glyphosate, which was designed to be antibiotic and is patented as such, disrupts bacterial ecosystems. It appears the good bacteria, like the Lactobacilli dominant in the vagina, are highly susceptible to glyphosate’s antibacterial tendencies while the bad bacteria, the bacteria that cause all sorts of infections, are not. Just like the medical antibiotics given to fight infections tend to disrupt microbial balance and have spurred the growth of super-pathogens, strains of bacteria that are resistant to all currently available antibiotics, glyphosate appears to do the same. Though the potency and dosages of residue glyphosate ingested by diet or absorbed intravaginally are likely reduced compared to medical antibiotics, the chronicity of exposure is incomparable. And if we have learned anything from the more advanced toxicology methods of recent decades, it is that smaller, continuous exposures tend to produce as significant ill-effects as the larger ones.

Perhaps not considered as deeply as it should be, when we disrupt bacterial populations with persistent antibiotics, we not only increase the prevalence of more virulent bacterial pathogens that are resistant to antibiotic therapies, but encourage the growth of more virulent fungal infections, like glabrata infections, now common with the increased use of bactericidal antibiotics like fluoroquinolones. Viral infections too can become more problematic. HPV and HIV, for example increase in women who use hormonal contraceptives. The mechanism suspected is the altered vaginal/cervical pH. Since Lactobacilli maintain the acid environment of the vaginal area and glyphosate kills lactobacilli, the ensuing change in pH by glyphosate alone, would increase a woman’s risk of serious viral infections. Add a hormonal contraceptive, and her innate protection is likely diminished significantly.

And last, but certainly not least.

Glyphosate Disrupts Hemostasis

One of the least well understand actions of glyphosate is its impact on blood clotting mechanisms. There is emerging evidence amongst a lot of speculation, that glyphosate disrupts the CYP enzymes involved in maintaining proper blood clotting: CYP5A1 – (thromboxane synthase) and CYP8A1 – (prostacylin synthase). This is particularly problematic for women who use hormonal contraception where the risk of developing blood clots is significantly higher than in the population as a whole. Additionally, here is where I think we’ll find the roots of the most common complaints amongst menstruating women – excessive menstrual bleeding along with increased menstrual blood clots. If we can map glyphosate’s role in bleeding, along with its role in vitamin A balance, I suspect we can shed light on some of the pressing health issues that women face.  A second post on this topic is necessary. For now, suffice it to say, glyphosate likely disrupts local, and potentially more systemic, clotting mechanisms.

Now What?

Honestly, I have no idea. This is quite overwhelming. Tampons are a wonderful invention and it is not feasible for women, especially athletic women, to stop using tampons (and yes, I know about menstrual cups, but they too have potential problems with polymers that could leach endocrine disrupting chemicals). Would organic products be better? Probably, but there will always be chemicals used in the processing of these products; in the adhesives, the absorbents, and other component parts. I am not sure we can fully remove ourselves from the chemical environment, at least not immediately. With some effort, however, I think we could change the dynamics of this situation within a generation or so. Perhaps it is time for women take control of these businesses or start new ones and develop safer products. It is certainly past time for women to demand better and safer products for themselves and their children.

Postscript

Since this article was published in 2015, to my knowledge, there has been only one additional study addressing glyphosate in tampons or other hygiene products. A review article published in 2022, found 24 studies addressing various chemical compounds in these products (metals, phthalates, dioxins, VOCs, bisphenols, and others) and only 3 studies involving the measurement of these compounds in human women. With the exception of a study from Belgium, where glyphosate use is restricted and banned in some areas, none of these studies assessed glyphosate exposure. In the majority of studies, however, chemicals used in the growth and production of these cotton products were identified in the tampons and pads and per the human studies, despite serious limitations in methodology, chemical exposure was confirmed.

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More people than ever are reading Hormones Matter, a testament to the need for independent voices in health and medicine. We are not funded and accept limited advertising. Unlike many health sites, we don’t force you to purchase a subscription. We believe health information should be open to all. If you read Hormones Matter, like it, please help support it. Contribute now.

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This article was published originally on November 2, 2015. 

Books I Like – Toxic Exposure: The True Story Behind the Monsanto Trials and the Search for Justice

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For this week’s book review: Toxic Exposure: The True Story Behind the Monsanto Trials and the Search for Justice
by Chadi Nabhan

If you see a theme emerging from the types of books I read, it is true, there is one. I spend a lot of time reading about environmental chemicals, health, and disease. Glyphosate is one of the chemicals I have spent years investigating. Unlike last week’s book that detailed the biological mechanisms altered by this agro-chemical, this week’s book presents an entirely different perspective. It is a first hand account of the legal proceedings against Monsanto, the makers of the glyphosate herbicide, Roundup*, written by the oncologist called upon to testify for the plaintiffs.

Prior to being asked to testify, the author was a professor in the division of hematology and oncology, the director of cancer clinics and a medical director for the international program at the University of Chicago. When asked to review the initial case that led to the landmark jury award against Monsanto, Dr. Chadi Nabhan was hesitant. While an expert in blood cancers, he was not familiar with research linking the consumer herbicide to non-Hodgkin lymphoma, or really, that there was even a connection between glyphosate and cancer. This speaks to how detached medicine and academia have become from the environmental contributors to diseases like cancer. To his credit though, he dug into the research and quickly realized how deep the connection was. Even so, this was a huge case with lots of risk to him and his career. It was a big decision. Ultimately, albeit somewhat reluctantly at first, he agreed to review the patient files and eventually testify. To say his foray into this type of case was bumpy would be an understatement though. The opposing lawyers were brutal and remained so at each juncture and with each case. He quickly gained his footing, however, and in the end, was instrumental in the plaintiff’s success in the first three cases against Monsanto.

The book reads in part like a diary, a first person recollection of events, and in part like a John Grisham novel with all of the intrigue and excitement one would expect. He takes us through the evidence linking glyphosate to cancer and eloquently portrays the human cost of those products. He also takes us through each phase of each case, from deposition to trial. He recounts the questions, the examinations and cross-examinations and the discussions pre and post trial amongst himself and the other players. We are with him as he navigates his position in these historical cases.

Toxic Exposure is a compelling read and an excellent resource for those of us interested in the broader context of corporate influence. I think it would make a great movie. In the meantime, it is a fantastic read. I thoroughly recommend it. If you purchase it through the link below, I get a few dollars that help support this website. Enjoy.

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Toxic Exposure: The True Story behind the Monsanto Trials and the Search for Justice

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Toxic Exposure: The True Story behind the Monsanto Trials and the Search for Justice*

by Chadi Nabhan

A behind-the-scenes look inside three key trials involving Monsanto’s weed killer Roundup, cancer, and the search for justice―written by an expert witness medical oncologist who lived it all.

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*Monsanto was purchased by Bayer in 2018 and the lawsuits continue.

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Books I Like -Toxic Legacy: How the Weedkiller Glyphosate Is Destroying Our Health and the Environment

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For today’s book review: Toxic Legacy: How the Weedkiller Glyphosate Is Destroying Our Health and the Environment.

I have followed Stephanie Seneff’s work on glyphosate for years now. I cited her work in our book, Thiamine Deficiency Disease, Dysautonomia and High Calorie Malnutrition, and in many of the articles where I have written about the ills of glyphosate. Her work on glyphosate is seminal and the foundation for much of my understanding, of not only this chemical, but of the industry itself. Because of that, I thought I knew much of what she would write in this book. I was wrong. There was so much more to understand about glyphosate’s mechanisms of destruction than I anticipated, all of which she adroitly takes us through.

Glyphosate is truly one of the most underappreciated culprits to modern disease. The mechanisms by which it exerts its ill-effects on health are vast and include glycine substitution, mineral chelation, microbiome destruction, phosphorylation disruption, sulfation errors, and on and on. These are some of the most basic and fundamental processes for organismal survival. Consider just one of its deleterious actions: glycine substitution. Glyphosate is an analogue of the amino acid glycine.

“Nearly every protein of any length has at least one glycine residue. There are a large set of proteins for which at least one specific glycine residue is essential for proper function.”

Collagen is one of those proteins and it is a big one. It happens to comprise up to 25% of all of the body’s protein. It turns out that every third residue of the collagen protein contains a glycine reside. What problems might ensure when glyphosate fills those position? Might some of the joint pain so many of experience be related to glyphosate substituting itself for glycine in collagen?

This is just the tip of the glyphosate iceberg, albeit a huge one.

If you like mechanisms and want a deeper understanding of why so many of us are fighting so many complex and chronic illnesses, this book is for you. The chemistry is complicated, but Dr. Seneff does a remarkable job making it accessible and easy to understand, even for the lay person.

I have to say, Toxic Legacy: How the Weedkiller Glyphosate Is Destroying Our Health and the Environment, by Stephanie Seneff, is one of the best science books I have read in a very long time. I highly recommend this book. If you purchase it through the link below, I get a few dollars that help support this website. Enjoy.

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More people than ever are reading Hormones Matter, a testament to the need for independent voices in health and medicine. We are not funded and accept limited advertising. Unlike many health sites, we don’t force you to purchase a subscription. We believe health information should be open to all. If you read Hormones Matter, like it, please help support it. Contribute now.

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The Brain Needs Protein, Say What?

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Although it is well known that muscles need protein to function, that the brain also needs protein is not common knowledge. In fact, the conventional interpretation of brain fuel leads many to believe that the brain relies almost entirely on glucose for survival. This is largely based on the oft-quoted statement that the brain represents only 2% percent of total body weight but consumes 20 % of the total glucose. Indeed, current research suggests that under normal, resting conditions, the brain consumes ~5.6 mg glucose per 100 g of human brain tissue per minute. That is an enormous amount of glucose. With injury, those numbers surely increase.

With that in mind, the shorthand assumption has become that the brain needs mainly sugar to survive and therefore carbohydrates are key to brain function. While to some degree this is true, it grossly oversimplifies the chemistry involved in brain and body metabolism, forgetting not only that mitochondria require micronutrients, vitamins, and minerals, to process said carbohydrates, but also, that other macronutrients, like proteins and fats, are necessary substrates for bioenergy, not to mention a whole host of other critical processes, like protein and lipid synthesis, the building blocks of any cell.

Macronutrients

In the brain and other compartments of the body, fuel source capabilities and preferences vary considerably. In the heart, for example, free fatty acids are preferred, unless or until there is injury and/or hormone changes (yes, hormones affect heart function and fuel preference) and then glucose becomes more prominent. How well this transition is handled and how effectively the cells manage the different fuel sources is part of what is called metabolic flexibility. As you might suspect, the more metabolically flexible one is, the more likely one is to survive an acute illness.

As was mentioned previously, in the musculature, protein, (and the amino acids therewith), fatty acids, and carbohydrates are all used, although there is much debate on how much of each and relative to which types of activity. Nevertheless, muscles need protein, perhaps far more than any other tissue. With athletes, this is a given. Performance hinges on one’s ability to balance, and really, outpace the breakdown of proteins caused by the demands of training or competition. Similarly, though less well appreciated, the synthesis of muscle protein must outpace the breakdown of proteins if one is to maintain health and any sort of muscle tone.

A skewed balance between protein synthesis and protein breakdown is common among the chronically ill, especially in patients with myopathy and myalgia (muscle weakness and pain) and cachexia (the catabolism of muscle proteins associated with an array of conditions including cancer). Among the more common contributing factors, a seemingly obvious one at that is a lack of protein in the diet (lack of activity follows as a close second).  The high carbohydrate, low nutrient diets that are common not only across Western populations but recklessly promoted by western medicine are deleterious to health.

What happens when dietary proteins are low or insufficient? A whole slew of compensatory actions are enacted both in the body and in the brain. Locally, muscle wasting or catabolism begins. Muscle tissue is broken down, and consumed, as an emergency fuel source and the synthesis of new proteins slows. In other words, that optimal cycle of increased protein synthesis to protein breakdown is reversed and muscle wasting begins.

Low Protein and the Brain: Energy Sensors and Survival Protocols

When protein stores become low enough, brain survival mechanisms kick in. Namely, an important set of nuclei in the hypothalamic region of the brain called the orexin/hypocretin neurons, stop firing and cease wakefulness. We have talked about these neurons before, here and here. The orexin or hypocretin neurons (same neurons, different names), are the ATP or energy sensors of the brain responsible for sensing when brain ATP becomes dangerously low and activating survival protocols. One such protocol is decreased wakefulness. That is, when ATP is low, the orexin/hypocretin system kicks in, stops firing, and puts us to sleep. Sleep is a key survival mechanism, allowing for the reallocation of resources to vital functions. Think about it for a minute, if there is only enough ATP floating around to maintain breathing and heart function, wakefulness goes out the window.

Another way we can shut down the orexin/hypocretin system is via increased temperature. Think fever. The orexin/hypocretin neurons are very sensitive thermosensors. And to make things even more interesting, this system regulates our motivation to eat and modulates pain. So when the orexin/hypocretin system is dysregulated, we cannot stay awake, have no motivation to eat, and our body hurts all over. Sound familiar? It should. These brain nuclei control what Hans Selye described as ‘sickness behaviors’; behaviors that every organism employs when ill, no matter the cause of the illness.

Interestingly, while many parts of the brain consume glucose like fiends, the orexin/hypocretin neurons do not like glucose at all. In fact, these neurons shut down entirely and stop firing in the presence of glucose. When extracellular glucose levels are high, an inward rectifying potassium (K+) channel that is ATP dependent kicks in, and intracellular ATP is allocated to open K+ channels and flood the cell with the inhibitory K+ ions.  The K+ hyperpolarizes the cell and prohibits it from firing. So high glucose or too many dietary carbohydrates, shut down these neurons, force us to sleep, decrease our motivation to eat, and increase pain sensitivity. From a behavioral standpoint, this explains why many of us feel rotten much of the time.

If high glucose diminishes the firing rate of the orexin/hypocretin neurons, one might wonder what activates these neurons. It turns out that these neurons want dietary protein, or more specifically, amino acids. Through a series of electrophysiological experiments, researchers from Cambridge and elsewhere delineated the fuel source preferences of orexin/hypocretin neurons. The methods were complicated but basically, they used sensors to measure cell firing in different media. More technically, brain cell patch clamps of locally (in culture) and peripherally and centrally (live mice fed various diets, activity levels measured, subsequently terminated, decapitated and brain slice measurements taken) administered amino acids, fatty acids, glucose, and other substrates were used to determine which fuels caused the most robust electrical signals.

They found that orexin/hypocretin neurons fire most strongly in the presence of several amino acids. The most potent among them, in order of potency included: glycine > aspartate > cysteine > alanine > serine > asparagine > proline > glutamine.

The essential amino acid leucine, which is critical for protein synthesis in the musculature, did not evoke detectable membrane current, e.g. induce the neuron to fire. Similarly, neither the fatty acids tested (oleic acid, palmitic acid, and palmitoleic acid) nor glucose evoked a response. While the lack of response to glucose is understandable given that it triggers the potassium currents that hyperpolarize the cell, the lack of response to leucine is surprising. Leucine and the other branched-chain amino acids are critical for muscle protein synthesis and are all the rage in the supplement world.

Also surprising, even though glucose alone causes these neurons to stop firing, glucose plus amino acids induced cell firing in a manner that was synergistic to that of the amino acids alone. That is, the firing rates increased somewhat over and above what the various amino acids alone produced. This tells us that like the rest of the body, the preferred fuels of different nuclei in the brain are a bit more complex and metabolically refined than appreciated. The brain, or at least this set of nuclei in the brain, requires amino acids to function.

One More Thing: Glycine and Glyphosate

Digging a little deeper, if we look at the most potent amino acid, glycine, we see something troubling. Glycine is very active in the brain and spinal cord, binding with its own receptors and capable of initiating all manner of signal transduction pathways by itself and along with other neurotransmitters like GABA and glutamate.  In adults, glycine quickly tempers the excitability of motor neurons, auditory processing, pain transmission, and other functions. Glycine is critical for one-carbon metabolism (which is folate- B9 and cobalamin- B12 dependent) and the synthesis of glutathione (a major antioxidant), creatine (phosphocreatine -ATP store for musculature), purine (nucleotides), and heme synthesis (iron complex). It is also a core component of many transporter and channel proteins.

Glyphosate, the key ingredient in Roundup, the herbicide used commercially in all conventionally grown produce and liberally by consumers for landscaping, is a glycine analog. This means that to the degree one is exposed to glyphosate, glyphosate will substitute itself for endogenous glycine, binding to the very same receptors, tricking them into thinking that there is sufficient glycine floating around. Perhaps more importantly, the glyphosate/glycine analog will embed itself into the polypeptide (protein) chains with aberrant or misfolded proteins likely. Misfolded proteins, like poorly designed tools, mean that things just don’t work the way they should. Imagine a hammer with a floppy handle, a drill that doesn’t spin quickly enough, a saw without teeth, etc. Just as building stable products from poor tools is difficult, so too is building healthy humans. While there are no studies to delineate what specific effects the synthetic glycine has on the orexin/hypocretin system, researchers Samsel and Seneff have demonstrated that this type of substitution is deleterious to health in general.

Bottom line: the brain and the body need protein, preferably organic proteins. If you or your loved ones are having health issues, consider reviewing your diet.

We Need Your Help

More people than ever are reading Hormones Matter, a testament to the need for independent voices in health and medicine. We are not funded and accept limited advertising. Unlike many health sites, we don’t force you to purchase a subscription. We believe health information should be open to all. If you read Hormones Matter, and like it, please help support it. Contribute now.

Yes, I would like to support Hormones Matter. 

This article was first published on June 28, 2018. 

The Glyphosate Problem

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Glyphosate is the active ingredient in Roundup® – the world’s most popular broad spectrum herbicide used by gardeners and farmers to increase crop yields and kill weeds. It is used widely in agriculture, but also in urban settings and to control weeds as part of conservation efforts.

Glyphosate is an analogue of the amino acid glycine. It works by interfering with the shikimate pathway – a seven-step process used by plants, bacteria (including our gut bacteria), archaea, fungi and some protozoa to synthesise folates and amino acids. Specifically, glyphosate inhibits an enzyme called EPSP synthase (5-enolpyruvylshikimate-3-phosphate synthase) which is required to produce the amino acids tryptophan, tyrosine and phenylalanine – all of which are needed for plants to grow.

Humans depend on the shikimate pathway working in our gut bacteria as well as in plants to supply us with essential amino acids. Glyphosate is absorbed by the foliage of plants and to a lesser extent the roots, so it cannot be used to prevent germination of a plant, only once the plant has started growing. Once the EPSP enzyme is inhibited, shikimate builds up in the plant, diverting resources from where it is needed and causing the plant to turn yellow and die.

Glyphosate was first discovered by a Swiss chemist in 1950. It was developed and brought to market in the 1970s by multinational agrochemical and biotech giant Monsanto (recently acquired by pharmaceutical company Bayer), under the name of Roundup®. Monsanto’s marketing tagline for Roundup was “a herbicide that gets to the root of the problem.”

Since the seventies, its use has grown by over 100-fold, making it the world’s most used herbicide, in part due to the rise in glyphosate-resistance amongst plants. There are now several hundred different glyphosate products on the market.

Monsanto has developed a number of genetically modified crops that are resistant to glyphosate, so that farmers can broadly apply the herbicide to their crops. As we will discuss later, this affects far more than just the crop. Glyphosate resistant crops include soy, cotton, canola, beets, sugar cane, alfalfa and maize. Currently, over 90 percent of U.S. corn, upland cotton, and soybeans are produced using genetically engineered varieties.

Ignoring Gut Bacteria: The Great Shikimate Debate

The human health impacts of glyphosate exposure is a heated topic. This is unsurprising considering Roundup delivered a whopping $4.8 billion in revenue to Monsanto in 2015. There are significant financial interests in suppressing comprehensive research into this topic. Companies like Monsanto argue that Roundup® cannot be toxic to humans because we do not have a shikimate pathway. However the bacteria in our guts do.

Glyphosate also disrupts methionine, an essential sulfur-containing amino acid, and glycine. Numerous other vital molecules including serotonin, melatonin, melanin, epinephrine, dopamine, thyroid hormone, folate, coenzyme Q10, vitamin K, and vitamin E, depend on the shikimate pathway metabolites as precursors. As such, glyphosate’s disruption of the shikimate pathway very likely affects our health, contrary to Monsanto’s assertions.

Glyphosate and Cancer

In 2015, the World Health Organization’s International Association for Research on Cancer identified glyphosate as a “probable carcinogen” whilst in the same year the European Food Safety Authority stated that glyphosate is unlikely to cause cancer, words that were echoed by the US Environmental Protection Agency (EPA) in 2018.

Although glyphosate is regularly found in human urine (both from those experiencing direct exposure and via food), there is no consensus on what a safe tolerable daily intake is. The US EPA sets a limit of 1.75mg per kilogram of body weight whilst the EU’s limit is much lower at 0.3mg per kilogram of body weight. Glyphosate residues in food are found up to a year after the herbicide’s application.

Despite this disagreement, there are a number of studies indicating glyphosate exposure is toxic to humans and animals. To this end, Bayer has been forced to payout almost $11 billion in the settlement of 95,000 non-Hodgkin lymphoma and cancer claims from sufferers linking their illness to RoundUp exposure.

In 2015, after reviewing approximately one thousand published studies on glyphosate, a working group of 17 World Health Organization experts from 11 countries deemed glyphosate a category 2a carcinogen. That means it is likely to cause cancer in humans and that there is sufficient evidence of its carcinogenic effects in animals. The WHO scientists also concluded there was strong evidence that glyphosate damages genes, causing mutations.

In 2019, the Agency for Toxic Substances and Disease Registry (part of the US Department of Health) released its draft toxicology report on glyphosate concurring and even strengthening the WHO’s findings. This was despite efforts from Monsanto, working in collaboration with the US EPA’s Pesticide Office, to suppress the report. In fact, US EPA’s Pesticide Official Jess Rowland was caught telling Monsanto’s Dan Jenkins, “If I can kill this I should get a medal”.

Glyphosate Linked to Neurodevelopmental and Neurodegenerative Disorders

In addition to demonstrating statistically significant links between glyphosate and cancer in humans, the ATSDR report also links glyphosate with developmental delays, gastrointestinal effects including nausea and vomiting, kidney and liver toxicity, and eye irritation in rodent and some human studies.

The ATSDR highlighted a link[1] between parental use of glyphosate among farm families and an increased risk of neural tube defects, miscarriage, preterm delivery, and small for gestational age (ATSDR Table 2-5, p. 40-41). Animal studies of early life exposure to glyphosate indicate an increased incidence of testicular lesions, elevated abnormal sperm, decreased testosterone, decreased sperm production, and skeletal malformations (ATSDR, p. 14). Long term studies by the US National Cancer Institute link glyphosate exposure to chronic bronchitis, wheezing and asthma (ATSDR, Table 2-5, p. 36; Ag Health Study).

Recent research has suggested a link between glyphosate and neurodegenerative disease, such as Parkinson’s, and prion diseases. This is thought to be due to glyphosate’s disruption of bile acid homeostasis, which causes a toxic buildup of manganese in the brain.

Laboratory studies have found evidence that glyphosate may contribute to endocrine disruption in animals and human cell lines, even when used at concentrations below those applied in agriculture. Ironically, chemicals that act as endocrine disruptors often have an inverted-dose effect, whereby low doses can cause more acute effects than high doses. Considering many of the published studies on glyphosate look at high dose effects, one might infer that they have missed the full picture.

Interestingly, the adjuvants in pesticides inflate the toxicity of the active ingredient. A 2014 study showed that Roundup® was 150 times more toxic than glyphosate on its own, stating:

Despite its relatively benign reputation, Roundup® was among the most toxic herbicides and insecticides tested.

Systemic Effects of Glyphosate

Whilst glyphosate is used to control weeds, its effects on our environment are clearly far more systemic than that. Other plants, animals, insects and surrounding ecosystems are exposed to its application in the soil, water and from run-off and precipitation. The full impact of these effects is poorly understood as toxicity studies have tended to be laboratory based, high dose and include a limited number of species – very different conditions to what is found in nature.

Once in the soil, glyphosate is rapidly degraded by microbes into aminomethylphosphonic acid (AMPA). When applied to hard surfaces (e.g. sidewalks) rather than soils, up to a quarter makes its way into the waterways through run-off. It is commonly found in soils and waterways, particularly those downstream from agricultural sites, and to a lesser extent in wetlands and groundwater.

So widespread is its use that it is found in rain (the US Geological Survey found glyphosate in 86% of rainwater samples). It persists longer in soil than in water, with a half life in soil of over 12 months in some cases, depending on the soil composition (soils with higher clay contents hold onto glyphosate for longer whereas it is washed out of sandy soils faster).

Once in the soil, glyphosate can form complexes with metal ions, which may affect the availability of soil nutrients. In fact, it has been shown to interfere with the uptake of key minerals in agricultural crops and to alter the composition of soil microorganisms, the full effects of which are poorly understood. For example, glyphosate reduces populations of fungi-suppressing microorganisms whilst reducing the growth of symbiotic fungi. Researchers find that earthworms, critical to soil health, are also adversely affected by glyphosate.

According to McGill University researchers, glyphosate can trigger biodiversity loss, which in turn affects all of us. We are already in the midst of unprecedented biodiversity loss, with over a million species at risk of extinction, according to the United Nations. The last thing we need is more damaging chemicals accelerating this process.

Non-target plants are impacted by glyphosate application. Studying the impact of glyphosate on 23 native non-target species, Argentinian researchers found that all species showed lethal or sub-lethal effects after just 25% of the recommended field application rate of glyphosate, with 50% of species exhibiting phytotoxicity or death.

The decline of the Monarch butterfly in North America has been linked to glyphosate use. Glyphosate obliterates milkweed – the plant on which Monarchs exclusively lay their eggs. By some estimates, over 850 million milkweeds have been lost since 1999 – over 70% of the plants relied upon by the Monarch butterfly. In 2019/20 alone, monarch caterpillars in Mexico plummeted by 53%. Butterflies are key indicators of ecosystem health and biodiversity, with their fragility making them quick to react to changes in the environment.

But the impacts aren’t limited to insects. Research indicates that glyphosate impacts upon the cardiovascular systems of mammals, with a 2015 French study linking abnormal heart patterns to glyphosate exposure. It has also been found to be toxic to amphibians, for example shortening the bodies of frog embryos and interfering with enzymes required for normal nervous system development in tadpoles. Toxic impacts have also been found among mussels, carp and eels, among other species.

Protecting Ourselves and the Environment

According to the United Nations Food and Agricultural Organization, we are on-track to reach over 9 billion people by 2050. How on earth do we feed a population like this? This is one of the arguments used by industrial agriculture – that we simply cannot feed the world without it and its arsenal of chemicals like Roundup®. In fact, this argument couldn’t be further from the truth.

We certainly need ways to grow more food, but we need to do it in ways that do not harm the natural resources that enable us to grow that food – which is exactly what industrial agriculture does.

Modern industrial agriculture is pumping our environment with harmful chemicals, creating monocultures and toxic waste products that are altering the natural ecosystems we depend upon. For example, food production (including post-farm processing) accounts for one quarter of all greenhouse gas emissions. Pollution from conventional agriculture (specifically the loss of nitrogen from farming in the Mississippi River Basin) is also a large contributor to the 9,000-square-mile dead zone in the Gulf of Mexico.

Organic agriculture, by comparison, can generate fewer greenhouse gas emissions, and uses less energy whilst protecting soils and sequestering carbon. Organic methods are also capable of producing competitive yields during stable weather conditions and out-producing conventional agriculture during times of drought and flooding, the latter of which we can expect a lot more of in a warming world. This is because organic soils retain more moisture, thereby producing higher yields during periods of drought.

According to a team of American scientists, organic farming could provide sufficient food for the entire human population, whilst causing less pollution and fewer health problems than conventional agriculture. Organic food has a higher nutrient content than conventionally farmed food, protecting us against illness.

When it comes to glyphosate, switching to an organic diet reduces glyphosate levels in the body significantly and rapidly. In a 2020 US study, researchers found that switching to an organic diet reduced urinary glyphosate levels by an average of 70% in just 6 days for both children and adults. But there are powerful lobbies and interests working hard to maintain the status quo, which is why organic and regenerative forms of agriculture currently make up such a small percentage of the global food supply.

To shift these numbers, all of us need to play a part. That includes lobbying our politicians to regulate companies that produce products which harm our health and environment, boycotting companies that pollute the environment and buying safer alternatives, including switching to chemical-free, organic products wherever possible. Many great schemes exist now where you can buy direct from producers to support local sustainable agriculture, cutting out the middle-man and accessing good, clean, healthy food at an affordable price.

Continuing business as usual and relying on harmful chemicals like glyphosate is not worth the loss of our health or that of our planet. Especially when there are already viable alternatives that can feed us and our world sustainably.

We Need Your Help

More people than ever are reading Hormones Matter, a testament to the need for independent voices in health and medicine. We are not funded and accept limited advertising. Unlike many health sites, we don’t force you to purchase a subscription. We believe health information should be open to all. If you read Hormones Matter, like it, please help support it. Contribute now.

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This article was published originally on January 18, 2021. 


[1] 90% confidence interval rather than the 95% required threshold, though still sufficient to prompt tighter regulation to avoid the risk of harm.

The Ethics Of It All

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What if there is no future? We have always assumed that there would be a future, that somehow no matter what we did to ourselves or to the environment, life would go on. What if we were wrong? What if the very actions we embrace to prolong life, the technologies and conveniences that make modern living palatable, actually shorten it and shorten not just our lives, but life in general. What if the possibility of future life is not automatic but something that demands active consideration lest it disappear completely?

I had never thought about the possibility that a future might not exist. Sure, I recognized that I would not exist at some point, but I never considered the possibility of the death of humanity, until recently. Now, it seems as though it is everything I can do not to think about it. The magnitude of the environmental crisis that we face is compounded daily by the inability of contemporary leaders and thinkers to frame the crisis in a way that might allow us to address it. If we think about these toxicants, honestly think about them, it is difficult not to wonder how we did not know that all of the chemicals that we dump into the environment and into our bodies would lead to a poisoned environment and poisoned bodies. Seriously, what did we think would happen when we release poisons into the environment daily, year in and year out? Did we think they would somehow magically be absorbed and detoxified by the environment, and thus, effectively disappear? I believe we did and many still do.

I know that until I began the work here, I never gave this notion much thought. I, like most of us, embraced synthetic chemistry and all of the cool things we could concoct and manipulate. It was not until I began seriously investigating the mechanisms of these chemicals, outside the confines of academia, that I began to question the rationale behind these conveniences. I was taught that the dose makes the poison. This suggests that so long as the dose is low enough and administered in a controlled fashion that we can control the outcomes. In reality, however, the poison makes the poison. Small doses are just as deadly as large doses, the only difference is the time scale of the reaction. The body recognizes these poisons and adapts accordingly; so too does the environment. We simply cannot see those reactions until they reach a critical threshold and even then we have to be willing ‘see’ what is before us.

Let us consider glyphosate, which among its many deleterious effects on health, is a potent endocrine disruptor. That is, glyphosate overrides endogenous hormones systems in the organism exposed to the chemical. Per the Environmental Protection Agency’s (EPA) safety standards the maximal ‘safe’ exposure of glyphosate is 2 milligrams per kilogram of body weight or about 140 milligrams per day for a 70kg/154lb adult, which on the surface, seems like a minute amount and too small to worry about, but is it? If we buy the dose makes the poison approach, then we need not worry, but if we evaluate the chemistry and the math a little more closely, then an entirely different picture emerges.

Synthetic hormones, endocrine disrupting chemicals, exert influence in the body at staggeringly low dosages. A well-known researcher in the field of chemical endocrine disruptors describes this aptly.

“The issue of the amount of hormone that actually causes effects is very difficult for scientists to talk to people about because we’re dealing with numbers that are outside of the frame of reference that anybody is going to be thinking about. We see changes, profound changes, in the course of development of essentially the whole body of experimental animals, and we’re working with mice and rats, and we see these changes at fifty femtograms [a femtogram equals a quadrillionith of a gram] of the hormone per milliliter of blood. That’s 0.05 trillionths of a gram of this hormone in a milliliter of blood.

But what you have is the entire field of toxicology thinking of a millionth of a gram of a hormone or a chemical as being this staggeringly tiny amount, and to most people if I said there’s only a millionth of a gram of it here you’d say, ‘How can it do anything?’ A millionth of a gram of estradiol in blood is toxic. The natural hormone is actually operating at something like a hundred million times lower than that. So when you have a physiologist thinking of a millionth of a gram, you have that physiologist thinking this is a toxic high dose. When you are raised in the field of toxicology you are looking at that from the other perspective of ‘My gosh, that’s such a tiny dose, it couldn’t do anything.’” – Fredrick Vom Saal, PhD

If we thought 2 milligrams per kilogram was a small enough dose to be considered safe, how do we even conceptualize something that operates in femtograms per milliliter of blood, especially when 1 milligram = a trillion femtograms? That amount is inconceivably small, and quite literally, beyond comprehension, and yet, that is all it takes to disrupt hormone systems and cause illness; hormone systems that control not only reproductive capacity for the exposed individual but also affect the outcomes and health of the offspring across multiple generations. These chemicals directly affect the possibility of a future. One has to wonder if this is all it takes to disrupt critical hormone systems, what happens when we blanket the environment with tonnes of chemicals like we have done over the last 50 years or so.

Returning to glyphosate for a moment, as of 2014, over 826 million kilograms/1.8 billion pounds were used worldwide; a 12 fold increase since 1995. That is staggering amount of chemical exposure, and yet, it is just one of thousands of chemicals we are exposed to daily. Just one. There are currently over 83,000 different chemical entities being ‘monitored’ by the EPA. So, on the one hand, we have standards for safety that only partially recognize the dangers of small exposures (kg/mg) but are yet ineffective inasmuch as they are still several magnitudes greater than the dosages where the damage begins. On the other hand, however, none of this matters because the economic drivers push exposures well above those minimal safety standards and what any reasonable person would consider safe. And finally, neither the toxicology, nor the ethics consider what the cumulative body and environmental burden is with regular exposures to thousands of chemicals daily.

This brings me back to my original question, what if the possibility of the future is something that we should have been protecting all along? What if it isn’t a given? Shouldn’t there be some discussion of the ethical implications of using chemicals that damage not only the current generation but subsequent generations? Even if we ignore the chemistry or plead ignorance to the mechanisms of transgenerational effects, shouldn’t we at least consider whether it is ethical to release chemicals into the environment and into our bodies that potentially pose risks to future generations? Those who come after us inherit the world we have left. Shouldn’t we consider their health and the health of the environment that we leave to them? I think we should. Indeed, I think this ought to be part of any discussion of safety. It is not; partly by choice and partly because we have bought into this notion that the dose makes the poison and ignored the fact that the poison is the poison. We have eliminated the poisonousness of the chemical from the equation and out of any cogent discussion of danger. This allows us to proceed as if we have everything under control, as if we can recognize and mitigate any and all dangers that a particular chemical poses. This allows us to ignore the prospect that current actions influence future health and well-being. This allows us to reap the rewards of our technological prowess now and kick the costs of our ignorance down the road. Where are the ethics in this?

We Need Your Help

More people than ever are reading Hormones Matter, a testament to the need for independent voices in health and medicine. We are not funded and accept limited advertising. Unlike many health sites, we don’t force you to purchase a subscription. We believe health information should be open to all. If you read Hormones Matter, like it, please help support it. Contribute now.

Yes, I would like to support Hormones Matter.

Image: Dicklyon, CC BY-SA 4.0 <https://creativecommons.org/licenses/by-sa/4.0>, via Wikimedia Commons

This was published originally on March 7, 2019.

Environmental Pollutants and the Microbiome

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The pollution we release into the environment affects all of us, not least of all the delicate ecosystem of gut microbes that keep us healthy. The gut microbiome plays a pivotal role in our health – from energy production and immune function, to cognitive development and homeostasis. In fact the metabolic activities of our gut microbes are so vital to health that the gut is now considered an organ in its own right. It should be no surprise then that the hundreds of environmental pollutants our bodies are exposed to every day have profound adverse effects on our microbiome.

This article focuses on three categories of environmental pollutants and their effects on our microbiome – air pollutants, pesticides and heavy metals. 

Air Pollution Linked to Obesity and Diabetes

Air pollution is the fourth leading cause of death worldwide. The particulate matter in air pollution can alter the gut’s composition and function by either inhibiting or promoting the growth of certain microbes. 

Air pollution greatly influences the rate of obesity and type 2 diabetes. In fact, the geographic distribution of diabetes globally correlates with air pollution. In 2016 alone, air pollution (particularly PM2.5) contributed to 3.2 million cases of diabetes globally. The mechanism by which air pollution drives these diseases is through particulate matter altering the gut microbiome and its metabolic activities as illustrated:

Pollution and Gut Bacteria

Reference: Bailey et al, Exposure to air pollutants and the gut microbiota: a potential link between exposure, obesity, and type 2 diabetes, 29 April 2020.

A number of studies demonstrate elevated levels of air pollution exposure are associated with several gastrointestinal diseases, including inflammatory bowel disease (IBD), irritable bowel syndrome, appendicitis, and GI disorders in infants. Cigarette smoke, which contains particulate matter that is also present in air pollution, has also been shown to alter gut composition in human and animal studies. 

A 2020 study of 101 young Southern Californians (averaging 19.6 years old) found that exposure to air pollutants was associated with alterations in gut bacterial diversity. The variation in diversity was significant with 4.0% variation for total Nitrogen Oxide (NOx) exposure, 4.4% for Nitrogen Dioxide and 11.2% for Ozone. This study also found that higher ozone exposure influenced gene pathways involved in fatty acid synthesis/degradation, all of which may play a role in gut barrier integrity, obesity and Type 2 diabetes. 

Another study of young people (aged 17-19) in Southern California, found that increased exposure to nitrogen oxide pollution near roadways influenced the abundance of gut bacteria (Bacteroidaceae and Coriobacteriaceae) that have been associated with obesity and altered metabolism. 

In a 2013 study of mice exposed to PM10 (very small particulates found in dust and smoke), for just 7-14 days, researchers found that the pollution altered the mice’s immune gene expression, enhanced pro-inflammatory cytokine secretion in the small intestine, increased gut permeability, and reduced white blood cell activity. When this exposure was increased to 35 days, even more inflammation in the colon was observed together with altered short chain fatty acid concentrations and changes in microbial composition. 

A 2019 epidemiological study in China found that gut microbes (particularly Firmicutes, Proteobacteria and Verrucomicrobia bacteria) play an important role in mediating the effects of particulate matter when it enters the body. However, both PM2.5 and PM1 reduce gut microbial diversity, in turn increasing the risks of developing Type 2 diabetes.

In summary, it is clear that air pollution negatively alters gut bacteria, setting the scene for increased disease risk in animals and humans, particularly Type 2 diabetes and obesity. Efforts to address the global obesity epidemic therefore should not overlook the role of our environment in driving disease, together with lifestyle and psycho-social factors.  

Pesticides Affect Gut Bacteria

Several studies demonstrate that gut microbiota help protect us against the toxicity of pesticides but once overwhelmed, disease can set in. For example, ingesting the broad-spectrum pesticide chlorpyrifos alters the gut microbiota of mice, contributing to obesity and insulin resistance

Some people (largely those connected to chemical companies) argue that certain pesticides are not harmful to humans because the pathways that they target do not exist in the human body. This is the argument made for glyphosate (RoundUp) in relation to the shikimate pathway. However this ignores the fact that many of these pathways do exist in the microbes living in our gut, thereby explaining the harmful effects that pesticides can have on our health. 

For example, herbicides like 2,4-D (used for lawn and weed control), may affect gut bacteria because not only plants but also bacteria can synthesize plant hormones. Both pure glyphosate and glyphosate-based formulations alter the bacterial makeup of the gut microbiome in rodents and honeybees.

Further, the fungicide imazalil (used as a preservative and to prevent decay and control fungal infections in fruits and vegetables) induces microbiota dysbiosis and hepatic metabolism disorder in zebrafish and causing adverse alterations to the microbiota of mice

Another study showed that the insecticide diazinon damaged the microbiomes and metabolic profiles of mice. Interestingly, exposure to diazinon and another insecticide called malathion influences the ability of gut bacteria to modulate gene expression (through a process called quorum sensing), yet another sign of the ways in which pollutants can drive disease through alterations to gut microbiota. 

Whilst there are fewer studies examining the effects on the gut of agro chemicals beyond glyphosate and chlorpyrifos, studies in adults across multiple species using a wide range of agro chemicals find gut microbiome alterations as well as impaired lipid metabolism, oxidative stress, and inflammation among other things. 

The Heavy Metals Toxins

Heavy metals are elements found in the Earth’s crust which are highly toxic even at low concentrations. Gut bacteria play an important role in metabolizing and eliminating heavy metals from the body. For example, human gut bacteria can transform inorganic arsenic into less toxic organic arsenic, whereas demethylation of methyl mercury by gut bacteria creates more toxic inorganic mercury. 

A 2014 study of mice exposed to arsenic in drinking water for four weeks, found disturbed gut microbiota and metabolic activities. A 2017 study of mice found similar results from lead exposure, with vitamin E, bile acid, and nitrogen metabolism all impaired. Similar results were found in a 2018 study that exposed rats to a range of heavy metals including arsenic, cadmium, cobalt, chromium, and nickel. In a 2019 study of frogs, cadmium exposure also altered gut microbiota, and so too with fish.

A 2018 study of fish (fathead minnows) and mice exposed to mercury found that it damaged their guts and impaired lipid metabolism and neurotransmission. Nutritional supplementation may help to soften these effects however, with selenium reversing some of the gut damage in mercury-poisoned rats. 

Like mercury, studies show that magnesium chloride damages the gastrointestinal tracts of mice and chickens, causing thicker muscle walls, wider submucosa, a decrease in goblet cells and necrosis in gut enterocytes. In chickens, magnesium chloride exposure also adversely altered the metabolism of xenobiotics (any substance that is foreign to animal life), and PAHs (chemicals found in coal, oil and gas).

A 2018 study found that protein rich diets can alter the microbiome, in turn assisting with mercury elimination, in humans. A 2019 study of adult Bangladeshis reported that arsenic exposure altered the gut microbiome and resulted in an overproduction of the Citrobacter bacteria, which can cause a range of health problems including urinary tract infections, respiratory diseases, gastrointestinal inflammation, and sepsis in immunocompromised individuals. Citrobacter is also associated with higher vascular intima-media thickness (IMT), a subclinical marker of atherosclerosis. As such, arsenic exposure may play a key role in the development of atherosclerosis.

A Fundamental Rethink Is Required

In conclusion, it is clear that pollutants profoundly influence the gut bacteria of humans and animals, impairing healthy metabolism and therefore increasing the risk of disease. Just as the pollution we create is damaging our environment, so too it is damaging us, yet another sign that we are more intimately connected with the environment than our extractivist economies acknowledge. Whilst there are many steps we can take as individuals to protect ourselves against environmental pollution, such as eating organic/chemical-free nutrient-dense whole foods, exercising, reducing stress, minimizing our exposure to known pollutants, and supplementing to strengthen our immune systems, ultimately it is the systems that drive this pollution which need to change. That requires a fundamental rethink of our politics and economies so that they no longer treat the earth and us as expendable resources to fuel unfettered growth. 

We Need Your Help

More people than ever are reading Hormones Matter, a testament to the need for independent voices in health and medicine. We are not funded and accept limited advertising. Unlike many health sites, we don’t force you to purchase a subscription. We believe health information should be open to all. If you read Hormones Matter, like it, please help support it. Contribute now.

Yes, I would like to support Hormones Matter. 

Image by Foto-Rabe from Pixabay.

This article was published originally on May 3, 2021. 

Could Altered Vitamin A Metabolism Be Responsible for Endometriosis and Fibroid Growth?

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Yes, and increased use of environmental toxicants may be partially to blame. Over the last decade researchers have uncovered connections between tissue level vitamin A activity – the retinoic acid pathway – hormone metabolism, and the cell cycle overgrowth noted in fibroid tumor development, breast and ovarian cancer, and endometriotic tissue growth. Moreover, researchers from the environmental side have found that the popular glyphosate-based herbicides alter vitamin A or retinoic acid metabolism which in turn alters androgen and estrogen metabolism. Connecting the dots, we may have a first step to reducing cell growth in these conditions; remove the toxicant exposure and increase nutritional resources. A second step may be to develop locally absorbed vitamin A, applied directly to the aberrant tissues.

What is Vitamin A?

Vitamin A, (retinol, carotene) is a fat-soluble nutrient that we derive solely from dietary sources. It is responsible for a myriad of functions in a vast number of tissues from the eye, to the ovary, to the heart. Historically, nutrition from diet, coupled with the old wives’ tales of good health, carrots for eyesight, and cod liver oil for all that ails you, were all that were needed to maintain healthy levels of Vitamin A in most individuals. However, with the increase in processed foods, modern farming, intense use of herbicides and pesticides, and the general replacement of the old wives’ nutritional wisdom with pharmaceuticals, many men, women, and children are vitamin A deficient and likely do not even know it. The WHO estimates vitamin A deficiency in 19 million pregnant women and 150 million children worldwide. When Vitamin A deficiency reaches its nadir night blindness, maternal mortality, and difficulty fighting infections are common. In women, the first signs of vitamin A deficiency may be unrecognized and include fibroids or endometriosis. Earlier signs of vitamin A deficiency in women could also be menorrhagia (heavy menstrual bleeding) that often precedes fibroid or endometriosis diagnosis, but research is lacking here, or even genital warts of the common HPV strains.

Why Retinoic Acid, Hormones, and Cell Growth

Retinoic acid (RA), is the form of vitamin A stored in the body. RA is what is called a paracrine, perhaps even an intracrine hormone regulator. That means it turns hormone metabolism on or off in the cells within its immediate vicinity (paracrine) or within its own cell (intracrine). This is compared to endocrine control of hormone metabolism – where hormones and the factors that regulate hormone synthesis and metabolism travel vast distances through the blood to reach their targets tissues (the hypothalamus-pituitary – ovarian system is an example of endocrine regulation) or autocrine where the hormone leaves its own cell only to turn around and bind to a receptor on that cell. In contrast, retinoic acid stays close to home and regulates local cell behavior, both internally and proximally. The vitamin A deficiency leading to fibroids or endometriosis represents a cell and tissue level disruption of the retinoic acid pathway that in turn interrupts the normal cell cycle (differentiation, proliferation, and apoptosis -cell death) and elicits all sorts of problems from decreased estrogen metabolism (too much estradiol at the cells), to cell overgrowth, or more specifically, not enough cell death where needed. The results include aberrant cell growth as in fibroids, tumors, and endometriosis.

Retinoic Acid, Progesterone and Estrogen Metabolism

With many women’s health conditions too much estradiol at the tissue level is at the root. Estradiol is an excitatory hormone that tells our cells to go forth and prosper. Progesterone, depending upon the tissue and the relative values of each circulating hormone can work synergistically to enhance estradiol’s actions or it can shut it down entirely via the upregulation of a specific estradiol metabolizing enzyme called 17 beta-hydroxysteroid dehydrogenase type 2  (17B -HSD2).  When these enzyme levels are high, more estradiol is converted to estrone. Since estrone is a less potent estrogen than estradiol, metabolism of estradiol to estrone somewhat inactivates the estrogen and slows cell proliferation. When the enzyme levels are low, more estradiol remains, and cell growth is enhanced.  Vitamin A or retinoic acid mediates the progesterone-dependent activation of this enzyme, effectively regulating estradiol concentrations locally. Too little retinoic acid or a disrupted retinoic acid pathway and estradiol is not converted to estrone – e.g. it is not inactivated. Cell proliferation dominates, while normal cell death or apoptosis is reduced. Fibroids, tumors, or endometriosis ensue.

What Causes Low Retinoic Acid or Reduced Functioning?

Vitamin A is derived entirely from diet. Foods high in vitamin A include brightly colored vegetables, dark leafy greens, carrots, pumpkin, sweet potatoes, bell peppers, and fatty fish oils, like cod liver oil and organ tissues like the liver. Meat and dairy also have high concentrations of vitamin A. Diets high in processed food do not contain sufficient vitamin A to maintain the proper cell cycle balance and so we get too much proliferation and too little apoptosis. Tissues grow and grow and do not die.

Alcohol intake reduces the body’s ability to metabolize retinoic acid because alcohol and the retinoic acid pathway use the same enzymes – alcohol dehydrogenase (ADH1) and aldehyde dehydrogenase (ALDH1) for metabolism. Alcohol competes for the enzyme and so vitamin A from diet cannot be converted to the usable retinoic acid.

Can Toxins Disrupt the Vitamin A Pathway?

Yes, but here is where it gets complicated. Environmental toxins like glyphosate used in common weed killers such as Round-up have a complex relationship with the vitamin A pathway and hormone metabolism. These herbicides and many pesticides are endocrine disruptors, meaning they disrupt ‘normal’ hormone metabolism, often towards a hyper-estrogenic state. Similarly, plastics like BPA and a host of industrial chemicals are also endocrine disruptors that move us towards hyper-estrogenism – a key component of fibroid and endometriosis.

Glysophate activates an enzyme called retinaldehyde dehydrogenase which increases retinoic acid synthesis. This is argued to be the mechanism by which environmental exposures during pregnancy cause birth defects. However, glyphosate also inhibits vitamin A metabolism by a similar mechanism as alcohol, by competing for ADH1 availability, thereby having the ability to reduce vitamin A synthesis. Glyphosate also increases aromatase activity (the enzyme that converts testosterone to estradiol), creating a hyper-estrogenic state and depending upon the time course and the exposure concentration, completely wipes out aromatase activity. So like any true hormone system, that uses a complex chain of compensatory reactions to maintain homeostasis, the reactions to environmental toxins are complicated and non-linear. Nevertheless, they warrant attention, particularly when one is suffering from a condition affected by the environmental toxin in question.

Managing Vitamin A Levels

To determine if you are vitamin A deficient, seek out a lab that specializes in micronutrient testing. The recommended daily values of vitamin A can be found in the Dietary Supplement Fact Sheet.

Vitamin A is a fat-soluble vitamin, meaning that it will be stored in fat, and toxicity from too much vitamin A is possible. It is rare, but nevertheless, if supplementing, vitamin A levels should be monitored by micronutrient testing.

My Two Cents

Much of the research presented here linking local vitamin A deficiencies with endometriotic, fibroid, and cancer growth has not crossed over into clinical care. Moreover, it is complex and far from settled. Except for cancer trials, mostly in males and mostly with oral supplementation, the research regarding dietary vitamin A is limited and mixed. However, I think a local application of an absorbable form of vitamin A or retinoic acid should be investigated for the treatment of endometriotic and fibroid growth in women. Similarly, dietary supplementation within acceptable levels and changes combined with environmental ‘cleaning’ may be of use, if only to improve the overall health status of women currently suffering from fibroids or endometriosis.

Postscript: This article was published previously in August 2013. 

Photo by Tamanna Rumee on Unsplash.