According to Monsanto, producer of Roundup®, the most popular herbicide used on the planet, the product is nearly nontoxic for humans. The usage of Roundup to kill weeds has skyrocketed around the world since the year 2000, in part because it went off patent that year, but also because of the enormous increase (especially in the U.S.) in the appearance of “Roundup-Ready” GMO crops.4
Glyphosate, the active ingredient in Roundup, kills weeds by interfering with what is called the shikimate pathway. This pathway is essential in plants for the synthesis of a class of amino acids called the “aromatics.” But this pathway is nonexistent in any mammalian cell. By simple logic, the fact that our cells don’t have this pathway means that glyphosate cannot harm us. Is there a fallacy in this argument?
GLYPHOSATE CONNECTION TO DISEASE
While mammals don’t possess the shikimate pathway, all of the microbes that take up residence in our digestive tract do have this pathway, and exposure to glyphosate, the active ingredient in Roundup, will cause them serious stress as a consequence. Studies have shown that glyphosate disrupts the gut bacteria in chickens, 54 cows,29 and pigs,10 causing inflammation in the gut along with an overgrowth of pathogenic forms and concurrent loss of beneficial bacteria. It is now becoming apparent that our gut bacteria, which outnumber our own cells by a factor of ten to one, play many important roles in supplying nutrients and protecting us from toxins.19 There’s also an intricate connection between the gut and the brain, such that an unhealthy digestive system translates into pathologies in the brain.35
Together with Anthony Samsel, I recently published a paper arguing that Roundup® could plausibly be the most important factor in the observed increase in a number of diseases and conditions like obesity and autism over the past two decades in the U.S.47 Despite spending nearly two and a half times as much on health care as our peer nations,36 the U.S. lags behind many of these other nations in basic metrics like infant mortality and life expectancy.34 The most recent figures for infant mortality place the U.S. at number forty-six, behind Cuba and Guam. Clearly we are doing something wrong, and our wholesale embrace of GMOs is an obvious candidate.
Ninety percent of the GMO crops (GMO corn, soy, cotton, sugar beets, and canola) are engineered to be “Roundup Ready,” which means that they can be sprayed with Roundup and they will happily soak it up into their tissues. The practice of “desiccating” crops like wheat and sugar cane just before the harvest by spraying them with Roundup is also becoming more and more popular as a way to reduce the amount of vegetation that needs to be cleared in preparation for planting next year’s crop. These two changes in agricultural practices almost certainly mean that Roundup is entering our food supply in record amounts. And most homeowners are likely careless in their use of Roundup to fight weeds on the lawn, due to a misconception that it is nearly nontoxic. A recent study involved sampling glyphosate in the urine of city-dwellers in eighteen European countries.23 Measurable amounts of glyphosate were found in 44 percent of these people, despite the fact that Europe has a much more conservative view towards GMOs than does the U.S.
So, why is the shikimate pathway so important? Plants and microbes use the shikimate pathway to produce the aromatic amino acids, tryptophan, tyrosine and phenylalanine.22 Because they don’t have this pathway, mammals can’t produce these essential nutrients, and therefore we depend on plants and microbes to provide them for us. So it is logical that glyphosate, by interfering with this pathway, would lead to a deficiency in these nutrients. Tryptophan is the sole precursor to serotonin, and serotonin deficiency is implicated in a litany of diseases and conditions that are prevalent today, including autism, obesity, Alzheimer’s disease, depression, suicide, and homicidal behavior.47 Serotonin is an appetite suppressant8 so it’s hard not to overeat when it is in short supply. If you are disciplined to resist these urges, then you run the risk of depression and Alzheimer’s disease, or autism in your children. Serotonin is the precursor to melatonin, the neurotransmitter that regulates the wake-sleep cycle, and melatonin deficiency is also implicated in autism.2,39 Tyrosine is the precursor to dopamine,41 and impaired dopamine supply is the key defect associated with Parkinson’s disease. Glyphosate activates an enzyme called phenylalanine ammonia lyase (PAL), which breaks down phenylalanine and releases ammonia as a by-product.33 Excess ammonia in the blood stream can trigger a cascade leading to encephalitis and seizures.30
AUTISM EPIDEMIC AND ROUNDUP USAGE
Autism is a condition characterized by cognitive and social deficits, which has been alarmingly on the rise in the last decade. Some children seem to be born with the condition, while others develop normally up to a certain point and then begin regressing into autism.55 Autism is associated with two comorbidities that may yield hints as to its underlying etiology: disrupted gut bacteria and impaired sulfur metabolism.57 A characteristic feature of children with autism is an overgrowth of pathogenic bacteria in the gut, which can lead to neurological defects arising from exposure of the brain to toxins produced by these bacteria.24,56,58
I have been studying autism for many years, trying to understand the environmental factors that might be causal in the current epidemic in this complex condition. Autism used to be rare, affecting one in ten thousand children. The latest numbers put out by the CDC in March 2013, show one in fifty.6 This is an alarming number, and, what is even more alarming is how quickly the number has been rising in recent years. Figure 1 shows a plot of autism rates over the past twenty years alongside a plot of total Roundup usage on corn and soy in the U.S., the two core crops of the processed food industry. It is remarkable how well these two plots line up. The Pearson correlation coefficient is 0.985 (1.0 would be perfect alignment). This plot also demonstrates the alarming increases in glyphosate application that have followed the insertion of the Roundup Ready GMO bacterial gene into the seeds.
Correlation does not necessarily mean causation, but if you can explain logically how A might lead to B, then the likelihood of causation goes way up. It took a long time before I thought of glyphosate as a possible factor in autism, probably because I believed Monsanto’s claims that it is relatively nontoxic. This all changed when I heard a lecture given by Professor Don Huber at the 2012 Indianapolis WAPF chapter conference. His explanation of the effects of glyphosate on biological systems filled in important gaps in the theory I was developing to explain the underlying pathologies in autism.
Most striking, of course, is the disruption of gut bacteria, something that Natasha Campbell McBride has been speaking about for many years at WAPF conferences and in her books.9 A recent study involving nearly three thousand children with autism spectrum disorder (ASD) found that a quarter of them suffered from chronic GI problems like constipation, diarrhea, and bloating.37 This subset had significantly higher rates of both anxiety and over-sensitivity to sensory stimulation.
AUTISM, PATHOGENS, AND SULFATE
As Anthony Samsel and I gathered information about glyphosate, we began to see a striking pattern linking glyphosate to specific pathogens like Clostridia difficile (C. diff ) and Pseudomonas aeruginosa, which are currently causing a major crisis in hospitals in the U.S. and elsewhere due to their increased prevalence and multiple antibiotic resistance.12, 28 Pseudomonas is among the very few bacterial forms that can metabolize glyphosate. A breakdown product is formaldehyde, a known carcinogen and neurotoxin.43 Formaldehyde may however be preferred over glyphosate as the lesser of two evils. So we surmise that this bacterium is allowed to survive in the gut precisely because it can dispose of glyphosate, but then you have to suffer the consequences of formaldehyde toxicity.
Figure 1: Autism rates in the U.S. school system and of the amount of glyphosate used on corn and soy acreage in the U.S. Figure generously provided by Nancy Swanson: www.examiner.com/article/data-show-correlations-between-increase-neurological-diseases-and-gmos.
Explaining the overgrowth of C. diff requires a digression. My extensive research has led me to believe that systemic sulfate deficiency may be the most important factor in many of the health issues facing us today.21, 48 Certainly it is a factor in autism. Autistic children have been found to have only one third as much free sulfate in the blood as their normal peers.57 The essential sulfur-containing amino acid, methionine, is a source of both sulfur and methyl groups to the body, both of which are crucial for normal brain development.17,21,26 Heparan sulfate is a sulfated molecule derived from sugar which plays remarkable roles in regulating ion and nutrient transport as well as molecular signaling cascades, for most of the body’s cells.5 It’s also crucial in brain development of the fetus.12 A loss of heparan sulfate in the gut lining results in protein leaks into the blood,7 which can then induce gluten and casein intolerance, which are common among autistic children. Mice engineered to be impaired in heparan sulfate synthesis in the brain exhibit all of the features of autism.27
C. diff produces a toxic phenol called p- Cresol, which has been identified as a factor present in the urine in association with autism.1 In fact, as we gathered more data on glyphosate and its effects on plants, we noticed that phenolic compounds, more generally, are produced by both plants and microbes upon exposure to glyphosate, along with the over-production of other compounds with carbon rings called flavonoids. You may be aware that flavonoids in coffee, tea, and brightly colored vegetables and polyphenolic compounds like resveratrol and curcumin are considered to be beneficial for their antioxidant properties. I believe that their beneficial effect may actually be due to their ability to safely transport sulfate, a feature they all possess, and a feature they share with the toxic phenols such as those produced by the pathogen C. diff.
SULFATE TRANSPORT AND CARBON RINGS
Extensive prior research has led me to a hypothesis that sulfate transport in the blood poses a special challenge to the body, and that this may be the main reason why there is a plethora of biologically interesting molecules that are typically sulfated when they are transported in the blood, as well as a huge number of sulfotransferases that can attach these sulfates15 and transfer them from one molecule to another. I suspect that one of the important but heretofore overlooked consequences is that they transport sulfate from a source site in the body such as the gut to a delivery site such as the liver, the pancreas, or the brain, and that this is a crucial part of their function in biology.
Two major classes of these biologically active sulfate-transporting molecules are the sterols (cholesterol, vitamin D3, DHEA, estrone) and the monoamine neurotransmitters (dopamine, serotonin, norepinephrine). All of these molecules have the interesting property that their biological effects are inactivated when they are sulfated. This is of course beneficial so that they are inert during transport, an attractive feature. But I believe that, more important than this, is the fact that the sulfate that is attached to these molecules is also inactive while being transported. And it might even be the case that one of the most important functions these molecules perform is to transport sulfate! All of these molecules share the property that the sulfate anion is attached to a carbon ring, and the ring distributes the negative charge on the sulfate, changing its biophysical properties in important ways.
What are these biophysical properties? Sulfate is a member of a class of anions called anionic kosmotropes. Other biologically important members of this class are phosphates and carbonates, both of which are also pervasive in biological systems. These three anions are essential for maintaining the water in the immediate vicinity of the cells’ plasma membranes in the tissues and of particles suspended in the blood in a structured almost crystal-like “liquid ice” configuration, creating a protective “exclusion zone” (the glycocalyx).45 Gelatin desserts are a familiar version of this structured water—it’s mainly carbonate that structures the water in this case. Water is by far the most common molecule in our bodies, yet this is hard to imagine given how firm our bodies are. With 99 percent of our molecules being water, it’s surprising that we don’t just collapse into a puddle! Pollack believes that the main reason our tissues are not liquid is that nearly all the water is maintained in a gelled state by these kosmotropes.45
However, the one big exception to this model is the blood. The blood that courses through our veins is definitely a liquid, and if it were to become gelled it would lead to a no-flow situation and a major catastrophe. This, to me, is the key reason why all these biologically active molecules travel through the blood stream in a sulfated form.
Figure 2: The molecular structure of glyphosate.
Now let’s consider what happens when glyphosate enters the picture. Glyphosate is almost certainly an anionic kosmotrope as well. As shown in Figure 2, it contains a carbonyl group and a phosphonyl group, and it doesn’t have any carbon rings. When a person takes an overdose of glyphosate in an attempt to commit suicide, a blood pathology called “disseminated intravascular coagulation” (DIC) ensues59 and this can easily be fatal. So glyphosate causes an increase in blood viscosity and competes with free sulfate, which also has this effect, for a limited load capacity. This problem would be especially acute in the hepatic portal vein carrying nutrients from the gut to the liver. The liver desperately depends on sulfate to make cholesterol sulfate, which is essential in the synthesis of bile acids, and bile acids in turn are essential for digesting fats. Cholesterol sulfate also plays an important role in the outer shell of LDL and HDL particles, to protect them from reactive agents in the blood (e.g., oxidizing and glycating agents). The “small dense LDL particles” that are most damaging in heart disease arise because of oxidation and glycation damage that disrupts the lock-and-key mechanism during reuptake in the liver after they have delivered their goods, and therefore prevents them from being recycled. So, insufficient sulfate leads to LDL and HDL particles that are more susceptible to such damage, a key factor in heart disease.
In addition to “jamming the waterways” in blood vessels, glyphosate also interferes with the supply of sulfate carrier molecules that depend on the shikimate pathway. Dopamine, serotonin and norepinephrine are all derived from the aromatic amino acids whose synthesis is blocked by glyphosate. Worse than this, glyphosate also interferes with a class of enzymes called cytochrome P450 enzymes (CYP enzymes for short),31 which play many different roles in the body, especially in the liver and the reproductive system.42 Certain members of this class are essential for bile acid synthesis. These enzymes are also involved in cholesterol homeostasis and vitamin D activation in the liver, whose disruption will further interfere with sulfate transport, among other problems.
In our recent paper on glyphosate47 we argued that the toxic phenolic compounds like p-Cresol that are produced by pathogenic bacteria like C. diff actually perform an important service by transporting sulfate from the gut to the liver and pancreas. According to this hypothesis, toxic phenolic compounds are produced because the sterols and monoamine neurotransmitters are impaired in their ability to perform this much-needed service. However, once the phenol drops off its sulfate, it becomes a highly reactive molecule, capable of doing damage to the lipids and DNA in the liver and pancreas, as well as in the gut, as a single phenol is likely cycled around again and again to deliver multiple sulfates to the liver and pancreas, and, whenever it’s not sulfated, it’s toxic.
In this paper, I have developed an argument that, contrary to Monsanto’s assurances, glyphosate is not a safe chemical for human exposure. On the contrary, glyphosate’s well established effects in biological systems can plausibly explain many of the diseases and conditions we are experiencing today in epidemic form. These include autism, Alzheimer’s, obesity, depression, excessive violence, colitis, inflammatory bowel disease, heart disease and diabetes. I now believe that, while several environmental toxicants, including mercury, aluminum, lead, fluoride, nitrates, insecticides and fungicides, are likely implicated in autism, glyphosate may be the single most important factor in the autism epidemic. I believe this not only because glyphosate usage has gone up in step with autism rates, but also because many of the pathologies associated with autism can be explained through glyphosate’s disruptive mechanisms.
I also would argue that Alzheimer’s disease arises from similar pathologies as does autism, and it might be characterized as “autism for the elderly.” Therefore, its recent alarming increases may also be due predominantly to glyphosate.
Glyphosate can also easily explain the obesity epidemic and depression through its disruption of the supply of tryptophan, the sole precursor to serotonin. I have shown how glyphosate disrupts both sulfate synthesis and sulfate transport, and my research has led me to believe that impaired sulfate supply to all the tissues is a common underlying pathology in most modern diseases.
The best way to minimize glyphosate exposure is to adhere strictly to a completely organic diet. Most important is to avoid all the Roundup-Ready GMO crops: corn, soy, sugar beets, canola oil, and cottonseed oil, as well as wheat and sugar cane, due to desiccation practices. Any use of Roundup to kill weeds in lawn maintenance should be abandoned.
OTHER HEALTH TROUBLES RELATED TO GLYPHOSATE
As if it weren’t enough already that glyphosate causes an overgrowth of pathogenic bacteria in the gut, interferes with the supply of critical neurotransmitters to the brain and nervous system, and likely disrupts vitamin D activation, bile acid synthesis, cholesterol homeostasis, and sulfate synthesis and transport, there are several other ways in which glyphosate could do harm. Here I will touch upon four topics: endocrine disruption, liver damage, abdominal obesity, and breast cancer. Additional topics are discussed in our original paper.47 For example, glyphosate also chelates important micronutrients like zinc and cobalt.14
ENDOCRINE DISRUPTION: Glyphosate is an established endocrine disruptor16 and studies have shown it inhibits aromatase, a CYP enzyme that converts testosterone to estrogen.46 Aromatase is synthesized in the testes,32 and this may explain why autism is far more prevalent in males than in females. Autism is associated with aromatase deficiency, and some have attempted to explain autism as a “super male” syndrome on the basis of overproduction of testosterone and insufficient estrogen.3 Retinoic acid is intimately involved in embryonic development. Low doses of glyphosate caused many deformities in frog and chick embryos44 due to overexpression of retinoic acid. The enzyme that breaks down retinoic acid is a CYP enzyme, so its disruption would explain glyphosate’s effects. One can expect similar effects in humans. Fertility rates have been declining sharply in many countries where glyphosate usage is increasing. Most striking are countries in South America such as Argentina and Brazil. Women in Brazil used to have six children on average, but now the fertility rate is less than that of the U.S. Argentina’s fertility rate has been declining ever since 1978. Both Brazil and Argentina produce a significant amount of the world’s supply of soybeans—most of which are engineered to be “Roundup® Ready.” While it’s difficult to sort out the role played by social pressure, it is possible that glyphosate’s disruption of aromatase and retinoic acid could be a factor in declining fertility rates.
LIVER DAMAGE : According to our hypothesis, phenols are sulfated in the gut and transported through the hepatic portal vein to the liver in this sulfated form. In the liver, the sulfate is detached and most likely transferred to cholesterol to produce bile acids. Once freed from sulfate, phenolic compounds become fat-soluble and highly reactive, and they can readily cross cell membranes and do damage to cell contents. Phenols have been shown to cause damage to the kidneys, liver, muscles, and eyes.40 They induce the formation of organic radicals and reactive oxygen species that can damage lipids and DNA, which explains their ability to induce cancer. However, a much worse problem in the liver is the disruption of CYP enzymes, because the liver contains many CYP enzymes that are involved in detoxifying xenobiotics—both drugs and environmental toxins. With impaired CYP function, these other toxic chemicals linger longer, causing much more damage than they would otherwise. In fact, an inability to break down acetaminophen (Tylenol) has been proposed as a possible factor in autism.49 This can easily be explained by glyphosate’s potential disruption of the CYP enzyme that detoxifies Tylenol. The inflammation associated with the overgrowth of pathogens in the gut leads to the production of cytokines like TNF-∂ by macrophages, brought in to keep the pathogens in check. Cytokines induce inflammation, which damages the gut, liver and pancreas. TNF-∂ has been identified as a key factor in fatty liver disease, which has emerged as a growing public health problem worldwide.11 In the extreme case, liver pathology develops into nonalcoholic steatohepatitis (NASH), which can lead to cirrhosis and liver failure.
ABDOMINAL OBESITY : It is easy to imagine a possible role for fat cells in protecting the liver from damage caused by the toxic phenols. Abdominal obesity can be viewed as providing a way station where sulfate can be transferred from one carrier molecule to another. The toxic phenols can thus deliver sulfate to fat cells in the belly, which then transfer it to a sterol to produce estrone sulfate, a well established “export” molecule from fat cells.52 Thus estrone then carries the sulfate to the liver, and the phenol never reaches the liver or the pancreas, where it could have damaged the DNA of cells with important roles. The liver and pancreas are never exposed to the toxic phenolic compound, and are therefore safeguarded from damage. Thus, abdominal obesity becomes a defense mechanism to deflect the phenols towards a tissue where damage is more forgivable, since the fat cells do not perform the kinds of critical metabolic roles that liver or pancreatic cells perform.
BREAST CANCER : One in eight women in the U.S. is now expected to develop breast cancer at some point in their lives. A study on rats that were administered food that had been treated with Roundup throughout their lives showed an alarming incidence of massive mammary tumors in the female rats50 along with liver and kidney disease in the males, and premature death for both males and females. After our paper was published, a study came out showing that glyphosate, even in trace amounts (parts per trillion) could induce breast cancer cells to proliferate; that is, it promotes tumor growth.53
GLYPHOSATE USAGE AND DISEASE RATES
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This article appeared in Wise Traditions in Food, Farming and the Healing Arts, the quarterly journal of the Weston A. Price Foundation, Fall 2013.