A new study has demonstrated glyphosate’s ability to interfere with gut biota and underlying metabolic functions. The conclusion that glyphosate is a major factor in nearly all modern chronic diseases is inescapable. Here’s how those disturbed metabolic functions are associated with conditions like autism, cancer, and Alzheimer’s disease.

by Heidi Stevenson

This is Part 2 of a three-part series:

Part 1, Glyphosate: Chronic Disease Degeneration
Part 2, Glyphosate: Disease Creator
Part 3, Glyphosate: A Trajectory of Human Misery

With the damage done to primary cellular function, it should not be a surprise that glyphosate is implicated in the modern health plague, chronic diseases. It seems likely that virtually all are, at the least, exacerbated by it. Following are discussions of a wide array of these condtions and likely associations with glyphosate.

Please note that the interrelationships among glyphosate’s effects are very complex. Therefore, as much as possible, health conditions are arranged so that associations with glyphosate’s effects can be best understood and repetition is minimized. Nonetheless, some points may seem a bit out of context, while others may appear to be repetitious—though I’ve attempted to reduce such irritations. It should also be noted that this is not a complete listing of diseases and conditions discussed by Samsel & Seneff’s report.

Most important of all, though, are the chilling effects that glyphosate and its symbiotic partner, Roundup, have on the human body.

Cholesterol and Vitamin D Deficiencies

Synthesis and breakdown of both cholesterol and vitamin D (which refers solely to vitamin D3 here) are affected by glyphosate’s effects on CYP enzymes. Though there’s certainly an association between sun avoidance and sunscreen use, it’s likely that part of this epidemic is associated with glyphosate.

The importance of glyphosate’s interference in synthesis of cholesterol cannot be overestimated. Cholesterol provides a wide array of functions throughout the body:

• Cholesterol is a precursor for synthesis of vitamin D, bile acids, and every steroid.
• Cholesterol is required to build and maintain membranes and membrane fluidity.
• Cholesterol is involved in cellular transport.
• Cholesterol is involved in cell signalling.
• Cholesterol is involved in nerve conduction.
• Cholesterol is part of the myelin sheath around nerves.
• Cholesterol may act as an antioxident.

It’s not difficult to see that glyphosate’s interruption in cholesterol synthesis can have domino effects throughout the body.

Obesity

Obesity is at the base of much modern ill health. However, a strong argument can be made that the obesity epidemic itself is caused by Agribusiness use of glyphosate. It’s already been proposed that synthetic chemicals in general are behind the obesity epidemic. However, high levels of them are better noted for causing anorexia. Samsel & Seneff, though, argue that glyphosate can be behind both problems.

Tryptophan supply is curtailed by glyphosate. Serotonin is derived from tryptophan. Therefore, it follows that depletion of tryptophan leads to deficiency in serotonin.

But the tryptophan tale is even worse. When inflammation is present, after glyphosate redirects production to flavonoids, the limited tryptophan that is produced faces another glyphosate-induced problem. Gut inflammation causes tryptophan to be converted to kynurenine by lymphoid tissues at the inflamed site. So it’s engulfed by two types of white blood cells, macrophages and neutrophils, for self-protection. Immune cells hoard kynurenine so they can defend themselves against DNA damage.

Although the popular press ties serotonin only to depression, it’s highly significant in obesity. It is the hormone that indicates satiety so that hunger stops. Confirmation of the tryptophan-serotonin connection is confirmed by studies documenting low tryptophan and serotonin levels in obese people.

Sadly, trytophan levels remain low after weight reduction, so it should not be surprising that maintaining weight loss can be so difficult. Obesity is a genuinely pathological condition—a genuine disease, not a character defect.

In an experiment, a strain of endotoxin-producing bacteria was transferred from a human gut to the guts of mice with neither beneficial nor harmful bacteria. During a 16-week period, these mice became obese on a high-fat diet. Lest you think that it was the high-fat aspect that made them obese, the same diet was also fed to normal mice, which didn’t gain weight.

Glyphosate changes the balance of gut bacteria to endotoxin-producers. That fact, in conjunction with the fact that the obesity epidemic has increased along with glyphosate’s increased use, provides a strong prima facie case for glyphosate as a factor in obesity. This same trajectory of obesity has also happened in conjunction with glyphosate introduction in other areas of the world. South Africa, which started using glyphosate in the 1970s, along with Roundup Ready genetically modified crops, has the highest obesity rate in Africa.

Inflammatory Bowel Disease

C. difficile is a known causative agent of inflammatory bowel diseases (IBDs), including Crohn’s disease and ulcerative colitis. The incidence of C. difficile has increased a great deal in North America over the last few years. A study in Wisconsin showed that, although C. difficile was almost unknown in people with IBDs prior to 2003, it was found in 3% of cases in 2003, 7% in 2004, and 16% in 2005.

It is likely that glyphosate is fueling the growth in people with IBDs infected with C. difficile.

Glyphosate can also lead to IBD through its disturbances of tryptophan production. Normally, tryptophan is taken up by the liver primarily for production of adenosine triphosphate (ATP), which is the chemical produced by cells for energy. Any that isn’t taken up circulates in the blood, making it available to cross the blood-brain barrier (BBB) into the brain, where it’s used to make serotonin and melatonin. As already noted, low serotonin levels can lead to obesity.

Obesity does provide some limited protection against inflammatory disease in the gut. There are two factors providing such protection. One is that adipose (fat storing) tissues can store endotoxin produced by gut bacteria, so the lining is spared inflammatory damage. The other reason may be even more significant. Adipose tissue can supply sulphated steroids.

Unfortunately, though, obesity’s protection against inflammation can be overcome by the disturbance in tryptophan creation and processing. The process is not yet well understood. However, experiments on mice have shown the protective effect of obesity does break down, leading to severe inflammatory bowel disease, bleeding, and diarrhea.

Anorexia/Cachexia

The term anorexia nervosa in this study is better understood to mean simply anorexia, which does not involve the psychological condition of refusing to eat. Anorexia, in this context, refers to an inability to eat instead of refusal, and is more closely related to cachexia, which refers to weakness and wasting of the body. It is an end stage of much disease, including tuberculosis, cancer, and aids.

A typical aspect of IBS is weight loss that results from loss of ability to transport nutrients across a damaged gut barrier. Thus, the processes that can lead to obesity are, paradoxically, the same ones that, when taken to greater extremes, can also lead to anorexia and cachexia.

Glyphosate triggers inflammation in a variety of ways, including tumor necrosis factor α (TNF-α), which promotes muscle breakdown, thus likely being a factor in the cachexia of some chronic diseases.

Autism

It’s now well accepted that gut disease is associated with autism.

As noted earlier, glyphosate’s interference with the shikimate pathway results in overactivity of the enzyme PAL, which leads to excessive ammonia, which plays a toxic role in autistic brains.

The synthesis of ammonia is a byproduct of anaerobic fermentation, and anaerobic Clostridia bacteria are found in excess in the feces of children with autism. In general, by-products of anaerobic bacteria, which include phenols, amines, ammonia, and hydrogen sulphide, are toxic to the bowel.

Hepatic encephalitis—confusion, personality changes, reduced consciousness, and coma resulting from liver failure—is related to autism. The connection is ammonia. Impaired liver function prevents detoxification of ammonia, leading to symptoms of both autism and hepatic encephalitis.

Reduction of serotonin in the brain, which is indirectly caused by glyphosate’s redirection of tryptophan synthesis into flavonoids, is associated with autism:

• One study comparing 40 autistic children with normal controls found that 35% of the autistic children had a far lower serum ratio of tryptophan to large neutral amino acids.
•  Inadequate dietary tryptophan is known to exacerbate autistic children’s anxiety and repetitive behaviors.
• Mice genetically designed with a defective gene that reduces availability of serotonin in the brain exhibited autistic-like behaviors.

Methylation impairment is seen in both autism and Alzheimer’s disease. It’s caused by an inadequate supply of methionine. An experiment on carrot cell lines demonstrated several pathologies resulting from glyphosate exposure. They were short of phenylalanine, tryptophan, and tyrosine. On top of that, levels of three other amino acids, serine, glycine, and methionine, are cut by 50-65 percent.

Glyphosate interferes with synthesis of methionine, which is necessary for methylation, clearly indicating a link between glyphosate and both autism and Alzheimer’s disease.

Alzheimer’s Disease

Ammonia, which is synthesized by gut bacteria as a result of glyphosate, plays a toxic role in Alzheimer brains.

Glyphosate fuels the growth of antibiotic-resistant Pseudomonas, which breaks it down into safe chemicals. Unfortunately, a byproduct of the process is formaldehyde, which can induce amyloid-like misfolding of proteins in the brain, a key trait of Alzheimer’s disease.

Lysosomes, structures in cells that break down waste materials, depend on sulphate—but glyphosate disrupts sulphate transfer. Liposomal dysfunction is a major factor in Alzheimer’s disease.

Excess ammonia, already demonstrated to be a problem caused by glyphosate, is a known issue in Alzheimer’s disease.

Glyphosate is a potent chelator of divalent cations, and zinc is one of them. Therefore, it’s likely that zinc is chelated and removed from the system, leading to zinc deficiency, which is noted for causing diarrhea and increasing risk of pneumonia and malaria. Glyphosate also reduces the number of friendly gut bacteria that help absorption of minerals, including iron and zinc.

Zinc is used in the brain in the process of degrading amyloid-β plaques. However, as a result of glyphosate, zinc can be in short order, so these plaques don’t get removed. The result is continued buildup of Alzheimer’s characteristic plaques, thus worsening, or possibly even causing, the condition.

Deficiencies of zinc and copper have been noted as likely factors in Alzheimer’s disease. A South Africa study found that supplementing zinc in Alzheimer’s patients known to be low in zinc did not help. However, when vitamins D and A were also supplemented at the same time, improvements were noted. This ties back to glyphosate’s impairment of CYP enzymes, which are required to synthesize vitamin D.

Parkinson’s Disease

Dopamine is synthesized from tyrosine, which is synthesized from phenylalanine—and phenyalanine is inhibited by glyphosate. Reducing tyrosine and phenylalanine in the diet reduces dopamine concentrations in the brain, so it’s reasonable to assume that reduction of tyrosine by glyphosate’s inhibition of phenylalanine will result in reduction of dopamine.

Parkinson’s disease is characterized by impaired dopamine signaling in the brain, and it has also been associated with several pesticides. Though glyphosate has not been named as one, that may be a result of preconceptions about its safety.

Sulphate deficiency has been noted in the brains of people with Parkinson’s disease, as well as Alzheimer’s and amytrophic lateral sclerosis, which though generally considered hereditary, has been increasing over the last few years. Thus, there is good reason to suspect glyphosate’s complicity in all three of these devastating brain conditions.

Multiple Sclerosis

Molecular mimicry is a theory of some autoimmune disorders. It suggests that abnormal entry into the body of a molecule that is similar to ones found in the body can result in an immune response that identifies normal tissues for attack and destruction because of the resemblance.

Multiple sclerosis (MS) is a disease in which the myelin sheath around nerves is attacked and destroyed by the immune system. MS sufferers often have inflammatory bowel disease. A search of the scientific literature found matching mimics in gut bacteria. Coupled with glyphosate’s ability to cause gut inflammation and leaky gut syndrome, a case can be made that the increasing rate of MS is related to the herbicide.

Liver Disease

Fatty liver disease is a growing threat to health. Nonalcoholic fatty liver disease leads to cirrhosis and liver failure. Several glyphosate-related factors may be involved.

TNF-α and other cytokines, which are triggered by glyphosate, induce liver-damaging inflammation. TNF-α inhibits insulin signaling, which is a factor in metabolic syndrome. Cytokines can induce fibrosis and lipid overloading in the liver.

Of course, obesity is associated with liver disease, and glyphosate can induce obesity.

Sleep Disorders

Typtophan is a precursor of melatonin, which is excreted from the pineal gland, and it’s a major factor in sleep cycle regulation. Glysophate’s disruption of tryptophan production may be a factor in sleep disorders.

Fertility

Zinc, which has been shown in the discussion on Alzheimer’s disease to be diminished by glyphosate, is necessary for male reproduction.

Cholesterol sulphate is essential in fertilization, so glyphosate-induced CYP inhibition, which can interfere with cholesterol production, can interfere with fertilization, helping to explain falling fertility rates.

In 1978, Argentina’s birthrate peaked, and has been in decline since then, but the rate of decline accelerated in the last five years of the 20th century. Roundup Ready soybeans were introduced there in 1996 and spread at an unprecedented rate. Argentina is now the leading soybean producer in the world.

The second largest soybean producer is Brazil, where the fertility rate has dropped from more than 6 per woman to under 2. Like Argentina, in the mid-90s they took to to Roundup Ready soybeans with the associated use of glyphosate. A plague of glyphosate-resistant superweeds has developed, which has resulted in massively increased usage of the herbicide. Since starting to grow genetically modified crops, both a rapid decrease in the birth rate and increase in still births have been noted.

The birth rates in both western Europe and the US have declined for several years. While other factors are certainly at play, it seems probable that glyphosate is also a culprit.

Glyphosate has been shown to interfere with testosterone production. In men, the steroidogenic acute regulatory protein (StAR) is required in the process to synthesize the hormone testosterone. A study on a rat cell line found that very low doses of Roundup interfere with StAR function, and higher doses cause necrosis and apoptosis of rat testicular cells. StAR protein levels were reduced by 90 percent.

Aside from StAR, another enzyme called the side chain cleavage enzyme (P450scc) is required to produce steroids. The research just described also found that Roundup inhibits P450scc activity by 71%.

Interestingly, glyphosate alone did not have this effect. Samsel & Seneff surmise that it was a combination of glyphosate and surfactants acting in synergy that had the effect. Significantly, StAR and P450scc are involved in producing several hormones, not only testosterone. Therefore, Roundup is also likely to have adverse effects not only on fertility, but also on the adrenal glands, which produce the glucocorticoids and mineralocorticoids steroids.

An in vitro study on synthesis of progesterone in testicular Leydig cells compared the effects of several pesticides: Ammo, Banvel, Cotoran, Cyclone, Dual, Fusilade, and Roundup. Only Roundup had an effect, and that effect was significant. It reduced progesterone synthesis as much as 94% in a dose-dependent manner.

Birth Defects

Glyphosate is known to cross the placental barrier, and it has been associated with birth defects. A study of a farming population in Ontario, Canada showed a statistically significant increase in spontaneous late-term abortions associated with exposure to glyphosate at any time during pregnancy.

Glyphosate’s inhibition of CYP enzymes causes an increase in retinoic acid. African clawed frog and chick embryos were exposed to low doses of glyphosate, 1/5,000 of the standard. The result was frog embryos that developed into tadpoles with cranial deformities and chick embryos with microcephaly, abnormally small heads. These defects were traced back to an increase in retinoic acid.

Glyphosate leads to inflammation and inflammation leads to excess reactive oxygen species (ROS) and reactive nitrogen species (RNS). Both ROS and RNS can damage DNA during replication, thus disrupting embryo development.

Cell cycle checkpoints exist in the life cycle of cells to verify whether there is any DNA damage before allowing progression to the next stage. This is of great importance in mitosis (cell division) to assure that defects are not passed on. Sea urchins, a very simple form of animal life, are used to study mitosis. Cyclin dependent protein kinases (CDKs) help verify whether cells should progress past checkpoints. A live sea urchin study found that Roundup delays activation of a CDK by dephosphorylation of tyrosine. This indicates a means by which glyphosate can cause birth defects and stillbirths.

Preeclampsia, a life threatening condition of pregnancy, may be caused by inadequate sulphate supply, which is caused by glyphosate. Preeclampsia is becoming a much more common problem in pregnant women.

Cancer

The last thing that glyphosate is generally accused of causing is cancer. That, though, may be far from true. Glysophate’s association with breast cancer is implicated as a result of glyphosate-exposed mice that developed massive breast tumors in a recent study. Breast cancer has recently skyrocketed in the US, with one in three women now expected to develop it.

The fact is that professional pesticide operators who are exposed to glyphosate through their jobs have been found to suffer an increased risk of myeloma, bone marrow tumors known to be associated with disease-causing agents. Glyphosate causes chronic inflammation, which is known to damage DNA. Depleted tryptophan is also linked to DNA impairment.

Multiple myeloma accounts for 15% of all lymphatohematopoietic cancers (cancers of blood and lymph production) and 2% of all cancer deaths in the United States. Glyphosate’s ability to trigger obesity is a likely factor in myeloma incidents.

Impaired sulphation is suggested as a cause of breast cancer because it could lead to slower metabolization of sex hormones, leading to increased breast density, which is associated with cancer. The CYP enzyme, CYP1A2, could be a factor as a result of inhibition by glyphosate, as well as its interference with sulphate transport.

Obesity is associated with breast cancer, which again leads to culpability of glyphosate. Inflammation has also been linked to it, so glyphosate’s ability to trigger inflammation implicates it again.

With so many aspects of glyphosate’s effects coming into play, it certainly shouldn’t be surprising that we’re seeing enormous increases in cancer rates.

Part 1, Glyphosate: Chronic Disease Degeneration
Part 2, Glyphosate: Disease Creator
Part 3, Glyphosate: A Trajectory of Human Misery

Source:

Samsel, Anthony; Seneff, Stephanie. 2013. “Glyphosate’s Suppression of Cytochrome P450 Enzymes and Amino Acid Biosynthesis by the Gut Microbiome: Pathways to Modern Diseases.” Entropy 15, no. 4: 1416-1463; doi:10.3390/e15041416