by Jeffrey Dach MD
The news media has been reporting the Zika virus as the cause of microcephaly. The story originated in a Monsanto chemical industry press release dated Feb 17, 2016 which was then copied over the news media. The Zika virus was discovered in Uganda in 1947, and there have been no reports of microcephaly in Uganda. A US news article says, according to Associated Press journalists who visited the Zika Forest in Uganda on Feb 1, 2016, local officials have no concern about the Zika virus.(24)
New England Journal Reports
A recent study published in the New England Journal of Medicine reported Zika Virus surveillance in Colombia.(80-81) Of 50 babies reported with microcephaly, only four (8 %) had laboratory evidence of congenital Zika virus infection on RT-PCR. The other 46 cases (92 %) were due to other causes.
Of 1850 pregnant women reported infected with Zika virus, no babies were born with microcephaly. The authors state: (80-81)
“maternal infection with the Zika virus during the third trimester of pregnancy is not linked to structural abnormalities in the fetus.”
Since 92% of microcephaly babies are not caused by maternal Zika virus, perhaps we should be looking for other preventable causes.
Dr Yaneer Bar-Yam reviewed this same data from the Colombia surveillance study After reviewing this data, Dr Yaneer Bar-Yam concluded in his own report entitled: “Is Zika the cause of Microcephaly?” that there is no direct link between zika virus and microcephaly, and he proposed pesticide exposure (pyriproxyfen) in the drinking water as an alternative explanation(99):
“This (data) would seem to rule out Zika as a cause of microcephaly. This gives a consistent interpretation that there is no direct link between Zika and microcephaly except for random co-occurrence.”….”An alternative cause of microcephaly in Brazil could be the pesticide pyriproxyfen, which is cross-reactive with retinoic acid, which causes microcephaly, and is being used in drinking water.”(99)
Dr Tiago Baptista Questions ZIka as Sole Cause of Microcephaly
Maternal viral infection with rubella or cytomegalovirus have been known to cause fetal malformation and fetal demise. There is no doubt that viral illness during pregnancy is best avoided.(47-55) However, Dr Tiago Baptista in a 2016 BMJ article questions “whether the surge in reported cases of microcephaly is entirely due to Zika virus infection“(55) He says:
“The risk of microcephaly after maternal infection is estimated at roughly one in 100 women… This is a relatively low risk compared with other causal infections such as cytomegalovirus.”(55)
A Distraction From the Real Cause- Exposure to Glyphosate Causes Microcephaly and other Congenital Anomalies
I suggest that the Zika virus is merely a distraction away from the real cause, agrichemical exposure from Monsanto’s Round-Up Herbicide, glyphosate, (1-4) Header image: Microcephaly (small head size) in newborn dated Jan. 30, 2016 in Bonito, Pernambuco state, Brazil. courtesy of AP Photo/Felipe Dana (11)
Left image: baby born with microcephaly. News media blames the Zika Virus courtesy of BBC News.
Dr Paganelli concludes: “(congenital malformations) “produced by Glyphosate Based Herbicides are mainly a consequence of the increase of endogenous retinoid activity. ” (8)
Dr Sylvia Lopez
“It is very well known that acute or chronic increase of retinoic acid (RA) levels leads to teratogenic effects during human pregnancy and in experimental models. The characteristic features displayed by Retinoic Acid embryopathy in humans include brain abnormalities such as microcephaly, microphtalmia, and impairment of hindbrain development; abnormal external and middle ears (microtia or anotia), mandibular and midfacial underdevelopment, and cleft palate.” (9) Note: Retinoic Acid is Vitamin A Derivative.
Upper Left image: Agricultural Worker spraying field with glyphosate courtesy of Indiana Public Media.
Dr Benitez-Leite reported 52 cases of malformations in babies born of women exposed to agricultural chemicals. The congenital malformations observed include anencephaly, microcephaly, facial defects, myelomeningocele, cleft palate, ear malformations, polydactily, syndactily all consistent with the well-known and expected syndrome caused by upregulation of the Retinoic Acid pathway.(10) Left image Monsanto’s Roundup herbicide contains glyphosate.
Upregulation of Retinoic Acid Pathway
A number of reports have linked arial spraying with the mosquito larvicide pyriproxyfen to birth defects such as microcephaly in the crop sprayed towns of Northeast Brazil.(106-108) Pyriproxyfen disrupts retinoic acid (vitramin A) signalling, a known mechanism for microcephaly (106-108) In 1995, Dr Kenneth Rothman reported in NEJM that High Vitamin A Intake causes birth defects. (109)
Increasing Anencephaly in Yakima Valley in Washington State
Over three years from 2010 to 2013, the Washington State Department of Health reported an unusual increase in anencephalic babies born in Yakima, Benton and Franklin counties, four times higher than the national average. (33-34)
Anencephaply, microcephaly and spina bifida are all related disorders of neural tube closure associated with maternal folate deficiency. Maternal folate supplementation is preventive. Maternal folate supplementation in Yakima was not at issue, as this was similar to the national average. Barbara Peterson, in Farm Wars, makes a compelling case for glyphosate exposure as the cause, since the Yakima river running through the affected counties had been heavily treated with glyphosate for weed control during that time period.(29) Left image Yakima River Washington State.
Glyphosate Disrupts Folate Metabolism
Glyphosate disruption of folate metabolism is discussed by Stephanie Seneff in her May 2016 article on Weston Price.(35) Glyphosate acts as an antibiotic, killing friendly bacteria by blocking the Shikimate pathway. These friendly bacterial are also involved in bacterial conversion of folic acid to methyl folate, its active form. Maternal methylfolate deficiency is associated with neural tube defects in the developing embryo.(85-87)
Glyphosate Disrupts Glycine Metabolism
Glyphosate is the amino acid glycine with an added phosphate group, so glyphosate may readily displace glycine in various biochemical reactions. Glyphosate disrupts glycine decarboxylase by displacing glycine as a substrate. In addition, glyphosate replaces glycine at insertion sites in amino acid chains during protein synthesis, producing defective enzymes (35). Glyphosate is basically the amino acid, glycine with a phosphate group added on to it.see chemical structure upper left image courtesy of ResarchGate.
Glyphosate is a Patented Antimicrobial, Anti-Folate Drug
Glyphosate is actually patented as an anti-microbial drug. (83,84) Glyphosate serves as an anti-folate agent working in synergy with other anti-folate drugs.(58,61) Other anti-folate drugs in common use include the urinary tract antibiotic, Bactrim (trimethoprim/sulfamethoxazole) the rheumatology drug, methotrexate, and the anti-seizure drug Dilantin (phentoin). Maternal exposure to anti-folate drugs such as methotrexate Bactrim and Dilantin increase risk of neural tube defects in the fetus up to six-fold. (85-87) Maternal folate supplementation has been shown to reduce incidence of fetal neural tube defects (NTD), and folic acid fortification in food supply was mandated in 1998. (85-87)(100-103)
Glyphosate Inhibits the Shikimate Pathway
Glyphosate’s known mode of action is inhibition of the shikimate pathway in plants, fungi, bacteria and parasites.(58) Glyphosate blocks the pathway which produces Folate, Ubiquinone (Co-Q10), Vitamin K, and the aromatic amino acids tryptophan, phenylalanine, and tyrosine.
Below image: Moms Across America Billboard Requesting Freedom from GMOs and Toxins. Courtesy of Organic Authority.
Government Regulators Deemed Glyphosate Safe for Humans
Government regulators deemed glyphosate safe for us humans because we lack the shikimate pathway. They forgot to consider that we humans depend on the shikimate pathway in plants and gut bacteria for our folate (vitamin B9), to prevents neural tube defects. If your lunch salad comes from an agricultural field treated with glyphosate which blocks the plant’s ability to synthesize folate, how much folate are you getting in your meal ? If you are ingesting glyphosate in your food, blocking your gut bacteria from synthesing folate, how soon will you be rendered folate deficient? Dr Bekaert says in 2008,
“Humans cannot synthesize folates (vitamin B9) and thus have to rely on plant food supplying these essential vitamins.“(104)
Dr Craig Roberts suggests that Glyphosate may serve as anti-folate, anti-parasitic drug ,He says:(58)
” it is likely that the shikimate pathway is important for supply of folate precursors in this parasite….inhibitors of EPSP synthase (such as glyphosate) can act in synergy with conventional antifolates and may be a useful addition to the agents used against apicomplexan parasites.”(58)
A quote from a University of Chicago Press Release 1998 (61) explains that Glyphosate blocks production of folate: “Effective new ways to inhibit parasites that cause malaria, toxoplasmosis and cryptosporidiosis” June 25, 1998.(61)
“Dr. McLeod’s team showed that glyphosate, …could block the production of folate, inhibiting parasite growth and survival. Glyphosate proved effective against malaria strains that were resistant to an anti-malarial medicine, pyrimethamine, which interrupts folate processing at a different point. To confirm the finding, they demonstrated that these folate-starved parasites could be rescued, in the test tube, by giving them folate.”(61)
Brazil Annual Pesticide Sales Surpasses the US
Left Image courtesy of Reuters. Brazil sales of herbicide (glyphosate) exceeds that of US.(81)
According to Paulo Prada in her 2015 article, Brazil has a huge appetite for pesticides and herbicides, surpassing annual sales in the US.(81)
Poalo Prado explains that in Northeast Brazil, irrigation canals were built, transforming previously arid land into fertile farm land. These open air irrigation canals are heavily contaminated with herbicides and pesticides liberally applied to the crop fields. Life is primitive for the agricultural workers who live without piped in water for their dwellings. The local workers use the open air irrigation canals for their drinking water, thus are heavily exposed to herbicide and pesticide runoff.
Above image open air irrigation canals in Brazil are source of drinking water for agricultural workers. These waterways are heavily contaminated with pesticide and herbicide runoff sprayed on nearby agricultural fields. Courtesy of Reuters. Fateful Harvest.
House Passes 1.1 Billion Zika Virus Bill. Methyl-Folate is Cheaper.
Instead of spending 1.1 Billion dollars on a “controversial” Zika Virus Bill, I have a better idea for prevention of microcephaly and neural tube defects. (90) Suppose we instead allocate 100 million dollars to give out free methyl-folate tablets to all pregnant women exposed to glyphosate here in the US, and in Brazil. That would solve the problem at a fraction of the cost, saving a Billion Dollars.(90)
53 Countries Have Mandatory Flour Fortification with Folate
Folate fortification of flour for prevention of neural tube defects (anencephaly, microcephaly, spina bifida etc.) is mandated in 53 countries. Fortification of flour with folic acid was mandated in the US in 1998, the most successful public health measure in history, with reduction of neural tube defects by 36%.(100-103) In 2009, Dr Oakley declared this success story a “modern miracle of epidemiology”.(103)
Study Blood Folate Levels in North East Brazil
Why not allocate research funds to study blood folate levels in women in Northeast Brazil at high risk for having babies with neural tube defects? This was done here in the US before and after starting folate fortification in 1998, showing reduction incidence of neural tube defects by 36%.(101) Folate deficiency (blood folate levels less than 3 ng/ml)) decreased from 21% to less than 1% of the population. (101)
In Australia, mandatory fortification of bread with folate and iodine was introduced in 2009, resulting in a 50-80 per cent reduction in neural tube defects in at-risk indigenous women and teenagers.(100-112)
Reducing Microcephaly in Brazil with Folate Fortification
Studies done in Brazil shows folate deficiency is severe, affecting 94% among the poor.(113) Folate fortification of flour in three south American countries (Brazil, Argentina, Chile) resulted in significant reduction in 52 different fetal anomalies including reduction in microcephaly and anencephaly.(114) Currently all South American countries except Venezuala have mandatory folate fortification legislation.(115) In populations using folate fortification there have been decreases in neural tube defects from 30-50%.(115)
How is Such an Error Possible ?
You might ask the obvious question, “how is such an error in thinking possible” that the government would waste a billion dollars on Zika instead of Folate Fortification? This is called CrimeStop or “Protective Stupidity“, aptly described in 1984 by George Orwell (91):
“The mind should develop a blind spot whenever a dangerous thought presented itself….Crimestop, they called it in Newspeak….the Party says the earth is flat’, ‘the party says that ice is heavier than water’—and trained himself in not seeing or not understanding the arguments that contradicted them.”
“Crimestop means the faculty of stopping short, as though by instinct, at the threshold of any dangerous thought. It includes the power of not grasping analogies, of failing to perceive logical errors, of misunderstanding the simplest arguments…”…”Crimestop, in short, means protective stupidity.”(91) Above Left Image courtesy of
Jan Blomqvist – I Don’t Think About You
Using Fear and Smear Tactics to Distract Attention from Monsanto
This article in the Huffington Post Feb 16 is typical of the Monsanto tactics to distract attention away from Roundup glyphosate as the cause of the birth defects in agricultural workers in Brazil; A Viral Story Links The Zika Crisis To Monsanto. Don’t Believe It. by Anna Almendrala Senior Healthy Living Editor Huffington Post. Anna’s piece is pure Monsanto propaganda masquerading as journalism, don’t believe a word of it. If you trust anything Monsanto says, then I have a bridge to sell you.
Monsanto Fights Back with Theatrics and Deception
This September 2016 article entitled, “The Right Chemistry: The fearmongers are wrong about glyphosate“ in the MONTREAL Gazette by Joe Schwarcz, an industry sponsored hit-man sent to discredit Steffanie Seneff’s publications exposing the harmful effects of Glyphosate. Instead of actually discussing any of the science in Dr Seneff’s publications. Joe Schwarcz relies on theatrics. During his video, the author eats a schnitzel sandwich and drinks tea, claiming similar safety profile with the Round-Up herbicide (glyphosate) on his desk. (116) Joe Schwarcz is a professor and Director of the Department of Science and Society at McGull University and receives heavy funding from “the Council for Biotechnology Information”, an industry front group for Monsanto. Here is information about funding sources for Dr Joseph SChwarz, a quote from “FoodBabe“:
“Dr. Joseph Schwarcz is the Director of McGill University’s “Office for Science & Society”, which has in the past received funding from the biotech (GMO) industry Dow, Monsanto, and Dupont through the Council for Biotechnology Information . Dr. Schwarcz is also on the Editorial Board for the magazine of the Chemical Institute of Canada, ACCN. Based on his advocacy, one could say Dr. Schwarcz hasn’t met a chemical he doesn’t like.“
Monsanto has known for decades that Glyphosate causes birth defects, see this report: Roundup and birth defects. Is the public being kept in the dark ? by Michael Antoniou Earth Open Source June 2011
Search Google Scholar for articles with key words “microcephaly pesticide“ : you will see 2160 articles pop up.
Glyphosate is “Probably Carcinogenic to Humans”
A number of studies show glyphosate exposure doubles the incidence of Non-Hodgkins Lymphoma.(92) As reported in Lancet Oncology by Dr Kathryn Guyton, on March, 2015, 17 experts from 11 countries met in Lyon France and classified glyphosate as “probably carcinogenic to humans” (89)
Zika Distraction from Glyphosate – The Elephant in the Room
Certainly, maternal viral illness with Rubella, (CMV) cytomegalovirus and Zika are all risk factors for fetal demise, and fetal malformations, and are best avoided.(93-95) However, the Zika Virus is a distraction from the real cause of the problem, massive glyphosate exposure to pregnant agricultural workers in Brazil. Glyphosate is a patented anti-folate drug, Anti-folate drugs are known to cause microcephaly and neural tube defects in animals and humans. Above Left image: Elephant in the Room is Glyphosate, courtesy of Stephanie Seneff PhD slide presentation.
Professor Don Huber, GMO Food and Glyphosate
Increased incidence of birth defects in the population caused by exposure to the anti-folate agent, glyphosate is only the “tip of the iceberg”. The adverse health consequences of GMO food and glyphosate contamination of our food and water supply are much more extensive as outlined in a series of articles posted on the Stephanie Seneff home page. Here is a quote from Professor Don M. Huber:(88) from his document GMO Failed Promises Flawed Science Serious Health Safety Issue
” Future historians may well look back upon our time and write, not about how many pounds of pesticides we did or did not apply, but about how willing we are to sacrifice our children and jeopardize future generations for this massive experiment we call genetic engineering that is based on failed promises and flawed science, just to benefit the bottom line of a commercial enterprise.” Dr. Don M. Huber
Link to this article: http://wp.me/p3gFbV-3En
Jeffrey Dach MD
7450 Griffin Road Suite 190
Davie, Fl 33314
Articles with related interest:
Links and references :
1) Zika can cause microcephaly even if moms have no symptoms, report says By Lena H. Sun June 15 Washington Post
2) Zika: The Epidemic at America’s Door
Zika may have already infected 80,000 Americans, just in Puerto Rico, and Congress has refused to act — what if Miami or New York is next? By Janet Reitman June 15, 2016 Rolling Stone
3) June 14, 2016 Florida’s Zika threat: ‘Not our first rodeo’ with these mosquitoes Miami herald
4) Ho, Mae-Wan. “Lab study establishes glyphosate link to birth defects.” ISIS (2010).
5) Carrasco, Andrés. “Teratogenesis by glyphosate based herbicides and other pesticides. Relationship with the retinoic acid pathway.” GMLS 2012 (2013): 24.Teratogenesis by glyphosate based herbicides Carrasco 2012 program key note
6) Antoniou, M., et al. “Teratogenic effects of glyphosate-based herbicides: Divergence of regulatory decisions from scientific evidence.” Journal of Environmental & Analytical Toxicology 2012 (2012).
7) Dzialowski Ed THE EFFECTS OF GLYPHOSATE BASED HERBICIDES ON CHICK EMBRYO DEVELOPMENT Diss. UNIVERSITY OF NORTH TEXAS, 2013 thesis. “The embryos had reduction in optic vesicles and microcephaly. Treated frog and chicken embryos also had increased endogenous retinoic acid activity,”
8) Paganelli, Alejandra, et al. “Glyphosate-based herbicides produce teratogenic effects on vertebrates by impairing retinoic acid signaling.” Chemical research in toxicology 23.10 (2010): 1586-1595. Glyphosate herbicides produce teratogenic effects by impairing retinoic acid signaling Paganelli Alejandra Chemical research in toxicology 2010
we conclude that the phenotypes produced by GBH ( Glyphgosate Based Herbicides ) are mainly a consequence of the increase of endogenous retinoid activity
9) Pesticides Used in South American GMO-Based Agriculture: A Review of Their Effects on Humans and Animal Models Silvia L. Lopez 2012, Pesticides South American GMO Agriculture Effects on Humans Animals Silvia L Lopez Advances in Molecular Research 2012
10) Benítez-Leite, S., M. L. Macchi, and M. Acosta. “Congenital malformations associated with toxic agricultural chemicals.” Pediatría (Asunción) 34.2 (2007): 111-121.
11) Header Image: Baby with Microcephaly Courtesy of Global News
In this Jan. 30, 2016 photo, Elielson tries to calm down his baby brother Jose Wesley, in Bonito, Pernambuco state, Brazil.
AP Photo/Felipe Dana
12) Comment by Mark WIlliam Houston on The Scientist
“I find it unusual that the Zika Virus, which comes from Uganda has never caused a single case of microcephaly in a child born in Central Africa. Now it may be argued that the Brazilian Zika Virus is a mutated strain, but, the Zika Virus was first discovered in 1947, in the Zika Forest, Uganda, and as such already has hundreds of different strains. Remember, the Zika Virus has been part of the Zika Forest ecosystem for possibly thousands of years, yet still, there is not a single recorded case of a hominid microcephaly and or a case involving any other mammal the virus has infected.”
Zika Microcephaly and the Problem with Smoking Gun Medicine Jun 9, 2016 by Chandler Marrs, PhD
14) THE QUESTIONABLE SCIENCE BEHIND ZIKA, MICROCEPHALY, & THE CDC 02 JUN 2016 POSTED BY ANTHONY TYLER
15) Big Breaking News from the Zika Virus Hoax Front BY PAUL FASSA JUN 10 2016
16) Rull, Rudolph P., Beate Ritz, and Gary M. Shaw. “Neural tube defects and maternal residential proximity to agricultural pesticide applications.” American journal of epidemiology 163.8 (2006): 743-753.
17) Lacasaña, Marina, et al. “Maternal and paternal occupational exposure to agricultural work and the risk of anencephaly.” Occupational and environmental medicine 63.10 (2006): 649-656.
18) Brender, Jean D., et al. “Maternal pesticide exposure and neural tube defects in Mexican Americans.” Annals of epidemiology 20.1 (2010): 16-22.
19) Schreinemachers, Dina M. “Birth malformations and other adverse perinatal outcomes in four US Wheat-producing states.” Environmental Health Perspectives 111.9 (2003): 1259.
20) Bell, E. M., I. Hertz-Picciotto, and J. J. Beaumont. “A case-control study of pesticides and fetal death due to congenital anomalies.” Epidemiology (Cambridge, Mass.) 12.2 (2001): 148.
21) Scientists Seek Ban On Monsanto’s RoundUp 06/16/2016 Judy Frankel Founder and CEO, Writeindependent.org Huffington Post
22) Thursday, 09 June 2016 The National Map of Monsanto’s Roundup in Parks and Schools REVEREND BILLY TALEN FOR BUZZFLASH AT TRUTHOUT
23) Is it Zika ‘Virus’ or Pesticides and Birth Defects? By Cal Crilly Global Research, February 01, 2016 January 2016
An Associated Press team this week visited the Zika Forest, which has 35-meter (38-yard) -tall trees and is, now fittingly, a research site for scientists with the Uganda Virus Research Institute. until the breakout of Zika in the Western Hemisphere, not much attention was paid to the virus in the forest, according to Ugandan officials. (AP Photo/Stephen Wandera) The Associated Press By RODNEY MUHUMUZA, Associated Press
25) Peltzer, Paola M., et al. “MORPHOLOGICAL ABNORMALITIES IN AMPHIBIAN POPULATIONS.” Herpetological Conservation and Biology 6.3 (2011): 432-442. full free pdf
Recently, Paganelli et al. (2010) demonstrated how concentrations of
glyphosate, lower than those considered relevant environmental concentrations in Argentina wetlands, increased endogenous retinoic acid activity in amphibian embryos and had teratogenic effects. This situation
could become even more of a concern with increased teratological risk to amphibians if we consider the effects of certain non-ionic surfactants containing ethoxylates (for example, POEA- polyethoxylates
tallawamine) that are added to herbicides. These ingredients are recognized for their influences on normal development on a native tadpole (Scinax nasicus) tails, gills, and cephalic structures (Lajmanovich et al. 2003).
26) Myers, John Peterson, et al. “Concerns over use of glyphosate-based herbicides and risks associated with exposures: a consensus statement.” Environmental Health 15.1 (2016): 1.
Since this (Shikimate) EPSPS-driven pathway does not exist in vertebrate cells, some scientists and most regulators assumed that glyphosate would pose minimal risks to mammals. However, several studies, some described below, now show that GBHs (Glyphosate Basd Herbicides) can adversely affect mammalian biology via multiple mechanisms.
Increased incidence of severe birth defects in Argentina and Paraguay in areas where GE Roundup Ready crops are widely grown may be linked to the ability of GBHs to increase retinoic acid activity during fetal development 4
27) Ginecol Obstet Mex. 2002 Nov;70:538-44.
[Risk for congenital malformations in pregnant women exposed to pesticides in the state od Nayarit, Mexico]. [Article in Spanish] Medina-Carrilo L1, Rivas-Solis F, Fernández-Argüelles R.
To measure the association between the use of pesticides and congenital malformations.
MATERIALS AND METHODS: We studied 279 newborn from mothers living in rural area of Nayarit, a state in the northwest region of México. Cases (n = 93) were defined as newborn with central nervous, face, genital, hip, foot or finger congenital malformations. Controls (n = 186) were newborns without any malformation. We considered as exposure any type of contact with any of the agrochemicals used as pesticides. We evaluated other risk factors such as medical drugs, fever, exposure to radiation, obstetric and family factors, as confoundings.
RESULTS: We registered 22 genital malformations, 20 from hip, 19 from the central nervous system, 18 from extremities and 14 cleft-lip or palate. Exposed mothers had high risk of having a malformed child (OR = 3.5, CI95% 2.05-6.34, p < 0.05). Risk was higher if the mother had occupational exposure to pesticides (OR = 6.33, CI95% 2.95-13.7, p < 0.0001) and in mothers living near areas under pesticides treatment (OR = 3.47, CI95% 1.91-6.33, p < 0.0001). Among obstetric factors, abortion and early delivery (OR = 15.05, CI95% 1.82-124.30, p < 0.01) were significant.
CONCLUSIONS: This study shows association between exposure to pesticides and congenital malformation. This is a public health problem in Nayarit state and in other rural areas with similar exposure to pesticides.
28) Coullery, Romina P., María E. Ferrari, and Silvana B. Rosso. “Neuronal development and axon growth are altered by glyphosate through a WNT non-canonical signaling pathway.” Neurotoxicology 52 (2016): 150-161.
The growth and morphological differentiation of neurons are critical events in the establishment of proper neuronal connectivity and functioning. The developing nervous system is highly susceptible to damage caused by exposure to environmental contaminants. Glyphosate-containing herbicides are the most used agrochemicals in the world, particularly on genetically modified plants. Previous studies have demonstrated that glyphosate induces neurotoxicity in mammals. Therefore, its action mechanism on the nervous system needs to be determined. In this study, we report about impaired neuronal development caused by glyphosate exposure. Particularly, we observed that the initial axonal differentiation and growth of cultured neurons is affected by glyphosate since most treated cells remained undifferentiated after 1 day in culture. Although they polarized at 2 days in vitro, they elicited shorter and unbranched axons and they also developed less complex dendritic arbors compared to controls. To go further, we attempted to identify the cellular mechanism by which glyphosate affected neuronal morphology. Biochemical approaches revealed that glyphosate led to a decrease in Wnt5a level, a key factor for the initial neurite development and maturation, as well as inducing a down-regulation of CaMKII activity. This data suggests that the morphological defects would likely be a consequence of the decrease in both Wnt5a expression and CaMKII activity induced by glyphosate. Additionally, these changes might be reflected in a subsequent neuronal dysfunction. Therefore, our findings highlight the importance of establishing rigorous control on the use of glyphosate-based herbicides in order to protect mammals’ health.
29) Glyphosate, Brain Damaged Babies, and Yakima Valley – A River Runs Through It Barbara H. Peterson, Farm Wars
30) Int J Environ Res Public Health. 2014 Apr 23;11(4):4449-527. full free
Non-Hodgkin lymphoma and occupational exposure to agricultural pesticide chemical groups and active ingredients: a systematic review and meta-analysis. Schinasi L1, Leon ME2.
This paper describes results from a systematic review and a series of meta-analyses of nearly three decades worth of epidemiologic research on the relationship between non-Hodgkin lymphoma (NHL) and occupational exposure to agricultural pesticide active ingredients and chemical groups. Estimates of associations of NHL with 21 pesticide chemical groups and 80 active ingredients were extracted from 44 papers, all of which reported results from analyses of studies conducted in high-income countries. Random effects meta-analyses showed that phenoxy herbicides, carbamate insecticides, organophosphorus insecticides and the active ingredient lindane, an organochlorine insecticide, were positively associated with NHL. In a handful of papers, associations between pesticides and NHL subtypes were reported; B cell lymphoma was positively associated with phenoxy herbicides and the organophosphorus herbicide glyphosate. Diffuse large B-cell lymphoma was positively associated with phenoxy herbicide exposure. Despite compelling evidence that NHL is associated with certain chemicals, this review indicates the need for investigations of a larger variety of pesticides in more geographic areas, especially in low- and middle-income countries, which, despite producing a large portion of the world’s agriculture, were missing in the literature that were reviewed.
31) A Viral Story Links The Zika Crisis To Monsanto. Don’t Believe It.
It would be a shame if bad information led to more Zika virus infections.
02/16/2016 Anna Almendrala Senior Healthy Living Editor Huffington Post
32) Swanson, Nancy L., et al. “Genetically engineered crops, glyphosate and the deterioration of health in the United States of America.” Journal of Organic Systems 9.2 (2014): 6-37 Genetically engineered crops Glyphosate Deterioration of Health_Nancy Swanson_2014
33) Morbidity and Mortality Weekly Report (MMWR)
Notes from the Field: Investigation of a Cluster of Neural Tube Defects — Central Washington, 2010–2013 Weekly September 6, 2013 / 62(35);728-728
34) CDC Key Findings: Investigation of a Cluster of Neural Tube Defects — Central Washington, 2010–2013
From January 2010 to January 2013, this area of Washington had four times as many pregnancies affected by anencephaly, an NTD, than were expected based on the most recent U.S.
35) Folic Acid and Glyphosate May 4, 2016 by Stephanie Seneff, PhD Weston Price
Neural tube defects (NTDs), such as spina bifida, anencephaly and exencephaly, are severe birth defects that result from failure of neural folds closure during embryonic development.1 While many factors may be involved in disrupting development in this way, it has been known since the 1970s that folate deficiency during the first trimester is a significant risk factor.2
36) Narisawa, Ayumi, et al. “Mutations in genes encoding the glycine cleavage system predispose to neural tube defects in mice and humans.” Human molecular genetics (2011): ddr585.
Neural tube defects (NTDs), including spina bifida and anencephaly, are common birth defects of the central nervous system. The complex multigenic causation of human NTDs, together with the large number of possible candidate genes, has hampered efforts to delineate their molecular basis. Function of folate one-carbon metabolism (FOCM) has been implicated as a key determinant of susceptibility to NTDs. The glycine cleavage system (GCS) is a multi-enzyme component of mitochondrial folate metabolism, and GCS-encoding genes therefore represent candidates for involvement in NTDs. To investigate this possibility, we sequenced the coding regions of the GCS genes: AMT, GCSH and GLDC in NTD patients and controls. Two unique non-synonymous changes were identified in the AMT gene that were absent from controls. We also identified a splice acceptor site mutation and five different non-synonymous variants in GLDC, which were found to significantly impair enzymatic activity and represent putative causative mutations. In order to functionally test the requirement for GCS activity in neural tube closure, we generated mice that lack GCS activity, through mutation of AMT. Homozygous Amt−/− mice developed NTDs at high frequency. Although these NTDs were not preventable by supplemental folic acid, there was a partial rescue by methionine. Overall, our findings suggest that loss-of-function mutations in GCS genes predispose to NTDs in mice and humans. These data highlight the importance of adequate function of mitochondrial folate metabolism in neural tube closure.
37) Pai, Yun Jin, et al. “Glycine decarboxylase deficiency causes neural tube defects and features of non-ketotic hyperglycinemia in mice.” Nature communications 6 (2015).
Glycine decarboxylase (GLDC) acts in the glycine cleavage system to decarboxylate glycine and transfer a one-carbon unit into folate one-carbon metabolism. GLDC mutations cause a rare recessive disease non-ketotic hyperglycinemia (NKH). Mutations have also been identified in patients with neural tube defects (NTDs), but the relationship between NKH and NTDs is unclear. We show that reduced expression of Gldc in mice suppresses glycine cleavage system activity and causes two distinct disease phenotypes. Mutant embryos develop partially penetrant NTDs while surviving mice exhibit post-natal features of NKH including glycine accumulation, early lethality and hydrocephalus. In addition to elevated glycine, Gldc disruption also results in abnormal tissue folate profiles, with depletion of one-carbon carrying folates
39) Roundup: Birth Defects Caused By World’s Top-Selling Weedkiller, Scientists Say 06/24/2011 Updated Aug 24, 2011 Lucia Graves
A comprehensive review of existing data released this month by Earth Open Source, an organization that uses open-source collaboration to advance sustainable food production, suggests that industry regulators in Europe have known for years that glyphosate, originally introduced by American agricultural biotechnology giant Monsanto in 1976, causes birth defects in the embryos of laboratory animals.
40) Krüger M, Schrödl W, Pedersen Ib, Shehata AA (2014) Detection of glyphosate in malformed piglets. J Environ Anal Toxicol 4: 230.
41) Are pesticides linked to health problems in Argentina?
By Linda Pressly BBC World Service, Assignment
42) Pesticides in paradise: Hawaii’s spike in birth defects puts focus on GM crops Local doctors are in the eye of a storm swirling for the past three years over whether corn that’s been genetically modified to resist pesticides is a source of prosperity, as companies claim, or of birth defects and illnesses
43) Zika Virus, Birth Defects, And Farm Chemicals In Washington State
February 14, 2016 Northwest Research & Covert Book Report
44) One Woman’s Fight Against Glyphosate October 14, 2015
2012 Goldman Prize winner Sofia Gatica is no stranger to the chemical’s human cost – just three days after her birth to a daughter, Sofia’s infant died of kidney failure, likely caused by pesticide exposure.
45) Sorry Monsanto: Brazil’s Federal Public Prosecutor Demands Ban on All Glyphosate Poisons Christina Sarich April 10, 2014 Natural Society
46) Ruthless power and deleterious politics: from DDT to Roundup vaggelos Vallianatos 18th July 2015
47) Rasmussen, Sonja A., et al. “Zika virus and birth defects—reviewing the evidence for causality.” New England Journal of Medicine 374.20 (2016): 1981-1987.
48) Dyer, Owen. “US agency says Zika virus causes microcephaly.” BMJ 353 (2016): i2167.
49) J Med Virol. 2016 Aug;88(8):1291-6. doi: 10.1002/jmv.24563. Epub 2016 May 5. Zika virus: An update on epidemiology, pathology, molecular biology, and animal model. Ramos da Silva S1, Gao SJ1.
Zika virus (ZIKV) was first described in 1947, and became a health emergency problem in 2016 when its association with fetal microcephaly cases was confirmed by Centers for Disease Control and Prevention (CDC) in the United States. To date, ZIKV infection has been documented in 66 countries. ZIKV is recognized as a neurotropic virus and numerous diseases manifested in multiple neurological disorders have been described, mainly in countries that have been exposed to ZIKV after the 2007 outbreak in the Federated States of Micronesia. The most dramatic consequence of ZIKV infection documented is the abrupt increase in fetal microcephaly cases in Brazil. Here, we present an update of the published research progress in the past few months. J. Med. Virol. 88:1291-1296, 2016. © 2016 Wiley Periodicals, Inc.
50) Cell Host Microbe. 2016 May 11;19(5):720-30. A Mouse Model of Zika Virus Pathogenesis. Lazear HM1, Govero J2, Smith AM2, Platt DJ2, Fernandez E2, Miner JJ2, Diamond MS3.
The ongoing Zika virus (ZIKV) epidemic and unexpected clinical outcomes, including Guillain-Barré syndrome and birth defects, has brought an urgent need for animal models. We evaluated infection and pathogenesis with contemporary and historical ZIKV strains in immunocompetent mice and mice lacking components of the antiviral response. Four- to six-week-old Irf3(-/-)Irf5(-/-)Irf7(-/-) triple knockout mice, which produce little interferon α/β, and mice lacking the interferon receptor (Ifnar1(-/-)) developed neurological disease and succumbed to ZIKV infection, whereas single Irf3(-/-), Irf5(-/-), and Mavs(-/-) knockout mice exhibited no overt illness. Ifnar1(-/-) mice sustained high viral loads in the brain and spinal cord, consistent with evidence that ZIKV causes neurodevelopmental defects in human fetuses. The testes of Ifnar1(-/-) mice had the highest viral loads, which is relevant to sexual transmission of ZIKV. This model of ZIKV pathogenesis will be valuable for evaluating vaccines and therapeutics as well as understanding disease pathogenesis.
51) Cell. 2016 May 19;165(5):1081-91. doi: 10.1016/j.cell.2016.05.008. Epub 2016 May 11. Zika Virus Infection during Pregnancy in Mice Causes Placental Damage and Fetal Demise.
Miner JJ1, Cao B2, Govero J1, Smith AM1, Fernandez E3, Cabrera OH4, Garber C1, Noll M1, Klein RS5, Noguchi KK4, Mysorekar IU6, Diamond MS7.
Zika virus (ZIKV) infection in pregnant women causes intrauterine growth restriction, spontaneous abortion, and microcephaly. Here, we describe two mouse models of placental and fetal disease associated with in utero transmission of ZIKV. Female mice lacking type I interferon signaling (Ifnar1(-/-)) crossed to wild-type (WT) males produced heterozygous fetuses resembling the immune status of human fetuses. Maternal inoculation at embryonic day 6.5 (E6.5) or E7.5 resulted in fetal demise that was associated with ZIKV infection of the placenta and fetal brain. We identified ZIKV within trophoblasts of the maternal and fetal placenta, consistent with a trans-placental infection route. Antibody blockade of Ifnar1 signaling in WT pregnant mice enhanced ZIKV trans-placental infection although it did not result in fetal death. These models will facilitate the study of ZIKV pathogenesis, in utero transmission, and testing of therapies and vaccines to prevent congenital malformations.
Zika Study Done in Rio De Janeiro not northeastern state of Pernambuco where increased cases of microcephaly reported.
53) N Engl J Med. 2016 Mar 4. …Zika Virus Infection in Pregnant Women in Rio de Janeiro – Preliminary Report. Brasil P et al.
Background Zika virus (ZIKV) has been linked to neonatal microcephaly. To characterize the spectrum of ZIKV disease in pregnancy, we followed patients in Rio de Janeiro to describe clinical manifestations in mothers and repercussions of acute ZIKV infection in fetuses. Methods We enrolled pregnant women in whom a rash had developed within the previous 5 days and tested blood and urine specimens for ZIKV by reverse-transcriptase-polymerase-chain-reaction assays. We followed the women prospectively and collected clinical and ultrasonographic data. Results A total of 88 women were enrolled from September 2015 through February 2016; of these 88 women, 72 (82%) tested positive for ZIKV in blood, urine, or both. The timing of acute ZIKV infection ranged from 5 to 38 weeks of gestation. Predominant clinical features included pruritic descending macular or maculopapular rash, arthralgias, conjunctival injection, and headache; 28% had fever (short-term and low-grade). Women who were positive for ZIKV were more likely than those who were negative for the virus to have maculopapular rash (44% vs. 12%, P=0.02), conjunctival involvement (58% vs. 13%, P=0.002), and lymphadenopathy (40% vs. 7%, P=0.02). Fetal ultrasonography was performed in 42 ZIKV-positive women (58%) and in all ZIKV-negative women. Fetal abnormalities were detected by Doppler ultrasonography in 12 of the 42 ZIKV-positive women (29%) and in none of the 16 ZIKV-negative women. Adverse findings included fetal deaths at 36 and 38 weeks of gestation (2 fetuses), in utero growth restriction with or without microcephaly (5 fetuses), ventricular calcifications or other central nervous system (CNS) lesions (7 fetuses), and abnormal amniotic fluid volume or cerebral or umbilical artery flow (7 fetuses). To date, 8 of the 42 women in whom fetal ultrasonography was performed have delivered their babies, and the ultrasonographic findings have been confirmed. Conclusions Despite mild clinical symptoms, ZIKV infection during pregnancy appears to be associated with grave outcomes, including fetal death, placental insufficiency, fetal growth restriction, and CNS injury.
We have been conducting active surveillance for dengue infection in the general population of Rio de Janeiro since 2007. In 2012, we established a prospective cohort for dengue surveillance in mother–infant pairs within the Manguinhos Rio de Janeiro area. In 2015, we noted an increase in cases of a denguelike illness that was characterized by a descending rash, generally without fever; this increase coincided with a surge in the number of cases in northeastern Brazil of illness characterized by a pruriginous rash. In early 2015, most cases were originally reported to surveillance systems as dengue; however, ZIKV was eventually identified.9 To identify ZIKV cases in our population, we modified our pregnancy cohort study and enrolled women at any week of gestation who presented with a rash. Here we report demographic, clinical, laboratory, and gestational ultrasonographic findings in the cohort of pregnant women enrolled in our ZIKV study to date.
northeastern state of Pernambuco,
54) Zika virus: Brazil’s surge in small-headed babies questioned by report
Organization says spike might be the result of heightened awareness because of possible link to Zika — but not everyone agrees.
Declan Butler28 January 2016
in October, Brazil’s health ministry reported an unusual spike in reported cases of microcephaly in the northeastern state of Pernambuco,
55) Baptista, Tiago, Gerardine Quaghebeur, and Ana Alarcon. “Neuroimaging findings of babies with microcephaly and presumed congenital Zika virus infection.” BMJ 353 (2016): i2194.
Questions remain about whether the surge in reported cases of microcephaly is entirely due to Zika virus infection, and whether heightened awareness and improved reporting may have led to some overestimation of the link. The risk of microcephaly after maternal infection is estimated at roughly one in 100 women.9 This is a relatively low risk compared with other causal infections such as cytomegalovirus.
56) Zika virus: Brazilian survey calls into question cause of microcephaly
AM By Norman Swan Feb 2016
57) Doctor: Are we sure it’s Zika? Added by Marie-Claire Williams on January 30, 2016.
58) Roberts, Craig W., et al. “The shikimate pathway and its branches in apicomplexan parasites.” Journal of infectious diseases 185.Supplement 1 (2002): S25-S36.
The shikimate pathway is essential for production of a plethora of aromatic compounds in plants, bacteria, and fungi. Seven enzymes of the shikimate pathway catalyze sequential conversion of erythrose 4-phosphate and phosphoenol pyruvate to chorismate. Chorismate is then used as a substrate for other pathways that culminate in production of folates, ubiquinone, napthoquinones, and the aromatic amino acids tryptophan, phenylalanine, and tyrosine.
The shikimate pathway is absent from animals and present in the apicomplexan parasites Toxoplasma gondii, Plasmodium falciparum, and Cryptosporidium parvum. Inhibition of the pathway by glyphosate is effective in controlling growth of these parasites. These findings emphasize the potential benefits of developing additional effective inhibitors of the shikimate pathway. Such inhibitors may function as broad-spectrum antimicrobial agents that are effective against bacterial and fungal pathogens and apicomplexan parasites.
The shikimate pathway operates in the cytosol of bacteria and fungi, but in plants it is also known to operate in plastid organelles. The pathway utilizes phosphoenol pyruvate and erythrose 4-phosphate to produce chorismate through seven catalytic steps [3, 4] (figure 1). It is a pathway with multiple branches. While branches exist from various intermediate products of the pathway, chorismate represents the major branch point, and various branches give rise to many end products. Derivatives of chorismate include tryptophan via an anthranilate intermediate [3, 4], phenylalanine and tyrosine via prephenate or arogenate [3–5], and vitamin K and metal chelators containing dihydroxybenzoic acid, such as enterochelin, via isochorismate [3, 4]. Chorismate also is used for production of ubiquinone and p-aminobenzoic acid (PABA), which is converted into folates.
it is likely that the shikimate pathway is important for supply of folate precursors in this parasite.
inhibitors of EPSP synthase can act in synergy with conventional antifolates and may be a useful addition to the agents used against apicomplexan parasites.
59) Elandalloussi, Laurence M., et al. “Shikimate and folate pathways in the protozoan parasite, Perkinsus olseni.” Molecular and biochemical parasitology 142.1 (2005): 106-109.
60) Biochem J. 2006 May 15; 396(Pt 1): 157–162.
Folate synthesis in plants: purification, kinetic properties, and inhibition of aminodeoxychorismate synthase
Tobias Sahr,* Stéphane Ravanel,* Gilles Basset,†,1 Brian P. Nichols,‡ Andrew D. Hanson,† and Fabrice Rébeillé*,2
pABA (p-aminobenzoate) is a precursor of folates and, besides esterification to glucose, has no other known metabolic fate in plants. It is synthesized in two steps from chorismate and glutamine, the first step being their conversion into glutamate and ADC (4-aminodeoxychorismate). In Escherichia coli, two proteins forming a heterodimeric complex are required for this reaction, but, in plants and lower eukaryotes, a single protein is involved. The Arabidopsis enzyme was expressed in E. coli and was purified to homogeneity. The monomeric enzyme (95 kDa) catalyses two reactions: release of NH3 from glutamine (glutaminase activity) and substitution of NH3 for the hydroxy group at position 4 of chorismate (ADC synthase activity). The kinetic parameters of the plant enzyme are broadly similar to those of the bacterial complex, with Km values for glutamine and chorismate of 600 and 1.5 μM respectively. As with the bacterial enzyme, externally added NH3 was a very poor substrate for the plant enzyme, suggesting that NH3 released from glutamine is preferentially channelled to chorismate. The glutaminase activity could operate alone, but the presence of chorismate increased the efficiency of the reaction 10-fold, showing the interdependency of the two domains. The plant enzyme was inhibited by dihydrofolate and its analogue methotrexate, a feature never reported for the prokaryotic system. These molecules were inhibitors of the glutaminase reaction, competitive with respect to glutamine (Ki values of 10 and 1 μM for dihydrofolate and methotrexate respectively). These findings support the view that the monomeric ADC synthase is a potential target for antifolate drugs.
61) Plant-like pathway in parasites provides new treatment targets effective new ways to inhibit parasites that cause malaria, toxoplasmosis and cryptosporidiosis . June 25, 1998
Dr. McLeod’s team showed that glyphosate, by interfering with just one of those enzymes, could block the production of folate, inhibiting parasite growth and survival. Glyphosate proved effective against malaria strains that were resistant to an anti-malarial medicine, pyrimethamine, which interrupts folate processing at a different point. To confirm the finding, they demonstrated that these folate-starved parasites could be rescued, in the test tube, by giving them folate.
62) Elandalloussi, Laurence M., et al. “Shikimate and folate pathways in the protozoan parasite, Perkinsus olseni.” Molecular and biochemical parasitology 142.1 (2005): 106-109.
63) Samsel, Anthony, and Stephanie Seneff. “Glyphosate, pathways to modern diseases II: Celiac sprue and gluten intolerance.” Interdisciplinary toxicology 6.4 (2013): 159-184.
64) Samsel, Anthony, and Stephanie Seneff. “Glyphosate, pathways to modern diseases IV: cancer and related pathologies.” The Journal of Biological Physics and Chemistry 15 (2015): 121-159.
65) free pdf
Cuhra, M., T. Bøhn, and P. Cuhra. “Glyphosate: Too Much of a Good Thing? Front.” Environ. Sci 4 (2016): 28.
66) Defarge, Nicolas, et al. “Co-formulants in glyphosate-based herbicides disrupt aromatase activity in human cells below toxic levels.” International journal of environmental research and public health 13.3 (2016): 264.
Abstract: Pesticide formulations contain declared active ingredients and co-formulants presented as inert and confidential compounds. We tested the endocrine disruption of co-formulants in six glyphosate-based herbicides (GBH), the most used pesticides worldwide. All co-formulants and formulations were comparably cytotoxic well below the agricultural dilution of 1% (18–2000 times for co-formulants, 8–141 times for formulations), and not the declared active ingredient glyphosate (G) alone. The endocrine-disrupting effects of all these compounds were measured on aromatase activity, a key enzyme in the balance of sex hormones, below the toxicity threshold. Aromatase activity was decreased both by the co-formulants alone (polyethoxylated tallow amine—POEA and alkyl polyglucoside—APG) and by the formulations, from concentrations 800 times lower than the agricultural dilutions; while G exerted an effect only at 1/3 of the agricultural dilution. It was demonstrated for the first time that endocrine disruption by GBH could not only be due to the declared active ingredient but also to co-formulants. These results could explain numerous in vivo results with GBHs not seen with G alone; moreover, they challenge the relevance of the acceptable daily intake (ADI) value for GBHs exposures, currently calculated from toxicity tests of the declared active ingredient alone.
67) Food Chem Toxicol. 2015 Oct;84:133-53. doi: 10.1016/j.fct.2015.08.012. Epub 2015 Aug 14. Potential toxic effects of glyphosate and its commercial formulations below regulatory limits. Mesnage R1, Defarge N1, Spiroux de Vendômois J2, Séralini GE3.
Glyphosate-based herbicides (GlyBH), including Roundup, are the most widely used pesticides worldwide. Their uses have increased exponentially since their introduction on the market. Residue levels in food or water, as well as human exposures, are escalating. We have reviewed the toxic effects of GlyBH measured below regulatory limits by evaluating the published literature and regulatory reports. We reveal a coherent body of evidence indicating that GlyBH could be toxic below the regulatory lowest observed adverse effect level for chronic toxic effects. It includes teratogenic, tumorigenic and hepatorenal effects. They could be explained by endocrine disruption and oxidative stress, causing metabolic alterations, depending on dose and exposure time. Some effects were detected in the range of the recommended acceptable daily intake. Toxic effects of commercial formulations can also be explained by GlyBH adjuvants, which have their own toxicity, but also enhance glyphosate toxicity. These challenge the assumption of safety of GlyBH at the levels at which they contaminate food and the environment, albeit these levels may fall below regulatory thresholds. Neurodevelopmental, reproductive, and transgenerational effects of GlyBH must be revisited, since a growing body of knowledge suggests the predominance of endocrine disrupting mechanisms caused by environmentally relevant levels of exposure.
68) Myers, John Peterson, et al. “Concerns over use of glyphosate-based herbicides and risks associated with exposures: a consensus statement.” Environmental Health 15.1 (2016): 1.
GBH use has increased approximately 100-fold since the first decade of its use in the 1970s. It is now the world’s most heavily applied herbicide.
Glyphosate provokes oxidative damage in rat liver and kidneys by disrupting mitochondrial metabolism Increases in the frequency of serious, chronic kidney disease have been observed among male agricultural workers in some regions in which there is a combination of heavy GBH use and ‘hard’ water. Glyphosate and GBHs disrupt endocrine-signaling systems in vitro, including multiple steroid hormones, which play vital roles in the biology of vertebrates. The incidence of non-Hodgkin’s Lymphoma (NHL) has nearly doubled in the U.S. between 1975 and 2006 . GBHs are implicated in heightened risk of developing NHL among human populations exposed to glyphosate occupationally, or by virtue of residence in an area routinely treated with herbicides.
Multiple studies on GBHs have reported effects indicative of endocrine disruption [21–24]. Based on knowledge from studies of other endocrine disruptors, the developing fetus, infants, and children are most at risk.
The action of glyphosate as an antibiotic may alter the gastrointestinal microbiome in vertebrates [33, 70–72], which could favor the proliferation of pathogenic microbes in humans, farm animals, pets and other exposed vertebrates.
Increased incidence of severe birth defects in Argentina and Paraguay in areas where GE Roundup Ready crops are widely grown may be linked to the ability of GBHs to increase retinoic acid activity during fetal development
neurotoxicity through multiple mechanisms . Replication of these studies using doses relevant to human exposures should be a high priority. Further work on GBH-induced neurotoxicity should be conducted to test whether glyphosate can act as a disruptor of neurotransmitter function given its similarity in structure to glycine and glutamate
77) Glyphosate Suppression Cytochrome P450 amino acid biosynthesis by the gut microbiome Pathways Modern Diseases Entropy Seneff 2013 Samsel, Anthony, and Stephanie Seneff. “Glyphosate’s suppression of cytochrome P450 enzymes and amino acid biosynthesis by the gut microbiome: Pathways to modern diseases.” Entropy 15.4 (2013): 1416-1463.
79) Samsel, Anthony, and Stephanie Seneff. “Glyphosate, pathways to modern diseases III: Manganese, neurological diseases, and associated pathologies.” Surg Neurol Int 6 (2015): 45.
No malformations in third trimester Zika Infection
80) Zika Virus Disease in Colombia — Preliminary Report Oscar Pacheco, M.D., et al. June 15, 2016DOI: 10.1056/NEJMoa1604037 New England Journal
Colombia began official surveillance for Zika virus disease (ZVD) in August 2015. In October 2015, an outbreak of ZVD was declared after laboratory-confirmed disease was identified in nine patients. Using the national population-based surveillance system, we assessed patients with clinical symptoms of ZVD from August 9, 2015, to April 2, 2016. Laboratory test results and pregnancy outcomes were evaluated for a subgroup of pregnant women. Concurrently, we investigated reports of microcephaly for evidence of congenital ZVD.
By April 2, 2016, there were 65,726 cases of ZVD reported in Colombia, of which 2485 (4%) were confirmed by means of reverse-transcriptase–polymerase-chain-reaction (RT-PCR) assay. The overall reported incidence of ZVD among female patients was twice that in male patients. A total of 11,944 pregnant women with ZVD were reported in Colombia, with 1484 (12%) of these cases confirmed on RT-PCR assay. In a subgroup of 1850 pregnant women, more than 90% of women who were reportedly infected during the third trimester had given birth, and no infants with apparent abnormalities, including microcephaly, have been identified. A majority of the women who contracted ZVD in the first or second trimester were still pregnant at the time of this report. Among the cases of microcephaly investigated from January 2016 through April 2016, four patients had laboratory evidence of congenital ZVD; all were born to asymptomatic mothers who were not included in the ZVD surveillance system.
Preliminary surveillance data in Colombia suggest that maternal infection with the Zika virus during the third trimester of pregnancy is not linked to structural abnormalities in the fetus. However, the monitoring of the effect of ZVD on pregnant women in Colombia is ongoing. (Funded by Colombian Instituto Nacional de Salud and the Centers for Disease Control and Prevention.)
From January 1, 2016, to April 28, 2016, a total of 50 infants with possible microcephaly were reported to the national surveillance system for birth defects. Of these cases, 26 are still under investigation, and 20 were deemed to have resulted from causes other than Zika virus infection, including STORCH (syphilis, toxoplasmosis, other agents, rubella, cytomegalovirus, and herpes) infections, genetic causes, neural-tube defects, and other causes among infants with negative results on Zika RT-PCR whose mothers had no symptoms of ZVD during pregnancy. Four infants with microcephaly had laboratory evidence of congenital Zika virus infection on RT-PCR assay, a negative STORCH evaluation, and normal karyotypes. Of the 4 infants, who were born between 37 and 39 weeks of gestation, 1 had abnormal brain findings on ultrasonography and 3 had abnormal findings on hearing evaluations. Other clinical findings for the cases included decreased muscle tone, problems sucking or swallowing, and amyoplasia of the lower limbs. None of the four mothers had symptoms of ZVD during pregnancy and therefore were not reported as part of ZVD monitoring.
81) No Birth Defects Seen In Babies Exposed To Zika Late In Pregnancy
Still, it’s “it is critically important” to continue to monitor those babies.
06/16/2016 1Huffington Post Julie Steenhuysen
82) Why Brazil has a big appetite for risky pesticides By Paulo Prada Filed April 2, 2015
83) Glyphosate formulations and their use for the inhibition of 5-enolpyruvylshikimate-3-phosphate synthase US 7771736 B2 Abstract
Protozoan parasites of the phylum Apicomplexa include some of the most important causative agents of human and animal diseases, in particular, malaria. The discovery that an organelle found inside parasites of this phylum probably stems from a plastid of plant origin has stimulated research on the effect of chemical herbicidal agents on Apicomplexa. Importantly, the growth of these parasites can be inhibited by the herbicide glyphosate, suggesting that the shikimate pathway will make a good target for the development of new anti-parasite agents. The present invention discloses the use of the herbicidal agent glyphosate in combination with the polyvalent anion oxalic acid for the prevention and therapy of these pathogenic infections.
84) Glyphosate is a patented anti-microbial & biocide (U.S. patent number 20040077608 A1 This invention relates to the in vivo use of N-phosphonomethyl glycine, commonly known as glyphosate, or a salt, ester or other derivative thereof, in combination with a dicarboxylic acid or a derivative thereof, for the treatment of pathogenic infections, including infections of mammals by apicomplexan parasites.
Maternal Exposure to Anti-Folate Drugs Increases NTD
85) Matok, Ilan, et al. “Exposure to folic acid antagonists during the first trimester of pregnancy and the risk of major malformations.” British journal of clinical pharmacology 68.6 (2009): 956-962.
First-trimester exposure to folic acid antagonists is associated with increased risk of congenital malformations.
A total of 117 960 deliveries took place at SMC in the study period, 84 823 (or 72%) of which to women registered at Clalit; 527 (0.62%) of the latter were exposed to at least one folic acid antagonist during the first trimester: 349 were exposed to dihydrofolate reductase inhibitors (346 to trimethoprim/sulfamethoxazole, two to methotrexate and one to sulfasalazine) and 179 to one or more ‘other’ folic acid antagonists (112 to carbamazepine, 35 to valproic acid, 21 to phenobarbital, 14 to phenytoin, eight to lamotrigine, and one to primidone and cholestyramine).
86) Wilde, Jonathan J., Juliette R. Petersen, and Lee Niswander. “Genetic, epigenetic, and environmental contributions to neural tube closure.” Annual review of genetics 48 (2014): 583.
Drugs that act as folate antagonists have continued to be implicated as risk factors for NTDs. Women who took folate antagonists in their first trimester were more than sixfold more likely to have an NTD-affected pregnancy. These included DHFR-inhibitors, such as methotrexate, which inhibit the conversion of folate to its active form, and the antiepileptic drug valproic acid (an HDAC inhibitor) (6, 112).
87) Au, Kit Sing, Allison Ashley‐Koch, and Hope Northrup. “Epidemiologic and genetic aspects of spina bifida and other neural tube defects.” Developmental disabilities research reviews 16.1 (2010): 6-15.
In a study in Israel, increased NTD risk was associated with exposure to one or more folic acid antagonists in the first trimester of pregnancy [Matok et al., 2009]. Preconceptional and first trimester usage of antibacterial medication was associated with increased risk of several birth defects included anencephaly but not SB [Crider et al., 2009]. Last, maternal use of selective serotonin-reuptake inhibitors was associated with an increased risk of anencephaly in a recent study [Alwan et al., 2007].
88) Don Huber GMO Failed Promises Flawed Science Serious Health Safety Issue Glyphosate ” Future historians may well look back upon our time and write, not about how many pounds of pesticides we did or did not apply, but about how willing we are to sacrifice our children and jeopardize future generations for this massive experiment we call genetic engineering that is based on failed promises and flawed science, just to benefit the bottom line of a commercial enterprise.” Dr. Don M. Huber is Emeritus Professor, Purdue University; COL AUS (Ret, Medical Intelligence); Former Chairman, USDA National Plant Disease Recovery Program; member, US Threat Pathogens Committee; former member of the Advisory Board, Office of Technology Assessment, US Congress; and OTSG Global Epidemiology Working Group.
89) Carcinogenicity tetrachlorvinphos parathion malathion diazinon glyphosate Guyton Kathryn Lancet Oncology 2015 Guyton, K. Z., et al. “Carcinogenicity of tetrachlorvinphos, parathion, malathion, diazinon, and glyphosate.” The Lancet. Oncology 16.5 (2015): 490.
IARC Monographs The Working Group classified glyphosate as ―probably carcinogenic to humans‖ (Group 2A). In March, 2015, 17 experts from 11 countries met at the International Agency for Research on Cancer (IARC; Lyon, France) to assess the carcinogenicity of the organophosphate pesticides tetrachlorvinphos, parathion, malathion, diazinon, and
glyphosate (table). These assessments will be published as volume 112 of the IARC Monographs.1
90) The Hill. House GOP pushes $1.1 billion Zika bill through Dem sit-in By Sarah Ferris – 06/23/16 House Republicans on Thursday approved a spending bill that includes a controversial $1.1 billion plan to fight the Zika virus in a late-night vote over Democrat protests. The 239-171 vote occurred in the 15th hour of a dramatic sit-in protest by dozens of Democrats demanding votes on gun control bills. House Appropriations Committee Chairman Hal Rogers (R-Ky.) announced the long-awaited Zika deal late Wednesday evening, describing it as a “responsible compromise that can and should be signed into law.”
(91) Orwell, George. Nineteen eighty-four. Everyman’s Library, 2009.
92) Schinasi, Leah, and Maria E. Leon. “Non-Hodgkin lymphoma and occupational exposure to agricultural pesticide chemical groups and active ingredients: a systematic review and meta-analysis.” International journal of environmental research and public health 11.4 (2014): 4449-4527.
93) Rasmussen, Sonja A., et al. “Zika virus and birth defects—reviewing the evidence for causality.” New England Journal of Medicine 374.20 (2016): 1981-1987.
94) Petersen, Lyle R., et al. “Zika virus.” New England Journal of Medicine 374.16 (2016): 1552-1563.
A temporal and geographic relationship has been observed between Guillain–Barré syndrome and Zika virus outbreaks in the Pacific and the Americas.
95) Driggers, Rita W., et al. “Zika virus infection with prolonged maternal viremia and fetal brain abnormalities.” New England Journal of Medicine 374.22 (2016): 2142-2151.
97) Increase in Reported Prevalence of Microcephaly in Infants Born to Women Living in Areas with Confirmed Zika Virus Transmission During the First Trimester of Pregnancy — Brazil, 2015
Weekly / March 11, 2016 / 65(9);242–247 . Wanderson Kleber de Oliveira, MSc1; Juan Cortez-Escalante, MD2; Wanessa Tenório Gonçalves Holanda De Oliveira, MSc1; Greice Madeleine Ikeda do Carmo, MSc1; Cláudio Maierovitch Pessanha Henriques, MD1; Giovanini Evelim Coelho, PhD1; Giovanny Vinícius Araújo de França, PhD1 (View author affiliations)
Pernambuco state reported the largest increase in number of reported cases of microcephaly.
98) Infectious Diseases – Convicting Zika Peter Doshi, associate editor,
BMJ 2016; 353 (Published 07 April 2016) Cite this as: BMJ 2016;353:i1847
“Zika virus has been forgotten for many years. I have to say rightfully so. It hasn’t been an issue, why make it an issue? There are so many viruses like it,” says virologist Leslie Lobel of the Uganda Virus Research Institute, which owns the Zika forest where the virus was first detected in 1947. Lobel, who studies Ebola virus, says that Zika is a relatively benign virus–even given the recent outbreak in the Americas. Pointing to a recent study14 that estimated the risk of microcephaly at around one in 100 women infected with Zika during their first trimester of pregnancy, Lobel says the risk is “quite low.” He says people have forgotten about German measles: “If you got infected [with rubella] you’d have a very high risk of birth defects.”
99) Is Zika the cause of Microcephaly Status Report Yaneer Bar-Yam 2016Yaneer Bar-Yam, Dan Evans, Raphael Parens, Alfredo J. Morales, Fred Nijhout, Is Zika the cause of Microcephaly? Status Report June 22, 2016, New England Complex Systems Institute (June 22, 2016).
“This would seem to rule out Zika as a cause of microcephaly. This gives a consistent interpretation that there is no direct link between Zika and microcephaly except for random co-occurrence.”An alternative cause of microcephaly in Brazil could be the pesticide pyriproxyfen, which is cross-reactive with retinoic acid, which causes microcephaly, and is being used in drinking water.
100) Crider, Krista S., Lynn B. Bailey, and Robert J. Berry. “Folic acid food fortification—its history, effect, concerns, and future directions.” Nutrients 3.3 (2011): 370-384.
In the United States, mandatory fortification of enriched cereal grain products with folic acid was authorized in 1996 and fully implemented in 1998
101) Centers for Disease Control and Prevention (CDC. “CDC Grand Rounds: additional opportunities to prevent neural tube defects with folic acid fortification.” MMWR. Morbidity and mortality weekly report 59.31 (2010): 980.
Neural tube defects (NTDs) are serious birth defects that result from the failure of the neural tube to close in the cranial region (anencephaly) or more caudally along the spine (spina bifida) by the 28th day of gestation. Infants born with anencephaly usually die within a few days of birth, and those with spina bifida have life-long disabilities with varying degrees of paralysis. Currently, identified risk factors for NTDs include a mother who previously had an NTD-affected pregnancy, maternal diabetes, obesity, hyperthermia, certain antiseizure medications, genetic variants, race/ethnicity, and nutrition (particularly folic acid insufficiency). In the United States, during 1995-1996, approximately 4,000 pregnancies were affected by an NTD. This number declined to 3,000 pregnancies in 1999-2000 after fortification of enriched cereal grain products with folic acid was mandated. Worldwide, in 1998, approximately 300,000 births were affected by an NTD.
U.S. NTD and blood folate trends. The mandatory fortification of standardized enriched cereal grain products in the United States resulted in a substantial increase in blood folate concentrations and a concomitant decrease in NTD prevalence. The percentage of the population with low serum folate (<3 ng/mL) declined from 21% in the period before fortification (1988–1994) to <1% of the total population in the period immediately following fortification (1999–2000) (5). NTD prevalence decreased by 36% after fortification, from 10.8 per 10,000 population during 1995–1996 to 6.9 at the end of 2006 (6).
Cost. Published economic evaluations have shown that folic acid food fortification is cost saving in the United States and other countries. A 2008 study estimated that current folic acid fortification produces an annual savings of about $300 million, or $100 for each $1 invested in fortification (9). Fortification also has resulted in substantial cost savings globally. Chile has demonstrated a savings of $11 (in international dollars) for each $1 invested in fortification (10).
102) Folic acid flour fortification Impact on congenital anomaly South American AmJMedGenet Lopez Cameloz 2010
Lopez-Camelo JS, Castilla EE, Orioli IM. 2010. Folic acid flour fortification: Impact on the frequencies of 52 congenital anomaly types in three South American countries. Am J Med Genet Part A 152A:2444–2458.
103) Oakley Jr, G. P. “The scientific basis for eliminating folic acid-preventable spina bifida: a modern miracle from epidemiology.” Annals of epidemiology 19.4 (2009): 226.
104) Folate biofortification in food plants Bekaert Samir Trends plant science 2008 Bekaert, Samir, et al. “Folate biofortification in food plants.” Trends in plant science 13.1 (2008): 28-35. “Humans cannot synthesize folates (vitamin B9) and thus have to rely on plant food supplying these essential vitamins.”
105) Zika virus may not cause microcephaly: Study IANS | Jun 26, 2016, 10.02 PM IST Times of India. A new study in Colombia found that the total number of pregnancies with Zika infections is much larger, with 11,944 cases with Zika symptoms being observed in clinical settings. But, no cases of microcephaly occurred in all of these pregnancies.
106) Huge New Doubts that Zika Causes Microcephaly by Sarah
The healthy home economist
107) Evans, Dan, et al. “A possible link between pyriproxyfen and microcephaly.” Available at SSRN (2016). Possible link between pyriproxyfen and microcephaly Evans Dan 2016
108) Report from Physicians in the Crop-Sprayed Towns regarding Dengue-Zika, microcephaly, and mass-spraying with chemical poisons. 2016. Physicians in the Crop-Sprayed Towns. Zika microcephaly mass chemical poisons pyriproxyfen BRAZIL 2016
109) KENNETH, J. ROTHMAN, et al. “TERATOGENICITY OF HIGH VITAMIN A INTAKE.” THE NEW ENGLAND JOURNAL OF MEDICINE (1995). Teratogenicity_of_High_Vitamin_A_Intake_NEJM_kenneth rothman_1995
110) Folate in bread sees drop in birth defects AAP June 28, 2016
Mandatory fortification of bread with folic acid and iodine was introduced in Australia in 2009 under the Australia New Zealand Food Standards Code.
A review of the bread fortification program, conducted by the government funded Australian Institute of Health and Welfare (AIHW), has found the overall rate of neural tube defects (NTDs) has decreased by 14.4 per cent since its implementation – in line with predictions.
What wasn’t expected was the even bigger decrease of NTDs among babies born to teenagers and Aboriginal and Torres Strait Islander women.
The rate of NTDs among teenagers decreased by almost 55 per cent, and by 74 per cent among Aboriginal women.
111) AIHW 2016. Monitoring the health impacts of mandatory folic acid and iodine fortification 2016. Cat. no. PHE 208. Canberra: AIHW.
The decrease in NTDs was most substantial for Aboriginal and Torres Strait Islander women and teenagers. There was a 74.2% decrease in the rate of NTDs among Indigenous women in the total study population (from 19.6 to 5.1 per 10,000 conceptions that resulted in a birth) and an 80.2% decrease among Indigenous women in the population omitting New South Wales residents (from 22.8 to 4.5 per 10,000 conceptions that resulted in a birth). These results were statistically significant.
112) Folate in bread reduces birth defects
The rates of spina bifida and other neural birth defects in Australian babies have declined since the mandatory introduction of folate to bread, according to a review conducted by the Australian Institute of Health and Welfare (AIHW). Mandatory fortification of bread with folic acid and iodine was introduced in Australia in 2009 under the Australia New Zealand Food Standards Code. The review found that there had been a statistically significant decline of 14.4% in the overall rate of neural tube defects (NTDs) since implementation – in line with predictions. What wasn’t expected was the even bigger decrease of NTDs among babies born to teenagers and Aboriginal and Torres Strait Islander women. The rate of NTDs among teenagers decreased by almost 55%, and by 74% among Aboriginal women.
113) Archivos Latinoamericanos de Nutrición versión impresa ISSN 0004-0622 ALAN vol.65 no.1 Caracas mar. 2015
Folic acid intake by pregnant women from Vale do Jequitinhonha, Brazil, and the contribution of fortified foods. Humberto Gabriel Rodrigues; Muriel Bauermann Gubert; Leonor Maria Pacheco Santos
Faculdades Integradas Pitágoras de Montes Claros, Montes Claros, MG, Brasil. Universidade de Brasília, Departamento de Nutrição, Departamento de Saúde Coletiva, Faculdade de Ciências da Saúde, Brasília, DF, Brasil.
SUMMARY: The folate deficiency can result in irreversible health damage, such as the neural tube defects. The aim of this article is to determine the folate intake of pregnant women in Vale do Jequitinhonha, Minas Gerais state, Brazil, one of the poorest regions in the world. A descriptive, cross-sectional study was done in 2013 with 492 pregnant women attending the basic health units run by the public health service (Sistema Único de Saúde, SUS) in 15 municipalities. A standard questionnaire was used to gather the data, which included socioeconomic indicators and a food frequency questionnaire. The data were analyzed and compared statistically based on prevalence ratios and 95% confidence intervals. The prevalence of inadequate folate intake was associated with some socioeconomic factors: it was higher amongst the low income and less educated women, in younger women and those who had fewer meals per day. The prevalence of inadequate folate intake in the diet was 94.7% when the contribution of food fortification was not considered, 49.2% taking into account fortified foods, and 17.1% considering food folate, fortified foods, and supplementation with folic acid. We conclude that fortifying foods with folic acid at the current levels reduces the inadequacy of folate intake in the diet, but not enough to assure safe levels and to meet the nutritional requirements of pregnant women in Brazil.
114) Lopez Camelo Folic acid flour fortification 52 congenital anomaly types South American AJ Med Gen 2010
López‐Camelo, Jorge S., Eduardo E. Castilla, and Iêda M. Orioli. “Folic acid flour fortification: impact on the frequencies of 52 congenital anomaly types in three South American countries.” American Journal of Medical Genetics Part A 152.10 (2010): 2444-2458.
Significant reductions in birth prevalence estimates after fortification
were observed for eight of the 52 investigated congenital
Nationwide and mandatory FA food fortification strategies are recommended for the primary prevention of NTDs in transitional developing countries, such as most of the Latin American ones.
115) Rosenthal J, Casas J, Taren D, Alverson CJ, Flores A, Frias J. Neural tube defects in Latin America and the impact of fortification: a literature review. Public health nutrition. 2014;17(3):537-550.
Currently, all Latin American countries except Venezuela have mandatory fortification legislation. The aggregate percentage decline in NTD prevalence ranged from 33% to 59%.
116) The Right Chemistry: The fearmongers are wrong about glyphosate. MONTREAL, QUE.: Joe Schwarcz, Special to the Montreal Gazette September 9, 2016 11:30 AM EDT
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