Food & Nutrition

Bees: The Only Evidence You’ll Need to Say “No” to GMOs

Disclaimer: I am a scientist. I am not a doctor or other medical professional. I analyze data and draw conclusions based on what I see. I do not diagnose or give medical advise. Any opinion or personal experience I have shared here is just that. Consult your doctor if something you read here resonates with you. I recommend a doctor of functional medicine if you want a doctor sympathetic to alternative medicine and options different than Western medicine practices.

Trees feed mushrooms.

Mushrooms feed bees.

Bees feed us.

Glyphosate can kill trees, mushrooms, bees, and us.

In 4 short sentences, this is the only evidence you need to protest GMO crops. Why? Well, let me tell you a story about a man named Paul Stamets.

Paul Stamets & The Bees

Paul Stamets is the ‘shroom guy. He’s dedicated his entire life to studying mushrooms. He’s also the guy who figured out how to save the bees. Over the last decade or so, a problem [1] has come to light concerning our bee population: it is poisoned and dying. Now you might not think a lot about bees, but without them, this is what our grocery store shelves would look like:Whole Foods grocery store without bees

Bees are an essential link in the chain of our food supply, as you can tell from the vacant shelves pictured above. We need them. However, scientists estimate that by this point, almost all bee populations have been infected with a virus that is shortening their lifespans en masse. When the worker bees start dying, the bees that work in the hive have to step up and take on the worker bee job, putting a massive strain on the hive. Within weeks, most of the bees in an infected hive die. Paul discovered that bees will feed on mushrooms with antiviral properties, and the bees get better and survive much longer! If you want to know more about his incredible research, I would recommend this presentation he did at the EcoFarm conference in January 2017. It is really astounding and exciting work.

So you might be asking yourself at this point “What does this have to do with GMOs?” or “What does ‘GMO’ even mean?” Both excellent questions. Here are the answers.

GMO: What is it?

GMO stands for “genetically modified organism”. The concept was launched to the public as a method to “end world hunger”; however, world hunger hasn’t ended and much money has been made by big companies in the process. Companies, Monsanto being the big one, alter the genetics of cash crops like soy, corn, wheat, canola, sugar, cotton, sugar beets, alfalfa, and even chocolate to make them resistant to Roundup. Roundup is an herbicide sold by Monsanto that allows companies to produce way more product without worrying about some of the crop being lost because it was eaten by bugs or strangled by weeds. The main active ingredient in Roundup is glyphosate, a highly controversial chemical that has been deemed “safe” by the government and studies done by groups with industry ties. Conflict of interest? I think so! Anyway, I’m far more interested in the science than the politics because, while I can’t control what the FDA deems “safe”, I can control what goes into my shopping cart and body. Vote with your dollar, as they say.

Connecting The Bees to GMOs

So let’s return to the problem at hand. We have discussed how bees are vital to our food sources, and bees are sick. We have also discussed how there is a cure for the bees that involves mushrooms and a guy named Paul Stamets. So how does this connect to GMOs? Well, there has been a review study [2] published in 2013 by Anthony Samsel and Stephanie Seneff. This one article covers all the bases and is an excellent read if you have some extra time on your hands. Otherwise, I will give you the highlights here so you can make you own informed decision about what your dollars are voting for.

sample and seneff paper heading: glyphosate's suppression of cytochrome P450 enzymes and amino acid biosynthesis by the gut microbiome: pathways to modern disease

I want to point out that we will take an innocent until proven guilty approach. We will assume glyphosate is safe until a study confirms dangerous side effects. I will not take time here to analyze studies that supposedly confirm the safety of glyphosate and GMO crops because we only need 2 truly excellent reports to deem glyphosate dangerous. One study initially provides evidence, and a second study demonstrates the repeatability of the first study. Lucky for you, I have far more than 2 examples!

Also, I want to remind you not to get bogged down in the big words if science is not usually your jam. Read what you can, focus on the big picture, and leave the rest for later.

Glyphosate: The Active Ingredient in Roundup

We’ll start with an overview of glyphosate. As mentioned above, glyphosate is the active ingredient in Roundup, and Roundup is sprayed on GMO crops. The FDA has deemed Roundup to be safe. Many studies claim glyphosate has negligent toxicity to mammals [3, 4]. Some studies have even gone so far as to claim that glyphosate is less toxic than aspirin [3, 5]. Because of this, it is often handled carelessly, and the quantity of glyphosate on and absorbed by plants we consume is not closely regulated.

A major issue I take with the safety check of GMO and Roundup (glyphosate) is the timeline. We have been told that GMO crops are safe and that Roundup won’t cause any damage in the short [6] or long term. However, human consumption of these treated crops spans only part of a generation of humans. There are no true long-term studies because the product hasn’t even been around long enough to do a long-term study. Monsanto or any other company researching and producing GMO crops can’t honestly tell me that their product will have no effect on me over the course of 50 years because that study has never been done. As you will see, the effects of Roundup, and specifically glyphosate, take time to manifest. So what can we prove?

Glyphosate can kill plants.

Plants sprayed with Roundup absorb the chemicals. A study [7] was done where glyphosate-tolerant and glyphosate-sensitive plants were treated with glyphosate. Both plants absorbed the glyphosate despite the genetic modification. The genetic modification is only meant keep Roundup from killing the crop, but it does not make it impermeable to chemical absorption.

We also know that glyphosate disrupts the shikimate pathway [8] in plants. The shikimate pathway is involved in the synthesis of essential amino acids, phenylalanine, tyrosine, and tryptophan. The shikimate pathway is not directly present in humans. However, it is present in gut bacteria, and the human gut is critical to maintaining the immune system [9], so anything that harms our good gut bacteria is definitely harming us.

Plants treated with glyphosate had decreased levels of tryptophan, phenylalanine, and tyrosine [7]. They also had a 50-65% decrease in levels of serine, glycine, and methionine [7]. A side-branch of the tryptophan synthesis pathway is a pathway for flavonoid synthesis. A 20-fold increase in the synthesis of a rate-limiting enzyme for the flavonoid synthesis pathway was observed as a result of glyphosate exposure [10]. Glyphosate also induced synthesis of monophenolic compounds and polyphenolic flavonoids in plants [11] and microbes [12]. An increase in synthesis of these two compounds uses up amino acids that are needed as supplies for other compounds.

Glyphosate was reported to interfere with root absorption of calcium and magnesium in soybeans [13] and levels of calcium, magnesium, iron, and manganese were lower in plant seeds produced by plants treated with glyphosate [14]. A study of carrots exposed to high doses of glyphosate found that the carrots produced significant levels of phenolic compounds and shikimic acid [15]. We’ll come back to the dangers of phenolic compounds soon. Benzoic acids were also found at higher levels [12]. If a plant is producing higher levels of phenolic compounds and benzoic acids, supplies to build other compounds needed by the plant get used up more quickly. As a result, aromatic amino acids do not get synthesized as abundantly as they are needed.

The Big Picture

You don’t have to understand all the details of the biological pathways to see the big picture. Glyphosate has been shown to be a detriment to plants that have been exposed. The nutrient levels are decreased, and the plants get sick, even if they don’t look like it on the outside. When you consume these sick, glyphosate-contaminated plants, you ingest glyphosate and don’t get as much nutritional value from your food. We’ll get to what happens when you ingest glyphosate.

Glyphosate can kill animals.

Before we move on to humans, I want to specifically mention some case studies performed on animals. I encourage you to look these up and do further reading.

Study #1: Mice with glyphosate in their drinking water showed signs of damage in liver and blood cells [16].

Study #2: In two weeks, a frog environment contaminated with glyphosate lost one-third of the population of frogs and 2 species of tadpoles were completely eliminated [17]. The species variation of the frogs decreased by 70%.

Study #3: Rats were given water tainted with glyphosate at the highest level of allowed human consumption for 30 days or 90 days showed indications of oxidative stress [18]. Pathologies occurred after 3 months; 3 months is a typical length of time for a toxicity study. Therefore, a 3 month study would not have detected changes in health.

Study #4: Rats were fed GMO maize or non-GMO maize over their lifetime. The female rats on the GMO diet developed mammary tumors. The chronically exposed rats, especially the males, also developed gastrointestinal, liver, and kidney pathologies. The male rats also developed skin and liver carcinomas [19].

Study #5: Cattle fed with a GMO diet had increased risk to Clostridium botulinum infection in Germany [20].

Glyphosate can kill humans.

Glyphosate poses a danger to humans (and other animals) on 2 fronts: impaired sulfate transport and suppression of cytochrome P450 (CYP) enzymes.

Let’s break this down, starting with impaired sulfate transport.

For starters, we need to identify why sulfur is important in the body. Sulfur is a component of 4 amino acids: methionine, cysteine, homocysteine, and taurine. Sulfur provides the location for methionine and cysteine to bind together to form proteins. The highest concentrations of sulfur can be found in joints, hair, nails, and skin. Insulin has high levels of sulfur-containing amino acids. Cysteine is found in the liver; taurine is a component of bile acid which aids in digestion; methionine and cysteine help metabolize homocysteine.

How does glyphosate cause impaired sulfate transport?

Glyphosate and sulfate are both considered kosmotropes (don’t get bogged down in the vocab, just roll with me). When glyphosate is introduced to the system, the kosmotropic level increases. When kosmotropic levels increase, phenolic compounds (such as p-cresol) are required to transport sulfate. This means a larger number of phenolic compounds are needed, so aromatic amino acids are oxidized into phenolic compounds. These phenolic compounds are sulfated in the gut, and the sulfate is transported through the hepatic portal vein in the presence of glyphosate. The phenolic compounds can be reused and perform several rounds of sulfate transport, but when the phenolic compounds are eventually unsulfated, they become toxic. Phenolic compounds react destructively with phospholipids and DNA [21].

What are the effects of impaired sulfate transport?

First, to counteract the elevated levels of kosmotropes, the level of chaotropes (the opposite of kosmotropes) increases in the blood to act as a buffer. Chaotropes include ammonia, nitric oxide, nitrite, and nitrate [22]. These compounds have been observed at elevated levels in patients with autism [23-25]. In fact, since 1990 autism has been connected to impaired sulfur oxidation and low levels of serum sulfate [26]. With autism, free sulfate levels in the blood around one-third the normal level [27-32]. Other serious problems can arise from impaired sulfate transport such as colitis and Crohn’s disease [33]. Deficiencies in sulfur-containing amino acids can lead to a range of health problems including arthritis, liver stress, digestive issues, and gut dysbiosis.

Gut dysbiosis is worth dwelling on for a few extra sentences because you’re probably less familiar with it than the other things listed here.

Gut dysbiosis is an imbalance between beneficial and harmful species of bacteria in the gut. It can lead to leaky gut [9], autoimmune diseases, weight gain, skin issues, thyroid conditions, food sensitivities, joint pain, and headaches. It has also been implicated in autism [34, 35]. Gut dysbiosis can occur when the sulfate supply to mucosa is insufficient. Phenolic compounds can correct this deficiency (as explained above), but they themselves are also inflammatory.

Let’s move to the suppression of CYP enzymes.

What are CYP enzymes?

Cytochrome P450 (CYP) enzymes are a class of enzymes present in plant, animal, and microbial biology. There are at least 18 CYP families present in humans. These enzymes participate in liver detoxification of xenobiotics [36], forming bile acid [37], synthesizing and breaking down vitamin D3 and cholesterol [38, 39], steroid synthesis [40], catobolizing retinolic acid [41], regulating blood clotting [42], regulating hemorrhaging [42], and stimulating platelet aggregation [42].

What are the effects of suppression of CYP enzymes?

Symptoms ranging from vitamin D deficiency to liver failure can be a result of CYP enzyme. Essentially, all of those functions listed above don’t happen properly when CYP enzymes experience interference.

How does glyphosate cause suppression of CYP enzymes?

Here are three ways glyphosate that can interfere with CYP enzyme activity:

1. Glyphosate can inhibit aromatase, a CYP enzyme that converts testosterone to estrogen. One study found that glyphosate at 10 ppm disrupted the amount of aromatase activity [43]. At 100 times less concentration than the recommended agricultural use, aromatase is disrupted in human placental cells [44]. Adjuvants, chemicals that enhance the body’s immune response to an antigen, found in Roundup enhance its toxcitiy. In oyster larvae, Roundup was toxic at 1/20 of the amount of glyphosate needed to be toxic [45].

2. Glyphosate can suppress the CYP enzyme involved in catabolizing retinoic acid. This causes an increase in retinoic acid. Neural defects and cranial malfunctions have been observed in babies born where glyphosate-based herbicides are used. A study examined the effects of chick and frog embryo development while exposed to glyphosate at a 1/5000 dilution of commercial glyphosate-based herbicide [46]. The tadpoles had cranial deformities. The chick embryos had microcephaly. These defects were due to an increase in retinoic acid as a result of CYP enzyme suppression.

3. Glyphosate can inhibit detoxifying CYP enzymes in both plants and animals. One study looked at the inhibition of a CYP enzyme that detoxifies benzene compounds in plants. At 15 microM (this means 0.000088 oz of glyphosate in 1 liter of water), CYP enzyme activity was reduced by a factor of 4. At 35 microM (or 0.00021 oz of glyphosate in 1 liter of water), CYP enzyme was completely eliminated. This happens because the nitrogen group in glyphosate binds to the CYP enzyme [47]. When rats were fed glyphosate for 2 weeks, a decrease in the level of CYP enzymes in the liver was observed [48].

Some researchers theorize that the major honeybee die-off is connected to increased glyphosate use. The bees collect pollen from plants that have been treated with glyphosate, and the glyphosate gets in their systems. Usually bees are very resistant to toxins from pesticides because of certain CYP enzymes that they have. However, since glyphosate suppresses the CYP enzymes that help the bees eliminate those toxins, they become susceptible to pesticides that didn’t harm them before [49-52].

And here were are full circle. Glyphosate kills trees, mushrooms, bees, and us.

The Big Picture

We’ve discussed the nitty gritty of glyphosate’s damage to humans, but what does this look like in our society? We are living in a culture of health epidemics. Some of these have already been mentioned in detail, but here are some of the major diseases and diagnoses whose sources we can link to the problems that glyphosate causes (this list is not exhaustive):

  • Autism [2, 53, 54, 55]
  • Obesity [2, 56, 57, 58, 59, 160, 61, 62]
  • IBD [2, 63, 64, 65, 66]
  • Anorexia Nervosa [2]
  • Alzheimer’s  [2, 67, 68, 69, 70, 71, 72, 73]
  • Parkinson’s [2, 74, 75, 76]
  • Liver Disease [2, 77, 78, 79]
  • Infertility [2, 80, 81, 82, 83, 84, 85]
  • Cancer [2, 86, 19, 87, 88, 89, 90, 91]

This list scares me. And it should scare you, too. It should make you run far and fast from touching anything labeled GMO or sprayed with Roundup. Well, let me help you with that. Here’s what to look for when you’re grocery shopping:

Non GMO Project Verified label

This website has extensive resources about GMOs, and any food with their label on the packaging has been cleared of being GMO. They also have an app where you can search products that have been added to their list of GMO-free products. You can even scan a barcode of a product to quickly find out if it’s on their list.

Non-GMO products are not necessarily organically grown, but all organic products are non-GMO. You can easily identify organic products by this label here:

USDA Organic label

Eat real food, and happy shopping!

If you have any suggestions for a featured article or if you are super excited about this series, leave a comment below!

Much love,

K

Sources:

[1] Schacker, M. A Spring Without Bees: How Colony Collapse Disorder Has Endangered Our Food Supply; Globe Pequot: Guilford, CT. USA, 2008.

[2] 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. 2013, 1416-1463.

[3] Duke, S.O.; Powles, S.B. Glyphosate: A once-in-a-century herbicide. Pest. Manag. Sci. 2008, 64, 319-325.

[4] Weed Science Society of America Committee. In Herbicide Handbook of the Weed Science Society of America, 4th ed.; Weed Science Society of America: Champaign, IL, USA, 2979.

[5] Williams, G.M.; Kroes, R.; Munro, I.C. Safety evaluation and risk assessment of the herbicide roundup and its active ingredient, glyphosate, for humans. Regul. Toxicol. Pharm. 2000, 31, 117-165.

[6] Smith, E.A.; Oehme, F.W. The biological activity of glyphosate to plants and animals: A literature review. Vet. Hum. Tocicol. 1992, 34, 531-543.

[7] Nafziger, E.D.; Widholm, J.M.; Steinrcken, H.C.; Killmer, J.L. Selection and Characterization of a Carrot Cell Line Tolerant to Glyphosate. Plant. Physoil. 1984, 76, 571-574.

[8] Herrmann, K.M., Weaver, L.M. The Shikimate Pathway. Annu. Rev. Plant. Physiol. Plant. Mol Biol. 1999, 50, 473-503.

[9] Axe, Josh. Eat Dirt: Why Leaky Gut May Be the Root Cause of Your Health Problems and 5 Surprising Steps to Cure It. Harper Wave, an Imprint of Harper Collins Publishers, 2017.

[10] Zhao, J.; Wililams, C.C.; Last, R.L. Induction of Arabidopsisl tryptophan pathway enzymes and camalexin by amino acid starvation, oxidative stress, and an abiotic elicitor. Plant Cell 1998, 10, 359-370.

[11] Hernandez, A.; Garcia-Plazaola, J.I.; Becerril, J.M. Glyphosate effects on phenolic metabolism of nodulated soybeen (Glycine max L. Merr.). J. Agric. Food Chem. 1999, 47, 2920-2925.

[12] Moorman, T.B.; Bercerril, J.M.; Lydon, J.; Duke, S.O. Production of hydroxybenzoic acids by Bradyrhizobium japonicum strains after treatment with glyphosate. J. Agric. Food Chem. 1992, 289-293.

[13] Duke, S.O.; Vaughn. K.C.; Wauchope, R.D. Effects of glyphosate on uptake, translocation, and intracellular localization of metal cations in soybean (Glycine max) seedlings. Pestic. Biochem. Phys. 1985, 24, 384-394.

[14] Cakmak, I.; Yazici, A.; Tutus, Y.; Ozturk, L. Glyphosate reduced seed and leaf concentrations of calcium, manganese, magnesium, and iron in non-glyphosate resistant soybean. Eur. J. Agron. 2009, 31, 114-119.

[15] Becerra-Moreno, A.; Benavides, J.; Cisneros-Zevallos, L.; Jacobo-Velazquez, D.A. Plants as biofactories: Glyphosate-induced production of shikimic acid and phenolic antioxidants in wounded carrot tissue. J. Agric. Food Chem. 2010, 60, 11378-11386.

[16] Manas, F.J.; Peralta, L.; Garca Ovando, H.; Weyers, A.; Ugnia, L.; Gorla, N. Genotoxicity of glyphosate and AMPA evaluated through comet assay in blood and hepatocytes of treated mice. Biocell. 2009, 33, A80.

[17] Relyea, R.A. The impact of insecticides and herbicides on the biodiversity and productivity of aquatic communites. Ecol. Appl. 2005, 15, 618-627.

[18] Larsen, K.; Najle, R.; Lifschitz, A.; Virkel, G. Effects of sub-lethal exposure of rats to the herbicide glyphosate in drinking water: glutathione transferase enzyme activities, levels of reduced glutathione and lipid peroxidation in liver, kidneys and small intestine. Environ. Toxicol. Pharmacol. 2012, 34, 811-818.

[19] Seralini, G.E.; Clair, E.; Mesnage, R.; Gress, S.; Defarge, N.; Malatesta, M.; Hennequin, D.; Sprioux de Vendomois, J. Longer term toxicity of a Roundup herbicide and a Roundup-tolerant genetically modified maize. Food Chem. Toxicol. 2012, 50, 4221-4231.

[20] Kruger, M.; Shehata, A.A.; Schrodl, W.; Rodloff, A. Glyphosate suppresses the antagonistic effects of Enterococcus spp. On Clostridium botulinum. Anaerobe 2013, 20, 74-78.

[21] Goldman, R.; Claycamp, G.H.; Sweetland, M.A.; Sedlov, A.V.; Tyurin, V.A.; Kisin, E.R.; Tyurina, Y.Y.; Ritov, V.B.; Wenger, S.L.; Grant, S.G.; Kagan, V.E. Myeloperoxidase-catalyzed redox-cycling of phenol promotes lipid peroxidation and thiol oxidation in HL-60 cells. Free Radic. Biol. Med. 1999, 27, 1050-1063.

[22] Cohen, B.I. The significance of ammonia/gamma-aminobutyric acid (GABA) ratio for normality and liver disorders. Med. Hypotheses. 2002, 59, 757-758.

[23] Sweeten, T.L.; Posey, D.J.; Shankar, S.; McDougle, C.J. High nitric oxide production in autistic disorder: a possible role for interferon-gamma. Biol. Psychiatry 2004, 55, 434-437.

[24] Sogut, S.S.; Zoroglu, S.S.; Ozyurt, H.; Ylmaz, H.R.; Ozugurlu, F.; Sivasli, E.; Yetkin, O.; Yanik, M.; Tutkun, H; Savas, H.A.; et al. Changes in nitric oxide levels and antioxidant enzyme activities may have a role in the pathophysiological mechanisms involved in autism. Clin. Chim. Acta. 2003, 331, 111-117.

[25] Zoroglu, S.S.; Yurekli, M.; Meram, I.; Sogut, S.; Tutkun, H.; Yetkin, O.; Sivasli, E.; Savas, H.A.; Yanik, M.; Herken, H.; Akyol, O. Pathophysiological role of nitric oxide and adrenomedullin in autism. Cell. Biochem. Funct. 2003, 31, 55-60.

[26] O’Reilly, B. A.; Waring, R.H. Enzyme and sulphur oxidation deficiencies in autistic children with known food/chemical intolerances. Xenobiotica. 1990, 20, 117-122.

[27] Sivsammye, G.; Sims, H.V. Presumptive identification of Clostridium difficile by detection of p-cresol in prepared peptone yeast glucose broth supplemented with p-hydroxyphenylacetic acid. J. Clin. Microbiol. 1990, 28, 1851-1853.

[28] Launay, J.M.; Ferrari, P.; Haimart, M.; Bursztejn, C.; Tabuteau, F.; Braconnier, A.; Pasques-Bondoux, D.; Luong, C. Serotonin metabolism and other biochemical parameters in infantile autism: A controlled study of 22 autistic children. Neuropsychobiology. 1988, 20, 1-11.

[29] Al-Yafee, Y.A. Al-Ayadhi, L.Y.; Haq, S.H.; El-Ansary, A.K. Novel metabolic biomarkers related to sulfur-dependent detoxification pathways in autistic patients of Saudi Arabia. BMC Neurol. 2011, 11, 139.

[30] Alberti, A.; Pirrone, P.; Elia, M.; Waring, R.H.; Romano, C. Sulphation deficit in “low-functioning” autistic children: A pilot study. Biolog. Psychiat. 1999, 46, 420-424.

[31] Waring, R.H.; Kovrza, L.V Sulphur metabolism in autism. J. Nutr. Environ. Med. 2000, 10, 25-32.

[32] Finegold, S.M. Therapy and epidemiology of autism-clostridial spores as key elements. Med. Hypotheses. 2008, 70, 508-511.

[33] Murch, S.H.; MacDonald, T.T.; Walker-Smith, J.A.; Levin, M.; Lionetti, P.; Klein, N.J., Disruption of sulphated glycosaminoglycans in intestinal inflammation. Lancet 1993, 341, 711-714.

[34] Willams, B.L.; Hornig, M.; Buie, T.; Bauman, M.L.; Cho Paik, M.; Wick, I.; Bennett, A.; Jabado, O.; Hirschberg, D.L.; Lipkin, W.I. Impaired carbohydrate digestion and transport and mucosal dysbiosis in the intestine of children with autism and gastrointestinal disturbances. PLoS One 2011, 6, e24585.

[35] Horvath, K.; Perman, J.A. Autism and gastrointestinal symptoms. Curren Gastroenterology Reports. 2002, 4, 251-258.

[36] Anzenbacher, P.; Anzenbacherova, E. Cytochromes p450 and metabolism of xenobiotics. Cell. Mol. Life Sci. 2001, 58, 737-747.

[37] Stiles, A. R.; McDonald, J.G.; Bauman, D.R.; Russell, D.W. CYP7B1: One cytochrome P450, two human genetic diseases, and multiple physiological functions. J. Biol. Chem. 2009, 284, 28485-28489.

[38] Wikvall, K. Cytochrome P450 enzymes in the bioactivation of vitamin D to its hormonal form (review). Int. J. Mol. Med. 2001, 7, 201-209.

[39] Schuster, I. Cytochromes P450 are essential players in the vitamin D signaling system. Biochim. Biophys. Acta 2011, 1814, 186-199.

[40] Miller, W. L. P450 oxidoreductase deficiency: a disorder of steroidogensis with multiple clinical manifestations. Sci. Signal. 2012, 5, 11.

[41] William, J. Ray, W.J.; Gerard Bain, G.; Min Yao, M.; and David I. Gottlieb, D.I. CYP26, a novel mammalian cytochrome P450, is induced by retinoic acid and defines a new family. J. Biol. Chem. 2997, 272, 18702-18708.

[42] Slofstra, S.H.; Speck, C.A.; ten Cate, H. Disseminated intravascular coagulation. Hematol. J. 2003, 4, 295-302.

[43] Gasnier, C.; Dumont, C.; Benachour, N.; Clair, E.; Chagnon, M.C.; Seralini, G.E. Glyphosate-based herbicides are toxic and endocrine disruptors in human cell lines. Toxicology 2009, 262, 184-191.

[44] Richard, S.; Moslemi, S.; Sipahutar, H.; Benachour, N.; S’eralini, G.E. Differential effects of glyphosate and roundup on human placental cells and aromatase. Environ. Health Perspect. 2005, 113, 716-720.

[45] Mottier, A.; Kientz-Bouchart, V.; Serpentini, A.; Lebel, J.M.; Jha, A.N.; Costil, K. Effects of glyphosate-based herbicides on embryo-larval development and metamorphosis in the Pacific oyster, Crassostrea gigas. Aquat. Toxicol. 2013, 128, 128-129, 67-78.

[46] Paganelli, A.; Gnazzo, V. Acosta, H.; Lpez, S.L.; Carrasco, A.E. Glyphosate-based herbicides produce teratogenic effects on vertebrates by impairing retinoic acid signaling. Chem. Res. Toxicol. 2010, 23, 1586-1595.

[47] Lamb, D.C.; Kelly, D.E.; Hanley, S.Z.; Mehmood, Z.; Kelly, S.L. Glyphosate is an inhibitor of plant cytochrome P450: Functional expression of thlapsi arvensae cytochrome P45071b1/reductase fusion protein in Escherichia coli. Biochem. Biophys. Res. Comm. 1998, 244, 110-114.

[48] Hietanen, E.; Linnainmaa, K.; Vainio, H. Effects of phenoxyherbicides and glyphosateon the hepatic and intestinal biotransformation activities in the rat. Acta. Pharmacol. Toxicol. 1983, 53, 103-112.

[49] Schacker, M. A Spring Without Bees: How Colony Collapse Disorder Has Endangered Our Food Supply; Globe Pequot: Guilford, CT. USA, 2008.

[50] Mao, W.; Schuler, M.A.; Berenbaum, M.R CYP9Q-mediated detoxification of acaricides in the honey bees (Apis mellifera). Proc. Natl. Am. Soi. 2011, 108, 12657-12662.

[51] Morandin, L.A.; Winston, M.L. Wild bee abundance and seed production in conventional organic, and genetically modified canol. Ecol. Appl. 2005, 15, 871-881.

[52] Foulk, K.E.; Reeves, C. Identifying the role of glyphosate-containing herbicides on honeybee mortality rates and colony collapse disorder. In Proceedings of Junior Science, Engineering, and Humanities Symposium, Camdenton, MO, USA, 2009; 2-23.

[53] Wakefield, A.J. The Gut-Brain Axis in Childhood Developmental Disorders. JPGN. 2002, 34, S14-S17.

[54] Basile, A.S.; Jones, E.A. Ammonia and GABA-ergic neurotransmission: Interrelated factors in the pathogenesis of hepatic encephalophathy. Hepatology. 1997, 25, 1303-1305.

[55] James, J.; Cutler, P.; Melnyk, S.; Jernigan, S.; Janak, L.; Gaylor, D.W.; Neubrander, J.A. Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism. Am. J. Clin. Nutr. 2004 , 80, 1611-1617.

[56] Baillie-Hamilton, P.F. Chemical toxins: A hypothesis to explain the global obesity epidemic. J. Altern. Complem. Med. 2002, 8, 185-192.

[57] Zimmerman, R.C.; McDougle, C.J.; Schumacher, M.; Olcese, J.; Mason, J.W.; Heninger, G.R.; Price, L.H. Effects of acute tryptophan depletion on nocturnal melatonin secretion in humans. J. Clin. Endocr. MeTable 1993, 76, 1160-1164.

[58] Breisch, S.T.; Zemlan, F.P.; Hoebel, B.G. Hyperphagia and obesity following serotonin depletion by intraventricular p-chlorphenylalanine. Science 1976, 192, 382-385.

[59] Zhao, J.; Williams, C.C.; Last, R.L. Induction of Arabidopsisl tryptophan pathway enzymes and camalexin by amino acid starvation, oxidative stress, and an abiotic elicitor. Plant Cell 1998, 10, 359-370.

[60] Cabellero, B.; Finer, N.; Wurtman, R.J. Plasma amino acids and insulin levels in obesity: response to carbohydrate intake and tryptophan supplements. Metabolism 1988, 37, 672-676.

[61] Breum, L.; Rasmussen, M. H.; Helsted, J.; Fernstrom, J.D. Twenty-four hour plasma tryptophan concentrations and ratios are below normal in obese subjects and are not normalized by substantial weight reduction. Am. J. Clin. Nutr. 2003, 77, 1112-1118.

[62] Woods, S.C.; Seeley, R.J.; Rushing, P.A.; DAlessio, D.; Tso, P. A controlled high-fat diet induces an obese syndrome in rats. J. Nutr. 2003, 133, 1081-1087.

[63] Hashimoto, T.; Perlot, T.; Rehman, A.; Trichereau, J.; Ishiguro, H.; Paolino, M.; Sigl, V.; Hanada, T.; Hanada, R.; Lipinski, S. et al. ACE2 links amino acid malnutrition to microbial ecology and intestinal inflammation. Nature 2012, 487, 477-483.

[64] Ashorn, M. Gastrointestinal diseases in the paediatric age groups in Europe: epidemicology and impact on healthcare. Aliment. Pharmacol. Ther. 2003, 18, 80-83.

[65] Bewtra, M.; Su, C.; Lewis, J.D. Trends in hospitalization rates for inflammatory bowel disease in the United States. Clin. Gastroenterol. Hepatol. 2007, 5, 597-601.

[66] Loftus, E.V. Clinical epidemiology of inflammatory bowel disease: Incidence, prevalence, and environmental influences. Gastroenterology. 2004, 126, 1504-1517.

[67] Fujii, H.; Sato, T.; Kaneko, S.; Gotoh, O.; Fujii-Kuriyama, Y.; Osawa, K.; Kato, S.; Hamada, H. Metabolic inactivation of retinoic acid by a novel P450 differentially expressed in developing mouse embryos. EMBO J. 1997, 16, 4163-4173.

[68] Seshadri, S.; Beiser, A.; Selhub, J.; Jacques, FP.R.; Rosenberg, I. H.; D’Agostino, R.B.; Wilson, P.W.F.; Wolf, P.A. Plasma homocysteine as a risk factor for dementia and Alzheimer’s disease. N. Engl. J. Med. 2002, 346, 476-483.

[69] Geldenhuys, W.J.; van der Schyf, C.J. Role of serotonin in Alzheimer’s disease: A new therapeutic target? CNS Drugs 2011, 25, 765-781.

[70] Meltzer, C.C.; Smith, G.; DeKosky, S.T.; Pollock, B.G.; Mathis, C.A.; Moore, R.Y.; Kupfer, D.J.; Reynolds, C.F., III. Serotonin in aging, late-life depression, and Alzheimer’s disease: The emerging role of functional imaging. Neuropsycholpharmacology. 1998, 18, 407-430.

[71] Seiler, N. Ammonia and Alzheimer’s disease. Neurochem. Int. 2002, 41, 189-207.

[72] Ejim, L.J.; D’Costa, V.M.; Elowe, N.H.; Conception Loredo-Osti, J.; Malo, D.; Wright, G.D. Cystathionine-Lyase is important for virulence of salmonella enterica serovar typhimurium. Infect. Immun. 2004, 72, 3310-3314.

[73] Heafield, M.T.; Fearn, S.; Stevenson, G.B.; Waring, R.H.; Williams, A.C.; Sturman, S.G. Plasma cysteine and sulfate levels in patients with Motor neurone, Parkinsons and Alzheimers disease. Neurosci. Lett. 1990, 110, 216-220.

[74] Seneff, S.; Lauritzen, A.; Davidson, R.; Lentz-Marino, L. Is endothelial nitric oxide synthase a moonlighting protein whose day job is cholesterol sulfate synthesis? Implications for cholesterol transport, diabetes and cardiovascular disease. Entropy 2012, 14, 2492-2530.

[75] Cryle, M.J.; De Voss, J.J. Is the ferric hydroperoxy species responsible for sulfur oxidation in cytochrome P450? Angew. Chem. Int. Ed. 2006, 45, 8221-8223.

[76] Friedman, L.G.; Lachenmayer, M.L.; Wang, J.; He, L.; Poulose, S.M.; Komatsu, M.; Holstein, G.R.; Yue, Z. Disrupted autophagy lead to dopaminergic axon and dendrite degerneration and promotes presynaptic accumulation of –Synuclein and LRRK2 in the brain. J. Neurosci. 2012, 32, 7585-7593.

[77] Carter-Kent, C.; Zein, N.N.; Feldstein, A.E. Cytokines in the pathogensis of fatty liver and disease progression to steatohepatitis: implications for treatment. Am. J. Gastroenterol. 2008, 103, 1036-1042.

[78] Peraldi, P.; Hotamisligil, G.S.; Burrman, W.A.; White, M.F.; Spiegelman, B.M. Tumor necrosis factor (TNF)-alpha inhibits insulin signaling through stimulation of the p55 TNF receptor and activation of sphingomyelinase. J. Biol. Chem. 1996, 271, 13018-13022.

[79] Plomgaard, P.; Bouzakri, K.; Krogh-Madsen, R.; Mittendorfer, B.; Zierath, J.R.; Pedersen, B.K. Tumor necrosis factor-alpha induces skeletal muscle insulin resistance in healthy human subjects via inhibition of Akt substrate 160 phosphorylation. Diabetes. 2005, 54, 2939-2945.

[80] Langlais, J.; Zollinger, M.; Plante, L.; Chapdelaine, A.; Bleau, G.; Robers, K.D. Localization of cholesterol sulfate in human spermatozoa in support of a hypothesis for the mechanism of capacitation. Proc. Natl. Acad. Sci. USA. 1981, 78, 7266-7270.

[81] Hidiroglou, M.; Knipfel, J.E.; Zinc in mammalian sperm: a review. J. Dairy Sci. 1984, 67, 1147-1156.

[82] Mose, T.; Kjaerstad, M.B.; Mathiesen, L.; Nielsen, J.B.; Edelfors, S.; Knudsen, L.E. Placental passage of benzoic acid, caffeine, and glyphosate in an ex vivo human perfusion system. J. Toxicol. Environ. Health A 2008, 71, 984-991.

[83] Seneff, S.; Davidson, R.M.; Liu, J. Is cholesterol sulfate deficiency a common factor in preeclampsia, autism, and pernicious anemia? Entropy 2012, 14, 2265-2290.

[84] Clair, E.; Mesnage, R.; Travert, C.; Seralini, G.E. A glyphosate-based herbicide induces necrosis and apoptosis in mature rat testicular cells in vitro, and testosterone decrese at lower levels. Toxicol. In Vitro 2012, 26, 269-279.

[85] Walsh, L.P.; McCormick, C.; Marin, C.; Stocco, D.M. Roundup inhibits steroidogenesis by disrupting steroidogenic acute regulatory (StAR) protein expression. Environ. Health Persp. 2000, 108, 769-776.

[86] de Roos, A.J.; Blair, A.; Rusiecki, J.A.; Hoppin, J.A.; Svec, M.; Dosmeci, M.; Sandler, D.P.; Alavanja, M.C. Cancer incidence among glyphosate-exposed pesticide applicators in the agricultural health study. Environ. Health Persp. 2005, 113, 49-54.

[87] Yong, M.; Schwartz, S.M.; Atkinson, C.; Makar, K.W.; Thomas, S.S.; Newton, K.M.; Bowles, E.J.A.; Holt, V.L.; Leisenring, W.M.; Lampe, J.W. Associations between polymorphisms in glucuronidation and sulfation enzymes and mammographic breast density in premenopausal women in the Unites States. Cancer Epidemiol. Biomarkers Prev. 2010, 19, 537-546.

[88] McCormack, V.A.; dos Santos Silva, I. Breast density and parenchymal patterns as markers of breast cancer risk: A meta-analysis. Cancer Epidemiol. Biomarkers Prev. 2006, 15, 1159-1169.

[89] Hakkak, R.; Holley, A.W.; MacLeod, S.L.; Simpson, P.M.; Fuchs, G.J.; Jo, C.H.; Keiber-Emmons, T.; Korourian, S. Obesity promotes 7,12-dimethylbenz(a)anthracene-induced mammary tumor development in female zucker rats. Breast Cancer Res. 2005, 7, R627-R633.

[90] Subbaramaiah, K.; Howe, L.R.; Bhardwaj, P.; Du, B.; Gravaghi, C.; Yantiss, R.K.; Zhou, X.K.; Blaho, V.A.; Hla, T.; Yang, P.; Kopelovich, L.; Hudis, C.A.; Dannenberg, A.J. Obesity is associated with inflammation and elevated aromatase expression in the mouse mammary gland. Cancer Prev. Res.( Phila.) 2011, 4, 329-346.

[91] Cleary, M.P.; Grossmann, M.E. Minireview: Obesity and breast cancer: The estrogen connection. Endocrinology 2009, 150, 2537-2542.

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