Monday, January 4, 2016

INDIVIDUALIZED APPROACH TO VACCINATION CAN PREVENT AUTOIMMUNE DISEASE ONSET IN SUBSET OF POPULATION WITH GENETIC TESTING TO RULE OUT RISK FACTORS

This is my final research paper for a class this term. Has not been graded. The research is firm. Feel free to share. (the formatting didn't translate well the blog. )

INDIVIDUALIZED APPROACH TO VACCINATION CAN PREVENT AUTOIMMUNE DISEASE ONSET IN SUBSET OF POPULATION WITH GENETIC TESTING TO RULE OUT RISK FACTORS
Written by Kaire Downin January 04, 2016 

Abstract
It is increasingly clear that scientific literature has been able to identify risk factors associated with adverse events following the administration of vaccinations in individuals who develop autoimmune disorders as a result of the vaccination. A comprehensive analysis of available literature shows that genetic markers have been identified for people who are susceptible for developing autoimmune diseases and that this population of people require an individualized approach to vaccinations to prevent serious adverse events and even death. Even though vaccines have been shown to be safe for a broad population, when evidence is found that would prevent the small subset that have predispositions to autoimmune diseases from developing serious complications, it is the duty of our medical community to become knowledgeable and take precautions as to not cause harm to the patients they serve.  Autoimmune disease that is not present before vaccination, can be realized after vaccination due to the combination of genes, adjuvants, and molecular mimicry that creates the environmental conditions for autoimmune disease to occur resulting in debilitating, life-long disease and sometimes death.
Intro
Comprehensive systematic review findings are being exposed at alarming rates in the previous few years regarding the incidence of autoimmune diseases and the link they have to vaccinations. Neither scientists nor doctors seem to have a clear understanding of the risk factors included in administering vaccinations to people who have a proven autoimmune disorder or if autoimmune disorders are negatively affected by vaccines, or even in some cases, caused by them. This paper will seek to identify vaccines that have a higher incidence of reports to Vaccine Adverse Event Reporting System (VAERS) for autoimmune disease onset after administration and to identify what groups of people may be at a higher risk of these events. The results will show where the scientific studies need to be directed to assure safety of our most vulnerable population, the children and infants receiving these vaccinations and ways to prevent the sudden onset of autoimmune diseases or the exasperation of preexisting autoimmune conditions.
            The Food and Drug Administration (FDA) recommends routine vaccinations starting at birth. At this time there is no clear way to identify if a newborn infant is genetically predetermined to have any kinds of autoimmune disease without doing genetic testing or waiting to see how the baby’s body develops before administering vaccinations. The FDA and World Health Organization (WHO) believe that vaccinations are the most effective way to prevent infectious diseases and have determined that vaccination must be started in early infancy to protect the population from any outbreaks. However, the long term effects and nature of autoimmune disease can take days to years to manifest in the body (Guimarães, Baker, Perricone, & Shoenfeld, 2015), complicating the identification of the possible cause being a result of the vaccination. At this time, the fact that autoimmune disorders can be caused by or exasperated by the routine use of certain vaccines is considered rare, but possible (Geier & Geier, 2004; Girard, 2005; Schattner, 2005; Waisbren, 2008; Israeli, Agmon-Levine, Blank, & Shoenfeld, 2011; Israeli, Agmon-Levin, Blank, Chapman, & Shoenfeld, 2012; Gatto, et al., 2013; Guimarães, Baker, Perricone, & Shoenfeld, 2015) and is called Autoimmune Syndrome Induced by Adjuvants (ASIA) (Agmon-Levin, Paz, Israeli, & Shoenfeld., 2009).
            Autoimmune conditions come in many forms. The American Autoimmune Related Disease Association estimates over 50 million Americans suffer from autoimmune diseases, however, the National Institute of Health (NIH) only reports numbers associated with 24 diseases that have enough epidemiological studies. Autoimmune diseases are listed in the top 10 causes of death among female children and adults up to 64 years old.  Research has shown autoimmune diseases to have a genetic component (Niewold, Goulielmos, Tikly, & Assassi, 2012) and to have the ability to interact with environmental influences (Oksenberg & Brassat, 2006). The most frequently used and available immune-suppressant treatments can cause debilitating side effects, including higher rates of infections for influenza and pneumonia (Gluck & Muller - Ladner, 2008). The initial signs and symptoms are often unspecific and often don’t occur until the disease has affected the body systems enough to become acute. The United States has the least amount of research on the mechanisms, causes, and treatments of autoimmune disorders. To compare the severity of this problem, the NIH recognizes 23.5 million Americans living with autoimmune disease; as opposed to 9 million living with cancer, and 22 million living with heart disease. Despite these numbers, cancer funding is at $6.1 billion compared to $591 million for Autoimmune diseases in 2003 (AARDA, 2004-2015).  To add one more comparison, the vaccine industry funds $1.4 billion for US vaccine research and development annually, 46% comes directly from vaccine sales (pharmaceutical companies), 36% from taxpayers (government agencies), and 18% from risk capital (private donors) (National Vaccine Advisory Committee*, 1997).  Figure one has a list of the most relevant associations between Vaccines and Autoimmune Diseases (Guimarães, Baker, Perricone, & Shoenfeld, 2015).

(Guimarães, Baker, Perricone, & Shoenfeld, 2015)


Methods
                Research databases were used to find full text articles about the risks involved of autoimmune diseases being caused by vaccinations.
            Using the JSTOR database and searching for (vaccinations cause autoimmune) pulls up 234 search results. Some of these are about vaccine research regarding trying to immunize against autoimmune diseases. The ones chosen for this paper were (Seppa, 1997;T. Gluck, 2008; Lankes, 2009).
Another search term in the same database (vaccinations autoimmune side effects) yields 4,204 results with no studies that were attempting to find links between autoimmune disease and vaccination.
The ACHS database returned 637,000 results with the terms “autoimmune diseases and vaccinations.” Pubmed retrieves 3128 results.  (Shoenfeld, 2000)
Pubmed retrieves 26 responses to “autoimmune disease side effect of vaccination,” however, not all of them fit the criteria for this meta-analysis. The ones that did were (Bedard, 2010; Guimarães LE, 2015).
Google search for “VAERS database autoimmune” returns 78,600 results. (Geier, 2004)
Using the Oregon State University library database online search resulted in 285 results directly related to the search terms “Vaccines and Autoimmunity.” (Israeli, Agmon-Levin, Blank, Chapman, & Shoenfeld, 2012), (Agmon-Levin, et al., 2014), (Gatto, et al., 2013).
After evaluating research, some citations were pulled from the original articles and further expanded on including information about autoimmune statistics, adjuvants, and previous research available about connects between autoimmunity and vaccinations.

Results of findings
           
Positive correlational findings
            The most recent comprehensive literature reviews and systematic analysis studies have identified Autoimmune (auto-inflammatory) Syndrome Induced by Adjuvants (ASIA) to include fibromyalgia (FM) and chronic fatigue syndrome (CFS) that occurs after the administration of vaccines. These conditions are part of a spectrum that includes irritable bowel syndrome (IBS) and temporomandibular joint disorders (TMJ).  All of these conditions are difficult to diagnose as they effect many systems in the body, have common symptoms, and can have a major impact on the quality of life for the patient (Agmon-Levin, Paz, Israeli, & Shoenfeld., 2009; Agmon-Levin, et al., 2014; Guimarães, Baker, Perricone, & Shoenfeld, 2015).
            The Hepatitis B vaccine is mentioned in several studies where adverse reactions that were reported included autoimmune diseases, such as Multiple Sclerosis (Oliveira, Mota, Santos-Neto, & et al., 2014), Macrophagic myofaciitis (Israeli, Agmon-Levine, Blank, & Shoenfeld, 2011), Guillain-Barre´ syndrome (Geier & Geier, 2004; Agmon-Levin, Paz, Israeli, & Shoenfeld., 2009), multiple antigenic mediated autoimmunity (MAMA) syndrome, rheumatoid arthritis (RA) and many more (Waisbren, 2008; Agmon-Levin, et al., 2014). It is shown that the combination of molecular mimicry of the antigens, the adjuvant(s) and genetic predispositions are the perfect storm for a result of autoimmune disease acquired by vaccinations (Geier & Geier, 2004; Waisbren, 2008; Israeli, Agmon-Levin, Blank, Chapman, & Shoenfeld, 2012; Agmon-Levin, et al., 2014; Shaw, 2014; Guimarães, Baker, Perricone, & Shoenfeld, 2015) The Hep B vaccine is commonly given within the first few days of birth, before any kind of genetic testing is performed to determine safety of administration of the vaccine. The majority of adverse events reported to VAERS for the Hep B vaccine were experienced by adult male and female patients within a few weeks of receiving the vaccine. The most common reported problem being a positive re-challenge of RA or arthritis in women in their 30’s, the most disabling event is neuropathy (Waisbren, 2008).
            The Human Papilloma Virus (HPV) vaccines, Gardasil and Cervarix, have been associated with the onset of debilitating autoimmune conditions such as systemic lupus erythematosus (SLE) and death (Guimarães, Baker, Perricone, & Shoenfeld, 2015) in otherwise healthy individuals. The studies conducted for safety, paid for by the pharmaceutical company GlaxoSmithKline, included control groups that were given the adjuvant aluminum. These studies show no significant difference and allowed the vaccine Cervarix to hit the market. In the studies for Gardasil, reports were made about the serious adverse effects, including venous thrombosis (which was occurring at higher rates than expected), hypersensitivity reactions, anaphylaxis, motor neuron disease, and even deaths. Autoimmunity was found to occur post-vaccination (Gatto, et al., 2013).  Furthermore, the incidence of autoimmune disease in adolescent girls is 53 in 100,000 and 389 per 100,000 in women aged 19-30, the target for these vaccines (Verstraetena, et al., 2008).
           
Negative correlational findings
            The WHO reports,
In a third study, a pooled analysis of data from 11 clinical trials involving nearly 30 000 participants aged >10 years, of which 16 142 received at least 1 dose of Cervarix and 13 811 received either a placebo containing aluminium hydroxide or 1 of 2 different hepatitis A vaccines. No increased risk for the onset of autoimmune diseases after administration of Cervarix was observed in comparison to the control group,” (The Global Advisory Committee on Vaccine Safety, 2014).

           This excerpt from the report, “Global Advisory Committee on Vaccine Safety, report of meeting held on 11-12 December 2013,” shares that the studies they are citing used placebos containing Aluminum Hydroxide which have been proven to cause Macrophagic myofasciitis, an autoimmune disease, that is triggered in genetically susceptible populations  (Agmon-Levin, Paz, Israeli, & Shoenfeld., 2009; Israeli, Agmon-Levine, Blank, & Shoenfeld, 2011). This is one of the conditions that has specific genetic markers that can be identified and used as evidence of contraindications for the use of vaccines containing Aluminum Hydroxide. This is also evidence of the blatant disregard the WHO has for science that explicitly contradicts the universal safety the WHO is trying to claim about administering vaccinations to entire populations of people without consideration for genetic testing. When the control group is receiving one of the possible causes of the autoimmune disorders, there is no doubt that the experimental group and the control group would have similar finding (Verstraetena, et al., 2008; Guimarães, Baker, Perricone, & Shoenfeld, 2015).

People with existing Autoimmune conditions have been given many vaccines due to the high risk of infections among this population. Small pox vaccines have been studied among recipients with rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, and spondyloarthritis, with no cases presenting with symptom flare up or adverse reactions (Oliveira, Mota, Santos-Neto, & et al., 2014). Influenza and pneumococcal vaccines have been recommended for people with autoimmune diseases on (Schattner, 2005). immunosuppressant therapies with results that show no adverse reactions among this population.  Among investigation, the average antibody titers measured at one month and one year after vaccination show equal or marginally less in the group of patients receiving immunosuppressant or corticosteroid treatments when compared to the control group.  Another study showed that the levels were low enough not to provide protective responses to the viruses that are being vaccinated against in 33% of patients with RA and 21% of patients with systemic lupus erythematosus (SLE) (Gluck & Muller - Ladner, 2008). 

 

Discussion and Recommendation


Georgetown University along with the Center for Biologics Evaluation and Research (CBER) of the Food and Drug Administration (FDA), is working on a project to identify the mechanisms of how autoimmunity is related to vaccinations using the reports through VAERS database. A problem with this kind of study is that because it is being overseen by the FDA, it holds a conflict of interest due to the way that pharmaceutical companies contribute to funding towards the FDA.

All of the research found for this study claiming a lack of evidence that autoimmune disorders can be caused or exasperated by vaccines has been funded or performed by entities with a direct interest in the successful campaign of vaccinations, including vaccine manufacturing companies. The British Medical Journal reported that, “published influenza vaccine studies sponsored by industry are treated more favorably by medical journals even when the studies are of poor quality,(Jefferson, Pietrantonj, Debalini, Rivetti, & Demicheli, 2009).

Research is available that shows successful trials with plant based vaccines that do not use the same adjuvants that are associated with these adverse reactions and long term injuries acquired through the administration of vaccines (Rybicki, 2014).

There are several states in the US that are now mandating vaccines along the FDA schedule with no mandatory testing to determine if the children being given the vaccines are at risk from receiving them. New protocols must be put into place to assure the safety of the routine schedule with the current vaccine products before blindly injecting children who may have genetic predispositions to autoimmune diseases. The study of Vaccinomics is identifying the “one size fits all” approach as dangerous to the populations at risk and calling for a more individualized approach that includes ruling out the risk factors mentioned in this paper (Goriely & Goldman, 2007; Verstraetena, et al., 2008; (Poland & Kennedy, 2013). Any parent who has a personal or familiar history of autoimmune disorders in their family should be delaying all vaccines until genetic testing can be completed to verify safety.

At this time, in the state of OR and many others, there are ways to get personal exemptions. However, even if the Physician attending to the patient knows of a documentable contraindication to vaccines, they are not allowed to write medical exemptions as per policy of health care provider teams and corporations. If a parent were to no longer be able to care for their child with documented contraindications, and that child was put in the care of another adult or agency that was not aware of or privy to the medical history or research the parent has completed, and there is nothing on that child’s medical file, another attending physician or pharmacist (who are allowed to administer vaccinations without looking at the patients’ medical history) could administer vaccines and injure the child. This is a very dangerous practice for the percentage of individuals with the genetic markers that could be affected due to the administration of vaccines containing adjuvants like aluminum hydroxide.  

The medical community holds that if there is evidence of wide spread success in a drug, it is worth the risk of the smaller incidence of adverse reactions. However, there is more than enough literature to show that there are specific risk factors that should surpass the bias of selective assessment, especially when the diseases most aim to prevent are now so rare and treatment for those diseases is more available (Girard, 2005). Routinely immunizing infants against sexually transmitted diseases and diseases of the blood in a low risk population is counterproductive when the risks of long term debilitating diseases can be ruled out with a simple blood test. 

Works Cited

AARDA. (2004-2015). Autoimmune Statistics. Retrieved from American Autoimmune Related Diseases Association, Inc.: http://www.aarda.org/autoimmune-information/autoimmune-statistics/
Agmon-Levin, N., Paz, Z., Israeli, E., & Shoenfeld., Y. (2009). Vaccines and autoimmunity. Nature Reviews Rheumatology, 648.
Agmon-Levin, N., Zafrir, Y., Kivity, S., Balofsky, A., Amital, H., & Shoenfeld, Y. (2014). Chronic fatigue syndrome and fibromyalgia following immunization with the hepatitis B vaccine: another angle of the ‘autoimmune (auto-inflammatory) syndrome induced by adjuvants’ (ASIA). PATHOGENESIS AND THERAPY IN AUTOIMMUNE DISEASES, 376-383.
Bedard Marrero, V., Osorio Figueroa, R., & Vázquez Torres, O. (2010). Guillain-Barre syndrome after influenza vaccine administration: two adult cases. Boletin de la Asociacion Medica de Puerto Rico, 39-41.
Desoto, M. (2010). Sorting out the spinning of autism: heavy metals and the question of incidence. Acta Neurobiologoiae Experimentus, 165-176. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/20628440
Gatto, M., Agmon-Levin, N., Soriano, A., Manna, R., Maoz-Segal, R., Kivity, S., . . . Shoenfeld, Y. (2013). Human papillomavirus vaccine and systemic lupus erythematosus. Clinical Rheumatology, 1301–1307. doi:10.1007/s10067-013-2266-7
Geier, M., & Geier, D. (2004). A case-series of adverse events, positive re-challenge of symptoms, and events in identical twins following hepatitis B vaccination: analysis of the Vaccine Adverse Event Reporting System (VAERS) database and literature review. Clinical and Experimental Rheumatology, 749-755.
Girard, M. (2005). Vaccination and autoimmunity: reassessing evidence. Medical Veritas, 549–554 .
Gluck, T., & Muller - Ladner, U. (2008). Vaccination in patients with chronic rheumatic or autoimmune diseases. Clinical Infectious Diseases, 1459(7).
Goriely, S., & Goldman, M. (2007). From Tolerance to Autoimmunity: Is There a Risk in Early Life Vaccination? Journal of Comparative Pathology, S57-S61. doi::10.1016/j.jcpa.2007.04.013
Guimarães, L. E., Baker, B., Perricone, C., & Shoenfeld, Y. (2015). Vaccines, adjuvants and autoimmunity. Pharmacological Research, 190–209. doi:10.1016/j.phrs.2015.08.003
Israeli, E., Agmon-Levin, N., Blank, M., Chapman, J., & Shoenfeld, Y. (2012). Guillain-Barre syndrome--a classical autoimmune disease triggered by infection or vaccination. Clinical Reviews in Allergy & Immunology, 121. doi:http://dx.doi.org/10.1007/s12016-010-8213-3
Israeli, E., Agmon-Levine, N., Blank, M., & Shoenfeld, Y. (2011). Macrophagic Myofaciitis a Vaccine (alum) Autoimmune-Related Disease. Clinical Reviews in Allergy & Immunology, 163-168. doi:10.1007/s12016-0108212-4
Jefferson, T., Pietrantonj, C. D., Debalini, M. G., Rivetti, A., & Demicheli, V. (2009). Relation of Study Quality, Concordance, Take Home Message, Funding, and Impact in Studies of Influenza Vaccines: Systematic Review. British Medical Journal, 531. doi:10.1136/bmj.b354
Lu, C.-C., Wang, Y.-C., Lai, J.-H., Lee, T. S.-H., Lin, H.-T., & Chang, D.-M. (2011). A/H1N1 influenza vaccination in patients with systemic lupus erythematosus: Safety and immunity. Vaccine, 444-450. doi:10.1016/j.vaccine.2010.10.081
National Vaccine Advisory Committee*. (1997). United States Vaccine Research: A Delicate Fabric of Public and Private Collaboration. Seattle, WA: American Academy of Pediatrics.
Niewold, T. B., Goulielmos, G. N., Tikly, M., & Assassi, S. (2012). Autoimmune Disease Genetics. Clinical and Developmental Immunology, 2.
Oksenberg, J. R., & Brassat, D. (2006). Immunogenetics of autoimmune disease. New York, NY: Springer Science and Business Media.
Oliveira, A. C., Mota, L. M., Santos-Neto, L. L., & et al. (2014). Occurrence of Autoimmune Diseases Related to the Vaccine against Yellow Fever. Autoimmune Diseases, 8. doi:10.1155/2014/473170
Poland, G. A., & Kennedy, R. B. (2013). Vaccinomics, adversomics, and the immune response network theory: Individualized vaccinology in the 21st century. Seminars in Immunology, 89-103.
Porto, F. D., Lagana`, B., Biselli, R., Donatelli, I., Campitelli, L., Nisini, R., . . . Rossi, F. (2006). Influenza vaccine administration in patients with systemic lupus erythematosus and rheumatoid arthritis Safety and immunogenicity. Vaccine, 3217–3223. doi:10.1016/j.vaccine.2006.01.028
Rubinstein, E. (2004). Vaccination and Autoimmune Disease: the Argument Against. IMAJ, 433-435.
Rybicki, E. P. (2014). Plant-based vaccines against viruses. Virology, 1-20. doi:10.1186/s12985-014-0205-0
Schattner, A. (2005). Consequence or coincidence? The occurrence, pathogenesis and significance of autoimmune manifestations after viral vaccines. Vaccine, 3876–3886. doi:10.1016/j.vaccine.2005.03.005
Shaw, C. A. (2014). Aluminum-Induced Entropy in Biological Systems: Implications for Neurological Disease. Journal of Toxicology, 1-27.
Siegrist, C.-A. (2007). Mechanisms Underlying Adverse Reactions to Vaccines. Journal of Comparitive Pathology, S46-S50. doi:10.1016/j.jcpa.2007.04.012
Sr., B. A. (2008). Acquired autoimmunity after viral vaccination is caused by molecular mimicry and antigen complimentarity in the presence of an immunologic adjuvant and specific HLA patterns. Medical Hypotheses, 346–348. doi:10.1016/j.mehy.2007.04.043
The Global Advisory Committee on Vaccine Safety. (2014). Global Advisory Committee on Vaccine Safety, report of meeting held on 11-12 December 2013. Geneva, Switzerland: WHO Weekly Epidemiological Record.
Verstraetena, T., Descamps, D., David, M.-P., Zahaf, T., Hardt, K., Izuriet, P., . . . Breuer, T. (2008). Analysis of adverse events of potential autoimmune aetiology in a large integrated safety database of AS04 adjuvanted vaccines. Vaccine, 6630–6638. doi:10.1016/j.vaccine.2008.09.049
Waisbren, B. A. (2008). Acquired autoimmunity after viral vaccination is caused by molecular mimicry and antigen complimentarity in the presence of an immunologic adjuvant and specific HLA patterns. Medical Hypotheses, 346–348. doi:10.1016/j.mehy.2007.04.043
Wraith, D. C., Goldman, M., & Lambert, P.-H. (2003). Vaccination and autoimmune disease: what is the evidence? The Lancet, 1659–1666. doi:10.1016/S0140-6736(03)14802-7

 


 

Thursday, August 27, 2015

The Lamiaceae family of plants have much to offer in the way of anticancer purposes.

While we are sharing final papers for this term, how about my Botany paper on the Mint family and how it has been proven to show anticancer properties? Also ungraded.

The Lamiaceae family of plants have much to offer in the way of anticancer purposes.
Kaire Downin, American College of Healthcare Sciences

Botany 501 Summer 2015

Abstract
Several studies showing many species of plants from the family Lamiacea have shown positive results as to their effectiveness in reducing cancer cells and helping to improve immune system function while treating for cancer in vitro and in vivo studies. Yet, many doctors do not utilize or understand the work of these complementary treatments. The Lamiaceae family of plants have much to offer in the way of anticancer purposes.
Introduction
Treating cancer is a difficult undertaking, often requiring harsh chemicals and long, expensive treatments. Scientists, doctors, and patients are welcoming to the possibilities that more effective complementary treatments are becoming more understood and available. These treatments can lessen the time needed to treat cancer with chemotherapy and in some cases, negate the need for chemotherapy all together. This paper will analyze existing research results showing that the Lamiaceae family of plants have much to offer in the way of anticancer properties and how they can be used to treat multiple cancers.
The Lamiaceae family has around 236 genera and between 6,900 and 7,200 species. The specimens tend to be aromatic and are frequently grown in home gardens for culinary uses, most familiarly basil, sage, rosemary, thyme, lavender, and oregano (Raja, 2012).  Structurally, The Lamiaceae family have stems that are square and leaves that are simple and grow opposite of each other. This family is highly aromatic with a high essential and volatile oil content which is responsible not only for the strong smells that the fresh plant produces but also its antimicrobial and antifungal properties (Bozin, Mimica-Dukic, Simin, & Anackov, 2006). The irregular flowers are 5 calyx toothed and display 2 lobes on the upper lip while having 3 lobes on the bottom.

Methods
Search terms “frequently used medicinal plants of Lamiaceae” was entered into Google and returned 228,000 results. The same terms in Google Scholar resulted in 18,600 results. The same terms used in the ACHS database library system revealed 110,000.
Search terms “anticancer properties in Lamiaceae” resulted 5,160 hits on Google Scholar, 12,500 on the ACHS library database, and 141,000 results on Google.
In order to determine which studies were useable for this review, the publications must be peer reviewed journals and the study must be focused on the Lamiaceae family and it’s use with anticancer purposes. Access to the full text also must be available, this ruled out several which didn’t have free access. Many of the results on the first page of each search had common listings. Most of the studies used for this review came from the first page of the search results.

Results
            Teucrium is a genus out of the family Lamiaceae and is commonly known as Germander. This group of plants has about 100 species, mainly from the Mediterranean. They are used in landscaping as a perineal shrub and have fragrant flowers (The Taunton Press, 2015). Teucrium has a long history of many species being useful in pharmacy around the world. The International Journal of Molecular Sciences published a study in 2011 that evaluated some species of Teucrium as potential antiproliferative and antioxidant agents with in vitro experiments with the human colon cancer cell line and extracts from nine species of the plant. The used the colon cancer cells because of the scientific evidence of the Teucrium having positive results on healing other digestive tract disease. The results indicated that four of the nine species (name species) tested had a strong antiproliferative effect and should be considered for further research. These extracts are a viable source of natural polyphenolic compounds (Stankovic, et al., 2011). Polyphenols are micronutrients in our diets that if consumed in enough amounts based on bioavailability, can have preventative effects on cancer and other degenerative diseases (Manach, Scalbert, Morand, Rémésy, & Jiménez, 2004).  
            Bangalore University sought out to identify and research the medicinal values of plants in the Lamiaceae family that grew in Karnataka, India. 109 plants have been identified from the Lamiaceae family which have medicinal qualities, ten of which were selected for the research review. (list plants) The researchers put together a table which lists the medicinal values shown in other research. The plants listed which have a history of anticancer, antiproliferative, or antioxidant properties were
·         Anisomeles indica which “inhibit inflammatory mediators and tumor cell proliferation,” and is used for “antimetastatic effects on human breast cancer cells.”
·         Hyptis suaveolens which has essential oil with antioxidant properties and enough results as an appetite increaser and anti-nausea to make it helpful as a complementary treatment along with other treatments that often cause digestive problems.
·         Leonotis nepetaefolia having biological activities including anticancer properties
This study concluded with acknowledging the rich amount of biologically active compounds that promote many therapeutic values (S.M.Venkateshappa & K.P.Sreenath, 2013).
Journal of Traditional and Complementary Medicine published a study in 2014 that evaluated anticancer properties of plants in the Lamiaceae family, among others, commonly used in folk medicine in India. Extracts of Lavendula bipinnata were made and experiments were performed using cancer cell lines obtained from the National Center of Cell Science. Results revealed that L. bipinnata demonstrated significant anticancer and moderate cytotoxic properties to several  cell lines. It was concluded that the plants used in the study, including L. bipinnata should be considered for further research in order to develop new anticancer drugs and that the current research suggests the validation of the continuing use of the existing natural treatments that include these plants in the ingredients (Shaikh, Pund, Dawane, & Iliyas, 2014).
The Iranian Journal of Pharmaceutical Research published a research article in 2013 about the medicinal qualities of Salvia, a genus of Lamiaceae with about 960 species. Eleven species were selected for the study that grow in Iran and were collected in their habitat. They were screened for cytotoxic activity and antimicrobial activity using extracts from the plants and then tested in three human cancer cell lines, two were leukemia lines and one was breast cancer. They were all shown to be affective against the cancer cell lines at different rates, the strongest being S. limbata, S. hypoleuca and S. aethiopis. At the end of the study, it was S. santolinifolia and S. eremophila that were considered to be “the most interesting bioactive plants in this study,” and recommended for further investigation of their active constituents (Omidreza Firuzi, 2013).
Papers have also been published out of Brazil showing the anticancer activity of Hyptis mutabilis, commonly referred to as common bushmint. This paper focuses on the anticancer activity from water extracts on mice with tumors. No adverse conditions were encountered during the experiment and there was antitumor activity displayed towards sarcoma tumors in the mice (Ximenes, Melo, Magalhães, Souza, & Albuquerque, 2012).
Discussion
            According to the results of a survey sent out to members of the American Society of Clinical Oncology in 2010, one of the barriers to doctors utilizing herbs and supplements in the treatment of cancer is their lack of knowledge. This survey revealed less than 40% of oncologists initiating conversations with their patients about the use and benefits of herbs and supplements while treating cancer (Lee, et al., 2014). Other potential complications that physicians report is that the herbs and supplements are managed by the patients while the doctors are managing the treatments. Some reported successful herbs that are used during cancer treatment in pediatric units are St. John’s Wort for depression, Ginger for nausea as well as Echinacea for immune system support (Quimby, 2007). Even though there are oncologists that find using herbs to treat the symptoms that are associated with the side effects of cancer treatments can be seen as a step in the right direction, there are available herbs that actually treat the cancer directly as we have seen through this summary research. It is recommended that oncologist have access to and are required to take continuing education classes on how to best utilize these less expensive and less destructive complementary treatments to help lessen the time of treatment and induce healing of cancers in the human population.
Conclusion and recommendation
It is clear from the multiple studies over many years that plants in the Lamiaceae family are effect agents of anticancer activity and have the potential to be used in anticancer drugs and technology.  After all the reports are in, it is also clear that there is room for improving the research to understand dosage and length of treatments. Many of these articles have used extracts that were produced with chemicals and not just the water extracts like the simple and common teas and infusions that are often used in folk or traditional medicine. There was no discussion on the risks or contraindications of using these compounds and most of the studies referred to being ready for more extensive research to determine these things.
            Publishing these findings in journals commonly read by oncologists and making the information available through workshops and classes for continuing education could expose the people who are working with the patients to a broader variety of treatments. Cancer treatments are costly and often put people in a large amount of debt and many only gain a few months from the destructive chemotherapy sessions. Complementary treatments that are proven to be effective should be employed by these doctors and patients in order to help save them money and time. When dealing with destructive and often terminal illnesses like Cancer, often people are not in the mind frame to do their own research and find these solutions. It is time we demand more from the medical community and put a stop to the price gouging practices of pharmaceutical technology and take advantage of the many options in plant medicine that are easily available and affordable to administer.
             

References

Bozin, B., Mimica-Dukic, N., Simin, N., & Anackov, a. G. (2006). Characterization of the Volatile Composition of Essential Oils of Some Lamiaceae Spices and the Antimicrobial and Antioxidant Activities of the Entire Oils. Journal of Agriculture and Food Industry, 1822-1828. doi:10.1021/jf051922u
Manach, C., Scalbert, A., Morand, C., Rémésy, C., & Jiménez, a. L. (2004). Polyphenols: food sources and bioavailability. American Journal of Clinical Nutrition, 727-747.
Omidreza Firuzi, R. M. (2013). Cytotoxic, Antioxidant and Antimicrobial Activities and Phenolic Contents of Eleven Salvia Species from Iran. Iranian Journal of Pharmaceutical Research, 801-810.
Raja, R. R. (2012). Medicinally Potential Plants of Labiatae (Lamiaceae) Family: An Overview. Research Journal of Medicinal Plant, 203-216.
S.M.Venkateshappa, & K.P.Sreenath. (2013). POTENTIAL MEDICINAL PLANTS OF LAMIACEAE. American International Journal of Research in Formal, Applied & Natural Sciences, 82-87.
Shaikh, R., Pund, M., Dawane, A., & Iliyas, S. (2014). Evaluation of Anticancer, Antioxidant, and Possible Antiinflammatory Properties of Selected Medicinal Plants Used in Indian Traditional Medication. Journal of Traditional and Complementary Medicine, 253-257.
Stankovic, M. S., Curcic, M. G., Zizic, J. B., Topuzovic, M. D., Solujic, S. R., & Markovic, S. D. (2011). Teucrium Plant Species as Natural Sources of Novel Anticancer Compounds: Antiproliferative, Proapoptotic and Antioxidant Properties. International Journal of Molecular Sciences, 4190-4205. doi:10.3390/ijms12074190
The Taunton Press. (2015). Genus: Teucrium. Retrieved from Fine Gardening: http://www.finegardening.com/teucrium
Ximenes, R. M., Melo, A. M., Magalhães, L. P., Souza, I. A., & Albuquerque, J. F. (2012). Antitumor Activity of Leaves from Hyptis mutabilis (A. Rich.) Briq. (Lamiaceae) in Mice Bearing Tumor. Dataset Papers in Pharmacology. Retrieved from http://dx.doi.org/10.7167/2013/169357

Final paper about GMO's and placental cells and other stuff you never wanted to know about

This paper was inspired by Robin Lim's letter expressing concern about increased placental deformities in her practice. You can find her letter here.  But once I got into the research, there was nothing that could put it all together, the info was either inaccessible or not there at all. But what I did find was equally disturbing. This paper is not being put out there in any way to prove anything, but to make you think and show some possible correlations that should have further research. In order to do that kind of research, data must be collected for it, and especially where placentas are concerned, that data is not quite available or what is available is largely incomplete as so many placentas are discarded with no more than a glance to check for specific things. I expect many people will read this and give me a lot of criticism, and that is fine. I want to know where I missed the mark. I don't understand this as much as I would like. So if anyone wants to use this start and take off with it and prove something, by all means, go for it. So here it is... This is after submission, before grading.

Genetically modified foods and associated chemicals are possible causes of the increase in placental abnormalities in humans.

A meta analysis of data surrounding the use of GM crops and glyphosate
Kaire downin, american college of healthcare science,
Summer 2015 anatomy and physiology 501


Abstract
             In a time where food is scarce in many areas of the world, scientist have employed the use of genetically modifying plants for food in a way that they can be resistant to chemicals meant to protect them from other weeds and insects from destroying thee much needed crops. This much interference with the natural make of plants and the addition of these toxic chemicals used to protect them has created a bigger problem than hunger when the bodies of our children and generations afterwards are effected genetically and physically starting from the development of placentas to the ability to reproduce later in life. This paper seeks to prove correlations to the use of glyphosate and Round-up products on genetically modified plants with the abnormalities that birth workers are finding in placentas. In the process of reviewing studies, other concerns are revealed such as the human reproduction rate drops in countries with high GM Soy production and the incidence of birth defects, genetic abnormalities and Celiac’s Disease.
Introduction
In May of 2009, Robin Lim, creator of the Bumi Sehat Birth Clinic in Bali and winner of the 2011 Hero of the Year Award, sent an email to a group of natural birth activists, doctors, writers and people concerned about some of the conditions she was witnessing in mothers who were giving birth at her birth clinic, conditions that used to be rare but were now becoming more common and life threatening. She was encountering anomalies such as retained placenta, velamentous umbilical cord insertion and short cords, decreases in Wharton's jelly, and still births due to cord malfunctions and destruction in late stages of gestation. Lim goes on to site 3 contributions to affected placentas being “malnutrition, pollution (including Roundup) and GMO soy,” (Lim, 2011). The implications for her concern could affect the way food is produced. Many studies have been performed that show direct malfunctions and malformations of the body as a result of GMO crops and chemicals. The purpose of this study is to identify how GMO and the chemicals associated with these crops are sources that may cause placental abnormalities and increase the risk to birthing mothers and babies.
Methods
Upon running searches through American College of Healthcare Science research data base, using these terms produced these numbers of results:
·         Genetically modified organism fetal development:  About 1,920,000 results (most of these results had to do with genetically modifying for reproduction , not the intake of foods. )
·          GMO foods fetal development: About 144,000 results
·         Genetically modified food fetal development:  About 1,310,000 results
With so many results, filtering for a common factor, which seemed to be GM Soy, seemed like a way to narrow some down. The next search was on Google Scholar using the terms “GMO Soy and placental abnormalities” which yielded about 3,590 results. None of the results had any direct scientific study to placental development in-utero.
Results
            The earliest study selected from the results was in 2002 and was about the feeding of glyphosate (GLYP) tolerant soybeans to mice and the resulting development through prenatal to adults. GLYP tolerant soy beans are the “Round-up Ready” brand made by Monsanto Corporation. The use of glyphosate is for weed control on major crops (S. R. Padgette, et al., 1995). In this study, scientists fed a transgenic soybean or non-transgenic soybean diet to groups of pregnant female mice and during their lactation period. The male mice born to these females were continuously fed on the same diet until certain intervals of age and then culled and their testes were dissected. The researchers also did multigenerational experiments in the same way, using adult males from the original group born to the mothers fed the diet to breed new stock. The results showed no difference in litter size, body weights, percentages of testicular cell populations, or macromolecular cell growth between mice fed the transgenic diet and the non-transgenic diets (Brake & Evenson, 2003). However, this study had no reference to the health or structure of the placentas created during the gestation of the female mice fed the diets.  
            A French Study from 2005 tested the Differential effects of GLYP and Roundup on human placental cells. GLYP and Roundup were prepared in a lab at the dilutions approved for agricultural use and used to test reactions with human placental cell cultures at different concentrations for either one hour, 18 hours, 24 hours, or 48 hours. The examinations included extracting the RNA and measuring aromatase activity with radioimmunoassay. Human placental tissue from full term placentas obtained from non-smoking women were used for the test which showed measurements of microsomal aromatase activity and other measurements of reductase activity. The results were different between the GLYP alone and the Roundup product which adds adjuvants to the solution. Even at 10 times lower the suggested agriculture use, the Roundup treated cells had reduced cell viability twice more than glyphosate alone. This study concludes that GLYP is a “disrupter of mammalian cytochrome P450 aromatase activity from concentrations 100 times lower than the recommended use in agriculture.”  Cytochrome P450 aromatase is the enzyme responsible for estrogen synthesis (SIMPSON, et al., 2013).  Cytochrome P450 aromatase is also responsible for sexual differentiation of neural structures, specifically the development of the central nervous system and sexual behavior and function (Lephart, 1996). The researchers on this team suggest that reproductive problems are a concern when exposure to GLYP occurs, even at lower than suggested use for agriculture levels (Sophie Richard, Sipahutar, Benachour, & Seralini, 2005).
Another study shows that the adjuvants in Roundup increase the toxicity of the GLYP after an experiment with oyster larvae where toxicity was induced using Roundup at 1/20th the amount of GLYP needed to produce the same toxic results (Mottier, et al., 2013).
            In Canada, the blood of 30 pregnant women and 39 non-pregnant women was analyzed to evaluate the correlation between mother and fetal exposure to GLYP and the levels in their bodies in 2011. GLYP has several metabolite toxins associated with it and can be traced in blood samples. In this experiment, they were looking for GLYP and its metabolite, aminomethyl phosphoric acid (AMPA), another herbicide called gluphosinate (GLUF), and its metabolite 3-methylphosphinicopropionic acid 3 (3-MPPA), and Cry1Ab Protein (a Bt Toxin).  The non-pregnant women were found to have GLYP (5%) and GLUF (18%) in their serum samples where pregnant women were not found not have it. This might be because some of these subjects had not been exposed to the GMO foods that contain these chemicals. The researchers express concerns and point out other findings in previous animal studies which they acknowledge use much higher levels of GLYP to test fetal development with results that show skeletal retardation in developing rats (Dallegrave, et al., 2003) and harm to human placental and umbilical cells (Sophie Richard, Sipahutar, Benachour, & Seralini, 2005; Benachour & Séralini, 2009). However, 3-MPPA were detected in 67% of the non-pregnant women and 100% of the pregnant women and the umbilical cords of their fetuses. Cry1Ab was found in the blood samples of 93% of mothers, 80% of fetuses and 69% of non-pregnant women. Furthermore, this toxin has been shown to be present in livestock fed on plants that have been treated with GLUF making it possible that people could have further contamination through meat consumption (Aris & Leblanc, 2011). This study was the first of its kind to detect pesticides associated with modified foods in women and their fetuses. It was not noted if the babies born to the women in the study experienced any trauma at birth, the cesarean rate, any placental abnormalities or fetal deaths.
            Hannah Landecker from the University of California Center for Society and Genetics wrote a research paper not based on experiments with GMO foods or toxic herbicides and pesticides, but from an Epigenetic stand point of food as exposure. Taking the understanding that food becomes part of one’s environment during gestation and lifetime and has the ability to influence gene expression, Landecker explains the social scientific aspect of food shaping our health as a cause and controller of disease. These epigenetic changes that can happen, as in the genetic changes seen in the 2005 French study by Simpson, et al, can have a role in resetting or reprogramming the gene expression in individuals through nutrient exposure as early in life as in the womb. The genetic expressions are then passed down to generations afterwards due to this interaction of the molecular make up of individuals. Landecker points out that this is ingrained in our culture from a political and technical network of food production, distribution and consumption and is transgenerational giving it a strong economic influence. When food is manufactured in an engineered state and is unintentionally toxic, it becomes an environmental exposure that influences the metabolism of the people inhabiting this specific point in history where we modify food in more ways than we have ever in all the years of agriculture. People have a limited control of what they consume when engineered products are in so many food items and consumed at such a high rate. This shapes the way our future generations will be able to receive and metabolize food, as it influences the gene expression of fetuses before they are even born and passes these gene to the next generation compounding the exposures. An addition to this collection of exposures to toxic chemicals, we are also breathing, bathing and living in environments with more engineered toxins than ever before, sure to change the physiology of our bodies (Landecker, 2011).  Even though this research paper did not expressively deal with genetically modified foods and GLYP or Roundup, it explains about how our bodies process foods and the molecules within the foods to influence genes and ties together some of the surrounding research that shows that these toxins effect our genetic expressions (SIMPSON, et al., 2013). A focus of this paper was on eating foods with purpose, not just for the nutritional make up or taste, but for their reaction on the body such as helping to lower cholesterol or having an antioxidant effect. We can eat with purpose to enhance our health but when the foods we are looking to for these health changing effects are also molecularly enhanced with other toxins that effect our genes in negative ways, we are also exposing ourselves to possible changes that induce disease. Which brings me to the next study.
            In 2013, Anthony Samsel, an independent scientist from New Hampshire, along with Stephanie Seneff, a computer scientist who does work with Artificial intelligence projects in Massachusetts, set off to show the correlations between GLYP and Celiac’s Disease and other related health complications that have been on the rise at the same rate as the increased use of GMO foods and GLYP or Roundup. Their findings were evident of the connection and bring to light just how devastating environmental toxins can affect the population. In their study they show that Celiac’s Disease, whose symptoms include diarrhea, skin rashes, nausea and depression, is affecting up to 5% of the population in North America and Europe. The imbalances of gut bacteria due to the Celiac Disease are directly related to the way that GLYP interacts with the microbiome of the body. People with Celiac’s often have reproductive challenges that include infertility in males, miscarriages and birth defects like microcephaly.  There is evidence that GLYP could be disrupting the metabolizing of complex proteins, leaving behind the larger protein fragments that could be triggering autoimmune reactions leading to injury to the small intestine, which is a symptom of Celiac’s Disease. GLYP’s known reaction with CYP enzymes creates excess retinoic acid (RA) that is associated with complications in pregnancy including teratogenic effects in the fetus (Samsel & Seneff, Glyphosate’s Suppression of Cytochrome P450 Enzymes and Amino Acid Biosynthesis by the Gut Microbiome: Pathways to Modern Diseases, 2013). These abnormalities include microcephaly and deformations of the skull and hindbrain underdevelopment. Other birth defects listed were cleft palate, ear malformations, polydactyly, syndactyly, and anencephaly. Also reported were in laboratory in vitro studies that showed DNA strand breaks, apoptosis, and plasma membrane damage. Rates of Celiac’s Disease, Thyroid cancer, hospitalizations for acute kidney injury, end stage renal disease death, deaths from Parkinson’s Disease, deaths due to intestinal infections, all plotted on a graph from 1990 to present compared with the GLYP use on corn, soy and wheat crops all show the same upward trend correlation (Samsel & Seneff, 2013).  Again, this research paper does not specifically address placental abnormalities but does show all the ways in which GLYP effects other body systems through exposure. If the digestive tract of people exposed to GLYP can be this disrupted, causing the inflammation, autoimmune and nutrient deficiencies mentioned in this and other studies cited in this paper, it could also be assumed that these problems will have an effect on growing healthy placentas in gestating women.  
Discussion
People have been genetically engineering food plants since the agricultural revolution began. Only now that it is being performed in labs, with the purpose of making plants resistant to chemicals, are people becoming concerned. Is it the GM foods that are dangerous or is it the chemicals that we are adding to them which is causing the problems seen in some of these studies. Can a study even identify the problems that Robin Lim has expressed concern about, or is it too late because we have seen multiple generations with exposure to the toxins reported?  Several of the above studies have been conducted after babies were born with not enough data to prove any placental structural differences in mothers who are exposed to GLYP or Roundup. However one thing remains indisputable, health problems are increasing at the same rate that GLYP and specifically, Roundup is being used over the whole world.
Part of the goal for this paper was to collect the data from when GMO crops were introduced to several countries and compare it to the rate of fetal deaths due to placental abnormalities and Sudden Infant Death Syndrome (SIDS) which is found to have a twofold increase in babies that are born to mothers who experienced placental abruption or placenta previa (Li & Wi, 1999). The only data that was available that suggested a similar correlation was a study from 2013 that explained that Argentina and Brazil, the world’s largest GM soy producers have been experiencing a drop in birth rates and an increase in still births and late term abortions starting at the same time the GM crops were introduced (Samsel & Seneff, Glyphosate, pathways to modern diseases II: Celiac sprue and gluten intolerance, 2013). It was not noted if pregnancy rates remained the same or dropped as well, and even if they did drop, with evidence showing that lack of fertility could be in relation to the use of GM crops, the only way one could show a correlation is if the rates of methods of birth control rose at the same time as birth rates dropped.  In a future study, comparing these numbers from other locales would help to determine if there is a correlation between the time that GMO crops have been in the country and the rates of fetal and infant deaths. It is also important for birth workers to carefully document the state of the placenta at the time of birth or termination so the date is available and further studies could be conducted on exactly what the consequences are from the beginning of life. 
Conclusions and Recommendations
            It is recommended that a study be conducted by collecting data of the state of placentas at birth, as well as reporting about the circumstances surrounding fetal death in a more clear and concise method with details surrounding the condition of the pregnancy and placental tissues. Only after this kind of data is available are we going to be able to tie together the possible correlations between the crops and/or GLYP and Roundup use and the destruction of human placental tissue and developmental abnormalities that are leading to fetal death and hemorrhage in mothers. In the meantime, there are plenty of studies showing the dangers of using these chemicals and the changes they are responsible for, not just in our environment but in our bodies and genetic make-up that are going to affect generations to come without any knowledge of just how much. More rigorous testing and wait periods for agricultural products with more oversight and regulations should be supported to avoid this in the future along with barring the people who have a vested interest in such companies, such as Monsanto, from having any political power or influence. Taking the profit motive out of food and medicine could tangibly help prevent some of these atrocities from happening. Monsanto has been responsible for some of the worst public experiments of the last century and the affects can be seen worldwide. With the decline of health and the decline of human birth rates, it is safe to say that the profits they have collected should be put back into the research to reverse the effects of the environmental toxins we have been exposed to.



Bibliography
Aris, A., & Leblanc, S. (2011). Maternal and fetal exposure to pesticides associated to genetically modified foods in Eastern Township of Quebec, Canada. Reproductive Toxicology, 528-533.
Benachour, N., & Séralini, G.-E. (2009). Glyphosate Formulations Induce Apoptosis and Necrosis in Human Umbilical, Embryonic, and Placental Cells. Chemical Research in Toxicology, 22(1), 97-105. doi:10.1021/tx800218n
Brake, D. G., & Evenson, D. P. (2003). A generational study of glyphosate-tolerant soybeans on mouse. Food and Chemical Toxicology, 29-36. doi:10.1016/j.fct.2003.08.003
Dallegrave, E., Mantese, F. D., Coelho, R. S., Pereira, J. D., Dalsenter, P. R., & Langeloh, A. (2003). The teratogenic potential of the herbicide glyphosate-Roundup® in Wistar rats. Toxicology Letters, 142(1-2), 45-52. doi:10.1016/S0378-4274(02)00483-6
Landecker, H. (2011). Food as exposure: Nutritional epigenetics and the new metabolism. BioSocieties, 6(2), 167-194.
Lephart, E. D. (1996). A review of brain aromatase cytochrome P450. Brain Research Reviews, 22(1), 1-26. doi:10.1016/0165-0173(96)00002-1
Li, D.-K., & Wi, S. (1999). Maternal Placental Abnormality and the Risk of Sudden Infant Death Syndrome. American Journal of Epidemiology, 149(7), 608-611.
Lim, R. (2011, August 15). GMO FOODS AND THE DAMAGE TO HUMAN BABIES, PLACENTAS & UMBILICAL CORDS. Retrieved from Birth of a New Earth: http://birthofanewearth.blogspot.in/2011/08/gmo-foods-and-damage-to-human-babies.html
Mottier, A., Kientz-Bouchart, V., Serpentini, A., Lebel, J. M., Jha, A. N., & Costil, K. (2013). Effects of glyphosate-based herbicides on embryo-larval development and metamorphosis in the Pacific oyster, Crassostrea gigas. Aquatic Toxicology, 128-129, 67-78. doi:10.1016/j.aquatox.2012.12.002
S. R. Padgette, K. H., Eichholtz, D. A., Peschke, V. M., Nida, D. L., Taylor, N. B., & Kishore, G. M. (1995). Development, Identification, and Characterization of a Glyphosate-Tolerant Soybean Line. Alliance of Crop, Soil and Environmental Science Societies, 35(5), 1451-1461. doi:10.2135/cropsci1995.0011183X003500050032x
Samsel, A., & Seneff, S. (2013). Glyphosate, pathways to modern diseases II: Celiac sprue and gluten intolerance. Interdisciplinary Toxicology, 6(4), 159-184. doi:10.2478/intox-2013-0026
Samsel, A., & Seneff, S. (2013). Glyphosate’s Suppression of Cytochrome P450 Enzymes and Amino Acid Biosynthesis by the Gut Microbiome: Pathways to Modern Diseases. Entropy, 1416-1463. doi:10.3390/e15041416
SIMPSON, E. R., MAHENDROO, M. S., MEANS, G. D., KILGORE, M. W., HINSHELWOOD, M. M., GRAHAM-LORENCE, S., . . . BULUN, S. E. (2013). Aromatase Cytochrome P450, The Enzyme Responsible for Estrogen Biosynthesis. Endocrine Reviews. doi:http://dx.doi.org/10.1210/edrv-15-3-342
Sophie Richard, S. M., Sipahutar, H., Benachour, N., & Seralini, G.-E. (2005). Differential Effects of Glyphosate and Roundup on Human Placental Cells and Aromatase. Environmental Health Perspectives, 113(6), 716-720.