Although statin drugs, otherwise known as HMG-coenzyme A reductase inhibitors, are very effective in reducing the serum levels of LDL, the so-called “bad” cholesterol, it is not clear that this is the reason why they reduce the incidence of heart attacks. Over the last decade or so, there has developed among the research community a strong opinion that statins prevent heart attacks via a so-called pleiotrophic effect unrelated to their ability to reduce serum LDL [7]. Recently, the idea that this pleiotrophic effect is tied to statins’ observed ability to increase the production of nitric oxide by endothelial cells lining the artery walls has gained considerable traction [1, 12, 14]. It’s been argued that nitric oxide has a lot of benefits in terms of relaxing the artery wall, as well as anti-proliferative and anti-migratory properties, which are considered to be protective features in cardiovascular disease in vessels [4].
Armed with this knowledge, I became interested in finding other examples from the literature of mechanisms that increase the production of nitric oxide. I stumbled upon an article on a rare disease called paroxysmal nocturnal hemoglobinurea (PNH) [13], first described in the literature in 1986 [8], only a few years after statins began to be widely prescribed.
This condition immediately caught my attention, because the health issues associated with it fit well with a set of side effects I had learned were associated with statins, such as difficulty swallowing, abdominal pain, and erectile dysfunction. Furthermore, the condition is caused by a genetic defect in a protein called PIG-A [2], which is essential to orchestrate glycosylphosphatidylinositol (GPI)-anchoring of proteins to cell membranes. Statins also interfere with GPI-anchoring, directly through their obstruction of the mevalonate pathway, by inhibiting the synthesis of isoprenoids, which, in turn, are essential for the GPI-mediated membrane attachment of signaling molecules like Rho GTPases [12].
PNH results in two major direct effects, one related to red blood cells (RBCs) and the other to platelets. The RBCs depend on the impaired protein to protect them from hemolysis – a breaking apart of their membrane and a spilling of their contents into the blood stream. Platelets depend on the same protein to protect them from forming blood clots.
RBCs have an important role and a difficult job in transporting a highly toxic element – oxygen – to all the tissues. Once they’ve picked up oxygen, the resulting oxyhemoglobin is a strong oxidizing agent. It is therefore very important that RBCs sequester hemoglobin within their walls to protect blood proteins and fats from oxidative damage. RBCs ordinarily produce an abundance of coenzyme Q10 (ubiquinone) to protect their own membrane from oxidation damage, and statins interfere with the production of coenzyme Q10 [11]. The genetic disease, sickle cell anemia, is associated with an excess of oxidizing agents in the blood and therefore the sickled RBCs maintain far more coenzyme Q10 than normal RBCs [9]. Statins’ known ability to deplete the supply of Coenzyme Q10 would result in excess oxidation damage to RBC membranes, which would further increase their vulnerability to hemolysis. This may mean that blacks, who have a much higher incidence of sickle cell anemia (due to the protection it affords against malaria), may also have a greater susceptibility to statin side effects.
What does all of this have to do with nitric oxide? It turns out that hemoglobin is an avid scavenger of nitric oxide – it binds strongly to the gas and disables its ability to signal arterial relaxation. Furthermore, RBCs contain a protein, L-arginase, that actively degrades the substrate for NO synthesis, L-arginine. As a consequence of hemoglobin and L-arginine now roaming freely in the blood stream, spilled out from the destroyed RBCs, there will be severe arterial constriction unless the endothelial cells greatly increase their production of nitric oxide. The mechanism is mediated by the protein erythropoietin (epo) which both stimulates the production of replacement RBCs from stem cells in the bone marrow and acts as a signaling agent to induce NO production in the artery wall [5]. So I would like to suggest that statins increase the production of nitric oxide as a compensatory mechanism to its active destruction by hemoglobin and its reduced substrate supply due to L-arginase.
I also found a series of articles on a fascinating breed of genetically engineered mice, which produce excessive human epo and therefore have too many RBCs in their blood serum [15, 10, 5]. These mice also dramatically overproduce NO. They don’t fare well, however; they develop paralysis in their hind legs and die young.
Statin drugs also interfere with mobility – many of the web side effect reports written by people who have taken statin drugs talk about muscle weakness, difficulty walking, and decreased mobility. These phrases all came up as highly significantly over-represented in statin reviews compared to age-matched reviews in our studies on statin side effects. Comparing the collective count of a number of phrases associated with “difficulty walking” in reviews on statin drugs vs other drugs yielded a skewed distribution with a p-value less than 0.0005.
Another indicator that I am on the right track with this idea comes from the observation that statins induce an increased synthesis of heme oyygenase in macrophages [3]. Macrophages typically produce heme oxygenase in order to break down hemoglobin into bilirubin and carbon monoxide, thus detoxifying the hemoglobin. So this is a strong indication that statins induce excess free hemoglobin in the blood, with the most plausible source being wrecked RBCs. The macrophages in atherosclerotic plaque have been shown to avidly take up hemoglobin and break it down with heme oxygenase, with the resulting accumulation of iron deposits in the plaque. It is believed that this iron is a significant contributor to the inflammatory processes in the plaque [6].
The really disturbing part of this story for me is the link between PNH and deep vein thrombosis – half of the deaths associated with PNH are due to venous thrombosis [13]. We have been hearing a lot more lately about deep vein thrombosis, with a warning issued regarding long airplane rides and massive prescriptions of blood thinners like Coumadin (i.e., rat poison!) to attempt to avert it. In PNS, deep vein thromobosis is a consequence of the platelets’ increased potential to form blood clots, due to the defect in GPI-anchoring of proteins, and I suspect that the leg paralysis in the mice is a consequence of suppressed circulation in the legs due to the excess risk of thrombosis. Might statin therapy be a direct contributor to the increased incidence of this highly critical condition?
PNH also leads to pulmonary hypertension, which in turn leads to increased risk to heart failure. This is hypothesized to be a direct consequence of the scavenging of nitric oxide by hemoglobin, which then induces increased pressure in the blood vessels supplying the lungs, putting excess strain on the heart [13]. It’s another one of those biological cascades that makes sense in that oxygen supply needs to be suppressed when there is so much free hemoglobin, because the hemoglobin is far more destructive to cell membranes and proteins when it is oxidized. Our studies showed a significant (p<0.05) increased risk to heart failure associated with statin therapy. Whether this occurs directly due to the depletion of coenzyme Q10 and cholesterol in the heart muscle, or indirectly due to the cascade from erupted RBCs to artery constriction in the lungs to inadequate oxygen supply to the heart is anybody’s guess. I suspect both paths contribute.
So now we must go back to the question of the pleiotrophic effect of statins that results in a reduced incidence of heart attacks. Experts are in agreement that statins don’t actually reduce the plaque, despite the fact that they interfere with the supply of cholesterol and fat. I don’t personally believe that nitric oxide synthesis is the right answer, as it would be more than cancelled out by the scavenging of NO by free hemoglobin. My own best guess at the moment is that statins interfere with the cells’ communication lines directly through their disruption of G-protein signaling mechanisms. I believe the consequence is that the little heart attacks don’t happen, because the cells can’t orchestrate a coordinated plan. As a result, the big heart attacks are more deadly. This idea is analogus to the consequences of preventing the small forest fires and watching the large ones rage out of control. Another analogy is with earthquakes – when the little ones don’t happen, the pressure builds up and the big one is highly destructive. This would explain why statins don’t consistently show improvement in mortality rates due to cardiovascular disease, despite their significant reduction in the frequency of heart attacks.
References
[1] P. Balakumar, S. Kathuria, G. Taneja, Sanjeev Kalra, and Nanjaian Mahadevan, “Is targeting eNOS a key mechanistic insight of cardiovascular defensive potentials of statins?” Journal of Molecular and Cellular Cardiology, To Appear, 2011.
[2] M. Bessler, P.J. Mason, P. Hillmen, T. Miyata, N. Yamada, J. Takeda, L. Luzzatto and T. Kinoshita, “Paroxysmal nocturnal haemoglobinuria (PNH) is caused by somatic mutations in the PIG-A gene,” The EMBO Journal 13(1):110-117, 1994.
[3] F. Gueler, J-K Park, S. Rong, T. Kirsch, C. Lindschau, W. Zheng, M. Elger, A. Fiebeler, D. Fliser, F.C. Luft, and H. Haller, “Statins Attenuate Ischemia-Reperfusion Injury by Inducing Heme Oxygenase-1 in Infiltrating Macrophages,” The American Journal of Pathology, 170(4):1192-1199, Apr. 2007.
[4] D.G. Harrison, “Endothelial control of vasomotion and nitric oxide production a potential target for risk factor management,” Cardiol Clin 14:115, 1996.
[5] K. Heinicke, O. Baum, O.O. Ogunshola, J. Vogel, T. Stallmach, D.P. Wolfer, S. Keller, K. Weber, P.D. Wagner, M. Gassmann and V. Djonov, “Excessive erythrocytosis in adult mice overexpressing erythropoietin leads to hepatic, renal, neuronal, and muscular degeneration,” Am J Physiol Regul Integr Comp Physiol 291:R947-R956, 2006.
[6] W. Li, L.H. Xu, and X.M. Yuan, “Macrophage hemoglobin scavenger receptor and ferritin accumulation in human atherosclerotic lesions,” Ann N Y Acad Sci. 1030, 196-201, Dec 2004.
[7] James K. Liao, and Ulrich Laufs “Pleiotropic Effects of Statins,” Annual Review of Pharmacology and Toxicology 45: 89-118, 2005.
[8] J.T. McCarthy, B.A. Staats, “Pulmonary hypertension, hemolytic anemia, and renal failure: a mitomycin-associated syndrome,” Chest, 89:608-611, 1986.
[9] P. Niklowitz, T. Menke, T. Wiesel, E. Mayatepek, J. Zschocke, J.G. Okun , and W. Andler, “Coenzyme Q10 in plasma and erythrocytes: comparison of antioxidant levels in healthy probands after oral supplementation and in patients suffering from sickle cell anemia,” Clin Chim Acta. 326(1-2):155-61, Dec. 2002.
[10] O.O. Ogunshola, V. Djonov, R. Staudt, J. Vogel, and M. Grassmann, “Chronic excess erythrocytosis induces endothelial activation and damage in mouse brain,” Am J Physiol Regul Integr Comp Physiol 290: R678-R684, 2006.
[11] G. de Pinieux, P. Chariot, M. Ammi-Said, F. Louarn, J.L. LeJonc, A. Astier, B. Jacotot, and R. Gherardi, “Lipid-lowering drugs and mitochondrial function: effects of HMG-CoA reducase inhibitors on serum ubiquinone and blood lactate/pyruvate ratios.” Br. J. Clin. Pharmacol. 42: 333-337, 1996.
[12] Yoshiyuki Rikitake, James K. Liao, “Rho GTPases, Statins, and Nitric Oxide,” Circulation Research 97:1232-1235, 2005.
[13] R.P. Rother, L. Bell, P. Hillmen, and M.T. Gladwin, “The Clinical Sequelae of Intravascular Hemolysis and Extracellular Plasma Hemoglobin: A Novel Mechanism of Human Disease,” JAMA, 293(13): 1653-1662, Apr 6, 2005.
[14] M. Sata, H. Nishimatsu, E. Suzuki, S. Sugiura, M. Yoshizumi, Y. Ouchi, Y. Hirata, and R. Nagai, “Endothelial nitric oxide synthase is essential for the HMG-CoA reductase inhibitor cerivastatin to promote collateral growth in response to ischemia.” The FASEB Journal 15(13):2530-2532, Nov 1, 2001.
[15] C. Wiessner, P.R. Allegrini, D. Ekatodramis, U.R. Jewell, T. Stallmach, and M. Gassmann, “Increased Cerebral Infarct Volumes in Polyglobulic Mice Overexpressing Erythropoietin,” J Cereb Blood Flow Metab, 21(7):857-864, 2001.
Sunday, October 30, 2011
Monday, September 19, 2011
Is it Time to Reevaluate Vaccination Policy in America?
Up until a few months ago, I held the majority view that a well maintained vaccination program is one of the hallmarks of a highly developed country. The U.S. leads the world with 24 requiredk vaccinations before the end of the baby’s first year: DTaP (3), polio (3), Hib Titer (3), hepatitis B (3), pneumonia (3), rotavirus (3) and influenza (2). We don’t however lead the world in infant mortality rates. Thirty three countries have lower infant mortality rates than we do, and there is a highly significant linear relationship (p < 0.0001) between infant mortality rates and the number of vaccine doses routinely given to infants [1]. Counterintuitively, nations that require more vaccines have higher infant mortality rates.
The autism community has long held the view that vaccines are contributing to their children’s autism. This is something that the vaccine industry vigourously denies. However, the incidence of autism is sharply on the rise over the last decade, and there are now several research articles pointing to a clear correlation between vaccination rates and autism [2, 3]. A 2011 article compared vaccination compliance records from the 50 states in the U.S., and found that a 1% increase in vaccination rates was associated on average with an additional 680 children having autism or speech and language delay in that state [4].
One might argue that, even if it’s true that vaccines cause autism, the price is still worth it – the childhood diseases that these vaccines protect from also carry a significant risk of permanent damage or even death. But supposing it’s also the case that vaccines are the major contributor to the alarming increases we’ve recently seen in food allergies [5], in asthma [6], in sudden infant death syndrome (SIDS) [7], and even in the E. coli epidemics? What if vaccines are a major contributor, not only to autism, but also to attention deficit hyperactivity disorder (ADHD), depression, manic depression, schizophrenia and Alzheimer’s disease? Would it still be worth it? What exactly is the cost to society of preventing the inconvenience of a childhood illness like chicken pox or measles that used to be a right of passage?
My recent studies have led me to believe that we have all been duped by the vaccine industry for a very long time. While Americans for the most part never even question the merit of a vaccination program, population studies have led some experts to argue that diseases can be kept in check more effectively by simply providing clean sanitation and better nutrition. It is not fair that the vaccine industry is not required to prove that its product is “effective.” Fear tactics are enough to convince most people that vaccination is absolutely necessary; that dire consequences would follow if we suddenly terminated the vaccination program.
This quote from the Natural News site’s Mike Adams aptly sums up the dismal situation we all face, with a wry sense of humor [8]:
(Mike Adams on MMR) : ”In layman’s terms, this is what’s known as a ‘scientific circle jerk’ where one group of bought-off scientists quotes another group of bought-off scientists as ‘authorities’ even though they all parrot the same medical quackery of their masters – the pharmaceutical companies.” Mike Adams was referring to the just-released Institute of Medicine (IoM) report which once again declares that the MMR (measles, mumps and rubella) vaccine is not linked to autism. Mike Adams begs to differ, and offers substantial support for his opinion drawn directly from the IOM report itself.
I am going to focus on Gardasil, the ”new kid on the block” in the vaccine arsenal. The story of the making and marketing of Gardasil is a triumph for both the National institutes of Health (NIH) and Merck, the company that brought the vaccine to market. Researchers at NIH, who patented their ideas and then handed them over to Merck for productization, have already gained enormous financial rewards, as well as formal recognition and high praise for their scholarly achievements.
The vaccine, touted as the first “anti-cancer” vaccine, immunizes against HPV (human papillary virus). The vaccine was rushed through the FDA approval process, and heralded as a magnificent example of what can be accomplished when government and industry work together towards a common, lucrative, goal. Heavy advertising was directed at the general public, priming them to be receptive when the vaccine became available. The governor of Texas, Rick Perry, wasted no time making it mandatory for preteen girls in his state. Mothers are lining up to get their 11 year old daughters vaccinated, hoping to give them one less thing to worry about health-wise in the future. California is even putting into law a bill called AB 499 [9], which would waive parental consent: young girls can make the decision for themselves whether they want to be vaccinated against HPV.
But the fairy tale is beginning to turn into a nightmare. A number of girls in the prime of their life, following a Gardasil vaccine, turned up dead from extremely rare conditions for their age group, like heart failure, deep vein thrombosis, and ALS (Lou Gehrig’s disease).
Mark Blaxill, who manages the “Age of Autism” web site, has written an astonishing 3-part article [10] detailing the dirty secrets behind Gardasil, and the much larger story of how the government, the media, and the drug companies have established an incredibly profitable revolving door arrangement that makes sure that only the public at large loses out. What amazes me most is the naivety of both the general public and the medical practioners, and their unfounded faith in the idea that vaccines are safe and effective, given the obviously huge confict-of-interest problems in the vaccine approval process. In the second installment of his article, Blaxill points out the audacity that the industry exhibits in designing severely flawed safety trials and getting by with it. A glaring loophole is that the so-called “placebo” administered to the control group does not have to be inert, and often the details of the contents of the placebo are not even revealed to the public, or are kept hidden in a terse description on page 303 of a long and wordy document. But Blaxill was able to discover that the placebo used in four out of five Gardasil trialscontained aluminum, as did the vaccine itself. And in these same fourtrials, the placebo group had many more adverse reactions than the one placebo group without the aluminum. Since Gardasil had only slightly more adverse reactions than the “placebo,” it was considered safe. Left unstated was the fact that the placebo itself was unsafe.
One admirable move that the U.S. government has done is to make the reports of vaccine adverse reactions available to the public for automatic download from the Web. The U.S. Centers for Disease Control have posted a large database of adverse events related to vaccines dating back to 1990, and I have downloaded this database and studied some of its characteristics [11]. It contains over 330,000 instances of recorded events, with information about which vaccine(s) were administered, the age of the person at the time, the symptoms encountered, relevant history, and whether death was an outcome.
I have thus been able to take a look for myself at Gardasil, comparing the frequency of various adverse reactions to the frequency observed in an age-matched control group of people receiving all other vaccines. It is mathematically very straightforward to use a log-likelihood ratio computation to determine the likelihood that a given count distribution could have occurred by chance [12].
Selected results we obtained, shown in Table 1 below, are astonishing. Some really severe reactions like seizure, loss of consciousness, and death, as well as a spontaneous abortion (miscarriage) for pregnant women obtaining the vaccine, are far more likely in the Gardasil data than in the random comparison set. Cynthia Janak, a freelance journalist, has produced a compellinganalysis of the dangers of Gardasil on the website, Renew America .
She too points out the dangers of the aluminum in the vaccine, which contains 225 mcg of aluminum as amorphous aluminum hydroxyphosphate sulfate adjuvant. I was able to find several web pages providing detailed accounts of the ingredients in various vaccines, such as this one, and I then did a study on the VAERS data comparing all thealuminum-containing vaccines I could confidently identify with vaccines that don’t contain aluminum, i.e., generalizing the experiments with Gardasil to include additional data: males as well as females, and over a much broader age range, since the flu vaccine, administered typically to the elderly, contains aluminum. Several of the adverse reactions that are statistically significantly associated with Gardasil are also statistically significantly associated with the other aluminum-containing vaccines that I identified, namely, DTaP, Hepatitis A and B, PREVNAR, and ANTHRAX. Some of the most significant adverse reactions showing up in all aluminum-containing vaccines are shown in Table 2.
It’s not as though it’s not known that aluminum is toxic to health. No known biological system makes use of aluminum for any purpose. People with end-stage kidney disease suffer from severe dementia after sufficient accumulation of aluminum in their brain, accidentally supplied to their blood stream from aluminum-containing water in the dialysis fluids [13]. If you ingest aluminum, only a quarter of a percent of it actually gets through the lining of the gut. But if you inject it in a vaccine, 100% goes directly into the blood stream.
You must be asking yourself at this point why on earth they’d be putting aluminum into vaccines in the first place. The vaccine industry is, quite frankly, caught between a rock and a hard place. Either they use live (weakened) pathogens in the vaccine (such as in MMR) or they use dead pathogens, but add some so-called ”adjuvants” to disrupt the immune response and make sure that the body will react sufficiently well for the vaccine to ”take.” With live pathogens, the vaccine can and does cause actual disease in susceptible individuals – it infects the person with the disease it’s trying to vaccinate against. But, with adjuvants like aluminum, you can get by with dead viruses, and you can get by with a lot fewer dead viruses in each vaccination, thus increasing the yield and saving money. However, and this is a huge consideration, the vaccine can add to an accumulated aluminum build-up in the brain, directly contributing to autism and Alzheimer’s disease.
It seems that the industry is well aware that they had better not combine both aluminum and live pathogen in the same vaccine, as the resulting adverse reactions would probably keep the vaccine from ever making it through safety trials. However, they don’t seem to mind injecting children with two vaccines simultaneously – one containing aluminum and the other containing live toxin. This is exactly the situation with DTaP and MMR, where DTaP contains aluminum and MMR contains live pathogens for measles, mumps and rubella. I suspect the combination wreaks havoc on the system of the immune-compromised child.
If you think that aluminum in vaccines is not a big deal, then you should read the paper called, simply, ”Aluminum Vaccine Adjuvants: Are they Safe?” by Tomljenovic and Shaw [14], which appeared just this year in the journal, Current Medicinal Chemistry. It is an eye-opener! They point out that the number of officially scheduled vaccines for U.S. children has increased sharply from 10 in the 1980s to 32 in the late 2000s, and that 18 of these vaccines contain aluminum adjuvants. Newborns in the U.S. and other developed countries receive 14.7 to 49 times more than the FDA safety limits for aluminum, just through their mandatory vaccines. They point out the very clear association between aluminum exposure and dementia in dialysis patients that I already mentioned earlier. In experiments with mice, injections of vaccine aluminum adjuvants showed up in the brain tissues a couple of days later, demonstrating that aluminum can cross the blood-brain barrier. Rabbits given aluminum phosphate experienced nerve degenration and neurofibrillary tangles similar to those that are characteristic of Alzheimer’s disease. Animals given dietary aluminum routinely show learning and memory deficits, along with confusion and repetitive behaviors, similar to those in autism. This is despite the fact that dietary aluminum is so poorly absorbed through the gut. These authors also reference several articles where vaccine safety tests were conducted by doping the so-called placebo with aluminum, sometimes in amounts in excess of the amount in the vaccine itself.
Although aluminum is probably the biggest problem with vaccines, it is not the only problem. I came across a web page proposing that the egg and peanut allergies, currently affecting 1-2% of the U.S. population, might be caused by vaccines, and then I started to explore all the other foods that show up in vaccines, finding, to my astonishment, that every one I checked had extensive hits in a web search in association with allergies. I then came upon an article written by Barbara Feick Gregory , who had done a far more extensive search than I had done, confirming much more exhaustively what I had suspected. The reason that small amounts of food in vaccines cause an intense allergic reaction is that the body develops a memory of the food in association with the toxin that’s also in the vaccine. The body is fooled into believing that the egg that the flu vaccine pathogen is grown in is somehow part of a strange new species, and it develops a response to the egg as well as, or perhaps even instead of, to the flu virus.
So this then explains the adverse reaction report #403192, which described the child’s reaction as follows: “Large welts and extreme itching in skin from the waist down, which are the typical reaction that he receives when he eats eggs.” This report concerned a5-year-old autistic child’s reaction to a flu shot. It was surely an earlier vaccine that had primed him for this kind of reaction. It’s surprising how many foods besides eggs and peanut oil show up in vaccines, including gelatine, lactate, yeast, glycine (soy), and lectin (wheat). It’s possible that most of these are intentionally added precisely because they are substances to which the body can build an immune response – this may make them useful as adjuvants toincrease the likelihood of the creation of a permanent memory of the pathogen, i.e., a protective response.
The recent major E. coli epidemic in Europe has led me to wonder whether these E. coli epidemics might also be due directly to vaccination. E. coli epidemics were unheard of until vaccines started to be routinely administered. If the body can overreact to foods in vaccines, then it stands to reason that it might also overreact to E. coli infection as a consequence of previous exposure to E. coli membranes in vaccines. E. coli cell membrane fragments are in fact another substance that is often put into vaccines, as a well-known effective adjuvant. E. coli are essential bacteria in our guts, helping with digestion and generally not causing any trouble. But I can easily imagine that our bodies can be fooled into believing that certain strains are toxic if they’re injected directly into our blood stream thoroughly mixed in with some severely toxic pathogen. While I was unable to trace the strain that caused the recent European outbreak directly to a vaccine adjuvant, I did determine that several strains of E. coli have been added to vaccines for the sake of their adjuvant properties, including strains known as 0111, 0127, 026, 055, and F583 (Vaccine Adjuvants) . Several mentions of an outbreak related to strain 0111 can be found on the web, such as this one in Oklahoma .
In closing, I want to return to Gardasil, to mention yet another severely problematic aspect of this vaccine that has just become public knowledge. Recently, it has been discovered that Gardasil contains contaminants in the form of HPV recombinant DNA, even though the vaccine label states clearly that it does not. A young girl developed juvenile rheumatoid arthritis the day after she received her last Gardasil vaccination, and the vaccine batch she received was then analyzed for contaminants. The Milford Hospital pathology laboratorywhere the tests were conducted found the recombinant DNA, and then tested several other batches of the vaccine from around the world, finding the contaminant to be present in every batch they tested. Dr. Sin Hang Lee, a pathologist at the Milford Hospital laboratory, has this to say about recombinant HPV: “Based on medical literature and some of the FDA/Mercks own publications, adventitious(coming from an outside source) DNA in an injectable protein-based vaccine may increase the risk of autoimmune disorders and gene mutation which may lead to malignancies.” [15] So these are just some other health problems we can look forward to as we increase our bodies’ vaccine load.
It is long past the time when we should be taking a hard look at the American vaccination program, to rigorously assess the risks and benefits of vaccines in the same way that we routinely do for drugs. It may be expedient to simply trust the industry; to blindly believe that the down side of vaccination is more than adequately offset by the up side. But this is not good science. Canadians have walked down this new path already, as eidenced by a thoughtful and rational article discussing a risk/benefit analysis for Gardasil [16]. Vaccines are costing us a great deal more pain than we realize, and it’s time to take stock.
References
[1] N.Z. Miller and G.S. Goldman, “Infant mortality rates regressed against number of vaccine doses routinely given: Is there a biochemical or synergistic toxicity?” Human and Experimental Toxicology, published online 4 May, 2011.
[2] A.J. Wakefield, “MMR vaccination and autism,” The Lancet 354:9182 949-950, Sep 11 1999; doi:10.1016/S0140-6736(05)75696-8
[3] O.M. Gallagher and M.S. Goodman, “Hepatitis B vaccination of male neonates and autism diagnosis, NHIS 1997-2002,” J Toxicol Environ Health A. 73(24):1665-77, 2010.
[4] G. DeLong “A Positive Association Found Between Autism Prevalence and Childhood Vaccination Uptake across the U.S. Population,” Journal of Toxicology and Environmental Health, Part A, 74:903916, 2011; DOI: 10.1080/15287394.2011.573736.
[5] http://barbfeick.com/vaccinations/allergy/951vaccine allergy.htm
[6] vactruth.com/2011/07/11/research-shows-vaccinations-are-causing-surge-of-asthma-in-children/
[7] A.M. Walker, H. JICK, D.R. PERERA, R.S. Thompson, and T.A. KNAUSS, “Diphtheria-Tetanus-Pertussis Immunization and Sudden Infant Death Syndrome,” AJPH 77(8):945-951, Aug 1987.
[8] P.F. Louis, “BMJ had secret financial ties to Merck during publication of articles attacking Wakefield,” NaturalNews, Wednesday, September 07, 2011; http://www.naturalnews.com/033516 BMJ financial ties.html
[9] www.catholicsun.org/2011/september/02/california-gardasil.html
[10] Mark Blaxill, “Rick Perry and the Conflicts of Government Licensed Corporate Profit: Merck and Gardasil,” Age of Autism Web site: http://www.ageofautism.com/2011/08/rickperryandtheconflictsofgovernmentlicensed-corporateprofitmerckgardasil.html
[11] CDC. Surveillance for safety after immunization: Vaccine Adverse Events Reporting System (VAERS)United States, 19912001. MMWR Surveill Summ. 52:124, 2003.
[12] T. Dunning,”Accurate methods for the statistics of surprise and coincidence,” Computational Linguistics 19(1):6174, 1993.
[13] M.R. Wills and J. Savory, “Water Content of Aluminum, Dialysis Dementia, and Osteomalacia” Environmental Health Perspectives 63:141-147, 1985.
[14] L. Tomljenovic and C.A. Shaw, “Aluminum Vaccine Adjuvants: Are they Safe?” Current Medicinal Chemistry 18:2630-2637, 2011.
[15] L.C.Botha, “SANE Vax Inc. Discovers Potential Bio-hazard Contaminant in Mercks Gardasil HPV 4 Vaccine,” http://sanevax.org/sane-vax-inc-discovers-potential-bio-hazard-contaminant-in-merck.
[16] A. Lippman, R. Melnychuk, C. Shimmin and M. Boscoe, “Human papillomavirus, vaccines and womens health: questions and cautions,” CMAJ, 177(5):484-487, 2007.
The autism community has long held the view that vaccines are contributing to their children’s autism. This is something that the vaccine industry vigourously denies. However, the incidence of autism is sharply on the rise over the last decade, and there are now several research articles pointing to a clear correlation between vaccination rates and autism [2, 3]. A 2011 article compared vaccination compliance records from the 50 states in the U.S., and found that a 1% increase in vaccination rates was associated on average with an additional 680 children having autism or speech and language delay in that state [4].
One might argue that, even if it’s true that vaccines cause autism, the price is still worth it – the childhood diseases that these vaccines protect from also carry a significant risk of permanent damage or even death. But supposing it’s also the case that vaccines are the major contributor to the alarming increases we’ve recently seen in food allergies [5], in asthma [6], in sudden infant death syndrome (SIDS) [7], and even in the E. coli epidemics? What if vaccines are a major contributor, not only to autism, but also to attention deficit hyperactivity disorder (ADHD), depression, manic depression, schizophrenia and Alzheimer’s disease? Would it still be worth it? What exactly is the cost to society of preventing the inconvenience of a childhood illness like chicken pox or measles that used to be a right of passage?
My recent studies have led me to believe that we have all been duped by the vaccine industry for a very long time. While Americans for the most part never even question the merit of a vaccination program, population studies have led some experts to argue that diseases can be kept in check more effectively by simply providing clean sanitation and better nutrition. It is not fair that the vaccine industry is not required to prove that its product is “effective.” Fear tactics are enough to convince most people that vaccination is absolutely necessary; that dire consequences would follow if we suddenly terminated the vaccination program.
This quote from the Natural News site’s Mike Adams aptly sums up the dismal situation we all face, with a wry sense of humor [8]:
(Mike Adams on MMR) : ”In layman’s terms, this is what’s known as a ‘scientific circle jerk’ where one group of bought-off scientists quotes another group of bought-off scientists as ‘authorities’ even though they all parrot the same medical quackery of their masters – the pharmaceutical companies.” Mike Adams was referring to the just-released Institute of Medicine (IoM) report which once again declares that the MMR (measles, mumps and rubella) vaccine is not linked to autism. Mike Adams begs to differ, and offers substantial support for his opinion drawn directly from the IOM report itself.
I am going to focus on Gardasil, the ”new kid on the block” in the vaccine arsenal. The story of the making and marketing of Gardasil is a triumph for both the National institutes of Health (NIH) and Merck, the company that brought the vaccine to market. Researchers at NIH, who patented their ideas and then handed them over to Merck for productization, have already gained enormous financial rewards, as well as formal recognition and high praise for their scholarly achievements.
The vaccine, touted as the first “anti-cancer” vaccine, immunizes against HPV (human papillary virus). The vaccine was rushed through the FDA approval process, and heralded as a magnificent example of what can be accomplished when government and industry work together towards a common, lucrative, goal. Heavy advertising was directed at the general public, priming them to be receptive when the vaccine became available. The governor of Texas, Rick Perry, wasted no time making it mandatory for preteen girls in his state. Mothers are lining up to get their 11 year old daughters vaccinated, hoping to give them one less thing to worry about health-wise in the future. California is even putting into law a bill called AB 499 [9], which would waive parental consent: young girls can make the decision for themselves whether they want to be vaccinated against HPV.
But the fairy tale is beginning to turn into a nightmare. A number of girls in the prime of their life, following a Gardasil vaccine, turned up dead from extremely rare conditions for their age group, like heart failure, deep vein thrombosis, and ALS (Lou Gehrig’s disease).
Mark Blaxill, who manages the “Age of Autism” web site, has written an astonishing 3-part article [10] detailing the dirty secrets behind Gardasil, and the much larger story of how the government, the media, and the drug companies have established an incredibly profitable revolving door arrangement that makes sure that only the public at large loses out. What amazes me most is the naivety of both the general public and the medical practioners, and their unfounded faith in the idea that vaccines are safe and effective, given the obviously huge confict-of-interest problems in the vaccine approval process. In the second installment of his article, Blaxill points out the audacity that the industry exhibits in designing severely flawed safety trials and getting by with it. A glaring loophole is that the so-called “placebo” administered to the control group does not have to be inert, and often the details of the contents of the placebo are not even revealed to the public, or are kept hidden in a terse description on page 303 of a long and wordy document. But Blaxill was able to discover that the placebo used in four out of five Gardasil trialscontained aluminum, as did the vaccine itself. And in these same fourtrials, the placebo group had many more adverse reactions than the one placebo group without the aluminum. Since Gardasil had only slightly more adverse reactions than the “placebo,” it was considered safe. Left unstated was the fact that the placebo itself was unsafe.
One admirable move that the U.S. government has done is to make the reports of vaccine adverse reactions available to the public for automatic download from the Web. The U.S. Centers for Disease Control have posted a large database of adverse events related to vaccines dating back to 1990, and I have downloaded this database and studied some of its characteristics [11]. It contains over 330,000 instances of recorded events, with information about which vaccine(s) were administered, the age of the person at the time, the symptoms encountered, relevant history, and whether death was an outcome.
I have thus been able to take a look for myself at Gardasil, comparing the frequency of various adverse reactions to the frequency observed in an age-matched control group of people receiving all other vaccines. It is mathematically very straightforward to use a log-likelihood ratio computation to determine the likelihood that a given count distribution could have occurred by chance [12].
Selected results we obtained, shown in Table 1 below, are astonishing. Some really severe reactions like seizure, loss of consciousness, and death, as well as a spontaneous abortion (miscarriage) for pregnant women obtaining the vaccine, are far more likely in the Gardasil data than in the random comparison set. Cynthia Janak, a freelance journalist, has produced a compellinganalysis of the dangers of Gardasil on the website, Renew America .
| Seizure | 538 | 150 | 0.00010 |
| Loss of Consciousness | 393 | 119 | 0.00046 |
| Depression | 109 | 11 | 0.0029 |
| Fatigue | 351 | 167 | 0.0042 |
| Miscarriage | 97 | 12 | 0.0044 |
| Anxiety | 170 | 56 | 0.0058 |
| Asthma | 142 | 49 | 0.0095 |
| Death | 35 | 7 | 0.040 |
She too points out the dangers of the aluminum in the vaccine, which contains 225 mcg of aluminum as amorphous aluminum hydroxyphosphate sulfate adjuvant. I was able to find several web pages providing detailed accounts of the ingredients in various vaccines, such as this one, and I then did a study on the VAERS data comparing all thealuminum-containing vaccines I could confidently identify with vaccines that don’t contain aluminum, i.e., generalizing the experiments with Gardasil to include additional data: males as well as females, and over a much broader age range, since the flu vaccine, administered typically to the elderly, contains aluminum. Several of the adverse reactions that are statistically significantly associated with Gardasil are also statistically significantly associated with the other aluminum-containing vaccines that I identified, namely, DTaP, Hepatitis A and B, PREVNAR, and ANTHRAX. Some of the most significant adverse reactions showing up in all aluminum-containing vaccines are shown in Table 2.
| Seizure | 2965 | 2161 | 0.0009 |
| Depression | 231 | 85 | 0.0050 |
| Fatigue | 1435 | 745 | 0.00016 |
| Death | 464 | 284 | 0.012 |
It’s not as though it’s not known that aluminum is toxic to health. No known biological system makes use of aluminum for any purpose. People with end-stage kidney disease suffer from severe dementia after sufficient accumulation of aluminum in their brain, accidentally supplied to their blood stream from aluminum-containing water in the dialysis fluids [13]. If you ingest aluminum, only a quarter of a percent of it actually gets through the lining of the gut. But if you inject it in a vaccine, 100% goes directly into the blood stream.
You must be asking yourself at this point why on earth they’d be putting aluminum into vaccines in the first place. The vaccine industry is, quite frankly, caught between a rock and a hard place. Either they use live (weakened) pathogens in the vaccine (such as in MMR) or they use dead pathogens, but add some so-called ”adjuvants” to disrupt the immune response and make sure that the body will react sufficiently well for the vaccine to ”take.” With live pathogens, the vaccine can and does cause actual disease in susceptible individuals – it infects the person with the disease it’s trying to vaccinate against. But, with adjuvants like aluminum, you can get by with dead viruses, and you can get by with a lot fewer dead viruses in each vaccination, thus increasing the yield and saving money. However, and this is a huge consideration, the vaccine can add to an accumulated aluminum build-up in the brain, directly contributing to autism and Alzheimer’s disease.
It seems that the industry is well aware that they had better not combine both aluminum and live pathogen in the same vaccine, as the resulting adverse reactions would probably keep the vaccine from ever making it through safety trials. However, they don’t seem to mind injecting children with two vaccines simultaneously – one containing aluminum and the other containing live toxin. This is exactly the situation with DTaP and MMR, where DTaP contains aluminum and MMR contains live pathogens for measles, mumps and rubella. I suspect the combination wreaks havoc on the system of the immune-compromised child.
If you think that aluminum in vaccines is not a big deal, then you should read the paper called, simply, ”Aluminum Vaccine Adjuvants: Are they Safe?” by Tomljenovic and Shaw [14], which appeared just this year in the journal, Current Medicinal Chemistry. It is an eye-opener! They point out that the number of officially scheduled vaccines for U.S. children has increased sharply from 10 in the 1980s to 32 in the late 2000s, and that 18 of these vaccines contain aluminum adjuvants. Newborns in the U.S. and other developed countries receive 14.7 to 49 times more than the FDA safety limits for aluminum, just through their mandatory vaccines. They point out the very clear association between aluminum exposure and dementia in dialysis patients that I already mentioned earlier. In experiments with mice, injections of vaccine aluminum adjuvants showed up in the brain tissues a couple of days later, demonstrating that aluminum can cross the blood-brain barrier. Rabbits given aluminum phosphate experienced nerve degenration and neurofibrillary tangles similar to those that are characteristic of Alzheimer’s disease. Animals given dietary aluminum routinely show learning and memory deficits, along with confusion and repetitive behaviors, similar to those in autism. This is despite the fact that dietary aluminum is so poorly absorbed through the gut. These authors also reference several articles where vaccine safety tests were conducted by doping the so-called placebo with aluminum, sometimes in amounts in excess of the amount in the vaccine itself.
Although aluminum is probably the biggest problem with vaccines, it is not the only problem. I came across a web page proposing that the egg and peanut allergies, currently affecting 1-2% of the U.S. population, might be caused by vaccines, and then I started to explore all the other foods that show up in vaccines, finding, to my astonishment, that every one I checked had extensive hits in a web search in association with allergies. I then came upon an article written by Barbara Feick Gregory , who had done a far more extensive search than I had done, confirming much more exhaustively what I had suspected. The reason that small amounts of food in vaccines cause an intense allergic reaction is that the body develops a memory of the food in association with the toxin that’s also in the vaccine. The body is fooled into believing that the egg that the flu vaccine pathogen is grown in is somehow part of a strange new species, and it develops a response to the egg as well as, or perhaps even instead of, to the flu virus.
So this then explains the adverse reaction report #403192, which described the child’s reaction as follows: “Large welts and extreme itching in skin from the waist down, which are the typical reaction that he receives when he eats eggs.” This report concerned a5-year-old autistic child’s reaction to a flu shot. It was surely an earlier vaccine that had primed him for this kind of reaction. It’s surprising how many foods besides eggs and peanut oil show up in vaccines, including gelatine, lactate, yeast, glycine (soy), and lectin (wheat). It’s possible that most of these are intentionally added precisely because they are substances to which the body can build an immune response – this may make them useful as adjuvants toincrease the likelihood of the creation of a permanent memory of the pathogen, i.e., a protective response.
The recent major E. coli epidemic in Europe has led me to wonder whether these E. coli epidemics might also be due directly to vaccination. E. coli epidemics were unheard of until vaccines started to be routinely administered. If the body can overreact to foods in vaccines, then it stands to reason that it might also overreact to E. coli infection as a consequence of previous exposure to E. coli membranes in vaccines. E. coli cell membrane fragments are in fact another substance that is often put into vaccines, as a well-known effective adjuvant. E. coli are essential bacteria in our guts, helping with digestion and generally not causing any trouble. But I can easily imagine that our bodies can be fooled into believing that certain strains are toxic if they’re injected directly into our blood stream thoroughly mixed in with some severely toxic pathogen. While I was unable to trace the strain that caused the recent European outbreak directly to a vaccine adjuvant, I did determine that several strains of E. coli have been added to vaccines for the sake of their adjuvant properties, including strains known as 0111, 0127, 026, 055, and F583 (Vaccine Adjuvants) . Several mentions of an outbreak related to strain 0111 can be found on the web, such as this one in Oklahoma .
In closing, I want to return to Gardasil, to mention yet another severely problematic aspect of this vaccine that has just become public knowledge. Recently, it has been discovered that Gardasil contains contaminants in the form of HPV recombinant DNA, even though the vaccine label states clearly that it does not. A young girl developed juvenile rheumatoid arthritis the day after she received her last Gardasil vaccination, and the vaccine batch she received was then analyzed for contaminants. The Milford Hospital pathology laboratorywhere the tests were conducted found the recombinant DNA, and then tested several other batches of the vaccine from around the world, finding the contaminant to be present in every batch they tested. Dr. Sin Hang Lee, a pathologist at the Milford Hospital laboratory, has this to say about recombinant HPV: “Based on medical literature and some of the FDA/Mercks own publications, adventitious(coming from an outside source) DNA in an injectable protein-based vaccine may increase the risk of autoimmune disorders and gene mutation which may lead to malignancies.” [15] So these are just some other health problems we can look forward to as we increase our bodies’ vaccine load.
It is long past the time when we should be taking a hard look at the American vaccination program, to rigorously assess the risks and benefits of vaccines in the same way that we routinely do for drugs. It may be expedient to simply trust the industry; to blindly believe that the down side of vaccination is more than adequately offset by the up side. But this is not good science. Canadians have walked down this new path already, as eidenced by a thoughtful and rational article discussing a risk/benefit analysis for Gardasil [16]. Vaccines are costing us a great deal more pain than we realize, and it’s time to take stock.
References
[1] N.Z. Miller and G.S. Goldman, “Infant mortality rates regressed against number of vaccine doses routinely given: Is there a biochemical or synergistic toxicity?” Human and Experimental Toxicology, published online 4 May, 2011.
[2] A.J. Wakefield, “MMR vaccination and autism,” The Lancet 354:9182 949-950, Sep 11 1999; doi:10.1016/S0140-6736(05)75696-8
[3] O.M. Gallagher and M.S. Goodman, “Hepatitis B vaccination of male neonates and autism diagnosis, NHIS 1997-2002,” J Toxicol Environ Health A. 73(24):1665-77, 2010.
[4] G. DeLong “A Positive Association Found Between Autism Prevalence and Childhood Vaccination Uptake across the U.S. Population,” Journal of Toxicology and Environmental Health, Part A, 74:903916, 2011; DOI: 10.1080/15287394.2011.573736.
[5] http://barbfeick.com/vaccinations/allergy/951vaccine allergy.htm
[6] vactruth.com/2011/07/11/research-shows-vaccinations-are-causing-surge-of-asthma-in-children/
[7] A.M. Walker, H. JICK, D.R. PERERA, R.S. Thompson, and T.A. KNAUSS, “Diphtheria-Tetanus-Pertussis Immunization and Sudden Infant Death Syndrome,” AJPH 77(8):945-951, Aug 1987.
[8] P.F. Louis, “BMJ had secret financial ties to Merck during publication of articles attacking Wakefield,” NaturalNews, Wednesday, September 07, 2011; http://www.naturalnews.com/033516 BMJ financial ties.html
[9] www.catholicsun.org/2011/september/02/california-gardasil.html
[10] Mark Blaxill, “Rick Perry and the Conflicts of Government Licensed Corporate Profit: Merck and Gardasil,” Age of Autism Web site: http://www.ageofautism.com/2011/08/rickperryandtheconflictsofgovernmentlicensed-corporateprofitmerckgardasil.html
[11] CDC. Surveillance for safety after immunization: Vaccine Adverse Events Reporting System (VAERS)United States, 19912001. MMWR Surveill Summ. 52:124, 2003.
[12] T. Dunning,”Accurate methods for the statistics of surprise and coincidence,” Computational Linguistics 19(1):6174, 1993.
[13] M.R. Wills and J. Savory, “Water Content of Aluminum, Dialysis Dementia, and Osteomalacia” Environmental Health Perspectives 63:141-147, 1985.
[14] L. Tomljenovic and C.A. Shaw, “Aluminum Vaccine Adjuvants: Are they Safe?” Current Medicinal Chemistry 18:2630-2637, 2011.
[15] L.C.Botha, “SANE Vax Inc. Discovers Potential Bio-hazard Contaminant in Mercks Gardasil HPV 4 Vaccine,” http://sanevax.org/sane-vax-inc-discovers-potential-bio-hazard-contaminant-in-merck.
[16] A. Lippman, R. Melnychuk, C. Shimmin and M. Boscoe, “Human papillomavirus, vaccines and womens health: questions and cautions,” CMAJ, 177(5):484-487, 2007.
Thursday, July 7, 2011
Is Autism Caused by Sulfate Deficiency and Excess Aluminum Exposure?
My best friend’s son was recently diagnosed with autism spectrum disorder, and this has inspired me to do some research on autism. Vast amounts have already been written on the subject, yet it seems that we are still far from understanding the elusive cause(s). The experts clearly believe there is a strong genetic component, yet they have been frustrated in their diligent efforts to identify those genetic causes [8]. At the same time, it is now pretty much indisputable that the incidence of autism, particularly in the U.S., has been steadily on the rise over the last few decades, now estimated to be over one in a hundred, an astonishing number.
Despite the fact that the vaccine industry has built a strong case that vaccines don’t cause autism, the autism community persists in claiming that they do. My research has led me to believe that the aluminum in vaccines plays a contributory role, as does the aluminum often found in sunscreen. Aluminum is a very common metal, yet it has never been incorporated into any biological system, and is clearly toxic to neurons, a subject I will return to later.
But I also believe that other environmental factors play probably a larger role than aluminum. Or, to say it another way, certain nutritional deficiencies predispose a child to be especially vulnerable to aluminum. My investigative research has led me to consider cholesterol [11] and vitamin D [3] deficiencies as prime candidates.
The brain represents only 2% of the total body mass, yet it houses 25% of the body’s total cholesterol. Because of the current obsession in the U.S. against dietary cholesterol and saturated fat, I was led to explore the question of cholesterol supply to the fetus during pregnancy. I was richly rewarded, and initially left baffled, by an article with a very surprising revelation [17]. Women with high serum cholesterol typically give birth to children with low serum cholesterol who already at birth have developed fatty streaks in their arteries, and are predisposed to developing heart disease much later in life. There seemed to be an inverse relationship between the mother’s and the fetus’s cholesterol levels!
Given the importance of cholesterol to the nervous system, remarkably little research has been done to characterize the mechanisms by which the fetus supplies itself with cholesterol. It had been hypothesized that the fetus synthesizes all of its own cholesterol supply, which would be surprising, given that cholesterol synthesis is a complex twenty-five step process that might be difficult for a fledgling organism to carry out. However, the biological machinery that would be necessary to transport cholesterol across the placental barrier to the fetus did not seem to exist [18].
I believe I have found the answer in a 1997 article by a team of Japanese researchers [14]. These authors were inspired to look at the concentration of cholesterol sulfate in the placenta and in the mother’s blood, as a function of time throughout pregnancy. They discovered that cholesterol sulfate concentrations in the mother’s blood rose from 1.85 to 2.23 to 3.09 over the course of the three trimesters of pregnancy, whereas non-pregnant women had a serum level of only 1.56. However, the more remarkable observation was the increase in cholesterol sulfate noted in placental villi, hairlike projections from the placenta that provide lots of surface area for contact with fetal blood supply. The concentration of cholesterol sulfate here went up from 3.93 to 18.35 to 23.75 over the course of the three trimesters, a six-fold increase from the first trimester to the third trimester! It might have been anticipated that cholesterol sulfate is important to the fetus, as it is in fact critically involved in the sperm decapitation stage that allows the sperm to fertilize the egg [13].
I am inclined to hypothesize (somewhat boldly) that certain mothers (and, more generally, certain people) have high cholesterol to compensate for the fact that their cholesterol sulfate level is deficient. Their fetus has low cholesterol because of inadequacies in the supply chain, obligatorily mediated by cholesterol sulfate. I might also boldly add that high cholesterol, a risk factor for cardiovascular disease in both the mother and the child, is, by deduction, an indicator of low cholesterol sulfate, and therefore that cholesterol sulfate protects from cardiovascular disease. I will need to revisit this topic in a later post!
Cholesterol sulfate is an interesting and elusive molecule. It is synthesized in the skin upon exposure to sunlight, alongside vitamin D3 sulfate [10, 2] and so this might be the connection between autism and vitamin D deficiency. It could well be that the sulfated form of vitamin D3 can substitute for cholesterol sulfate to some extent in supplying the fetus with sulfate. And it might then be supposed that sulfate is a critical nutrient that is in short supply in fetuses destined to later develop into autistic children.
This idea gains strong support from an article in Press in the timely subject of sulfate in fetal development [5]. From several studies on humans with rare genetic disorders and on animal models involving genetically engineered defective genes, it is abundantly clear that sulfate is absolutely essential to healthy fetal development. Furthermore, sulfate plays an important role in detoxifying drugs that might damage the fetus or the infant, such as acetaminophen, the active ingredient in tylenol. In fact, an interesting review article proposes that vulnerability to damage by Tylenol given subsequent to a vaccine-induced fever may have been a risk factor for autism [6]. Further support for a sulfate deficit in autism comes from a study showing, with a highly significant p-value of ¡ .00002, that severely autistic kids are unable to sulfate (and therefore detoxify) toxic chemicals [1].
Another really remarkable thing about cholesterol sulfate is that, in part because of its negative charge, it is “amphiphilic”: soluble in both water and fat. This means that it can travel freely in the blood stream (does not have to be packaged up inside LDL particles), and easily enters cell walls (ten times as agile as cholesterol itself in penetrating cell walls) [19]. I suspect these unique properties make it also much easier for cholesterol sulfate to get across the placental barrier than would be the case for cholesterol. Furthermore, cholesterol sulfate plays an important role in the outer skin, in protecting the body from invasion by pathogens [16]. A deficiency in cholesterol sulfate in the skin might explain the fact that autistic children often have skin problems and are more prone to infection.
I’d like to now return to the subject of the supposed genetic component to autism, which has been justified in part because an identical twin is much more likely to also have autism given that his twin has autism than is the case for fraternal twins. However, there is a further interesting observation that even fraternal twins are much more likely to both have autism than two siblings who are not twins. The genetic distance between fraternal twins is the same as that between brothers, and therefore genes can not explain this phenomenon. Furthermore, just being a twin is a risk factor for autism [7]. It would seem to me that all of these observations can be nicely explained if the assumption is that inadequate supply of a scarce resource (e.g., cholesterol sulfate) is the source of the problem. Twins would place double the demand on the mother’s limited supply. And identical twins often share a single placenta, which means that the villi would have to be twice as proliferous to fully supply two fetuses simultaneously, an unlikely feat. This could account for the increased risk in identical twins, without involving genetics at all.
Finally, I would like to return to the subject of aluminum, by discussing a fascinating article involving an experiment with aluminum exposure to pregnant mice, followed by an investigation of the properties of neurons harvested from the brains of the offspring. But first I should mention a couple more facts about features of autism. One novel characteristic of the autistic brain is that it actually is larger than the non-autistic brain at the age of two or three [9]. This is a time when ordinarily the brain goes through a massive pruning process, to weed out neurons that have failed to build up sufficient synaptic connections to be worthy of survival.
Two biological molecules that pair up on either side of the synapse to promote the memory of synaptic stimuli are neurexin and neuroligin. Several of the rare genetic defects that sometimes show up in connection with autism are related to either neurexin [12], on the input side of the synapse, or neuroligin [21] on the output side, where these two work together synergistically to coordinate transmission of the neurotransmitter glutamate. Glutamate plays an important role in wiring up the brain during early development, and this function has been hypothesized to be disturbed in autism. Glutamate is also intimately involved in the stage where neurons are pruned due to the fact that they received little input and are thus deemed extraneous. Furthermore, cholesterol, through a scissors mechanism, has been shown to play a crucial role in greatly increasing the ability of two neurons to make contact at a synapse [20]. In line with this observation, in-vitro studies have shown that cholesterol deficient neurons exhibit impaired glutamate transport, causing excess glutamate to accumulate outside the neuron [3].
In this light, the experiment on the mice that were exposed to aluminum prenatally was highly relevant. One of the important roles glutamate carries out is to signal to an unworthy neuron that it should die: that it should commit “programmed cell death” or “apoptosis” during the massive pruning stage. The mouse experiment [15] showed that neurons taken from the brains of mice prenatally exposed to aluminum responded abnormally to glutamate exposure that should have led to apoptosis. Whereas the number of neurons in the petri dish harvested from control mice sharply decreased upon exposure to glutamate, the aluminum-exposed neurons were quite happy to keep on growing, effectively ignoring the glutamate signal. This seemed to be exactly the same thing that the neurons in the autistic brains were doing when they weren’t pruned!
In summary, it seems to me that a possible explanation for the recent steady and alarming increase in the rate of autism in the U.S. is the confluence of a number of factors leading to a perfect storm. The problem centers on the two American obsessions of avoiding dietary fat and cholesterol and overprotection from the sun. The problem is further compounded by the relentless increase in the number of vaccinations against a multitude of childhood diseases, increasingly mandated by the U.S. government. These environmental influences conspire to produce children who are grossly deficient in cholesterol sulfate, which leads to impaired neurotransmission in the brain and impaired immune systems. The infiltration of aluminum into the brain compounds the problem, by further disrupting the already impaired glutamate transmission. The aluminum toxicity builds up due to the combination of exposure to both vaccines and sunscreen applied far too frequently to the skin, in the context of sulfate deficiencies that impair natural detoxification processes. It seems that some major changes in the American attitude towards what constitutes healthy living will need to take place before this epidemic can be brought under control.
References
[1] A. Alberti, P. Pirrone, M. Elia, R.H. Waring and C. Romano, “Sulphation deficit in ’low-functioning’ autistic children: a pilot study,” Biol Psychiatry, 46(3):420-4, 1999.
[2] M. Axelson, “The cholecalciferol sulphate system in mammals,” J. Steroid Biochem. 26(3), 369-373, 1987.
[3] T. Borisova, N. Krisanova, R. Sivko and A. Borysov, “Cholesterol depletion attenuates tonic release but increases the ambient level of glutamate in rat brain synaptosomes,” Neurochem Int. 2010 Feb;56(3), 466-78, 2010.
[4] J.J. Cannell, “Autism and vitamin D,” Med Hypotheses, 70, 750-9, 2008.
[5] P.A. Dawson, “Sulfate in fetal development,” Seminars in Cell and Developmental Biology in Press, 2011.
[6] P. Good, “Did acetaminophen provoke the autism epidemic?,” Altern Med Rev.
14(4), 364-72, 2009.
[7] D.A. Greenberg, S.E. Hodge, J. Sowinski and D. Nicoll, “Excess of Twins among Affected Sibling Pairs with Autism: Implications for the Etiology of Autism,” Am. J. Human Genetics 69, 1062-1067, 2001.
[8] D. J. Guerra, “The Molecular Genetics of Autism Spectrum Disorders: Genomic Mechanisms, Neuroimmunopathology, and Clinical Implications,” Autism Research and Treatment, Article ID 398636, 2011.
[9] H. C. Hazlett, M. Poe, G. Gerig, R.G. Smith, J. Provenzale, A. Ross, J. Gilmore and J. Piven, “Magnetic Resonance Imaging and Head Circumference Study of Brain Size in Autism: Birth Through Age 2 Years,” Arch Gen Psychiatry, 62, 1366-1376, 2005.
[10] M. F. Holick, “Environmental factors that influence the cutaneous production of vitamin D,” Am. J. Clin. Nutr. 61(suppl), 638S-45S, 1995.
[11] R.I. Kelley, “Inborn errors of cholesterol biosynthesis,” Adv Pediatr. 47, 1-53, 2000.
[12] H-G Kim, S. Kishikawa, A.W. Higgins, I-S Seong, D.J. Donovan, Y. Shen, E. Lally, L.A. Weiss, J. Najm, K. Kutsche, M. Descartes, L. Holt, S. Braddock, R. Troxell, L. Kaplan, F. Volkmar, A. Klin, K. Tsatsanis, D.J. Harris, I. Noens, D.L. Pauls, M.J. Daly, M.E. MacDonald, C.C. Morton, B.J. Quade and J. F. Gusella1, “Disruption of Neurexin 1 Associated with Autism Spectrum Disorder,” Am J Hum Genet. 82(1), 199-207, 2008.
[13] J. Langlais, M. Zollinger, L. Plante, A. Chapdelaine, G. Bleau, and K.D. Roberts, “Localization of cholesteryl sulfate in human spermatozoa in support of a hypothesis for the mechanism of capacitation,” Proc. Natl Acad. Sci. USA 78(12), Biochemistry, 7266-7270, 1981.
[14] B. Lin, K. Kubushiro, Y. Akiba, Y. Cui, K. Tsukazaki, S. Nozawa and M. Iwamori, “Alteration of acidic lipids in human sera during the course of pregnancy: characteristic increase in the concentration of cholesterol sulfate,” Journal of Chromatography B, 704, 99-104, 1997.
[15] M. Llansola, M-D Minana, C. Montoliu, R. Saez, R. Corbalan, L. Manzo, and V. Felipo, “Prenatal Exposure to Aluminum Reduces Expression of Neuronal Nitric Oxide Synthase and of Soluble Guanylate Cyclase and Impairs Glutamatergic Neurotransmission in Rat Cerebellum,” J. Neurochem., 73(2), 712-718, 1999.
[16] H. Nakae, O. Hanyu, H. Fuda and C.A. Strott “Novel role of cholesterol sulfate in gene regulation during skin development,” The FASEB Journal, 22:782.2, 2008.
[17] C. Napoli, F.P. D'Armiento, F.P. Mancini, A. Postiglione, J.L. Witztum, G. Palumbo and W. Palinski, “Fatty streak formation occurs in human fetal aortas and is greatly enhanced by maternal hypercholesterolemia. Intimal accumulation of low density lipoprotein and its oxidation precede monocyte recruitment into early atherosclerotic lesions,” J Clin Invest. 100:2680 2690, 1997.
[18] W. Palinski, “Maternal Fetal Cholesterol Transport in the Placenta: Good, Bad, and Target for Modulation,” Circ. Res. 104, 569-571, 2009.
[19] W.V. Rodrigueza, J.J. Wheeler, S.K. Klimuk, C. N. Kitson and M.J. Hope, “Transbilayer Movement and Net Flux of Cholesterol and Cholesterol Sulfate between Liposomal Membranes,” Biochemistry 34(18), 6208-6217, 1995.
[20] J. Tong, P.P. Borbat, J.H. Freed and Y-K Shin, ”A scissors mechanism for stimulation of SNARE-mediated lipid mixing by cholesterol,” PNAS 106(13), 5141-5146, 2009.
[21] T. Ylisaukko-oja, K. Rehnstr ̈om, M. Auranen, R. Vanhala, R. Alen, E. Kempas, P. Ellonen, J.A. Turunen, I. Makkonen, R. Riikonen, T. Nieminen-von Wendt, L. von Wendt, L. Peltonen and I. J ̈arvel ̈a, “Analysis of four neuroligin genes as candidates for autism,” European Journal of Human Genetics 13, 1285-1292, 2005.
Despite the fact that the vaccine industry has built a strong case that vaccines don’t cause autism, the autism community persists in claiming that they do. My research has led me to believe that the aluminum in vaccines plays a contributory role, as does the aluminum often found in sunscreen. Aluminum is a very common metal, yet it has never been incorporated into any biological system, and is clearly toxic to neurons, a subject I will return to later.
But I also believe that other environmental factors play probably a larger role than aluminum. Or, to say it another way, certain nutritional deficiencies predispose a child to be especially vulnerable to aluminum. My investigative research has led me to consider cholesterol [11] and vitamin D [3] deficiencies as prime candidates.
The brain represents only 2% of the total body mass, yet it houses 25% of the body’s total cholesterol. Because of the current obsession in the U.S. against dietary cholesterol and saturated fat, I was led to explore the question of cholesterol supply to the fetus during pregnancy. I was richly rewarded, and initially left baffled, by an article with a very surprising revelation [17]. Women with high serum cholesterol typically give birth to children with low serum cholesterol who already at birth have developed fatty streaks in their arteries, and are predisposed to developing heart disease much later in life. There seemed to be an inverse relationship between the mother’s and the fetus’s cholesterol levels!
Given the importance of cholesterol to the nervous system, remarkably little research has been done to characterize the mechanisms by which the fetus supplies itself with cholesterol. It had been hypothesized that the fetus synthesizes all of its own cholesterol supply, which would be surprising, given that cholesterol synthesis is a complex twenty-five step process that might be difficult for a fledgling organism to carry out. However, the biological machinery that would be necessary to transport cholesterol across the placental barrier to the fetus did not seem to exist [18].
I believe I have found the answer in a 1997 article by a team of Japanese researchers [14]. These authors were inspired to look at the concentration of cholesterol sulfate in the placenta and in the mother’s blood, as a function of time throughout pregnancy. They discovered that cholesterol sulfate concentrations in the mother’s blood rose from 1.85 to 2.23 to 3.09 over the course of the three trimesters of pregnancy, whereas non-pregnant women had a serum level of only 1.56. However, the more remarkable observation was the increase in cholesterol sulfate noted in placental villi, hairlike projections from the placenta that provide lots of surface area for contact with fetal blood supply. The concentration of cholesterol sulfate here went up from 3.93 to 18.35 to 23.75 over the course of the three trimesters, a six-fold increase from the first trimester to the third trimester! It might have been anticipated that cholesterol sulfate is important to the fetus, as it is in fact critically involved in the sperm decapitation stage that allows the sperm to fertilize the egg [13].
I am inclined to hypothesize (somewhat boldly) that certain mothers (and, more generally, certain people) have high cholesterol to compensate for the fact that their cholesterol sulfate level is deficient. Their fetus has low cholesterol because of inadequacies in the supply chain, obligatorily mediated by cholesterol sulfate. I might also boldly add that high cholesterol, a risk factor for cardiovascular disease in both the mother and the child, is, by deduction, an indicator of low cholesterol sulfate, and therefore that cholesterol sulfate protects from cardiovascular disease. I will need to revisit this topic in a later post!
Cholesterol sulfate is an interesting and elusive molecule. It is synthesized in the skin upon exposure to sunlight, alongside vitamin D3 sulfate [10, 2] and so this might be the connection between autism and vitamin D deficiency. It could well be that the sulfated form of vitamin D3 can substitute for cholesterol sulfate to some extent in supplying the fetus with sulfate. And it might then be supposed that sulfate is a critical nutrient that is in short supply in fetuses destined to later develop into autistic children.
This idea gains strong support from an article in Press in the timely subject of sulfate in fetal development [5]. From several studies on humans with rare genetic disorders and on animal models involving genetically engineered defective genes, it is abundantly clear that sulfate is absolutely essential to healthy fetal development. Furthermore, sulfate plays an important role in detoxifying drugs that might damage the fetus or the infant, such as acetaminophen, the active ingredient in tylenol. In fact, an interesting review article proposes that vulnerability to damage by Tylenol given subsequent to a vaccine-induced fever may have been a risk factor for autism [6]. Further support for a sulfate deficit in autism comes from a study showing, with a highly significant p-value of ¡ .00002, that severely autistic kids are unable to sulfate (and therefore detoxify) toxic chemicals [1].
Another really remarkable thing about cholesterol sulfate is that, in part because of its negative charge, it is “amphiphilic”: soluble in both water and fat. This means that it can travel freely in the blood stream (does not have to be packaged up inside LDL particles), and easily enters cell walls (ten times as agile as cholesterol itself in penetrating cell walls) [19]. I suspect these unique properties make it also much easier for cholesterol sulfate to get across the placental barrier than would be the case for cholesterol. Furthermore, cholesterol sulfate plays an important role in the outer skin, in protecting the body from invasion by pathogens [16]. A deficiency in cholesterol sulfate in the skin might explain the fact that autistic children often have skin problems and are more prone to infection.
I’d like to now return to the subject of the supposed genetic component to autism, which has been justified in part because an identical twin is much more likely to also have autism given that his twin has autism than is the case for fraternal twins. However, there is a further interesting observation that even fraternal twins are much more likely to both have autism than two siblings who are not twins. The genetic distance between fraternal twins is the same as that between brothers, and therefore genes can not explain this phenomenon. Furthermore, just being a twin is a risk factor for autism [7]. It would seem to me that all of these observations can be nicely explained if the assumption is that inadequate supply of a scarce resource (e.g., cholesterol sulfate) is the source of the problem. Twins would place double the demand on the mother’s limited supply. And identical twins often share a single placenta, which means that the villi would have to be twice as proliferous to fully supply two fetuses simultaneously, an unlikely feat. This could account for the increased risk in identical twins, without involving genetics at all.
Finally, I would like to return to the subject of aluminum, by discussing a fascinating article involving an experiment with aluminum exposure to pregnant mice, followed by an investigation of the properties of neurons harvested from the brains of the offspring. But first I should mention a couple more facts about features of autism. One novel characteristic of the autistic brain is that it actually is larger than the non-autistic brain at the age of two or three [9]. This is a time when ordinarily the brain goes through a massive pruning process, to weed out neurons that have failed to build up sufficient synaptic connections to be worthy of survival.
Two biological molecules that pair up on either side of the synapse to promote the memory of synaptic stimuli are neurexin and neuroligin. Several of the rare genetic defects that sometimes show up in connection with autism are related to either neurexin [12], on the input side of the synapse, or neuroligin [21] on the output side, where these two work together synergistically to coordinate transmission of the neurotransmitter glutamate. Glutamate plays an important role in wiring up the brain during early development, and this function has been hypothesized to be disturbed in autism. Glutamate is also intimately involved in the stage where neurons are pruned due to the fact that they received little input and are thus deemed extraneous. Furthermore, cholesterol, through a scissors mechanism, has been shown to play a crucial role in greatly increasing the ability of two neurons to make contact at a synapse [20]. In line with this observation, in-vitro studies have shown that cholesterol deficient neurons exhibit impaired glutamate transport, causing excess glutamate to accumulate outside the neuron [3].
In this light, the experiment on the mice that were exposed to aluminum prenatally was highly relevant. One of the important roles glutamate carries out is to signal to an unworthy neuron that it should die: that it should commit “programmed cell death” or “apoptosis” during the massive pruning stage. The mouse experiment [15] showed that neurons taken from the brains of mice prenatally exposed to aluminum responded abnormally to glutamate exposure that should have led to apoptosis. Whereas the number of neurons in the petri dish harvested from control mice sharply decreased upon exposure to glutamate, the aluminum-exposed neurons were quite happy to keep on growing, effectively ignoring the glutamate signal. This seemed to be exactly the same thing that the neurons in the autistic brains were doing when they weren’t pruned!
In summary, it seems to me that a possible explanation for the recent steady and alarming increase in the rate of autism in the U.S. is the confluence of a number of factors leading to a perfect storm. The problem centers on the two American obsessions of avoiding dietary fat and cholesterol and overprotection from the sun. The problem is further compounded by the relentless increase in the number of vaccinations against a multitude of childhood diseases, increasingly mandated by the U.S. government. These environmental influences conspire to produce children who are grossly deficient in cholesterol sulfate, which leads to impaired neurotransmission in the brain and impaired immune systems. The infiltration of aluminum into the brain compounds the problem, by further disrupting the already impaired glutamate transmission. The aluminum toxicity builds up due to the combination of exposure to both vaccines and sunscreen applied far too frequently to the skin, in the context of sulfate deficiencies that impair natural detoxification processes. It seems that some major changes in the American attitude towards what constitutes healthy living will need to take place before this epidemic can be brought under control.
References
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[2] M. Axelson, “The cholecalciferol sulphate system in mammals,” J. Steroid Biochem. 26(3), 369-373, 1987.
[3] T. Borisova, N. Krisanova, R. Sivko and A. Borysov, “Cholesterol depletion attenuates tonic release but increases the ambient level of glutamate in rat brain synaptosomes,” Neurochem Int. 2010 Feb;56(3), 466-78, 2010.
[4] J.J. Cannell, “Autism and vitamin D,” Med Hypotheses, 70, 750-9, 2008.
[5] P.A. Dawson, “Sulfate in fetal development,” Seminars in Cell and Developmental Biology in Press, 2011.
[6] P. Good, “Did acetaminophen provoke the autism epidemic?,” Altern Med Rev.
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[7] D.A. Greenberg, S.E. Hodge, J. Sowinski and D. Nicoll, “Excess of Twins among Affected Sibling Pairs with Autism: Implications for the Etiology of Autism,” Am. J. Human Genetics 69, 1062-1067, 2001.
[8] D. J. Guerra, “The Molecular Genetics of Autism Spectrum Disorders: Genomic Mechanisms, Neuroimmunopathology, and Clinical Implications,” Autism Research and Treatment, Article ID 398636, 2011.
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[10] M. F. Holick, “Environmental factors that influence the cutaneous production of vitamin D,” Am. J. Clin. Nutr. 61(suppl), 638S-45S, 1995.
[11] R.I. Kelley, “Inborn errors of cholesterol biosynthesis,” Adv Pediatr. 47, 1-53, 2000.
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[13] J. Langlais, M. Zollinger, L. Plante, A. Chapdelaine, G. Bleau, and K.D. Roberts, “Localization of cholesteryl sulfate in human spermatozoa in support of a hypothesis for the mechanism of capacitation,” Proc. Natl Acad. Sci. USA 78(12), Biochemistry, 7266-7270, 1981.
[14] B. Lin, K. Kubushiro, Y. Akiba, Y. Cui, K. Tsukazaki, S. Nozawa and M. Iwamori, “Alteration of acidic lipids in human sera during the course of pregnancy: characteristic increase in the concentration of cholesterol sulfate,” Journal of Chromatography B, 704, 99-104, 1997.
[15] M. Llansola, M-D Minana, C. Montoliu, R. Saez, R. Corbalan, L. Manzo, and V. Felipo, “Prenatal Exposure to Aluminum Reduces Expression of Neuronal Nitric Oxide Synthase and of Soluble Guanylate Cyclase and Impairs Glutamatergic Neurotransmission in Rat Cerebellum,” J. Neurochem., 73(2), 712-718, 1999.
[16] H. Nakae, O. Hanyu, H. Fuda and C.A. Strott “Novel role of cholesterol sulfate in gene regulation during skin development,” The FASEB Journal, 22:782.2, 2008.
[17] C. Napoli, F.P. D'Armiento, F.P. Mancini, A. Postiglione, J.L. Witztum, G. Palumbo and W. Palinski, “Fatty streak formation occurs in human fetal aortas and is greatly enhanced by maternal hypercholesterolemia. Intimal accumulation of low density lipoprotein and its oxidation precede monocyte recruitment into early atherosclerotic lesions,” J Clin Invest. 100:2680 2690, 1997.
[18] W. Palinski, “Maternal Fetal Cholesterol Transport in the Placenta: Good, Bad, and Target for Modulation,” Circ. Res. 104, 569-571, 2009.
[19] W.V. Rodrigueza, J.J. Wheeler, S.K. Klimuk, C. N. Kitson and M.J. Hope, “Transbilayer Movement and Net Flux of Cholesterol and Cholesterol Sulfate between Liposomal Membranes,” Biochemistry 34(18), 6208-6217, 1995.
[20] J. Tong, P.P. Borbat, J.H. Freed and Y-K Shin, ”A scissors mechanism for stimulation of SNARE-mediated lipid mixing by cholesterol,” PNAS 106(13), 5141-5146, 2009.
[21] T. Ylisaukko-oja, K. Rehnstr ̈om, M. Auranen, R. Vanhala, R. Alen, E. Kempas, P. Ellonen, J.A. Turunen, I. Makkonen, R. Riikonen, T. Nieminen-von Wendt, L. von Wendt, L. Peltonen and I. J ̈arvel ̈a, “Analysis of four neuroligin genes as candidates for autism,” European Journal of Human Genetics 13, 1285-1292, 2005.
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