Chapter Nine
Risk Factors
Autism exists on a spectrum because inflammation is variable in both its strength and timing. More severe inflammation at critical points during pregnancy can strongly disorder neuron arrangements and result in severely disabled ASD. Also, severe inflammation can damage DNA, creating genetic mutations that disable important functions.
In contrast, less severe increases of inflammation during pregnancy may make a high-functioning ASD individual. Therefore, avoiding risk factors that raise inflammation is important to reducing ASD risk and severity.
One risk factor is refined carbohydrates, which can spike blood glucose, increasing glucose metabolism. Excessive glucose metabolism is a risk factor for more inflammation because it creates a higher ratio of NADH/FADH2 than fat metabolism.
As discussed in Chapter 6, this ratio is critical because complex I in electron transport chains of mitochondria uses NADH. Excessive activation of complex I makes too many superoxide molecules, a reactive oxygen species. If cells cannot regulate these reactive oxygen species, then inflammation increases.
High blood glucose levels also increase inflammation by creating advanced glycation end-products. Inflammation also increases because of multiple other factors, such as those mentioned in this book.
Genetics
Because ASD occurs more frequently in specific families, ASD appears strongly influenced by genetics and not as affected by the environment.
However, an overlooked factor is that some families have epigenetically enhanced inflammation, as discussed in Chapter 5. This epigenetic enhancement is itself mainly caused by inflammation that results from environmental and lifestyle factors.
Inflammation alters many different genes epigenetically without a definite pattern. There are extreme differences in epigenetic changes, but they often increase the inflammatory response. The many various inflammatory effects and its epigenetic changes explain why ASD has such a wide spectrum.
If families of an ASD child already experience enhanced inflammation, then there may be relatives in the family that have health conditions associated with inflammation, such as autoimmune diseases. Multiple researchers note there are links between autoimmune diseases and increased inflammation (613) (614) (615).
In agreement with this concept, research found relatives of ASD children were more likely to have an autoimmune disease (39). Also, reviews found an increased chance of ASD occurrence if relatives had autoimmune diseases (616) (617).
Interestingly, some maternal antibodies may accurately predict the risk of having an ASD child (618). Research notes these antibodies may affect fetal development (619).
These studies indicate the involvement of autoimmunity, often caused by inflammation. Considering this and other information in this book, then understanding the factors that increase inflammation is likely the secret to solving the autism mystery.
However, the current trend of technology-driven science is to seek specific genes to find the cause of ASD. The fact that identical twins have an increased risk of both being autistic strongly affects this focus on genetics. Research found the chance of both twins being ASD was 31% for fraternal twins and 88% for identical twins (620). While other research, using a strict definition of ASD, found the rate to be about 60% for identical twins of the same sex (621).
However, twin studies are not an accurate measurement of genetic impact. Twins share not only genetic material but also intrauterine environments (37). Researchers note the rate of identical twins sharing a placenta is 60% (622). The researchers also note how “animal studies support the point that two-thirds of” identical twins “share the same placenta, which means that they are sharing key environmental factors” not shared by most fraternal twins (622).
If more than one placenta is in the womb, then the mother’s body may better control the damage in one placenta to increase the chance of survival for at least one of her children. Environmental problems can negatively affect one placenta much more than the other. This placenta difference explains why fraternal twins are less likely to both be autistic than twins that share the same placenta.
In further support of a greater environmental impact are a few observations.
The first observation is identical twins have significant variation in how ASD affects them (623). Also, there are a lot of epigenetic differences between identical twins (55). This is because reactive oxygen species change the epigenetic arrangements differently in each person.
The second observation is the differences in cerebellar morphometry in identical ASD twins (569). This variance occurs because of the different ways inflammation affects individuals.
The third observation is a single gene may only explain 1% of ASD (192). This is an incredible fact that really should shift ASD research money away from genetics.
The fourth observation is reactive oxygen species cause many genetic mutations (624) (625) (626) (627).
This is a critical point.
Beyond epigenetic changes, reactive oxygen species can cause DNA mutations. This means environmental and lifestyle factors can be the original cause of many genetic health conditions.
Inflammation also affects the ability to repair DNA copy errors. This is because methylation inefficiency limits the DNA repair activities. As discussed in Chapter 3, inflammation can cause methylation inefficiency.
These observations mean that the obsessive focus on ASD genetics is incorrect. The more likely causes of ASD and many other health conditions are nutritional, environmental, and lifestyle factors that lead to excessive reactive oxygen species generation.
Of course, research does find a few associations between genetics and ASD, but a major cause of those variants is DNA damage from reactive oxygen species. In addition, other genetic problems, such as copy errors, are often a result of reduced genome stability caused by methylation inefficiency, which itself is frequently a result of reactive oxygen species inhibiting methylation cycle enzymes.
Therefore, factors that increase inflammation may be the main cause of many different health conditions, including conditions with well-established genetic problems, like Fragile X, cystic fibrosis, and Huntington’s disease. For example, many generations ago an ancestor could have gotten the genetic condition from environmental factors and then passed those genes on to future generations.
Genetic researchers need to frequently ask the following questions:
What factors increase the risk?
What is causing genetic changes?
Do the genetic changes have a useful purpose?
How does inflammation affect this pattern?
Genetic alterations may often be the middleman between inflammation and many health effects. As an analogy, a lightbulb emits light, but electricity is the source of the light. Redirecting research money away from genes and towards environmental, nutritional, and lifestyle factors will lead to a significantly better return on investment.
Immigration
Another risk factor for ASD is recent immigration. A study found that children with an immigrant parent had high CRP levels, a sign of inflammation (628). Also, researchers found ASD affected a Somalian immigrant community at about a three to four times higher rate than the other groups (629). Another study found recent immigrants from Somalia living in Minnesota had a slightly higher rate of ASD (630). In all these studies, the Somalians were recent immigrants to the area.
There is significant stress involved in moving to a new country, especially if not starting with many resources. Additionally, recent immigrants may consume unhealthy foods because of limited money. The stress of moving to a new country combined with fewer healthy food options may lead to increased inflammation and higher ASD risk.
Vaccines
One of the most sensitive topics is vaccines. Some parents report their child began to display ASD symptoms after vaccinations. However, research studies found there is no association between vaccinations and ASD risk (631) (632).
Unfortunately, these research studies do not compare the vaccinated to the fully unvaccinated. Instead, the design of the research is to measure the differences created by removing one vaccine, measles-mumps-rubella (MMR). This only indicates MMR risk and does not provide much useful information about overall vaccine risk because the control group could still receive multiple other vaccines.
Other researchers did studies comparing the vaccinated to the fully unvaccinated, but their research focused on different health risks (633) (634) (635). Also, some of this research may have flaws. The number of subjects included in the research is too small to detect potential negative health effects that already have a low occurrence. In addition, the vaccinated group may not be fully vaccinated. They may also have a much higher education and income, which alters many other variables. Furthermore, none of these studies measured ASD risk.
Rather than these studies that look at other health risks, the media may refer to large epidemiological studies on vaccines and ASD as proof vaccines do not cause ASD.
However, as previously mentioned, many of these large studies only compare removing one vaccine, MMR. These research designs allow the control group to still receive multiple other types of vaccines. Logically, these designs are not an adequate assessment of actual overall vaccine risk.
Furthermore, healthy user bias is a significant problem in many epidemiological vaccination studies. This bias happens when the healthy population is more likely to receive treatment, in this case, vaccines. Families with children that already have more health challenges may be less likely to seek vaccination for their children due to fear and concern. As researchers note, this type of bias is a “general problem for studies of adverse reactions to prophylactic interventions, as they may be withheld from some individuals precisely because they are already at high risk of the adverse event (636).” This might cause the unvaccinated group to have overrepresentation of ASD people. This bias can hide potential risks that may exist with vaccination. Therefore, epidemiological studies are not an adequate assessment of potential risks.
Now, this is not to say vaccines cause autism. The point is researchers need to do better research. Many vaccine studies are epidemiological and possibly incorrect because of healthy user bias and lack of a true control group. The vaccine issue will continue to receive attention until researchers complete randomized, double-blind research studies that compare the fully vaccinated to the fully unvaccinated.
However, there is an explanation that indicates vaccines do not cause ASD. As previously mentioned, many ASD children have depleted antioxidant defenses and excess reactive oxygen species because of many factors. When ASD children are born, they already have a disordered neuron network because of inflammation in the womb. This lack of connectivity frequently does not fully appear until around two years of age, which is coincidentally the time when children receive multiple vaccines.
As previously mentioned, at around two years of age, the number of glutamate receptors increases, which allows glutamate to further enhance inflammation. This sudden inflammation increase may lead to ASD symptoms.
Another factor to consider is the brain uses more glucose as a child ages. Researchers found the brain’s metabolic requirements increase from birth and peak in childhood, a time when the brain “uses glucose at a rate equivalent to 66% of the body’s resting metabolism and 43% of the body’s daily energy requirement (637).” Also, more neurons are created with age, increasing total metabolic activity in the brain. This extra metabolic activity can increase inflammation.
The inflammation, in combination with the CDR, causes the neurons to retract, exposing the disordered neuron network. This disorganization was already established in the womb because of the previously mentioned reasons.
When a child gets a vaccine, this may happen at the same time there is a natural increase in inflammation. Parents may start seeing ASD symptoms around two years of age, which coincidentally is the same time many children get vaccinated.
Parents are right to notice change, but vaccines are likely not the cause. Correlation is not causation. Just because events happen together, does not mean one event causes the other event.
The point here is some children already have an altered arrangement of neurons, weakened antioxidant defenses, and too many reactive oxygen species. The first increase of inflammation might reveal what was always going to eventually appear, symptoms of a disorganized neuron network.
This concept is very important. If a child has significant inflammation while in the womb, then ASD may already exist, waiting to appear when inflammation increases later in life.
The design of vaccines is to slightly challenge immunity to train the body to resist specific pathogens. However, a concern about vaccines is just how much vaccines might affect inflammation in a vulnerable individual.
Compared to all the other factors mentioned in this book, many vaccines barely activate the immune system at all. As an analogy, vaccines might be like turning on a fan while already inside a hurricane. If someone already has severe inflammation, symbolized by a hurricane, then a vaccine, symbolized by a fan, may cause no difference.
However, perhaps certain vaccines can cause a powerful inflammatory response. Maybe this response is strong in children with a severe depletion of antioxidant enzymes and weak immune defense systems. Perhaps vaccination worsens ASD symptoms in some people. There may need to be specific screening of vulnerable people to determine antioxidant ability and immune system power. Of course, these are just ideas, and vaccines are likely not a concern.
Because ASD begins in the womb, then vaccines cannot cause ASD. Vaccines are unlikely to even create enough inflammation to significantly affect a sensitive person. Although I do not think vaccines influence ASD, like any decent researcher, I will keep my mind open to future developments.
In summary, the most frequent cause of ASD is excessive inflammation while the child is in the womb. A natural increase of glutamate receptors, synapse pruning, and glucose metabolism happens as the child ages, increasing brain inflammation. This process further activates the CDR, which exposes the neuron network disorganization that already happened in the womb. The natural increase of inflammation around two years of age may then appear as ASD regression and a worsening of symptoms.
As mentioned, these natural increases of inflammation often happen around the same time that children receive vaccines. This timing makes vaccines appear as if they are causing ASD symptoms. The design of vaccines is to challenge the immune system, but as mentioned, the effect might be like turning on a fan in a hurricane. Still, non-epidemiological ASD research comparing the fully vaccinated to the fully unvaccinated needs to be done to better understand if there are risks for more vulnerable people.
Parental Age
A risk factor associated with ASD is parental age. Many research studies found older women have an increased risk of having an ASD child (638) (639) (640). Older men are also more likely to have an ASD child (641) (642). These facts are not surprising, considering inflammation often increases with age (643). Older age also features increased epigenetic changes, which inflammation affects. For example, there is a link between older age and hypomethylation (644).
Methylation levels are such a good predictor of age that there is an epigenetic clock. DNA methylation levels may determine an individual’s age “with an average accuracy of 5.2 years (645).” The association with age and methylation is important because older parents are much more likely to have epigenetically enhanced inflammatory responses, DNA mutations, and fewer nutrients in the body. These changes may then transfer to the next generation, which increases the child’s inflammatory response and the risk of a significant health condition.
Prenatal Risk
An important area of ASD research is the study of various prenatal risk factors. Pollution, discussed earlier, is one of the prenatal factors that increases ASD risk (646) (647) (648). Significantly, the firstborn child tends to receive most of the mother’s pollution (649). Researchers found the firstborn child has an increased risk of ASD (650) (651). Perhaps this occurs because the mother’s body uses the first pregnancy to remove some pollutants so future pregnancies have a better chance of survival.
Unsurprisingly, given earlier discussions, inflammation in the mother during pregnancy is a risk factor for having an ASD child. Infection in the mother that causes her to have inflammation affects the developing brain (652). Also, there is an association between the mother having a viral infection during pregnancy and ASD risk in her child (653). Autoimmune psoriasis, asthma, or type 1 diabetes in the mother all associate with increased chances of having an ASD child (40). These seemingly different health conditions all involve increased inflammation.
Limiting the multiple factors that increase inflammation, especially during pregnancy, will dramatically reduce the risk of having an ASD child. Some of the biggest factors to focus on improving are psychological stress, pollution, and nutrition, which are discussed in other chapters.
Inflammation Balance
As an important side note, some inflammation is needed at specific times during pregnancy. The fetus increases inflammation for the process of synapse pruning, which typically happens during the third trimester. Taking too many anti-inflammatories limits this process. Increased consumption of proanthocyanidins and anthocyanins in the third trimester affects prenatal closure of the ductus arteriosus and may cause heart problems in the child (654). Both molecules have anti-inflammatory effects.
Another study found IL-10 limited the pro-inflammatory response, but excessive IL-10 in the fetal mice had an association with behavioral abnormalities (655). This study and the previous study indicate that some inflammation is necessary during pregnancy
The point here is that inflammatory balance is extremely important. Too many anti-inflammatories will create an imbalance and have negative health effects.
This warning brings up the fact that inflammation is the most beneficial when activated in short bursts, such as when the body needs more inflammation for an injury or pathogenic attack. The acute inflammation response is essential for defending the body and stopping pathogens, which cause damage if unchecked.
Therefore, unnatural methods of reducing inflammation may cause health problems. For example, anti-cytokine therapies “block the activity of various kinases and show a significant decrease” in host ability to defend against infections (656). Research also found too much of the anti-inflammatory curcumin contributed to a worsening of a disease caused by parasites (657).
The goal is to have a balanced immune system rather than excessive suppression of inflammation. There is a complex dynamic involved between the pro- and anti-inflammatory pathways (658). Frequently think about how balance is important and exists throughout Nature.
Gender
Another important risk factor is gender. The risk of ASD is four times greater in a male child (659). The reason for the risk difference may be that the hormone estrogen gives additional protection from inflammation. Both women and men have estrogen, but women have much more. This hormone affects survival, development, plasticity, and regeneration in the brain (660). In contrast, treatment with an anti-estrogen blocked the neuroprotective effects of estrogen (661).
Critically, estrogen also has direct antioxidant activity (662). Estrogen can capture and neutralize the reactive oxygen species hydroxyl through the formation of a nonphenolic quinol upon the capture of hydroxyl (663). The body can then convert the quinol back into estrogen with the assistance of NADPH, a cofactor required for many reactions. Once the quinol is back in estrogen form, estrogen can reduce another hydroxyl, continuing this cycle. The support of estrogen in removing hydroxyl helps to reduce reactive oxygen species and associated inflammation. This action of estrogen helps to save more glutathione. Interestingly, research found higher glutathione in female cells (664).
Females also have many other differences. Researchers note “mitochondria from females produce significantly less hydrogen peroxide than those from males and have higher levels of mitochondrial reduced glutathione” as well as more antioxidant enzymes, such as manganese superoxide dismutase and glutathione peroxidase (665). The researchers then remark how ovary removal “abolishes” the gender differences between males and females, whereas estrogen replacement reverses the effects caused by ovary removal (665).
The researchers also note oxidative damage is “fourfold higher in males than in females (665).” Amazingly, the ASD rate is also about four times higher in males.
If estrogen has protective activity, then avoiding factors that reduce estrogen activity is important. One negative factor is xenoestrogens, which affect estrogen receptors. Xenoestrogens are found in solvents, papers, fungicides, herbicides, and plastics (161). They can mimic estrogen and disrupt natural hormone activity (666). Therefore, avoiding xenoestrogens improves estrogen function in the body.
As previously discussed, glyphosate potentially inhibits the aromatase enzyme. One of the reasons this enzyme is important is because aromatase increases the conversion of testosterone to estrogen to help reduce excess reactive oxygen species. If glyphosate inhibits aromatase, then less estrogen will be available to assist with controlling inflammation. This is just one of the many reasons avoiding foods exposed to glyphosate may benefit health.
Aromatase brings up the importance of testosterone. A deficiency of testosterone in women and men may cause “apathy, depression, a diminished or lost sex drive, fat gain, joint aches and pains, loss of exercise endurance, and osteoporosis (161).”
As mentioned, aromatase may convert some testosterone into estrogen during increased inflammation (667). Because of the increase in estrogen, the body may also create more testosterone to try and keep estrogen and testosterone in a proportional balance according to gender. This creation of additional testosterone because of inflammation is why women sometimes have high levels of testosterone, which can cause health problems.
Since excess inflammation in the womb can cause ASD, then higher levels of estrogen would need to be available to the female fetus to create the 4 to 1 ASD gender ratio. Interestingly, amniotic fluid around the fetus has extra estrogen if it’s female (668). The protective effects of extra estrogen cause, on average, a female fetus to have better control of reactive oxygen species than a male fetus.
Discussed in Chapter 8, excess reactive oxygen species leads to the Cell Danger Response (CDR), which causes reduced connectivity between neurons and disrupts the organized formation of the neuron network in the womb. The CDR, combined with excess inflammation, is the main cause of ASD. Because a female fetus often has less inflammation, then this explains the gender risk.
Estrogen also affects a few of the other differences found between male and female cytokine expression. Research notes there is a more pro-inflammatory condition in male preterm placentas compared to female placentas (669). Also, there is an association between female fetal sex and high levels of cytokines that help to regulate inflammation (670). Studies found IL-10, which helps regulate inflammation, was higher in females (671) (672). There are extra regulatory cytokines in females, so pregnancy is more protected from an excess inflammatory response.
There are also gender differences in how the fetus grows. The male fetus directs more energy into increasing size, whereas the female fetus directs its energy on developing the placenta (673). This growth of the placenta contributes to female fetuses having more reserve capacity than male fetuses, which helps the female fetus survive a challenge.
Another difference is females get an X chromosome from both parents, while males only get an X chromosome from the mother, except in rare situations. Since women have two X chromosomes, cells randomly inactivate one of the X chromosomes, so each cell has one active X chromosome. This inactivation is visible in the patchwork coloring of a calico cat.
The random inactivation of X chromosomes increases the genetic variety in females and allows the X chromosome to have much more influence. This is significant because “several regulatory and metabolic proteins participating in hormonal effects, signal transduction, apoptosis, carbohydrate metabolism, superoxide production, and xenobiotic and antioxidant defense are encoded on the X chromosome (674).” The natural X chromosome variations may strongly affect the better immune system regulation in females.
If females often have more protection from inflammation than males, then for a female to be autistic, there would have to be much more inflammation. Since reactive oxygen species can create a significant amount of DNA variation, then an ASD female would likely have more variants in her DNA than an ASD male. In line with this concept, research found more DNA mutations in females with neurodevelopmental disorders (675). The study noted this supports the idea that females are more protected than males (675).
Nutrition Risk
Probably the most important factor affecting ASD risk is nutrition. Incorrect nutrition in the parents, especially the mother, greatly increases the risk of having an ASD child. Certain foods increase inflammation, while other foods are lacking in essential micronutrients. Refer to Chapter 7 to learn more about various factors affecting nutrition quality.
As a brief recap of this previously mentioned information, a significant negative health influence is eating industry meat. This meat might come from concentrated animal feeding operations (CAFOs), where animals often receive multiple antibiotics and hormones to limit the diseases associated with harmful and unnatural living conditions. This industry meat may contain a significant number of pollutants because the industry may feed animal parts to successive animal generations, which causes a gradual accumulation of pollution as the pollutants pass from one generation to the next. The meat industry also often feeds animals grains to fatten up the animals and make more money. This creates higher levels of omega-6 fat in most of the meat at the supermarket.
For all these reasons and more, purchasing meat from a local farmer’s market is frequently healthier. However, if careful about meat selection, then the supermarket may also have a few good choices. In either market, investigate to know more about the treatment of the animals because their treatment impacts the health effects of the meat.
Overall, having most of the food plan be plant-based with enough fiber content to slow down glucose absorption will be better. Eating more plants is also better because of the many problems with meat production, such as pollution, environmental destruction, and cruel animal treatment.
Fortunately, there are many plants to eat. As mentioned, many plants have more vitamin and minerals than other forms of food. Chapter 7 has a discussion of the benefits associated with eating plants.
As previously mentioned, there is a significant difference in health benefits between a plant-based eater who eats food such as bread, corn, carrots, romaine lettuce, and tomato, compared to a person eating broccoli, blueberries, kale, peppers, and apples. Although both people may eat plant-based, one does not get as much helpful nutrition and phytochemical content.
This difference is important because many restaurants serve basic lettuce salads containing a couple of carrots, a tomato, some onions, and dressing. Many people then think they are improving health by eating these salads. Even worse, many restaurants also use salad dressings containing a lot of omega-6 and sugar, which are harmful to health.
In contrast, a salad prepared at home could have romaine lettuce, spinach, kale, apples, broccoli, carrots, peppers, berries, and a healthier dressing. Future research should compare the nutrient and phytochemical values found in the average restaurant salad versus a customized homemade salad containing different types of ingredients.
As mentioned in Chapter 7, avoiding most supermarket meats and foods that have high glycemic loads are two of the best ways to improve health. Because fat metabolism generates fewer reactive oxygen species than glucose metabolism, then another big change is to increase fat intake to around 30 to 40 percent of total daily calories.
However, this type of fat needs to be a balanced mixture of monounsaturated and saturated fat that comes from a good source. Increasing this type of fat should not happen if refined carbohydrate or other foods with high glycemic loads are still part of the food plan.
The body also requires polyunsaturated fats. These are available in their natural forms in food. Completely avoid refined polyunsaturated fats. See Chapter 6 and Chapter 7 for more information about metabolism and fat.
There is a lot of information here that some people can find overwhelming. Therefore, working with a consultant that knows about the impact of nutrition may be helpful.
In general, incorrect nutrition is one of the most harmful lifestyle choices that significantly increases both the risk of ASD and the severity of daily symptoms. Choosing to understand and take control of nutrition is one of the best life decisions.
Cart Watch
Next time you are at the grocery store, pay attention to the shopping cart of the average consumer. The cart will likely be full of processed high glycemic load foods containing chemicals and added sugar. There will likely also be a lack of fruits and vegetables in the shopping cart. Shockingly, many people also add multiple two liters of soda, ice cream, and frozen pizzas.
However, do not judge the other person because that is not kind. Many people simply do not know how various foods can lead to severe health conditions. This practice of looking at shopping carts is more about reinforcing the understanding of why so many people are suffering from various health conditions in modern society.
Unfortunately, this lack of awareness about health and nutrition includes many researchers. These researchers often have terrible nutrition while conducting expensive research projects that finish without effective solutions to health conditions.
Thankfully, the main way to heal many health conditions is as simple as changing shopping cart contents, reducing psychological stress, and making a few lifestyle changes.