Environmental Chemicals, Nutrition, and Autism Spectrum Disorder: An Update

The prevalence of autism has increased from 1 in 100 in 2009 to almost 1 in 25 recently. The rapid increase of the prevalence of autism spectrum disorders (ASD) suggests that exposure to chemicals may impact the development of ASD. Any genetic cause of ASD contributes the same always and therefore, if ASD were a genetic disease only, the prevalence would have remained stable over the years. This rapid increase of the prevalence in recent decades implies that there is more into the cause of ASD than just genetics. 

Recent reviews of the existing literature investigated the relationship of various environmental chemicals and nutrients with the development or prevention of ASD. 

1. 1. Smoke/tobacco consumption
      1. The findings are controversial but recent studies indicate that the association of the use of tobacco products may be more related to the confounding effects of the socioeconomic status of the family; tobacco products use is more common among poor and socioeconomically disadvantaged societies (Fujiwara T. et al., Front. Neurosci. 10:174, April 2016
   2. Excess alcohol
      1. Maternal alcohol during pregnancy was not associated with any risk for ASD. (Daniels et al., 2008 and Eliasen et al., 2010). It is important here that all alcoholic drinks are not equal and common sense is important. Having a glass of red wine with dinner a few times is different from having hard liquor. So, do not throw caution to the wind. 
   3. Air pollution
      1. Most studies have shown a positive relationship between air pollution and ASD (Suades-Gonzales et al., 2015). Defining environmental pollution however inside people’s homes is not easy and most studies used extrapolations to assess air pollution. Furthermore, there is a strong correlation between living in polluted locales and low socioeconomic status which might confound the results. 
   4. Pesticides
      1. Numerous studies have documented the effect of organophosphates and organochlorides which are unfortunately still in use. This is true for residential as well as agricultural use. In fact, living within a mile of a farm using such pesticides has been associated with increased prevalence of ASD. They also found increase use of pyrethroids in patients with ASD. Finally, flea/tick treatment with imidacloprid through pregnancy was associated with increased risk for a child with autism. 
      2. Fungicides that are used in conventional berry (strawberries, blueberries, etc.) production cause damage to the ovarian granulosa cells and reduce ovarian reserve. Similar effects in men’s testicular granulosa cells exert negative and damaging effects on the number and quality of sperm. 
   5. Endocrine disrupting chemicals (endocrine disruptors)
      1. Polychlorinated biphenyl (PCB) and several dioxins were banned by the Stockholm Convention in 2001 but they are still detected in humans due to their persistence in the environment. Bisphenol A (BPA) chemicals are still used in many countries and they are associated with increased risk of ASD. 
      2. Phthalates are associated with increased risk of ASD. Phthalates exist in many commercial products and exposure to these endocrine disruptors is very common. Phthalates are used in many beauty products, in polyvinyl chloride flooring (vinyl flooring covers), and in house-dust. 
   6. Heavy metals
      1. Lead, mercury, cadmium and arsenic are responsible for many neurodevelopmental disorders and restrict infant growth even in small quantities. In addition, aluminum, fluoride, manganese, chromium, nickel, uranium, and tin have been associated with ASD. The strongest association has been found with arsenic, lead, and mercury. Airborne mercury has the strongest association with ASD among all forms of mercury. Women who live near industries that use such metals, have high risk to deliver children destined to develop ASD. Therefore, it is extremely important to know your environment.
   7. Micronutrients
      1. Deficiencies in micronutrients such as magnesium, zinc, selenium, vitamin A, vitamin B complex, vitamin D, vitamin E, and carnitine have been associated with neurodevelopmental problems and ASD. Strong associations with the folic acid metabolism and vitamin D deficiency are well documented; furthermore, correction of such deficiencies in children with ASD, improves the child’s condition. Vitamin B complex deficiencies are very important because, about 80% of autistic children are homozygous for the MTHFR gene polymorphism which affects the one carbon metabolism. Supplementation of such children with B complex vitamins such as, B6, L-methylfolate, B12 and riboflavin improves the clinical picture of these children. Likewise, autistic children who are vitamin D deficient, improve significantly when their deficiency is corrected with administration of supplemental vitamin D. 
   8. Fatty Acids
      1. Children with ASD were found to have lower levels of essential fatty acids in their red cells as well as in plasma. It is not about the specific acid but the balance between omega-3 and omega-6 fatty acids. A healthy ratio is between 1 and 4 (omega-6/omega-3). The average American Omega-6/Omega-3 ratio is unfortunately between 15 and 20. This is detrimental to the overall health and activates the physiological process that causes systemic inflammation in the body. Elevated inflammatory cytokine levels in the amniotic fluid have a strong positive correlation with ASD. So, rebalancing the Omega-6/Omega-3 ratio to a value less than 4 prior to conception or even during pregnancy, can be of significance in reducing the risk of ASD in future offspring. Likewise, correcting the omega-6/omega-3 ratio in autistic children can help. You can find your level by getting an Omega-3 index test. (ask one of our nurses on how to get this test).
      2. The best way to obtain good essential fatty acid in proper proportions is to eat fish. However, because fish has been contaminated from the polluted environment, it is not possible to safely eat fish without the collateral damage from the heavy metals and other carcinogens present in fish. All fish contain mercury in significant amounts but here are some judicious statements about fish:
         1. Never eat predatory fish (shark, sword fish, tuna) and all large fish; they are rich in heavy metals and carcinogens. The larger the size of the fish, the longer it has been around loading on heavy metals and carcinogens. Eating such fish is more harmful than the benefit it provides. 
         2. Small size fish that is less than 6lbs in size is safer and could be eaten two times a week. (salmon, cod, black seabass, striped seabass, porgies etc.)
         3. The tiny fish like sardines, fresh anchovies, and similar fish are the most beneficial and provide the highest level of Omega-3 per gram of tissue with minimal contaminants. You can eat such small fish at least 4 times a week without any fear of contamination.
         4. Farm raised fish: you should never eat consistently farm raised fish, pregnant or not. Farmed fish is fed with fishmeal that is 50% soy (mostly genetically modified soy, GMO) and the other 50% is produced from the biproducts of the processing of large predator fish as well as other large fish that is loaded with heavy metals and carcinogens. Soy contains a lot of Omega-6 fatty acids and the combination of excessive Omega-6 along with the heavy metals and carcinogens, makes farm-raised fish a poisonous food. On top of all these bad things, farm raised fish are loaded with various antibiotics, fungicides, artificial coloring dyes, and persistent organic pollutants (POPs), such as polychlorinated biphenyl (PCB), and dioxins among other carcinogens. 

• Ninety-five percent of the “Atlantic Salmon” is farm raised. Only a handful of restaurants cook wild salmon because wild salmon meat has highly variable consistency and the size of the various cuts varies also; this makes it almost impossible to cook salmon consistently. In contrast, farm raised salmon and other fish, come in standard sizes and they always have the same amount of excess fat and the time to cook is always the same and predictable. Chefs hate wild salmon and other wild fish for this reason. Do not fall for the term “organic salmon”. It is a farm raised salmon with organic soy instead of the GMO soy; it is still a polluted fish with too much omega-6. Wild means wild caught and some of the best wild caught fish like cod and salmon, are sourced from the pristine waters of Alaska, are flash-frozen and can be shipped to your home overnight in dry ice. This method preserves the integrity of the tissue and when thawed overnight in the refrigerator, it feels, smells and tastes just as fresh as when it was caught. (Hites, Ronald A. et al. Global Assessment of Organic Contaminants in Farmed Salmon. Science, vol. 303, January 2004)

2. Parental obesity
   1. Fatty tissue is a source of inflammation. Adipocytes (fat cells) produce significant amounts of proinflammatory cytokines. In addition, obesity is usually, but not necessarily, associated with poor nutrition with little nutritive value and a lot of empty calories, derived from highly processed foods. Regardless of the cause, we know that excessive body inflammation is associated with increased risk of ASD among other things. So, women planning a pregnancy, should seek nutritional advice aiming at reducing as much fat as possible while increasing the intake of highly nutritional foods; this will prepare the body for a healthy pregnancy and a healthy newborn. 
   2. Body fat is a tissue that accumulates endocrine disruptors, carcinogens, heavy metals and all other harmful chemicals that are part of our lives. Endocrine disruptors are man-made chemicals that resemble structurally our natural hormones and they interfere with their function, mostly in a negative and disruptive way. Thus, the name endocrine disruptors. Here is a small sample of such chemicals: all artificial sweeteners, food coloring, phthalates and paraben present in almost all beauty products, fungicides, pesticides and the list include 70,000 chemicals that are used in the food, produce, packaging and household product industries. 
   3. Paternal obesity has also been associated with ASD in the offspring; in fact, one study found a stronger association with paternal obesity and ASD than maternal obesity. However, because there are too many confounding factors in such types of studies, one thing that is important to remember, family obesity is usually associated with inflammatory changes that can affect the neonate’s health in many different ways far and beyond ASD. 
3. Vitamin D deficiency
   1. There is increasing evidence that maternal Vitamin D deficiency may be one of the primary causes of neurodevelopmental diseases as shown below:
      1. Autism spectrum disorder
      2. Schizophrenia
      3. Attention deficit hyperactivity disorder
   2. Vitamin D plays an essential role in the regulation of various signaling pathways in the brain that regulate neuron development and interconnectivity. Individuals with ASD suffer also from oxidative stress due to the lack of glutathione which is caused by vitamin D deficiency. N-acetyl-cysteine (NAC) supplementation increases the levels and availability of glutathione and in combination with Vitamin D supplementation decreases the risk of ASD in offspring. A number of studies have revealed that providing Vitamin D supplementation during pregnancy can markedly reduce the onset of autism (Stubbs et al 2016; Cannell 2017; Vuillermot et al 2017). The symptoms of vitamin D deficient autistic children can be improved significantly by providing supplemental Vitamin D (Jia et al 2015; Saad et al 2016; Cannell 2017).
4. Small for gestational age and prematurity
   1. Small for gestational age and premature neonates have a 300% increase in the risk of ASD. Both these conditions/complications are associated with placental and intrauterine inflammatory changes. As noted above, inflammation in utero is a potent factor associated with ASD later in life. Therefore, the association here is most likely not the prematurity or the reduced growth, but the underlying condition that leads to or is the result of the inflammatory changes. 

In conclusion, it is clear from all we know so far that the cause of ASD is a multifactorial one and it is in part the result of some genetic predisposition but for the most part, it is the result of the environment the child is growing in, including maternal nutritional status prior to conception, fetal life during pregnancy and subsequent neonatal and infant development. 

I have not discussed the associations of ASD with some vaccines here because the subject has been “politicized” and it is difficult for anyone to talk about vaccines and autism in a scientific and honest way without been called a “conspiracy theorist”. There is plenty of evidence in the scientific literature that vaccines might be one of the many environmental factors that contribute to the appearance of ASD, in an otherwise predisposed infant. It is well known that even now, certain vaccines contain various forms of mercury; although the amount of mercury is considered by the authorities insignificant, because of preexisting environmental overload, the mercury contained in the vaccines can in some cases be the proverbial “straw that breaks the camel’s back”. Furthermore, almost all vaccines use aluminum salts in order to increase the immune systems reaction to the particular vaccine. As we noted above, aluminum salts are associated with ASD. The problem here is not that there is no evidence of the association of certain vaccines and ASD, but the fact that health care authorities deny the problem and refuse to study the long-term effects of all vaccines. Such studies are costly and difficult to design and execute and nobody is willing to pay the bill for such long-term studies; therefore, neither side of the controversy will be able to amass the solid, high-quality scientific evidence necessary to accept or reject the contributing role of some vaccines to the development of ASD. Enough said!

For now, the best all future mothers can do to reduce the risk of autism spectrum disorder in their offspring is to pay attention to the following information:

1. Maintain a healthy wait, before and during pregnancy
2. Eat whole foods with high nutritional density (Mediterranean diet with whole foods and moderate amount of calories is unequivocally the best dietary approach according to clinical randomized trials).
   1. All other diets are fads with one exception
      1. Keto diets have a special role for quick weight loss but only for a short period of time.
   2. Only the Mediterranean diet was, is, and will be the healthiest diet and this has been shown over and over again with hundreds of major clinical trials
3. Check your body for systemic inflammation and seek advice on how to reduce it. Blood levels of C-reactive protein (CRP) is a good first step. 
4. Exercise 
   1. Aerobic exercise, as well as resistance exercise have the following benefits:
      1. Improve cardiovascular performance and this contributes to a healthy uteroplacental circulation and a well-functioning placenta
         1. Healthy placenta means reduced risk of fetal growth restriction and
         2. Reduced risk of prematurity and
         3. Reduced risk of autism as a result
      2. Increase the production of brain-derived neurotrophic factor (BDNF)
         1. BDNF stimulates new neuronal (brain nerve fibers) development and orchestrates the inter-connectivity of the various neurons that create the foundation for a healthy functional brain. 
         2. Elevated BDNF as a result of maternal exercise during pregnancy is associated with improved memory and higher IQ levels in the offspring
         3. In contrast, reduced BDNF leads to a number of psychiatric disorders including major depressive disorders.
5. Take all the supplements we recommend at Kofinas Perinatal. Our recommendations are based on the best available scientific evidence and our recommendations are upgraded several times annually as new information becomes available. With our protocols, we have helped many patients whose previous children suffered from ASD to have a healthy neonate despite the odds. 
6. Consider practicing intermittent fasting prior to conception:
   1. Complete your daily eating early (between 5-7 pm) and do not consume anything but water until 14-16 hours later. Doing so at least 3-5 times a week can have significant benefits on your health such as:
      1. Improved metabolism with all the associated benefits
      2. Increased fat loss
         1. Reduced inflammation as a result of fat loss
         2. Healthy weight loss 
         3. Improved cardiovascular performance
         4. Increased production of ketones which help reduce harmful epigenetic changes on our DNA (Ketones promote histone deacetylation) and promote DNA repair
      3. Deceleration of the internal biological epigenetic clock which slows down the aging process and prevents chronic diseases (diabetes, high-blood pressure, cardiovascular disease, autoimmune disorders, premature death etc.)
   2. If one combines intermittent fasting with a Mediterranean style diet, it can only get significant benefits that lead to a healthy pregnancy and subsequently, a healthy long life. What could be better than that?

I know that many of you will consider my advice too difficult to implement. There could be nothing further from the truth. It is all about priorities in life and you must think hard and wisely in order to make the right choices. Fetal life lasts only nine months but the negative effects of your improper life style choices can have detrimental effects on the child’s life until long into the future. Please, take this advice seriously and make no excuses.