Professor of Pharmacology

Northeastern University

Boston, Massachusetts

Summary

The developmental disorder autism has both genetic and environmental origins, and its forty-fold increase during the past two decades reflects an increased role for environmental factors. It has been proposed that increased use of vaccines containing the ethylmercury derivative thimerasol is the major contributing factor. Published research from my laboratory has revealed that thimerosal is an exceptionally potent inhibitor of biochemical pathways that transfer single carbon atoms between molecules. These “methylation” pathways are critically involved in several important functions including the regulation of gene expression and the molecular mechanism of attention. Recent studies from my lab indicate that thimerosal exerts its toxic effect on methylation by interfering with formation of the active form of vitamin B12, also known as cobalamin. Dietary B12 must be converted to methylB12 (methylcobalamin) in order to assist in the transfer of single-carbon methyl groups from the folic acid pathway by the enzyme known as methionine synthase. By reducing methylB12 formation, thimerosal inhibits this enzyme and thereby interferes with methylation events. Autistic children have abnormal plasma levels of methylation-related metabolites and exhibit higher frequencies of genetic mutations that affect this pathway.  These genetic risk factors make them less able to detoxify thimerosal and also increase their sensitivity to its mechanism of toxicity. In many cases, autism can be effectively treated by the administration of methylB12 along with other agents that augment methylation capacity. Taken together, these facts indicate that increased exposure to thimerosal has combined with genetic risk factors in a sensitive subpopulation to cause the recent rise in autism.

Outline

1. The Puzzle of Autism

2. Physiological and Biochemical Roles of Methylation

3. Activity of Methionine Synthase

4. Effects of Thimerosal and Heavy Metals

5. Autism-associated Metabolic and Genetic Abnormalities

6. Methylation-related Treatments for Autism

7. Conclusions

1. The Puzzle of Autism

Autism is a pervasive developmental disorder characterized by deficits in language, attention, cognition and learning, frequently accompanied by abnormal behavior including social isolation, repetitive activity and emotional lability. Severe deficits may be recognized at birth, but a failure to achieve standard milestones during initial years of life remains the primary basis of diagnosis in most cases. While the underlying cause(s) remains obscure for many developmental disorders, metabolic abnormalities (e.g. Lesch-Nyhan Syndrome and adenylsuccinate lyase deficiency) or impaired methylation-dependent gene silencing and/or imprinting (Rett and Fragile-X Syndromes) (1-4) suggest biochemical mechanisms that may be involved. Development disorders can also be caused by exposure to toxins (e.g. ethanol, in fetal alcohol syndrome; heavy metals, in lead poisoning) (5,6), although the precise molecular mechanisms underlying their toxicity are not known. The recent increase in the incidence of autism has led to speculation that environmental exposures including vaccine additives (i.e. aluminum and the ethylmercury-containing preservative thimerosal) might contribute to the triggering of this developmental disorder (7).

Based upon a high concordance in twin studies, genetic factors are thought to play an important role in causing autism. However, it is clear that the recent dramatic rise in autism rates is not caused by a genetic phenomenon. The more likely scenario is that autism is caused by the interaction of genetic risk factors with environmental risk factors and the importance of the environmental factors has increased during the past twenty years.  As illustrated in Fig. 1, the “Puzzle of Autism” therefore is the challenge of understanding exactly which genes provide the inborn risk, and which environmental factor(s) is serving as the trigger. The molecular mechanism at the intersection of genetic and environmental factors should be capable of accounting for the observed symptoms of autism, and knowledge of this mechanism should help identify effective treatments for autism. The findings summarized in this report indicate that impairment in the biochemical pathways that allow for the transfer of single carbon groups (i.e. methylaion) is a major factor contributing to the cause(s) of autism.

Boil parsley bunch in water for 20 min(water turns green).  Let cool, drink the fluid.

-Add Cranberry capsules.

Yeast infections:

CandiGONE and ParaGONE

(purchase at www.renewlife.com/products/detail/paragone.)

*** We suggest Carlson’s brand which can be purchased in our clinic.  For patients who are Vegan, we offer UDO’s oil (a plant based option)

• Avoid long periods of standing or sitting.  Take rest periods several times during the day to elevate your legs above heart level.
• Avoid crossing your legs.
• After bathing, apply castor oil directly over the problem veins and massage from the feet up.
• Avoid scratching the itchy skin above the varicose veins.  Scratching can cause ulceration and bleeding.

VARICOSE VEINS

-       Fish Oil 4000 mg/day (containing EPA & DHA in a 2:1 ratio)

*** We suggest Carlson’s brand which can be purchased in our clinic.  For patients who are Vegan, we offer UDO’s oil (a plant based option)

-       Avoid long periods of standing or sitting.  Take rest periods several times during the day to elevate your legs above heart level.

-       Avoid crossing your legs.

-       After bathing, apply castor oil directly over the problem veins and massage from the feet up.

-       Avoid scratching the itchy skin above the varicose veins.  Scratching can cause ulceration and bleeding.

“The average number of prescriptions [drugs] per 

person, annually, in 1993 was seven. 

The average number of prescriptions [drugs] per 

person, annually, in 2000 was eleven. 

[The average number of prescriptions drugs per 

person], annually, in 2004 was twelve. 

The total number of annual prescriptions [drugs] in 

the United States now stands at about 3 billion. 

The cost per year is about $180 billion, 

headed to an estimated $414 billion by 2011. 

Toxic Fat 

Barry Sears, PhD 

2008 

“The underlying cause of chronic disease comes from increased production of a 

natural fatty acid called arachidonic acid (AA), which can be incredibly toxic at high 

concentrations. This is the toxic fat that is key to not only understanding our obesity 

epidemic but also providing the linkage between obesity and chronic disease.” P. 2 

“Classic inflammation hurts; silent inflammation slowly kills.” P. 25 

“All forms of inflammation (including silent inflammation) are ultimately controlled by 

a group of hormones known as eicosanoids.” 

“It is the balance of eicosanoids in your body that is the ultimate key to wellness.” 

“All eicosanoids are ultimately derived from dietary fat, in particular the 

polyunsaturated essential fatty acids that must be supplied by the diet.” 

“Virtually all chronic diseases can be viewed as a consequence of a continuing 

imbalance of good and bad eicosanoids.” P. 259 

“There are only three such essential fatty acids that can be made into eicosanoids: 

Dihomo-gamma-linolenic acid (DHGLA) 

Arachidonic acid (AA) 

Eicosapentaenoic acid (EPA)” P. 19 

Smoking marijuana dramatically increases appetite; it gives one the “munchies.” This 

is because of the chemical tetrahydrocannabinol or THC. 

The brain makes its own endocannabinoid hormones, making one dramatically more 

hungry, from the toxic fat arachidonic acid. P. 39 

Silent inflammation causes both insulin and leptin resistance. P. 45 

Sleep deprivation and stress create both insulin and leptin resistance. 

“From AA come all the pro-inflammatory eicosanoids that in excess accelerate chronic 

disease.” P. 77 

“From DHGLA come very powerful anti-inflammatory eicosanoids that accelerate 

cellular rejuvenation.” P. 77 

“EPA dilutes AA concentration in cell membranes, making it difficult to make 

pro-inflammatory eicosanoids.” P. 77-8 

“It is excess insulin that makes you fat and keeps you fat” p. 87

2 

The Numbers 

TG = triglycerides 

HDL = high density lipoprotein (good) cholesterol 

If the TG/HDL ratio is greater than 4, you probably have Toxic Fat Syndrome because 

it means you have insulin resistance. 

If your fasting insulin is greater than 10 uU/ml you have increased activity of the 

delta-5-desaturase enzyme that is the key to the production of arachidonic acid. 

Ideally, fasting insulin should be less then 5 uU/ml. “The lower your fasting insulin 

levels, the longer and better you are going to live.” P. 77 

“The true marker of Toxic Fat Syndrome is the AA/EPA ratio. If it is greater than 10, 

then you have Toxic Fat Syndrome, regardless of how good you look in a bathing 

swimsuit. A good ratio is 3, and the ideal ratio is about 1.5.” p. 78 

Chronic disease people tend to have an AA/EPA ratio greater than 20. p. 78 

Markers of Malignant Toxic Fat: p. 80 

AA/EPA > than 15 

Fasting insulin (uU/ml) > than 15 

TG/HDL ratio > than 4 

Dangerous Poor Good Ideal 

AA/EPA >15 10 3 1.5 

Fasting Insulin >15 10 5 <5 

TG/HDL >4 3 2 <1 

AA/DHGLA <> 

Condition (p. 113) Amount of EPA + DHA Required 

No chronic disease 2.5 grams / day 

Overweight, obese, type 2 diabetes, 

heart disease, before starting any 

weight-loss program 5 grams / day 

Chronic pain 7.5 grams /day 

Neurological Disorders 10 grams / day 

“You will also need to take at least one hundred times more EPA compared to the 

levels of supplemented GLA not to have problems.” P. 268 

“The AA/DHGLA ratio will indicate where you stand in terms of the body’s ability to 

increase cellular rejuvenation (anti-aging).” P. 259 

“The AA/EPA ratio will tell you the extent of silent inflammation in the body.” P. 258