Cholesterol supplementation reverses many symptoms
of autism in SLOS disorder. This deficiency is also common in "regular" autism.
Dr. Richard Kelly, a research physician at John
Hopkins University has found, along with his colleagues, that autistic
symptoms prevalent in the genetic disorder SLOS quickly reversed after
supplementation with dietary cholesterol. Some of the many improvements
included sleeping through the night, overcoming aberrant behaviors,
learning to walk, speaking for the first time and becoming more responsive
and social family members. In addition, other benefits of cholesterol
supplementation included a decreased rate of infections, reduced skin
rashes, marked reduction in self-hurtful behaviors, improved muscle
tone, decreased tactile defensiveness, more rapid growth and improved
behavior overall. Parents reported their children having significant
decreases in autistic behavior and even some adults, without speech,
spoke for the first time - all within days of taking cholesterol supplements.
These changes occurred before cholesterol values had increased in the
blood, which indicates that the improvements may be a result of cholesterol
forming its derivatives - such as steroid hormones or bile salts.
SLOS and Autism
Smith-Lemli-Opitz syndrome (SLOS) is an
autosomal recessive genetic disorder associated with autism, multiple
malformations and mental
retardation syndrome initially described by Smith Lemli, and Opitz.
The syndrome (SLOS) is due to a deficiency of 7-dehydro-cholesterol
(7DHC) reductase, the enzyme responsible for catalyzing the final step
in cholesterol synthesis indicated in a simplified figure of cholesterol
metabolism on page 2. As a result of this enzyme deficiency, 7-dehydro-cholesterol
accumulates and the level of cholesterol dramatically decreases. Although
some children with SLOS have severe physical abnormalities, many are
only mildly affected and autistic behaviors may be their only major
abnormality. Since the biochemical test for this disease is done so
rarely, it may be possible that there are many other children with
SLOS, with fewer anatomic abnormalities, in which the diagnosis is
missed. As a result of this enzyme deficiency, individuals with this
disorder have extremely low cholesterol values but extremely high values
of 7-dehydrocholesterol. One person with SLOS had the lowest cholesterol
value (< 1mg/dL) ever measured in serum while most Americans have
values between 150-250 mg/dL.
Because cholesterol levels are insufficient in persons with SLOS, virtually
none of the normal steroid hormones and bile salts derived from cholesterol
can be adequately produced. However, abnormal forms of these hormones
derived from 7-DHC can be produced instead. It is important to note
that cholesterol is an essential element in myelin, which is the insulating
material essential for nerve function (especially in the brain). Persons
with SLOS will possess varying degrees of cognitive abilities ranging
from borderline intellectual functioning to profound mental retardation.
It is common for them to also exhibit sensory hyper-reactivity, irritability,
language impairment, sleep cycle disturbance, self-injurious behavior,
and autism spectrum behaviors. In one study, nearly 50% of children
with SLOS met the DSM-IV criteria for autism. In another study, 86%
of children with SLOS had an autistic spectrum disorder. Many of the
behavioral abnormalities of SLOS significantly respond to supplementation
If autism is prevalent in SLOS, and the autistic symptoms improve
with cholesterol supplementation, then it is conceivable that any severe
biochemical abnormality leading to de-myelination needs to be explored
as a possible cause of autism.
Lithium deficiency common in mental illness and social ills
Jim Adams found that in an evaluation of
hair samples from children with autism that lithium values were significantly
in young children of autism and their mothers. I have made similar
observations on many children with autism tested through The Great
Plains Laboratory. The lithium values of some children with autism
are in the lowest one percentile.
Ironically, the use of highly purified water to prevent ingestion of
toxic chemicals may have deprived pregnant
women of a trace amount of lithium found in tap water needed for normal
brain development and this deficiency appears to be a significant autism
risk factor. This switch to purified bottled water has taken place
in the past 20 years during the same time as the surge in the autism
epidemic. The tenfold increase in bottled water consumption coincides
nearly exactly with an approximate ten-fold increase in autism incidence
over the same time period. It is possible that
this factor might in fact be equal in importance to mercury exposure
as an autism risk factor.
In very small amounts lithium appears to be an essential element needed
for good mental health. Areas of the country where lithium is present
at high levels in the drinking water have less violence and crime.
A study of 27 Texas counties found that the incidences of suicide,
homicide and rape were significantly higher in counties whose drinking
water supplies contained little or no lithium compared to counties
with higher water lithium levels, even after correcting for population
density. Corresponding associations with the incidences of robbery,
burglary and theft were also significant, as were associations with
the incidences of arrests for possession of opium, cocaine and their
derivatives. In addition, I have commonly found very low lithium values
in hair samples of patients with schizophrenia. Furthermore, hair lithium
has been shown to be a good indicator of lithium deficiency. Scalp
hair lithium levels reflect the average intakes of bioavailable lithium
over a period of several weeks to months and represent a noninvasive
means of determining the dietary lithium intakes. Furthermore, lithium
is needed to transport folate and vitamin B-12 into the brain. The
common deficiencies of lithium may be one of the reasons children with
autism require such high doses of certain forms of these vitamins.
A typical hair profile of a child with autism is shown in the adjoining
diagram, demonstrating the extremely low lithium intakes common in
autism. Blood tests done at conventional medical laboratories measure
lithium but only are useful to measure the extremely high lithium levels
associated with lithium drug therapy. Such tests are useless for the
measurement of the very low lithium levels associated with nutritional
A provisional Recommended Daily Allowance (RDA) for a 70 kg adult
of 1,000 mcg/day (about 1% of the dose of lithium commonly used as
a pharmaceutical agent) has been suggested for a 70 kg adult, corresponding
to 14.3 mcg per kg body weight. Note carefully that mcg stands for
micrograms, not milligrams (mg)! Doses of lithium between 150-400 mcg
per day (doses that are nutritional rather than pharmacological) resulted
in improved mood in drug abusers, some of whom had a long history of
drug abuse. The nutritional use of lithium is completely safe. No safety
assessments or blood tests need to be done for nutritional supplementation
of lithium in contrast to the use of lithium as a drug, which requires
blood testing to prevent toxic overdose. If hair values are low or
a person only drinks purified deionized or reverse-osmosis water, I
think the person should take lithium supplements. New Beginnings Nutritionals
has a convenient liquid that contains 50 mcg lithium per drop. I remember
when the bottled water products were first launched and I was incredulous
that people would pay for a product they could get for virtually nothing
simply by turning on their faucets. Now I drink reverse-osmosis water,
which is essentially free of trace elements (and toxic chemicals),
and I take 500-mcg lithium daily by adding lithium drops to my orange
Cholesterol doses to treat SLOS
Doses of cholesterol used in therapeutic trials have
varied from 20-300 mg/Kg body weight/day. In some SLOS treatment studies,
supplemental bile acids were also incorporated into the diet. In early
studies, 50 mg /Kg of pure crystalline cholesterol was used and showed
beneficial results. Other options for cholesterol supplementation include
use of egg yolk, whipping cream, and butterfat. A single egg yolk contains
about 250 mg of cholesterol. A 100-Kg adult with SLOS would have to
consume 40 egg yolks per day to consume enough cholesterol to attain
a dose of cholesterol of 100 mg/Kg per day. In addition, organ meats--like
liver and kidneys--are particularly rich in this compound. A 3 oz (85
g) serving of beef liver, for example, contains about 372 mg of cholesterol.
A similar portion of brain from animal sources has close to triple
this amount. In some of the treatment studies, patients with SLOS were
dosed with purified cholesterol supplements, instead of food sources.
Benefits of cholesterol feeding in SLOS
Kelley RT. Inborn errors of cholesterol biosynthesis. Adv
Pediatric 2000;47 :1-53
* Beginning to walk
* Starting to run
* Growth improvement
* Less infections
* Less UV light sensitivity
* Increased alertness
* Head banging stops
* Decreased tactile defensiveness
* Increased sociability
* Behavior improves
* Talking has started in adults who were not talking before
* Verbal people say they feel better
* Many improvements in only a few days after supplement
* Decreased irritability
Cholesterol deficiency: common in regular ASD as well
as in SLOS
Dr. Tierney and her colleagues
involved in SLOS research wanted to determine if cholesterol deficiency
is also common in "ordinary" autism.
They investigated the incidence of cholesterol deficiency in blood
samples from a group of subjects with autism spectrum disorder (ASD)
from families in which more than one individual had ASD, but not SLOS.
Using highly accurate gas chromatography/mass spectrometry, cholesterol,
7-DHC and its related molecules were quantified in 100 samples from
subjects with ASD. Although no sample had values consistent with SLOS,
19 samples (19%) had total cholesterol levels lower than 100 mg/dl,
values that are much lower than those found in normal children of the
same age. In addition, these researchers found that cholesterol was
low, not as a result of excessive breakdown, but because of reduced
This work was confirmed at The Great Plains
Laboratory which performed cholesterol testing on 40 children with
autistic spectrum disorder
(see adjoining graph). In this study, as in Dr. Kelly's study,
extremely low cholesterol values are defined as the lower fifth percentile
of normal children (less than 100 mg/dL) which was determined in a
nationwide study of the Center for Disease Control. The results of
the two studies were similar, with The Great Plains Laboratory percentage
of extremely low values being 17.5% versus 19% of values being low
for the Tierney study. In addition, 57.5% had cholesterol values less
than 160 mg/dL. NIH had concluded in 1990 from a meta-analysis of 19
studies, that men and women (to a lesser extent) with a total serum
cholesterol level below 160 mg/dL. had approximately a 10% to 20% increased
death rate compared with those with a cholesterol level between 160
to 199 mg/dL. Specifically, people with these lower cholesterol levels
were more likely to die from cancer (primarily lung and blood), respiratory
and digestive disease, violent death (suicide and trauma), and hemorrhagic
stroke. It is interesting to note that in The Great Plains Laboratory
study, only one child on the autistic spectrum had an extremely high
cholesterol level, with a value over 340 mg/dL.
The concept of "good" and "bad" for
dietary substances depends on the circumstances of the individual
of the information that the public receives is oversimplified. To a
person dying of thirst in the desert, any water is very good. To a
person, who just drank two gallons of water on a dare, another glass
of water might be fatal. The concept of good and bad cholesterol is
similar to the water analogy.
type of cholesterol that is associated with high density lipoproteins
and helps to remove cholesterol from certain tissues was termed "good
cholesterol" or HDL cholesterol (High Density Lipoprotein-associated
cholesterol). The type of cholesterol associated with low density
lipoproteins and which transports cholesterol to tissues that require
it was designated as "bad cholesterol" or LDL cholesterol
(Low Density Lipoprotein-associated cholesterol). If, however,
the tissues of a certain person have a significant overall deficiency
of needed cholesterol, then both LDL and HDL cholesterol are
good for that person.
Therefore, a purified cholesterol supplement
cannot be inherently "good" or "bad" and
the body will distribute it to the locations where it is needed the
most. If the person has adequate amounts of cholesterol, however, no
additional supplementation would be needed.
Abnormalities in cholesterol metabolism
present in SLOS and autism may also impair the function of a developmental
signaling protein with
the bizarre name "sonic hedgehog". Sonic hedgehog (SHH)
is named after the character from the popular Sega Genesis video game.
The original hedgehog gene was found in the fruit fly Drosophila and
was named for the appearance of the mutant fly offspring in which the
embryos are covered with pointy spines resembling a hedgehog. The first
two types of hedgehog proteins were named after certain species of
hedgehogs and the third was named after the video game character.
Cholesterol must covalently bond to SHH before SHH can function properly.
In addition, some forms of SHH have both cholesterol and the fatty
acid palmitic acid covalently attached to the protein. (Palmitic acid
is required for the production of a soluble Hedgehog protein complex
and long-range signaling in humans). The attachment of cholesterol
activates the sonic hedgehog protein and without adequate cholesterol,
SHH protein function is impaired.
Benefits of cholesterol in the diet
Every day supplementation
with high cholesterol foods, such as egg yolks, might prove to be
a useful therapy to try for a
few months for children with autism who have cholesterol values that
are low (<160 mg/dL). Unfortunately egg allergy is common in autism
and may increase with a steady egg diet and compliance may be difficult
for children who dislike eggs. Although very high blood serum cholesterol
values are associated with heart disease, values that are low (below
160 mg/dl) are associated with increased violent behavior, suicide,
depression, anxiety, bipolar disease, Parkinson's disease, and
increased mortality from cancer. Surprisingly, high cholesterol protects
against some infectious diseases like tuberculosis, which has been
uncommon in the USA since The Great Depression, during which there
was a substantial lack of high cholesterol foods because of financial
hardship. Vegetarians have a much higher incidence of tuberculosis
than meat eaters. It is possible that the overemphasis on a low cholesterol
diet may also be associated with the recent marked increase in cases
of tuberculosis. Low cholesterol values are also associated with manganese
deficiency, celiac disease, hyperthyroidism, liver disease, malabsorption,
and malnutrition. Pregnant women with low cholesterol are twice as
likely to have premature babies or babies with small heads.
LDL cholesterol (so-called bad cholesterol) protects humans against
infection. Deadly staphylococcus bacteria produce endotoxins that have
the ability to kill human cells including red blood cells. LDL was
found to protect human red blood cells from this toxic effect of endotoxin
while HDL was not protective. A study at the University of Pittsburgh
found that in young and middle aged men, those that had LDL-cholesterol
below 160 mg/dl had a significantly lower number (of total and various
types) of white blood cells than men with LDL-cholesterol above 160
Functions of Sonic Hedgehog (SHH):
- Plays a central
role in developmental patterning, especially of the nervous
system and the skeletal system.
- Important in the growth
and differentiation of a variety of cell types, including
the development of T cells in the thymus.
- Purkinje neurons
secrete SHH to sustain the division of granule neuron precursors
in the external granule layer
in cerebral development. Abnormal
cerebellar development and especially purkinje cell development has
been associated with autism.
- As a transcription regulating
protein, SHH alters which genes function at a given time.
Testing for cholesterol, cholesterol transport proteins,
and homocysteine at
The Great Plains Laboratory
The Great Plains Laboratory has developed
a special cholesterol related panel that will help to determine whether
deficiency or abnormalities in cholesterol transport are present. This
panel will include the following markers: Total cholesterol, apolipoprotein
A-1, apolipoprotein B, Lipoprotein (a), and homocysteine. Lipoproteins
are involved in cholesterol, lipid, and vitamin E transport.
Total cholesterol: Total cholesterol measures
all types of cholesterol including esterified and free. Low values
(generally values less than
160 mg/dL) are associated with genetic diseases of cholesterol metabolism
such as SLOS, Tangier's disease, and abetalipoproteinemia. Low
values are more common in hyperthyroidism, liver disease, malabsorption,
malnutrition, autism, violent behavior, celiac disease, anxiety, bipolar
disease, alcoholism, lung cancer, suicide, depression, and obesity
associated with human adenovirus-36 infection. In China, where mean
cholesterol is much lower than in the Western world, chronic hepatitis
B virus infection is ubiquitous. Chronic carriers of hepatitis B, but
not individuals with eradicated hepatitis B, have significantly lower
total cholesterol than non-carriers, suggesting a cause-effect relationship.
High cholesterol values are associated with atherosclerosis.
Apolipoprotein A-I (Apo
A-1): The main protein component of HDL (high
density lipoprotein). It accounts for approximately 65% of the total
protein content of HDL. Apo A-I activates lecithin cholesterol acyltransferase
which catalyses the esterification of cholesterol. The resulting esterified
cholesterol can then be transported to the liver, metabolized and excreted.
Values of Apo A-I have been shown to decrease during infection.
Apolipoprotein B (Apo
B): The main protein component of LDL (low density
lipoprotein). It accounts for approximately 95% of the total protein
content of LDL. Apolipoprotein B is necessary for the reaction with
LDL receptors in the liver and on cell walls and is thus involved in
transporting cholesterol from the liver to the cells. Recently the
Mind Institute found that low values of Apo B are associated with autism,
with the lowest values being found in low-functioning autism. LDL has
found to have protective effects against endotoxins from deadly staphylococcus.
Lipoprotein (a): Consists of two components,
the low-density lipoprotein (LDL) and a glycoprotein, which are linked
by a disulfide bridge. High
values have been implicated as a risk factor for cardiovascular disease,
Alzheimer's disease,Crohn's disease, and rheumatoid arthritis.
Low values have also been found in those with autism who have higher
doses of Apolipoprotein E epsilon-4 gene variants that are associated
with increased risk of Alzheimer's disease. Lipoprotein (a) is
biochemically unrelated to Apolipoprotein A.
Homocysteine: A sulfur-containing amino
acid that can be converted to methionine by methionine synthetase
or by betaine methyl transferase.
The role of homocysteine in atherosclerosis gained attention after
finding massive atherosclerosis in young people with the genetic disorder
homocystinuria. Methionine synthetase requires the folic acid derivative
5-methyl tetrahydrofolate. Abnormally high values have been reported
in stroke, cardiovascular disease, and in Alzheimer's disease.
Both low and high values have been reported in autism.
All of the Great Plains testing for the cholesterol panel is done
with FDA-approved diagnostic laboratory reagents.
Why the brain needs cholesterol
- There is a direct correlation between the concentration
of cholesterol in the brain, particularly in the myelin, and how
well the brain functions.
- The brain is the most cholesterol-rich organ
in the body.
- In the central nervous system (CNS), essentially all
(99.5%) cholesterol is the free or unesterified form (unattached
- The majority (70%) of cholesterol present in the CNS
is believed to reside in the myelin (the material that insulates
fibers) sheaths and the plasma membranes of astrocytes (brain
- Half of the white matter, which contains the
nerve axons that allow for transmission of brain signals, may be
Paulina's story and cholesterol
By Dr. William Shaw
The cholesterol story really made an impact
on me because of my stepdaughter Paulina, a delightful 18-year old
girl with severe autism. Biomedical
treatment including GF/CF diet, antifungal therapy, control of Clostridia,
and heavy metal chelation had been successful in controlling severe
hyperactivity, abnormal sleep patterns, and self-abusive behavior.
However, Paulina still had very little use of the hands, had lost all
speech at the age of four, and had a physical abnormality in which
her fourth toe was much smaller than the fifth. All of these symptoms
led to her diagnosis of the genetic disease Rett's syndrome at
the local children's hospital, but her DNA test was inconsistent
Paulina was always energetic and would
sometimes burst into a run when going for a walk. At the beginning
of the school year, we were
receiving unfavorable school reports (which were unusual) indicating
that she was losing interest in participating in school activities
and was becoming increasingly withdrawn. She was even falling asleep
in class after a full night's sleep. At home, she was becoming
more and more withdrawn as well and overall, more "autistic".
The notes from school became more and more disturbing and Paulina was
obviously not the same happy person that she used to be. She began
wanting to go to bed earlier and earlier until she was going to sleep
immediately after arriving home at 3:00 pm. Even after sleeping 15
hours at night, she was still falling asleep in school. Thyroid tests,
an obvious abnormality associated with low energy, were normal.
One morning my wife burst into tears at
the breakfast table and sobbed to me: "I think Paulina is dying".
I decided to review all of Paulina's test results
and treatments but the only thing I could find was the egg allergy. "When
did you take the eggs out of Paulina's diet?" I asked my wife. "At
the beginning of the school year" she responded. That was exactly
the timeframe when we started getting the unfavorable reports from
the school noticing her regression. I realized it was the eggs! The
lack of eggs and cholesterol! Paulina has cholesterol deficiency and
we needed to give her eggs again." (Please
note that Paulina had IgG egg allergy. A child with IgE egg allergy
might have an anaphylactic
reaction to eggs and should not get eggs at all.) Paulina's
cholesterol was 142 mg/dL, a very low value.
Within a few days of giving two eggs for
breakfast every day, the smiling, happy, alert, and energetic (but
still autistic) Paulina had
returned. Once again, she was smiling, full of energy, and difficult
to get into bed before 11 pm in the evening. Glowing reports from the
teacher became common again. Even though the eggs upset her stomach
as a result of the allergy, the cholesterol from the eggs had proven
to be essential for her well-being. After six months on the egg-enriched
diet, Paulina's cholesterol had increased to 157 mg/dL, indicating
how slowly cholesterol increases. With the arrival of the purified
cholesterol supplement from New Beginnings Nutritionals, we are now
able to give her the much needed cholesterol her body needs without
giving her eggs.
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R Kelley Abnormalities of Cholesterol Metabolism in Autism Spectrum
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in psychiatric inpatients. J Clin Psychiatry. 1994 Jun;55(6):252-4.
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Eur Arch Psychiatry Clin Neurosci. 2002 Jun;252(3):110-4.
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diet accelerates bacteriologic sterilization in pulmonary tuberculosis.
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Copyright © 2007 The
Great Plains Laboratory