What’s Going On?
NEUROPEPTIDES AND SUPPLEMENTS
What biochemical factors might cause a problem
with the synthesis of neurotransmitters and hormones in autism?
A deficiency of the intestinal enzyme DPP-IV (dipeptydal
peptidase), which acts to catalyze the breakdown of proteins into amino acids,
has been hypothesized as a contributing factor to autism. If proteins aren’t
being degraded into the amino acid substrates necessary to form hormones and
neurotransmitters, the resultant metabolic havoc would be severe indeed,
compromising both brain and body function. The proliferation of yeast or toxins
in the intestinal tract, yeast induced pancreatic atrophy, and/or problems with
the synthesis or activation of the hormone secretin, could also cause a problem
with protein catabolism resulting in a deficit of critical polypeptide
These gastrointestinal problems would also
cause problems with the synthesis and degradation of the glucose necessary
to fuel the electro-chemical processes in the brain. A deficiency or uneven
supply of glucose would result in a deficiency or uneven supply of the glucose
energy derivative ATP (adenosine triphosphate), which is required for the
synthesis, degradation and “firing” of neurotransmitter molecules. ATP is
converted to cystic AMP (cAMP), an important messenger system and reaction
substrate in the brain and body. An inadequate supply of ATP would result in an
inadequate supply of the cAMP required for the phosphorylation of tryptophan
hydroxylase into serotonin.
In addition to forming ATP, the breakdown of
glucose through glycolysis forms the substrates NAD (nicotinamide dinucleotide)
and NADH. The phosphorylated forms of these chemicals, NADP and NADHP are
precursors to the coenzymes dihydrobiopterin (BH2) and tetrahydrobiopterin
(BH4), necessary for the activation of the enzymes tryptophan hydroxylase and
tyrosine hydroxylase, precursors to the neurotransmitters dopamine and serotonin,
respectively. As dopamine is catabolized to form norepinephrine and epinephrine,
any problem with NAD production would affect the synthesis of all four of these
neurochemicals that have been closely linked to autism.
NADHP is also necessary for the formation of
progesterone, which is the precursor to all the other steroid hormones,
including estrogen, testosterone and adreno-corticotropic hormone or ACTH.
How might certain neurotransmitters cause or
contribute to autism?
The brain chemical most commonly linked to
autism is serotonin, which is formed from the hydroxylation of the amino
acid tryptophan. Serotonin is an excitatory neurotransmitter, meaning its
release makes neurons more likely to fire, so an excess of this chemical could
account for a lack of modulation of sensory input, leading to overstimulation
and anxiety. Some studies have documented a significant elevation of blood
serotonin in many autistic children, an abnormality that has been attributed to
an alteration in the uptake or storage of serotonin by blood platelets.154 Other
studies show, however, that the surge in serotonin levels that normally takes
place in a child’s formative years is significantly diminished in children
It seems more likely to me that autistic
processing problems are caused by a deficit or uneven supply of serotonin. This
would slow or impede the impulse or message transmission of serotonin releasing
neurons, which have axons distributed throughout the brain from the cerebellum
to the cerebral cortex.156 The anterior cingulate gyrus in the limbic system, an
area rich in 5-HT (hydroxy tryptophan) receptors, is involved in higher
cognitive functions, the expression and recognition of facial emotions,
vocalized emotional responses, mother-infant interactions, pain response and the
ability to initiate goal directed, context dependent behavior.157 If the 5-HT
receptors in this area are not being properly activated these functions would be
impaired, as they are in autism. There is also a correlation between repetitive
and compulsive behaviors and the level of metabolic activity in the anterior
The largest amount of serotonin, however, is
found not in the brain but in cells of the intestinal mucosa.159 If the
functions of these cells have been undermined, due to the proliferation of
yeast, bacterial or viral infection, and/or the presence of toxic or opioid
microbials, the ability of serotonin to regulate sleep, pain perception,
temperature and blood pressure might be compromised, which could account for the
sleep problems and elevated pain thresholds experienced by many people with
The excitatory neurotransmitter dopamine
is formed from the hydroxylation of the amino acid tyrosine. The inability of
schizophrenics to filter out incoming sensations is thought to be attributable
to raised levels of dopamine in the brain, or to the increased sensitivity of
dopamine neural receptors which induce a high state of arousal.160 Autistic
brains may be equally susceptible to overstimulation due to the exaggerated
effects of dopamine. Uta Frith postulates that the problem could be attributable
to dopamine cells not dying back as they should in normal development. The
result would be an increased number of dopamine neurons and therefore an
As the major dopamine pathways or projections
in the brain originate in tiny structures at the tip of the brain stem and
spread out to every cortical lobe, the impact of either an excess or deficiency
of this chemical on information processing would be significant. If the dopamine
system in the autistic brain is overactive, however, at the very least neural
impulses would be routed through all the proper processing channels, so that
people with autism would be better able to grasp the “big picture” and be
able to base their thoughts and behavior on precise perceptions. As dopamine
activity is regulated in the frontal lobe, and as circuits to this lobe are
likely to be compromised to some degree in autism, it might be that at times
there is too much activity and at other times much too little.
Two other neurotransmitters that may be
implicated in causing or contributing to autism are norepinephrine and epinephrine,
dopamine derivatives in the same catecholamine family. In the brain, nerve cells
that release norepinephrine are clustered in the brain stem with their axons
projecting to many brain regions. As a neurotransmitter, norepinephrine is both
excitatory and inhibitory and is involved in arousal level as well as in
autonomic control of body functions.162
Norepinephrine and epinephrine have important
physiologic functions outside the nervous system as well. They act as regulators
of carbohydrate and lipid metabolism, increasing the degradation of
triacylglycerol and glycogen to glucose as well as increasing heart beat and
blood pressure in response to fright, exercise, cold and low levels of blood
glucose.163 If there is a shortage of these “fight or flight” molecules in
the blood, the
breakdown of carbohydrates to glucose would be
slowed, as would the body’s reaction to emergency situations.
Norepinephrine as well as dopamine and
serotonin have their effect on receptor cells through a time and energy
consuming ‘second messenger’ system, so any irregularity in the supply of
the energy source ATP would have a significant negative impact on the ability of
these neurotransmitters to function smoothly.
Another brain chemical linked to autism is GABA
or gamma-aminbutyric acid. As this neurotransmitter is inhibitory, a deficiency
of GABA in people with autism would help explain the poor inhibition that allows
their brains to become overaroused, causes them to live in a constant state of
may also play a role in autism. Formed from glycogenic amino acids, this
chemical acts as an excitatory neurotransmitter in the brain, activating some
receptors in the hippocampus.164 Any deficit of glutamate would result in
decreased activation of receptors in the limbic system that influence emotion,
learning, memory and motivation.165 Receptors in the amygdala, located directly
atop the hippocampus, might also be affected, further affecting the formation of
declarative memories and throwing off the coordination of autonomic and
endocrine responses with emotional states.
A deficiency of another neuropeptide, Oxytocin,
may also contribute to autism. Oxytocin is a hormone that is intimately involved
in social functions, with numerous receptor sites in the limbic system. Oxytocin
receptive fields are labile, and significant shifts in receptor density occur in
early development. A failure to shift from an infantile to a mature pattern,
resulting in decreased central oxytocin receptor function, may contribute to the
social impairment in autism.166 The correlation of low plasma oxytocin levels
has been found in low functioning or “aloof” autistic children, but the
correlation is not found in high functioning or “active-but-odd”
The steroid hormones, progesterone,
estrogen, testosterone and adreno-corticotropic hormone or ACTH are
also relevant to autism. The production and secretion of ACTH is activated by
the hypothalamus when the body is stressed. This hormone stimulates the adrenal
cortex to synthesize cortisol, which in turn acts to promote gluconeogenesis in
the liver and to stimulate the breakdown of proteins to amino acids in the
muscles.168 So, the ingestion of the ACTH precursor, progesterone, in the form
of birth control pills, would cause an increase in ACTH, making a person better
equipped to handle stress. The resultant increase in cortisol would also
activate glucose and amino acid synthesis, helping the brain and body to
How do drugs work to control neurotransmitter
All mind-affecting drugs have their action at
the synaptic gap. They work by modifying the way neurons communicate across this
gap. Some drugs alter the amount of neurotramsmitters released or the rate of
release. Others have their effect by either blocking or increasing the
availability of receptor sites. Still others work by reducing the action of
enzymes that break down neurotransmitters, rendering them inactive.169 The
catecholamines (dopamine, norepinephrine and epinephrine) and serotonin are
inactivated by oxidative deamination, catalyzed by the enzyme monoamine oxidase
(MAO). MAO inhibitor drugs (antidepressants) serve to inactivate this enzyme,
permitting neurotransmitter molecules to escape degradation and to activate
dormant receptor systems.
Some neurotransmitters are reabsorbed into
axons from fluid surrounding the nerve cells for reuse (endocytosis). Selective
serotonin reuptake inhibitor drugs (SSRIs), including fluoxetine (Proxac),
sertraline (Zoloft), fluvoxamine (Luvox), paroxetine (Paxil) and venlafaxine (a
serotonin and norepinephrine reuptake inhibitor) work by blocking the re-uptake
or recycling of serotonin and norepinephrine, thereby reducing their excitatory
effect on the brain. The use of these drugs can be effective in curbing the
restrictive, repetitive and obsessive behaviors associated with autism.
In attempting to curb or control the symptoms
of autism, is it better to use drugs or dietary supplements?
Its better to use whatever works! As autism has
a biochemical basis, pharmacological intervention is certainly warranted and
often effective. In my daughter’s case, we've used both at different junctures
in Meg's life. If there are no severe symptoms or medically warranted
reason to resort to seizure medication, antidepressants or SSRIs, I
would recommend supplements to begin with, as nutrients are part of the body’s
normal physiology and given to facilitate normal functioning, while drugs are
blocking agents, foreign to the body and given to interfere with normal
How do specific supplements work to make the
brain and body function better?
Quite simply, supplements work by building up
or activating the biochemicals in the body responsible for normal functioning.
If we are deficient in any nutrient, or if the nutritional value of the foods we
eat is compromised by over-cooking and over- processing, whole chains of
metabolic processes may go awry.
The following is a brief list of the
supplements that act as coenzymes (or precursors to coenzymes) in the synthesis,
activation or metabolism of some neuropeptides that have
been causally linked to autism.
- Riboflavin is needed for synthesis of
the amino acid tryptophan (precursor to serotonin).
- Niacin is needed for activation of the
enzymes tryptophan hydroxylase and tyrosine hydroxylase (to form serotonin and
the catecholamines: dopamine, norepinephrine and epinephrine)
- Niacin and Pantothenic Acid are
needed for synthesis of the steroid/adrenal hormones.
- B6 is needed for synthesis of the
amino acids cysteine, taurine and tryptophan and, along with Folic Acid,
synthesis of the nucleic acids RNA and DNA.
for the proper transmission of nerve impulses) and Inositol are needed
for synthesis of many hormones and of lecithin, a component of all cell
is needed for synthesis of anti-stress hormones and the metabolism of folic
acid, tyrosine and phenylalanine.
is needed for the synthesis of RNA and DNA and for the activation of digestive
enzymes like lipase that break down fats.
a vital catalyst in of enzymes involved in energy production. It assists in
calcium and potassium uptake.
is needed for hormone secretion and for catalyzing chemical reactions within
as a group are necessary for the synthesis of all protein substances, so I will
only list a few specific examples.
- Arginine stimulates the pancreas to
- Glycine forms RNA and DNA and the
amino acid serine.
- DMG helps to produce choline and the
amino acid methionine.
- Serine forms transferase enzymes and
pyruvate (the substrate for gluconeogenesis). It can also be converted into the
amino acids cysteine and glycine (as long as the vitamin B6 is present).
- Cysteine, the main source of free
sulfur in the body, is needed for the synthesis of taurine and undergoes
desulfurization to yield pyruvate.
- Glutamine can be converted to Glutamic
Acid or GABA.
- Methionine can be converted to
cysteine and/or taurine (as long as the B6 is present).
- Phenylalanine converts to tyrosine,
which converts to the neurotransmitter dopamine.
- 5-HTP (5- Hydroxytryptophan) converts
to tryptophan, which converts to the neurotransmitter serotonin.
Vitamin C, Iron, Lysine and Methionine are needed to synthesize Carnitine,
a transferase enzyme that functions to transport long chain fatty acids across
cell membranes so that they can be broken down and metabolized into energy.
Omega 3 and
6 essential fatty acids form prostaglandins, hormone-like substances that
act as chemical messengers and regulators of various body processes. They are
also precursors to the plasmologens that form myelin.
How might specific supplements help people with
autism to feel and function better?
I’ve grouped the supplements below according
to the specific roles they may play in remediating autistic biochemistry.
1. Supplements that regulate mood; reduce
anxiety and hyperactivity
B-complex (particularly Niacin, Pantothenic acid (B5) B6 and Inositol. Minerals:
Calcium and Magnesium. Amino Acids: GABA, Glycine, Taurine, Phenylalanine,
Tyrosine, Tryptophan (5-HTP)
2. Supplements that enhance digestion and
energy metabolism, resulting in the delivery of more glucose (ATP) to brain
B-complex (particularly Thiamine, Riboflavin, Niacin, Biotin, B6 and Folic Acid)
Choline, Inositol and Coenzyme Q10. Minerals: Calcium, Potassium and
Magnesium. Amino Acids: Alanine, Serine, Taurine, Glutamine, Glycine and
DMG. Enzymes: Bromelain, Papain, Pancreatin and Pepsin.
3. Supplements that help maintain a healthy,
gastrointestinal tract and acid/base balance of digestive fluids:
B-complex (particularly Thiamine, Riboflavin, Niacin and B6). Minerals:
Potassium and Sodium. Amino Acids: Glutamine, Glycine and Taurine. “Friendly”
bacteria: Acidophilus and Bifudus supplements.
4. Supplements that stimulate blood circulation
and oxygen delivery to the brain, thereby boosting cognitive function:
B-complex (particularly Thiamine), Vitamin E and Coenzyme Q10. Amino Acids:
Methionine. Herbal: Kyolic Garlic and Ginkgo Biloba.
5. Supplements that abet the transmission of
neural messages to and within the brain, thereby enhancing learning and memory:
B-complex (particularly Thiamine, Niacin, B6, Folic Acid) and Choline. Minerals:
Calcium, Potassium and Magnesium. Amino Acids: Glutamine, Phenylalanine,
Tyrosine. Fatty Acids: DHA, Evening Primrose Oil, Ultimate Oil and
6. Supplements that promote neural cell
development, fatty acid metabolism and myelin formation:
Vitamin A, B-complex (particularly B12, Biotin, B6 and Folic Acid), Lecithin
(formed from Choline and Inositol) and Vitamin C. Amino Acids: Serine,
Taurine, Methionine and DMG. Omega-3 and Omega-6 Fatty Acids, Carnitine
and Phosphatidlyserine complex.
7. Supplements that bolster immune system
function by promoting red or white blood cell and antibody production:
B-complex (particularly Riboflavin, B6 and Folic acid) Vitamin C, Coenzyme Q10
and DMG. Minerals: Iron and Sulfur. Amino Acids: Arginine and
Serine. Herbal: Kaolic Garlic
8. Supplements that aid in protecting the body
and brain from the harmful effects of toxic substances:
Aspartic acid, Glutamine (removes ammonia from the brain and intestinal mucosal
cells), Cysteine and Methionine.
9. Supplements that lessen allergies by
reducing histamine levels:
Coenzyme Q10. Amino Acids: Methionine and Taurine.