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Alzheimers 4 - Getting
Dyslexics Vitamin D Celiac and skin conditions Holy Powder
What APP does Celiac Insights Too clean for our own good Maybe the molecule of the century Bile acid Is Christmas a hazard to your health?
study has shown that many 'truths' believed by the public and by
medical professionals, including doctors, are false.
makes kids hyperactive.
increase over the holidays.
lose most of your body heat through your head. (only if your head is
the main uncovered part of your body)
at night makes you fat. (only if it increases your total calorie
intake for the day)
can cure a hangover with… (there is no effective hangover cure)
researchers themselves were surprised that some of these were false.
Alzheimers 4 - Getting old
Age is a risk factor for many neurodegenerative diseases, such as
Alzheimer’s. A protein called MOCA (Modifier of Cell Adhesion) has
been identified as key. It is also known as DOCK3 (Dedicator of
cytokinesis protein 3), PBP (Presenilin-binding protein) and KIAA0299.
MOCA is found in neurons and the amount decreases with age.
The protein has a long list of actions. The one that may be at the
heart of neuron death is MOCA’s protection of the cytoskeleton in the
long axons. In Alzheimers, ALS and Huntington’s the disease
the degeneration of axons and eventually working up to the cell body
“After documenting the sequence of physiological and behavioral events
that characterize the axon degeneration, Chen then sought to piece
together the molecular pathway behind it, starting with MOCA and
connecting findings from disparate studies that previously had
identified parts of the pathway. He ended up with a single,
step-by-step process for axon degeneration that for the first time
linked together a number of diseases and conditions, including a form
of mental retardation in humans. Now we know that MOCA is essential to
the functional integrity of axons and have defined a complete pathway
for axon degeneration."
This should lead to fitting it explanations of other risk factors in
the pathway and perhaps treatments.
A group in Holland
has been looking at adult dyslexics (who have learned to read) with
fMRI scans while they match letters and speech sounds. Although they
do the task correctly, their scans differ from normal readers doing
the same matching. They have learned to integrate letters and speech
sounds but in a different way then non-dyslexics. They appear to make
less use of the superior temporal cortex when doing the matching.
This is not research into the causes of
dyslexia, whether there is one or many. It is simply looking at how
dyslexics do read when they learn to. The front-runner in possible
causes is still the inability to properly process phonological
sounds. And the most obvious source of this problem is a lack of the
fast pathway in analyzing sounds and therefore the inability to hear
the fine structure of speech.
I must say, this different method of
reading in cured dyslexics sounds right to me. I have always had the
feeling that I was forging a new pathway to reading and spelling –
go around some blockage or dead end. Doing what others did to read or
spell did not work, no matter how hard or long I tried. So I am not
surprised that the mechanisms I use to read and write are somewhat
different from others.
- Vitamin D deficiency is very common and this is especially true of
Some are saying that the hype about Vitamin D is unwarranted, but I'm
giving it a try. According to the pro vioces -
- There is revision of the guidelines for vitamin D intake underway –
- Low vitamin D can increase inflammation even in women who appear
but have suboptimal health.
- Vitamin D deficiency has been linked to heart disease, high blood
multiple sclerosis, rheumatoid arthritis, obesity, diabetes, metabolic
syndrome, inflammatory bowel disease, chronic liver disease,
osteoporosis, muscle weakness, stroke, and perhaps fatigue joint pain,
depression, cancer and infections.
The case has not been made for all of these diseases but it is clearly
needed for bone and
muscle health (including heart muscle). And its connection to
inflammation is strong. The reason I take this seriously is that
vitamin D is part of the system that regulates calcium in the body
and calcium is not just what bones are made of but it is one of the
most important signals in many processes, in all cells and in all
parts of the body. Calcium metabolism is important.
A receptor for Vitamin D in cells is responsible for regulating calcium
metabolism and for the transcription of over 900 genes largely to due
Some researchers are saying that the link to
inflammation may be the other way around. Those with auto-immune
disease may have low levels of Vitamin D as a result rather than a
cause. They go further and warn that taking ligh doses of vitamin D may
actually make auto-immune disease worse.
So I am taking a cautious approach and only having a smallish dose of supplement.
Celiac and Skin Conditions
There are three skin conditions that
seem to go with celiac.
The most obvious is dermatitis
herpetiformis which has only one cause, inflammation due to glutin
intolerance and only one cure, a glutin free diet. Then there is
palmoplantar pustulosis which is often associated with glutin
intolerance and there is psoriasis where some but not a large
proportion of cases are due to glutin intolerance. The symptoms of
these conditions are similar but apparently they can be distinguished
in biopsy. But how often would a biopsy be done I ask? Dermatitis
herpetiformis, and the many cases of palmoplantar pustulosis and the
fewer cases of psoriasis that are linked to glutin intolerance, may
actually be the same condition. There are antibodies to gliadin (AGA)
and inappropriately activiated T- cells attack the skin in these
diseases. The same antibodies are found in celiac and the same type
of T-cell attack occurs in the gut.
Specifically this is a Th1 immune
response to the body's own cells. There are a number of types of T
lymphocytes. Th1 produce cytokines that are responsible for killing
intracellular parasites (viruses and microorganisms that enter the
body's cells) rather than free pathogens and toxins. Interferon gamma
is the main Th1 weapon and it causes inflammation. When Th1
lymphocytes recognize normal healthy tissue as a target they cause
Why should these skin conditions be
slightly different when they have the same cause. One reason may be
the lack of some nutrients in celiac. Vitamin A, vitamin C and fatty
acids are needed for healthy skin and if these are not absorbed by a damaged gut, the skin
may not be as able to withstand the immune attack.
I have what I thought was psoriasis on
my face and it got worse slowly over the years. Now it is improving
slowly but still there. I also had what was probably the start of
palmoplantar pustulosis on my palms but it disappeared shorted after
I stopped eating glutin.
If you love curry like I do, you will
like this news. Scientists are finding the reason that the molecule,
curcumin, in turmeric spice is good for us. At least four papers have
been published in the last few weeks by different groups, all showing
the power of curcumin. So like garlic, I can not only eat it and
enjoy it, I can approve of myself while I'm doing it.
Turmeric is a bit like snake oil in the
number of illnesses in is supposed to cure: bad teeth, bacterial
infections, wounds, diarrhea, inflammations, cancers, liver
conditions, heart conditions, type2 diabetes, Alzheimers and many
others. I was eating quite a lot of it before I was aware that it was
supposed to be good for me because I just love the taste. The way I
eat it is that I mix curry powder with mayonnaise and put it on
boiled egg or whatever I think could go with it. Curry restaurants
are not thick on the ground in France so I don't get a proper curry
Here is the news:
Curcumin molecules insert
themselves into cell membranes and makes the membranes more stable.
This helps cells to resist infections and the effects of
It suppresses angiogenic activity
(the formation of new blood vessels) in fat tissue and this inhibits
the growth of fat tissue.
It seems to lower blood
cholesterol and levels of fat in the liver.
It stimulates apoptosis (a
programmed type of cell suicide) in some types of cancerous tumors.
It can prevent and reverse
hypertrophy of the heart.
It reduces the formation of scar
tissue. This may be part of its healing effect on damaged hearts.
This reduction of 'bad scar' tissue is probably due to curcumin
acting on the cell nucleus to prevent the unraveling of chromosomes
under stress and therefore preventing excessive abnormal protein
production during healing.
Anti-inflammatory and anti-oxidant
ingredients of turmeric (mainly curcumin) seem to be the reason that
turmeric reduces fat and liver inflammation and insulin resistance
in metabolic syndrome and type2 diabetes.
Hoorrah for India's holy yellow powder.
What APP doesCeliac Insights
Biologists knew that amyloid precusor
protein (APP) has an important function in the brain but not what it
was. Now there is a model of what it does:
APP and a protein called reelin work
together to create and maintain synapses in the brain. The synapses
are very narrow structures where two neurons almost touch. One neuron
releases neurotransmitters into the narrow gap and the other neuron
takes them up in order to send signals from the one neuron to the
other. This process needs to be controlled and so the synapse is a
complicated structure. It appears that APP is like a structural
bridge that stabilizes the synaptic space and organizes the flow of
When a synapse is no longer needed it
is destroyed - the APP bridging is cut apart. This cutting produces
amyloid including the beta amyloid associated with Alzheimers
disease. Reelin increases the number of dendrites and axons that
neurons grow and the synaptic connections between them. It requires
APP in order to do this as the two proteins work together.
The search for a Alzheimer treatment or
cure is helped by knowledge of the functions of the various proteins
Here is the full text of
an article in the Scientific American Magazine from its website July
27 2009 - Study of a potentially fatal food-triggered disease has
uncovered a process that may contribute to many autoimmune disorders
– Scientific American Magazine July 27 2009. It is written by
Celiac Disease Insights: Clues to Solving Autoimmunity
My vote for the most important scientific revolution of all time
would trace back 10,000 years ago to the Middle East, when people
first noticed that new plants arise from seeds falling to the ground
from other plants—a realization that led to the birth of
agriculture. Before that observation, the human race had based its
diet on fruits, nuts, tubers and occasional meats. People had to move
to where their food happened to be, putting them at the mercy of
events and making long-term settlements impossible.
Once humans uncovered the secret of seeds, they quickly learned to
domesticate crops, ultimately crossbreeding different grass plants to
create such staple grains as wheat, rye and barley, which were
nutritious, versatile, storable, and valuable for trade. For the
first time, people were able to abandon the nomadic life and build
cities. It is no coincidence that the first agricultural areas also
became "cradles of civilization."
This advancement, however, came at a dear price: the emergence of
an illness now known as celiac disease (CD), which is triggered by
ingesting a protein in wheat called gluten or eating similar proteins
in rye and barley. Gluten and its relatives had previously been
absent from the human diet. But once grains began fueling the growth
of stable communities, the proteins undoubtedly began killing people
(often children) whose bodies reacted abnormally to them. Eating such
proteins repeatedly would have eventually rendered sensitive
individuals unable to properly absorb nutrients from food. Victims
would also have come to suffer from recurrent abdominal pain and
diarrhea and to display the emaciated bodies and swollen bellies of
starving people. Impaired nutrition and a spectrum of other
complications would have made their lives relatively short and
If these deaths were noticed at the time, the cause would have
been a mystery. Over the past 20 years, however, scientists have
pieced together a detailed understanding of CD. They now know that it
is an autoimmune disorder, in which the immune system attacks the
body’s own tissues. And they know that the disease arises not only
from exposure to gluten and its ilk but from a combination of
factors, including predisposing genes and abnormalities in the
structure of the small intestine.
What is more, CD provides an illuminating example of the way such
a triad—an environmental trigger, susceptibility genes and a gut
abnormality—may play a role in many autoimmune disorders. Research
into CD has thus suggested new types of treatment not only for the
disease itself but also for various other autoimmune conditions, such
as type 1 diabetes, multiple sclerosis and rheumatoid arthritis.
After the advent of
agriculture, thousands of years passed before instances of seemingly
well-fed but undernourished children were documented. CD acquired a
name in the first century A.D., when Aretaeus of Cappadocia, a Greek
physician, reported the first scientific description, calling it
koiliakos, after the Greek word for “abdomen,” koelia.
British physician Samuel Gee is credited as the modern father of CD.
In a 1887 lecture he described it as “a kind of chronic indigestion
which is met with in persons of all ages, yet is especially apt to
affect children between one and five years old.” He even correctly
surmised that “errors in diet may perhaps be a cause.” As clever
as Gee obviously was, the true nature of the disease escaped even
him, as was clear from his dietary prescription: he suggested feeding
these children thinly sliced bread, toasted on both sides.
Identification of gluten as the trigger occurred after World War
II, when Dutch pediatrician Willem-Karel Dicke noticed that a
war-related shortage of bread in the Netherlands led to a significant
drop in the death rate among children affected by CD—from greater
than 35 percent to essentially zero. He also reported that once wheat
was again available after the conflict, the mortality rate soared to
previous levels. Following up on Dicke’s observation, other
scientists looked at the different components of wheat, discovering
that the major protein in that grain, gluten, was the culprit.
Turning to the biological effects of gluten, investigators learned
that repeated exposure in CD patients causes the villi, fingerlike
structures in the small intestine, to become chronically inflamed and
damaged, so that they are unable to carry out their normal function
of breaking food down and shunting nutrients across the intestinal
wall to the bloodstream (for delivery throughout the body).
Fortunately, if the disease is diagnosed early enough and patients
stay on a gluten-free diet, the architecture of the small intestine
almost always returns to normal, or close to it, and gastrointestinal
In a susceptible person, gluten causes this inflammation and
intestinal damage by eliciting activity by various cells of the
immune system. These cells in turn harm healthy tissue in an attempt
to destroy what they perceive to be an infectious agent.
A Diagnostic Discovery
Fuller details of the
many mechanisms through which gluten affects immune activity are
still being studied, but one insight in particular has already proved
useful in the clinic: a hallmark of the aberrant immune response to
gluten is production of antibody molecules targeted to an enzyme
called tissue transglutaminase. This enzyme leaks out of damaged
cells in inflamed areas of the small intestine and attempts to help
heal the surrounding tissue.
Discovery that these antibodies are so common in CD added a new
tool for diagnosing the disorder and also allowed my team and other
researchers to assess the incidence of the disease in a new way—by
screening people for the presence of this antibody in their blood.
Before then, doctors had only nonspecific tests, and thus the most
reliable way to diagnose the disease was to review the patient’s
symptoms, confirm the intestinal inflammation by taking a biopsy of
the gut, and assess whether a gluten-free diet relieved symptoms.
(Screening for antibodies against gluten is not decisive, because
they can also occur in people who do not have CD.)
For years CD was considered a rare disease outside of Europe. In
North America, for example, classic symptoms were recognized in fewer
than one in 10,000 people. In 2003 we published the results of our
study—the largest hunt for people with CD ever conducted in North
America, involving more than 13,000 people. Astoundingly, we found
that one in 133 apparently healthy subjects was affected, meaning the
disease was nearly 100 times more common than had been thought. Work
by other researchers has confirmed similar levels in many countries,
with no continent spared.
How did 99 percent of cases escape detection for so long? The
classical outward signs—persistent indigestion and chronic
diarrhea—appear only when large and crucial sections of the
intestine are damaged. If a small segment of the intestine is
dysfunctional or if inflammation is fairly mild, symptoms may be less
dramatic or atypical.
It is also now clear that CD often manifests in a previously
unappreciated spectrum of symptoms driven by local disruptions of
nutrient absorption from the intestine. Disruption of iron
absorption, for example, can cause anemia, and poor folate uptake can
lead to a variety of neurological problems. By robbing the body of
particular nutrients, CD can thus produce such symptoms as
osteoporosis, joint pain, chronic fatigue, short stature, skin
lesions, epilepsy, dementia, schizophrenia and seizure.
Because CD often presents in an atypical fashion, many cases still
go undiagnosed. This new ability to recognize the disease in all its
forms at an early stage allows gluten to be removed from the diet
before more serious complications develop.
From Gluten to Immune Dysfunction
disease provides an enormously valuable model for understanding
autoimmune disorders because it is the only example where the
addition or removal of a simple environmental component, gluten, can
turn the disease process on and off. (Although environmental factors
are suspected of playing a role in other autoimmune diseases, none
has been positively identified.)
To see how gluten can have a devastating effect in some people,
consider how the body responds to it in most of the population. In
those without CD, the body does not react. The normal immune system
jumps into action only when it detects significant amounts of foreign
proteins in the body, reacting aggressively because the foreigners
may signal the arrival of disease-causing microorganisms, such as
bacteria or viruses.
A major way we encounter foreign proteins and other substances is
through eating, and immune soldiers sit under the epithelial cells
that line the intestine (enterocytes), ready to pounce and call in
reinforcements. One reason our immune system typically is not incited
by this thrice-daily protein invasion is that before our defenses
encounter anything that might trouble them, our gastrointestinal
system usually breaks down most ingested proteins into standard amino
acids—the building blocks from which all proteins are constructed.
Gluten, however, has a peculiar structure: it is unusually rich in
the amino acids glutamine and proline. This property renders part of
the molecule impervious to our protein-chopping machinery, leaving
small protein fragments, or peptides, intact. Even so, in healthy
people, most of these peptides are kept within the gastrointestinal
tract and are simply excreted before the immune system even notices
them. And any gluten that sneaks across the gastrointestinal lining
is usually too minimal to excite a significant response from a
normally functioning immune system.
CD patients, on the other hand, have inherited a mix of genes that
contribute to a heightened immune sensitivity to gluten. For example,
certain gene variants encoding proteins known as histocompatibility
leukocyte antigens (HLAs) play a role. Ninety-five percent of people
with CD possess the gene either for HLA-DQ2 or for HLA-DQ8, whereas
just 30 to 40 percent of the general population have one of those
versions. This finding and others suggest that the HLA-DQ2 and
HLA-DQ8 genes are not the sole cause of immune hyperactivity but that
the disease, nonetheless, is nearly impossible to establish without
one of them. The reason these genes are key becomes obvious from
studies of the function of the proteins they specify.
The HLA-DQ2 and HLA-DQ8 proteins are made by antigen-presenting
cells. These immune sentinels gobble up foreign organisms and
proteins, chop them, fit selected protein fragments into grooves on
HLA molecules, and display the resulting complexes on the cell
surface for perusal by immune system cells called helper T
lymphocytes. T cells that can recognize and bind to the displayed
complexes then call in reinforcements.
In patients with CD, tissue transglutaminase released by
intestinal epithelial cells attaches to undigested gluten and
modifies the peptides in a way that enables them to bind extremely
strongly to DQ2 and DQ8 proteins. In consequence, when
antigen-presenting cells under intestinal epithelial cells take up
the complexes of tissue transglutaminase and gluten, the cells join
the gluten to the HLAs and dispatch them to the cell surface, where
they activate T cells, inducing the T cells to release cytokines and
chemokines (chemicals that stimulate further immune activity). These
chemicals and enhancement of immune defenses would be valuable in the
face of a microbial attack, but in this instance they do no good and
harm the intestinal cells responsible for absorbing nutrients.
CD patients also tend to have other genetic predispositions, such
as a propensity for overproducing the immune stimulant IL-15 and for
harboring hyperactive immune cells that prime the immune system to
attack the gut in response to gluten.
Guilt by Association
What role might
antibodies to tissue transglutaminase play in this pathological
response to gluten? The answer is still incomplete, but scientists
have some idea of what could happen. When intestinal epithelial cells
release tissue transglutaminase, B cells of the immune system ingest
it—alone or complexed to gluten. They then release antibodies
targeted to the enzyme. If the antibodies home in on tissue
transglutaminase sitting on or near intestinal epithelial cells, the
antibodies might damage the cells directly or elicit other
destructive processes. But no one yet knows whether they, in fact,
cause such harm.
In the past nine years my colleagues and I have learned that
unusual intestinal permeability also appears to participate in CD and
other autoimmune diseases. Indeed, a growing body of evidence
suggests that virtually the same trio of factors underpins most, and
perhaps all, autoimmune diseases: an environmental substance
that is presented to the body, a genetically based tendency of the
immune system to overreact to the substance, and an unusually
Finding the Leak
It is fair to say that the
theory that a leaky gut contributes to CD and autoimmunity in general
was initially greeted with great skepticism, partly because of the
way scientists thought of the intestines. When I was a medical
student in the 1970s, the small intestine was described as a pipe
composed of a single layer of cells connected like tiles with an
impermeable “grout,” known as tight junctions, between them. The
tight junctions were thought to keep all but the smallest molecules
away from the immune system components in the tissue underlying the
tubes. This simple model of the tight junctions as inert, impermeable
filler did not inspire legions of researchers to study their
structure, and I was among the unenthused.
It was only an unexpected twist of fate, and one of the most
disappointing moments of my career, that drew me to study tight
junctions. In the late 1980s I was working on a vaccine for cholera.
At that time, the cholera toxin was believed to be the sole cause of
the devastating diarrhea characteristic of that infection. To test
this hypothesis, my team deleted the gene encoding the cholera toxin
from the bacterium Vibrio cholerae. Conventional wisdom
suggested that bacteria disarmed in this way would make an ideal
vaccine, because the remaining proteins on a living bacterial cell
would elicit a strong immune response that would protect against
But when we administered our attenuated bacteria to volunteers,
the vaccine provoked enough diarrhea to bar its use. I felt
completely disheartened. Years of hard work were literally down the
toilet, and we were faced with two unattractive options: giving up
and moving on to another research project or persevering and trying
to understand what went wrong. Some intuition that there was
more to this story prompted us to choose the latter path, and this
decision led us to discover a new toxin that caused diarrhea by a
previously undescribed mechanism. It changed the permeability of the
small intestine by disassembling those supposedly inert
tight junctions, an effect that allowed fluid to seep from tissues
into the gut. This “grout” was interesting after all.
Indeed, at nearly the same time, a series of seminal discoveries
clarified that a sophisticated meshwork of proteins forms the tight
junctions; however, little information was available on how these
structures were controlled. Therefore, the discovery of our toxin,
which we called the “zonula occludens toxin,” or Zot
(zonula occludens is Latin for “tight junction”),
provided a valuable tool for clarifying the control process. It
revealed that a single molecule, Zot, could loosen the complex
structure of the tight junctions. We also realized that the control
system that made this loosening possible was too complicated to have
evolved simply to cause biological harm to the host. V. cholerae
must cause diarreha by exploiting a preexisting host pathway that
regulates intestinal permeability.
Five years after the formulation of this hypothesis, we discovered
zonulin, the protein that in humans and other higher animals
increases intestinal permeability by the same mechanism as the
bacterial Zot. How the body uses zonulin to its advantage remains to
be established. Most likely, though, this molecule, which is secreted
by intestinal epithelial tissue as well as by cells in other organs
(tight junctions have important roles in tissues throughout the
body), performs several jobs—including regulating the movement of
fluid, large molecules and immune cells between body compartments.
Discovery of zonulin prompted us to search the medical literature
for human disorders characterized by increased intestinal
permeability. It was then that we first learned, much to my surprise,
that many autoimmune diseases—among them, CD, type 1 diabetes,
multiple sclerosis, rheumatoid arthritis and inflammatory bowel
diseases—all have as a common denominator aberrant intestinal
permeability. In many of these diseases, the increased permeability
is caused by abnormally high levels of zonulin. And in CD, it is now
clear that gluten itself prompts exaggerated zonulin secretion
(perhaps because of the patient’s genetic makeup).
This discovery led us to propose that it is the enhanced
intestinal permeability in CD patients that allows gluten, the
environmental factor, to seep out of the gut and to interact freely
with genetically sensitized elements of the immune system. That
understanding, in turn, suggests that removing any one factor of the
autoimmunity-causing trinity—the environmental trigger, the
heightened immune reactivity or the intestinal permeability—should
be enough to stop the disease process.
Therapies to Topple the Trinity
As I mentioned
before, and as this theory would predict, removing gluten from the
diet ends up healing the intestinal damage. Regrettably, a lifelong
adherence to a strict gluten-free diet is not easy. Gluten is a
common and, in many countries, unlabeled ingredient in the human
diet. Further complicating adherence, gluten-free products are not
widely available and are more expensive than their gluten-containing
counterparts. In addition, sticking perfectly over years to any diet
for medical purposes is notoriously challenging. For such reasons,
diet therapy is an incomplete solution. Consequently, several alternative therapeutic strategies have been
considered that disrupt at least one element of the three-step
process. Alvine Pharmaceuticals in San Carlos, Calif., has developed
oral protein-enzyme therapies that completely break down gluten
peptides normally resistant to digestion and has an agent in clinical
trials. Other investigators are considering ways to inhibit tissue
transglutaminase so that it does not chemically modify undigested
gluten fragments into the form where they bind so effectively to
HLA-DQ2 and HLA-DQ8 proteins.
No one has yet come up with safe and ethical ways to manipulate
the genes that make people susceptible to disease. But researchers
are busy developing therapies that might dampen some of the genetically controlled factors that
contribute to the immune system’s oversensitivity. For example, the
Australian company Nexpep is working on a vaccine that would expose
the immune system to small amounts of strongly immunogenic forms of
gluten, on the theory that repeated small exposures would ultimately
induce the immune system to tolerate gluten.With an eye toward blocking the intestinal barrier defect, I
co-founded Alba Therapeutics to explore the value of a zonulin
inhibitor named Larazotide. (I am now a scientific adviser for Alba
and hold stock options, but I no longer participate in making
decisions for the company.) Larazotide has now been tested in two
human trials examining safety, tolerability and signs of efficacy in
celiac patients who ate gluten. These were gold-standard
trials—randomized, placebo-controlled tests in which neither the
drug deliverers nor the patients know who receives treatment and who
receives a sham, until the trial is over.Together the tests showed no excess of side effects in patients
given Larazotide rather than the placebo. More important, the first,
smaller study demonstrated that the agent reduced gluten-induced
intestinal barrier dysfunction, production of inflammatory molecules
and gastrointestinal symptoms in celiac patients. And the second,
large study, reported at a conference in April, showed that CD
patients who received a placebo produced antibodies against tissue
transglutaminase but that the treated group did not. As far as I
know, this result marks the first time a drug has halted an
autoimmune process, interfering specifically with an immune response
against a particular molecule made by the body. Other drugs that
suppress immune activity act less specifically. Recently Alba
received approval from the U.S. Food and Drug Administration to
expand studies of Larazotide to other autoimmune disorders, including
type 1 diabetes and Crohn’s disease.These new prospects for therapy do not mean that CD patients can
abandon dietary restrictions anytime soon. Diet could also be used in
a new way. Under the leadership of Carlo Catassi, my team at the
University of Maryland has begun a long-term clinical study to test
whether having infants at high risk eat nothing containing gluten
until after their first year can delay the onset of CD or, better
yet, prevent it entirely. “High risk,” in this case, means
infants possess susceptibility genes and their immediate family has a
history of the disorder.
We suspect the approach could work because the immune system
matures dramatically in the first 12 months of life and because
research on susceptible infants has implied that avoiding gluten
during the first year of life might essentially train that developing
immune system to tolerate gluten thereafter, as healthy people do,
rather than being overstimulated by it. So far we have enrolled more
than 700 potentially genetically susceptible infants in this study,
and preliminary findings suggest that delaying gluten exposure
reduces by fourfold the likelihood that CD will develop. It will be
decades, however, until we know for certain whether this strategy can
stop the disease from ever occurring.
Given the apparently shared underpinning of autoimmune disorders
in general, researchers who investigate those conditions are eager to
learn whether some therapeutic strategies for CD might also ease
other autoimmune conditions that currently lack good treatments. And
with several different approaches in the pipeline to treat CD, we can
begin to hope that this disease, which has followed humanity from the
dawn of civilization, is facing its last century on earth.
A Clue to Delayed Onset
People with celiac
disease are born with a genetic susceptibility to it. So why do some
individuals show no evidence of the disorder until late in life? In
the past, I would have said that the disease process was probably
occurring in early life, just too mildly to cause symptoms. But now
it seems that a different answer, having to do with the bacteria that
live in the digestive tract, may be more apt. These microbes, collectively known as the microbiome, may differ
from person to person and from one population to another, even
varying in the same individual as life progresses. Apparently they
can also influence which genes in their hosts are active at any given
time. Hence, a person whose immune system has managed to tolerate
gluten for many years might suddenly lose tolerance if the microbiome
changes in a way that causes formerly quiet susceptibility genes to
become active. If this idea is correct, celiac disease might one day
be prevented or treated by ingestion of selected helpful microbes, or
Too clean for our own good
Someone (I know him by the name
Daedalus) has looked at the items on this page, noticed the diseases
I am interested in, and sent me some information on research at
Warwick University that he is involved in.
This research is, indeed, interesting
to me for a few reasons: it involves microbiology, it involves human
evolution, and it involves metabolic syndrome/Alzheimers/auto-immune
One paper* is about the
Whitlock-Feelisch Hygiene hypothesis and goes like this:
There is a increase in certain
diseases in the affluent, urban, developed world that are not as
prevalent in the rural, poor, undeveloped world. The changes in the
incidence of these diseases over time points to the cause being
better hygiene – more bathing, more soap, more detergents, more
disinfectants, cleaner water. 'Good bacteria' are 'old friends'
through human evolution and we may depend on some of their good
works. Hygiene decreases good as well as bad bacteria.
These diseases involve the immune
system and inflammation (asthma, allergies, type 1 diabetes,
inflammatory bowel disease, obesity, some degenerative diseases).
The conditions are made worse by obesity and by stress. They are
probably connected by some common biochemical pathways and
regulatory mechanisms of those pathways. The authors put forward the
pathways that are regulated by nitric oxide (NO) as a likely set to
be responsible from these diseases.
Normal skin bacteria are only now
being studied and there are two ways in which they could affect
nitric oxide and nitrite: by reduction nitrate (NO3-) to nitrite
(NO2-) and by oxidation of ammonia (NH4) to nitrite (NO2-). The
later would be done by ammonia oxidizing bacteria. Bacteria in the
mouth produce nitrite (NO2-) from nitrate (NO3-) in food and water.
Nitric oxide (NO) is a gas with a
signaling role in a number of cellular processes. It diffuses
through tissue and where is it above a threshold level activates NO
sensors. The enzyme, nitric oxide synthases, produces it from the
amino acid L-arginine. The amount produced depends on the amount of
reactive oxygen species (peroxide, free radicals, oxygen ions –
the sort of chemical that anti-oxidants scavenge). The ratio of
nitric oxide and reactive oxygen determines the action of many
critical proteins. Nitrite (NO2-) can act like nitric oxide (NO) but
is not a gas and so acts only locally as it cannot diffuse through
The basal level of nitric oxide
(NO) gas in the tissues affects the response to any additional
signaling gas. A change to basal level will change the range and
timing of any signal, 'good regulation with a bad setpoint'. The
pathways using NO signals are highly complex and basal level
disturbances would affect them all in complex ways. Nitrite (NO2-)
shortage and oxidative stress both increase the need for higher NO
levels for the same signaling effect. Not only does stress lower NO
levels but lower NO heightens stress. The balance of NO and reactive
oxygen has complex affects on inflammation. Inflammation is at the
root of the type of diseases associated modern hygiene.
Modern hygiene has eliminated
ammonia oxidizing bacteria from the skin. These bacteria do not use
complex foods and get all their energy and make the molecules they
need for growth from oxidation of ammonia (NH4) to nitrite (NO2-).
They live on the skin, use the ammonia in sweat and supply nitrite
to their host. Scalp, pubic and underarm hair provides the sweat,
warmth, humidity and protection from light needed by the ammonia
oxidizing bacteria. There are other mutual advantages between us and
these bacteria. Without the levels of hygiene we now have, our skin
would have these bacteria and they would be supplying NO2- and
reducing the problems in NO supply.
Ammonia oxidizing bacteria are
safe. Autotrophic bacteria are not infectious because they cannot
fed on the organic matter than makes up our cells. They are very
slow growing. They are everywhere in the soil and water in the
natural world. They are very susceptible to detergents and other
hygiene products. Plants take nitrate (NO3-) and produce amino
acids. Heterotropic bacteria and other organisms (including us)
oxidize amino acids and release ammonia, the ammonia is used by the
autotrophic ammonia oxidizing bacteria – it is one of those
Removal of NO from the body is
done mainly by hemoglobin and hemoglobin also produces NO3- from
NO2- and so any process that takes higher levels of NO or NO2-
cannot go on in the presence of hemoglobin. The outer skin lacks
hemoglobin and gets oxygen from the air rather than the blood. NO
and NO2- delivered to the skin would be available for the regulation
of Tcells. The skin could be quite important to the body's immune
If NO and NO2- cannot be delivered
to the skin by ammonia oxidizing bacteria because of our level of
hygiene, then perhaps they could be delivered in creams or powders.
However, a cream or powder would not deliver just when needed like
bacteria would. There is a company working on bacterial based
products (see http://nitroceutic.com)
Daedalus is not alone in finding
nitrate, nitrite and nitric oxide metabolism important. Researchers
from Michican State and Amsterdam are advocating more plant sourced
nitrate and nitrite in the diet for their benefit to the arteries.
And researchers in Houston are investigating Chinese herbs for their
ability to convert nitrate and nitrite to nitric oxide and thereby
treat cardiovascular illness.
* found in The Hygiene Hypothesis and
Darwinian Medicine (Rook GAW,ed.) Birkhaeuser Publishing, Basel, 2009
- Soil bacteria, nitrite, and the skin by David R Whitlock and
Maybe the molecule of the century
Haptoglobin is a molecule that has been
known for many years as a marker of inflammation in the body.
Haptoglobin 1 is the original form of the haptoglobin molecule, and
scientists believe it evolved 800 million years ago. Haptoglobin 2 is
a permutation found only in Homo species. It's believed the mutation
occurred in India about 2 million years ago, spreading gradually
among increasing numbers of people throughout the world. A few years
ago a protein was discovered that was involved in celiac disease and
other autoimmune conditions. This protein was called zonulin. It has
now been shown that zonulin is the same molecule as the precursor of
haptoglobin 2. Precursors usually have no purpose or effect but
precursor haptoglobin 2 is different – it opens a gateway in the
intestines to let gluten into the body. The body produces antibodies
against this foreign gluten and these antibodies, in celiac
sufferers, attack the body's own tissues.
Autoimmune disease is very rare in
other primates but humans can get more than 70 different forms of
autoimmune conditions. It is now believed that the presence of
precursor haptoglobin 2 or zonulin in 80% of humans is the reason for
the difference between us and other primates. Zonulin is probably the
critical missing piece of the puzzle of all the autoimmune diseases,
allergies and maybe some cancers, that are related to loss of
protective barrier in the gut, the blood-brain barrier and barriers
in other areas of the body. The identification of this molecule will
probably led to many new treatments.
People who have their gall bladders
removed should be warned about bile acid diarrhea.
Bile acids are made in the liver from
cholesterol, and move into the gut through the bile duct. There they
emulsify fat so that it can be absorbed. The bile acids that are not
re-absorbed with fat are eliminated through the large intestine. The
production of bile acids is under feedback control so that if more is
re-absorbed, less is made. In at least 1 in 100 people, large amounts
of bile acid reach the colon, irritate it and cause it to leak water
and salt, giving sudden bouts of extreme diarrhea. This type of
diarrhea is often not diagnosed or mis-diagnosed.
Problems occur when:
Now that I avoid gluten, I have much
less trouble with diarrhea. Occasionally I suffer from it and the
symptoms are like those for bile acid diarrhea. This makes sense as I
have had my gall bladder removed.
- There is mal-absorption of the
bile acids. This can be due to the decreased synchronization of bile
release and food intake that occurs when the gall bladder is removed
or with some diets or with damaged intestines.
- There is a fault in the feedback
system and re-absorption does not turn off production of bile acids.
Usually lack of the hormone Fibroblast Growth Factor 19.
- There is a bad pH or damage in the
colon leading to the bile acids being more irritating.
Is Christmas a hazard
to your health?
Well, you would
We get all
stressed working ourselves up to Christmas: shopping, planning,
cooking, decorating. We worry about money. Kids get ratty. We have
lots of little accidents. By the time Christmas comes, most people
are a wreck. Then Christmas is the time to over eat, eat the wrong
things, over drink, under exercise. Even if we survive without being
one of the people who is in a car accident, has a heart attack or
commits suicide, it will take the whole week to New Years to regain
the feeling of being human and to make peace with the relatives and
friends that you have argued with (or even with the boss that you
insulted at the works party). Definitely not healthy!
So why not look at
Christmas a different way – as therapy.
Here we are in the
darkest part of the year and looking forward to the coldest part of
winter and you just want to cry. It is just too long to April to
bear. Its called SAD, seasonal affective disorder, and it brings
depression, fatigue, sleepiness, vague illnesses and aches. SAD is a
good name. What we need is a party and there seems to be one near the
winter solstice in every culture. We need to get some light, warmth,
exercise, good food and negative ions. We need wood fires and
flickering candles. We need tacky shiny bobbles. We need music and
hugs. We need to feel full of comfort food and mellow with drink. We
need less melatonin and more serotonin.
If you feel a little the worse for
Christmas then just imagine how you would feel without it.