news views family info
Health items from before 2009:
Backs and Bricks
Backs and Bricks
is an idea that no one takes
seriously as far as I know. THE SPINE DOES NOT WORK LIKE A PILE OF
BRICKS WITH LITTLE PILLOWS BETWEEN THE BRICKS.
I read a book about Buckminster Fuller's ideas once, a long time ago.
One of the items was a mast. I think he called it a DiMaxion Mast. It
was held up by tension rather than compression. There were a number of
solid pieces, one above the other but they were not actually touching.
Each piece was like an old fashion jack that kids used to play jacks
with, or like a cross shape where two opposite arms of the cross were
bent upward and the other two arms bent downward. Each piece was placed
in the pile so that its up arms were between the down arms of the peice
above and its down arms were between the up arms of the peice below.
Now a cable or string is put around the mast between each pair of
peices. This cable is attached to the four arms between each pair of
pieces, (the up arms from the lower one and the down arms from the
upper one). Now the cable is tightened and this aligns the ends of the
arms so that they are all in a plane, and that separates the two
pieces. The mast is held up by the tension on those cables. Each piece
is sort of resting in a hammock provided by the up arms of the piece
beneath it. Finally 4 cables run length-wise through each set of arms
up the mast from bottom to top and they are tensioned. This makes the
mast stay vertical.
One day many years later, I was looking at a model of the spine. And
hey, for a lot of the spine each vertbra has two downward projections
and two upward ones. There are little muscles and connective tissue
banding around the spine and some long muscles going up and down. I
thought, that looks like Fuller's mast.
Full of excitement about this idea, I told my doctor the next time I
was there. I got no reaction. But I thought, that's doctors-and-backs.
The next time I exposed the idea was at a session on looking after your
back being given by a physiotherapist. At one point she said, "think of
the back as a pile of bricks". So after the session I took her up on
that. I asked, "if the back is a pile of bricks, how can I just stand
here and stretch myself a little taller?" Well she says I do that with
my lungs and abdominal muscles. Which is true. So I hold my nose and
keep a hand on my stomach to make sure I'm not tightening and I still
think I can stretch taller, but she thinks I am fooling myself. She had
no more time for such silly ideas. "Believe me", she says, "it works
like a pile of bricks."
For my own peace of mind I tried stetching after I had abdominal
surgery. I was sure I could tell if I used my abdominal muscles because
they were so tender. I held my nose. I lined my eye up on a point along
the window frame. I stetched and I was taller because I could see the
shift in the background against the frame. I also noticed that people
could stretch their necks. I am convinced that the back is not like a
pile of bricks but is an active and reactive system of muscles holding
the vertebra in various states of posture and tone. Believe me, it is
not like a pile of bricks.
A lot has been
about dyslexia since I last had a look. Unlike the theories a few years
back, the current contenders seem to fit much better with my
Researchers are going after the genes responsible and have found at
least four. All the genes probably have not been found yet, but the
ones found so far all point to a similar cause for the condition. I was
excited when I told Harry about this and he said I might as well be
talking gibberish - so this time I will start in a different place.
When the brain is forming in the embryo, the cells that are going to
become neurons migrate from a central place where they have multiplied
and accumulated to the outside layer of the cerebrium, to form the
neocortex. They do this by climbing up a scaffolding formed by cells of
another type, glia cells. The scaffolding already contains axons from
the parts of the brain that have grown earlier. Each radiating line of
glia scaffolding will form one column module of the neocortex, a group
of neurons that cooperate to process a particular type of information.
For example, one module might end up registering whether there is a
movement to the left in a little spot of the visual field or whether a
given spot is red. When these modules are being assembled, waves of
neurons migrate up the glias and past the previous wave to settle on
the outside. Then another wave pasts them. Once the cells of a module
have all arrived in the cortex, they change to the different types of
neurons needed in a working module. The module, as a whole, sort of
remembers where it came from, what it passed on the way, where it is
and what outside axons run through it. Some of its cells grow axons to
specific places in the rest of the brain and then the module is ready
to take on its job. Imagine billions of cells with trillions of
connections organizing themselves with a number of adhesives, chemical
tags, attractants etc. in an extremely complex process. A slightly weak
adhesive for example would create a finally structure that was not
Well, all this, so I can say that three of the genes that cause
dyslexia are involved in this migration process. One of these is only
active if inherited from a father. The fourth is involved in the
guidance of axon growth, a similar process to migration. It
control an axon's crossing of the midline of the brain and therefore
the connections between the left and right hemisphere. Therefore,
dyslexia is a result of an architectural or wiring fault during the
brain's development. There are other conditions that are now being
associated with inherited faults in neuron migration: schizophrenia,
autism, epilepsy, some mental retardation, attention deficit syndrome
and a number of oddly specific conditions like dyslexia. Of course, the
same disruption can occur from poisons and other environmental factors
if they occur at just the right time, perhaps fetal alcohol syndrome.
What is implied by this fault in brain architecture?
1. These genes are very old and occur in all vertebrates (the
axon growth one even occurs in invertebrates). They have been conserved
although many millions of years. Therefore they have nothing to do with
language, as such. There is likely to be some generalized functional
fault between the errors in migration and the inability to learn
written language, a way that the structural fault causes a particular
functional fault. That is for next month.
2. It seems unlikely that the architectural abnormalities can
ever be 'cured'. The brain would always have the same faults. So
overcoming the learning problem involves finding ways to bypass the
faults and learn in a different way. That is how I feel about my
learning - the brick wall is still there but I have found ways around,
over and under it. The plasticity of the brain may allow some
structural compensations to develop.
3. The migration fault would exist in people whether they
learned to write a dyslexia-unfriendly language like English, a written
language with clean phonetics, or never attempted written language at
all. The severity of the condition would depend on the language, the
teaching, the individual's other strengths and weaknesses as well as
the severity of the architectural fault in the brain.
4. For dyslexia to be at 10% or so in the population, there
be (or have been) an advantage to extremely mild cases or to the
offending genes when they occur without causing the condition. (As with
sickle cell anemia and resistance to malaria). Another time for this.
While I was nosing about, I had a look at the left-handedness gene too,
and found at least one gene has been firmly identified as a lefty gene.
There is not a consensus on whether there is any tie between
left-handedness and dyslexia.
seems to me that there
is more than one kind of dyslexia. Especially there is a difference
between those dyslexics that have poor short-term memory, poor
mathematics skills and are poor organizers of their lives and those
dyslexics that are the opposite with good memories, mathematical skills
and are good organizers. As a good memory and the ability of organize
are such a help to dyslexics, it is not too surprising that those
dyslexics that can hone these abilities do so. This creates even more
of a difference between the two types of dyslexia.
The symptoms that I have found in the literature are:
1. Dyslexics have phonological problems. They do not naturally
identify the component sounds in a syllable and the idea that this is
possible does not occur to them. They have difficulty in connecting
sounds with letters. This may be on top of the phonological problem or
a result of it. (true of me)
2. Reading is slow and hesitant with many misread words.
has erratic spelling, often phonetic, and there is a tendency to
reverse letters, as b for d or was for saw. (true of me)
3. Dyslexics may have difficulty with memory, organizing
thoughts and sequencing actions. There may be difficulties with
mathematics. (not true of me- but I have a problem when saying numbers
out loud of saying the wrong number and not realizing it, I did have
problems when young with learning sequences like making a knot, and I
cannot hold a string of letters longer than about 4 in my mind without
writing them down. On the other hand I have an extremely good memory
with organized thoughts and fairly good mathematical skills.)
4. The condition is often not apparent before a child attempts
to read and write. (true of me)
5. Dyslexics may confuse directional words such as up/down,
in/out and left/right. They may have a poor sense of direction. (true
of me except that I have a good sense of direction - I have great
difficulty with left and right and mirror images do not appear to be
really different in any important way.)
6. Young dyslexics may enjoy being read to but show no
or curiosity in the letters or printed words. (true of me)
7. Young dyslexics may have problems learned to count, days of
the week, months of the year, the alphabet, times tables and other
sequences.(not true of me)
8. Dyslexics may start to talk later than expected. (not true
9. Young dyslexics may have problems learning nursery rhymes
and rhyming words. (not true of me)
10. Dyslexic children may jumble phrases, use substitute words
or be unable to remember words of common objects. (not generally true
of me, although I have a little tendency in this direction which is
getting worse as I age)
11. Dyslexics may appear clumsy. They may have difficulty in
clapping a simple rhythm. (true of me)
12. Dyslexics can have difficulty reading long words, places,
times and dates. (partly true of me - times and dates are OK but proper
names for people and places just don't register when reading unless I
know them well.)
13. It is common for dyslexics to have good days and bad days
for reading and writing. (true of me)
14. Dyslexics are often unable to concentrate and are
day-dreamers. (was true of me until I learned to concentrate at about 7
or 8 and then I was able to concentrate better than most but I still
can be unaware of events that others take in.)
15. Dyslexics tend to think more in images and less in words than many
others. (true of me)
16. Dylexics are often prone to motion sickness. (true of me
although it has got better with age)
17. Dyslexics usually can to master reading and writing as
children or as adults. They are helped by learning phonetics. (true of
18. Adult dyslexics have poor reaction times. (true of me)
19. In autopsy, dyslexics show at least two abnormalities.
Normally the left temporal lobe (an important language area) is larger
than the right temporal lobe. In dyslexics they tend to be more
symmetrical. In dyslexics the magocellular layers of the lateral
geniculate nucleus have fewer large neurons than in non-dyslexics. The
same is true of the medial geniculate nucleus. These are the pathways
that can process very short duration changes in visual and auditory
treatments/aids for dylexics, the most universally effective is
training in phonetics. ( From my experience I think that young
dyslexics at least and maybe older ones to cannot, by themselves,
deduce the phonetic rules of a language and need to get a start at the
process before they can advance. I needed some phonetic rules to
identify component sounds and therefore could not use the sounds to
figure out the phonetic rules.)
sort of disability accounts for the set of symptoms in Dyslexia 2?
There are a number of theories but two are very interesting to me. One
theory (Gaab) brings together many of these symptoms with an inability
to processing quickly-changing sights and sounds. Again we have to
start in a different place or we will have gibberish.
The signal from the eyes goes through the optic nerve to the left and
right lateral geniculate nucleus of the thalamus and from there to the
visual cortex at the back of the skull. Signals move from one part of
the visual cortex to another and also feedback goes to the part of the
thalamus that the signal originally came from. It is like a map of the
retina exists in the thalamus and several other maps of the retina
exist on the surface of the visual cortex. Signals stream in both
directions between the different maps. The important thing here is that
there is a fast and a slow processing layer in the thalamus map. The
fast is called the magnocellular pathway. The slow, with more precision
but less speed, is called the parvocellular pathway. Dyslexics have a
less well populated magnocellular layer and therefore are less able to
perceive quickly changing visual events. The same is true of the medial
geniculate nucleus which receives signals from the ears, passes them to
the auditory cortex and receives feedback from the auditory cortex. It
is the same type of system but in this case it is the ear's cochlea
membrane that is mapped in the thalamus and several times in the
cortex. And again the problem is the underdevelopment of the fast
channel. As well as this anatomical evidence, the weakness of a
magnocellular pathway can be shown experimentally in dyslexics in both
the visual and auditory systems. Non-dyslexics easily differentiate
sounds and lights that are more than about 150 milliseconds apart,
dyslexics need 350 or more milliseconds. Speech sounds change over tens
of milliseconds, out of the range of the slow system. As a metaphor, it
is like the dyslexic has twice the 'blur' in sound and vision. This
difference in the resolution of sounds is probably the source of
phonological problems. It may also contribute to slow reading by not
allowing the letters to be seen clearly if the eyes move too fast. It
may contribute to motion sickness and to poor reaction times. Dyslexics
improve with training on progressive faster and faster sound changes.
This theory rings true to me.
Another theory (Shaywitz) deals with a lack of coordination in timing
between visual and auditory processing. Much of the brain's
functioning depends on the communication between areas of the brain
being accurately timed, simultaneously in some cases and sequentially
in others. The inferior frontal gyrus of the cerebral frontal lobe is
particularly important to language - it is more than Broca's area but
for simplicity I will call it that. In the left hemisphere it is larger
than in the right, except in dyslexics where the two sides are near
equal. As with the rest of the cerebrum, an area on one side has a lot
of nerve connection with the corresponding area on the other side. In
the left Broca's area phonological processing is done, both to produce
and perceive speech. It also controls the timing of language processes.
The right 'Brocas' does similar processing of written phonological
When trying to sound out words, dyslexics show a pattern of more
communication between the two areas then do normal people. Also there
is a lot more metabolic energy being consumed by the dyslexics meaning
a lot more short-term memory use. After special phonetic training, the
pattern appeared more normal - less simultaneous activity of the two
'Broca's' and less overloading of memory. It is believed that the
improvement is in the timing of communication between the two 'Broca's'.
Dyslexics use between 4 and 5 times as much energy and brain area to
sound out written words as non-dyslexics use. This seems to me to be
something like the 'wall' feeling, when no matter how hard I try,
nothing happens. For example, I remember when I was a teenager and a
very poor but somewhat phonetic speller, there were times when I went
blank, before I learned to relax and doing something completely
different for a while. It was little words that got me. 'Yet', for
example, I knew I knew how to spell it but I could not find any sound
or letter to start to build around. The word was like a fog that could
not be grasped. Sometimes when reading there would be a word, I knew
it's meaning and I knew it was part of my working vocabulary but I just
couldn't get a handle on what was the first sound to say. I would have
to close my eyes and relax, think of the meaning of the word and then
try to say it.
When I first encountered 'threshing' in early computers, where the
machine stops doing anything useful but has maximum activity, I thought
'I know that tiring brick wall'. Old computers literally sounded and
shook like a threshing machine in this condition. The computer had been
asked to do too many things simultaneously with limited resources and
it could not do any of them because of interference from the other
So I now tentatively understand:
1. I cannot process quickly changing sounds because
of - a
structural fault in the brain - caused by a fault in neuron migration
in my embryo - which did not produce enough of some vital chemical -
because of a genetic condition.
2. Language sounds are crowded in at about 10 per
second - so
my brain did not naturally identify the sounds as separate component
sounds - and therefore could not connect them with corresponding
letters - therefore did not get the hang of the connection between
sound and letters.
3. I had to be given a hint through contact with phonetics of
the existence and basic nature of the link between letters and sounds
and between sounds and whole words.
4. Attempting to make the connection in the normal way
in a 'threshing-like state' - so I then had to develop in my own ways
of mastering reading and spelling - by finding other pathways in my
brain. These both improved my ability to hear the individual sounds and
conversely allowed me to do without individual sounds and deal with
larger sound/print units - also making the attempt to hear the
differences in sounds, that phonetics pointed to, helped to find novel
ways to notice the differences.
But in my whole life I have never felt that there as any problem with
my verbal communication. I was a fair speaker and listener, even maybe
a very good one.
are some bits and pieces left to discuss:
Males are more at risk
There is a funny thing about some of the conditions that are now being
linked genetically with faults in neuron migration during development:
Schizophrenia, Autism, Attention deficit hyperactivity disorder and
Dyslexia all have higher percentages of males with the conditions then
females. Also men have more striking lateralization of the brain and
therefore are less able to regain speech after a stroke in the left
hemisphere, while women find it easier to shift their language
processing to the right hemisphere. Little boys are later developing
their language skills than little girls. I could not find accurate
figures for gender differences in Asperger's Syndrome because of the
lack of consensus on what it is. Those that have a tight definition
have small or no gender differences but those that have definitions
corresponding to 'nerd's disease' have a higher male incidence. This is
not surprising as it is more men who have nerdy interests (math,
engineering, IT etc.). Maybe testosterone has an effect on the
development of some areas of the brain that exacerbates these
conditions or maybe the X chromosome has genes that offer protection.
Lefties may be more at risk
Some studies have left-handed people with more dyslexia and some
studies have no effect for handedness. Of course they all differ in the
group they study, their definitions and their corrections. I am
assuming that there is a very small and highly specific connection.
Left-handed people differ in the lateralization of their brains. Most
people (about 96%) including presumably all right-handed people have
their language centers in the left hemisphere. Of left-handed people
about 70% similarly have their language centers in the left hemisphere.
The majority of the rest of left-handed people have a mirror image with
their language centers in the right hemisphere. A small number of
left-handed people have various placements of language centers that
split the language group between the two hemispheres. It may be that
one of these sub-sets of left-handers is more prone to dyslexia.
So far there is no indication of any genetic connection between
handedness and dyslexia, although the tendency to both is inherited.
The severity of dyslexia may be affected by the distribution of
language centers. It is hard to image that it would not be.
Those taught without phonetics are at risk
Basically there are three educational theories about the teaching of
reading (but currently teachers tend to use a mixture of techniques).
Over the years there has been almost outright war between the camps:
1. phonics - words recognized by decoding them letter by
2. holistic word recognition - words are recognized by learning their
3. whole language - words are recognized by their context.
All of the methods work with at least some children but it seems none
are best for all children. Some students are bored by phonics and turn
off, some never get a creative urge to write without the whole language
approach, and dyslexics need the phonetics to get started. After
reading is mastered apparently all the ways of recognizing words are
used in reading and their contribution to reading speed is additive,
not redundant (66% from the phonics, 16% from the shape of words, 22%
from meaning in context).
I was taught with absolutely no phonics during my first two years at
school (at the height of the whole word fad) and very little phonics at
any time later in school. I learned the bits that I did learn in
elementary school from one teacher and my family at home. My first
encounter with phonetics (with my family) near the end of my second
year in school was a frightening revelation that started me learning to
read. But now that I do read, I think my percentages, if I had to
guess, would be 10% phonics, 40% shape and 50% context.
It does make me angry to think of any children being deprived of any
teaching method because of dogmatic educational theories. Dyslexia is
not the only learning problem. Educational fads are also found in
mathematics, music etc. probably hurt of some of the students.
English speakers are at risk
Some people have the idea that dyslexia only occurs in languages that
are not phonetically spelt. It seems this is not true but the severity
of the condition is worst in a language such as English which is not
English has 1120 ways of writing its 40 sounds (both a sound can have
more then one representation and also a group of letters can represent
more than one sound). Italian has 33 ways of writing its 25 sounds (no
group of letters can stand for more than one sound). The neurological
nature of dyslexia is the same in the two languages but there is twice
the incidence of dyslexia in the USA as in Italy. This seems to be
because the severity is worse in English and therefore it is more
likely to be detected and the person labeled as dyslexic.
I assume that hieroglyphic languages would not show up dyslexia and
that languages using a syllabic representation would have even less
severe effect in dyslexic individuals then would a perfect phonetic
Why no effect on the oral language
To most people the written language seems just a simple extension of
the spoken one. So to them dyslexia is a little baffling. For example,
if you know the meaning of a word and you know that you use it in
speech and it is there written in front of you, why can't you read it
aloud. But actually there is not that much processing in common between
oral and written language. Only the act of pronouncing a written word
or of spelling a heard word really uses both systems.
I have often thought that there must be some advantages to
left-handedness or it would have a much lower prevalence. And the
thought crossed my mind about dyslexia but the more obvious reason that
dyslexia has a high prevalence is that it is a very new disadvantage.
There has not been time to eliminate it from the population.
Human language has evolved slowly over a couple of million years and
has probably had very close to its current form for 100 thousand years
or so. This is plenty of time to integrate verbal language into the
structure of the brain and stabilize its genetics. On the other hand,
written language is about 5 thousand years old and for the first part
of that time it was not phonetic at all but rather 'pictures' of ideas.
It is only in the last few centuries that there has been anything like
general literacy. Taking the world as a whole, literacy is still fairly
patchy. There has been practically no time for an evolutionary process
to integrate written language skills into the language facilities of
the brain. For example, it takes about 50,000 years for populations
that move from tropics to high latitude or vice versa to achieve the
right amount of pigment in their skins. Written language may be 'sort
of stuck on willy nilly' to oral language and therefore prone to
Verbal language doesn't have to be taught; children are able to learn
language if they are with people who speak, without any instruction.
Normal children have mastered all the basic elements of their mother
tongue by age three. We have to wait until children are older and then
spent a few years of formal instruction to give children written
language skills. It seems that the skill is not easy for any children,
but many seemingly normal children have very great difficulty learning
to read and write.
Some more bits and
It may soon be possible to diagnosis the inability to discriminate very
quick sound changes (the assumed cause of most dyslexia) in young
children, long before school age. So in the future we can probably see
training to overcome the dyslexia problem started well before it is
needed for language learning.
Recent research (Walsh) shows disorganized and meandering nerve fibers
affect reading skills.
Periventricular nodular heterotopia is a genetic disease which has
nodules of gray matter deep in the brain in the white matter areas.
Usually gray matter is confined to the surface of the brain and white
matter to the interior. They have reading problems. "In PNH patients,
unlike in normal readers, white matter fibers took circuitous routes
around the misplaced gray matter, and in some cases, didn't organize
into uniform bundles, which could leave regions of gray matter poorly
connected. Importantly, the more disorganized the PNH patients' white
matter, the less fluent their reading."
Other scientists have found white matter disorganization in ordinary
dyslexics. The researchers (Chang) have put forward a theory that
reading depends on white matter organization. "When we read, we need to
take in information visually, hook it up with our inner dictionary of
what letters and words mean, and when we're reading aloud, connect that
with the region that gives us our ability to speak. For smooth,
automatic reading, the white matter is there to connect different
regions of gray matter and allow them to function seamlessly. When
reading fluency is the primary problem, it may be that the areas of the
brain that are important for reading are not connected efficiently,"
There is another type
It seems that another pattern of dyslexia exists. There are children
who can read and do not have difficulty recognizing individual sounds
within words but are nevertheless poor spellers. They are usually
strongly right-handed and they appear to have special problems with
homophonic words ("to here but not sea"). There are indications that
the problem is visual and perhaps involves inter-hemisphere
A little test
At the site here
there is a test of how fast you can read letters. I took the test and
it does seem that I am not very quick at it. Harry did the test and was
at the other end of the scale. There was one set of characters that I
could not see clearly at the top end (300msec). Harry did not see the
effect of disappearing letters even at the bottom end (20msec). I guess
I really do not have the fast perception mode.
I find that my
weight is higher than
my bathroom scales will go! My attempts to lose weight are not working
- panic stations. For the whole of my life - barring exceptional
situations - my weight has slowly crept up. It has dropped when I have
been very ill on a couple of occasions. I had anorexia for a short
period when I was a teenager and lost a lot of weight because I ate
nothing but sunflower seeds most days. One day Mom said I looked like I
had some incurable tropical disease and I was not going to live by
myself anymore; I was going to live at my aunt's. It was caught early
and I started eating proper meals. Twice I have done the Atkins diet
and lost lots of weight and another time I lost some but then stopped
because it was inconvenient to continue. All the rest of the time, I
have gained slowly, except when I took a jump in weight after I quit
smoking. I eat more, I eat less, I have more exercise, I have less, but
I gain weight at a slow even pace. Only very extreme circumstances
reverse or accelerate the pace.
When people say that I real should do something about my weight, I am
not offended. They are just showing their concern for me. But when
people, especially friends, say that there is no problem losing weight,
just eat a little less, I become hurt and angry. Eating a little less
has not worked for me in 68 years. I am too arthritic to want to
exercise more. I had read that the Atkins diet was not healthy and it
was the only one that had ever worked. It seemed that I was in a hole.
My weight made exercise painful but I was not getting the exercise
needed to lose weight without extreme dieting and the diet that worked
was unhealthy. Because I react to gluten, I had already cut out all
things made with flour from my diet. I eat very little sugar as a rule.
There was getting to be very little to avoid. Great! Then I read an
article about how fat people deserved to be hated and discriminated
against because they were unwell and ugly and it was all their fault.
"How does anybody increase their body mass to 16 stone (220 lbs) 'by
accident'? These kinds of weight entail industrious and committed
eating. It's eating as a career. It involves the consumption,
python-like, of about six whole rotisserie chickens a day washed down
with 16 pints of double cream, half a cow and probably the entire
produce of Ireland's potato farms, deep-fried and with a coating of
beer batter." I'm used to that kind of sympathy!
I have 'hit the books' so to speak. I know a bit of biology and so I
thought I should be able to find what is happening and a way out, if
there is one. After looking at close to a hundred science reports I
think I understand what is happening and I am going back on the Atkins
diet along with a few other things.
I am writing a little series on this in my web page - this is the first
part. I may not have all the relevant science but I am sure I have
enough to understand the general picture accurately even if some
details are missing or wrong.
What I think I have is called metabolic syndrome. Being overweight is
just a symptom of something much more dangerous; the condition leads to
diabetes, cardiac problems and other serious problems. I want to avoid
Metabolic syndrome is also called Syndrome X or Insulin resistance. It
is a grouping of abnormal fat metabolism, insulin resistance, high
blood pressure and tissue inflammation. Various medical bodies have
differing definitions but they are all very similar. There is a list of
symptoms of which the patient must have at least a certain number to
meet the definition. Then there are other lists of conditions that are
somewhat confirming. The bodies also have similar lists of
that have a higher risk for people with metabolic syndrome.
Abdominal obesity; a high waist circumference (I have this)
High serum triglycerides (? 15 or so years ago this was OK)
Low serum HDL cholesterol ( ?15 or so years ago this was OK)
High blood pressure (I have this)
High fasting blood glucose and/or high post meal blood glucose/high
blood insulin (? 10
years ago fasting glucose was OK but non-fasting glucose has always
been a little higher than normal - it has not been measured for a very
General obesity (I have this)
Fatty liver (?)
Albumin in the urine (?)
Sleep apnea (mild if at all)
Polycystic ovary syndrome (no)
Cognitive decline in elderly (not since taking high blood
pressure medicine but worrying before that)
Prothrombotic state/ abnormalities in blood flow and coagulation (?)
Proinflammatory state/ markers of inflammation (arthritis
seems to be inflammation)
Old age more at risk (yes)
Hispanic or Asian more at risk (no)
Family history of type 2 diabetes, cardiovascular disease or
hypertension more at risk (brother had all)
Sedentary lifestyle more at risk (yes)
Cardiovascular disease (?)
High LDL cholesterol (?)
Cholesterol gallstones (yes)
Acanthosis nigricans (no)
Gestational diabetes (no)
Increased risk of developing:
Type 2 Diabetes
There is a surprising logic to why these seemingly different types of
symptoms and associations are grouped together. That is the subject of
Resistance, Obesity and Inflammation - the vicious circle
The most important aspect of Metabolic Syndrome is Insulin Resistance.
Insulin is a hormone secreted by the pancreas that stimulates muscle
and liver cells to absorb glucose from the blood and store in as
glycogen or use it for energy. After a meal the level of insulin raises
in the blood until the extra glucose in the blood has been lower by the
muscle and liver. When the muscle and later the liver cells stop
responding to insulin several things happen:
levels of insulin in the blood become abnormally high because the
glucose level remains high for longer. High insulin can cause harm.
- the levels of glucose in
the blood remain high for longer. High glucose can cause harm.
cells respond to the high glucose by converting glucose to fats so that
levels of blood fat rise. High blood fats, especially LDL, can cause
is removed from the blood and stored in fat cells, muscles and in
organs such as the liver. Increased fat storage, especially in the
organs, can cause harm.
abnormal glucose and fat metabolism can produce periods of very low
energy and of hunger as a result. Lack of exercise and over eating can
So insulin resistance increases weight gain and leads to obesity. But
it is not that simple because being overweight is one of the things
that increases the resistance to insulin. We can look at it one way and
see that insulin resistance is the cause of obesity and we can look at
it the other way and see that obesity is the cause of insulin
- obesity causes
inflammation. Inflammation can cause general harm.
are released by inflammatory macrophages. These are what cause insulin
resistance in muscle. They also affect liver cells and fat cells in a
stored in the liver is especially dangerous and causes more disruption
of liver functions leading to increased resistance to insulin.
The only way out of this terrible spiral is to eat a low carbohydrate
diet and to exercise. A low carbohydrate diet means that there is much
less glucose in the blood after a meal. (Starches and sugars are
converted into simple sugars, mostly glucose, in order to be absorbed
into the body). Less glucose stimulates less insulin production. Less
glucose means less is converted to circulating fat (triglyceride,
saturated fatty acids, cholesterol, LDL). A 'high carb' diet results in
more fat in the blood after a meal than a 'high fat' diet. 'Very low
fat' diets (but not just 'low fat' diets) cause an increase in blood
fats. This is counter intuitive; you would think you would cut fats in
order to have less fat in the blood but, no, it is important to cut
carbohydrates rather than fat. Less circulating fat means there is less
fat for fat cells to store away.
Exercise has the result that the fat that is circulating in the blood
is taken up by muscle cells and oxidized for energy. The muscles end up
taking in more fat than they need and store the excess as IMTG
(intramuscular triglyceride). Again this lowers the fat available for
fat cells to store away and also makes the muscle cells slightly less
resistant to insulin. It is not a question of getting fit, it is just
exercise that is needed. Even Tai Chi, which is hardly strenuous, is of
some benefit. If the exercise is shortly after the meal it is more
It is not hard to see how metabolic syndrome gets worse and involves
more organs (heart, liver etc.). And it is not hard to see how it is
hard to reverse metabolic syndrome. But how does it start in the first
place. This seems to be a genetic thing. There are a lot of genes
controlling various aspects of metabolism that can give someone a
tendency to fall into the spiral. One theory has it that fat
accumulation is favoured by genes selected for adapting to a cold
climate in the stone age - very little heating and a sometimes lack of
food. Fat can be oxidized in a way that is not connected with muscle
contractions but simply creates heat. Those genes for cold adaptation
do not work well in good warm housing and clothing, abundant rich food
and less need for strenuous work.
A particular study shows just how much of a genetically thin person
someone can be. "Sims put thin people on a forced-eating diet. Sims
wanted to know whether people 'would have a hard time gaining weight.
In his first experiment with college students, Sims found that these
subjects found it all but impossible to gain much weight; no matter how
much they tried to eat, they just could not become obese. Sims reasoned
that perhaps the students raised their activity levels and were burning
off more calories. He thought of the perfect subjects, people who
really have no chance to cheat and burn off calories: prisoners. The
study volunteers in prison did indeed gain weight. But producing
obesity turned out to be much harder than Sims had anticipated. The men
increased their weight by 20 to 25 percent, but it took four to six
months for them to do this, eating as much as they could every day.
Some ended up eating 10,000 calorie a day, an amount so incredible that
it would be hard to believe, were it not for the fact that the
researcher study had attendants present at each meal who dutifully
recorded everything the men ate. In this and other similar experiments,
Sims showed that men gained weight at different rates, that metabolism
rates change, and together these play a central role in the biological
differences between naturally fat versus thin people. The implications
were clear. There is a reason that fat people can't stay thin after
they diet and that thin people can't stay fat when they force
themselves to gain weight. The body's metabolism speeds up or slows
down to keep weight within a narrow range."
It is also the case that people are genetically more or less prone to
inflammation and therefore more or less likely to fall into metabolic
syndrome. Inflammation is part of the immune response, protecting the
body from pathogens. But it can attack the body's own cells causing
various autoimmune conditions. The longer the metabolic syndrome lasts,
the more likely there will be a progression to diabetes, heart disease,
liver disease or kidney disease.
There are a few pieces of advice about diet that are helpful:
carbohydrate reduces triglyceride, saturated fatty acids, cholesterol,
cytokines, chemokines, adhesion molecules, glucose and insulin in the
blood. This response to carbohydrate is almost a definition of
carbohydrates that are most dangerous are those with a high glycemic
index (meaning they are digested and absorbed faster than other
carbohydrates giving more of a glucose peak in the blood). Examples of
high glycemic index foods are unrefined sugars, white breads, unrefined
corn products, potatoes. Low glycemic carbohydrates are found in whole
grain breads, brown rice and non-starchy vegetables.
made 'trans fats' are bad for us. Some naturally occurring
are good for us. Trans vaccinic acid is found in dairy and meat
products. It reduces total cholesterol and LDL. It also reduces the
production of chylomicrons. (particles of fat that form in
intestine following a meal, travel through the lymph and get dumped
into the blood stream at the thoracic duct). This is the raw dietary
fat before it has been processed by liver, fat cells or muscle.
Presumably less chylomicrons means less fat actually absorbed from the
wine contains resveratrol which activates SIRT1 enzyme and therefore is
likely to increase insulin sensitivity. Low doses have an effect and so
moderate consumption is beneficial.
chocolate especially only lightly sweetened and containing plant
sterols as well as flavanols lowers cholesterol, LDL and blood
pressure. This has not been shown for sweet milk chocolate.
drinks, both diet and containing sugar, are not good for metabolic
syndrome or for weight loss. Fruit juice and milk are good.
- oil from fish
(polyunsaturated) is better than from olive and nut (monounsaturated)
and they are both better than saturated fat.
Here are a few of
the more interesting bit and bobs from the literature.
Fat tissue produces hormones
We tend to think of fat as inactive. But fat (adopose tissue) is now
recognized as an endocrine gland at the heart of a complex network
influencing energy regulation, glucose and lipid metabolism, blood
pressure, immune response and reproduction. Virtually all known adipose
secreted proteins are dysregulated when the fat mass is markedly
altered, either increased in the obese state or decreased in
is a hormone produced by fat tissue that regulates appetite and
metabolism. The gene of the leptin receptor is one that shows clear
differences in cold adapted populations. The 'cold' version of the
receptor gene is associated with increased respiratory quotient (using
oxygen and releasing carbon dioxide) which would allow more heat
production. This version is also linked to lower body mass index, less
abdominal fat and lower blood pressure and so is protective against
metabolic syndrome. Mice that have been bred to lack the leptin hormone
are extremely obese. Lower body fat produces lower leptin levels. When
working properly this system should be able to sense the bodies amount
of fat and adjust its intake, use and storage appropriately. There are
a number of receptors as leptin affects a number of different organs
including the brain. Cells can become resistant to leptin; especially
in obese people there are high levels of leptin but it is not effective.
hormone is produced only by fat cells but opposite to what would be
expected, the level circulating in the blood is inversely correlated
with body fat and therefore reduced in obesity. It lowers glucose
production and stimulates cells to use fats. It suppresses the
conditions leading to type2 diabetes, obesity, fatty liver and
antherosclerosis. It reduces protein loss into urine, reduces oxidative
stress and inflammation.
is produced by fat cells but also by other tissues. There is a
scientific disagreement about whether resistin is the link between
obesity and insulin resistance. It is clear that there is a connection.
Levels in the blood rise with waistline fat accumulation and it
promotes inflammation. Insulin inhibits the production of
Cytokines are produced by fat cells. Cytokines are messenger molecules
between cells. One of many cytokines from fat cells is interleukin-6,
an inflammatory IL. A deficit of IL-6 increases insulin resistance,
leptin resistance and obesity. IL-6 production is stimulated by
- Adipsin is acts like a
thermostat for fat production. Reduction in adipsin can result in
(acylation-stimulating protein) increases the production of insulin
when blood glucose is high but does not have any effect on insulin
is produced by the liver and fat cells. Normally it is modified by
renin in the kidneys to produce angiotensin-1 and then by ACE in the
lungs to produce angiotensin-2. Angiotensin-2 produces constriction of
blood vessels and high blood pressure but it also has effects on blood
clotting, the adrenal gland, the brain and the kidneys.
plasminogen activator inhibitor is produced by the lining of blood
vessels and by fat tissue. It inhibits the breakdown of blood clots
such as those in thrombosis.
- Some steroid hormones
There are articles in the literature that link disruptions of circadian
rhythms with metabolic syndrome. Aging, jet lag, steep disorders, and
shift work may all have effects on weight gain. Seasonal
seem to be implicated.
The two big effects of appetite are leptin and ghrelin.
Leptin binds to the 'appetite centre' in the hypothalamus and
suppresses appetite. As leptin is produced by fat tissue this should be
a good feedback system. However, leptin resistance can develop (like
insulin resistance). Ghrelin is produced by an empty stomach and
stimulates appetite. Ghrelin production is also increased by lack of
sleep and leptin production is decreased during sleep. There are a
number of less well studied appetite influences.
Appetite is a real problem for many obese people. Food intake is not
voluntary in the long term. You can hold your breath voluntarily for a
short period of time and then you gasp for air. You can not take in
liquid voluntarily for a medium period of time and then you must drink.
You can not take in food voluntarily but not for ever. Hunger is one of
the most powerful biological signals from an ancient brain area. It
cannot be fought with just will power in some people.
disease. That is one of the reasons that my memories of her differed
from my Mother's and those of others, older than me. I only just manage
to remember her before the Alzheimer's. When I was 16-17 she had all
the signs of the disease and was with Aunt Marjorie and Uncle Walter. I
remember her most clearly from that time as I lived in the house. When
I was 12-13, I lived with Grandma and Grandpa in Yellowgrass. As far as
I know, no one thought she was ill then, just getting old. But in
hindsight, the disease had already started. She puttered around in a
distracted sort of way, accomplished very little and said very little.
This was not the woman who was a marvel of efficiency and know-how. She
was not how my mother, aunts and older cousins remember her. I lived
with my grandparents when I was 7-8 and she was active then. It took
about 10 years for her to go from her normal self to being hospitalized
with dementia and more years to die.
The time in Regina with Marjorie and Walter was disturbing. Grandma
called me May and thought I was my mother. She walked through the house
and picked up little things (pens, keys, books and the like). She
carefully wrapped each item she found in kleenex and put it somewhere
(a drawer, behind a picture, under a pillow etc.). We were forever
looking for things she had 'put away'. The most heartbreaking thing was
that she would sit with a little pillow and rock it. She though she was
looked after her dead daughter Marion. She rocked Marion at night for a
number of years before Marion finally died and she was reliving that
time of her life. Uncle Calvin's wife at the time bought a very
realistic and life-sized doll for her. Grandma rocked it. The problem
was that every once in a while she seemed to realize that she was
looked after a doll and not a baby. This would throw her into a
terrible rage and she would hurl and doll across the room and then
shout about her disgrace for a while. This didn't happen with the
little pillow - I suppose because she was not forced to think she had
been playing with it. I tried to hide the doll when this happened but
soon she would be looking for Marion and worry about where she was. I
would have to give her the doll.
(a sidelight: Oh how I hated that doll. When Grandma died many things
were returned to the people who had given them and so the doll was
given back to Olla and she immediately gave it to me 'to remember
Grandma by'. All my dealings with Olla to that point had been very
unsatisfactory and so I simply thanked her, waited until she was gone
and put the doll in the garbage. I have never regretted throwing the
doll away and I still avoid contact with dolls that look as realistic
as that one.)
Many years later, my Mother started to be forgetful. She died of cancer
before her cognitive impairment got very bad. But it did have the
hallmarks of Alzheimer's rather than just old age. She was not aware of
the extent of her memory loss and told me several times that her
husband, Melvin, was telling lies about her. It hurt her deeply. He was
not, of course, but I could not convince her of it. She did not realize
she forgot and that she was doing the things Melvin said she was doing.
She was beginning to lose some of her intellectual ability too. We
played games: scrabble, the 5 letter game, tile rummy. Her ability to
play these games took a sharp fall but again she did not realize the
extent. She became interested in fewer things and was showing
depression. Melvin had to start doing the cooking and laundry because
she made mistakes with the stove and washing machine. She did not
wander but that was because she had limited mobility. I have no doubt
that my Mother had the first stages of Alzheimer's.
So when my memory failed me a bit, I decided to look into Alzheimer
research. My memory improved when my blood pressure was treated, but it
was still a little scare.
Alzheimer's is a dementia usually found in older people. It starts with
memory loss, difficulty in forming new memories and poor learning.
Later people suffer confusion, anger, loss of older memories and
skills, and difficulty with language. Finally people loss bodily
functions and die. The whole course of the disease takes many years. It
is difficult to diagnose in its early stages and can only be
definitively seen in an autopsy. Current treatments are usually fairly
ineffective. There is no cure.
The burden on care-givers and relatives/friends of patents is terrible
and the cost of care is very high. Alzheimer's is an important disease
for medicine to tackle, both because of its effect on individual
sufferers, their relatives and friends, and the health care system
finances. So there is a great deal of current research aimed at
understanding the disease and finding preventions, treatments and cures.
Physically the disease shows accumulations (plaques) of beta-amyloid,
fibrillary tangles within neurons, death of neurons and shrinkage of
grey matter. These can be seen in autopsy. There are two types of
Alzheimer's: a rarer, early onset type that runs in families; and a
commoner type that occurs in old age is a not as clearly inherited.
There are similarities between Alzheimer's and other forms of dementia:
Parkinson's, vascular dementia, Creutzfeldt-Jakob disease (human mad
cow disease) and other rarer dementias.
There have been a number of theories about the causes and development
of Alzheimer's. The favourites today vary in many details but have the
following general picture in common.
1. A small bit of protein (a peptide) is produced badly
(genetically wrong, in too high an amount, cut wrong, or folded wrong).
During this faulty process a toxin (maybe the peptide) affects neurons.
In more detail - A large protein, amyloid precursor
sticks through the cell membranes of neurons. It seems to be an
important molecule but its function is not known. The part of this
molecule that sticks outside the cell membrane is cut off by the beta
secretase enzyme leaving the rest still sitting through the membrane.
Gamma secretase splits the remaining molecule from within the membrane
to produce a beta-amyloid peptide free outside the cell. Again the
reason for this processing is not known. Beta-amyloid is soluble and
can be from 39 to 43 amino acids long. The type that is 42 units long
can undergo a refolding and can form small aggregates, then insoluble
fibrils and finally the fibrils can aggregate into plaques. Some parts
of this process (such as a component of secretases has been conserved
unchanged through both animal and plant evolution) are extremely
important but of unknown function. Amyloid plaques are found in other
diseases such as Creutzfeldt-Jakob and in normal senile brains, so the
plaques themselves do not dictate the nature of Alzheimer's but they
are a defining part of the condition. A form of beta-amyloid (not the
newly produced or the final plaques but some form between - a soluble
adhesion of very few molecules, perhaps three) is definitely the
trigger for the start of memory loss. It has been shown that
beta-amyloid blocks the function of a key signaling receptor, the
nicotinic acetylcholine receptor in the hippocampus, the seat of
memory, motivation and emotion in the brain.
2. The faulty peptide molecules stick together to form fibers
and then plaques. The plaques appear to start an inflammation.
In more detail - Surrounding neurons in the brain are other cells that
outnumber them about 10 to 1, the glia cells. These are important in
guiding the development of neurons, supporting and feeding them,
insulating their electrical fields, repairing them and also acting as
the brain's immune system. There is a barrier between the brain's
fluids and the blood (the blood-brain barrier) and so the normal immune
system does not operate in the brain. Microglia and astrocytes are
attracted to plaques. They do not destroy the plaques but appear to be
part of an inflammation response and attempts to protect and repair the
3. The toxin, inflammation or some other process disrupts the
transport mechanism within neuron axons leaving 'tangles'.
In more detail - Cell have a sort of skeleton made of microtubules. In
the long axons of nerve cells the microtubules transport chemicals
between the cell body and the synapses at the very end of the axons.
The protein tau is associated with microtubules and acts like railway
ties between pairs of microtubules. Tau is regulated by having
phosphate added or subtracted from its structure. In Alzheimer's (and
Creutzfeldt-Jakob, Parkinson's and other dementias) tau is
hyperphosphorylated and the microtubule structure collapses.
Neurofibrillary tangles form within the neurons. Without a
cytoskeleton, neurons cannot function as nerve signal processors.
4. Affected neurons die. Neurons in the hippocampus are the
first to be affected.
In more detail - Cells can either die in a pre-programmed tidy type of
suicide, apoptosis; or they can be murdered in a very messy manner,
necrosis. In this case neurons die by apoptosis. Some event (damage
they sustain or some signal they receive) causes them to wind-up all
their cellular processes and shrivel up. Neuron death in a series of
regions starting with the hippocampus would account for the series of
symptoms that follow simply memory loss and mild cognitive impairment:
loss of intelligence, personality and bodily control. Other dementias
have different patterns of neuron death.
Also - Some genes, iron, lead, infections, free radicals etc. may be
but they are not part of the agreed picture yet. Calcium signaling is
definitely implicated as an important part of the story but it is not
clear how. Cholesterol signaling has been implicated.
Without an understanding of how memories are formed, conserved and
removed, it is difficult to understand a disease of memory.
Existing medicines not very effective
1. The oldest hypothesis is the "cholinergic hypothesis" that
Alzheimer's begins as a deficiency in the production of the
neurotransmitter acetylcholine. Early medicines were
acetylcholinesterase inhibitors (galantamine, donepezil, rivastigmine)
and this was a little helpful with symptoms but did not halt, reverse
or cure the disease. The hypothesis is no longer being pursued.
2. Excessive glutamate, another neurotransmitter, can
overstimulate the brain and lead to cell death. A receptor antagonist,
memantine, is sometimes used to stop this problem and can help somewhat
in the later stages of Alzheimer's.
3. Anti-psychotics are used to manage behavior but not for the
4. The drugs often given for incontinence can make Alzheimer's symptoms
Possible treatments on the way
A hundred or so possible medicines are being investigated. With so much
activity and so many leads, there may soon be effective medicines. It
is not clear yet which theories are going to be fruitful.
1. The enzyme gamma-secretase that makes the fateful cut
be inhibiting because it is involved in cutting other important
proteins. Ways are being looked for to interfere with the production of
beta-amyloid without touching gamma-secretase.
a) Inhibiting beta-secretase and therefore blocking the cutting of APP
might work. A drug to do this is in trials.
b) Gamma-secretase modulators (GSM) reduce the amount of long sticky
beta-amyloid and increase the amount of short non-sticky instead. They
work in three ways at the same time: inhibit production of long
beta-amyloid, block aggregation of beta-amyloid, and increase
production of shorter beta-amyloid which also inhibits aggregation. GSM
does not act on the enzyme but on the protein itself to give it a
different structure and thereby change the point of the enzyme's cut.
One GSM being tested is tarenflurbil or r-flurbiprofen.
c) There are groups looking for a way to affect the production of BACE1
or A-secretase in the belief that it is the faulty cutting by this
enzyme (found to be increased in Alzheimer's) that is the key to
reducing the faulty beta-amyloid rather than gamma-secretase.
2. It appears that the plaques of beta-amyloid are not
to the disease but that beta-amyloid in smaller aggregates is. So drugs
are sought to prevent aggregates and even clear them.
a) A small molecule called DAPH attaches itself to amyloid fibers and
stops their growth.
b) Transthyretin (TTR) protein is naturally produced by diminishes as
people get older. TTR transports vitamin A and thyroid hormone and can
bind to beta-amyloid to stop toxicity and plaque formation. The search
is for way to increase TTR production in aging.
c) The omega-3 fatty acid, docosahexaenoic acid (DHA), from fish oil
increases the production of a protein LR11, which is low in
Alzheimer's. LR11 prevents plaque formation. It is effective in animals
and human tissue culture. Humans do not make DHA although it is the
most abundant essential fatty acid in brain tissue. All DHA comes from
d) Vaccines or stimulation of immune system to recognize and attack
beta-amyloid or plaques has been tried. Trials on the first vaccine
were stopped as it made the patients more ill through inflammation in
the brain. Another vaccine has been shown to reduce plaques but it did
not improve symptoms, showing that the plaques are not themselves
dangerous but an earlier from of beta-amyloid. A third vaccine has also
failed. Some vaccine ideas have not yet been tested. A vaccine based on
the potato virus might work because it is not human tissue but
resembles beta amyloid. Another packages some beta amyloid that would
trigger the immune response with interleukin-4 to stop inflammation.
e) PBT2 (derived from clioquinol) counteracts the production and
build-up of beta amyloid. It seems to interrupt the interaction between
metal ions and beta amyloid and return levels of zinc and copper in the
brain to normal levels. Early trails are promising.
3. An extract of grape seed is being tested for controlling
beta-amyloid production. The major compounds in the extract are
catechin and epicatechin found in wine, tea, chocolate, and some fruits
4. It has been found that a molecule p75 neurotrophin receptor
is necessary for beta-amyloid to cause nerve cell death. Blockers of
p75 are being tested in animals.
5. The tau tangles may be the source of many symptoms in
Alzheimer's although it is not a primary cause. Tau effecting drugs are
being pursued to provide good treatment rather than cure.
a) Agents that can inhibit or reverse the tau tangles include an
extract of cinnamon.
b) Thiazoline is an enzyme inhibitor that effectively tricks the brains
own enzymes into installing a sugar on to tau in place of phosphates.
c) AL-108 is under test. A protein ADNP is made by glia cells to
protect neurons under threat. It is too large to pass the blood-brain
barrier but a small part of it (NAP) appears to be protective. It
appears to stop the death of cells due to the destruction of
microtubule transport by tau dysfunction.
d) Pin1 (prolyl isomerare) promotes the removal of phosphates from tau
and detangles the protein. It also inhibits the production of toxic
beta-amyloid. Pin1 activity is inhibited in Alzheimer's by stress and
other conditions. Pin1 has the opposite effect in frontotemporal
dementia whose primary cause is a tau mutation.
e) The drug Rember gave an 80% difference in the rate of mental decline
in trails. It is methylthioninium chloride or methyline blue which has
been used in various ways in medicine since the 19th century. It was
tested because in dissolves tau tangle filaments in a test tube. In the
brain it blocks the toxic effects of aggregated tau. It has completed
phase II trial. It slows or even stops cognitive decline, increases
blood flow and halts the spread of tangles.
6. Reducing inflammation might help slow Alzheimer's.
a) A number of non-steroidal anti-inflammatory drugs (NSAIDs) are being
tested. Ibuprofen has shown promise. Some but not all studies have
shown naproxen and aspirin to be equally effective.
b) The drug etanercept used to treat inflammation and arthritis has
been tested on Alzheimer's with good preliminary results. Etanercept
administered by a unique perispinal method reduces elevated TNF-alpha.
TNF-alpha is an important part of the brain's immune system. There have
been was tests with good results by without the controls needed in
c) A new anti-inflammatory drug called CN1-1493 is in testing. It may
be more effective than ibuprofen against Alzheimer's.
d) Dimebon was a Russia allergy medication that is no longer in use. It
appears to help Alzheimer's patients with memory, thinking and
behaviour. It will enter trails soon.
7. Enkephalins are part of the endogenous opiod system which
modulates learning and memory. They are produced by cells in the brain
areas affected by Alzheimer's and are released with neurotransmitters
like glutamate at synapses. The precursor of enkephalins is increased
in early stages of Alzheimer's. It is not known if it is a cause or
compensation, but compounds that blocked opoid receptors reduced
cognitive damage. Ways to limit enkephalin production and signaling are
being looked for.
8. Oxidative stress from free radical is thought by many to be
involved in the damage.
a) There were clinical trials of Vitamin E to see if antioxidants and
free radical scavengers were beneficial but the results were
disappointing. The hypothesis was that free radicals were causing blood
vessel damage. Other drugs limiting vascular damage are being looked
at. Vitamin E does seem to prolong life in Alzheimer's patients without
improving the symptoms.
b) Mitochondria, the energy producing organelles in cells, become less
efficient with age. This leads to less ATP energy produced, less oxygen
used, more free radicals released. This accounts for an energy deficit
in the Alzheimer brain. It was thought that estrogen protects against
Alzheimer's by protecting mitochondria, but recent studies show that
estrogen is not effective against Alzheimer's. Other drugs that protect
mitochondria are being sought.
c) Oxidative stress from the accumulation of iron in the brain may be a
trigger for Alzheimer's. CSF can contain reactive and non-reactive
iron. Reactive iron rises from normal with mild impairment and then
falls abruptly with the start of Alzheimer's; total iron stays level.
Iron may be sequestered in amyloid plaques. This is being studied in
hope of understanding the role of iron so that it could be treated.
9. It seems that cholesterol is somehow involved in
a) The cholesterol lowering drug, lovastatin can also reduce nerve cell
death in Alzheimer's. The statin stimulates nerve cells to produce a
receptor molecule for tumor necrosis factor-alpha. TNF-alpha has a
strong beneficial effect on nerve cells.
b) A link between cholesterol lowering statins and dementia is not
settled. Some studies show improvement with statin medication and some
the opposite. Glial progenitor cells (stem cells of the brain) can
become the various types of glia cells. The progenitor cells use the
cholesterol-signaling pathway in development. Some statins spur
progenitor cells to become oligodendrocytes rather than astrocytes.
This would give fewer progenitor cells and an imbalance in the glia
cells produced. This may be true of some diabetic medications too.
c) Apolipoprotein E (ApoE) is a cholesterol transport protein and also
a regulator of brain beta-amyloid levels. It is likely that regulation
of ApoE activity with influence beta-amyloid deposition and clearance.
The genetic form of ApoE affects its ability and so does the number of
lipid molecules it carries. Activation of liver receptors (LXRs)
enhances the ability of ApoE to degrade beta-amyloid.
d) High cholesterol can damage the blood-brain barrier and caffeine can
provide protection from this damage (equivalent of one cup coffee a
day). The barrier is weakened in Alzheimer's which may be why high
cholesterol is a risk factor.
10. Endocytosis is one way in which a cell takes in chemicals.
The cell membrane is sucked in to make a bubble enclosing some of the
liquid that was outside the cell. It is pinched off and becomes part of
the inside of the cell. Shutting down endocytosis in Alzheimer mice
dropped the levels of beta-amyloid dramatically. Most of the
endocytosis that was stopped was that involved in normal nerve cell
communication at the synapses. The endocytosis is essential to nerve
function. So the search is for drugs that can stop the membrane binding
the precursor to beta-amyloid production, APP, so that it is not taken
in during endocytosis.
11. Culling of memories goes on in the brain and some
researchers believe this is hyper-activated in Alzheimer's. There is a
biochemical 'switch' associated with the cleavage of amyloid precursor
protein by capases. In Alzheimer's the 'switch' gets stuck in the
breaking memories mode. It is not the beta-amyloid that is at fault by
the process it is intended to regulate. The researchers are looking for
a way to affect the down stream processes.
12. There is some indication that ginkgo biloba extract may be
13. A cocktail of nutrients that increase dendritic
synapses is in the trial. The idea is to help neurons recover function
when damaged. The cocktail contains the following. Omega-3 fatty acids
are not produced in the body but are found in a variety of sources,
including fish, eggs, flaxseed and meat from grass-fed animals. Choline
can be synthesized in the body and obtained through the diet; it is
found in meats, nuts and eggs. Uridine cannot be obtained from food
sources, but is a component of human breast milk and can be produced in
14. There is a lot of work concentrating on calcium
Recent indications that dysfunction of a calcium channel for calcium to
enter neurons is the earliest event in the development of Alzheimer's.
Researchers will be looking for way to compensate for this calcium
signaling fault. Calcium is important to brain growth, learning and
memory. It is involved in cell death too. One drug lead is to inhibit
an enzyme called calcineurin to control calcium overload which can
15. Proteins called calpains are involved in memory formation.
Two drugs that inhibit calpains improve Alzheimer mice. There are
indications that the drugs restore signaling between cells in the
16. Calorie restriction increases proteins known as sirtuins
which seem to be responsible for reduction of Alzheimer's symptoms in
mice. SIRT1 is a sirtuin being studied.
17. One group has taken skin cells from patients, cultured
genetically engineered them to make human nerve growth factor and
injected them into areas of the brain where cells were dying due to
Alzheimer's. There was improvement but time will tell if it lasts.
Better diagnosis is ahead
There is also work underway to make diagnosis easier, more accurate and
possible earlier in the disease's course. Currently diagnosis relies on
reviewing medical histories, administering physical exams, and taking
into account the results of a battery of neuropsychological assessments
that measure cognitive performance. After death a definitive diagnosis
can be made at autopsy.
1. Until now accumulation of beta-amyloid was only found on
autopsy. A project has demonstrated that a neuro-imaging scan called
PiB PET can be used to identify amyloid and therefore individuals who
may develop Alzheimer's disease up to 18 months earlier than all
currently available diagnostics. Using positron emission tomography
(PET) and a radiotracer known as Pittsburgh Compound-B (PiB) that is
capable of binding to plaques found in the brains of AD patients.
Unfortunately plaques are found in patients with other dementias and
simple old age. But by showing which areas of the brain are affected,
this procedure may be able to differentiate between conditions.
2. Redox-active iron levels in the CSF increased with the
of cognitive impairment from normal to MCI subjects, while AD patients
showed an abrupt decrease to levels close to zero. However, no
difference in the total CSF iron was found between the different
groups. This discovery offers the possibility to monitor iron levels in
the CSF in relation with cognitive impairment and perhaps be used as
part of a battery of biomarkers for an early diagnosis of these
3. A company using the proteomics method has patented several
blood proteins associated with neurodegenerative disease and a test
that measures a suite of 59 protein biomarkers. They say the test can
distinguish between Parkinson's, Alzheimer's, and Lou Gehrig's. The
test is being tested. Another group is trying to identify markers in
blood and spinal fluid that can be used to show the early 'silent'
stage of Alzheimer's and to track the progress of the disease. They
hope for a screening test that can be used in massive programs like
mammograms in example.
4. Fluorodeoxyglucose positron emission tomography (FDG-PET)
measures blood glucose metabolism in the cerebral cortex. Less glucose
uptake means less active cells. Using this technique shrinkage in
various parts of the brain can be calculated. This may help in
diagnosis of Alzheimer's. Comparing the change in various areas of the
brain allow different dementia to be differentiated. In Alzheimer's
disease, nerve cell death and tissue loss cause all areas of the brain,
especially the hippocampus region, to shrink. MRI with high spatial
resolution allows radiologists to visualize subtle anatomic changes in
the brain that signal atrophy, or shrinkage. But the standard practice
for measuring brain tissue volume with MRI, called segmentation, is a
complicated, lengthy process. Using sophisticated computer programs the
accuracy of this method is improved dramatically.
5. Work is going on to detect alterations in the optical
properties of the brain using near-infrared light which passes through
the skull and brain without harm. How the light is scattered can
identify the amount of plaques.
6. Preliminary studies indicate that Alzheimer's appears to
involve the formation of strongly magnetic iron compounds. These
compounds have a strong MRI signal and may by a way to diagnose
7. A technique called functional magnetic resonance imaging
(fMRI) examines the patterns of brain activity. Networks can be found
with this technique and Alzheimer's patients had fewer functional hubs
in their networks. A compensating increase in connectivity in the
frontal lobes in Alzheimer's was seen. Increase accuracy of diagnosis
is likely to develop with this method.
8. "Combining a megapowerful magnet, multiple detectors, and
carefully tweaked contrast, a new MRI technique developed at the
National Institutes of Health (NIH) provides an unprecedented look at
the fine structure of the brain. Using an MRI machine equipped with a
magnet more than twice as powerful as one in an ordinary device, the
researchers created a way to measure the magnetic field changes caused
by tissue properties to optimize contrast in the image. Picking up on
such differences may help researchers look more deeply into the brain's
subdivisions, allowing them to map it in greater detail… It may also
bring about advances in diagnosing diseases like Alzheimer's and
multiple sclerosis, both of which involve abnormal iron accumulation in
9. The size of the brain's fluid-filled cavities, ventricles,
becomes larger with cognitive impairment and Alzheimer's. MRI scans can
measure changes in brain ventricle size and with recent computer
programs to measure the ventricles quickly and accurately, the method
could be used to follow the progression of the disease.
Because Alzheimer's may exist for some time before symptoms are
noticed, it is difficult to know which things that seem to come with
Alzheimer's are causes and which are consequences.
There are two types of Alzheimer's. (a) The early onset familial type
is explained by mutations in three genes (amyloid precursor protein
gene and two presenilins genes, all of which result in increased
beta-amyloid with 42 units. (b) Late onset sporadic Alzheimer's also
has genetic risk factors. Half of patients have a particular allele of
the apolipoprotein E gene (APOE). There are other genes that affect
Four genes that control tau have been found to not be risk factors for
Alzheimer's but to be risk factors for earlier symptoms of the disease
if the person does get Alzheimer's.
Another gene that has been implicated as a risk factor is the TRPC4AP
gene. It is believed to regulate calcium and calcium dysregulation can
result in inflammation, nerve call death and
possibly plaque production. A mutation of a gene, CALHM1, for a calcium
receptor may be a risk factor.
The strongest risk factor is age. In the US, 5% of people 65-74 have
Alzheimer's, 20% of people 75-84, and 50% of people 85 and older.
Incidence is lower in some other countries but is still higher in old
Women are more prone to Alzheimer's. The general picture is different
as well. "Men with mild cognitive impairment were more likely to be
overweight, diabetic, and to have had a stroke. Men who had had a
stroke were almost three times as likely to progress to Alzheimer's.
Women with mild cognitive impairment were more likely to be in poorer
general health, disabled, suffering from insomnia and to have a poor
A bad diet seems to be a risk factor. There may be advantages to a
Mediterranean diet (bread, cereals, olive oil, fish, and red wine).
There may be advantages to vitamin B, C, and folic acid. Lack of omega
3 fatty acids is definitely is risk factor. Cur cumin in curry appears
to have some protective effect.
5. Brain size and use:
There seem to be a risk from low levels of social interaction and
intellectual activities. This may be simply a question of the early
stages of Alzheimer's being hidden and therefore an effect not a cause.
There is also an association with small brain size especially smaller
hippocampus. It may be that neuron death takes longer to affect a brain
with more neurons to start with.
6. High blood pressure:
Hypertension appears to damage the blood vessels in the brain. It can
also cause a type of mild impairment (reversible) that is not related
to Alzheimer's. Hypertension may also be associated with Alzheimer's.
7. High cholesterol:
High levels of cholesterol seem to be a risk factor. High cholesterol
in a person's 40s increases the risk of Alzheimer's in old age.
This seems to be due to high glucose levels and damage to blood vessels
in the brain. Diabetes in mid-life increases the risk of Alzheimer's
Depression was thought to be an early symptom of Alzheimer's but is now
thought to be a risk factor that predates the condition. Perhaps the
brain is less resiliant to damage when depressed. Perhaps the
hippocampus becomes smaller. Perhaps anticholinergic drugs are a risk.
The risk is greater in women.
Stroke as a risk factor applies mostly to men. After a stroke the
amount of beta-amyloid produced increases.
This may or may not be a risk factor. There is some evidence for
spirochetes, Chlamydia pneumoniae and Herpes simplex virus type 1. The
route may be chronic inflammation.
12. Short arms and legs/ early nutrition:
People with shorter arms and legs are more likely to get Alzheimer's
and this is thought to be because of poor nutrition in the first two
years of life.
13. Anesthesia with desflurane and low oxygen levels combined
(not either alone) is a risk factor.
14. Heavy drinking and heavy smoking:
These do not increase the risk of Alzheimer's but lowers the age of
15. Perhaps some metals:
16. Lack of exercise
The Problem of Grief
The hardest thing for the loved ones of Alzheimer victims is that they
are often caring for the person for a long before they are taken into
professional care in a home or hospital. It is almost unbearable for
1. The disease robs the care-giver of the support and
companionship they once had from the patient.
2. There is no hope of improvement or even of things not
3. There are often financial problems.
4. There is very little time for the caregiver to relax from
5. Much of the work is physically hard.
6. The sufferers become very difficult to handle and upset or
even attack their caregivers. They are often confused, angered,
depressed. They say and do hurtful things.
7. The biggest problem is losing someone and grieving for them
for years before they actually die. This is called 'anticipatory grief'
and 'ambiguous loss'.
8. Others do not understand the difficulties, caregivers can
isolated and sometimes they are blamed for not providing enough care.
It seems I have
celiac disease. After
years of trying to find what would stop my diarrhea I have discovered
that avoiding gluten is the answer. So I am one of those many people
who have seen a number of doctors, had many tests and medicines,
followed lots of advice. These helped some but really not a great deal.
I had undiagnosed celiac, probably for 30 or more years. A year or so
after I heard that an adult cousin had celiac and I got used to the
idea that adults could have it, it suddenly occurred to me that …oh,
maybe me. I looked to see if it had an inherited tendency and it does.
Further that tendency is shared with other autoimmune diseases like
type 1 diabetes. My father and uncle had type1 diabetes, my mother
rheumatoid arthritis; two cousins have celiac as children and one at
least as an adult. I stopped eating gluten and started improving.
Put very simply, celiac is an allergic reaction to gluten (from wheat,
rye and barley - possibly oats) that damages the small intestine so
that it causes malnutrition and diarrhea. That is just the simply
story. The symptoms are extremely varied and the cause is a little more
complicated than a simple allergy. There is only one treatment - avoid
eating any gluten.
Here are the symptoms:
bloating and pain
chronic diarrhea or
pale, foul-smelling, or
weight loss/weight gain
unexplained anemia (a low
count of red blood cells causing fatigue)
bone or joint pain
tingling numbness in the
legs (from nerve damage)
missed menstrual periods
(often because of excessive weight loss)
delayed growth in children
failure to thrive in
pale sores inside the
mouth, called aphthous ulcers
tooth discoloration or
loss of enamel
itchy skin rash called
Here is a summary of the disease:
1. It is an inherited disease.
In more detail: Celiac runs in families. Celiac
a specific tissue type that recognizes wheat proteins. The HLADQ tissue
type gene is part of a system which presents antigens to white blood
cells and distinguishes between self and non-self molecules. Celiacs
have the variants DQ2 and DQ8. The receptors formed by these genes bind
gliadin peptides from wheat very tightly and therefore are more likely
to activate T lymphocytes. But not all the people with this tissue type
get celiac. The ones who do also lack a protective DNA sequence in the
region of interleukin-2 and -21. These cytokine proteins are produced
by white blood cells to control inflammation. The missing DNA sequence
probably leads to different amounts of the cytokines being produced.
Four of the nine known gene regions implicated in celiac are also
implicated in type 1 diabetes. Risk of celiac is higher in those with
auto-immune diseases. It is a package that sounds familiar to me -
relatives with type 1 diabetes, celiac, auto-immune disease. Celiac is
more common in Northern European people then others. Recent studies
have shown that close relatives of celiacs have a 1 in 22 chance of
having celiac disease, for those not closely related to a celiac the
chance is 1 in 133.
2. In adults, at least, there is often an environmental
trigger to the onset of the disease.
In more detail: A trigger is often the case in
disease. Some infection (such as rotavirus or human intestinal
adenovirus), stress or damage starts the attack by the immune system on
the body's own cells. Smoking is somewhat protective and so quitting
smoking may be a trigger. Baby's who get celiac disease usually need no
trigger other than gluten itself.
3. A component of gluten, gliadin, resembles proteins in the
intestinal lining. Immune attacks on gliadin also attack the intestine.
In more detail: Gluten is a protein in wheat; a
is found in all grains but only wheat (normal, spelt, triticale,
kamut), rye, and barley cause celiac. Gluten is not fully digested in
humans. It is partially broken down and the fragments cause the harm in
celiac - gliadin is the harmful component of wheat gluten, hordein in
barley, secalin in rye. An enzyme, tissue transglutaminase, modifies
the gliadin and it then resembles protein in intestinal tissue. This
starts an inflammation that destroys the villi and microvilli in the
lining of the small intestine which are responsible for much the
absorption of food. This results in pain, diarrhea and malnutrition.
The decreased surface area of the intestine do to the loss of
microvilli leads to a decreased production of lactase and therefore the
symptoms of lactose intolerance may add to those of inflammation.
Gliadin also stimulates membrane cells, enterocytes, to allow larger
molecules around the sealant between cells. The two way
liquid to enter the intestine through the intestinal walls and allows
large proteins and other molecules that have not been broken down yet
by digestion to enter the body. Gliadin entering the body can cause
4. Celiac symptoms are varied because it attacks a number of
organs as well as the bowels.
In more detail:
Different symptoms can show at different times. It has been estimated
that it takes about 10 years for a patient to be correctly diagnosed.
They are often diagnosed with other conditions first.
Classic intestinal symptoms are do to damage to the intestine. Some
symptoms are caused by malnutrition. Other symptoms are due to the
triggering of inflammation in other areas of the body. Some conditions
may be the result of shared genetic risk rather than being related to
5. The condition can be diagnosed but is often missed.
In more detail:
It is thought that most cases go undiagnosed, often because it is
assumed that other diseases cause the symptoms or because symptoms are
mild in some people. Diagnosis can be made by blood tests (for IgA
antibodies against reticulin, gliadin, endomysium, tissue
transglutaminase), HLA tissue type testing, endoscopic examination for
villi in the duodenum, biopsy of intestine and by a gluten free diet
followed by a gluten challenge. There has been debate on proposals to
screen everyone with certain conditions for celiac in some countries.
In the UK, NICE recommends to doctors that they should screen for
celiac in newly diagnosed cases of chronic fatigue syndrome and
irritable bowel syndrome and say it is justified in cases of type1
diabetes, iron-deficiency anemia, Down's syndrome, Turner's syndrome,
lupus, Crohn's disease, and autoimmune thyroid disease.
6. There is no treatment except to avoid eating gluten.
In more detail
Avoiding gluten is easier said then done. An amount of gluten that is
harmless has not been agreed and varies from person to person. US
'gluten-free' labeling is not regulated and can mean anything. Other,
regulated, labeling for gluten probably allows too much and will be
changed in future.
Traces of gluten are found in foods that would not be expected to
contain gluten. Celiac are often advised to cook from scratch. Hidden
sources of gluten include additives such as modified starch,
preservatives, stabilizers, thickeners, and texture enhancers. Gluten
may also enter other foods as contaminates in factories manufacturing
many products. Oats is often contaminated with gluten. It can even be
found in some medicines.
Even with strict avoidance of gluten, it takes time for the body to
heal (as much as 6 months in children or 2 years in adults) and some
symptoms may persist, especially if the condition has been present for
a long time before diagnosis.
Having had celiac often leaves people with other sensitivities (milk
products, mold-based cheeses, mushrooms, yeast and yeast products). One
lingering sensitivity can be particularly problematic - sensitivity to
xanthan which may be used as a binder in gluten-free products.
7. Dermatitis Herpetoformis is a complication in some celiacs.
In more detail
This also called Dulring's disease and is sometimes called 'celiac
disease of the skin' as opposed to 'celiac disease of the gut'. The
symptoms are small papules or vesicles on the skin, red bumps and
blisters. These are intensely itchy and burning or stinging. The
blisters come in bouts and may take from 7 to 10 days to lose their
itching. They then crust over. They are rarely inflamed and don't
contain pus. The only real treatment for the condition is a gluten-free
diet. Dapsone is used to control severe symptoms but has unfortunate
side effects. People can have the skin condition without the intestinal
condition and vice versa.
Celiacs can eat plain meat and fish, eggs, legumes and other sources of
protein. They do
have to avoid breading, flouring, gravy and sauces which contain
gluten. They can eat all fruits and vegetables. For carbohydrates,
there is rice, corn, potatoes and more rare foods like millet,
buckwheat, flax, arrowroot, soy, sorghum, nuts and so on. Again
prepared foods are a problem. Potatoes are OK but prepared fries often
have a flour coating, so do many potato chips and corn and tortilla
chips. Oats is safe except that it is often contaminated with other
grains. Watch out for candy, cold cuts, hot dogs, salami, sausage, soy
sauce, self-basting turkey, imitation fish or meat, and on and on with
processed foods. Processed foods are likely to have some gluten.
And, of course, avoid at all costs anything made of flour (bread, cake,
cookies, pastry etc), pasta, semolina/couscous, porriage/most cereals.
I really do not
have too much faith in
some areas of modern medicine: back pain and nutrition. Recently I ran
across a reference to an article from 2005 by John Allen Paulos on
health research, Why Medical Studies are Often Wrong. He is a professor
of mathematics and interested in statistics.
A study of papers from major journals between 1990 and 2003 by J.
Ioannidis showed that a third were contradicted or significantly
weakened by later work.
Hormone replacement does not protect against heart disease; vitamin E
does not protect against cardiac problems. And on… Single studies can
not be trusted. They may be statistically flawed in some way. Studies
as they are presented in the popular media may mislead us even if the
originals are reliable. Unfortunately researchers may not be impartial
and may even be supported by a drug company and pressure group. I think
that the type of information that is most prone to being unreasonably
hyped by the press is nutrition studies.
In the past I have fallen for some nutrition myths. One was vitamin C
in large doses - if I felt off colour I would take a lot of vitamin C
for a couple of days. But some fads I didn't touch. I remember when
fancy margarines came out with their poly-unsaturated fats and they
were supposed to be so much more healthy than butter. Well, I just
could not believe that something that came out of a chemical factory
was healthier than something that came out of a dairy. I cut way back
on the butter but I didn't replace it with margarine, so I have not
been taking in trans-fats from any margarines all these years.
Then there were eggs. Would an egg do any harm? (Which reminds me of a
story about Harry's mother: Harry heard about pies at school and what a
special treat they were so he bugged his mother to bake pies. Harry's
mother was a very experienced and good cook but in a Ukrainian cuisine
that did not include pastry. She got a recipe from somewhere and
started to make a pie. The crust had only flour, water and lard. What
was that for food? Where was the nutrition - could an egg do any harm?
It was a spectacular failure.) One day eggs became unhealthy because of
their cholesterol. We must not eat anything high in cholesterol. I
could not believe that cholesterol, something that the body could make
for itself and that was important for metabolism, was not regulated. If
we ate more then we would make less and if we ate less then we would
make more. Something would be setting the level of cholesterol in our
bodies and it would not be how much we ate. I have not stopped eating
those eggs, full of so many healthy things.
The phrase - 'you are what you eat' - has caused a lot of
misunderstanding. By and large, the body can make what it needs from
what it gets. It can make carbohydrates from fats and fats from
carbohydrates and so on. What it cannot make and so you must supply in
your diet is minerals, vitamins, essential fatty acids and essential
amino acids. If you eat a well balanced and varied diet than you will
get these essentials (or you can get them from pills). And, of course,
you want to avoid the things that are poisonous. Then you would aim to
get enough calories but not way too many. Finally if you have some
medical problem, you may have to eat more of some things and less or
none of others. Metabolism is complex and controlled by feedback loops
(some still being discovered) and we are very definitely not
what we eat.
The writer Jonah Lehrer says about 'Nutritionism', "There
are many good reasons to eat sardines, beets, turmeric, etc. But don't
eat them because of some correlation in a medical study. There's a good
chance, after all, that such a correlation will turn out to be dead
It seems clear to
me that I do not get enough exercise.
Recent reports have conclusions like:
1. Exercise reduces blood pressure, cholesterol, diabetes and
2. It improves blood flow and nerve cell growth in parts of the brain
associated with memory. It improves both memory and cognition in
3. It reduces calorie intake - suppression of appetite by increased
brain-derived neurotrophic factor. Apparently this effect does not
apply in obese women, those that are resistant to the hormone leptin.
They must diet and
exercise in order to lose weight.
4. The bain works better when using lactate rather than glucose.
Lactate is the by-product of strenuous exercise which can be cleared by
5. Genetic susceptibility (by FTO gene) to obesity is blunted by a very
6. Older people lose less muscle mass if they do low-intensity exercise
and take nutrient supplements. When older people diet without
exercising they lose valuable muscle mass.
7. Lifestyle, more than heredity, contributes to insulin resistance in
obese people. Physical inactivity contributes (alon with genetics) to
defects in mitochondrial oxidative phosphorylation.
8. Exercise helps trim the faty liver that complicates diabetes, heart
disease and liver failure.
9. Older people decrease risk of disability aramatically with a walking
10. Age-related changes to circulation in the brain are reduced by
exercise - resulting in better blood flow and more small blood vessels.
recommendations prescribe 30 minutes of moderate physical
activity on most days of the week, for a total of 150 minutes per week.
However, a growing consensus suggests that more exercise may be needed
to enhance long-term weight loss.
I have to lose weight but it seems that I should do it with exercise
rather than just diet alone. But how to get exercise? What I have to
figure out is how to be active without my joints getting painful and
the pain stopping the exercise for a few days until I have recovered.
If I lose some weight I should have less trouble with my joints but
that will be a long time in the future. In hindsight, I should have
watched my weight when I quit smoking, but I thought I could deal with
it later. So I have to slowly work up to more than 30 minutes a day of