DISORDERS RELATED TO BLOOD SUGAR DEREGULATION, ie SCHIZOPHRENIA, PANIC ATTACKS, EPILEPSY, ASTHMA. (All brand new stuff and all mine.)

There is a very common misconception that certain individuals have some sort of endemically low blood glucose, ie persistent hypoglycaemia. Normal regulation but set to a low average. There CAN be long periods of low blood glucose but primarily in response to a sharp peak, due to consumption of refined sugar, monosaccharides etc., followed by a deep low. This low is because the pancreas overreacts, thereby pushing BG (blood glucose) way down below the fasting level followed by a VERY SLOW RECOVERY. When a BG reading is taken during that period the assumption is that it is like that all the time.

Hence the doctor prescribing a migraineur I met TWELVE CUPS OF COFFEE A DAY WITH SIX HEAPED TEASPOONS OF SUGAR IN EACH CUP. Get it up and keep it up. Now I know that’s very difficult to believe, but he got shitty when I said ‘you’re kidding’. When his BG slipped through the sugar net he copped migraines so excruciating he would have to inject morphine and they would last up to 4 days. Being so nauseas during the attack he couldn’t just scoff more sugar. So that’s the prolonged period of hypoglycaemia that creates the confusion and it’s a product of both impaired liver storage AND the livers inability to MAKE glucose via gluconeogenesis, ie OVERALL liver pathology. In his case he was prescribed beta blockers to limit the blood pressure rise associated with the migraine. However these are a major factor in prolonging the migraine as they don’t just block the effect of adrenalin on myocardium but also on fat and skeletal muscle cells, thereby blocking gluconeogenesis because glycerol from fat cells and lactic acid from skeletal muscle cells is needed .

THE PHYSIOLOGY of BLOOD SUGAR DEREGULATION ASSOCIATED WITH PANIC ATTACK, SCHIZOPHENIA ETC.
This is the theory of what is taking place in the body and brain leading up to and during a panic attack.. Assume that the dietary sugar has gone into the bloodstream too quickly and glucose shoots up to be followed by a big fall to a very low level because too much insulin has been released. Insulin release is BIPHASIC, two peaks, one immediately and one around 20 minutes later. Beta cells of the pancreas normally retain some insulin from their previous release, whereas de novo synthesis takes around 20 minutes, ie transcription, splicing, translation, folding, adding di-sulphide links and zinc binding.

The first immediate insulin peak nips in the bud any BG rise from the quick entry of glucose into the bloodstream AND IS LOST with reactive hypoglycaemia due to the pancreas releasing ALL stored insulin each time. So without the first immediate release there is the 20 minute delay combined with the premature flood of glucose into the bloodstream. So the entry of glucose and the release of insulin are hopelessly OUT OF PHASE with each other. Thus the pancreas produces TOO MUCH insulin, probably because of impaired GIP axis detection and BG is driven down to an abnormal low as it is taken up and stored. The bigger the peak the lower the low.

Because the liver is not storing much glucose as glycogen, most of it has gone into the skeletal muscles instead, so muscles have to take over the role of the disordered liver. But muscles were not ‘designed’ for this role. Hence the very convoluted reaction that follows. Normally GLUCAGON is released by the pancreas in response to a fall in BG to bring it back up by acting on liver glycogen, so that the glycogen is hydrolysed to glucose and this is released into the bloodstream. But because of impaired liver storage glucagon release is ineffectual. Glucagon also has a mild effect on the heart to slightly raise blood pressure.

With a sudden ‘fight or flight’ adrenalin is released by the adrenals and it too acts on the liver to raise BG, as well as acting on the heart to increase it’s output, constricting blood vessels supplying the GI tract and associated organs and kidneys, whilst dilating those to liver, skeletal muscles, heart, lungs and brain. In other words reducing blood flow from organs not essential to ‘fight or flight’ whilst increasing it to those that are

THE CENTAL MECHANISM.
The following, as far as I know, is is exclusive to me and the result of 42 years of research. It is hypothetical based on an arrangement of the known bits and pieces. If there is ONE mechanism central to understanding schizophrenia, migraine, epilepsy etc. it is THIS. Muscle cells cannot release glucose back into the bloodstream as they do not express the enzyme Glucose-6-phosphatase, whereas the liver does. With impaired liver storage of glycogen, the muscles have to take over the role of glucose storage but because they cannot release it as glucose have to ferment it to lactic acid instead for conversion in the liver to glucose. Adrenalin is required to increase the metabolic rate of the muscles and dilate the blood vessels to wash the lactic acid out, however, the dilated blood vessels supply oxygen which stops fermentation. Alternatively noradrenalin does constrict the blood vessel, but has no metabolic effect on muscle cells and of course restricts blood flow. Enter muscle spasm, hot and cold flushes as the two hormones alternate. It seems to be hot first followed by cold.

NORADRENALIN is associated with extreme fear, but here it’s not fear in response to an external perceived threat. The threat is internal and NOT understood by the person experiencing it thus aggravating the attack. The crisis is life threatening cerebral hypoglycaemia (low blood glucose in the brain) which can only be alleviated by increased lactic acid synthesis by the muscles. Liver pathology means not just impaired liver glycogen storage but also impaired gluconeogenesis (the liver making glucose from lactic acid) thereby necessitating even more secretion (release) of adrenalin and noradrenalin by the adrenal glands and in the brain ‘Panic attack’ exacerbated (made worse) by the individual not understanding what on Earth is going on. “I must be going mad”. (and all that entails).

THE RUNAWAY CASCADE OF FEAR.
The brain metabolises 40% of the body’s glucose. The more neural activity (thought), the more glucose consumption. The more glucose consumption, the worse the cerebral hypoglycaemia and with it the greater the secretion of adrenalin and noradrenalin. ‘Jesus, I’m going to die, right now when I am least prepared for it’

Enter HYPERSUGGESTABILITY plus religion, almost universal in schizophrenia. The more frightened you become the greater the imagination for possibilities. ‘I’m going to burn in Hell. I might lose my mind and go berserk!!! People are coming to get me, try me, and burn me at the stake. They can read my mind. God can read my mind and I can’t stop blasphemies pouring into my mind. Every atom in the Universe is conspiring to get me. Everything looks, sounds, smells and feels sinister and threatening. (Visual contrast is altered making shadows much deeper and sinister, eg in Cyprus pines.) Hell. I AM IN HELL. (More glucose more noradrenalin) TERROR and it is forever and ever. Thousands of volts of electricity are pouring through me (hypersensitivity to greatly elevated sympathetic nervous transmission).

Now frozen stiff in a catatonic trance. Noradrenalin now predominates to constrict the blood supply to skeletal muscles persistently, along with immobility of the body to conserve energy. Catatonia is the worst case scenario and can go for DAYS ON END in a psyche hospital. However it doesn’t happen these days with the advent of the antipsychotics in 1950. This state is the most enigmatic of all as the schizophrenic catatonic appears to be totally non compost (joke), not even blinking, whereas the precise opposite is the reality, he or she is HYPER aware.

Thus when one intern jokes to another after waving his hand over the patients eyes and seeing no response whatsoever, ‘Vegetable, maybe a lobotomy might be in order’, he does not show a great deal of sensitivity. This is the very thing the patient is terrified of, ie LOSING HIS MIND. Mind you, how CAN the intern know without having been through it himself. He could by taking a big dose of LSD in paranoid circumstances as I did, many times, although each time I tried to avoid it. However, each time it happened I experienced the most indescribable nirvana as I came out of the catatonia and it seemed that I had to go down into hell to ascend into heaven.

It was trying to have nirvana without hell that I began to design and build a range of biofeedback equipment. But I had to study neurology to know how the ‘trip’ worked. That was futile without endocrinology and biochemistry and haematology and general physiology and on and on. In the back of my mind over all of these years was to try to understand the catatonic coma. Having been a Christian it became obvious that Lazarus was not dead but catatonic. Indeed Jesus said, ‘He is not dead but sleepeth.’ Then a few months ago the last pieces fell into place.

COMING OUT THE OTHER SIDE.
So how does the the individual pull out of the attack? Going into ketosis? Part of the process of gluconeogenesis is ketosis where fatty acids from fat cells are broken down in the liver to ketones, three different kinds. Two of these, betahydroxybutyric acid and diacetate, when in excess, come out in the urine and can be tested for using Ames Ketostix, a good idea straight after a panic attack. One, acetone, comes out in the breath as the “smell of rotting apples”. Most body cells adapt to using ketones but like ketosis itself this takes time especially with liver pathology.

Gluconeogenesis is also impaired thus delaying restoration of BG to normal. It is a complex process, requiring 3 substrates, lactic acid and amino acids from the muscles and glycerol from fat cells. Fatty acids are also released from the adipose fat cells, not as substrate for gluconeogenesis, but to provide the energy to drive the process, as gluconeogenesis is an energy negative process unlike glycolysis in the opposite direction which has a net production of 2 ATP’s. Fatty acids are first beta oxidised to ketones in liver cells, then to acetylCoA which enters the TCA (tricarboxalic acid, Kreb, citric acid) cycle to produce the ATP needed to drive gluconeogenesis. Carbon skeletons from some skeletal muscle derived amino acids, after deammination, also enter the TCA cycle as intermediates and are also metabolised to produce ATP..

Glycerol from adipose fat cell triglycerides and other skeletal muscle derived amino acid carbon skeletons, enter the gluconeogenesis pathway as substrate for the synthesis of glucose. Ketone production by the liver by far exceeds that needed to drive gluconeogenesis and excess ketones poor into the bloodstream for use by most body cells ONCE THEY ADAPT by up regulating the associated genes. However that adaption is also delayed so body cells continue to require glucose for days. Obviously transcription, splicing, translation ect. of the associated genes requires energy but as the BG is so low there is not enough fuel for these processes.

The two main endocrine hormones required for the process of ketosis and gluconeogenesis are cortisol and adrenalin. Cotisol acts on the skeletal muscles to get them to release amino acids whilst adrenalin acts on adipose fat cell to get them to break down triglycerides to fatty acids and glycerol for release into the bloodstream. Whilst not necessary for fat catabolism, cortisol also acts in synergism with adrenalin in this task and greatly increases the supply of fatty acids and glycerol to the liver.

EPILEPSY.
I always ask myself what do symptoms do. Now add a black out and convulsions, ie a grand mal epileptic fit, as an alternative to the above runaway cascade. The unconsciousness of blackout shuts off the panic cascade thereby conserving glucose and the CONVULSIONS PUMP LACTIC ACID OUT OF THE SKELETAL MUSCLES. Veins have non return valves along them so that by the convulsions stretching and contracting them they act as a series of pumps to speed up the delivery of lactic acid back to the liver. I’ve had a few fits myself years ago and with one massive fit I was fully conscious during the entire fit. That was very enlightening. I was extremely paranoid, with the very obvious visual distortions mentioned above which got increasing more obvious. Then projectile vomiting followed by the very violent convulsions, which changed in pattern from the last. Now a period of calm in which the visuals distortions were minimal but gradually built up to another round of vomiting and convulsions. This confirmed what was known that when schizophrenics who also suffer epilepsy have a fit it dramatically reduces the symptoms. It was this that inspired ECT to induce convulsions.

Brain tumours don’t directly trigger seizures. They use a lot of glucose the more malignant they become (what’s called the Warburg effect)and so exacerbate (make worse) the cerebral hypoglycaemia. I believe that the majority of these tumours are caused by the severe hypoxia in the brain associated with the vasoconstriction phase of migraine or simply severe reactive hypoglycaemia

ASTHMA.
Most people know that if an asthmatic tries to hyperventilate to overcome the breathlessness it just makes the attack worse. So they have to slow their breathing right down and relax as much as possible. (Alexander technique) Strange. What’s going on? How can an increase in oxygen going into the body be detrimental. Speaking to one asthmatic I knew she said that a cup of tea made it easier to breath. She thought it was because it was a hot drink, but I fixed on the sugar replacing sugar produced by gluconeogenesis. With gluconeogenesis turned down there wouldn’t need to be a noradrenalin adrenalin reaction on muscle cell to produce lactic acid. But what if there was a very weak adrenergic response, especially noradrenalin and it’s vasocontricting effect to the skeletal muscles cutting back on their oxygen supply. So too much oxygen is reaching the skeletal muscles for fermentation of muscle glucose to lactic acid to take place for the liver to make glucose from. So instead HISTAMINE is released in the lungs to reduce oxygen transport into the bloodstream instead. Just a hunch, but a big one.