Sunday, June 8, 2008

More on the magic light helmet for Alzheimer's

I blogged earlier about the magic light helmet which has been reported to help with symptoms of Alzheimer's.

I have been working on my post on the mechanisms of how immune system activation causes mitochondria turn-off. This is a "normal" property of the immune system and of mitochondria. There is nothing special about vaccines, any immune system activation (if sufficiently severe) can do it (as can some other things). It has nothing to do with any toxins of any sort.

Some of the stuff on mitochondria turn-off is related to the magic light helmet so I thought I would put that up first. There is a section here that talks about the woman who was poisoned by dimethyl mercury, who received a lethal dose and then had no symptoms for 5 months despite carrying a lethal body burden of mercury. Her experience at a gigantic dose puts quite severe constraints on what possible effects mercury can have at the microscopic doses in vaccines.

I had a chance to go to the library and look up some more background on the effects of NIR (near infra red) on physiology. There are plenty of real effects that are well known and well described. NIR is also called IRA (the way that the UV spectrum is divided up into A, B and C). IRA is from visible to about 1400 nM (700 to 1400 nM). The energy of these photons is 1.77 to 0.89 eV/photon. For comparison, the mitochondria membrane potential is about 150 mV, so these photons have much higher energy than the electrons that mitochondria are gathering energy from. The energy is considerably lower than the energy of UV photons, UVA, UVB, UVC (400 -320 nM, 320-280 nM, or less than 280) having energies of 3.1-3.87, 3.87-4.43 eV. For comparison, the usual germicidal wavelength from mercury vapor lamps is 254 nM or 4.88 eV. This is a high enough energy to break chemical bonds including those in DNA.

Melanin absorbs strongly in the visible, but is essentially transparent beyond 800 nM so skin color doesn't affect IR transmission through the skin much. The major absorption of skin in that region is due to water. The major reflectance of skin in that region is due to scattering due to the difference in index of refraction of the different tissue compartments, water, lipid, protein. Reflectance due to scattering may not be particularly relevant in the Magic Light Helmet because the inside of the helmet might be reflective and light scattered out would be reflected back in. The tissue being treated, the brain, can receive scattered light from any of the light sources, or via reflection after being scattered out of the skin.

There are at least 3 relevant parameters when thinking about light interactions, wavelength, total dose, and dose rate. All natural sources of NIR such as the Sun, fire, hot objects are continuous wave that is they are on continuously and the average dose rate and the instantaneous dose rate are the same. They are also "black body", that is they have a continuous spectrum not a single wavelength. This is not true for some artificial sources of NIR such as are used in the Magic Light Helmet. They use pulsed solid state sources so the instantaneous dose rate may be many times (or even many orders of magnitude) higher. Doses of anything that may be safe at one rate may be completely unsafe at another. For example, the daily RDA of sodium (as salt) is less than 6 grams. In other words, 6 grams a day is ok, but if you got a year's worth of salt in a day (about 5 pounds) it would kill you.

Similarly an NIR dose rate that is ok indefinitely, lets say 10 Watts on your head from the Sun might cause problems if it is delivered as 10 megaWatts in a microsecond from a pulsed monochromatic source. At high dose rates non-linear things start to happen with light, there are multiple photon absorption events.

These non-linear effects increase dramatically as the dose rate increases. Two photon absorption goes as the intensity squared. Double the dose rate and there are 4 times more two photon events. My presumption is that the people developing the magic light helmet noticed that as they increased the dose rate by using pulsed NIR sources it worked "better". That is a sign of non-linear effects going on.

If multiple NIR photons are absorbed, the cumulative energy might be enough to cleave bonds the same way that UV can. Tissues are mostly opaque to UV, they are not opaque to NIR. I don't know at what dose rate NIR starts to cause problems, but neither do the people pushing the magic light helmet (or if they do they have not reported either what levels they are using or what safe levels are by what theory of safety). There are a great many potential sites of damage, none of which have been characterized.

If there is damage from pulsed NIR, that damage can accumulate over the lifetime of the things being damaged. Neurons don't divide. The DNA in neocortical neurons is not replaced over their lifetime and neocortical neurons are only generated in the perinatal period. If the NIR exposure did damage neuronal DNA in addition to what ever positive effects, that damage would accumulate and at some point would cause problems. Without knowing what dose is required to cause problems, the dose at which problems do not occur can't be known.

There are mechanisms where IR can reduce the UV damage to skin cells. IR is also known to deactivate activated chemical species in a non-damaging way. This is the photostimulated emission of visible light that is sometimes used as a detector of IR. This is explained as the reason why people burn worse on a cloudy day. The clouds don't block the UV which causes the damage (they scatter it) but do block the IR from the Sun which deactivates the excited bonds in a non-damaging pathway before they can decay via a damaging pathway. Broad spectrum IR as from the Sun or thermal sources is probably more effective than is monochromatic IR from diodes. The photon energy has to couple to the activated bond to deactivate it. The energy usually needs to be in a narrow window for that to happen. With a broad spectrum there are lots of photons of different energy available.

NIR does cause the photodissociation of things like cyanide from cytochrome c oxidase. It would also cause the photodissociation of NO. This has the effect of increasing consumption of O2 by accelerating the removal of electrons from the respiration chain onto O2 and causing the respiration chain to become more oxidized. In other words, with the activity of cytochrome c oxidase accelerated by the photodissociation of NO, there are fewer electrons hanging out on complex I and complex III which are the major sites of superoxide production, so superoxide levels go down. I think this acute reduction in superoxide is the likely mechanism for the perceived beneficial effects of the magic light helmet. With less superoxide produced, NO levels go up, and there is an improvement in the ATP level due to sGC. That is there is an improvement observed in Alzheimer's until physiology adapts. This improvement is transient and illusory (in my opinion) and will very likely be followed by rebound. In other words, the transient increase in ATP levels (above the regulatory setpoint) will cause the regulatory setpoint for ATP to be moved still lower. The magic light helmet might provide a temporary boost to ATP levels, but will likely accelerate the long term decline.

When mitochondria are irradiated by NIR, there is a transient reduction in membrane potential, and also a release of cytochrome c. After 18 hours the membrane potential is substantially restored. My interpretation is that the photodissociation of NO from cytochrome c oxidase increased electron flow to O2, this reduced the membrane potential which reduces superoxide production, resulting in a loss of superoxide production. This loss of a necessary part of mitochondria regulation is intolerable, so the mitochondria respond by releasing cytochrome c, to interrupt the respiration chain after complex III but before cytochrome c oxidase. This restores the production of superoxide.

This restoration of mitochondria potential and superoxide production comes at a cost, the loss of cytochrome c. Cytochrome c is a small soluble protein that is in the space between the inner membrane and the outer membrane. It ferries electrons from complex III to cytochrome c oxidase. Cytochrome c is coded for in nuclear DNA, and so is only capable of being produced in the cell body of a neuron. Once mitochondria in a neuron lose cytochrome c, that cytochrome c is gone for good. Could the cytochrome c be recaptured by the mitochondria that lost it? No, all proteins in mitochondria that are coded for in the nucleus are targeted to mitochondria by the addition of a special hydrophobic targeting sequence attached to the protein. That targeting sequence pulls the protein through a special pore. Heme is only attached to proteins inside mitochondria. Cytochrome c is produced as the apo enzyme, is transported to the mitochondria outer membrane where it binds, and then a special enzyme, cytochrome c lyase attaches heme to the apo enzyme making cytochrome c. Cytochrome c is the only heme containing enzyme where heme is covalently bound to the protein. In all other heme containing enzymes the heme is not chemically bound but is only held by the conformation of the protein.

Could there be a mechanism by which intact cytochrome c was transported back to mitochondria? Maybe, it seems doubtful. Better regulation of cytochrome c loss in the first place would be a better evolutionary target. Cytochrome c loss is a critical event in apoptosis. Apoptosis is not something cells want to do partially. The damage to a cell very rapidly becomes irreversible. Cytochrome c level inside mitochondria has to be something that each mitochondrion regulates by itself independently of its surroundings (and the level of cytochrome c in those surroundings which is usually zero). Usually there is no excess cytochrome c in the cytoplasm a mitochondrion is in, so there would be no way that a mechanism to import it would have any utility. The time scale that mitochondria require for regulation of cytochrome c levels doesn't allow transcription of cytochrome c DNA into RNA, generation of cytochrome c protein (necessarily heme free) and then transport to the mitochondria where heme could be added. There simply isn't time, and in neurons it simply can't happen because mitochondria may be inches away from the cell nucleus.

This progressive loss of cytochrome c is (in my opinion) an effect of the NIR irradiation of mitochondria that will make the side effects of the magic light helmet unacceptable. I expect that there will be serious and irreversible neurodegeneration with prolonged use of the magic light helmet, even in previously normal individuals. I suspect that this irreversible neurodegeneration may creep up and not be noticed until it reaches a threshold beyond which recovery is not possible.

The fundamental control paradigm of mitochondria is for them to produce more superoxide when they require producing ATP at a higher rate. Mitochondria biogenesis can only occur when the superoxide level is low. If the number of mitochondria drops below the level where they can produce sufficient ATP while maintaining a superoxide level sufficiently low for mitochondria biogenesis to happen, then mitochondria biogenesis will stop and cannot be resumed. This is the point of no return beyond which the cell it occurs in is doomed.

Mitochondria are necessarily producers of superoxide. That superoxide production cannot be blocked without disrupting normal mitochondrial function. Mitochondria won't allow their superoxide level to fall to zero, they will compensate by interrupting the respiration chain by releasing cytochrome c into the cytosol. That can also be a trigger for apoptosis, but I will leave a discussion of that for another time.

What does chronic lack of mitochondria biogenesis look like?

I suspect the symptoms will mimic the delayed symptoms of mercury poisoning such as the dimethylmercury poisoning experienced by a woman heavy metals researcher where she had a lethal body burden of dimethyl mercury following acute exposure (estimated at 1,344,000 micrograms at exposure) with no symptoms for 5 months. At 5 months (time of diagnosis) she had a measured blood level of 20,000 nM/L, and a body burden of 336,000 micrograms. This has nothing to do with the non-existent mercury poisoning that the quacks and frauds attribute autism to (which they assert occurs promptly (days) following vaccination with a trivial quantity of mercury (~15 micrograms). These delayed symptoms are for real mercury poisoning, which occurs at levels that are unmistakably diagnosed via testing of any specimen, blood, urine or hair. The level she was exposed to was roughly 100,000 times the level in vaccines.

The very long symptom free period demonstrates that even these extremely high mercury levels are not acutely toxic to mitochondria. If they were acutely toxic, she would have died much sooner. Nerve cells can only function for a few seconds without mitochondria. Cells that can do glycolysis can function longer, perhaps minutes. There are essentially no cells that can function indefinitely only on glycolysis. Red blood cells can, but they have a finite lifetime. The major important tissues, muscle, liver, kidney, gut, skin, etc. all require mitochondria.

Since the exposure was through essentially a point contact, a spill of pure material on her skin, the local dose to those skin cells was absolutely gigantic. Essentially pure dimethylmercury ended up on her skin. There was no report of acute necrosis of the skin, presumably it didn't happen. If it had happened, perhaps her exposure would have been recognized and she would have been treated. That treatment might have saved her life.

I think the delay is due to the normal turnover of mitochondria without replacement due to a blockage of mitochondria biogenesis due to the extremely high levels of mercury. I think this relates to the interference with the recycling of mitochondria during autophagy, and specifically in the blunting of the NO/NOx signal that occurs during autophagy. What is interesting is that the organ that failed was the brain, not the other organs. My explanation of this is that these levels of mercury disrupted the normal feedback regulation of mitochondria biogenesis, but only in neuronal tissue.

With zero mitochondria biogenesis I would expect the onset of symptoms of failure of the CNS to occur pretty abruptly as observed in the dimethyl mercury poisoning. There is significant redundancy and fewer mitochondria running at high potential can produce the same ATP as many running at low potential. I would expect the abruptness of the transition from essentially no symptoms to death to be pretty rapid. The abruptness relates to the average of the mitochondria and the number that fail at any one time. The higher the metabolic load each mitochondria experience, the faster it will age and ultimately fail. The longest nerves are the ones affected first, as experienced by peripheral numbness. This is typically the same pattern observed in other neurodegenerative diseases such as amyotrophic lateral sclerosis. The peripheral nerves are (typically) the ones that go first. Mitochondria biogenesis likely doesn't go to zero in ALS the way it likely did in the mercury poisoned woman.

That the disruption is only in neuronal tissue puts quite severe constraints on what the mercury could be doing. It is likely not due to inhibition of key mitochondrial enzymes (that would lead to acute mitochondrial inhibition in many tissues and prompt death) or even inhibition of enzymes that make key mitochondrial enzymes (that would lead to reduced mitochondria biogenesis in all tissues and multiple organ failure). Mitochondria in neurons are the simplest mitochondria. They don't oxidize lipid so they likely have only a subset of the enzymes that all other mitochondria have. They should be the most resistant to toxicity because they have fewer enzymes to be disrupted.

In short, I see the magic light helmet as potentially quite dangerous, even if it works. Non-physiological treatment (subjecting the brain to NIR fluxes many orders of magnitude above normal) can't have effects via normal physiological mechanisms. There is no reason to suppose that a non-physiological mechanism is benign or has no side effects.

I will discuss mitochondria depletion due to immune system activation in a future post.


Cristian said...

Major “Missed” Biochemical Pathway Emerges As Important in Virtually All Cells

A new study by Duke University researchers provides more evidence that the nitric oxide (NO) system in the life of a cell plays a key role in disease, and the findings point to ways to improve treatment of illnesses such as heart disease and cancer.

The nitric oxide system in cells is “a major biological signaling pathway that has been missed with regard to the way it controls proteins,” and it is linked to cancer and other diseases when the system goes awry, said Jonathan Stamler, M.D., a professor of medicine and biochemistry at Duke University Medical Center who worked on the study.

In the body, nitric oxide plays a role in the transport of oxygen to tissues and physiological activities such as the transmission of nerve impulses, and the beating of the heart. When things go awry with the nitric oxide system, bad things can happen in bodies, according to recent studies. For instance, there may be too little nitric oxide in atherosclerosis and there may be too much in Parkinson’s disease; there may not be enough nitric oxide in sickle cell disease and there may be too much in some types of diabetes, Stamler said.

The new findings, which Stamler said change understanding of how the nitric oxide system is controlled, appear in the May 23 issue of the journal Science.

“What we see now for the first time in the Science paper is that there are enzymes that are removing NO from proteins to control protein activity,” Stamler said. “This action has a broad-based effect, frankly, and probably happens in virtually all cells and across all protein classes. Nitric oxide is implicated in many disease processes. Sepsis, asthma, cystic fibrosis, Parkinson’s disease, heart failure, malignant hyperthermia — all of these diseases are linked to aberrant nitric-oxide-based signaling.”

An important factor that previously wasn’t appreciated, he said, is that the target of nitric oxide in disease is different in every case. The finding of how nitric oxide binding to proteins is regulated opens the field for new refinement in biochemical research, said Stamler, who has been studying nitric oxide in cells for 15 years.

“Now we will need to study whether the aberrant cell signals are a matter of too much NO being produced and added to proteins or not enough being removed from proteins,” he said. “It is not simply a matter of too much or too little NO being in cells, but rather how much is being added or taken away from specific proteins, which is quite a different thing.”

First author on the paper, Moran Benhar, Ph.D., and co-author Douglas Hess, Ph.D., are both in the Duke Department of Medicine. Co-author Michael Forrester is a graduate student in the Duke Department of Biochemistry.

The research explains that the enzymes thioredoxin 1 and thioredoxin 2 remove nitric oxide from the amino acid cysteine within mammalian cells, thereby regulating several different actions in cells. One result of this removal is the activation of molecules that begin apoptosis, which is the normal programmed death of a cell. This process has potential importance for many diseases, including inflammatory diseases, heart failure and cancer. Because thioredoxins are established targets of drug therapy for arthritis, the research suggests potential therapeutic applications of the process.

The nitric oxide system is analogous to the much more studied phosphorylation system, in which phosphates are added and removed from proteins, the paper said. Changes in phosphorylation are among the most common causes of disease, and proteins that regulate phosphorylation are major drug targets, Stamler said.

“Aberrant dephosphosphorylation causes disease. Expect the same for denitrosylation,” Stamler said.

Similar research at Duke that was published in the journal Nature on March 16 supports Stamler’s findings. Christopher Counter, an associate professor in the Duke Department of Pharmacology and Cancer Biology, and colleagues found that eNOS (endothelial nitric oxide synthase), an enzyme that enhances the creation of nitric oxide, promoted tumor development and tumor maintenance in mice.

“The Chris Counter work is especially exciting because he shows that a nitric oxide synthase is linked to cancer, and he specifically identifies the protein that is the target of the nitric oxide, the protein that gets turned on through S-nitrosylation,” Stamler said. Blocking S-nitrosylation of this protein prevented cancer.

The steady stream of new papers on nitric oxide seems to underscore Stamler’s long-held belief that nitric oxide affects cells in bigger ways than many had appreciated. “When we began our studies two decades ago, we hypothesized that nitric oxide was part of a significant, broad-based system,” Stamler said. “Our hypothesis never changed.”
Source: Duke University
Author: Mary Jane Gore -

Eric Wheelman said...
This comment has been removed by the author.
daedalus2u said...

The marker for damage I would expect to see on MRI would be what is called white matter hyperintensities, or leukoaraiosis. These are regions of reduced water diffusion in the brain in the white matter, which are primarily axons (called white because of the myelin).

Mild leukoaraiosis is reversible if what ever is causing it is reversed in time. It represents the brain operating at reduced ATP levels where there is more wear-and-tear and less repair. The wear-and-tear is to some extent irreversible. Once cell bodies are ablated, they do not come back. Many long range connections don’t come back either.

What you describe is pretty much what I would expect. The acute resolution of depression and AS does fit with low NO causation for both. That the benefits of using the IR irradiation go away with continued usage indicates that what ever is being affected is being compensated for. To me, this somewhat confirms the mechanism I expected.

If it takes ever higher dosages to achieve the same effects, to me, that is a clear sign that this approach is not working and if you continue to increase the dose will result in a state where the physiological pathways can not compensate any more. That may lead to severe and irreversible injury in a very short time.

daedalus2u said...

Just to reiterate in somewhat stronger terms, the transition from where the magic light helmet seems to be helping to where it kills you may be very abrupt and your judgment may be very clouded at that point. By the time you realize there are adverse effects it may be too late. The transition might occur in a single day and be irreversible.

It may be analogous to the hyperpyrexia that some types of stimulants of abuse cause, such as PCP. I see them as causing mitochondrial uncoupling, that uncoupling lowers ATP levels and induces the euphoria of the near death state. I think that is the same euphoria that results from solvent huffing and autoerotic asphyxiation. It is the mitochondrial uncoupling that causes the hyperpyrexia. The ATP is being dissipated as heat and is not available to do the things necessary to maintain life.

Doing anything to your brain that makes you feel good or euphoric should be done very very carefully. Some things like solvent huffing cause irreversible neuronal damage the first time. Something like the magic light helmet may be similar.

Anonymous said...

- Hi, - I've been reading your posts about NO, - really fascinating...hard for me to follow it all with just school chemistry/physics etc, but I've been trying to find out more about my own problems with fatigue & low salt/high potassium. Somewhere along the line I was trying to follow some research about superoxide, and superoxide dismutase - that seemed to point to superoxide and nitric oxide being a sort of pairing on/off in various areas.
- I've been trying to follow as much as possible, but just wondered if you'd mind me asking about these ammonia oxidising bacteria that you're working on..... I can't find much about them, but I'm really intrigued as to whether they are obtainable commercially in some form anywhere? - Cheers, DC

domino said...
This comment has been removed by the author.
Unknown said...

WOW! I am glad I found this website!
Good Job! Thank u..
Your information is inspiring to me and these things did help to others.
Thanks for sharing.

My url:
I also invite people to use my links and read more.

Anonymous said...

Can you tell me if excess Nitric Oxide can do damage? My daughter took large doses 3 days in a row and ended up in hospital. She now has all the symptoms of Chronic Fatigue. She was a brilliant fitness enthusiast up to this.

daedalus2u said...

You might be thinking of nitrous oxide, N2O. It is a not so good anesthetic and is used as a propellant to make whipped cream. It can be inhaled. It isn’t toxic per se, but there can be asphyxiation from lack of oxygen.

Nitric oxide is NO, and is completely different. There is essentially no way to get an excess of NO. NO is used by inhalation for people with pulmonary hypertension, at 10's of ppm levels.

NO2 is nitrogen dioxide and is acutely toxic.

There is nothing over the counter that could give anyone too much NO.

Things like nitroglycerine, alkyl nitrites, and other NOx can be toxic, but not via making too much NO.

I think that chronic fatigue is caused by not enough NO, not from too much. I can’t think of a mechanism where too much NO would cause CFS unless it occurred during something like sepsis severe enough to require hospitalization.