In Physics as in all the hard sciences, one looks for principles that are never violated and for which there are no exceptions in nature. We call these first principles the foundation of Physics and they are our guiding lights as we explore the universe around us. In biology there are also first principles though they are not well known and not translated well to the management of patients. This is because Biology and the allied medical sciences have for most of their history been observational science as distinct from the more theoretical sciences such as Physics and Mathematics with first principles as their foundation and expressed in elegant as well as simple mathematical formulas.
I explore here one of the guiding principles of medical science and indeed all biological science. That principle is that tissue demand for the supplies delivered to meet that demand will ALWAYS match. Failure to match supply/demand in small ways or briefly leads to cell suicide or apoptosis and catastrophic failure to match supply/demand leads to death of the entire organism. Starvation or hibernation or the “dauer” state is an example of smaller tissue demand for energy to match the lower supplies of oxygen and carbon bonds (nutrients) available while starving or hibernating. As such, these low demand states like the dauer state are adaptations to survive a relative lack of supply and recently proven for CFS by Naviaux et al, PNAS July 2016 using next generation metabolomics. Whether or not that deficient supply be nutritional and/or blood flow (ie low cardiac output) does not matter from the point of view of the cell. In the face of reduced supply, the tissue or cells MUST adapt to a lower energy state or the outcome will lead eventually to a fatal disease, either over time or acutely with a diagnosis of acute organ failure and shock which is fatal within minutes.
There are a number of mechanisms or levers that can be pulled by the individual to prevent supply/demand mismatching. At the cell level, the quickest way to correct a supply problem is to desaturate hemoglobin which delivers extra stored oxygen otherwise bound to hemoglobin. When one sees excess desaturation of greater that 3 points using pulse oximetry after a 30 second, end-expiratory breathhold, in the setting of CFS is proof of on-going supply/demand mismatching. Other ways to correct a supply/demand problem includes increased sympathetic tone from the brain sympathetic nuclei as well as the release of epinephrine and cortisol from the adrenals. This increased sympathetic tone drives up supply via heart rate and vasomotor responses as well as increased LV and RV strain and increased EF% we see in nearly all CFS cases. Unfortunately, this increased sympathetic tone causes severe sleep disturbance and a feeling of being wired and tired. Furthermore, the adrenals can be exhausted causing a functional collapse. Nocturnal pulse oximetry can provide details of CNS hypoperfusion in CFS and thus supply/demand mismatching during stage IV sleep if we observe low nocturnal baseline oximetry and excessive desaturation during the first four hours of sleep. The treatment for this would be low dose oxygen starting at 1-2 lpm via nasal cannula during sleep. Oxygen above 1-2 lpm should be guided by nocturnal pulse oximetry. Otherwise, excess oxygen can be deleterious to CFS cases as excess oxygen ends up as free radicals and can cause down-regulation of the mitochondria as compensation to preserve the redox buffer.
The reason behind the lethality of a mismatch of supply/demand is that re-perfusion injury to hypoxic cells (ie insufficient supply of oxygen), causes a lethal but programmed release of oxygen free radicals that threatens the cell and the DNA with corruption. Corruption of the DNA will not be tolerated as it will lead to species extinction. Likewise, chronic mismatching leads eventually to organism death to avoid DNA corruption which will never be tolerated as it causes extinction of the species. Reduction of cell mass and therefore demand via cell suicide serves to improve supply/demand matching and is a survival mechanism. Failure of this mechanism to achieve supply/demand matching will eventually lead to a fatal outcome for the organism to prevent DNA corruption and the potential loss of the entire species.
When you take the principle of supply/demand matching and apply it to CFS, a whole new world of looking at CFS treatment strategies emerges. Many of the best treatments we have used over the decades and the ones that have best stood the test of time either reduce demand or increase supply. Typically, the best immediate treatments for CFS reduces demand and include such treatments as Klonopin, Doxepin, Trazadone, LDN and transdermal CBD CSF oil as well as staying within boundaries with long periods of rest. There are other treatments that improve supply in an indirect as opposed to a direct manner. These include redox buffer support measures such as Magnesium, hydroxyB-12, Inosine, Aronia Berry Concentrate, California Heritage olive oil, catabolic paste CSF, anabolic paste CSF and MTF paste CSF. By improving the redox buffer, mitochondria will automatically up-regulate and that will improve blood supply immediately. Direct stimulation of supply via stimulants or exercise or stress or SSRI’s or T3 hormone are dangerous in the setting of an impaired redox buffer state like CFS as it challenges the redox buffer further and will backfire over time as it may cause a supply/demand mismatch and eventual collapse of function to compensate if you are lucky and a fatal disease if you do not collapse function.
Going forward, NanoVi technology (see www.eng3corp.com) which improves the functionality of all 30,000 human enzymes all at once and in all cells within minutes can be a conundrum. After testing 17 consecutive CFS patients on NanoVi, we see a drop in mitochondrial function within minutes while on NanoVi by IVRT criteria in real time. I believe this is due to the fact that NanoVi increases oxygen demand at the cell level faster than organ systems can adapt to this and thus creates a supply/demand mismatch with a positive or negative clinical effect that depends on how long one breathes the activated water vapor using NanoVi. We also see this effect when we use oxygen alone by nasal cannula if there is normal baseline oximetry of 97-98% and termed oxygen toxicity by IVRT criteria. Excess oxygen demand or oxygen supply above the ability of the cell to functionally adapt its redox buffer to that increased supply or demand causes a downregulation of the mitochondria seen as a rise in IVRT in real time on the echocardiogram. It is a dramatic demonstration of the dauer state coming on line in real time. There have been no exceptions to these observations after 17 consecutive patients examined with NanoVi using echocardiography and after over 500 patients examined with oxygen alone at 4 lpm NC using echocardiography.
On the flip side, we notice that the combined use of oxygen at 4 lpm and NanoVi at the same time seems to cause oxygen toxicity to be abolished or even reversed and is associated with dramatic clinical improvement on the table in real time. Two recent patients felt a sense that they had recovered on the table with both treatments given simultaneously and their brain function improved immediately on the table. One of the patients started to cry as he felt normal for the first time in a very long time. I believe what happened was that the increased oxygen demand with NanoVi was met with increased oxygen supply using oxygen by nasal cannula so there was matching of increased supply of with increased demand for oxygen. The clinical benefit was astonishing and immediate. I therefore believe that NanoVi should only be used with nasal oxygen at the same time in CFS patients for a period of time between 4 and 12 minutes on the professional NanoVi model (~$8,500) per day and between 8 and 24 minutes per day on the home NanoVi model (~$5,500). Sicker patients should start at 2-4 minutes per day using both NanoVi and nasal oxygen set at 4 lpm TIW. The primary endpoint will be the clinical response over three months and the effect of this treatment on Nitrotyrosine blood levels as a redox buffer biomarker pre- and post-treatment over that ninety days. Patients wishing to be part of this study should contact Dixie. Be aware that no such study has ever been done on CFS cases so we cannot know whether this will be worth the cost or even the exact risks. I do think, however, that the gain could be significant and the risks low and I base this judgement on the use of NanoVi by a few CFS cases in the Pacific Northwest that are not my patients. It is also advisable to use all or most of the primary steps in the treatment hierarchy previously posted BEFORE the use of NanoVi and oxygen combined.
©2017 Cheney | firstname.lastname@example.org