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People have remarked how could medicine not understand how powerful circadian biology and the sun are for humans?  How did we swing and miss on thiamine, deuterium, and mitochondrial biology?

Might it be how we collect our evidence in medicine?

I think so.

Why?  When I went through my own awakenings in 2004 and 2005 a key paper came out in the literature.

In 2005, Dr. John Ioannidis, a well-known meta-researcher, published an article in PLoS Medicine called Why Most Published Research Findings Are False. This article caused a splash and has been making waves in the medical research community ever since.

When I first read his article, I wasn’t the least bit shocked as a clinician because my patients were not getting better with any Evidence Based Medicine recipe that was published up until this.  This raises the question, if our evidence is bad, what could possibly go right in healthcare for patients?   The article left me begging the clinical question for my patients, what should I do now for my patients?

The answer was to go back and look how the evidence was collected and then try to link it back to nature’s laws.

I think we must increase value by reducing waste in research.  Too many studies are being funded in areas that are useless to move the needle for the public good.  The reason this happens is because Big Pharma is paying the bill for RCT’s.

Nature doesn’t make mistakes – but people sure do with poor choices around light.  None of this is reflected in our evidence.  THIS IS A PROBLEM.

Modern evidence based medicine (EBM) via algorithms is a flawed process. The data that were sent to clinicians from the researchers are nothing more than fruit from a poison tree. How good is evidence if you are asking the wrong question and using a flawed metholodology in your data collection and testing? The process now used by medicine to harvest research data to make guidelines is scientific illegitimate, therefore it is clinically inappropriate.

Why EBM does not work is illustrated by Michel Accad having (mis)quoted the definition of EBM as “the conscientious, explicit, and judicious use of best evidence in making decisions about the care of individual patients”, in cite one below.

The correct quote should be:

“Evidence based medicine is the conscientious, explicit, and judicious use of CURRENT best evidence in making decisions about the care of individual patients”.

Most of today’s EBM is based on the drug cartel ideas of what we should study so they can gain more customers while they remain sick and untreated. Vested interests, such as the drug and medical device companies, often fund medical research. This means quality marks or guidelines based on this research may not represent the best clinical practice but rather the treatment option that benefits these companies.

The laudable goal of making clinical decisions based on evidence can be impaired by the restricted quality and scope of what is collected as “best available evidence.” The “authoritative aura” given to the collection alone, however, may lead to major abuses that produce inappropriate guidelines or doctrinaire dogmas for clinical practice. Today medicine’s algorithms are run by these horrendous ideas. This is why the public is getting a small benefit from healthcare today.

This illustrates the reasons why EBM is broken by those who use it:

1. Evidence comes in quality and selective reporting, either by publication bias or post-hoc subgroup analysis to obtain statistically and clinically significant results. It is quite common to use the examples illustrated by ISIS-2 study researchers to warn against frivolous subgroup analysis, in this case astrological signs, in blind pursuit of the holy grail of statistical significance.

2. Misquotation or taking the conclusion out of context is another expected way of forming the wrong basis for change in practice. The classic example for this is the conclusion drawn from NASCIS 2 involving the use of corticosteroids in spinal cord injury. This has been a huge issue in neurosurgery and spine care my entire career.

3. Garbage in, garbage out. This is my favorite reason why EBM is today’s best example of HOT GARBAGE. Most research today is not worth the paper it is written on. They ask the wrong questions and never serve the public good by helping lower diseases. This is why human epidemics are running wild. There are increasingly more observational studies in which causative links are suggested when the link can only be concluded as associative. These studies are retrospective research on prospectively collected data which is often flawed in certain aspect and cannot be used for anything other than what is it originally intended for.

4. Slow and out of date. Guidelines are often EBM in concept but can be biased due to institutional support, financial or material conflict of interest by various members of the committee and quickly out of date after publication. It is not unusual for various national clinical network to take 5+ years to form a consensus which itself is soon overtaken by new revelations and technology. The new guideline for AHA ACLS training come to mind. Over 330 new guidelines and only three have class one evidence? WHY ARE WE CHANGING A THING IN THIS CASE?

5. Bias in researchers/opinion makers: conscious and unconscious. Except for triple-blind studies, most results can be influenced (to various extents) by the conduct of the study which is dependent on researchers. Unconscious bias can occur based on individual outlook, professional training and past experience when a group of experts come to consider inclusion or exclusion of prospective studies to base their recommendations on.

6. The temple of Meta-analysis and Randomized Controlled Trials (RCTs) and their worshippers. Many EBM converts enthusiastically proclaim that without RCT or Meta-analysis, all treatments warrant review. THIS IS LUDICROUS. Workman’s compensation guideline use this to block PBM/LLLT treatments to people with TBI. However, many questions cannot have RCT to be performed due to rarity of the conditions or ethical issues. Some questions (for example, benchmarking diagnostic tests) do not need RCT to be performed. Well-conducted RCTs are often expensive, labor-intensive and take time to perform and reach their conclusion, sometimes being overtaken by other technological and social changes. TBI is one such area.

7. No evidence of effect is not the same as evidence of no effect. Many confuse the state of having no studies showing effect as the same as having studies showing no effect. Some suggest that certain treatment should be stopped when there are no high quality studies showing effectiveness of a therapy; that may be a valid assertion but as suggested by the definition of EBM, we ‘make do’ with whatever CURRENT evidence is available until something better comes along (we should remain vigilant for new knowledge). However, when there is high quality evidence of no effect, it is unethical to persevere with treatment proven to make no difference.

8. What matters to you does not necessarily matter to me. The recent move towards Patient Reported Outcome Measures (PROMs) and Patient Reported Experience Measures (PREMs) when designing new studies may still not be relevant to patients. Various studies looked at outcomes when the treatment was never intended to solve the problem. A recent example found paracetamol ineffective in long term back pain underlies the common sense that short acting symptom-relieving paracetamol was never meant to be used as a disease modifying drug. Evidence-based guidelines often map poorly to complex cases where the patient has multiple co-morbidities. Most specialist care cases fall here.

9. Ask the right questions, do the right maths in statistics. Today, this methodology is vastly ignored. It is often perplexing when considering large studies where some researchers appear to demonstrate lack of care in the most important aspects of the study both asking the question that is clinically relevant, choosing the right outcome indicators to measure, and harnessing the skills of a clinical statistician to determine what is needed to be done. 2 meta-analyses published with 12 months of each other can reach opposite conclusions; the difference lies in what question is really (and not reportedly) asked, which studies are chosen for analysis. Statistically significant benefits of one treatment over another may be marginal in clinical practice, but this information may not be included in CDS or other tools.

10. Academic and Institutional integrity of Centers and Hosptals must be questioned because of how they are using guideline to police clinicians. Inflexible treatment recommendations from evidence-based medicine tools may produce care that is management-driven rather than patient-centered. Clinicians can be punished by hospitals for not doing their dirty profitable work that never suits the patient.

Moreover, often times 2 apparently similar studies reach different conclusion in spite of similar setting and control; chance occurs providing conflicting answers. On the other hand, there are times when deliberate acadmic misconduct occurs and it can take years to identify the culprits of the misdeed. Being aware of websites like https://retractionwatch.com keeps people up to date but all researchers should be considered with some initial suspicion; even the work of a scientific icon like Mendel has been considered by some as ‘prescient’. No authors should be immune to the vigors of scientific curiousity and testing.

Does evidence based medicine adversely affect clinical judgment?

Yes, but only because the clinicians allow this to occur. In the age of information overload and excesses, it is important for clinicians to be professional is their approach to evidence, be it single landmark studies or national guidelines.

If the evidence is important enough to change your practice, then make sure the quality of research is high, the analysis is correct, the conclusions are reasonable and the relevance is current and applicable. If clinicians want to ignore the study conclusion or guideline recommendation, the onus is still on them to prove without bias why this should be.

The obligation rests with clinicians who are in direct therapeutic relationship with patients; hence they have the ultimate responsibility as learned sentinels advising the patient.

11. The current volume of evidence, especially clinical guidelines, has become almost unmanageable for ANY CLINICIAN.

Oculi tanquam speculatores altissimum locum obtinent = The eyes, like sentinels, occupy the highest place in the body.

Consistent with hypoxia/ischemia, thiamine deficiency stabilizes and activates Hypoxia Inducible Factor-1α (HIF-1α) under physiological oxygen levels.  Oxygen levels and thiamine control the intake and outtake systems of the mitochondrial matrix…………How did medicine miss these basics?

This series will continue to abolish more of your beliefs.

The reality is this:  the induction of HIF-1α mediated transcriptional up-regulation of pro-apoptotic/inflammatory signaling contributes to astrocyte cell death in the CNS and PNS during thiamine deficiency.  This destruction begins in the mitochondria and destroys neurons everywhere in your body.

Maybe now we can see why the evidence and treatment guideline has not yet supported why our modern environment is causing neurodegeneration? 

CITES:

Sackett DL, Rosenberg WMC, Gray JA, Haynes RB, Richardson WS. Evidence based medicine: what it is and what it isn’t. BMJ1996;312:71-2

David H. Freedman (November, 2010) Lies, Damned Lies, and Medical Science, The Atlantic

Ebrahim S, Sohani ZN, Montoya L, et al. “REanalyses of Randomized Clinical Trial Data.” JAMA 312, no. 10 (September 10, 2014): 1024–32. doi:10.1001/jama.2014.9646.

Ioannidis, John P. A. “Why Most Published Research Findings Are False.” PLoS Med 2, no. 8 (August 30, 2005): e124. doi:10.1371/journal.pmed.0020124.

Ioannidis JA, and Khoury MJ. “Assessing Value in Biomedical Research: The Pqrst of Appraisal and Reward.” JAMA 312, no. 5 (August 6, 2014): 483–84. doi:10.1001/jama.2014.6932.

Young, Neal S, John P. A Ioannidis, and Omar Al-Ubaydli. “Why Current Publication Practices May Distort Science.” PLoS Med 5, no. 10 (October 7, 2008): e201. doi:10.1371/journal.pmed.0050201.

The poem above was written for me by Anna P., a college freshman at Spring Hill University in Mobile Alabama..  

There’s a reason why the first thing we often ask someone when we meet them, right after we learn their name, is “where’s home for you?”

For me home is 100% in Nature.  It does not require a house for me.  This makes my perspective unique in the West.  

We may use our homes to help distinguish ourselves, but the dominant Western viewpoint is that regardless of location, the individual remains unchanged. It wasn’t until I stumbled across the following notion, mentioned in passing in a book about a Hindu pilgrimage by William S. Sax, that I began to question that idea:  People and the places where they reside are engaged in a continuing set of exchanges; they have determinate, mutual effects upon each other because they are part of a single, interactive system.

What I learned from Eastern philosophy is that while in the West we may feel sentimental or nostalgic attachment to the places we’ve lived, in the end we see them as separate from our inner selves. Most Westerners believe that your psychology, and your consciousness and your subjectivity don’t really depend on the place where you live, They come from inside — from inside your brain, or inside your soul or inside your personality. But for many Eastern cultures, a home isn’t just where you are, it’s who you are.

I realized I am relentless chaos years ago.  That is where my home is built.

In the modern Western world, perceptions of home are consistently colored by factors of economy and choice. There’s an expectation in our society that you’ll grow up, buy a house, get a mortgage, and jump through all the financial hoops that home ownership entails.

The endless options can leave us constantly wondering if there isn’t some place with better schools, a better neighborhood, more green space, and on and on. We may leave a pretty good thing behind, hoping that the next place will be even more desirable.

In some ways, this mobility has become part of the natural course of a life for this Black Swan. The script is a familiar one: you move out of your parents’ house, maybe go to college, get a place of your own, get a bigger house when you have kids, then a smaller one when the kids move out. It’s not necessarily a bad thing. Even if we did stay in one place, it’s unlikely we would ever have the same deep attachment to our environment as those from some South Asian communities do. It just doesn’t fit with our culture.

But in spite of everything — in spite of the mobility, the individualism, and the economy — on some level we do recognize the importance of place. The first thing we ask someone when we meet them, after their name, is where they are from, or the much more interestingly-phrased “where’s home for you?” We ask, not just to place a pushpin for them in our mental map of acquaintances, but because we recognize that the answer tells us something important about them. My answer for “where are you from?” is usually NYC, but “where’s home for you?” is a little harder for me to answer because I do not resonate with the concrete jungle any longer.

That environment taught me what not to seek in a home.

Home is where my heart beats well in Nature, then by its most literal definition, my home is wherever I am at that moment. I make the best of it because I a confident that I am making the choices of where I should be living for me.

Home is where I have all my skin in my own game.

And the truth is, the location of your heart, as well as the rest of your body, does affect who you are. The differences may seem trivial (a new subculture means new friends, more open spaces make you want to go outside more), but they can lead to lifestyle changes that are significant.

Memories, too, are cued by the physical environment we choose these days. We remain clueless about how the nnEMF footprint changes our feelings about the place we live now. When you visit a place you used to live and feel the difference now, these cues can cause you to revert back to the person you were when you lived there. You realize for the first time just how relative time is.

The rest of the time, different places are kept largely separated in our minds. The more connections our brain makes to something, the more likely our everyday thoughts are to lead us there. But connections made in one place can be isolated from those made in another, so we may not think as often about things that happened for the few months we lived someplace else. Looking back, many of my homes feel more like places borrowed than places possessed, and while I sometimes sift through mental souvenirs of my time there, in the scope of a lifetime, I was only a tourist in my own journey.

I can’t possibly live everywhere I once labeled home, but I can frame these places on my walls. My decorations can serve as a reminder of the more adventurous person I was in New York City, the more carefree person I was in Connecticut, and the more ambitious person I was in New Orleans. I can’t be connected with my home in the intense way Easterns are, but neither do I presume my personality to be context-free. No one is ever free from their social or physical environment. This is ever more true in todays social media terroir. And whether or not we are always aware of it, a home is a home because it blurs the line between the self and the surroundings, and challenges the line we try to draw between who we are and where we are.

For me right now as a soloist, home isn’t a place. It is a person. And I think I am finally getting home right.

I live in my own little world. But its ok for me. It appears they know me here well and I like that discomfort.

Reading Anna’s poem made me realize discomfort is the price of admission to a meaningful life………….I rather like that.

Thiamine, also known as vitamin B1, is now known to play a fundamental role in energy metabolism.  When we are deficient in B1 the mitochondrial matrix suffers from pseudohypoxia.   Its discovery followed from the original early research on the ‘anti-beriberi factor’ found in rice polishings. After its synthesis in 1936, it led to many years of research to find its action in treating beriberi, a lethal scourge known for thousands of years, particularly in cultures dependent on rice as a staple.

Thiamine pyrophosphate (TPP) is the active co-enzyme form of thiamine and it is abundant in human RBC’s.  For this reason it is a reasonable marker that we can use in mitochondrial matrix failure associated with higher heteroplasmy states.  When we see abnormal peripheral smears in patients it signifies that we might want to clinically assess TPP activity and thiamine levels in our patients.  Some disease states associated with high mitochondrial density show these clinical features more often than not because certain organs have higher mitochondrial capacity.

When TPP is abnormal so is transketolase in RBC’s.  Transketolase is an enzyme of both the pentose phosphate pathway in all organisms and the Calvin cycle of photosynthesis.

When RBC transketolase is abnormal this is a beacon that RBC might not have a high fidelity signal connecting the sun to our colony of mitochondria.  This fosters the development of heteroplasmy in an insiduous way.  If one is not looking for it, a relative thiamine deficiency can manifest in many disease or non disease states.

In humans, transketolase connects the pentose phosphate pathway (EMF 4) to glycolysis, feeding excess sugar phosphates into the main carbohydrate metabolic pathways. Its presence is necessary for the production of NADPH (PPP), especially in tissues actively engaged in biosyntheses, such as fatty acid synthesis by the liver and mammary glands, and for steroid synthesis by the liver and adrenal glands. Thiamine diphosphate is an essential cofactor, along with calcium as a co-factor.

THE KEY LINK:

Thiamine Pyrophosphate (TPP) is the cofactor needed for the following reactions, Thiamine is required for only 4 biochemical reactions in the body  1. Pyruvate dehydrogenase 2. α ketoglutarate dehydrogenase  3. Branched-chain ketoacid dehydrogenase  4. Transketolase  TPP is involved in energy metabolism. Deficiency of TPP will affect the link reaction and TCA cycle. This leads to reduced ATP production and can alter function of the Pentose phosphate pathways I wrote about in EMF 4 blog post.  Red light from the sun can augment this ATP loss from thiamine deficiency.

Transketolase is an enzyme that uses a thiamine pyrophosphate (TPP) as its KEY cofactor to conduct a 2 carbon transfer from ketoses onto aldoses in humans. In the Pentose Phosphate Pathway (EMF 4 blog), it performs both a transfer of carbons from xylulose-5-P onto Ribose-5-P and onto Erythrose-4-P, setting them up for reaction with transaldolase.

Transketolase activity is decreased in deficiency of thiamine and can be used as a marker of heightened heteroplasmy by enlightened physicians.

RBC transketolase activity is reduced in deficiency of vitamin B1, and may be used in the diagnosis of Wernicke’s encephalopathy and other B1-deficiency syndromes if the diagnosis is in doubt. Apart from the baseline enzyme activity (which may be normal even in deficiency states), acceleration of enzyme activity after the addition of thiamine pyrophosphate may be diagnostic of relative thiamine deficiency from any causes.  This altered activity can be quantified as follows:

a. 0-15% normal

b. 15-25% deficiency

c. >25% severe deficiency

CENTRAL LEPTIN RESISTANCE:  LONG LOOP OF BAZAN

Liver disease is one such disease state that causes central leptin resistance (Leptin resistance Part Deux blog).  Most cases of liver disease have central leptin resistance associated with them due to damage of the long loop of Bazan (image below).  This limits the reincorporation of DHA into human cell membranes and fosters inflammation because the elvanoids cannot be made to curtail the inflammatory cascade.

 

Simultaneously, thiamine can be depleted because of altered matrix functioning.   There is brisk evidence that thiamine deficiency is found in many liver diseases.  The literature reports 58% of patients with chronic liver disease have B1 deficiency, moreover, the incidence is higher in alcoholic than in non-alcoholic hepatic patients. It has also been shown that daily supplementation with high doses of thiamine hydrochloride (200 mg/day) for one week can restores levels of thiamine pyrophosphate (TPP) in most cases.  Since TPP is the active co-enzyme form of thiamine, it also stimulates synthesis of the enzyme transketolase. Because of the essential role of TPP as a co-factor in intermediary metabolism of carbohydrates, lipids, and protein it can be a proxy marker for mitochondrial matrix dysfunction.  It maybe a NOVEL new way for us to indirectly measure heteroplasmy levels in humans.

THE LINK TO TECHNOLOGY:

Because thiamine is a major factor in the metabolism of glucose, it has long been known that ingestion of simple carbohydrates, processed in the body mainly to glucose, automatically increases the need for dietary thiamine. Since Frey and Volkow work, we know exposure to nnEMF also increase AMPK and glucose metabolism it should be clear that technology use and abuse can mimic nutritional problems historically associated with Vitamin B1.  Thus, high calorie malnutrition and technology abuse should be commonly associated with a chronic relative thiamine deficiency, irrespective of its fortification in food substances or the diet of any patient.  This relative deficit might lead to unusual presentations of disease linked to elevated heteroplasmy in humans.

QUICK SUMMARY:

Thiamine is normally present in pastured  lean pork and other meats, wheat germ, liver and other organ meats, poultry, eggs, fish, beans and peas, nuts, and whole grains. It is lower in foods like those mentioned above that have been altered by man’s input into food webs.  Blue light screens and nnEMF field deplete cells of thiamine because of how they affect AMPk pathways and glucose metabolism to mimic high calorie malnutrition.  Modern dairy products, fruit and vegetables are not good sources of B1.  In fact most of them deplete thiamine stores.  Humans only have the ability to store 14-18 days of this essential vitamin.  This storage ability is decreased by technology abuse and by vegan/vegetarian diets.   The RDA is 0.5 mg per 1000 kcal, adequate for a healthy individual consuming a healthy diet. Considerable losses occur during cooking or other heat-processing of food. Polyphenolic compounds in coffee and tea inactivate thiamine so that heavy use of these beverages could compromise thiamine stores in tissues.  

CITES:

http://jackkruse.com/emf-4-why-might-you-need-carbs-for-performance/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6435462/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6459027/

When a wise person speaks he understands fully the intent of the words, but what the ignorant person hears is subject to their present set of knowledge. There is an inherent disconnect. There is always a loss of information and energy transfer in this case which is why social media is not the ideal place to explain yourself in order to teach.

This requires the student having skin in the game to understand things well and it is best done in person. Where misunderstanding dwells, misuse will not be far behind in the under-educated mind. It is far safer and wiser for the quantum biologist to remain on the solid ground of the physics of light and eschew the shifting sands of philosophic extrapolations found in modern physics. The ignorant among us can know things, but the point of life is to understand how all things link back to the fabric of nature and life.

Life also has another surprise for those with natural wisdom: When we talk sense to a fool they often try to label you foolish only because of their own ignorance. If your audience is not wise this can lead to meme creation and control of many other lean minds. The goal is to make the curious wise with nature’s wisdom quickly to overcome the wasteful inertia of a paradigm’s core beliefs. This is why I am allergic to a closed mind who buries curiosity. What is the core message for a curious mind? Just because you don’t understand it, doesn’t mean or imply that the truth is not being delivered to you. Your wisdom myopia does not trump the deep truths buried in nature’s laws. There is a science of light out there to understand, and to bring it to biology is to brighten everyone’s perspectives. Today, biology is in the dark ages of understanding how light works with and within cells and innovates life from abiotic atoms.

This must change if medicine is to advance. An age in science is called dark, not because the light fails to shine, but because people refuse to see what is already published in the literature but still have yet to understand how it links back to life. Their educational myopia allows them to remain in the dark because they continue to misunderstand the implications of this data.

Your friends and family might not understand your new found ideas so this might help you help them to improve your relationships with in your circle of six.

I covered this in Levee 25 of the Quilt long ago and now this series will visit this in depth:

Hypoxia/pseudohypoxia.  Hypoxia is a cellular state that disrupts normal oxygen supply to the tissue (mitochondria), causing cellular dysfunction. Examples of t 25.his are altitude sickness at high elevations and clots in a blocked artery in an organ causing an organ to fail and die. Apoptosis and autophagy allow cells to adapt over their lifespan to many situations. Hypoxia is directly toxic to mitochondrial energy production. In humans, when oxygen is in short supply we can shift to anaerobic energy production, but it is not as efficient as mitochondrial energy production. Athletes with proper training can perform well in anaerobic conditions but it does appear that they pay a steep price for this adaptation by depleting their stem cell supply.  The gateway in mitochondria for hypoxia is pseudohypoxia by blockade of pyruvate which sits atop the TCA cycle inside the matrix.  The gatekeeper of the creation of Acetyl-CoA from pyruvate is thiamine.  It is the major controller of substate movements in the matrix.  As it drops we lose control of UCP-2 and this alters the matrix concentration of hydrogen isotopes.

Thiamine deficiency causes a relative pseudohypoxia and is closely linked to heteroplasmy rate elevation in aging.  Coffee and polyphenols destroy thiamine levels.  As this occurs there is massive signaling to the SIRT system to affect mitochondrial biology.

As a consequence of pseudohypoxia, NAD+ levels drop and this funnels all the way back to how the aromatic amino acid tryptophan is catabolized in cells.  It has multiple pathways it can travel and the pathway chosen will lead to the cell’s fate.

Hypoxia plays a role in aging because as one age the amount of blood to organs declines as the heart fails to deliver the same amount of blood through a stiffened arterial tree throughout the body. THIS IS A PROTECTIVE STATE FOR POOR MITOCHONDRIAL FUNCTION = higher heteroplasmy rate.

This causes cellular oxygen levels to fall and usually is a signal to mitochondrial biogenesis to offset the deficits. As one age, this signaling system is not as accurate in sensing changes to the oxygen level. This can be measured in the pyruvate/lactate levels. Low oxygen tension is a signal to autophagic pathways that normally help repair cells. If this gets impaired, signaling autophagy becomes less effective as we age and results in more organ failure and diseases of aging. Hypoxia is critical signaling in the cell for repair processes. This is disordered in heart disease and in sleep abnormalities such as sleep apnea. Hypoxia decreases cell mass and improves leptin resistance by forcing a calorie restriction via a relative thiamine deficiency state. This only operates well if the person remains in a strong solar environment.

This, below, is the deep lesson of levee 25.

Free radicals and reactive oxygen species (ROS) in particular play an important part in aging because they direct repair and regeneration and taking antioxidants ruins this endogenous signal. Free radicals are (usually small) molecules lacking an electron needed for stability; they will steal an electron from the first thing they bump into. Like pulling a cog out from clockwork, stealing an electron from a protein or enzyme is usually not good for the finely-tuned biochemical machinery of our cells. The free radical might be rendered safe in the process, but it has left some form of chaos and damage in its wake.

Free radicals are sufficiently dangerous to biochemical machinery that some of our body’s defenders use bursts of free radicals as a kill mechanism. That is why Denham’s belief has died too slowly. Science changes though as data comes in.

Scientists now generally concur that accumulated damage throughout the body due to free radicals is one important root cause of age-related degeneration – but the devil is in the details. The vast, overwhelming majority of those free radicals are generated by your own metabolism as an unavoidable byproduct. The rate of free radical generation increases greatly with age as the basic mechanisms of your metabolism are themselves damaged by the free radicals they created. This is not a one-step process, however. I’ve tried to walk through it at a high level at my blog, cribbing from the mitochondrial free radical theory of aging that was proposed by Wallace and working its way into general acceptance because of new data

Within each of your cells are many mitochondria, tiny biochemical power plants that convert chemicals from food to ATP, the basic fuel molecule used by your cells to provide energy for life.

You have to beware of people who take advantage of the antioxidant theory of aging and have no earthly idea of how mitochondrial creation of free radicals really works. This is why supplement makers and coffee makers are pushing the false narrative that antioxidant use is wise. Marketing is legalized lying.

Mitochondria were once a separate organism that came to live in symbiosis with ancestral cells. As such, they brought their own DNA to the party; some of it still remains within our mitochondria, separate from the DNA we carry in chromosomes in the cell nucleus.

Mitochondria have a couple of ways of generating ATP. The more efficient of these methods – oxidative phosphorylation (OXPHOS) – generates some amount of free radicals as a natural byproduct, and requires the proteins coded in the mitochondrial DNA to function. It is the predominant way by which healthy cells generate their power.

Free radicals created through OXPHOS within a mitochondrion are most likely to damage that mitochondrion; they’re very reactive, so they won’t get far before sabotaging something. The components that really matter are (a) a membrane that helps organize the movement of various chemicals in the process of generating ATP, and (b) the mitochondrial DNA.

Sufficient free radical damage to mitochondrial DNA shuts down OXPHOS within that mitochondrion, as the necessary proteins can no longer be produced. The mitochondrion switches over to using a less efficient method of producing power, one that doesn’t produce free radicals but has to run at a much higher rate to produce the same level of ATP.

Mitochondria, like most cellular components, are recycled on a regular basis. Components called lysosomes are directed around the cell in response to various signals, engulfing and breaking down damaged or worn components. After the herd has been culled, surviving mitochondria within a cell divide and replicate, much like bacteria, to make up the numbers.

The signal to break down a mitochondrion is triggered by sufficient damage to its membrane: a sign that it’s old, leaky, inefficient and needs to be replaced with a shiny new power plant.

BUT: if a mitochondrion has had its DNA damaged to the point of stopping OXPHOS/beta-oxidation/alpha-oxidation, it will no longer be producing NORMAL free radicals that can damage its membrane. So it will never get broken down by a lysosome. When the time comes to divide and replicate, it will replicate its damaged DNA into new mitochondria and disease is spread like a bacterial infection in your tissues. None of those new mitochondria will be producing free radicals via OXPHOS, and so will not be recycled either (autophagy).

One DNA-damaged, non-OXPHOS mitochondrion will eventually take over the entire mitochondrial population of a cell in this way. At that point, the trouble really gets started.

By the time you hit late life, perhaps 1% of your cells are in this state of being taken over by non-OXPHOS mitochondria. As for any neighborhood or city, it only takes a small proportion of dangerous criminals to make life really unpleasant for the rest of us. Same true here at the tissue level.

Non-OXPHOS mitochondria have the unfortunate effect of depleting a needed molecule used in many cellular processes, NAD+. This is a carrier molecule in the OXPHOS process, given an electron (and turned into NADH in the process) to port between point A and point B within the mitochondria. Once the electron is delivered, the NADH becomes NAD+ again. But without a working OXPHOS process to return NAD+ into circulation, the cell would quickly build up a deadly excess of NADH, run out of NAD+ and hypoxia occurs and cells die. (Sinclair, 2013)

Fortunately for the cell, and unfortunately for us, there is another way to recycle NADH into NAD+. Since NADH is just NAD+ with [amongst other things] an electron stuck to it, all the cell has to do is export those unwanted electrons to other proteins via the Jablonski diagram I have posted over and over.

In the points above, I omitted details of the reaction that transforms NAD+ to NADH in order to focus on the electron that is ported around. Wikipedia gives an introduction to the full picture, which also involves an extra hydrogen atom (non-deuterium) – NADH is NAD+ with the addition of a hydrogen atom (one proton, one electron), and an additional electron. Nonetheless, it is the shuttling and exchange of electrons that is important here.

In a form of chemical waste dumping, this is just what the cell does. Structures on the cell membrane known as the plasma membrane redox system (PMRS) export electrons from NADH, recycling it into NAD+. This process is only very active in cells that have been taken over by DNA-damaged, non-OXPHOS mitochondria, but their outer surfaces are little hotspots of electron dumping.

What do these electrons do? Well, for one, they combine with oxygen molecules – which are abundant in any of our living tissue – to create reactive oxygen species (ROS): more free radicals. Sick cells have pseudohypoxia to limit the damage and try to survive as autophagy is defective. This causes organ failure. So you have the Rube Goldberg system outlined above whereby a few free radicals have caused a cell to become an ongoing, major exporter of free radicals into the surrounding environment. These will make life unpleasant for surrounding cells, but that is most likely not the real problem. ROS just can’t travel far enough to explain how a corrupt 1% of our cells can cause a large fraction of the difference between being young and being old.

A more likely target for all the newly created ROS is cholesterol. Cholesterols, such as low-density lipoproteins (LDL) are used everywhere in the body and travel widely. If ROS reacts with nearby LDL – and there will always be nearby LDL – to form damaged, oxidized cholesterol, that damaged cholesterol can then be incorporated into and further damage biochemical processes throughout the body. For example, its effects on our arteries is well known: What is not well known is how the light that excites that electron damages cholesterol rings by how it is programmed. If the right frequency of light is on the electron cholesterol works well……if not you get a disease.

In conditions with elevated concentrations of oxidized LDL particles, especially small LDL particles, cholesterol promotes atheroma formation in the walls of arteries, a condition known as atherosclerosis, which is the principal cause of coronary heart disease and other forms of cardiovascular disease.

There are many other ways in which accumulations of oxidized cholesterol can send biochemical processes awry. This, then, seems to be a good candidate for the plausible, systematic method by which a small number of cells can work such varied damage upon your entire body.  Mitochondrial damage acts just like an infection does at the tissue level.  Aging does the same.  This is why health is the slowest form of death we chose by using the right light that excites electrons.  Mitochondria deal the right electrons to the right tissues to build health.

Do you only value something if you know it’ll end?

So what do you do with your significant other when it is over? Ponder the question before you pull out a piece of paper and answer this question.

What would a Black Swan do?

Would they sacrifice themselves and leave what is left for the person they are cutting out of their life?

Do you believe there is addition by subtraction?  Many people talk a big game but are they capable of writing a goodbye letter to a spouse who ruined your life?

I think Neil Young had it right when he said, ” “It’s better to burn out than to fade away.”

Sometimes we need to look past the chemistry and the butterflies to what is really going on at the base of it all. Who is the person you’re looking at in this moment? Do they match the idealized figure you’ve built up in your mind? What behaviors are confirming or denying that belief?

Will you end your relationship quickly or will you bleed it slowly?  Most people will go for the slow death of a relationship because they have little experience with death.  This is a grave error.

How many lost days are you willing to sacrifice before you give up?

For those who value time the answer will be different than the rest of you reading this.

Do you believe there’s a beginning in an end ? It’s true that you can’t reclaim what you had, but you can lock it up behind you. You can start fresh if you cut the head off the snake soon.

Are our relationship’s just a bunch of accidents, connected by one perfect end?

Does the end of your relationship  justifies the means. Might it be true that sometimes you have to do the wrong thing to get the right result?

Have you considered unusual mechanisms to solve your relationship dilemma?

How much do you know about discernment counseling?

Discernment counseling is not couples counseling. It doesn’t aim to fix any problems. Instead, in just a handful of sessions (both joint and individual), it helps couples on the verge of relationship breakdown understand why their problems have become so intractable, helping them trace the downward spiral and examine their patterns from a different perspective. In a sense, it’s an exit interview for a relationship, but one that leaves the door open to reconciliation.

And in an instant it all changed.

When I decided to get divorced I did discernment counseling before I signed my divorce papers………..I wanted to make sure my decision tree was plumb with my reasoning before I ended my relationship.

In this therapy I found out 50% of people who hire this type of therapist save their relationship before they transition into more traditional therapy. I found out many people who do this have even backed out of divorces. This peaked my interest. This why I did it. I did it on my own. I beleive many couples are unhappy for a long stretches, but many feel they can’t just leave. because they haven’t really done any work to address the problems in the relationship in any meaningful way.

Before my final exit I had to know I covered all my bases. So I jumped and did it.

When our partners aren’t right for us, they have a funny way of showing us that truth, but it takes a dose of radical honesty to see these warnings for what they are. To see these red flags for what they are and accept them, we have to start loving ourselves and setting boundaries both inside and out. Only when we learn how to love ourselves can we truly start loving others and receiving the love we deserve.When we love, we love deeply and that can often cause us to overlook critical red flags and warning signs that are best faced head-on and in the moment. Part of forming happy and lasting relationships is learning how to confront issues in those relationships as they happen, something that takes both time and understanding to carefully manage.

Most of the couples who sign on for discernment counseling are “mixed agenda,” meaning one is eager to walk (me), and the other wants to make things work (her).

I did it because I was sure I was done……..but I wanted exogenous validation that my feelings where solid before i dropped the hammer on my partner.

I suffered deeply from relationship ambivalence—this is the agonizing process of feeling uncertain about a romantic partner even while going through the daily motions of a relationship.

I think I had hoped I’d find an answer to why I felt why it was worth while staying, or maybe that I may conclude that I shouldn’t stay at all.

With either conclusion, the mark of successful discernment counseling is when a person can step outside themselves to view the relationship — and its dissolution — more objectively.  You have to remove your cognitive biases about the other person before you decide to stay or go.

Research suggests that couples struggle with relationship difficulties for an average of six years before seeking help. When you’re nursing a deepening hurt over that amount of time, it’s easy to become a bit solipsistic, favoring acts of self-preservation over generosity. It’s harder to see past old and recent wounds to adopt another perspective on the problem, even when doing so might provide a solution.

We confuse feelings with the stories we make up about those feelings.

My suggestion is to avoid couples counseling and try discernment counseling solo for yourself to figure things out for you before you call an attorney.

Discernment counseling made me feel like I did my homework, regardless of the outcome.  I felt that  this is the Black Swan thing to do before burning a relationship bridge down and trying to start over.

CITES

1. https://www.gottman.com/about/research/couples/

Harmony makes small things grow. properly in nature…… Lack of it makes big things decay around and in us.  Factor Y is a term I use for the sixth extinction that has begun about 120 years ago.  The political left, in my opinion is using climate change narrative to hide the real fact that the electromgnetic force is behind the 6th extinction.  Why do I believe this?  C02 thermodynamically cannot act fast enough to explain the Permian extinction or the current one ongoing.  The electromagnetic force can.  It is the strongest of the 4 forces and it has unlimited range and power so this means it can cause quick changes that will often be hidden for a time because many of the effects will be non-linear in nature.  5G from above courtesy of Elon Musk is one such non-linear change.

Technology use and abuse cause the capricious cohabitation of the human’s mind. Nature’s harmony makes small things grow. Lack of it makes big things decay. Technology ruins biologic coherence and induces degeneration of the mind and a lapse into cancer as the US National Toxicology Program’s final release is warning us.

Human behavior is fascinating. We like to think of ourselves as intelligent, rational beings. But we regularly fail to recognize basic logical fallacies. Our hedonistic propensities propel us to accept correlation as causation when it appears to validate behaviors we like to engage in, like abusing light technology under the guise of “progress” and crafting the narrative the sun is toxic. It is pure insanity.

Give me some examples of a non-linear effects Jack.

A small stimulus leads to massive amplification = a non-linear effect

1. A nuclear weapon can be thought of as non-linear action. It is the size fo a small car yet it can level a city.

2. A star like the sun can be thought of the same way. It is relatively small yet it can warm 9 planets over billions of miles.

3. Small amounts of UV light from the sun can leach into the eye (1%-3%) yet they have the greatest effect on the RPE dense core granules to drive the central retinal pathway that connects to the SCN and leptin receptor to control the growth and metabolism of every human on Earth.

4. The change in networking power used on the internet went from 0G in 1995 to 5G today. That is only 23 years.  That small change in the electromagnetic force  is fully capable of leading living things to the sixth extinction level event on Earth.

Those are some examples of non-linear effects.

All epigenetic effects are also non-linear. Blue light and nnEMF cause HYPERMETHYLATION of DNA and RNA. <——- That is the major change agent of the epigenome and we saw how Scott Kelly went up into space for 340 days and sustained massive epignetic genome changes compared to his identical brother left on Earth.

I think the increase in network power is now speeding up Factor Y among us but I think few realize it because the sands of time appear to move slower when you are in the mid of the 6th extinction.  The evidence is all around us if your dopamine level is high enough to sense the trend.   That assumes of course youre capable of looking for it by deciding to look for evidence of it.

Human and animal infertility are now at unbelievable levels inside of cities.

What is the mitochondrial reality of this event?

Do we have any historical evidence for the mechanism and how it might be devloping ?  We do.

Smog affects oxygen tensions, and oxygen tensions affect the NAD+/NADH ratio’s in your mitochondria.  Some anniversaries pass with little notice. Herewith a reminder that 70 years ago people dropped dead from air pollution in the Monongahela Valley town of Donora. Unfortunately throughout India and China today, similar conditions can be found with levels of particulate sometimes averaging more than 1000 ppm.  This explains where China and India fertility rates are dropping rather dramatically in the 21st century.  Introducing and industrial and tech economy to an agrarian lifestyle built over the last 5000 years will have a non-linear effect on mitochondria.  Light and oxygen always have nonlinear effects in biology and this trips up most conventional thinkers in biology.  This is why we have historical anecdotes that matter a great deal to the Black Swan in training.

MITOCHONDRIAL OXYGEN

For example: Another interesting link between the air and life is found in the Andes of South America. When the Spanish came to conquered the Indians who lived up at their altitude and settled with them there were no Spanish couples able to have children there for 53 years. It was only when they began having intercourse with the native people that they were able to have children at these altitudes. The reason was simple In Spain has oxygen tensions at 21% but in the Andes where the Indians were at serious altitude the oxygen levels were only 12.5%. This decrease in consumption in th emitochondria means that more oxygen is dissolved in the cell and this fosters more free radicals that make DNA more unstable. The Indians offset this risk by altering their epigenomic marks with methyl groups and histone acetylation.

Generally at sealevel, where the Spainards came from, and most people are, you need oxygen to act as the terminal electron acceptor and not be dissolved in the cell. This supports conversion of pregnenolone to the sex steroid hormones and for leptin to allow fecundity.

This basic mitochondrial fact should wake up modern humans who have demolished their hormone panel and need fertility docs to have a kid. This is huge evidence you are a TECHNOLOGY abuser. Technology use induces pseudohypoxia and upregualtion of AMPk pathways and sets the tone for mitochondrial diseases by lowering the matrix redox power from NAD+/NADH to oxygen as the picture below shows.

This lowers the electrical power difference between the beginning and end of electron transport. Taking NAD+ or using HBO to increase oxygen cannot fix this situation either. If you do this you will INCREASE free radicals that will damage your colony of mitochondria further by destroying heme proteins in the cytochromes and this will reduce the water that cytochrome 4 can make. So vet your expert advice well before buying their solutions for your infertility problems. A repair of your technology diet is more wise than clomid is for your offspring. forcing nature to do something with bad mitochondria in your germline is not a wise move if you want to have a healthy kid.

So there is a deep link of air pollution to a lack of sun and lowered fertility……but air pollution also brings low oxygen tensions and the two phenomena involve different mechanisms both acting on different parts of the mitochondrial biologic programs. This is an interesting Black Swan lesson contained here about the Andes and native Europeans.

HOW DOES THIS WORK MECHANISTICALLY?

According to mitochondrial data, when the pH of water drops (acidic = more H+ or D), so does it’s ability to absorb oxygen.

Therefore, a life or germline without sun or ground should result in a dynamic state of hypoxia, assuming the above is true.

If the mitochondrial respiratory processes are compromised and water is not able to absorb oxygen effectively from the lungs, where does this excess oxygen go? It goes to the broken mitochondrial engines where free radicals are made by the cytochrome proteins. How do mitochondria make free radicals to signal? ELF-UV bio-photons and oxygen must be present. Is this why oxygen levels are quantized precisely with mitochondrial damage in cells? YES INDEED.

If the mitochondrial respiratory processes are compromised and water is not able to absorb oxygen effectively from the lungs, where does this excess oxygen go? It goes to the broken mitochondrial engines where free radicals are made by the cytochrome proteins. How do mitochondria make free radicals to signal? ELF-UV biophotons and oxygen must be present. Is this why oxygen levels are quantized precisely with mitochondrial damage in cells? YES INDEED. As biophotons are released from the cell and NAD+ drops at cytochrome one. Why? Freed vitamin A destroys the heme protein at this cytochrome. There is no catalase, another heme chromophore to control it. We call this the pseudohypoxia state that David Sinclair found in Dec 2013 study published in Cell on this very topic. Even he has not put it all together. When all these things occur heteroplasmy is rising and cell volumes rising and ubiquitin marking increasing how aging really occurs in a quantum fashion. So do aging old people have kids? No………this is why when this state happens in young people they are infertile.

Let us go further……..What does pseudohypoxia (low NAD+) mean to our hormone panel in the sex steroids region? The cost of a high aerobic capacity is low fertility. This is why the pregnenolone steal syndrome exists and why males suffer low testosterone and females have an upside down PG/E2 ratio in menopause. their mitochondria can no longer make water well at cytochrome 4 and this is why infertile and aging people have markers of dehydration on labs. It is not what the anti-aging or functional medicine docs think or believe. This is quantum biology 101 for a Black Swan.

This formula above goes hand and hand with what I said in the November 2018 webinar about the 5G risks humans all face. If you think taking NAD+ analogs are wise you clearly are no Black Swan.

Producing cortisol over sex steroid production is survival mode for the cell and it is due to the use of oxygen as the terminal electron acceptor in human mitochondria in a really bad light environment (blue or nnEMF). As this occurs in a women’s gut at menopause their lower esophageal sphincter (LES) allows more O2 into the gut lumen because its myoglobin (another heme photoreceptor protein) is destroyed by the freed Vitamin A and this simplifies the gut flora changing the microbiomes biophoton light release to the enterocytes. This alters its circadian biology and affect activation of the GALT and the liver. This allows too much deuterium into the liver = fatty liver.

The liver is where most catalase is located in humans. This raises more free radicals in the liver making its deuterium load greater and lowering hormone production further. Remember the liver controls the long loop of the Bazan effect.

This cause global reduction of DHA in cell membranes ruining circadian control in many organs. The mitochondria also make thyroid hormone, specifically T2. This lowers thyroid hormones T2 and T3 and women cannot absorb the sun’s light even if they are naked at the equator. Lack of catalase ( increasing H2O2) and lack of AM UV/IR light fuel this low fertility. Catalase is most commonly found in the liver of humans.

Artificial light, with a lack of sunlight makes fertility doctors rich and busy. It’s not our abilities that show what we truly are, it’s our choices of light we live under that determine our fate when it comes to fertility. This is why people are infertile in a blue-lit microwaved world.

CITES:

1. https://www.telegraph.co.uk/news/2018/10/31/italys-populist-government-plans-reward-fertile-families-state/?fbclid=IwAR2C7qzb3JzD4H-jk9-9pz2tqgBR98im5fWUx_YbJZoj3AOrjI0l-C48-yc

2. Elizabeth Kolbert: The Sixth Extinction.

3.   https://www.smithsonianmag.com/history/deadly-donora-smog-1948-spurred-environmental-protection-have-we-forgotten-lesson-180970533

How do you process death? Most people struggle with death but what happens when you see somebody you love dying before your eyes while they are still living? How do you approaching the living dead about the choices that brought them to this place in your life?

How do you process their choices that have imprisoned their thinking and their mindset?

The causes of death are many and varied. It might be due to a mood disorder or depression because of life of night shift work. That chronic depression might lead to a suicide attempt. The very same scenario might not ever get to suicide but it could lead to dementia after 20 years of decline. The mood disorder might be caused by indoor office work that eventually lead to obesity, diabetes, stroke, that eventually lead to heart disease and an early death. On the way to any of these diagnosis, your relationship with that person might be radically affected by their choices. If you love them, do you ignore their choices and let them do what they want as you suffer and watch them die?

How do you salvage a relationship with a friend or partner who is hell bent on continuing to make choices that will ultimately cost them time……time in their life.

In survivor training they teach us how to not die when you’re helping rescue a drowning person who is anxious and fighting to survive.  If we get this decision wrong, you both drown.  Is this a wise choice?  I think there is a way to help a friend or partner when they are in dying mode while they are actively living and breathing.

The mode of how they are dying is the key to understanding what your best choice might be.  I don’t believe there is any correct answer for any relationship on life support.

THE GOODBYE CHECKLIST

1. You’d be wise to enlist the help of your cicle of six when trying to help another

2. Write them a goodbye love letter

3. Look them in the eyes while handing them an appointment to see a doctor to get a term life insurance policy you as the beneficiary.

4. Ask the dying while living what you can do to help.

What happens if the continue to ignore you? Are you prepared to force them to see a life without you in it?

Can you walk away to teach them how much you really care?  In relationships, people often get complacent with time because they become imprisoned by comfort and luxury.  They begin to avoid the discomfort of thinking.  This is how “comfortable thinking” creates cognitive biases.  Sometimes those biases can harm you and lead to illness or death.

Have you ever cared so much that you were willing to create a perfect dismount scenario for your significant other?  Dying while your living comes with many contexts in life.  It is a very tough situation to navigate.  There is no one recipe for all.

You have to try to got others who pack your parachute help you navigate these rough seas.  These people often can help you help the dying person see their self worth to once again love themselves again.  Without this love they will never be capable of loving you or anyone else.  Don’t we have to try help others see the value of time?

Nothing is harder than seeing your best friend kill themselves while they are alive, in my opinion.

Are you prepared to follow them to their grave?  Are you prepared to dig yourself in deeper into redox hell for them?  Is their a time limit that you’ll impose on them?  Or will you continue to give them a pass for their choices?  How long will you give them this pass?  How many of your body parts are willing to sacrifice?

When you love someone there are a few key questions to consider.  Do you love them unconditionally?  Are you in love with them now after their choices have changed the relationship between both of you?

Do you believe you can love someone, yet let them go completely for their own good?  Do you accept that it might be regal to release a person you love or loved, when their end is near?  Isn’t it true that real love is like a boomerang; it should be expected to come back if it was true?   Cutting your love loose is a wicked game.  Would you gamble this big if it was your only option left?

People only focus on your wisdoms, until they see the depth of how much you care.  I believe you can love deeply, without being in love, because love does not operate like a light switch.  Once the switch is flipped off, it cannot be easily turned back on.

Would you still be willing to help as choices continue to be made that will extinguish their light?  What happens when you finally realize the choices of others are the hinges of destiny in our relationships?

The differences in the stumbling blocks in relationships and stepping stones is in how we use them.

Are you ready to make them see you are willing to do the hard things to make the blind see again?  Can your actions put windex on the glass eyes of the dying?

You cannot make progress without making decisions in relationships. I have found a peacefulness follows any decision, even the wrong one.  It’s not hard to make decisions when you know what your values are.  How do you value your life?  How do you value time?   When one bases his life on principle, 99 percent of your decisions are already made.  They are made by the choices we make.

How all in are you really?  for you or for them?

Are you waiting for someone to put flowers on your casket or are you willing to plant your own garden to decorate your life right now?

We don’t heal anyone’s past by dwindling there with them and allowing them to remain imprisoned there by old choices.   We can only fully heal them by teaching them to live fully in the present even it that present no longer includes them any longer.

As a surgeon I am addicted to helping and saving the person dying an acute death.  It is what I am trained to do.  As a man in a relationship on life support, I found out that saving someone I love, is a lot more like trying to save a person drowning in the sea.

You have to be careful of how you attempt to save them, because you might go down with them.  This serves neither person or your family.  This is why living fully, while being solo might be the toughest goodbye that contains the best long term Rx.

In realtionships, actions prove who you really are. Words are just who you pretend to be…………..