Posts made by Amazoniac

Amazoniac

@Amazoniac said in cancer:

@Jennifer, are the clinics based on Gerson's protocol in Mexico an option to consider? Battling a relative for one small win at a time can be draining and lead to loss of valuable time. You may also face pressure from the entire family if you oppose their opinion.

The cancer program offered by these clinics would demand a series of interventions at once, him and the rest of the family would probably be less resistant when clinicians are involved, and part of the responsibility would be lifted from you (food preparation, supplements, decisions).

The protocol should rely on the support of substances that you're familiar with. A few examples:

Aspirin

Niacin

Caffeine (through the other end, but still)

(Pro)poison A

Thyroid hormones (with Lugol's solution)

Regarding the clinics, some are depressive, but others look like a spa with people on vacation. They can be pricy; however, it's possible to find alternatives, such as the remote (yet supervised) version of the treatment.

We read on occasion the miraculous recoveries after minor changes, but comprehensive approaches increase the chances of success. If you had difficulty convincing him to let go of a beverage, a marked change in diet for therapeutic purposes doesn't seem likely without an external driver.

Nevertheless, in addition to the listed substances, Ray's cascara sagrada (check this out as well) to keep the bowels clean would be simple to apply for now.

Thank you, Gustavo. I appreciate the suggestions. My dad takes aspirin daily, gets provitamin A from mainly dairy and eggs, and though not enemas, he has coffee twice a day and regular elimination. As far as pressure from family goes, I’m the only one now with any real involvement in my dad’s life so the only opinion, and really the only one that matters, is his and he’s set on having conventional treatment. I essentially control his diet, but with my family’s failure to thrive on a diet of predominantly plants, let alone one centered on juice, and my mum’s success treating her cancer with more of an animal-based diet combined with some of Ray’s recommendations, I feel more confident in that than the Gerson Therapy.

Jennifer,

A diet with rich in animal products is compatible with healing, but failing to thrive on plant-based diets can be advantageous if the approach is tweaked to limit the undernourishment to cancer cells as best as possible. The therapeutic diets are intentionally designed this way and the exclusion of most animal products is not unique to Gerson's protocol, other experimenters arrived at similar conclusions (Koch, Breuss and Kelley are examples). Considering that they dealt with people who were debilitated and wasting away at a dangerous rate, it's probable that your dad could tolerate a restrictive phase fine. Yet, cheese and solid meals are part of Gerson's program.

He's skipping to an aggressive option before giving a chance to the multitude of alternatives available, that could be tried under the right medical supervision.

I know your perspective on cravings, intuition and boundaries, so please don't crush me.

If a marked change in diet is out of question, a share of the nourishment of cancer cells is derived from tissue mobilization, which is something that you can control with supplements.

Regarding Progest-E, its vitamin E is sourced from soybean, that has desirable anti-cancer profile:

Antioxidant Micronutrients | Human Nutrition

γ-Tocopherol or combinations of vitamin E forms induce cell death in human prostate cancer cells by interrupting sphingolipid synthesis

"To evaluate whether various forms of vitamin E act synergistically, we examined the combinations of γT with αT, δT, or γTE that are rich in tissues and/or diets (30). Combinations of γT (25 μM) and δT (10 μM) or γT (25 μM) and γTE (2.5 μM) inhibited proliferation additively or synergistically (Fig. 3). Interestingly, these combinations exhibited antiproliferative potency similar to that of γT alone at 50 μM. αT, which is the most abundant vitamin E form in tissues and supplements, did not significantly enhance or counteract the inhibitory effect from γT alone (Fig. 3B)."

"It is noteworthy that the tumor cell lines we have tested appear to be more sensitive to γT-induced anti-proliferation or apoptosis compared with normal prostate epithelial cells. γT and combinations of vitamin E forms are therefore potentially attractive candidates as anticancer agents."

"It is becoming clear that individual vitamin E forms possess different chemical and biological activities (6) and have distinct tissue distributions (46, 47). We therefore hypothesize that combinations of different forms of vitamin E may be superior to each alone. Consistently, combinations of γT and δT or γT and γTE showed additive or synergistic effects. Importantly, αT did not interfere with the effect of γT, although αT is known to deplete γT in vivo (48). Although high doses of γT supplementation would be necessary to achieve relatively high concentrations of γT, i.e., 50 μM, the combination effect indicates that a similar biological outcome may be achieved by a moderate supplementation with mixed vitamin E forms such as γT and δT or γTE. The significance of this observation awaits further investigation"

Different Roles of Natural Forms of Vitamin E in Chemoprevention and Treatment of Prostate Cancer

"Starting from 2002, traditionally ignored vitamin E forms have been researched on their ability to modulate PCa, including γT, δT, and TEs (mainly γTE and δTE) in preclinical cell and animal studies. In particular, these vitamin E forms show much stronger anti-PCa effects than αT in cell studies, with relative potency concerning antiproliferation and proapoptosis of δTE, γTE > δT > γT >> αT. Further, γT, γTmT, and δT have been found to be effective for inhibiting relatively early-stage PCa, as indicated in carcinogens-induced and genetically engineered PCa models, whereas display modest effects against late stage cancer as indicated in PCa cell-implanted xenograft models. Meanwhile, γTE and δTE are shown to strongly inhibit development of prostate adenocarcinoma in genetically engineered spontaneously tumor-developing models. For this effect, δTE appears to be stronger than δT, the latter being more effective than γT. Additionally, amber evidence also suggests that γTE can block implanted PCa cells associated tumor development in xenograft models and is stronger than γT for this effect. γTE can also enhance anti-PCa effects of chemotherapeutic drugs in mice. Overall, these anti-PCa effects of γT, δTE, γTE, and δTE observed in preclinical studies provide evidence supporting the notion that these compounds may be useful for preventing early stage PCa progression in people at moderate-risk and high-risk of PCa. Considering their good safety, these compounds should be considered in RCT trials for secondary and tertiary (especially γTE and δTE) chemoprevention."

Unknown author:

And in line with Summer's comment:

Effects of fenbendazole and vitamin E succinate on the growth and survival of prostate cancer cells

@Jennifer said in New "Mission" of RPF:

It makes me happy to know my log brought people comfort. I wish I had something worth reading, but my log would most likely be just a bunch of random thoughts like my current thoughts on previous eras and how that energy has been passed down through the generations and potentially affected present day health. I’ve been watching Outlander and I think it’s a fantastic show, but brutal. It depicts a draconian time and it made me think of how staying silent and/or suppressing certain emotions thought to be “weak” to avoid persecution and for survival in general, may have an effect on the thyroid in particular. Since the thyroid is located in the throat chakra, the throat chakra being our truth, would not speaking our truth cause that energy that needs to be expressed to get trapped there and wreak havoc on our thyroid function and overall health? Something I find interesting is in First Nations culture, turquoise is believed to be protective to the bones and is often worn around the neck. Turquoise is blue and blue is the color that represents the throat chakra, and the thyroid and parathyroid are the main glands responsible for calcium metabolism and the integrity of our connective tissues, including our bones.

If this is what you refer to as worthless, keep up with the unworthy posts.

Ryke Hamer took the psychophysiological principle to the extreme, but you might find some validity in it.

Amazoniac

Hey, curer. "Seal" this:

Hodgkin and Reed–Sternberg cells of classical Hodgkin lymphoma are highly dependent on oxidative phosphorylation

Amazoniac

Individual cristae within the same mitochondrion display different membrane potentials and are functionally independent

"The IMM consists of subcompartments called cristae and inner boundary membrane (IBM) (Palade, 1953). Cristae are invaginations protruding into the mitochondrial matrix, whereas the IBM runs parallel to the outer mitochondrial membrane (OMM). Cristae and IBM are connected via narrow tubular or slit‐like structures, known as crista junctions (CJs). In recent years, studies show that components of the electron transport chain (ETC) are confined to the lateral surfaces of the cristae rather than equally distributed along the IMM (Vogel et al, 2006; Wilkens et al, 2013). Moreover, dimers of F1F0 ATP Synthase assemble in rows along the edges of the cristae (Dudkina et al, 2005; Strauss et al, 2008; Davies et al, 2011). The CJs can be kept in a closed state by oligomers of the inner‐membrane dynamin‐like GTPase, OPA1 (Frezza et al, 2006; Pham et al, 2016), as well as components of the mitochondrial contact site and cristae organizing system (MICOS complex) (John et al, 2005; Rabl et al, 2009; Barrera et al, 2016; Glytsou et al, 2016)."

"Measurement of ΔΨm in individual cristae reveals that crista junctions provide electrical insulation and sustain polarization of individual mitochondrial cristae within a single mitochondrion even when neighbouring cristae are damaged.

Cristae have higher ΔΨ compared to their adjoining inner mitochondrial membranes.

Cristae are electrically insulated, allowing individual cristae within any given mitochondrion to have different membrane potentials.

Cristae can remain polarized despite depolarization of neighbouring ones.

Disruption of crista junctions impairs the electrical insulation of cristae, equilibrating their ΔΨ with those of inner mitochondrial membranes."

"This study raises interesting questions as to why mitochondria organize the ΔΨm in this way. One advantage, for example, could be related to the fact that ΔΨm constitutes the main energy available to drive protons through F1F0 ATP Synthase to produce ATP. As such, the localization of F1F0 ATP Synthase at the cristae rims appears to be advantageous in terms of proximity to the batteries. Another possible advantage could be compartmentalization of ΔΨm in each crista may serve as a safeguard mechanism restricting the impact of localized damage. In the case of the equipotential model, where the inner membrane of the entire mitochondrion represents a single capacitor, a breach in membrane integrity in one crista would cause a collapse in voltage in all cristae and compromise the function of the whole organelle. If, on the other hand, the IMM could maintain numerous, discrete electrochemical gradients, like a group of batteries, then failure of one or more would not invariably jeopardize the entire mitochondrion. This may be of particular relevance in cells harboring a highly interconnected mitochondrial network as opposed to cells with less elongated and/or branched mitochondria. Furthermore, the hetero‐potential model suggests that cristae with higher ΔΨCr‐IBM could compensate for cristae with impaired function."

"Hyperpolarized and depolarized IMM potentials are associated with different states of respiration. While both uncoupling and an increased rate of ATP synthesis dissipate ΔΨm, a decrease in ATP synthesis may result in hyperpolarization and increased ROS production. The hetero‐potential model of the mitochondrion allows for different cristae to serve different functions. In this model, some cristae could be more dedicated to ATP synthesis, whereas neighboring cristae could play a role in ROS signaling. The hetero‐potential model further allows for the consideration that different cristae may engage in primarily complex II vs. complex I respiration, which are associated with different membrane potentials and could be driven by different fuels."

Protonic Capacitor: Elucidating the biological significance of mitochondrial cristae formation

"[..]excess protons (positive charges) in an aqueous liquid on one side of a membrane will repel each other to become electrostatically localized along the membrane surface, attracting an equal number of excess hydroxyl anions (negative charges) to the other side of the membrane and thus resulting in a “protonic capacitor structure” (Fig. 2)."

Consequences of Folding the Mitochondrial Inner Membrane

"The greater the energy requirements of a cell, the more inner membrane surface area it contains. Because there are practical limits to the volume fraction that cells can reserve for mitochondria, crista packing is maximized where energy demand is greatest, e.g., in cardiomyocytes the surface area of the inner membrane is more than tenfold that of the outer membrane."

"Although internalizing the chemiosmotic membrane is essential for mass production of ATP, it creates a complex and potentially risky situation for the cell. In particular, conditions that swell the matrix will cause the inner membrane to unfold and, eventually, rupture the outer membrane. In fact, cells use this demolition mechanism when death is the intended outcome. For example, inner membrane “herniation” of the outer membrane is observed in late stages of programmed cell death (extrinsic apoptosis) in FAS-activated liver (~~Figure 1~~). Crista contents, including cytochrome c, spill into the cytosol, resulting in irreversible loss of membrane potential and ATP production (Mootha et al., 2001). Matrix swelling in this case was attributed (Feldmann et al., 2000) to the mitochondrial permeability transition pore, MPTP, the opening of which can drive an osmotic influx of water sufficient to unfold the inner membrane and rupture the outer membrane (e.g., Rasola and Bernardi, 2011)."

"Extreme crista swelling is as perilous to the cell as uncontrolled matrix swelling, e.g., the total volume of a few fully expanded cristae in a single muscle mitochondrion easily exceeds the volume enclosed by the outer membrane. In fact, rupture of the outer membrane by crista (not matrix) swelling occurs in insect flight muscle as a prelude to apoptosis (Walker and Benzer, 2004). Clearly, the process of unfolding the inner membrane is as important to cell survival as generating the crista folds and likely is regulated as carefully."

"Although, at first glance, it seems risky to fold a large membrane within an outer membrane, rupture of which is fatal, this situation actually provides the cell an advantage. When mitochondria are suspended in hypo-osmotic media, outer membranes lyse at sucrose gradients tenfold greater than liposomes or mitochondrial inner membrane vesicles of similar size, typically 20–30 mM (Douce et al., 1972; Li et al., 1986). This dramatic protection against osmotic stress directly accrues from the outer membrane being osmotically inactive, i.e., very permeable to small solutes. The chemiosmotic inner membrane is the mitochondrial osmometer. Swelling of the matrix caused by osmotic influx of water compresses the cristae before significant pressure is applied to the outer membrane by outward expansion of the inner membrane. In effect, unfolding the inner membrane absorbs significant osmotic stress and delays irreversible damage to the mitochondria. Equally important, this indirect rupture mechanism provides the cell the opportunity to regulate outer membrane lysis."

"A mechanism has been proposed that would protect mitochondria against outer membrane lysis and inner-membrane domain mixing during crista swelling: fusion of tubular cristae to form larger cristae more adaptable to volume changes. Crista fusion was suggested by the first EM tomograms of mammalian mitochondria, which revealed complex cristae with tubular and lamellar regions (Mannella et al., 1997; Perkins et al., 1997). Larger cristae are more prevalent in condensed mitochondria; decreased matrix volume brings cristae into closer proximity, favoring fusion (Mannella et al., 2001). It is likely that crista fusion in response to matrix contraction is quite extensive. Condensed liver mitochondria have large dilated cristae with multiple (up to seven) junctions (Mannella et al., 1997) and condensed yeast mitochondria may have a single dilated internal cavity with much of the inner membrane pulled away from the outer membrane and no well-defined crista junctions or cristae (Mannella et al., 2001)."

Amazoniac

Gluconeogenesis - Waheeda Nargis | SlideShare

The metabolic steps responsible for the ATP difference in the breakdown and synthesis of dextructose:

Glycolysis (↓)	Enzyme	Gluconeogenesis (↑)
–1 ATP	HK	~~N/A~~
–1 ATP	PFK	~~N/A~~
+2 ATP	PGK	–2 ATP
+2 ATP	PK	~~N/A~~
~~N/A~~	PEPCK	–2 ATP (⇄ 2 GTP)
~~N/A~~	PC	–2 ATP
Total		Total
+2 ATP	(–4 ATP/↺)	–6 ATP

With the exception of PGK, these are the irreversible steps; the others not included are reversible.

If forming and unforming lactate occurred in the same cell, it would have a neutral effect. However, for pyruvate to reappear elsewhere, NADH is consumed in the origin and NAD⁺ in the destination.

Amazoniac

A summary of proton movement in oxidative phosphorylation:

Matrix		IMS	IMS		Matrix
	→			←
2H⁺ + 4H⁺ →	Complex I	4H⁺		Complex II	2H⁺
	2H⁺			2H⁺
2H⁺ →	Complex III	4H⁺	4H⁺	Complex III	← 2H⁺
2H⁺ + 2H⁺ →	Complex IV	2H⁺	2H⁺	Complex IV	← 2H⁺ + 2H⁺
	←			→
H₂O ←	½O₂ + 2H ↲			↳ 2H + ½O₂	→ H₂O
10H⁺ ←	Complex V	10H⁺	6H⁺	Complex V	→ 6H⁺

The arrows weren't supposed to be stylized.

Amazoniac

One more experiment showing that it's possible to make selected cancer cells increase respiration just by inactivating lactate dehydrogenases. If such cells were forced to depend on glycolysis as a predictable consequence of mitochondrial mishandling of electrons as suggested by that predatory quack, simply compromising LDH couldn't rewire them to a defective pathway. Interestingly, no thiamin stunts were needed for the effect. Since proliferation was slowed down with the inactivation of lactate dehydrogenases, it points to fermentation being an advantageous adaptation (for cancer cells) rather than invariably a result of faulty mitochondria. But silicon, his mitochondrial sealer, must have leached from the glass containers whenever LDH was suppressed.

Double genetic disruption of lactate dehydrogenases A and B is required to ablate the “Warburg effect” restricting tumor growth to oxidative metabolism

Wild type in comparison to LDHA or LDHB gene knockout, or both (DKO). These are responsible for the synthesis of different forms of LDH.

"Most publications state that LDHA mainly reduces pyruvate to lactate, whereas LDHB catalyzes the reverse reaction, lactate oxidation to pyruvate, coupled with NADH formation. However, this assumption was already challenged by Vesell (24.), who showed that the enzymatic activity of purified LDH-5 (four LDHA subunits) resembled that of LDH-1 (four LDHB subunits) at physiologic temperature. Furthermore, in zymography, which combines electrophoresis with activity staining to separate and detect the five LDH isoenzymes, both pyruvate and lactate have proven to be suitable substrates (25.), further supporting the notion that both LDHA and LDHB are capable of catalyzing the conversion of pyruvate to lactate (22., 26.)."

Amazoniac

@Jennifer, are the clinics based on Gerson's protocol in Mexico an option to consider? Battling a relative for one small win at a time can be draining and lead to loss of valuable time. You may also face pressure from the entire family if you oppose their opinion.

The cancer program offered by these clinics would demand a series of interventions at once, him and the rest of the family would probably be less resistant when clinicians are involved, and part of the responsibility would be lifted from you (food preparation, supplements, decisions).

The protocol should rely on the support of substances that you're familiar with. A few examples:

Aspirin
Niacin
Caffeine (through the other end, but still)
(Pro)poison A
Thyroid hormones (with Lugol's solution)

Regarding the clinics, some are depressive, but others look like a spa with people on vacation. They can be pricy; however, it's possible to find alternatives, such as the remote (yet supervised) version of the treatment.

We read on occasion the miraculous recoveries after minor changes, but comprehensive approaches increase the chances of success. If you had difficulty convincing him to let go of a beverage, a marked change in diet for therapeutic purposes doesn't seem likely without an external driver.

Nevertheless, in addition to the listed substances, Ray's cascara sagrada (check this out as well) to keep the bowels clean would be simple to apply for now.

Amazoniac

The following simplified reactions may give an impression that the hydrogens accepted by ubiquinone (UQ) to become ubiquinol (UQH2) are derived from 'NADH + H+' or 'FADH2'.

[NADH] + H+ → [NAD+ + H–] + H+
NADH + H+ → NAD+ + (H– + H+)
NADH + H+ → NAD+ + (2H)
⠀
FADH2 → FAD + (2H)
⠀
UQ + 2H → UQH2

The first issue is that the lone proton released by dehydrogenases in the production of NADH is lost to the medium. When NADH reaches complex I to be oxidized, it won't have its original pairing proton, and it can only donate the incorporated hydrogen.

FMN in Complex I accepts it as a hydride ion (H– ⇄ H+ + 2e–) from NADH:

NADH + FMN → NAD+ + FMNH–

Even though this hydrogen could land on ubi(semi)quinone after a series of reactions, it doesn't seem to.

Energetics and Dynamics of Proton-Coupled Electron Transfer in the NADH/FMN Site of Respiratory Complex I

You may focus on the dark blue to track the proton and red to track electrons, knowing that the top of the rectangle is NAD and the bottom is FMN. Note that when NAD dissociates, the rectangle only shows FMN. The proton is eventually released into the medium.

Protons appear to enter respiratory complexes laterally, near the innermost surface, as electrons are channeled.

More specifically:

Water route for proton pumping in mitochondrial complex I

Therefore, the protons liberated in the oxidation of NADH and FADH2 can reach ubiquinone, but likely indirectly when they add to the pool of protons in the matrix. Since the number of free protons is low, they might be buffered or metabolized as fast as they appear.

Amazoniac

Benedicte, you suggested the neutralization of aspirin with calcium carbonate.

Some of the therapeutic effects of salicylates depend on their high local concentration.

Colonic targeting of aminosalicylates for the treatment of ulcerative colitis

One possible advantage of the suggested combination would be if calcium formed an insoluble salt with aspirin after leaving the stomach (alkaline environment). This could carry it down the intestine, at least to a lower level than usual.

Calcium must be in excess of aspirin to maximize the chances of precipitation; it's the same issue in dealing with unwanted phosphate or oxalate. Otherwise, dilution alone could perhaps prevent their combination.

Aspirin in an acidic medium must occur uncharged and cross barriers more easily, making the risk of irritation greater. Getting it out of the stomach as fast as possible (as recommended by Chris Masterjohn in a video) seems reasonable, and I think that proper acidification is a factor that controls emptying.

For calcium carbonate to be taken along with and in excess of aspirin, it can neutralize stomach acid and delay emptying. However, the alkalinization and charging of aspirin may counteract a longer retention. But there's the transition pH range and a moderately acidic environment might be enough to turn it into the acid form.

The victim can ingest calcium carbonate beforehand, wait for those 30-40 min that's usual for the stomach to reestablish acidity after it's neutralized, and then drink the aspirin solution.

When substantial amounts of calcium start to be emptied from the stomach, the consumption of the dissolved aspirin will stop the process and conserve calcium to pair with aspirin. This can give a hefty amount of calcium without risking maintaining aspirin in the stomach for an exaggerated length.

Amazoniac

@Jennifer said in New "Mission" of RPF:

As far as what’s next, mainly caring for my dad and starting my orchard. I wouldn’t know what to log about now that I’ve achieved my health goals. My thyroid crashed around the same time my dad got his cancer diagnosis, but a simple course correction, i.e., giving into intense cravings for fruit, turned things right around.

What can you share about the situation of your dad? What have you tried so far that did and didn't help?

Amazoniac

@Jennifer said in New "Mission" of RPF:

@Amazoniac said in New "Mission" of RPF:

@Jennifer said in New "Mission" of RPF:

@Amazoniac said in New "Mission" of RPF:

I think that it's wise of you to bring up a defect in attempt to pass off as human.

You're one of the most sensible.. persons that I've met on that forum, reliable enough that I can predict that someone who is on the opposite side that you take is probably wrong. It's great to have you around.

Considering how patient and tolerant you are with us, mortals, I knew that the Garrey Pith Forum screwed up badly when you mentioned your departure to another member, for finding the situation unmanageable.

Haha! Thank you for that, Gustavo. I’m no pboy, but I try my best.

Life has shown me in the most sobering ways how precious it is and the importance of how we spend our time and what and who we give our energy to. Though, I empathize with those who have endured pain, no matter how much we think our actions are justified, our suffering does not give us a free pass to bully people into perceiving, thinking and acting like us, and my continuing to participate on the old forum would have meant condoning the abuse of power and disrespect toward the man whose name the forum bears and those who give the forum life. As much as admins deserve respect for all they do to keep online communities running smoothly, members deserve just as much for their contributions because without them forums would be nothing. We’re the content creators, and as far as I’m concerned, we are the Ray Peat Forum.

In my last conversation with pboy, it seems that he was being targeted by the forum staff (I think that it was tara and the lion at the time) and started to have problems posting. As usual, I don't know case details, but he was peaceful, so it's unlikely that he was frustrated for unfair reasons.

I share your views of collaboration.

What's next? Do you plan to create a new log?

When you have some time, can you make a comprehensive list of the products and companies that you endorse? Food, apparel, gear, furniture, and so on. Those in the US and A will benefit the most from it.

Wow. I’m surprised tara would target pboy but then again, from my understanding it was tara who initially banned VoS so I suppose I shouldn’t be. It’s all so disheartening but even still, I don’t hate the players, I hate the game.

As far as what’s next, mainly caring for my dad and starting my orchard. I wouldn’t know what to log about now that I’ve achieved my health goals. My thyroid crashed around the same time my dad got his cancer diagnosis, but a simple course correction, i.e., giving into intense cravings for fruit, turned things right around. The only thing I’m currently experimenting with is hydroxyapatite toothpaste and I doubt members would find my adventures testing the many brands on the market riveting. I mean, it would have a hint of controversy, since I’m pro nano (Fluidinova’s nanoXim nHAp only)—but still a snoozer.

I’d be happy to post a list of companies and products I endorse, but it will take some time to compile it because my list of resources was in the folder with my research notes and journal I lost at the end of last year, and I scaled way back on the products I use quite some time ago.

I read the exchanges again to certify. What's fine to share is that he was indeed frustrated from the issues posting, was getting warnings, and his attempts to discuss the problem with the staff were ignored. I doubt that it was something concerning or difficult to negotiate.

Your log used to be a comforting space for many, that helped to counteract the daily dose of online madness.

Make the list when possible for you, it's going to be quite useful. Supplement companies, water and air filter, oral care, bedding, painting, lighting, clothing, earbuds..

Amazoniac

Coenzyme Q-cytochrome c oxidoreductase (Complex III) | Wikipedia
↳ Q cycle | Wikipedia

I thought that improvising a stepwise animation would clarify the cycle better than text. The transfer molecules towards cytochrome c are not shown.

Q cycle.gif

Kekel is a harsh critic of the conventional model, but understanding both sides helps to form an opinion.

Amazoniac

Check out his remarks on acne:

"Acne does not just occur on the face, although that is usually the source of our dislike since it muddies up our appearance. One of the reasons that acne is so concentrated on the face is because of where the iron excreted on the face comes from. Iron seems to be excreted in the fastest route possible via the skin, rather than circulating through the body, and while some organs like the liver and spleen will store iron, the rest of the body does not readily release it back into the blood stream once absorbed. In the case of the head, where large incidents of acne occurs, this iron comes from our most metabolically demanding organ—the brain. Since the brain is surrounded by skull, excreting iron would be extremely slow and difficult if it traveled through bone, so it instead goes through the face."

Want more? In line with pumpkins, how about his declaration that a lack of carotene is a main cause of gut problems?

"[..]carotene deficiency is one of the primary causes of gut dysbiosis and other gastrointestinal problems."

Yet more? He used to assert that the cause of body malodor is iron. Try to consume plenty of sulfur compounds (garlic, onion, eggs, acetylcysteine, thiamin) and smell the fragrance afterwards. It's iron mobilization?

It's an author who tells the audience that, by the time that you're 40, you're already old, proceeding to explain that you should accept that you'll live most of your life as an old person. But don't worry, you can be a healthy oldie.

Moving on, he asserted:

"The idea of a superfood is in reality wishful thinking, which is a nice way to cope with life but comes with some very serious consequences if it gets out of hand. If you struggle with health problems, limiting your diet is one of the absolute worst things you can do to yourself. This usually leads to the obsessive search for some miracle food you are missing, when in reality you are just missing all the foods."

By the same individual:

"A List of Helpful and Unhelpful Foods"

Where he stipulated that rice, potatoes and nixtamalized corn are foods that should be avoided most of the time. Oh, along with yogurt, vegan diets are categorized by him as "SHIT THAT GAVE YOU THE CANCER FROM WHICH YOU DIE IN 15 YEARS", which is funny considering how therapeutic diets for cancer adapt towards veganism.

He declared to someone pondering thyroid hormones supplementation, natural or synthetic:

"Thyroid supplements don't really do anything."

These are a few more examples that I remember stumbling upon, but we could go on. I hope that it's getting clearer where I'm coming from.

Amazoniac

NAD is used here as the generic term for NAD+ and NADH. Despite their reactive site in evidence, both have an overall negative charge because of the phosphate groups.

ATP, NAD AND FAD | Brigham Young University

In addition to being charged molecules, they're bulky.

These factors make mitochondrial matrix unable to exchange NAD with the cytosol. For similar reasons, glucose is trapped once inside the cell after phosphorylation by hexokinase.

NADH within the matrix is oxidized locally and the electrons are channeled to oxygen. However, a fraction of NADH is formed in the cytosol (GAPDH). This NADH has to be oxidized as well, to regenerate NAD+ for glycolysis to continue.

The inability to import cytosolic NADH into the matrix is circumvented by the known mitochondrial shuttles. NADH can transfer its electrons to a temporary carrier, one that's importable, and the electrons (with protons) can be recovered once inside.

The method on the left appears to be the predominant in tissues with high energy demands, although both can be important. In support:

Thyroid Hormone Regulation of the NADH Shuttles in Liver and Cardiac Mitochondria

This way, most of the NADH is reformed on the matrix side. Or else, transferring the electrons to FAD would result in less energy production, whether we go by the traditional model (10 H+/NADH versus 6 H+/FADH2) or Kekel's approach.

The external layer of the mitochondria is much more permeable than the internal. For the specific location of mGPDH:

How neutrophil metabolism affects bacterial killing

But prior to crossing comparments, pyruvate and NADH are in equilibrium with lactate and NAD+.

Mitochondrial lactate metabolism: history and implications for exercise and disease

Keq (equilibrium constant) = [Lactate][NAD+] / [Pyruvate][NADH]

A high ratio of lactate to pyruvate is a normal occurrence in tissues. We have authors who go to the extent of treating lactate as the final product of healthy glucose breakdown in the cytosol (but acknowledge the problems when elevated in disease).

Lactate:pyruvate	Tissue
Error	Kvothean
7:1	Liver
13:1	Skeletal muscle (rest)
23:1	Brian (not to be confused with brain)
≥25:1	Traumatic brian injury
159:1	Skeletal muscle (immediately after exhaustive exercise)

A generic ratio would be lactate 10:1 pyruvate.
⠀
NAD+/NADH and skeletal muscle mitochondrial adaptations to exercise

Cytosol

[NAD+] = 0.15 mM

[NADH] = 0.00028 mM

NAD+ ~540:1 NADH

Mitochondrial Matrix

[NAD+] = 3.15 mM

[NADH] = 0.5 mM

NAD+ ~6:1 NADH

It's an advantage to not have NAD moving freely between compartments to maintain the desired ratios in each.

From the information above, an example with skeletal muscle (assuming cytosolic ratios for both):

Lactate	13:1	pyruvate
NAD+	540:1	NADH

(Keq = 7020)

Therefore, the favored molecules are products of the LDH reaction in one direction.

Pyruvate + NADH (+ H+) -(LDH)→ Lactate + NAD+

Lactate dehydrogenase has 'very high activity', that 'exceeds glycolytic capacity', which contributes to their proportional variations respecting the ratio in the given tissue, possibly under great influence of NAD. If pyruvate and NADH levels increase, a corresponding increase in lactate and NAD+ tends to follow.

Through lactate formation, NAD+ can be regenerated without depending on the matrix (glycolysis can function independently from oxidative phosphorylation), and this lactate can be distributed to other cells if it can't be metabolized locally. It's a feature that's advantageous for cancer cells.

The Regulation and Function of Lactate Dehydrogenase A: Therapeutic Potential in Brain Tumor

You'll find two lactate shuttles being discussed by researchers:

Intercellular (cell-to-cell)
Intracellular (cytosol-to-matrix)

The redistribution of lactate between organs is a well-known phenomenon, hence the lactate (Cori) cycle. It's a wasteful cycle because glycolysis net-produces 2 ATP and 'reverse glycolysis' (gluconeogenesis) consumes 6 ATP. But lactate doesn't have to undergo reverse glycolysis to reform glucose elsewhere, to then be metabolized by other tissues from scratch.

If an equilibrium exists between pyruvate and lactate, and lactate formation is favored in non-Kvothean cells, they need to have means to recover pyruvate. The oxidative component is overlooked, but lactate dehydrogenase occurs in mitochondria for this purpose; the controversy lies in where.

Role of mitochondrial lactate dehydrogenase and lactate oxidation in the intracellular lactate shuttle

It may be present:

On the outer surface of the inner membrane (mLDH in the middle, positioned similarly to mGPDH shown earlier); or
In the matrix (mLDH at the bottom).

The benefit of it occurring in the matrix would be to function as another mitochondrial shuttle, which would take advantage of the pyruvate-lactate distribution with preferential lactate formation. However, the same distribution tendency can be problematic in the matrix for diverting pyruvate and NADH away from their expected fate when levels rise from origins other than lactate oxidation. Lactate dehydrogenase would tend to metabolize them into lactate and NAD+ in place of pyruvate dehydrogenase (PDH) and NADH dehydrogenase (Complex I).

Recall that the equilibrium between lactate and pyruvate is also dictated by NAD+ and NADH. Considering how many sources of NADH there are in the matrix, it would be concerning to have LDH competing for its oxidation.

This is a situation where the different (iso)forms of lactate dehydrogenase would be of help, so that the enzyme had a specific function:

Lactate → pyruvate: Ach, ja.
Pyruvate → lactate: Nicht, nicht.

But it doesn't seem to be the case and the location of mitochondrial LDH is deemed to be outside of the matrix to avoid these issues:

Amazoniac

@wrl

I don't, but supplementation must be safer than in pregnancy.

The concentrations aren't increased to a worrying extent, can elevate the content to 5 mcg/L. An infant might consume up to 1 L a day and the inflated recommended intake for them is 10 mcg/d.

The excessive supplementation to enrich milk with vitamin D may induce deficiencies in the mother, than may manifest in milk.

Amazoniac

@Jennifer said in New "Mission" of RPF:

@Amazoniac said in New "Mission" of RPF:

I think that it's wise of you to bring up a defect in attempt to pass off as human.

You're one of the most sensible.. persons that I've met on that forum, reliable enough that I can predict that someone who is on the opposite side that you take is probably wrong. It's great to have you around.

Considering how patient and tolerant you are with us, mortals, I knew that the Garrey Pith Forum screwed up badly when you mentioned your departure to another member, for finding the situation unmanageable.

Haha! Thank you for that, Gustavo. I’m no pboy, but I try my best.

Life has shown me in the most sobering ways how precious it is and the importance of how we spend our time and what and who we give our energy to. Though, I empathize with those who have endured pain, no matter how much we think our actions are justified, our suffering does not give us a free pass to bully people into perceiving, thinking and acting like us, and my continuing to participate on the old forum would have meant condoning the abuse of power and disrespect toward the man whose name the forum bears and those who give the forum life. As much as admins deserve respect for all they do to keep online communities running smoothly, members deserve just as much for their contributions because without them forums would be nothing. We’re the content creators, and as far as I’m concerned, we are the Ray Peat Forum.

In my last conversation with pboy, it seems that he was being targeted by the forum staff (I think that it was tara and the lion at the time) and started to have problems posting. As usual, I don't know case details, but he was peaceful, so it's unlikely that he was frustrated for unfair reasons.

I share your views of collaboration.

What's next? Do you plan to create a new log?

When you have some time, can you make a comprehensive list of the products and companies that you endorse? Food, apparel, gear, furniture, and so on. Those in the US and A will benefit the most from it.

Amazoniac

In another strike of openness to counterviews, the thread is now invisible to me, probably as a result of getting blocked by its creator. If I didn't have it linked elsewhere, I wouldn't be able to access it again. The discussions that appear are those that the originators allow them to.

I skimmed through the guy's article proposing the following antiviral arsenal:

Riboflavin
Sunlight
Vitamin C
Aspirin

The latter 3 are known to help and are widely promoted by other authors. I have some comments on the unique touch of his proposal: irradiated riboflavin.

He was conservative with the tone of this publication (from body to title), and included some of the consulted material. I suspect that the atypical behavior is because it was a heated mainstream topic, so he knew that he could get in trouble to announce its cure on social media. The inconsistency suggests awareness on where to tread.

"While there is some speculation that vitamin D is helpful for resisting viral agents, it is not our primary protective factor against them nor the factor which influences the seasonal occurrence of the flu or that of the current COVID-19 outbreak, and SARS as well occurred during the winter season (they’re all related to the flu, I believe). The one factor all this has in common, however, is sunlight. But, more specifically, how our bodies respond to or benefit from sunlight. There is an abundance of evidence that the B vitamin riboflavin, which is highly sensitive to light, is the agent which assists our bodies to restrain viral infections, and the mechanisms of action by which riboflavin helps protect us against both bacterial and viral pathogens is pretty well understood. Because riboflavin is extremely light sensitive our body uses it in pathways which regulate circadian rhythms. But when riboflavin is exposed to light, as it is in our skin when we get exposure to sun or bright light, it is actually energized from the interaction with photons and itself becomes irradiated. Then, in the irradiated state riboflavin is moderately to highly destructive to bacteria and viruses. These studies often show direct irradiation of riboflavin, but the same natural irradiation occurs simply from riboflavin created in our gut microbiome or obtained through diet or supplementation and the body’s exposure to natural sunlight. This is why the flu is restrained to seasonal patterns rather than being an ubiquitous affliction all year long, and why those with more Northerly climates or societies with prudish ideas of public skin exposure are being harder hit (or those with poor nutrition caused by economic inequality). Exposure to sufficient sunlight in humans during warmer months irradiates riboflavin in the body which in turn confers herd immunity (which is the collective resistance of an entire group of people against a pathogen on account of most of them being resistant) and thus prevents the spread of the flu until seasonal changes result in reductions of sun exposure thus impairing riboflavin irradiation which in turn allows such viruses to flourish."

The light absorption spectrum of riboflavin:

Peaks within the UVc, UVb, UVa, and blue light range. Image from one of the materials below.

However, these shorter wavelengths are barred at the superficial layer of the skin and barely reach the layer beneath.

I didn't find the source.

If you search for photodynamic therapy with flavins as photosensitizers, the results are almost entirely for irradiation of blood products (such as plasma, where the liquid is spread in a flat container) or for the treatment of external conditions. It's no wonder that the material linked by him falls into these superficial categories.

For light therapy in humans, I did find one experiment involving riboflavin in viral infections, but it was poorly-designed and not much can be concluded from it.

Successful Reduction of SARS-CoV-2 Viral Load by Photodynamic Therapy (PDT) Verified by QPCR – A Novel Approach in Treating Patients in Early Infection Stages

Riboflavin has many systemic effects and the population can be running low on it. How to claim success with photodynamic therapy relying on riboflavin as a photosensitizer if there was no group taking riboflavin without light application to compare? Also, people were asked to wear a dubious bracelet with 2 tiny blue LEDs for whole-body effects through circulation (which is comical), but the majority of LEDs were off from the absorption spectrum of flavins that they shared (also comical).

These wavelengths introduce confounders. For example, red light prevails, it enters tissues, and one hour for a session is a considerable exposure.

But they knew that higher chances to attack riboflavin were near the surface, asking people to use a riboflavin (5-phosphate) solution and later irradiating the regions:

Even though they selected people in the early stages of infection, I'm not sure how useful irradiation was at that point, as people were already complaining of breathing difficulties. But these were the internal sites that they had accessible.

Benefits might have stemmed from fixing a long-standing riboflavin insufficiency or from light therapy in general.

To prevent infections from spreading, the body tries to contain them at mucosal barriers (areas of first contact), where shorter sunlight wavelengths won't hit and distant radicals won't reach, for being short-lived and quickly quenched. Riboflavin has to be next to targets because the reactions are local and instantaneous, involving radical attack. It's why photosensitizers that absorb red light are favored for internal tissues, and riboflavin is not one of them.

Therefore, the listed substances are of help, but the explanations are doubtful.

Amazoniac

Amazoniac

A while ago I came across this publication through GembaRed's articles:

Blood contains circulating cell-free respiratory competent mitochondria

However, Tony questioned its validity:

Human blood contains circulating cell-free mitochondria, but are they really functional?

"As noted by Bertero et al. (7), the evidence provided by Dache et al. (4 ⇈) was not sufficient to assess the functionality or the respiratory competence of human circulating cell-free mitochondria. By conducting a comprehensive analysis of mitochondrial bioenergetics of human circulating cell-free mitochondria in direct comparison with mitochondria extracted from platelets of the same blood samples, we found no significant support for the functionality or the respiratory competence of those cell-free mitochondria. Indeed, there was no significant evidence that cell-free mitochondria possess a functional electron transport system since they exhibited no responses to mitochondrial substrates, ADP, or inhibitors. Yet, when fueling directly complex IV with exogenous electrons (i.e., Asc + TMPD), a significant mitochondrial O2 consumption was detected [similarly to Dache et al. (4), except that no negative control was provided in their study]."

"Although fully rejecting the hypothesis that human circulating cell-free mitochondria are functional would require a way larger sample size (e.g., n > 90 for reaching a statistical power of 0.80 for OXPHOSCI + II based on data presented in Fig. 1B), our results do not support the functionality of circulating cell-free mitochondria. Further studies investigating the functionality or lack of functionality of circulating cell-free mitochondria are now required, since this appears as a critical point to elucidate their potential physiological role(s) [e.g., (8)]."

Amazoniac

@Jennifer said in New "Mission" of RPF:

@ThinPicking said in New "Mission" of RPF:

Ah sorry that was probably confusing.

I recalled an Isadora Duncan quote from RPF, my brain had folded in to a meta-meme with the Rolling Stones. From the other side, with memory and (probably) an unhealthy degree of humour.

Ah, okay, my signature on the old forum. I thought maybe you were referring to something I said, but I couldn’t recall saying anything about wild horses so knowing you often quoted song lyrics in the music thread, I figured I’d take a shot with the Rolling Stones. Wild Horses is a great song, just don’t tell Amazoniac I said that or he’ll have my hide. lol

I think that it's wise of you to bring up a defect in attempt to pass off as human.

You're one of the most sensible.. persons that I've met on that forum, reliable enough that I can predict that someone who is on the opposite side that you take is probably wrong. It's great to have you around.

Considering how patient and tolerant you are with us, mortals, I knew that the Garrey Pith Forum screwed up badly when you mentioned your departure to another member, for finding the situation unmanageable.

@Regina said in New "Mission" of RPF:

Mike Fave!

https://www.youtube.com/watch?v=QsMwvtKeuUc

@Regina said in The Ray Peat Forum is DEAD - Mike Fave video:

You rock Mike!!!
So much respect that you did this. Proving Ray Peat lifestyle builds cajones.

heehee. I got called an "OG".

Regina, in addition to being an original gangster, it seems that you're hailed in music. The forum state calls for the positioning of members, so props to Mike for dedicating a video to it. It would've been more convenient to stay indifferent and not create indisposition for personal benefit on all ends. It can be argued that he was targeted, but only because he was incisive in the first place.