NAD/NADH Ratio - The One Metabolic Cause To Rule Them All

[haidut]

@haidut

what would help oxidative phosphorylation?
I was told that MB and Palmitic acid could be helpful. Are there any other things to take or not to take to help this?

Well, oxidative phosphorylation is everything beyond glycolysis. So, everything mentioned in this thread and the original post applied. Palmitic acid and fructose are some of the things mentioned that would help.

 

[yerrag]

The Warburg Effect drives oncogenesis: researchers at Lawrence Berkeley National Lab and in Japan show cancer really does have a sweet tooth • r/science

"...There's been a long running debate over whether or not the well known Warburg Effect is a result of genetic transformation of cells into a malignant state or whether the Warburg Effect is a key driver of the transition. The debate may now be beginning to be over. What's very interesting that in the paper, many of the authors' findings are clearly dependent on 3D culture. Many pathways and proteins such as mTOR, AMPK, and HIFs that have long been studied in cancer are shown to be not important players in inducing oncogenic signaling by increased glucose uptake and metabolism in 3D culture. The authors provide very concrete evidence that increase aerobic glycolysis transforms cells into cancer phenotypes. Simply taking away glucose consumption, as the authors show, can revert cancerous cells back into phentotypes with more organized structure; conversely, the authors are also able to show that healthy cells can be transformed into malignant phenotypes by just increasing glucose uptake alone. Furthermore, this ability to transform phenotypes of cancer cells via glucose metabolism manipulation is not dependent on arresting cell proliferation."

Because fat oxidation systemically (aside from inside muscle at rest) is not optimal for health. It is absolutely vital for tumor growth and suppresses glucose oxidation through Randle cycle. Glucose is the preferred fuel in healthy organisms, and muscles burn fat at rest. That changes in exertion and disease and that is why fatty acid oxidation inhibitors are therapeutic and can even serve as doping agents (e.g. Sharapova and Mildronate).

@haidut, maybe I'm not reading it right but I wanted to clarify the two above posts you made as it seems they contradict each other. The first post had it that if glucose is not consumed, the cancer cells revert back to an organized structure, which to me is another way of saying they become normal cells. Yet the second post says that fat oxidation is vital for tumor growth.

In the first post, should I be interpreting the statement a that in a condition where mitochondrial metabolism is impaired, and where aerobic glycolysis is the metabolic pathway used, removing glucose as substrate would arrest the growth of cancer?

Btw, since you asked if the metabolic congestion from infection can be relieved by supplements alone. It seems St. Gyorgyi believed it could - by quinones.
Quinones are too powerful an oxidizing agent... | Ray Peat Forum

"Quinones are too powerful an oxidizing agent to take part in normal respiration. Evidently the quinones are meant to destroy the bacteria which invade the damaged cells. ..The quinones do more than kill bacteria. They tan the protein in fruits and vegetables, making them unfit food for bacteria. The tanned protein forms a protective sheet over the damaged tissue. [Plants and their defense]"

Other than destroy bacteria, would quinones also be able to restore the mitochondria to a fully functional state, e.g. lead toxicity where lead is embedded in the mitochondrial structure ? Perhaps the quinones could restore structure by giving the mitochondria the energy to expel the lead? If alone it can't do so, but with other remedial supplements to assist, it would also help restore the mitochondrial integrity it once had before being damaged by lead toxicity?

It feels like ETC is the problem for most because of past PUFA intake and b vitamins can make this worse.

By thus, do you mean that PUFA limits the availability of glucose as a substrate, and with the intake of b vtamins such as niacinamide, the exhaustion of glucose would lead to the cells to adapt in ways that would produce by-products that contribute to an increase in stress?

Saturated fat improves oxidative phosphorylation for sure. This has been the most helpful thing for me whenever I can digest enough of it.

And if I'm following your thought process correctly, you are finding that intake of saturated fat is a preferred way, over b vitamin intake, because it can sidestep the effects of past PUFA intake (lack of glucose getting to the cells) by enabling the body to use the saturated fats as a substrate in oxidative phosphorylation?

I think a proper dose is closer to 25mg every 2 hours, until a good tone of breath is established.

What do you mean by a good tone of breath?

Actually, LDH is a mitochondrial enzyme and should not be present in blood in high amounts under normal circumstances. If it is then there is usually cell damage somewhere and the cell(s) ruptured and spilled these enzymes in the blood. It happens with overtraining, muscle damage, heart attacks, infections, burns, cancer, etc. Peat wrote that high estrogen is one of the main causes of LDH leaking into the blood. Lactate is what needs to be measured to get the pyruvate/lactate ratio and yes you can have discrepancy between LDH and lactate as LDH levels are simply indicative of cell damage, not how much lactate is produced. You can have normal or even low LDH with high lactate if the LDH enzyme is very active in the cell. So, I would test for pyruvate and lactate and get the ratio. A more worrying case would be where both LDH and lactate are high, but it seems this is not your case.

I get it now, so LDH being high in the blood does not mean that it will increase the lactate in the blood. High LDH in the blood is the result of leakage of LDH from the cells mitochondria, and the reason the LDH is leaking is because the cell is damaged, and causing the LDH to leak through to the blood. In a cell, LDH is an enzyme that converts pyruvate to lactate.

LDH values are known to be possibly distorted by poor serum specimen handling.
Lactate dehydrogenase - Wikipedia
"A blood sample that has been handled incorrectly can show false-positively high levels of LDH due to erythrocyte damage."

If the LDH value was a single report, rather than a trend for a series of reults, it may be helpful to repeat the test as next serum testing before making decisions on a single lab test report.

Thanks for the heads up!

 

[haidut]

@haidut, maybe I'm not reading it right but I wanted to clarify the two above posts you made as it seems they contradict each other. The first post had it that if glucose is not consumed, the cancer cells revert back to an organized structure, which to me is another way of saying they become normal cells. Yet the second post says that fat oxidation is vital for tumor growth.

That's the unfortunate/wrong conclusion of the sugar-hating crowd currently in power. The issue is not glucose but the wasting of glucose into lactate due to downregulation of PDH and indrease in PDK (hence the therapeutic effects of thiamine or DCA). It is the lactate overproduction that drives cancer growth through activation of VEGF. Cancer cells use glucose to synthesize lactate and fatty acids, but they can't properly oxidize glucose. Lowering the lactic acid decreases tumor growth and inhibiting fatty acid oxidation can revert tumor metabolism back to normal.
Cancer Addiction To Fat Confirmed; Niacinamide As Possible Treatment

Restricting glucose is NOT a solution as the Warburg study on Reddit unfortunately recommends. It has been tried before and there is even a chemical synthesized specifically for that purpose because it was thought it would treat cancer. It does not, it actually accelerated tumor growth after a brief hiatus.
2-Deoxy-D-glucose - Wikipedia

The most likely reason is that if you restrict glucose the tumor will increase cortisol production to get glucose from muscle tissue catabolism, thus accelerating cachexia and death. Most cancer patients die from either cachexia or immune-suppression side effects from radiation/chemotherapy.

Don't know much about quinones and lead chelation, usually amino acids, malic acid, succinic acid, and even citric acid are much better chelators of heavy metals.

 

[yerrag]

That's the unfortunate/wrong conclusion of the sugar-hating crowd currently in power. The issue is not glucose but the wasting of glucose into lactate due to downregulation of PDH and indrease in PDK (hence the therapeutic effects of thiamine or DCA). It is the lactate overproduction that drives cancer growth through activation of VEGF. Cancer cells use glucose to synthesize lactate and fatty acids, but they can't properly oxidize glucose. Lowering the lactic acid decreases tumor growth and inhibiting fatty acid oxidation can revert tumor metabolism back to normal.
Cancer Addiction To Fat Confirmed; Niacinamide As Possible Treatment

Restricting glucose is NOT a solution as the Warburg study on Reddit unfortunately recommends. It has been tried before and there is even a chemical synthesized specifically for that purpose because it was thought it would treat cancer. It does not, it actually accelerated tumor growth after a brief hiatus.
2-Deoxy-D-glucose - Wikipedia

The most likely reason is that if you restrict glucose the tumor will increase cortisol production to get glucose from muscle tissue catabolism, thus accelerating cachexia and death. Most cancer patients die from either cachexia or immune-suppression side effects from radiation/chemotherapy.

Don't know much about quinones and lead chelation, usually amino acids, malic acid, succinic acid, and even citric acid are much better chelators of heavy metals.

Thanks for the clarification!

 

[aquaman]

In summary, a combination of MB, niacinamide, thiamine, and biotin can be a very powerful pro-metabolic stack which should benefit virtually all conditions. Thyroid (T3) may also be needed in the most extremely deranged cases but the stack should provide noticeable benefit to the vast majority of people.

It's an interesting coincidence I read this today, because I'm feeling hugely better today, and was just writing down what I took yesterday and today and what was different.

My list is MB 0.5mg (haven't taken in months), biotin 5mg, 200mg Inosine, T3/T4 mix, Thiamine 300mg, vitamin A 20,000 Iu on skin, and magnesium bath.

The world feels incredibly good today, I'm full of energy, extremely warm hand and extremely happy.

Also combined with high protein (dairy/seafood), high fruit sugars, and low fat food, and consistent eating schedule.

Will keep reporting if this continues to have such a positive effect.

 

[aquaman]

B2 has been the only thing added to supplements I was taking long before like thiamine, niacinamide, B6, cordyceps, so I am 100% sure the massive increase in functioning is due to the B2 plus whatever it does to make other supplements and foods work better. https://www.amazon.com/gp/product/B012YIVRM0/ref=oh_aui_detailpage_o00_s00?ie=UTF8&psc=1

That Russian combo-drug Haidut mentioned above, Cytoflavin, contains: Inosine + Nicotinamide + Riboflavin + Succinic Acid

 

[haidut]

That Russian combo-drug Haidut mentioned above, Cytoflavin, contains: Inosine + Nicotinamide + Riboflavin + Succinic Acid

Yep, it is pretty good but I think it is taken IV, not orally. That is why it is in ampules. To achieve the same effects with oral dose I would guess doses 10x higher of each substance may be needed.

 

[Dhair]

Yep, it is pretty good but I think it is taken IV, not orally. That is why it is in ampules. To achieve the same effects with oral dose I would guess doses 10x higher of each substance may be needed.

What do you think about IV glutathione infusions? It's something that a lot of people with flouroqinolone poisoning do.

 

[AlexanderR]

Yep, it is pretty good but I think it is taken IV, not orally. That is why it is in ampules. To achieve the same effects with oral dose I would guess doses 10x higher of each substance may be needed.

Here in Minsk Cytoflavin is also sold in tablets. 1 tablet contains: Succinic Acid 300mg, Inosine 50mg, Nicotinamide 25mg, Riboflavin 5mg. Doses: 2 tablets twice a day 30 min before eating.
10ml ampule contains: Succinic Acid 1000mg, Inosine 200mg, Nicotinamide 100mg, Riboflavin 20mg. Once a day.

 

[Drareg]

It's an interesting coincidence I read this today, because I'm feeling hugely better today, and was just writing down what I took yesterday and today and what was different.

My list is MB 0.5mg (haven't taken in months), biotin 5mg, 200mg Inosine, T3/T4 mix, Thiamine 300mg, vitamin A 20,000 Iu on skin, and magnesium bath.

The world feels incredibly good today, I'm full of energy, extremely warm hand and extremely happy.

Also combined with high protein (dairy/seafood), high fruit sugars, and low fat food, and consistent eating schedule.

Will keep reporting if this continues to have such a positive effect.

My guess is you wouldn’t need this that regularly? It seems your in decent health as it is so maybe using this to let’s say spark up metabolism and see where the stress of life takes you before doing it again,it could be every second day or 3 days even once per week.

 

[haidut]

What do you think about IV glutathione infusions? It's something that a lot of people with flouroqinolone poisoning do.

I would not use GSH directly. You can easily raise GSH (if needed) much more safely by ingesting glycine as the body has plenty of NAC floating around and GSH is just a glycine/NAC conjugate. If infusion is needed I would go with the oxidized version GSSG, as it raises the GSSG/GSH ratio and it is another biomarker of good metabolism/health.

 

[haidut]

Here in Minsk Cytoflavin is also sold in tablets. 1 tablet contains: Succinic Acid 300mg, Inosine 50mg, Nicotinamide 25mg, Riboflavin 5mg. Doses: 2 tablets twice a day 30 min before eating.
10ml ampule contains: Succinic Acid 1000mg, Inosine 200mg, Nicotinamide 100mg, Riboflavin 20mg. Once a day.

Great, thanks. Do you know what the tablets are prescribed for or what people usually take them for?

 

[AlexanderR]

Great, thanks. Do you know what the tablets are prescribed for or what people usually take them for?

No, I don't. This is what is written in the instruction.

Pharmacological action.
Metabolic drug. Pharmacological effects are due to complex effects included in the drug Cytoflavin components. Stimulates cellular respiration and energy production, improves the processes of oxygen utilization by tissues, restores the activity of enzymes, providing an antioxidant effect.
The drug activates intracellular protein synthesis, promotes utilization of glucose and fatty acids, resynthesis of GABA in neurons through the shunt Roberts.
Has a positive effect on the bioelectrical activity of the brain.
Cytoflavin improves cerebral and coronary blood flow, activates metabolic processes in central nervous system, reduces reflex disorders, contributes to restoration of sensitivity and intellectual-mnestic functions of the brain.
Makes a positive effect on the parameters of the neurological status: reduces the severity of asthenic, cephalgic, vestibular-cerebellar, cochlear-vestibular syndrome, as well as eliminates the disorder in the emotional-volitional sphere (reduces anxiety, depression). Improves cognitive and memory function and quality of life.
When administered intravenously contributes to the restoration of a disturbed mind. Has a fast wake-up effect on oppressed consciousness after anesthesia. The application of Cytoflavin in the first 12 hours after the onset of stroke leads to benefits for ischemic and necrotic processes in the affected area (decrease of focus), restoration of neurological status and reduction of disability in the long term.

There can be mistakes in translation.

 

[Regina]

No, I don't. This is what is written in the instruction.

There can be mistakes in translation.

Nice description!

I wonder if the inosine would have an effect on ceruloplasmin.

 

[yerrag]

"Makes a positive effect on the parameters of the neurological status: reduces the severity of asthenic, cephalgic, vestibular-cerebellar, cochlear-vestibular syndrome, as well as eliminates the disorder in the emotional-volitional sphere (reduces anxiety, depression)."
Seems like something that could benefit people suffering meneuire's disease, involving a loss of balance relating to the cochlea.

 

[Regina]

"Makes a positive effect on the parameters of the neurological status: reduces the severity of asthenic, cephalgic, vestibular-cerebellar, cochlear-vestibular syndrome, as well as eliminates the disorder in the emotional-volitional sphere (reduces anxiety, depression)."
Seems like something that could benefit people suffering meneuire's disease, involving a load of balance relates to the cochlea.

My thoughts as well. We, on the forum, are no stranger to B2, B3, and inosine; the addition of succinic acid is interesting. Restrain FAO and adrenalin; promote sugar oxidation and "fountain of youth" riboflavin.
Best of luck to anybody thinking they are going to stress (fast, endurance exercise, and otherwise flip the switch to alt energy) themselves to health.

 

[haidut]

No, I don't. This is what is written in the instruction.

There can be mistakes in translation.

OK, thanks.

 

[Amazoniac]

Control of oxidative phosphorylation by vitamin A illuminates a fundamental role in mitochondrial energy homoeostasis

 

[bodacious]

Very few other chemicals can match MB in its systemically pro-metabolic effects.

Any evidence on MB as a weight loss aide?

 

[haidut]

Any evidence on MB as a weight loss aide?

Not sure if that was ever measured in studies since most of them did not have that goal. However, if MB can help with psychosis and depression which are mostly due to cortisol/serotonin then I would not be surprised if it has that effect.