September 2020 - Very Interesting Newsletter On Lactic Acid

[lampofred]

He talks about how lactic acid interacts with nerve cells specifically.

Since he mentions a B2 deficiency increases lactic acid, and B2 is destroyed by blue light, then could that mean screen use increases lactic acid?

One thing he mentions is that high lactate is associated with extreme nerve excitation and fatigue, and with a "waking" brain. So is high lactate associated with "woke" mentality?

He also mentions that lactic acid is contagious. That reminds me of the old concept of miasma, contagious "bad air" which spreads plague, which has been discredited as "magical" thinking.

I also thought it was interesting that high lactate cells tend to migrate and not stay fixed in one spot. (I wonder if a high lactate person can be viewed analogously to a high lactate cell.)

I wonder if copper is something that would help to lower lactate, by lowering blood sugar and thus suppressing glycolysis. Maybe that's why it helps to restore myelin in MS (which is probably related to high lactate, since Dr. Peat has said it involves extreme nerve excitation).

Also, since aspirin increases glycolysis, should we be more careful about using aspirin now?

EDIT: NVM about aspirin.

 

[cjm]

I just skimmed, but had a little "aha" moment reading this paragraph:

"Senescent cells accumulate in the body with age, and as they lose their normal functions, they shift to the regressed glycolytic metabolism, and begin emitting inflammatory signals, as well as lactate, into their surroundings, inducing senescence in the nearby cells (da Silva, et al., 2019). In the 1960s Leonard Hayflick believed that he had discovered an intrinsic aging mechanism in cells, a “limit” that made it impossible for a human or animal cell to divide more than 50 times. It didn’t occur to him that events in a laboratory culture dish might not be relevant to the function of a cell in its normal place in an organism. Cells in culture quickly (Bittles and Harper, 1984) begin reorganizing in relation to their liquid and plastic or glass environment, and they begin reverting to the basic glycolytic metabolism, beginning to produce lactate; prolonged exposure to lactate accelerates the process. While exposure to lactate can cause a shift from oxidative to glycolytic metabolism (Kozlov, et al., 2020), addition of pyruvate can prevent that, by increasing the ratio of NAD/NADH (Kim, et al., 2018)."

Am I picking up what he's putting down, that in vitro studies are pretty worthless for comparison to an in vivo situation?

Edit: lol, readin skillz, he says it directly before: "It didn’t occur to him that events in a laboratory culture dish might not be relevant to the function of a cell in its normal place in an organism."

 

[lvysaur]

where's the newsletter link?

 

[cjm]

He talks about how lactic acid interacts with nerve cells specifically.

Since he mentions a B2 deficiency increases lactic acid, and B2 is destroyed by blue light, then could that mean screen use increases lactic acid?

One thing he mentions is that high lactate is associated with extreme nerve excitation and fatigue, and with a "waking" brain. So is high lactate associated with "woke" mentality?

He also mentions that lactic acid is contagious. That reminds me of the old concept of miasma, contagious "bad air" which spreads plague, which has been discredited as "magical" thinking.

I also thought it was interesting that high lactate cells tend to migrate and not stay fixed in one spot. (I wonder if a high lactate person can be viewed analogously to a high lactate cell.)

I wonder if copper is something that would help to lower lactate, by lowering blood sugar and thus suppressing glycolysis. Maybe that's why it helps to restore myelin in MS (which is probably related to high lactate, since Dr. Peat has said it involves extreme nerve excitation).

Also, since aspirin increases glycolysis, should we be more careful about using aspirin now?

EDIT: NVM about aspirin.

Interesting associations. I can't add anything, other to say that they caused me to pause and reflect. Not much going on upstairs today.

Where is the "contagious" reference? Had trouble finding it.

 

[LeeLemonoil]

@lampofred

There is definitive a correlation - very probably much more, a „mirrowing“, a mimetic between physiology and how the conscient human behaves politically and socially.
I frequently observe and kind of discover these pattern, that everything that happens on a cellular level in human physiology happens in our social behavior, history, civilization too. I never write these thoughts down, I should, because I‘m inclined to say they are pretty brilliant, no bragging.

Maybe we should just start such a thread

 

[Tenacity]

@lampofred

There is definitive a correlation - very probably much more, a „mirrowing“, a mimetic between physiology and how the conscient human behaves politically and socially.
I frequently observe and kind of discover these pattern, that everything that happens on a cellular level in human physiology happens in our social behavior, history, civilization too. I never write these thoughts down, I should, because I‘m inclined to say they are pretty brilliant, no bragging.

Maybe we should just start such a thread

As above, so below.

 

[yerrag]

I just skimmed, but had a little "aha" moment reading this paragraph:

"Senescent cells accumulate in the body with age, and as they lose their normal functions, they shift to the regressed glycolytic metabolism, and begin emitting inflammatory signals, as well as lactate, into their surroundings, inducing senescence in the nearby cells (da Silva, et al., 2019). In the 1960s Leonard Hayflick believed that he had discovered an intrinsic aging mechanism in cells, a “limit” that made it impossible for a human or animal cell to divide more than 50 times. It didn’t occur to him that events in a laboratory culture dish might not be relevant to the function of a cell in its normal place in an organism. Cells in culture quickly (Bittles and Harper, 1984) begin reorganizing in relation to their liquid and plastic or glass environment, and they begin reverting to the basic glycolytic metabolism, beginning to produce lactate; prolonged exposure to lactate accelerates the process. While exposure to lactate can cause a shift from oxidative to glycolytic metabolism (Kozlov, et al., 2020), addition of pyruvate can prevent that, by increasing the ratio of NAD/NADH (Kim, et al., 2018)."

Am I picking up what he's putting down, that in vitro studies are pretty worthless for comparison to an in vivo situation?

Edit: lol, readin skillz, he says it directly before: "It didn’t occur to him that events in a laboratory culture dish might not be relevant to the function of a cell in its normal place in an organism."

Makes me think that non-Peaty fasting would be the way to get rid of senescent cells. What do you think @LLight ?

where's the newsletter link?

No link available. Ray Peat sends to subscribers by email his newsletters.

 

[yerrag]

Also made mention is that lactate causes atherosclerosis. It's the first time I've heard of it so I'll need to check his reference.

The first thing I thought about is the possibility that this is could explain why long-distance runners have low heart rates.

Could it be that the plaques in blood vessels cause less tissue oxygenation, and with less oxygen, there is lower metabolism and along with that lower heart rate? Metabolism is downregulated. Yet the runner can still run long distances at a rapid clip, because the body is adapted to using its metabolic energy production towards running and not toward building, which is why runners have very slim builds.

When he settles down to a normal life, the plaque has accumulated and he is not able to restore metabolism and heart rate. Maybe the plaque has to be slowly lysed away by proteolytic enzymes and other lytic products.

It would be interesting to check his oxygen saturation levels, as that could be an indication of how thick his plaque is. The higher the oxygen saturation level, the thicker the plaque is. I've noticed that taking systemic enzymes has led to a lowering of my spO2 level from 99 to 98. I believe if I continued taking the enzymes, the spO2 levels would continue to go down. But I had to stop it because I noticed my blood pressure greatly increasing, which I attribute to the release of immune complexes (IC)intertwined in the plaque. The ICs were causing an inflammatory response in my kidneys that are causing high blood pressure.

 

[R J]

If one signs up for newsletter sub do they get access to back issues?

 

[yerrag]

If one signs up for newsletter sub do they get access to back issues?

No, but I remember someone saying something about being able to request to purchase particular back issues. But I don't recall how to go about it. Perhaps just a note to Ray would do.

 

[RealNeat]

Such a good one

 

[yerrag]

Since he mentions a B2 deficiency increases lactic acid, and B2 is destroyed by blue light, then could that mean screen use increases lactic acid?

Of all the b vitamins, why b2 and not b1 and b3, as these seem to me to be more associated with sugar metabolism? And b2 more tied in with fatty acid metabolism?

This is one newsletter where I'm inclined to dig deeper into his references.

 

[Jessie]

Yes, I've seen Peat mention numerous times that lactate appears to be one of the worst things. In one of the recent interviews with Danny and Haidut, Ray essentially said those with high serum lactate won't live long. Thus low lactate is critical for longevity. Glycolysis is needed for glucose metabolism, it's actually the first step in the whole energy cycle. I feel like Ray sometimes forgets he's talking to a bunch of laymen that aren't scientists, lol. When he refers to glycolysis as being bad, he's referring to "excessive glycolysis." The excess is what results in higher lactate, because the pyruvate isn't being cleared in a timely manner. This is essentially the diabetic metabolism (or cancer metabolism). So aspirin may not be the best thing to be taking if you have excessive glycolysis. But you can prevent excessive glycolysis by suppressing endotoxin, getting enough b vitamins & magnesium, balance phosphate/calcium, and maybe take thyroid for some people.

 

[yerrag]

One thing he mentions is that high lactate is associated with extreme nerve excitation and fatigue, and with a "waking" brain. So is high lactate associated with "woke" mentality?

That's terrible! Is there a blood test for "wokeness?"

He also mentions that lactic acid is contagious. That reminds me of the old concept of miasma, contagious "bad air" which spreads plague, which has been discredited as "magical" thinking.

That contagion is limited to cell to adjoining cell interaction, not to individuals. But wasn't miasma the same miasma of Wuthering Heights, which I think is tubercolosis?

I wonder if copper is something that would help to lower lactate, by lowering blood sugar and thus suppressing glycolysis. Maybe that's why it helps to restore myelin in MS (which is probably related to high lactate, since Dr. Peat has said it involves extreme nerve excitation).

Copper deficiency affects the pancreas' ability to produce enzymes and hormones, and so could affect the production of insulin.

 

[yerrag]

By the 1960s, when I started studying biology at the university, the average person knew quite a bit about lactic acid, such as the fact that a deficiency of vitamin B2 causes an excess of lactate to be produced, and that lactic acid can cause the growth of blood vessels in the corneas or whites of the eyes, but the medical profession was already relegating information of that sort to the category of “lore,” not to be taken seriously.

Can anyone add to this? I can't find specific mention of B2 deficiency in his references, as far as I can glean from the titles.

Does lack of B2 cause FADH2 to not be produced in the citric acid cycle and this cause metabolism to be stuck at aerobic glycolysis, whereupon which lactate is produced?
@redsun @Hans

 

[redsun]

By the 1960s, when I started studying biology at the university, the average person knew quite a bit about lactic acid, such as the fact that a deficiency of vitamin B2 causes an excess of lactate to be produced, and that lactic acid can cause the growth of blood vessels in the corneas or whites of the eyes, but the medical profession was already relegating information of that sort to the category of “lore,” not to be taken seriously.

Can anyone add to this? I can't find specific mention of B2 deficiency in his references, as far as I can glean from the titles.

Does lack of B2 cause FADH2 to not be produced in the citric acid cycle and this cause metabolism to be stuck at aerobic glycolysis, whereupon which lactate is produced?
@redsun @Hans

FAD is necessary in the pyruvate dehydrogenase complex in the dihydrolipoamide dehydrogenase. So a FAD deficiency will likely lead to higher lactic acid levels because in general it will affect the efficiency of oxidative metabolism. But the main reasoning as the below article suggests, is reduced oxygenation since riboflavin is needed for heme synthesis, retinol to retinoic acid conversion (and thus ceruloplasmin), and other things involved for optimal RBC formation and oxygenation. Also in the article, inducing vitamin A deficiency in the rats cause vascularization as well. So likely the main cause behind it is reduced oxygenation.

This study was on rats. The gist is riboflavin deficiency will cause hypoxia, triggering vascularization.

"
Behavior of the Blood Vessels in Recovery from the Deficiency

Slit-lamp observation reveals the capillaries in the 4th to 6th week of the deficiency. Turbidity of the cornea does not appear until many days and often several weeks after the vessels are conspicuous under the slit-lamp. Moderate degrees of turbidity of the cornea disappear as soon as 12 hours after giving 60 ~,of riboflavin by mouth. Unless severely damaged, the cornea is clear within 48 hours. After 2 weeks' treatment with 20 ~, of riboflavin daily, the blood vessels can no longer be seen by an experienced observer with the slit-lamp. 6 They may, however, be demonstrated in sections and by India ink injection. We do not know how long they persist, but they are present in abundance in perfectly clear apparently normal corneas as late as 58 days under adequate riboflavin treatment. They persist long after leucocytic infiltration has disappeared and the tunica propria is restored to normal in all other respects. "

"
DISCUSSION
The riboflavin used in the repair experiments and in the purified diets used in control experiments was pure synthetic riboflavin made by one of us. Therefore, the effects described by us could not have been due to an impurity.
The clinical observations and histological studies rule out demon- strable injury of any nature as the inciting factor of the vasculariza- tion. The role of riboflavin as a respiratory carrier suggests that the vascularization is a response to asphyxia. Since the prevailing opinion is that the cornea respires through its external surface, the failure of the epithelium to transport oxygen seems to be an explanation of the sequence of histologic events. However, it is also reasonable to assume that the vascularization may be a response to the respiratory needs of the epithelium itself. If respiration of the cornea is de- pendent upon the epithelium by virtue of riboflavin activity, the vascularization in vitamin A deficiency could also be accounted for on the basis of an altered physiology accompanying the keratinizing metaplasia. We have not seen vascularization of the cornea of guinea pigs, either in riboflavin deficiency or in vitamin A deficiency. In the rat in riboflavin deficiency, there is no vascularization of cartilage."

"
As a means for the study in a mammal, of growth and regression of capillaries, riboflavin deficiency has obvious advantages which we have made little attempt to explore. Our only histological observation that may possibly be relevant to the problem is that in common with vitamin A deficiency, there is disappearance of the yellow material in the acini of the Harderian glands. In both de- ficiencies, the vascularization is present before the pigment has en- tirely disappeared.
SUMMARY AND CONCLUSIONS Vascularization of the cornea of the rat in the absence of antecedent pathology isprobably a specificand the most reliable criterion of riboflavin deficiency.
Its initiation and repair may be used for testing the biological activity of compounds structurally related to riboflavin.
The facts that the invading capillaries are easily visible in the living animal and that thegrowth and regression of the blood vessels are under dietary control and for a considerable period of time un- accompanied by other pathological reactions, make this method very suitable for the study of problems related to capillary growth.
Wc believe that the best hypothesis in explanation is that the vascularizationisa response to asphyxia of the tunica propria."

 

[Lejeboca]

I can't find specific mention of B2 deficiency in his references, as far as I can glean from the title

From: Rosacea, inflammation, and aging: The inefficiency of stress

"Riboflavin, vitamin B2, is an essential component of the mitochondrial respiratory enzymes, and it is very easily destroyed by light (blue light and especially ultraviolet). When it is excited by high energy light, it can spread the damage to other components of the mitochondria, including the cytochromes and the polyunsaturated fatty acids. The other B vitamins are affected when riboflavin's actions are disturbed."

"The cornea normally contains more riboflavin even than the retina, which has a much higher rate of metabolism. When the cornea isn't able to get enough oxygen from the air for its needs (and if riboflavin is deficient, its need for oxygen is increased), surrounding blood vessels at first dilate in response to the diffusing lactic acid, to increase the blood supply to the edges of the cornea. If the problem is prolonged, the conjuctiva becomes chronically blood-shot, hyperemic, and larger more visible blood vessels grow, surrounding the cornea, or even invading the cornea. Many people, especially women, experienced problems of this sort from wearing contact lenses, especially when the lenses were made of materials very impermeable to oxygen (Dumbleton, et al., 2006)."

 

[yerrag]

By the 1960s, when I started studying biology at the university, the average person knew quite a bit about lactic acid, such as the fact that a deficiency of vitamin B2 causes an excess of lactate to be produced, and that lactic acid can cause the growth of blood vessels in the corneas or whites of the eyes, but the medical profession was already relegating information of that sort to the category of “lore,” not to be taken seriously.

Can anyone add to this? I can't find specific mention of B2 deficiency in his references, as far as I can glean from the titles.

Does lack of B2 cause FADH2 to not be produced in the citric acid cycle and this cause metabolism to be stuck at aerobic glycolysis, whereupon which lactate is produced?
@redsun @Hans

From: Rosacea, inflammation, and aging: The inefficiency of stress

"Riboflavin, vitamin B2, is an essential component of the mitochondrial respiratory enzymes, and it is very easily destroyed by light (blue light and especially ultraviolet). When it is excited by high energy light, it can spread the damage to other components of the mitochondria, including the cytochromes and the polyunsaturated fatty acids. The other B vitamins are affected when riboflavin's actions are disturbed."

"The cornea normally contains more riboflavin even than the retina, which has a much higher rate of metabolism. When the cornea isn't able to get enough oxygen from the air for its needs (and if riboflavin is deficient, its need for oxygen is increased), surrounding blood vessels at first dilate in response to the diffusing lactic acid, to increase the blood supply to the edges of the cornea. If the problem is prolonged, the conjuctiva becomes chronically blood-shot, hyperemic, and larger more visible blood vessels grow, surrounding the cornea, or even invading the cornea. Many people, especially women, experienced problems of this sort from wearing contact lenses, especially when the lenses were made of materials very impermeable to oxygen (Dumbleton, et al., 2006)."

Thanks guys! Makes a lot more sense now.

 

[yerrag]

The determinists generally followed Descartes in seeing the body as a machine, but they argued that the machine could be completely explained by its genes, and sometimes argued that the genes controlled all its functions, making a soul or mind unnecessary. The dissenters from that view saw the nature of life (and of existence in general) as
an open question, to be answered by studying how it comes into being, how it functions, and what happens during its survival and disintegration. Metabolism’s essential meanings of change and interaction put it at the center of non-determinist biological thinking, and cause the other, genetic and mechanistic, style of thinking to keep it in the background. Around 1950, powerful cultural forces (especially the US government) began massively supporting the genetic explanation for everything, cutting support to those who continued to explore the meaning of life in terms of its energy and metabolism. The futile “War on Cancer” looked for the cause of cancer in viruses and mutant genes, and denied that metabolism could be relevant. The Human Genome Project and the application of genetic engineering to virology, immunology, and other branches of medicine involved a similar belief in the irrelevance of metabolism.

The Catholic Church likes to take pride in its role in establishing the university system, in the pursuit of higher learning. If it truly is in search of objective truth, why has the church pushed for the deterministic view of biology, in effect collaborating with the US government and big pharma on making the study of medicine one that produces a weak metabolic in people, one requiring the need for expensive and wasteful healthcare insurance?

Why have the protestant and evangelical sects of Western Christianity gone along with this false dichotomy?

@Inaut Being that you are an Orthodox Christian, do you see Orthodox and Eastern Christianity going along with this?

Muslims, what is Islam predisposed to?

Jews?
Taoists?
Buddhists?
Zionists?

I think personally that a lot of religions are set up as a means of control by their states, or if not, they have been adopted by states to further states' control. To achieve that, the subjects have to be made to believe they are helpless without the state and without a diety. If a person were to be metabolically healthy, and be free of health concerns, and of the need for expensive medicine and surgery, he would not need the state or employer to provide him would health insurance, and he would be in less need for divine intervention in the form of miracles. He would not necessarily lose belief in a god, but he would be in a less dependent relationship with a god, and with the state. His actions would not be guided by fear, but of love. Decisions and actions based on fear are about self-preservation that could be manipulated to prejudice others, but those based on love is about self-preservation with a common good in mind, as it is less susceptible to manipulation.

A fear of eternal damnation would make an Aztec capture his siblings for human sacrifice, but without that fear he would be more likely to kill the high priest at the first opportunity, and abolish that religion.

If we believed in a non-deterministic biology, we would think we have the ability to decide how developed we can be, as our metabolism would shift from being constrained by chronic disease and become an enabler of our development. Our brains would keep developing over a more fruitful and extended lifetime, and our wisdom would not be wasted in an early demise, with more of this wisdom retained and passed on to future generations.

If we are to develop ourselves and to integrate ourselves in the true image of God, we would have gone from a state of despondency to a state of groundedness, and be more like the birds and the bees.

 

[LLight]

Makes me think that non-Peaty fasting would be the way to get rid of senescent cells. What do you think @LLight ?

Hi @yerrag

I'm not sure if it has been shown rigorously in humans (I doubt it) but this review seems interesting: A periodic diet that mimics fasting promotes multi-system regeneration, enhanced cognitive performance and healthspan

They talk about a reversal of the "senescence" of the immune system and organ regeneration (which could necessitate the death of senescent cells I guess).