Blocking inflammation from PUFA stops progression of cancer

haidut · Dec 11, 2015

This study is quite timely given the other recent one showing that stopping brain inflammation reverses aging in the brain.
viewtopic.php?f=155&t=8269
Both of the studies are also important because they highlight the primary role PUFA play in both processes. Both studies looked at the effects of antagonizing the leukotrienes - inflammatory mediators derived from arachidonic acid (omega-6 PUFA).
This study showed that inhibiting 5-LOX, an enzyme which synthesizes the leukotrienes, blocks the progression/spreading of cancer. Well known 5-LOX inhibitors in Peat-world include minocycline, vitamin E, caffeic acid, and curcumin. Less known ones are meclofenamate, and zileuton. Leukotriene antagonists include montelukast, zafirlukast and of course cyproheptadine.

http://www.nature.com/nature/journal/va ... 16140.html
http://www.cancerresearchuk.org/about-u ... cer-spread

"...Researchers found that chemical messengers - made by immune cells called neutrophils - can help spreading cancer cells to grow in a new environment. When the scientists looked at breast cancer in mice, they found that these messengers – known as leukotrienes – helped the disease to spread to the lungs."

"...The messengers helped make the lungs more welcoming to cancer by homing in on cancer cells with the highest potential to form a secondary tumour and helping them to multiply. The research showed that using an inhibitor drug** to block these messengers from being produced reduced cancer spread in mice."

brandonk · Dec 11, 2015

I don't think one can assume (as the title of the post seems to me to imply?), that the danger of inflammation comes from exogenous or dietary PUFAs, though ingested PUFAs may be a part of the danger. Nor that eating less PUFAs will reduce the risk of cancer, or in the previous study reduce the risk of aging of the brain.

Reducing the PUFAs you eat may help, of course, but the source of the inflammatory messengers is the visceral adipose depot, such as the omental depot around the stomach, or the mesenteric one around the intestines. It seems likely to lead to disappointment to suggest that people will somehow "get better" simply by reducing PUFAs in their diet. There's not evidence for that in this study, nor in any study I've ever seen.

What all the studies show, at most, is that one needs to reduce or perhaps eliminate the actual source of the inflammation, which, as I've posted elsewhere, is well-known to be the chronic, low-grade inflammation of visceral adipose depots, now often called "visceral obesity" and typically reflected in the waist-to-hip ratio, or detected in an MRI. This requires more than merely eliminating PUFAs in the diet, though eliminating PUFAs never does any harm!

What is your waist-to-hip ratio? Have you ever had an MRI to detect visceral obesity?

haidut · Dec 11, 2015

brandonk said:
post 114082 I don't think one can assume (as the title of the post seems to me to imply?), that the danger of inflammation comes from exogenous or dietary PUFAs, though ingested PUFAs may be a part of the danger. Nor that eating less PUFAs will reduce the risk of cancer, or in the previous study reduce the risk of aging of the brain.

Reducing the PUFAs you eat may help, of course, but the source of the inflammatory messengers is the visceral adipose depot, such as the omental depot around the stomach, or the mesenteric one around the intestines. It seems likely to lead to disappointment to suggest that people will somehow "get better" simply by reducing PUFAs in their diet. There's not evidence for that in this study, nor in any study I've ever seen.

What all the studies show, at most, is that one needs to reduce or perhaps eliminate the actual source of the inflammation, which, as I've posted elsewhere, is well-known to be the chronic, low-grade inflammation of visceral adipose depots, now often called "visceral obesity" and typically reflected in the waist-to-hip ratio, or detected in an MRI. This requires more than merely eliminating PUFAs in the diet, though eliminating PUFAs never does any harm!

What is your waist-to-hip ratio? Have you ever had an MRI to detect visceral obesity?

My waist to hip ratio is 0.8 and I haven't had an MRI to see visceral fat. The study does point to PUFA b/c the leukotrienes are synthesized from arachidonic acid, which comes from linoleic acid, which comes only from food. Clearly if you stop eating PUFA and you have a lot of stored PUFA the situation is not going to magically fix itself but you will be better off than continuing to eat it. Also, eating PUFA would increase even more the synthesis of leukotrienes instead of being stored in tissue.
Again, no PUFA (both stored and eaten) means no inflammation. For the people that have to deplete PUFA stores first that would take some time but limiting further PUFA intake will certainly lower the risk and eventually deplete the stored PUFA and stop all inflammation.

brandonk · Dec 11, 2015

Not to argue, but just to state what we both know is not really arguable, as Ray Peat explains in his article "Fats and degeneration", the fetus is completely depleted of PUFAs such that no inflammation occurs, and wounds are repaired without any swelling.

After birth, PUFAs accumulate in the newborn from mother's milk, and many foods in the diet.

Once PUFAs have accumulated, Inflammation can be brought on when estrogen and stress cause stored PUFAs to be released.

Eating PUFAs likely does make this inflammation possible and worsens it. However, not eating PUFAs can never return the body to that pure fetal state of zero PUFAs that can stop inflammation.

To test this for yourself, next time you have a cut see if your wound repairs itself without any inflammation as it does in a fetus. If the cut swells, then you have PUFAs sufficient to make inflammation (and literally, of course, everybody does).

Hugh Johnson · Dec 12, 2015

brandonk said:
post 114171 . However, not eating PUFAs can never return the body to that pure fetal state of zero PUFAs that can stop inflammation.

Going to need a citation on that.

brandonk · Dec 12, 2015

Hugh Johnson said:
post 114203

brandonk said:

post 114171 . However, not eating PUFAs can never return the body to that pure fetal state of zero PUFAs that can stop inflammation.

Click to expand...

Going to need a citation on that.

Unless you're living in the relatively germ-free womb as the fetus is, you're going to need the protective form of inflammation that comes from phagocytosis. I find Elie Metchnikoff's discovery of phagocytosis in the late 1800s to be truly inspiring. Phagocytosis requires that unsaturated fatty acids be liberated from the adipose tissue when needed.

The practical problem is not the absolute amount of PUFAs. which is never zero outside the womb. The problem is that eating PUFAs worsens the ratio of saturated to unsaturated, as Ray Peat explains in his article "Unsaturated Vegetable Oils: Toxic."

On a highly restrictive diet that completely eliminated PUFAs, you might over a period of three years or so improve this ratio to 2:1 in favor of saturated fats, but you'll never eliminate unsaturated fat, nor would you want to, as long as you're living outside a germ-free bubble.

Eating food that has saturated fat is a more practical way to improve this ratio, especially if the fat is fully saturated.

zooma · Dec 12, 2015

brandonk said:
post 114247 Eating food that has saturated fat is a more practical way to improve this ratio, especially if the fat is fully saturated.

I've seen a few people say this. But hasn't Ray said that the body will preferentially burn the saturated fat and store the PUFA, meaning that over time you will continue to accumulate the PUFA that you eat regardless of how much saturated fat is with it. So eating lots of saturated fat will only improve the ratio stored if you eat enough to gain fat?

brandonk · Dec 12, 2015

zooma said:
brandonk said:

post 114247 Eating food that has saturated fat is a more practical way to improve this ratio, especially if the fat is fully saturated.

Click to expand...

I've seen a few people say this. But hasn't Ray said that the body will preferentially burn the saturated fat and store the PUFA, meaning that over time you will continue to accumulate the PUFA that you eat regardless of how much saturated fat is with it. So eating lots of saturated fat will only improve the ratio stored if you eat enough to gain fat?

From a recent interview, he seems to be experimenting (as I am) with eating fully saturated fat, for example the specific saturated fats in fully hydrogenated coconut oil. Other fully saturated fats he's mentioned as improving the ratio are the medium chain triglycerides found in palm oil or coconut oil.

"Gaining fat" is something that happens constantly and invisibly, because adipose tissue is widely distributed across numerous depots literally all over the body, even the neck and collarbone. For this reason, I try not to use the word "fat" because it's imprecise and often misunderstood, and perhaps as a result, the whole topic of "being fat" or "skinny" is emotionally charged.

Put another way, enlargement of the more visible adipose tissue around the waist is typically a sign of visceral obesity, which is a well-known source of chronic, low-grade inflammation. However, the enlargement of these visible depots around the waist is often rapidly reversed by eating the specific saturated fats or medium chain triglycerides in coconut oil.

zooma · Dec 12, 2015

brandonk said:
post 114270 However, the enlargement of these visible depots around the waist is often rapidly reversed by eating the specific saturated fats or medium chain triglycerides in coconut oil.

These are the deposits that will be largely PUFA, correct? So eating lots of the MCTs will reverse the obese/overweight state and improve the sat/PUFA ratio?

Hugh Johnson · Dec 12, 2015

brandonk said:
post 114270

zooma said:

brandonk said:

post 114247 Eating food that has saturated fat is a more practical way to improve this ratio, especially if the fat is fully saturated.

Click to expand...

I've seen a few people say this. But hasn't Ray said that the body will preferentially burn the saturated fat and store the PUFA, meaning that over time you will continue to accumulate the PUFA that you eat regardless of how much saturated fat is with it. So eating lots of saturated fat will only improve the ratio stored if you eat enough to gain fat?

Click to expand...

From a recent interview, he seems to be experimenting (as I am) with eating fully saturated fat, for example the specific saturated fats in fully hydrogenated coconut oil. Other fully saturated fats he's mentioned as improving the ratio are the medium chain triglycerides found in palm oil or coconut oil.

"Gaining fat" is something that happens constantly and invisibly, because adipose tissue is widely distributed across numerous depots literally all over the body, even the neck and collarbone. For this reason, I try not to use the word "fat" because it's imprecise and often misunderstood, and perhaps as a result, the whole topic of "being fat" or "skinny" is emotionally charged.

Put another way, enlargement of the more visible adipose tissue around the waist is typically a sign of visceral obesity, which is a well-known source of chronic, low-grade inflammation. However, the enlargement of these visible depots around the waist is often rapidly reversed by eating the specific saturated fats or medium chain triglycerides in coconut oil.

Maybe, but my weight had been stable until I switched from regular to hydrogenated coconut oil in my daily poutine. I gained I think 12 kg. Can't seem to got rid of it.

Also , thanks for the answer on the other one. I'll look into it.

barefooter · Dec 12, 2015

brandonk said:
post 114247 Unless you're living in the relatively germ-free womb as the fetus is, you're going to need the protective form of inflammation that comes from phagocytosis. I find Elie Metchnikoff's discovery of phagocytosis in the late 1800s to be truly inspiring. Phagocytosis requires that unsaturated fatty acids be liberated from the adipose tissue when needed.

So, in a sense inflammation is a sort of trade off to deal with the germs and stress of living in a dangerous world, but is not ideal for healing? Is inflammation not the healing process at all, but merely the way the body quarantines damaged tissues to prevent spread of damage by microbes or other factors? I'm starting to get this impression as I'm reading Hans Selye's, "The Stress of Life". And looking at things this way really makes sense why anti-inflammatory factors like reducing PUFA, aspirin, niancinamide, etc. are so beneficial since we don't live in a very dangerous world and would rather heal more perfectly than safe guard from infection.

brandonk · Dec 12, 2015

barefooter said:
brandonk said:

post 114247 Unless you're living in the relatively germ-free womb as the fetus is, you're going to need the protective form of inflammation that comes from phagocytosis. I find Elie Metchnikoff's discovery of phagocytosis in the late 1800s to be truly inspiring. Phagocytosis requires that unsaturated fatty acids be liberated from the adipose tissue when needed.

Click to expand...

So, in a sense inflammation is a sort of trade off to deal with the germs and stress of living in a dangerous world, but is not ideal for healing? Is inflammation not the healing process at all, but merely the way the body quarantines damaged tissues to prevent spread of damage by microbes or other factors? I'm starting to get this impression as I'm reading Hans Selye's, "The Stress of Life". And looking at things this way really makes sense why anti-inflammatory factors like reducing PUFA, aspirin, niancinamide, etc. are so beneficial since we don't live in a very dangerous world and would rather heal more perfectly than safe guard from infection.

It's been a century-old mystery since Metchnikoff's discovery of phagocytes why these amazing creatures attack our own seemingly health tissue and cause inflammation.

In the Ray Peat view of biology, it could be in response to the trillions of unimaginably dangerous cell-like things that escape our intestines, either dead or alive, and invade other tissue in a way that's nearly impossible to detect.

It could also be a response to an increasingly dangerous world of industrial particles that phagocytes have never before encountered, such as refined starch, unsaturated fat, processed iron and meat and even radioactive isotopes. With all this, you might imagine why phagocytes would be a little confused about where their enemy is.

Keeping a very clean, highly motile intestine (with antibacterial coffee, aspirin and emodin), avoiding industrial particles in food, and fueling mitochondria with ketones and niacinamide seems to be one way of making life easier for the phagocytes and mitochondria that maintain us in the very essence of life.

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Blocking inflammation from PUFA stops progression of cancer

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