Dietary Fat And Its Oxidation Drives Cancer Metastasis

haidut

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Yet another study that discover cancer cells love for fat. As I posted in a few other threads, cancer cells actually need fat (preferably PUFA) for metastasis and survival, and use sugar for ATP generation.
Achilles Heel Of Cancer Found - Its Addiction To Fat
Cancer Cells Addicted To Fat And Use Fat Oxidation For Survival

Mainstream media like NYT has been publishing recently about the "change of direction" in treating cancer - i.e. focusing on restricting sugar supply to cancer cells, with likely tragic consequences.
This new study not only confirms the formidable appetite and preference of cancer cells for fat but also proposes a therapeutic mechanism for completely blocking metastasis - inhibition of the protein CD36. While the study used synthetic inhibitors of CD36, natural ones already exists and one of them is good ol' niacinamide. As I posted in another study, low dose niacinamide (<300mg daily) prevented liver fibrosis and one of the effects of niacinamide was the complete reversal of the abnormal upregulation of CD36.
Low Dose Niacinamide Prevents NAFLD / Cirrhosis
"...Consistent with the high SAMe levels, the liver expression of methionine adenosyltransferase 2A (MAT2A), a gene whose expression is inhibited by SAMe (16), was markedly reduced in GNMT-KO mice but normal in NAM-treated KO animals (Figure 3e). Similarly, the livers of 3-months old GNMT-KO mice showed marked alterations in the expression of critical genes involved in lipid metabolism (CD36, ADFP, PPARα and PPARγ), oxidative stress and inflammation (CYP2E1, CYP39A1, CYP4A10, CYP4A14, UCP2, PPARγ, IL6and iNOS), and extracellular matrix regulation (COL1A1, TIMP-1, α-SMA); and the treatment of GNMT-KO mice with NAM prevented completely (CD36, ADFP, CYP4A10, CYP4A14, CYP39A1, UCP2, IL6, iNOS, COL1A1, α-SMA) or largely (PPARα, PPARγ, CYP2E1, TIMP-1) the abnormal expression of these genes in the liver (Figure 3a-e)."
"...Moreover, the finding that the administration to GNMT-KO mice of NAM, an inhibitor of SIRT1 activity (28), prevented rather than aggravated the abnormal expression of CD36, ADFP, PARPα and PARPα further supports the conclusion that the development of steatosis in GNMT-KO mice is independent of SIRT1. This may be due to the low dose of NAM used in the present experiments (50 μM) as compared to the high concentration used to inhibit SIRT1 activity in culture cells (5 mM) (29)."

I supposed, in light if these new findings and the effects of niacinamide on CD36, it is not surprising that niacinamide was highly effective against cancer spread in an animal model, as I posted in another thread.
Niacinamide Fully Prevents Breast Cancer Metastasis

I am not aware of any other natural inhibitors of CD36 but if someone is please share as they have the potential to completely prevent/stop cancer metastasis, as the study below says. A combination with aspirin will likely increase the anti-cancer effect of niacinamide, especially considering the ability of aspirin to inhibit the enzyme FAS, which is required for primary and metastatic tumor growth.

Finally, another important finding from the study was that high-fat diets promote cancer metastasis. Given that rodent chow used in studies is about 60% PUFA, I think this study should end the argument on whether sugar or fat oxidation is better for our health, and whether PUFA is good or bad for our health.

http://www.nature.com/nature/journal/vaop/ncurrent/full/nature20791.html
Cancer consumes fat to feed its metastatic march in mice
Fat fuels cancer’s spread in mice
"...The cells responsible for cancer’s spread — and for most deaths from cancer — may have a fatal weakness according to studies in mice: a reliance on certain fats to fuel their invasion. It is a difficult and hazardous undertaking for a cancer cell to uproot itself, travel through the bloodstream and take hold in an entirely different part of the body. (Non-cancerous cells are often programmed to self-destruct if they leave the tissue they live in.) Researchers have long struggled to understand which cancer cells can manage the feat, and how they do so. But a study published on 7 December in Nature1 has identified a population of oral tumour cells that are able to make the journey in mice, and has found that such cells may feast on fats to fuel the trip. Determining how certain cancer cells spread throughout the body — a process called metastasis — is a big step forward, says Xiang Zhang, a cancer researcher at Baylor College of Medicine in Houston, Texas, who was not involved in the study. “Now people have a suspect they can follow.”

"...Such lipids could serve as an energy source for wandering tumour cells, they reasoned. “Metastasis takes a lot of energy,” says Ernst Lengyel, a gynaecological oncologist at the University of Chicago in Illinois, who was not involved in the project. “As a cell you must be able to adapt to changing environments, reprogram protein expression, establish a beachhead and start proliferating as soon as possible.”

"...Benitah and his team found that high CD36 expression was required for metastasis in mice. Antibodies that blocked CD36 — and eliminated its interaction with fatty acids — completely inhibited metastasis, although they did not affect the development of primary tumours. The researchers also mined public databases and found that high expression of CD36 correlated with poor medical outcomes in bladder, lung, breast and other cancers in people. Benitah’s team is now working to develop antibodies against CD36 that could be used in clinical trials, although he estimates it would take at least another four years to reach that milestone. Benitah notes that such a therapy may be effective even after cancer has started to spread: in mice, experimental antibodies eradicated metastatic tumours 15% of the time. The remaining metastatic tumours shrunk by at least 80%. The team is also looking at the implications of another finding: feeding the mice a high-fat diet led to more and larger tumours in the lymph nodes and lungs — a sign of metastasis — compared with mice on normal diets. Benitah’s team is now carrying out a study that aims to enrol 1,000 people with cancer, profiling lipids in their blood to look for any links to the spread of cancer cells.
 
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Tarmander

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It's almost becoming a meme where Haidut says they used a "8325gerjd" inhibitor...but niacinamide will do the same thing.
 

haidut

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It's almost becoming a meme where Haidut says they used a "8325gerjd" inhibitor...but niacinamide will do the same thing.

Lol, I know right? Niacinamide for everything!
But seriously, if anybody knows of other CD36 inhibitors please share.
 
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Welp, low fats where its at.

When I look at this list of mine from two years ago:

Any Other Plant Fats That I'm Missing From This List?

the only ones that are enjoyable to me are olives, which can't be eaten raw because of oleuropein, so they are cured, coconut, which I only like with sugar like a sweet coconut sorbet, and chocolate fat, similar to the way I like coconut, I like with sugar. And I do like mac nuts. So I don't see the point of eating much plant fat. Animal fat is another topic. But for experiment, imagine a big bowl of avocados, a big bowl of boiled/steamed potatoes, a big bowl of nuts of your choice, a big bowl of papaya flesh, a big bowl of a muscle meat of your choice, and a big bowl of butter, all the same amount in about 2-3000 calories worth. Then imaging choosing which one you have to eat every day for a month. Which one would make you feel best? I think the answer should be clear. It would be the potatoes or papayas.
 

Stryker

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Welp, low fats where its at.

When I look at this list of mine from two years ago:

Any Other Plant Fats That I'm Missing From This List?

the only ones that are enjoyable to me are olives, which can't be eaten raw because of oleuropein, so they are cured, coconut, which I only like with sugar like a sweet coconut sorbet, and chocolate fat, similar to the way I like coconut, I like with sugar. And I do like mac nuts. So I don't see the point of eating much plant fat. Animal fat is another topic. But for experiment, imagine a big bowl of avocados, a big bowl of boiled/steamed potatoes, a big bowl of nuts of your choice, a big bowl of papaya flesh, a big bowl of a muscle meat of your choice, and a big bowl of butter, all the same amount in about 2-3000 calories worth. Then imaging choosing which one you have to eat every day for a month. Which one would make you feel best? I think the answer should be clear. It would be the potatoes or papayas.

potatoes everytime ... i think they are the only food i can gratuitous amounts of and not suffer any symptom of overeating.

i had 2kg of gourmandine potatoes the othernight cooked in an infared oven with just salt and caprylic acid and i felt amazing afterwards LOL
 
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@Westside PUFAs If you have time to answer, what do you consider low fat? Do you think 10% of calories is too high?

It's all up to you. All I know is that for me, the fat I eat is the fat I wear. And no, Durianrider didn't come up with that line. Neither did McDougall. Someone from the "natural hygine" movement came up with it decades ago. But it's not just about aesthetics. For me, when I go too high in fat I start to get blood sugar dysregulation, and sleep and mood problems. But outside of body fat, and those things I just mentioned, I'm also concerned with dietary fat and cancer like what this post is about but also heart disease. The amount of dietary fat for you is the amount that keeps you happy with your body fat, sleep, blood sugar, and mood, and longevity if you care about that.

I just think dietary fat is just different than protein and carbohydrate. It's just a different animal. Dietary protein and dietary carbohydrate don't do the same things that dietary fat does.

.
 
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superhuman

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@Westside PUFAs i like that you are deep into low fat and i agree with it as well. Its just hard to really find evidence to support metabolic effects in terms of calories in vs calories out and fat loss when calories are equal. It seems like the body adjust rather quickly and up regulates DNL when fat er low and carbs are high after a few days.

I saw a study that just got published but i dont remember the link where they showed high carb low fat vs high fat low fat in regards to satiety and the high carb group won. Both groups got to eat as much as they wanted each meal from the foods and the high carb group ate like 500 kcals+ lower daily
 

burtlancast

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Interesting.

Q. Would it not be advantageous for the cancer patients to remain permanently on a vegetarian diet for the rest of their lives?

A. That depends on how far the liver can be restored. If it can be restored entirely, after say 1½ years, we tell the patients only to avoid fats and salt.

(Max Gerson)
 

Wagner83

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@Westside PUFAs i like that you are deep into low fat and i agree with it as well. Its just hard to really find evidence to support metabolic effects in terms of calories in vs calories out and fat loss when calories are equal. It seems like the body adjust rather quickly and up regulates DNL when fat er low and carbs are high after a few days.

I saw a study that just got published but i dont remember the link where they showed high carb low fat vs high fat low fat in regards to satiety and the high carb group won. Both groups got to eat as much as they wanted each meal from the foods and the high carb group ate like 500 kcals+ lower daily

You mean they only ate 500 kcal three times daily?
 

DaveFoster

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Interesting.

Q. Would it not be advantageous for the cancer patients to remain permanently on a vegetarian diet for the rest of their lives?

A. That depends on how far the liver can be restored. If it can be restored entirely, after say 1½ years, we tell the patients only to avoid fats and salt.

(Max Gerson)
Their data is probably polluted by associations of the two. Salt is necessary and a universal craving, for some more than others. Dr. Brewer demonstrated the importance of salt in his treatment of pre-eclampsia, and sodium opposes the sympathetic response and estrogen at a fundamental level.

I was reading through Peat's work, and I realized he already made a similar argument:

"Pre-eclampsia and pregnancy toxemia have been corrected (Shanklin and Hodin, 1979) by both increased dietary protein and increased salt, which improve circulation, lower blood pressure, and prevent seizures, while reducing vascular leakiness. The effectiveness of increased salt in pre-eclampsia led me to suggest it for women with premenstrual edema, because both conditions typically involve high estrogen, hyponatremia, and a tendency toward hypo-osmolarity. Estrogen itself causes sodium loss, reduced osmolarity, and increased capillary leakiness. Combined with a high protein diet, eating a little extra salt usually helps to correct a variety of problems involving edema, poor circulation, and high blood pressure."

Water: swelling, tension, pain, fatigue, aging
 

burtlancast

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Their data is probably polluted by associations of the two. Salt is necessary and a universal craving, for some more than others. Dr. Brewer demonstrated the importance of salt in his treatment of pre-eclampsia

How many cancer patients did Dr Brewer work with?
 

DaveFoster

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How many cancer patients did Dr Brewer work with?
Point taken, as with glucose deprivation of the tumors.

I suppose it depends on the particular approach.
 

andy

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I have had neck cancer .so far so good .Regular checks show no metastasis after 5 years.should my diet be fat free?I have tried to eliminate fats and get really dry skin with cracks on the corner of the mouth.(alleviated by Gla and oily fish).My carbs are lots of white sugar and chocolate.I was previously having a lot of potatoes but made me feel sluggish and bunged up.Eating lots of steamed veg and bowels working better although not quite sure I am taking in enough carb calories.If low fat is the way to go then it is really difficult get in the calories unless one eats huge amounts of sugar(as in my case)
 

Amazoniac

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This is interesting:
Cancer: Disorder and Energy
"The alkaline cancer cell surrounds itself by the acid that it emits, and this extracellular acidity increases the ability of fatty acids to enter the cell (Spector, 1969); cancer cells, although they are synthesizing fat, also avidly take it up from their environment (Sueyoshi and Nagao, 1962b). This fat avidity is so extreme that cancer cells in vitro will eat enough polyunsaturated fat to kill themselves. This has been offered as proof that fish oil kills cancer. Saturated fats, however, have a calming effect on cancer cells, inhibiting their aerobic glycolysis (Marchut, et al., 1986) while permitting them to resume the respiratory production of energy."
 

haidut

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