PUFA Causes Hypoxia And Hypoxia ALWAYS Causes Cancer

[haidut]

both cholesterol and stearic acid stiffen the cell membrane and slow division

Caprylic acid has also been shown to do that and arguably the chemical that is most effective at this is adamantane and its derivatives. I suspect all SFA are capable of doing this in varying degrees, and this is why they have anti-cancer effects. I listed a few interesting studies on that in the DeFibron thread.

 

[Captain_Coconut]

When scientific literature speaks of adulterated PUFA, are they simply referring to trans fats or are there other things that are considered adulterated PUFA?

 

[benaoao]

just FYI after accessing the full paper, you didn't highlight the whole section

Fairly recent study, with a good review of the role of PUFA in the hypoxia that, if maintained chronically, always leads to cancer.

Chronic cellular hypoxia as the prime cause of cancer: what is the de-oxygenating role of adulterated and improper ratios of polyunsaturated fatty ... - PubMed - NCBI

"...Trans fats, partially oxidized PUFA entities, and inappropriate omega-6mega-3 ratios are all potential sources of unsaturated fatty acids that can disrupt the normal membrane structure. In this paper, we explore this hypothesis by examining the evidence, and additionally propose an appropriate PUFA dosage for humans by analyzing requirements and taking into account current PUFA consumption patterns."

What disrupts the cells?
- trans fats, oxidized PUFAs (they say up to 2.5% of the total calories in Americans!!)
- a bad ratio

What are they recommending?
- avoiding too much omegas 3; so balancing the ratio through the reduction of EXCESS omegas 6. EPA isn't as pro inflammatory as Arachidonic Acid (AA) but it's close enough
- the optimal amount of PUFAs isn't and should never be super low like it seems to be recommended sometimes in here. I think Ray Peat is a brilliant scientist and can only be discussing what an excess of PUFA is. Granted it's likely that most people have been in such an excess their whole life. But once people are back on track, it's time to move on from the PUFA fear.

PUFA deficiency causes substitution with inferior fats, and results in the systemic deficiency of the cholesterol structure, and incapability of sufficient oxygen transport. Physico-chemical experiments show that LA can bind twice as much oxygen, which disassociates at a much higher pressure, much closer to the binding dynamics of hemoglobin, than does oleic acid [58]. Given that the oxygen disassociation curves for oleic acid compared with LA, show a 50% reduction in oxygen transfer, the cancer-causing 35% reduction threshold could easily be reached during PUFA deficiency.

I'm not an expert on cancer and oxygen transfer, however this seems understandable.

Based on 2 unique ALA deficiency case reports [62,63] and other studies reporting energy intakes cited by Sinclair et al [38], it is proposed that the ALA energy intake in humans should be between 1% and 1.5%, with a ratio of between 1:1 and 2.5:1 parent omega-6mega-3 PUFAs. For a human consuming a diet of 2000 kcal that contains 65 g of fat, this would translate to approximately 5.8 g of LA and 3.3 g of ALA at an energy intake of 1.4% at an LA:ALA ratio of 1.8:1.

so, about 4-5% of the total calories.

One could also increase the LA:ALA ratio slightly to allow for the fact that extra LA is needed to reduce incorporation of any trans or oxidized fatty acids into cellular membranes through substrate competition. Correct PUFA supplementation also shows promise as an adjunct in cancer treatment

turns out LA isn't bad at all really. Only in massive excess. Will the LA be converted in AA? Yes, but only according to the needs. Whereas AA (eggs, fatty animal cuts) is converted into prostaglandines, thromboxanes, leucotrienes et al.

Many studies list all the benefits seen when consuming stuff like seeds, nuts, avocados, olives. Not their oils obviously, unless cold pressed extracted from the most holy virgin nuts/seeds, I guess. And even then I doubt they'd pack the antioxidants found in the whole product.

 

[haidut]

just FYI after accessing the full paper, you didn't highlight the whole section



What disrupts the cells?
- trans fats, oxidized PUFAs (they say up to 2.5% of the total calories in Americans!!)
- a bad ratio

What are they recommending?
- avoiding too much omegas 3; so balancing the ratio through the reduction of EXCESS omegas 6. EPA isn't as pro inflammatory as Arachidonic Acid (AA) but it's close enough
- the optimal amount of PUFAs isn't and should never be super low like it seems to be recommended sometimes in here. I think Ray Peat is a brilliant scientist and can only be discussing what an excess of PUFA is. Granted it's likely that most people have been in such an excess their whole life. But once people are back on track, it's time to move on from the PUFA fear.



I'm not an expert on cancer and oxygen transfer, however this seems understandable.



so, about 4-5% of the total calories.



turns out LA isn't bad at all really. Only in massive excess. Will the LA be converted in AA? Yes, but only according to the needs. Whereas AA (eggs, fatty animal cuts) is converted into prostaglandines, thromboxanes, leucotrienes et al.

Many studies list all the benefits seen when consuming stuff like seeds, nuts, avocados, olives. Not their oils obviously, unless cold pressed extracted from the most holy virgin nuts/seeds, I guess. And even then I doubt they'd pack the antioxidants found in the whole product.

LA has other detrimental effects. The conversion to AA is just one mechanism. LA is itself estrogenic and promotes cortisol release, activates aromatase, increase serotonin synthesis, block insulin signalling, etc.
Pufa Stimulates Cortisol Production Even In The Absense Of Acth
PUFA Is Directly Catabolic (without Cortisol/estrogen), SFA Is Anabolic
PUFA Initiate & Promote The Stress Response (ACTH/cortisol), SFA Inhibit It

It is the signalling effects that are most detrimental. The structural estrogenicity of LA changes cellular affinity for water and inhibits differentiation, while promoting cell division and growth. There are many other studies on PUFA detrimental effects scattered around the forum so if you search you will find them.

 

[benaoao]

I'm not saying PUFA excess isn't a problem, nor that PUFA consumption in sick individuals is fine, I'm saying the recommendations outlined in my post above are correct in a healthy individual.

Also like I said I'm not an expert in cancer and hypoxia, however the title of this topic seems to be in direct contradiction with the quote from the publication.

 

[benaoao]

LA has other detrimental effects. The conversion to AA is just one mechanism. LA is itself estrogenic and promotes cortisol release, activates aromatase, increase serotonin synthesis, block insulin signalling, etc.
Pufa Stimulates Cortisol Production Even In The Absense Of Acth
PUFA Is Directly Catabolic (without Cortisol/estrogen), SFA Is Anabolic
PUFA Initiate & Promote The Stress Response (ACTH/cortisol), SFA Inhibit It

It is the signalling effects that are most detrimental. The structural estrogenicity of LA changes cellular affinity for water and inhibits differentiation, while promoting cell division and growth. There are many other studies on PUFA detrimental effects scattered around the forum so if you search you will find them.

Yeah and there are many studies all over the internet saying a bunch of rather concerning things about SFA.

Study 1 talks about oxidized LA. Nothing that contradicts my previous posts. Increasing p450scc activity doesn't sound bad at all, it's pretty normal to have foods that increase and others that decrease it.

P-450scc activity was assessed by measuring basal and cAMP-stimulated pregnenolone production in the presence of cyanoketone (1.1 microM). EKODE (13.1 and 26.0 microM) significantly increased basal and cAMP-stimulated (0.1 mM) pregnenolone production.

this part wasn't highlighted. The point remains; a balanced diet is key. Stimulating pregnenolone production is bad now?

Image in study 2 seems to discuss other eicosanoids. I don't see the PUFAs found in whole plants though, nowhere. Indeed, like I said, arachidonic acid (not found in plants) and EPA+DHA found in algae but most commonly in fatty fish. So not ALA, which is converted by the same desaturase enzyme that transforms LA according to the needs.

None of the lipids influenced cell viability or corticosterone radioimmunoassay. The latency of the steroidogenic response, the putative requirement for intracellular oxidation, and the apparent lack of involvement of cAMP suggest a mechanism of action of FFA distinct from that of ACTH, yet still requiring protein synthesis. It is concluded that the modulation of steroidogenesis by these abundant naturally occurring lipids may be an important component of the control mechanisms within the HPA pathway in disorders of lipid homeostasis (e.g., obesity, starvation, or diabetes).

Study 3 is similar to study 1; Stimulating steroidogenesis - in this case, upon high excitation, which leads to cortisol. What if there's no excitation and your steroidogenesis is stimulated? What's the problem actually - the abundance of those lipids. No abundance (should I say, a balanced diet) no problem. It's clear that uncontrolled steroidogenesis leads to estrogen, prolactin, cortisol. Especially in the typical westerner abusing sugar and other insulin spiking foods - obesity and diabetes often show a low SHBG.

None of it seems to be a reason to say that PUFAs found in whole plants are the worst thing ever, like vegans say eating anything animal is the worst thing ever, or keto people say looking at a cherry is the worst thing ever.

As a pharmacist, I appreciate that there's a number of PUFAs that many people could study in petri dishes or rodents. I appreciate even more an unbiased comprehensive sharing of a study, and what this means in real people eating real food.

The study in your OP sure points towards PUFA deficiency being a major issue long term, and a proper consumption of ALA/LA is a very natural solution to the issue.

 

[Captain_Coconut]

Once again: "When scientific literature speaks of adulterated PUFA, are they simply referring to trans fats or are there other things that are considered adulterated PUFA?"

Another question: Why do human cells preferentially absorb PUFA over SFA? That seems evolutionarily quite flawed, SFA is touted as being the healthiest fat but for some crazy reason it is harder to hold on to... Which brings me back to the question about adulterated PUFA vs PUFA in an un-processed state (e.g. avocado). I have asked here before if all PUFA is just as bad and the answer I got was pretty much Yes, however I find it hard to believe that consuming PUFA via french fries is as damaging as eating the same amount of PUFA on a baked potato with some canola oil drizzled on it (not that I would want to eat that, but still).

 

[haidut]

Yeah and there are many studies all over the internet saying a bunch of rather concerning things about SFA.

Study 1 talks about oxidized LA. Nothing that contradicts my previous posts. Increasing p450scc activity doesn't sound bad at all, it's pretty normal to have foods that increase and others that decrease it.



this part wasn't highlighted. The point remains; a balanced diet is key. Stimulating pregnenolone production is bad now?

Image in study 2 seems to discuss other eicosanoids. I don't see the PUFAs found in whole plants though, nowhere. Indeed, like I said, arachidonic acid (not found in plants) and EPA+DHA found in algae but most commonly in fatty fish. So not ALA, which is converted by the same desaturase enzyme that transforms LA according to the needs.



Study 3 is similar to study 1; Stimulating steroidogenesis - in this case, upon high excitation, which leads to cortisol. What if there's no excitation and your steroidogenesis is stimulated? What's the problem actually - the abundance of those lipids. No abundance (should I say, a balanced diet) no problem. It's clear that uncontrolled steroidogenesis leads to estrogen, prolactin, cortisol. Especially in the typical westerner abusing sugar and other insulin spiking foods - obesity and diabetes often show a low SHBG.

None of it seems to be a reason to say that PUFAs found in whole plants are the worst thing ever, like vegans say eating anything animal is the worst thing ever, or keto people say looking at a cherry is the worst thing ever.

As a pharmacist, I appreciate that there's a number of PUFAs that many people could study in petri dishes or rodents. I appreciate even more an unbiased comprehensive sharing of a study, and what this means in real people eating real food.

The study in your OP sure points towards PUFA deficiency being a major issue long term, and a proper consumption of ALA/LA is a very natural solution to the issue.

Like I said, there are plenty of other effects we cannot possibly cover in this thread. The main negative effect is not so much through metabolites but through signalling and change of cellular water structure (e.g. bulk water) as well as "membrane" permeability. PUFA = estrogenic signalling, more or less. Here are a few other things to consider.
PUFA Increases Alcohol Damage By Increasing Cell Fluidity; SFA Are Protective
Unsaturated Fats Role In Non-alcoholic Fatty Liver Disease

The second link is especially revealing. Even mainstream medicine admits that LA causes liver disease. SFA has the opposite effects but as benign as SFA is carbohydrate oxidation is still preferable.
Contradictory Information On PUFAs
Dietary saturated fatty acids down-regulate...
A Combination Of Dietary Linoleic Acid And Alcohol Consumption Exacerbate Liver Injury
Fish oil (omega-3) damages liver, saturated fat protects it

 

[Mito]

- the optimal amount of PUFAs isn't and should never be super low like it seems to be recommended sometimes in here. I think Ray Peat is a brilliant scientist and can only be discussing what an excess of PUFA is. Granted it's likely that most people have been in such an excess their whole life. But once people are back on track, it's time to move on from the PUFA fear.

What is your definition of “super low” PUFA intake?

It’s not just Ray Peat and members of this forum that recommend a very low PUFA intake. One example is Paul Jamiet. Before I had heard of Ray Peat, I read his book “The Perfect Health Diet”. Paul Jaminet has a paleo/ancestral health viewpoint and would disagree with Peat on several things. But on the subject of PUFA, they are not far apart.

From “The Perfect Health Diet”:
“Thus the peak health range for PUFA can be entered by consuming as little as 1 percent of energy as PUFA (0.5 percent each of omega-6 and omega-3).”

“A number of toxicity effects appear with omega-6 intake above 4 percent of calories.”

So Jaminet is suggesting PUFA intake somewhere between 1% and 4% of energy. Assuming a 2,200 calorie diet, 1% of calories from PUFA would be 2.4 grams and 4% would be 9.6 grams.

This is similar to Peat’s typical recommendation of limiting PUFA to 4 or 5 grams/day.

 

[Wagner83]

Androgens modulate chronic intermittent hypoxia effects on brain and behavior. - PubMed - NCBI

Androgens modulate chronic intermittent hypoxia effects on brain and behavior.
Snyder B1, Duong P1, Trieu J2, Cunningham RL3.
Author information
Abstract
Sleep apnea is associated with testosterone dysregulation as well as increased risk of developing neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD). A rodent model of the hypoxic events of sleep apnea, chronic intermittent hypoxia (CIH), has been previously documented to impair cognitive function and elevate oxidative stress in male rats, while simultaneously decreasing testosterone. Therefore, androgens may modulate neuronal function under CIH. To investigate the role of androgens during CIH, male rats were assigned to one of four hormone groups: 1) gonadally intact, 2) gonadectomized (GDX), 3) GDX + testosterone (T) supplemented, or 4) GDX + dihydrotestosterone (DHT) supplemented. Each group was exposed to either normal room air or CIH exposure for one week, followed by memory and motor task assessments. Brain regions associated with AD and PD (entorhinal cortex, dorsal hippocampus, and substantia nigra) were examined for oxidative stress and inflammatory markers, key characteristics of AD and PD. Gonadally intact rats exhibited elevated oxidative stress due to CIH, but no significant memory and motor impairments. GDX increased memory impairments, regardless of CIH exposure. T preserved memory function and prevented detrimental CIH-induced changes. In contrast, DHT was not protective, as evidenced by exacerbated oxidative stress under CIH. Further, CIH induced significant spatial memory impairment in rats administered DHT. These results indicate androgens can have both neuroprotective and detrimental effects under CIH, which may have clinical relevance for men with untreated sleep apnea.

 

[Peatress]

Unbelievable

Healthy Cooking Oils

Replacing bad fats (saturated and trans) with healthier fats (monounsaturated and.

www.heart.org

Here’s an alphabetical list of common cooking oils that contain more of the “better-for-you” fats and less saturated fat.

• Canola
• Corn
• Olive
• Peanut
• Safflower
• Soybean
• Sunflower