Omega-3 Fatty Acids Fight Inflammation Via Cannabinoids ?

[Nestito]

https://www.sciencedaily.com/releases/2017/07/170718142909.htm

?

 

[michael94]

hmm

 

[michael94]

@burtlancast

 

[burtlancast]

Cannabinoids have been patented as anti inflammatory agents for decades.
Omega 3 have been known to have the same anti inflammatory properties.

But the difference is cannabinoids have been shown as well to kill cancer cells, especially in self treatment with Rick Simpson oil. In contrast, while there are some studies on omega 3 reducing tumor size and spread, the same dramatic effect hasn't been reported (to my knownledge at least).

This is a very interesting development.
Let's too remember flaxseed oil Is rich in both CBD (cancer cell killer) and omegas 3. It contains too linmarin, a form of B17 vitamin.

 

[Frankdee20]

Cannabinoids have been patented as anti inflammatory agents for decades.
Omega 3 have been known to have the same anti inflammatory properties.

But the difference is cannabinoids have been shown as well to kill cancer cells, especially in self treatment with Rick Simpson oil. In contrast, while there are some studies on omega 3 reducing tumor size and spread, the same dramatic effect hasn't been reported (to my knownledge at least).

This is a very interesting development.
Let's too remember flaxseed oil Is rich in both CBD (cancer cell killer) and omegas 3. It contains too linmarin, a form of B17 vitamin.

Is Flaxseed oil estrogenic ?

 

[burtlancast]

Is Flaxseed oil estrogenic ?

It's complicated.

 

[Travis]

I thought ω−3 fatty acids "worked" by blocking eicosanoid production. Only linoleic acid (ω−6) can be used to make eicosanoids.

Aspirin, colchicine, and indomethacin are also thought to reduce inflamation by inhibiting eicosanoid production.

Eicosanoids are powerful since they can bind to PPARγ, a nuclear receptor that—when activated—can direct the transcription of what I call "diabetes mode". An upregulation of proteins such as fatty acid synthesase and GLUT4 that orchestrate fat-storing activities in adipose tissue.

Although ω−3 fatty acids are "safe" from the perspective of eicosanoid production, they are still more prone to peroxidation that saturated fatty-acids. But from reading about lipofuscin, excessive iron and low antioxidant levels seem to be a bigger cause of intracellular peroxidation than unsaturated fats themselves.

Cold-pressed oils should have enough vitamin E and antioxidants to partially mitigate the susceptibility of unsaturated fatty acids to lipid peroxidation.

 

[Amazoniac]

I thought ω−3 fatty acids "worked" by blocking eicosanoid production. Only linoleic acid (ω−6) can be used to make eicosanoids.

Aspirin, colchicine, and indomethacin are also thought to reduce inflamation by inhibiting eicosanoid production.

Eicosanoids are powerful since they can bind to PPARγ, a nuclear receptor that—when activated—can direct the transcription of what I call "diabetes mode". An upregulation of proteins such as fatty acid synthesase and GLUT4 that orchestrate fat-storing activities in adipose tissue.

Although ω−3 fatty acids are "safe" from the perspective of eicosanoid production, they are still more prone to peroxidation that saturated fatty-acids. But from reading about lipofuscin, excessive iron and low antioxidant levels seem to be a bigger cause of intracellular peroxidation than unsaturated fats themselves.

Cold-pressed oils should have enough vitamin E and antioxidants to partially mitigate the susceptibility of unsaturated fatty acids to lipid peroxidation.

Mr Fahrenheit,
Some time ago I asked tyw about dairy and coconut fat and how they compare to each other in terms of PUFA. Do you have an opinion on it? Coconut has slightly less but it's practically all omega-6.

 

[Travis]

Well after reading quite a few animal studies on how only ω−6 linoleic acid causes cancer (eicosanoid pathway), I think the two most important ways of comparing fatty acid profiles are the iodine number and total linoleic acid content.

The iodine number is a decent estimation of peroxidation potential, and ties-in with free radicals and lipofuscin.

Linoleic acid is the only fatty acid that correlates very highly with cancer in animals, and the fully-saturated stearic acid is the only one consistently found protective.

The linoleic acid content of goat milk is low, and seems to vary little with diet.
Click to embiggen

From what I remember, the linoleic acid content of coconut is around 1–3%.

And the iodine value of butter is very low. Only coconut and palm out have lower iodine values.
Click to embiggen

The fatty-acid profile of milk is almost as Peatish as the coconut. The only strong criticisms of dairy products, that I am aware of, revolve around the hormone (both steroid and peptide) content and the potential of casein to form β-casomorphins.* The casomorphins aren't harmful physically, but can effect nociception and emotions in certain people.

There is also a tad more methionine in cow's milk than in coconuts (per gram protein), but less than the cow itself (beef). These can form polyamines which have interesting biological effects. I have only begun to read about polyamines.

*There is also the tie-in with vaccines, as casein is often used to culture the bacteria in which the vaccine's antigens derive from. Being injected with a protein can cause anaphylactic sensitization to that protein. For more information on this, see Charles Richet's Nobel Lecture and Vinu's articles on researchgate.

 

[Amazoniac]

Well after reading quite a few animal studies on how only ω−6 linoleic acid causes cancer (eicosanoid pathway), I think the two most important ways of comparing fatty acid profiles are the iodine number and total linoleic acid content.

The iodine number is a decent estimation of peroxidation potential, and ties-in with free radicals and lipofuscin.

Linoleic acid is the only fatty acid that correlates very highly with cancer in animals, and the fully-saturated stearic acid is the only one consistently found protective.

The linoleic acid content of goat milk is low, and seems to vary little with diet.
View attachment 6188 Click to embiggen

From what I remember, the linoleic acid content of coconut is around 1–3%.

And the iodine value of butter is very low. Only coconut and palm out have lower iodine values.
View attachment 6189 Click to embiggen

The fatty-acid profile of milk is almost as Peatish as the coconut. The only strong criticisms of dairy products, that I am aware of, revolve around the hormone (both steroid and peptide) content and the potential of casein to form β-casomorphins.* The casomorphins aren't harmful physically, but can effect nociception and emotions in certain people.

There is also a tad more methionine in cow's milk than in coconuts (per gram protein), but less than the cow itself (beef). These can form polyamines which have interesting biological effects. I have only begun to read about polyamines.

*There is also the tie-in with vaccines, as casein is often used to culture the bacteria in which the vaccine's antigens derive from. Being injected with a protein can cause anaphylactic sensitization to that protein. For more information on this, see Charles Richet's Nobel Lecture and Vinu's articles on researchgate.

That's very helpful. Thanks!

 

[Amazoniac]

Travis, I'm going to send you some casein powder derived from Holstein cows on your birthday as a retribution for all of the good content that you post.

 

[Travis]

So I can get high on β-casomorphin?

Send some trypsin too! That way, I can convert the casein into small opioid peptides in a jar.

[I have always wanted to mainline β-casomorphins, and take lines of it mixed with cocaine.]

When it's purified and given to rats, it works essentially just like morphine. It is also inhibited by the morphine antagonist naloxone. It reduces the pain response and nerve transmission in rats in a naloxone-dependent manner.

 

[Amazoniac]

Well after reading quite a few animal studies on how only ω−6 linoleic acid causes cancer (eicosanoid pathway), I think the two most important ways of comparing fatty acid profiles are the iodine number and total linoleic acid content.

The iodine number is a decent estimation of peroxidation potential, and ties-in with free radicals and lipofuscin.

Linoleic acid is the only fatty acid that correlates very highly with cancer in animals, and the fully-saturated stearic acid is the only one consistently found protective.

The linoleic acid content of goat milk is low, and seems to vary little with diet.
View attachment 6188 Click to embiggen

From what I remember, the linoleic acid content of coconut is around 1–3%.

And the iodine value of butter is very low. Only coconut and palm out have lower iodine values.
View attachment 6189 Click to embiggen

The fatty-acid profile of milk is almost as Peatish as the coconut. The only strong criticisms of dairy products, that I am aware of, revolve around the hormone (both steroid and peptide) content and the potential of casein to form β-casomorphins.* The casomorphins aren't harmful physically, but can effect nociception and emotions in certain people.

There is also a tad more methionine in cow's milk than in coconuts (per gram protein), but less than the cow itself (beef). These can form polyamines which have interesting biological effects. I have only begun to read about polyamines.

*There is also the tie-in with vaccines, as casein is often used to culture the bacteria in which the vaccine's antigens derive from. Being injected with a protein can cause anaphylactic sensitization to that protein. For more information on this, see Charles Richet's Nobel Lecture and Vinu's articles on researchgate.

Do you know if coconut fat as good as dairy fat to protect you from dietary PUFA? Our Oregon instructor (not the one from New Hampshire) mentioned that one of the reasons why coconut oil keeps stable for a long time despite its PUFA content and lack of antioxidants is because the saturated fats don't allow destructive chains to propagate. However those fats are oxidized quickly once ingested, also they're not stored as easily as dairy fat and so I wonder if the protective effect only lasts while they are being oxidized. If possible, can you destroy my self-esteem on this?

 

[Travis]

Our Oregon instructor (not the one from New Hampshire) mentioned that one of the reasons why coconut oil keeps stable for a long time despite its PUFA content and lack of antioxidants is because the saturated fats don't allow destructive chains to propagate.

Yeah. There is also less chance of the first double-bond reacting with oxygen. I just read this passage in a book by Ilya Prigogine:

For the sake of example, let us take a simple reaction such as A + X = B + Y. This "reaction equation" means that whenever a molecule of component A encounters a molecule of X, there is a certain probability that a reaction will take place and a molecule of B and a molecule of Y will be produced. A collision producing such a change in the molecules involved is a "reactive collision." Only a usually very small fraction (for example, 10⁻⁶ of all collisions are of this kind. In most cases, the molecules retain their original nature and merely exchange energy.

The rate of lipid peroxidation in bulk oils is usually modeled by the Arrhenius equation: ln(k) = ln(A) − E/RT

Coconut oil has a low rate constant (k), but not as low as palm oil. This is thought to be because of the slightly higher percentage of free fatty acids in coconut oil. When they are packed as triglycerides, they are more resistant to oxidation. Besides steric hindrance, you would think that the extra mass of triglycerides would slow their kinetic diffusion rates.

Coconut oil came in third place. The bulk oil that is most resistant to peroxidation might surprise you. It was sesame seed oil:

Its remarkable stability may be caused by the presence of the endogenous antioxidants sesamol and sesaminol, together with tocopherols (24). Another contradictory result was found with the CtO [coconut oil]. The IV [iodine value] of CtO in the present study was almost half of that of PKO [palm kernal oil] (Table 1). However, the k [kinetic oxidation rate] value at a given T [temperature] for CtO was almost 60% faster compared to PKO. This may be caused by the initial high free fatty acid content in CtO. Unbound fatty acids are more prone to oxidation compared to fatty acids bound to the glycerol molecules. We postulate that this may be the main reason for the deviation from the norm for the k values in CtO.

Perhaps it could be fluidity as well? We all know that coconut oil is the least viscous, so it's molecules are moving around much faster than the other oils. You would expect more collisions with oxygen with coconut oil.

The resistance of sesame seed oil probably comes from the antioxidants, but the sesamol and the sesaminol are phenols and would diffuse away when eaten. These will probably be eliminated from the body within a day, so we should be cautious when extrapolating bulk oil peroxidation values to membranes in vivo. Maybe the iodine value is still the best index? (This study† was carried-out at 400°C with pure O₂ so I'm not sure how practical the results are.)

However those fats are oxidized quickly once ingested, also they're not stored as easily as dairy fat and so I wonder if the protective effect only lasts while they are being oxidized.

This seems logical, but don't underestimate palmitic acid. This lipid can be found in cell membranes, and makes-up roughly ¹⁄₅ of the cell membranes in red blood cells in "average" people* from Pittsburgh, PA.

But dairy has stearic acid. This also can make-up ~¹⁄₅ of cell membranes* and would be a bit more resistant to being burned for energy. This is the only fatty-acid consistently found cancer-protective in the classic 1970s rat feeding studies.


*Yao, Jeffrey K., Daniel P. van Kammen, and James A. Welker. "Red blood cell membrane dynamics in schizophrenia. II. Fatty acid composition." Schizophrenia research 13.3 (1994): 217-226.
†Tan, C. P., et al. "Application of Arrhenius kinetics to evaluate oxidative stability in vegetable oils by isothermal differential scanning calorimetry." Journal of the American Oil Chemists' Society 78.11 (2001): 1133.

 

[Such_Saturation]

Cannabinoids are PUFA derivatives.

 

[Amazoniac]

@tyw,

I get the impression from reading your posts that you believe once you consume a diet that's consistently low in PUFA, the body will regulate them with less problems regardless of the ingestion of saturated fats as protection (previous posts here). This goes against the conception that it's the proportion of intake that matters. Can you massage my neurons with your opinion on this?

Why did you disappear?

 

[tyw]

@tyw,

I get the impression from reading your posts that you believe once you consume a diet that's consistently low in PUFA, the body will regulate them with less problems regardless of the ingestion of saturated fats as protection (previous posts here). This goes against the conception that it's the proportion of intake that matters. Can you massage my neurons with your opinion on this?

Why did you disappear?

No time to read or post much . With yet another tech startup for the last 3 months. Horrible time sink, bad for health (and thus more time dedicated to recovery), and hard to context switch between the business of software and random scientific research ..... Maybe more time in future, but no promises.

As such, I will just write whatever comes to mind below. Do not expect it to be coherent or useful, and do not expect follow-up ....

----

Regarding the topic, the question that I ask is as usual: What is the context?

This question is scale-independent.

Example at the level of serum testing:

What is the broad context of a person's serum circulating lipids?
Here, we are looking at the probability for a cell to uptake a fatty acid, depending on its chain unsaturation.

NOTE: and again, not all PUFAs can be treated the same. Number of double bonds clearly affect behaviour significantly.

2-double-bond Linoleic Acid is very different from 4-double-bond Arachidonic acid, is different from 6-double-bond docosahexaenoic acid.​

Example at mitochondrial level, scoped by organ:

What is the context of mitochondrial mechanics in the fasted liver. The liver is a primary site of fatty acid processing, but requires XYZ cofactors for that fat to be processed.

This site will determine for example, how much of the very-long-chain PUFAs (like EPA and DHA) will be bound to transport phospholipids, and thus these bound PUFAs made available to tissues like neuro-ectoderm (ie: nervous system, gut, skin). The rest will then get dealt with via beta-oxidation, or stored in adipose tissue.

(The discussion then continues ...)​

Once we define a context, we can talk about what sort of mechanics are at play.

In general, it is generally accepted that the more double-bonds a fatty acid has, the "more reactive" it is. Note that I say "more reactive" is a general mechanic, and not as a "good" or "bad" mechanic.

More reactive compounds are subject to a higher degree of probabilistic damage when not-regulated (ie: "bad"), but are in turn, more able to be regulated (because they are easily "reacted with" by regulator compounds).

An example to illustrate this -- we know from many studies that the more double bonds a fatty acid has, the more "membrane-affinity" it has. This seems to be the case across almost all types of membranes in the human body, from the cell membrane, to mitochondrial membranes. This leads to displacement behaviour, whereby you see DHA (6-double-bonds) preferentially being incorporated into membranes over ARA (4-double-bonds), and ARA being preferentially incorporated into membranes over LA (2-double-bonds).

We have here an "eager" or "greedy" system, whereby the higher-double-bond fatty acid will be preferred for use, so long as there is the presence of sufficient regulator components on the membrane (NOTE: these regulator components are relatively unknown, but probably come down to charge differentials between hydrophilic membrane proteins, other hydrophobic membrane lipids, and amphiphilic lipoproteins. There are then regions of "higher and lower charge / charge sinks and spouts" which PUFAs to be reactive with).

Again, such a system will continue to be greedy until saturation of regulator components is achieved. In many contexts, this is the case -- eg: brain and nervous tissue often is provided less PUFA than it can actually deal with. I won't get into all the regulator mechanisms here, but even a cursory look at at the blood-brain-barrier and its tight regulation, will give people a sense of just how stubborn these tissues are in accepting PUFAs.

In such greedy contexts, absolute levels of PUFA matter more than proportions. It is of course, my view that tissues that fall under these contexts specifically need the more reactive nature of PUFAs for some purpose, and thus suck them up to a level of usage saturation. Many of my prior posts on this forum get into that, so I won't re-hash some of the mechanics here.



Then there are contexts where regulation takes a back seat, where pipes are filled as quickly as possible, and often where fatty acid supply exceeds the ability of the tissue to use it. This is where relative proportions of fatty acids can play a role in ultimate behaviour.

The 2 tissue contexts that I like to bring up are the liver and heart, especially in the post-prandial state. The liver will get flooded with whatever fatty acids that have recently been eaten, and the heart is known to preferentially use any sort of fatty acid (saturated or not) that are given to it from the serum. This is a stochastic scenario, limited only by how quickly the machinery can push substrate to use in the factory (eg: how good is the carnitine shuttle work, how much NAD+ is floating around to act as electron acceptors).



My philosophy around PUFAs has always been to fulfil the obligate need for PUFA in the tissues that require them, while avoiding the probabilistic scenarios as much as possible.

NOTE: I have talked about low-level mitochondrial mechanics in the past, and how PUFA can accelerate mitochondrial transport. These mechanics hold true, and come down to the "more reactive" nature of PUFAs. Again, "more reactive" is not "good" or "bad".​

The statement of saturated fats being "protective" rarely apply to the heavy-regulated context, and more so to the probabilistic context. Of course, "protection" is only relevant with regard to some "aggressor"; avoidance of aggressors is always the most efficient path.

Regulation of fatty acids almost always involves some other large machinery like binding proteins and other enzymes, which are highly highly specific, and I have not seen much of a role for inter-fatty-acid interactions to take place (and thus the discussion of "proportions of fatty acids" is less relevant).

And of course, as a final aside, once we are talking about PUFAs being bound up by regulators in specific contexts, all bulk fatty acid oxidation mechanics do not apply -- context-specific discussion needs to be had (Example: PUFA-laden Cardiolipin near mitochondrial complex 4 being uniquely exposed to potential ROS flux from the complex).

.....

 

[Travis]

My philosophy around PUFAs has always been to fulfil the obligate need for PUFA [!!!]...

Obligatory PUFA!

[sniffles] Say it ain't so, twy.