Endotoxin And Fat Consumption

Discussion in 'Scientific Studies' started by tyw, Jun 9, 2016.

  1. tyw

    tyw Member

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    I wanted to state a couple of opinions regarding endotoxin in the context of 3 papers:


    There are going to be many papers like this, but these 3 papers represents the points that I want to make, which I state up front:

    (1) Eating Dietary Fat increases the observed gut-derived endotoxin in the bloodstream. The effect usually starts 2-4 hours after eating fat, and lasts for up to 12 hours in healthy subjects [see paper (a)]

    (2) The more double bonds in a fat, the LESS endotoxin gets into the serum. A PUFA like DHA will cause less endotoxin to be transferred into the bloodstream, as compared to a Saturated Fat like Coconut Oil. [paper (a)]

    (3) In Diabetics, this effect is much more pronounced -- 60% greater levels of circulating endotoxin in serum after eating fat, as compared to "healthy" subjects [paper (b)]

    (4) Endotoxin is transported by chylomicrons -- the lipoprotein "Fat Carriers" which transport dietary fat from the GI tract, and deliver them to tissues.

    This DOES NOT involve any compromise to intestinal barrier function [paper (c)], but as a result, it is a completely inevitable side effect of consuming fat. ie: if you eat fat, existing endotoxin in the gut can and will be transported into the bloodstream within chylomicrons.

    Quote from paper (c):

    The paper of Ghoshal et al. (20) in this issue of the Journal of Lipid Research addresses these important questions. Using both animal models and polarized, cultured gut cells, they show that endotoxin, which is internalized into gut cells, is secreted into the circulation during the formation and secretion of chylomicrons.

    Polarized CaCo-2 cells secrete endocytosed endotoxin when incubated with oleate, which forms chylomicrons in those cells, but not when incubated with butyrate, which does not. Importantly, Pluronic L-81, an inhibitor of chylomicron formation, blocked the effect of oleate.

    Thus endotoxin is transported into the circulation in conjunction with chylomicron formation and secretion, not just translocated due to breakdown of the intestinal barrier.
    (5) This transport of endotoxin by Chylomicrons is a normal immune response. Chylomicrons "neutralise" endotoxin during transport (endotoxin is not free to disperse like in a case of sepsis), while simultaneously stimulating the inflammatory cascade required for healthy immune response.

    It is important to remember that you must have acute inflammation in order for proper immune responses to be established.

    Quote from paper (c):

    Mesenteric lymph nodes are activated by the endotoxin on chylomicrons. Mesenteric lymph nodes likely play an important role of scavenging the loosely attached endotoxin and decreasing the amount that reaches the systemic circulation. But scavenging means activating the cells in the lymph nodes to secrete cytokines, hence inducing systemic inflammation.

    Systemic administration of chylomicrons and chylomicron-like particles have been shown to bind endotoxin and not only protect from the toxicity of administered endotoxin (19), but also to protect from cecal ligation and puncture (23), a model of gut sepsis that even anticytokine agents fail to block.
    Paper (a) will elaborate on why PUFAs do not cause as big of a response -- they suppress the initial inflammatory cascade within intestinal cells. The pro-PUFA observer sees this as a "good thing", because "less inflammation bro".

    This is faulty logic -- the pro-PUFA stance claims that suppressing the alarm bells (stuff like NF-kB and TNF-alpha) is equivalent to decreasing the harm caused by the objects that are raising the alarm in the first place. I will elaborate more in the "Personal interpretations" section below.
    ----

    Personal Interpretations

    We cannot take observed high endotoxin levels in serum to mean that we are burning in a pit of :fire::fire:destruction:fire::fire:. Knowing how the endotoxin got there is an important question to ask.

    If the intestinal barrier is compromised through whatever means -- be it infection, or gluten consumption :muted:, then we get a fairly free-flow of endotoxin from the gut into the bloodstream. This is undoubtedly bad, and if high endotoxin is observed in conjunction with intestinal barrier compromise, then things are bad :penguin:

    Note that what was described in the previous section are just mechanics. :borg::borg::borg: Mechanics need to be applied to a particular context to become useful.

    Sidenote: Medium Chain Triglycerides (MCTs) do not stimulate chylomicron production, and thus do not provide this immune regulated endotoxin transport. They can be incorporated into chylomicrons, but do not actually stimulate the formation of chylomicrons.

    Practically speaking, there is no MCT-only diet -- which is seen only rarely in certain hospitalisation cases where few other nutrients can be absorbed. Any naturally occurring fats will contain other types of fatty acids, which will stimulate chylomicron formation and the associated endotoxin transport.

    In the real world, we need to explain situations where eating something like Coconut Oil "improves gut health" in some people, and then in others makes the gut worse (eg: comment by @Ewelina -- Why Does Starch Make Me Extremely Sick?). We also need to explain why diabetics seem to transport even more endotoxin.

    In my opinion, this comes down to the Robustness and Sensitivity of the Immune Response.

    All that eating fat does, is to provide the mechanical pathway for a "as safe as possible" endotoxin-mediated immune response to whatever endotoxin is already present in the gut. ie: Bundling up endotoxin into chylomicrons, is like a "quarantine function", whereby the invaders are then delivered to immune cells to be dealt with.

    NOTE: eating fat only helps transport this endotoxin -- if there is little or no endotoxin in the first place (caused by too much gut flora), then there isn't anything to be Immune against :ghost:.​

    IMO, this generally means that less gut flora is better in this regard. However, it may be a case whereby the key factor is less endotoxin-producing gut flora.​


    However, what happens when your immune system breaks down? :banghead: For whatever reason, this transported endotoxin is not able to be dealt with. The endotoxin in chylomicrons will now only serve to keep asking the immune system for something it cannot provide, and the system is put into further stress.

    This may be why some people find that saturated fat causes them to have "an immune shock", with symptoms like anxiety, nausea, shivering, etc ....

    It is plausible that this cascade leads to breakdown of gut barrier function, which would then allow for even more un-regulated endotoxin entry into the bloodstream, making the immune over-reaction even worse.

    Again, note the assumptions:
    • There is already an existing high level of endotoxin in the gut
    • Immune system cannot handle any incoming endotoxin

    Conversely, if dietary fat is only transporting manageable quantities of endotoxin from the gut, I can see a situation whereby this leads to gradual clean-up of endotoxin and gut flora excess. This scenario can be achieved, again, by reduction of existing gut endotoxin levels, and bolstering of the immune system through all the usual Bio-energetic-enhancing strategies.

    Also, this will explain why PUFAs like DHA seem to help the situation in the short term. These PUFAs shut down any sort of immune response, an isolate all endotoxin to the gut. The gut may be having a bad time, but there will be no systemic effect :pompous:. One wonders how well an acute administration of DHA + antibiotics will work (DHA to transiently shutdown immune response, and then antibiotics to kill the gut-localised bacteria in hopes of reducing endotoxin formation)

    Another interesting note will be the context of very low fat diets. In this case, you do not get as much of the Chylomicron-mediated endotoxin transport. You can still potentially feed the gut bacteria if you choose fermentable / slow-digesting foods, but you're not going to get as much endotoxin-triggered immune effects.


    In light of this, my personal opinion is that if one has some sort of clear immune dysfunction, a lowered fat intake of all forms is preferred. :oldman: Until sufficient energetics are restored, it is not a good thing to push more endotoxin from the gut into the bloodstream and lymphatic system, and ask the immune system to do more than it can.

    ....
     
  2. Amazoniac

    Amazoniac Member

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    Interesting stuff.
    What's also interesting is that many people that are dealing with MS, arthritis, etc. find a lot of improvement after restricting saturated fats and consuming more freely PUFAs (this is important to note, otherwise people would justify the improvements on PUFA restriction); even when the diet consists mostly of starches for energy - which is supposed to generate a lot of endotoxin.
    @Westside PUFAs right again!
    Thank you for sharing, tyw.

    Edit: forgot to mention that it makes sense that endotoxin are transported along with lipoproteins, which are known for their role on immunity, including sensing to target specific microbes.
     
  3. Westside PUFAs

    Westside PUFAs Member

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    Yaasss. (yes)
     
  4. Agent207

    Agent207 Member

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    Great discussion. I think I read you used to look into Kruse ideas; theres lately one of them (not uncovered by him really but he echoes it) that worries me a lot, the supposed protective rol of dha against EMF damage. And I find to be more and more researched evidence that supports this.

    Putting aside the general and already known negative facts of PUFA, did you ever think about or considered this theory?


    Long chain saturated fats are known to tend to clog arteries and other tissues under some circumstances, thats why they're said to avoid or not overdo on problematic scenarios, like the lectins. I guess MCT oil would prevent this.
     
  5. Amazoniac

    Amazoniac Member

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    At some point I think that the recommendation to obtain saturated fats via diet will reach full circle. Many doctors realized in practice that restricting fats alone improved a lot of conditions, for reasons unknown at that time.

    But now people use dairy to justify that saturated fats cannot be something unsafe as it is meant to nourish a newborn on the best way possible. But there are two points missing: one is that babies have gut microbes that are much safer compared to adults; second point is that the milk is consumed alone.

    At this point I'm slowly realizing how it seems safer to obtain most of your fats consuming carbs; that exact quote that West posted before:
    "I think it's best to get as much sugar and starch in your diet, preferably sugar from fruit and milk"
    Olive oil is also much more associated with longevity than coconut oil or butter.

    Thanks to you guys I'm slowly piecing together this numbing cloud of information.
     
  6. OP
    tyw

    tyw Member

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    Well, we need to ask what "EMF damage" means in the first place :cyclops:

    Broadly speaking, there are only 2 ways that EMF can cause damage:

    (1) By interfering with natural resonant mechanisms used in signalling.

    This is why ELF-EMFs that are below 1,000 Hz are very harmful. This is the shared resonance of many compounds (like Ca2+) that we use in biology, and ELF-EMF emitters like Power Lines push out 50-60Hz frequencies that are in the Earth's Natural Schumann band.

    We are talking about fundamental disruptions to the way that molecules send energy to each other, and ELF-EMFs disrupt that.

    PUFA incorporation into cell membranes "help" in the sense that they make cells less sensitive to all stimuli -- Free, long-chain, polyunsaturated fatty acids reduce membrane electrical excitability in neonatal rat cardiac myocytes.

    This is why I say PUFAs "shut down the entire system". You may not be as sensitive to ELF-EMF damage, but you also won't be sensitive to anything else that your body outputs (Thyroid hormones, all sex steroids, etc ...).

    PUFAs shut down EVERYTHING, and no longer allow for robustness of the organism. "Robustness" here means to able to respond to potentially stressful stimuli, and adapt to become better at responding to that stimuli.

    ie: PUFAs will help you maintain the status quo, if and only if you do not provide additional stressors to the system. "Hibernation mode" must be attained if going the high PUFA route, else the organism will slowly break under the inability to adapt to new incoming stressors.


    (2) By brute-force energetic insult to the cell

    This is literally a full on high-energy impact to the cell, and will be achieved by EMFs that are above around 100,000 Hz (100 kHz) in frequency. Note that cell towers, WiFi modems, etc ... all output at least 2 Ghz (2,000,000 Hz) frequencies. X-rays and Gamma ray are obviously harmful, and they differ from Cell Tower Radiation only in terms of their per-photon energy.

    Sidenote: I have written how the 20 kHz to 100 kHz range does not seem to be harmful -- Kilohertz Range EMF is Likely Less Harmful . This likely indicates that individual photons in this range are not enough to cause stress to biological tissues.​

    PUFAs will not help you here at all, and will probably make your condition worse. The cell is being stressed hard by large absolute quantities of energy.

    The only way out is to:

    (a) Try and avoid these stressors as much as possible -- this is an energetic assault, and getting away from the energy is an easy solution. eg: 3m away from my WiFi router, and the energy goes <0.5 mW/cm^2

    (b) Keep your cells fully functional and adaptive -- ie: cut the PUFAs ;), keep mitochondrial energetics good, allow novel solutions to the incoming stressors



    Yup. Transient improvements :bag:, long-term loss of resiliency :bored:, and having to maintain an ever-stricter lifestyle.


    .....
     
  7. dd99

    dd99 Member

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    Thanks, very interesting. This meshes with Ray Peat's view of autoimmune disorders being caused by endotoxin.
     
  8. OP
    tyw

    tyw Member

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    @Amazoniac and @Agent207

    Some random points about your posts ;)

    ----

    I have not studied Long chain fats extensively. They may be potentially harmful, but barely occur at all in "Peat recommended" foods.

    Example: Butter usually has nothing above C18, and is mostly C14 and C16. Long chain fats contain at least 20 carbons.

    In fact, these long chain saturated fats are usually found in plant oils (like peanut oil).

    Therefore, if you eat mostly tropical vegetable fats, animal fats, and even olive oil, the chances of getting substantial long chain fatty acids is very low.

    ----

    Regarding the statement from Amazoniac -- "Olive oil is also much more associated with longevity than coconut oil or butter."

    I personally don't think this is true at all. The many downsides of Oleic Acid have been discussed on this forum, ranging from oxidisability, to effects on insulin, and all the way down to mitochondrial mechanics.

    Associations can be helpful, but mechanics take precedence.

    eg: a mechanic like Mitochondrial NADH:FADH2 ratio comparisons are mechanical, and help to determine the potential metabolic effects of particular fats (which is what we are looking for at the end of the day)

    eg: whereas associations depend on what you study .... Olive oil eating populations just happen to be the ones that are studied more often than not, and the comparison is often to other Junk-filled Diets. If we compare these diets to something like say, the high coconut oil and carbohydrate Kitavan diet, or the <12% fat Okinawan diet, then Olive Oil looks worse off ....

    I dislike this sort of subjectivity, and thus don't really look to associations to determine plausible truth. Mechanics are what allow us to reason about things! :)

    ....
     
  9. CoolTweetPete

    CoolTweetPete Member

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    Very interesting @tyw, thank you.

    Haidut mentioned on a podcast that for some people improving SFA : PUFA ratio by consuming moderate amounts of SFA would be helpful before going on low fat. My immune system seems to have improved markedly since transitioning to Peat (used to get sick every couple months on keto), so I think i'm ready to trim the fat (pun intended).

    I think I potentially have some compromised barrier function from years of consuming gluten, so with that in mind -- Is there a possibility low fat could be harmful for me considering there would be less "quarantining" of endotoxin out of the gut? Is there a way you know of to DIY test intestinal permeability (seems far-fetched)?

    Thank you again. Great thread! :hattip
     
  10. Agent207

    Agent207 Member

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    Wow very elaborated reply, its a pleasure to read you.

    As for the EMF (HF) you seem quite confident about safety beyond those 2 points. You're not sold on the cumulative damage over time? living under low (but growing more year after year) intensities, on cities plagued with antenas, hotspots, wimax, surrounded at home with wifis from neighbours... etc. My main concern is this constant non-stop increase in our enviroment linked to the plaussible cumulative effect long-term, as warned by legit indepenent sources like BioInitiative Report and several prestigious scientifics. And no doubt about the conflict of interests on the other side by the industry and the insane amount of money involved.

    This cumulative damage (and not the short-termed one) not considered on your view, is the supposed thing that some studies suggest dha may cushion in some degree.

    Some facts;

    1. WHO, is probably the most public-oriented mainstream institution that have been researching on this for the last years and its recent conclusion, by now, is to be "possibly carcinogenic to humans" (Group 2B).
    2. WHO headquarters are located at Geneva, Switzerland.
    3. Some time ago, SWISSCOM -which is owned (52%) by the Swiss government- had all their schools to quit wifi and switched to wired fiber networks as a MUST, when they has always had free internet access before and could use wifi if they wanted to.
     
  11. OP
    tyw

    tyw Member

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    Personally do not see yet mechanics supporting the idea that "keeping bacteria in the gut" is going to be harmful.

    All the issues with endotoxin and gut-borne stressor, all happen when that stressor gets out of the gut into the rest of the body. This isn't going to be caused by low fat alone, but NOTE that it could be caused by specific carbohydrates you choose to use in the diet -- eg: some compounds in Potatoes can cause leakiness in the intestinal barrier.

    I know of no real-time test for intestinal permeability :(

    .....
     
  12. OP
    tyw

    tyw Member

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    Correct, I make the explicit assumption that there is no such thing as "Cumulative Damage" :angelic:. (note my signature ;) -- I will always Assert statements first, and then try to prove them wrong after the fact)

    Anyway, this term "Cumulative Damage" is poorly defined. What accumulates? Can you measure it? What is being damaged? etc ...

    I don't even believe in "DNA damage". Though you can damage some cells, the organism is intelligent -- www.basic.northwestern.edu/g-buehler/cellint0.htm . If there is sufficient energy, cells will know how to kill the basket cases, repair the faulty ones, and lead to prolonged proliferation of the organism as a whole.

    Sidenote: In this sense, I agree with Peat that cells can be reproduced indefinitely. This does not mean that the organism lives forever, just that their cells can constantly reproduce. Death likely comes when there is some systemic failure of multiple systems at the same time, which is a natural process that as far as I can tell is MAGIC .... ​

    All I personally see is the same measures of generic stress on the system. Increased glucocorticoids, reduced metabolic enzyme activity, intestinal brush border function, etc ....

    ie: EMF stress is just like any other stress, except that as you pointed out, it is very widespread, and almost un-avoidable.

    "Carcinogenic" also basically just means "metabolism is screwed". Again, generic stressors which can and should be fixed by generic energy-addition strategies.

    PUFAs will not help with this at all, unless you can truly live a stress-free boring life with not much change. This does not describe the "war-time world" that we live in, whereby fighting for everything from Financial to Political freedoms is the norm :lock:. That fight demands energy :wtf:. Not something that an elevated PUFA intake will support.


    And in terms of EMF mitigation, I personally do what I can, by living away from major emitters (I don't live in a big city), not using a cellphone much at all (maybe like once a week), staying away from my WiFi device, etc .... That's about all one can do. The rest comes down to improving energetics.

    Personally, I'm much more concerned with major E/M shifts in the environment, like the coming Solar Minimum and Global Cooling, which is very hard to avoid, rather than man-made EMFs (which are avoidable if you have enough creative and physical energy to avoid them.)

    .....
     
  13. Agent207

    Agent207 Member

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    Well, by long chain (saturated) fatty acids I was refering to C12:0 and above. Lauric acid is considered medium just on the paper, but not by technically.

    --------------------
    What are MCFA's?
    Unlike long chain fatty acids, MCFAs are readily utilized by the liver, which leads to greater energy expenditure and enhancement of thermogenesis.
    --------------------

    Were those, long and saturated, the ones I suggested it may be related to the inflamatory conditions that Amazoniac linked to saturated fat.
     
  14. Agent207

    Agent207 Member

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    Before care about death, you should care about aging :)
     
  15. sugarbabe

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    Great post @tyw ! So maybe the only reason I am doing okay on my higher saturated fat diet is that I occasionally take cyproheptadine which supposedly protects against endotoxin. Without it my anxiety gets more and more severe and I started having adrenaline after eating ice cream. The endotoxin seems to cause low blood sugar. Definitely a perpetual stress to the body. I just find low fat not as palatable or enjoyable.

    I'm surprised it hasn't been mentioned that there was a study showing orange juice protects against fat induced endotoxin as well.
     
  16. OP
    tyw

    tyw Member

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    It is always a question of dose. The people on this forum have mentioned the negative side effects of high Free Fatty Acids of any form many times. And like I stated here, palmitate in excess, especially with glucose, literally degrades cellular proteins -- EFA Linoleic Acid?

    Regarding an inflammatory response, again, we must de-complect the markers of Inflammation, from the actual negative side effects of cell damage (which we term "inflammation").

    I can just as easily say something like:

    - Higher saturated fat intakes usually support higher cholesterol production.

    - Oxidation of Cholesterol is required to HEAL cardiovascular damage (see notes -- A novel hypothesis for atherosclerosis as a cholesterol sulfate deficiency syndrome)

    - Therefore the higher cholesterol deposits in cardiovascular disease is just an indicator of cholesterol doing exactly its job, but still being unable to protect the heart sufficiently against the backdrop of massive energetic deficiencies and stressors.

    The problem is the underlying stressor (whatever that may be in the specific case), and not the cholesterol or the fat.


    Again, excessive FFAs are stressful, and this could cause problems, but saturated fat is probably less stressful compared to unsaturated fats when in FFA form.


    "Ageing" and natural death are almost separate processes, and can be treated separately.

    The form of natural death of the organism I describe is the sudden loss of systemic coherence of the organism -- "coherence" here means that components can all communicate with each other with low latency. Any breakdown of this communication to a significant degree will cause death. Arsenic may cause this. "Ageing" may cause this.

    "Ageing" does not have a good definition. Some will see "less hormones" and call it "ageing". Some will se reduced metabolic rate and call it "ageing". The only distinction that is made here is that these effects happen when the person is "old" (whatever that means).

    How is this different from a person who has early stage breast cancer? Those cells are metabolically challenged like an "aged cell" would be, but the cause is some unknown localised energetic deficiency (metabolism not working efficiently).

    The distinctions and terminology start to become imprecise, and therefore, not useful ....

    I prefer the straight up "These particular systems in your body lack the appropriate energy to function properly". The task then becomes diagnosing those systems, and figuring out what the best energy addition strategy is going to be. This is completely independent of age.

    As far as we're concerned, all we can do is support as much high energy function of the body as possible, which will support whatever "inevitable ageing" comes about from inevitably leaky mitochondria. (I've discussed the mitochondrial leakiness and longevity mechanic before on this forum)


    .....
     
  17. OP
    tyw

    tyw Member

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    Well, to be clear, fat-mediated transport of endotoxin isn't harmful per se. It's just a mechanic, and the "good" or "harm" is a result of whether or not your immune system can handle this transport of endotoxin.

    There are many factors to consider, and all I do is state some mechanics that may explain some seemingly conflicting scenarios. Experimentation (ideally with the awareness of such mechanics) is still required.

    Note that it is more than plausible that some people do better with some additional "safe endotoxin stimulus" via chylomicrons due to inherently less active immune systems. eg: http://www.cell.com/cell/abstract/S0092-8674(05)00451-4

    We have no idea how these immune functions are modulated in adulthood, given all the variance in the way that people are genetically different, and raised differently. For example, I can guarantee that breast feeding at birth will impact this sort of immune response.


    ....
     
  18. Jayfish

    Jayfish Member

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    Interesting post but my personal experience was the exact opposite if this. When I ate a zero fat diet with only a Tiny amount of of CO, I got sever endotoxin shock reactions. Now that I eat zero fiber, zero starch and a lot of saturated fat I get zero endotoxin symptoms, it's like night and day.

    The biggest thing I think is how much endotoxin is in the gut in the first place. Carbs will almost certainly contribute more to feeding bacteria and producing way more endotoxin, also it will create fermentaton which will cause the digestive tract to expand and become more leaky. Lastly, what about the saturated fat that is produced in the large intestine? Could this cause the same reaction as dietary saturated fat?
     
  19. sugarbabe

    sugarbabe Member

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  20. redred

    redred Member

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    Very good thread. Ive always wondered why bread (imagine a fresh crusty baguette) tastes so good but are harmful to us.

    Interesting that you also bring up the coming solar minimum.
     
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