The Secret Cholesterol Theory
Completely accidentally I bumped into an article about osteocalcin, and it turned out to be something pretty important. My research about the fight-or-flight mechanism, which is associated with migraine, led me to this article. Those of you who follow me know that my research is in migraines and not with cholesterol. My understanding had been that when humans encounter danger or stress they respond with a “fight or flight” which is initiated by the central nervous system and stress hormones, such as adrenaline(1). According to this article this is not the case.
The initiation is performed by osteocalcin (defined and discusses below.) What’s osteocalcin’s connection to cholesterol? Actually, nothing directly but plenty indirectly, through calcium. Atheroma is calcified (calcium filled) cholesterol forming atherosclerosis in all the wrong places, and a very negative condition. The sequence leading to it is as follows:
Stress => Osteocalcin = T2D, Atheroma, Calcium, CVD
Indeed! Who would have thought? As you know, there is a war going on about cholesterol and its role in cardiovascular disease, atherosclerosis, and death. The main, traditionalist camp is convinced that the cause of atherosclerosis is high LDL.
An opposing camp, rapidly gaining more and more adherents, suggests that atherosclerosis is caused by inflammatory processes, which may be the consequence of eating industrially produced PUFA oils–vegetable and seed oils; and/or consuming too much sugar—sugar is inflammatory and is associated with type 2 diabetes (T2D) and obesity. This camp also posits that there is no cardiovascular disease without T2D, the two are associated.
The predominant theory of the inflammatory concept suggests that the problem starts in the arteries where the artery walls are crossed by LDL particles—usually they mention small dense LDL particles. They are small and dense because they are oxidized and are not functional. These then lodge in the wall of the arteries, and after a host of immune attacks by macrophages, calcium also moves in from the blood and deposits, making the atheroma hard. This then may burst one day as the calcium gets loose (not much explanation on how and why that happens). According to this theory, the LDL particles magically cross like ghosts though the endothelium (a thin single-layer cell surface separating the lumen, which is where the blood flows from the smooth muscles of the artery) without any damage to the endothelium, and after they reached the outer wall, where the smooth muscle is, then settle…
This is a great theory up until this last part, and that is because examining such atheroma under microscope reveals that there are torn smooth muscle pieces in the atheroma. If so, the crossing of the LDL must have happened from the other side, the smooth muscle and not the lumen side through the endothelium.
Another inflammatory theory suggests that LDL crosses from the outside of the arteries—by Vladimir M. Subbotin in his awesome article here. His theory differs from the LDL particles crossing via the lumen, noting that the concentration of the atheroma is actually not close to the lumen but is deep inside on the bottom of the artery wall, closer to the tunica intima, the side of the artery facing the body. So, if the atheroma has torn smooth muscle cells in it, then clearly the entry is the region of the tear… right? Well that’s just me thinking too logically…
The fourth theory is the one that just came to my attention. Most of the articles on this theory are new. This discusses osteocalcin as the reason for calcification of the atheroma, independent of where the LDL managed to cross into the artery wall. This is the only theory it seems that ignores LDL’s presence and focuses instead on calcification.
Oddity
Before we continue, I must also mention that there is at least one tribe living today, Tsimane, that has high levels of atherosclerosis without CVD (2). Very few members had CAC scores over zero in this tribe, though many had high levels of inflammatory marker c-reactive protein, which was way over 3, the maximum normal cutoff in Western societies. This would indicate that the factor of importance really is the calcification of the atheroma and not the atheroma itself.
What is Osteocalcin?
Osteocalcin “is a non-collagenous protein hormone found in bone and dentin, first identified as a calcium-binding protein in chick bone. Because it has gla domains, its synthesis is vitamin K dependent.” (wikipedia)
The Role of Osteocalcin
Few argue that Cardiovascular Disease (CVD) is a metabolic disease and that it is somehow connected to glucose and insulin mismanagement of the body. The modern CVD theories agree and incorporate metabolic disease, many of them even define CVD as a metabolic disease. However, the development of the connection between metabolic disease and CVD is less understood and seldom discussed.
Crucially, osteocalcin is associated with glucose management: “One of the functions regulated by bone through osteocalcin, an osteoblast specific hormone, is glucose homeostasis” (here). Studying up more about osteocalcin, we can learn that “bone is an endocrine organ regulating a growing number of physiological processes“(3)
As most of us who are students of heart disease, T2D, obesity, or other forms of metabolic diseases know, calcium is key marker of atherosclerosis. It is said that calcium appears at the site of the budding deposit that turns into atheroma, which provides support to the atheroma so it has less chance of bursting(4). While we may disagree about which side the LDL enters the artery to cause its trouble, we may most certainly agree that it is causing trouble most when it gets calcified.
When does osteocalcin enter the picture? Glad you asked. It comes with stress! And I think this is the real culprit and not T2D. That’s because stress initiates hormones that are responsible for generating glucose, initiating insulin resistance, and modifying glucose homeostasis. And what hormone may do all this? Osteocalcin.
Conclusion
I pride myself in finding holes in many arguments. I may not be always correct, but I strongly believe holes definitely exist in the current explanations of CVD. Could it be that the real cause of CVD is stress? See some article here or here(5) or here or here.
My suspicion is that we have been chasing the wrong suspect. Food certainly has much to do with CVD because eating the wrong food can cause stress—sugar is well understood to trigger stress and stress is well-understood to cause elevated blood sugar. And chronic elevated blood sugar leads to T2D which then leads to inflammatory processes. But stress on its own is also causing the release of osteocalcin, which then is just very happy to stick to wherever it can, causing calcification of atheroma. This is a new and intriguing theory, deserving your attention.
Comments are welcome, as always, and are moderated for appropriateness.
Angela
Sources:
1 Berger, J. M. et al. Mediation of the Acute Stress Response by the Skeleton. Cell Metabolism, doi:10.1016/j.cmet.2019.08.012.
2 Kaplan, H. et al. Coronary atherosclerosis in indigenous South American Tsimane: a cross-sectional cohort study. The Lancet 389, 1730-1739, doi:10.1016/S0140-6736(17)30752-3 (2017).
3 Wei, J. & Karsenty, G. An Overview of the Metabolic Functions of Osteocalcin. Current Osteoporosis Reports 13, 180-185, doi:10.1007/s11914-015-0267-y (2015).
4 Aimilios, K. et al. Basic Mechanisms in Atherosclerosis: The Role of Calcium. Medicinal Chemistry 12, 103-113, doi:http://dx.doi.org/10.2174/1573406411666150928111446 (2016).
5 Choi, B.-h. et al. Coronary artery calcification is associated with high serum concentration of undercarboxylated osteocalcin in asymptomatic Korean men. Clinical Endocrinology 83, 320-326, doi:10.1111/cen.12792 (2015).
I responded to this site because I ran across your comment regarding osteocalcin and wanted you to know about MGP about all the interesting complexities of VK. I didn’t really delve into them, just mentioned searching more. And there’s so much finally being considered and published now that there may actually be hope. Probably not, but maybe.
In my case, I learned about many things when I had some debilitating issues that were not resolved with conventional medicine – specifically, I suffered autoimmune Hashimoto’s and was never helped by T4 monotherapy and had a crazy epiphany when T3 was finally added to my treatment. It was literally like when the black and white of The Wizard of Oz goes Technicolor. This led me to questioning what the heck had just happened?
It surely wasn’t just an overnight resolution, as dosages were messed with, I unloaded stupid docs, looked for help from other docs, but it was over two decades of active researching that began with this epiphany that opened my eyes to how misguided we are regarding health/food/environment.
I read the literature. It’s not easy, but it’s there for all to pursue. And it’s sometimes contradictory.l
It’s nice to try for change – God knows…we surely need it – but your speculation of how to get through to consumers by avoiding anything too cerebral, too off-putting may be misguided, too.
Yes, we influence what foods are available as consumers, via purchasing power, but few care to dig too deeply, and those medical industries that you cite that are threatened if we actually promoted optimal health WOULD be negativity affected, but the real industry threat to those most damaged (poor, minorities, less educated) would be deletion of fast foods. They’re ubiquitous and beyond damaging. And they’re the job opportunities for those so marginalized as well as their food sources.
During this pandemic, I have been gob-smacked by the lines if cars to them.
Animal foods are only as good as their diets, as good as whether they’ve been processed with excessive and novel phosphorus containing additives, so to just advocate eating them misses such. I’m a fan, don’t doubt, but the massive changes in foods are so widespread, disparate, and toxic that it’s tough to explain to most folks.
Just as we are so polar in politics, we are polar in our population regarding what folks can hear and understand about health and how best to optimize it.
About half cannot recognize that they’re starving and ooisoned. They rely on docs, who are arguably brainwashed.
It’s nice that you took DEXA and CAC, but why?
Why did you go down that rabbit hole?
To confirm your dietary and lifestyle choices?
I could go on and on – 2 decades of daily researching leads to a lot of information – but I seek an understanding of mechanisms. How did so many become so stinking obese in my lifetime? (I, too, am old. I too, watch our extinction coming with some bemusement)
So I have concluded that calcium dysregulation is a fundamental mechanism behind our sick/fat population after all this reading. VK is a player. VK isn’t the only player in calcium regulation, but it’s a biggie.
And I wondered if you’re eating fermented foods?
Liver?
It would be nice if you advocated for such, explaining all the newest insights into VK in your blog.
VK is MUCH more than intake. It’s having sufficient VKDPs, it’s not interfering with VK processes (from being able to cleave all forms of dietary VK in VK3 and putting this in chylomicrons to sent to the body via lymph to creation of MK-4 by way of UBIAD1 which also directly controls both cholesterol and calcium).
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Cynthia,
I got the DEXA scan because when one gets old, Medicare requires it. I had no choice and glad it confirmed that I have strong bones. The CAC scan I got out of curiosity and also wanted to see my hubby’s since males are at a higher risk for bad outcomes than females. So this was my way of ensuring he gets his done as well–his was also zero. None of this had anything to do with confirming our dietary choices.
The confirmation of our dietary choice came from our healing of all of our health conditions!
No, I don’t eat fermented foods because I mostly eat hypercarnivore. I don’t eat any vegetables but I do eat some fruits seasonally, so an occasional salt pickle (cucumbers are fruits), but maybe once or twice a year, and seasonal berries. I don’t eat fermented dairy and dislike most strongly fermented cheeses. I also don’t eat any sweeteners, naturals or substitutes. I only eat real foo, mostly animal products, including milk.
Calcium dysregulation is only one part of the sick population–I clearly had no calcium dysregulation and was still sick. My original field is mathematics, in which a simple example that comes up when none is expected can disprove a theory. So one person without calcium dysregulation who is still metabolically ill suggests that calcium dysregulation is not a causal thing. It may be the outcome of the sick population and the outcome of being metabolically sick but not the cause–and even as an outcome, it is not necessarily there.
I would suggest that you look into studies evaluating the harm caused by processed foods from the perspective of nutrient deficiencies, such as protein, and to the overload of seed/vegetable oils, which are inflammatory. The mix of malnutrition combined with high carbs (carbs provide only fuel but no nutrition), low salt, and the forever increasing stress around people are much more likely to be the cause of sickness.
You discuss Hashimoto’s as a “disease” but Hashimoto’s is not a disease. It is an autoimmune condition. All autoimmune conditions are caused by an overreacting immune system to something the person eats, drinks, inhales, or soaks in. The most common causes of autoimmune conditions are grains, soy, and cruciferous veggies, but other vegetables are right up there as well, since all plants (except for some fruits) contain high amounts of antinutrients, which are potent toxins specifically to attack plant-grazing animals, to prevent overgrazing. And what do humans do with all this plant-based eating nonsense? They overgraze.
I already see lots of vegans and vegetarians with all kinds of autoimmune diseases and I have also seen Hashimoto’s reversed on a pure animal-based diet. It really is just based on what you eat. So eat mostly animal products for your health. I started my new way of living over 8 years ago, of which over 7 years was without grains (all grains), and over 5 years without a drop of vegetables. I am now 68 years old and have zero health issues–other than some minor lung injuries I have collected over the years of smoking (I quit in 1982) and some back and neck injuries from Ehlers-Danlos Syndrome (genetic condition) that I was born with.
It is also important to note that animal products are full of K2 and ketosis upregulates the use of calcium for the proper purpose, so people on the ketogenic or carnivore diets get their K2 in their diet.
Cheers,
Angela
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You’re definitely looking…which is great!
I’m not going to get into much of what you claim here, but since you’re interested in migraines.*
*NOTE: Cynthia I removed your link because migraine is my specialty and that article was a bunch of bull, pushing vitamin K.
Calcium is a signaling molecule….not just hydroxyapatite, so looking at how much and where it deposits is not considering all aspects of calcium.
Check out effects of K status and diabetes, for example, or other metabolic diseases/conditions.
Note that K supplements increase insulin sensitivity.
And also check out how microcalcifications are what become CAC – since migraine-riddled folks are at increased risk of a cardiovascular event, why do you think this is?
Hypothyroid folks are, too.
It’s about calcium regulation.
Someone can suffer calcium dysregulation and have a zero CAC…for a while.
Vegetables are real foods, too.
Fermented foods are actually super foods, so I’m sorry to hear you don’t care for them.
Also… about animal foods:
Stable isotopes in hair reveal dietary protein sources with links to socioeconomic status and health (2020)
[Open access]
Seems that feeding animals unnatural diets leads to messed up animal foods, huh? So specify that animal foods needed their diets to be right, please.
You are about my age and so I’m sure you’ve noticed how very fat folks have become since when we were young. What happened?
Lots of folks have various ideas, but I am suggesting that the many, many ways we have messed up calcium (also as a signaling molecule) are unidentified factors. And there are so many and ubiquitous ways we’ve done this.
I actually blame my hypothyroidism on fluoride.
Good luck with eliminating that.
Check out all the Rx drugs based in it.
And, of course, we fluoridate water.
Anyway, good luck and keep eating real food!
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Cynthia,
Studies “speculate” that K helps insulin sensitivity because of K’s lipid lowering effects. But we know that lowering lipids is not beneficial. There has never been a clinical trial that showed that lowering lipids does any good other than having lower lipids. But considering that the human brain is over 85% fat and cholesterol, I dare to say that “high lipids” is meaningless and is only making billions of dollars to the pharmaceutical companies, while hurting millions of people. And in the rare cases when lowering cholesterol ends up helping, the expected life increase as a result of taking statins for life is 3.5 days.
Therefore, anything that provides a benefit as a result of lowering lipids is stupid.. In addition, over 85% of our body uses fat (a lipid) for fuel and not glucose. Most people don’t know that under normal conditions the heart runs on fat. The heart doesn’t want to run on glucose becuase glucose use in muscles generates lactic acid (we call that muscle ache) and its repair in the heart requires the heart to stop. 😉 Good luck with that heart stopping…
Calcium is a signaling molecule and has huge roles in neurotransmission, anything to do with electrical operations, including the heart and brain, and other functions. For some of its roles, calcium doesn’t need K vitamins. K is actually 2 vitamins: K1, which is a coagulating vitamin and is a plant-form and K2, which is the animal form and which is fat-soluble and has nothing to do with coagulation but helps to move D3, Ca, and other things, keeping the vascular system also clean and bones strong.
I edited your post and removed your link since it links to a page pushing K. K and migraine are independent. I specialize in migraine. It has absolutely nothing to do with migraines. So let’s put that law down right away. Migraine is my specialty, I can create it, stop it, prevent it. I know the cause and K isn’t it.
I don’t know why you think that everyone’s existence is dependent on K supplementation. I am starting to suspect that you are selling this supplement.
I have been drinking fluoridated water and using fluoride toothpaste, eating animals that weren’t always the “well-fed” organic, pasture raised type, and I have never had hypothyroidism. So here again, your theory fails.
Thanks for your comments. I will not respond to more on this subject.
Thanks for understanding,
Angela
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Holy beejeebs…I have not mentioned lipids. I would not discuss them in the way that you think that I would. You’re picking a fight with the wrong person about the wrong things. If you recall, I noted that such as cholesterol are among the biomarkers that are misguided. This is in spite of the fact that we measure them in great amounts and try as all sam-hell to ascribe cause/effect to such and CVD. I happen to be discussing fat soluble vitamins (when discussing such as vitamin K… or D or it could be also A or E…all misunderstood by so many).
The speculations around effects of vitamin K supplementation or even just considering K status via the activation status of the various vitamin K-dependent proteins are often about such as their anti-inflammatory effects, their effects on gene expressions, and also around the synthesis of MK-4 (menaquinone-4, the only vitamin K2 not made via fermentation, but instead via UBIAD1, the enzyme that directly controls cellular calcium and cellular cholesterol and has been described in the literature as ‘anti-tumor’). Lipids that you are fighting against is an argument that is so yesterday!
I could have offered your ‘arguments’ for lipids – and there’s a lot there upon which we can agree – and put much more mechanistic support into it, to boot – but my claim is that we made fundamental mistakes when we categorized lipids via their bonds, when that is not the pertinent factor in any of them. Instead, I claim that it is their nutrients in them that is pertinent to health effects.
Here’s a little support for that claim:
Vitamin K1 is very high in some oils (soy, canola, olive)
When it is hydrogenated, it creates what we have called ‘trans fatty acids’ and we know quite well that these hydrogenated oils cause havoc – but also with this hydrogenation, K1 becomes what is called dihydrophylloquinone (I call it dK) and this substance does not act like regular vitamin K1 and thus, it messes up downstream effects – in fact, that there was trans fatty acid was nothing, just as the low amounts of trans fats in dairy are nothing…but the dK causes holy hell
As far as ‘I don’t know why you think that everyone’s existence is dependent on K supplementation. I am starting to suspect that you are selling this supplement.’ I mean, WTH? I do not endorse supplementation at all. Never such. God knows, you’re in a fight, but it’s not with me. those trials with supplementation are just that – ways to investigate more K2 in known dosages with known forms of K2. I endorse foods. Always have. And it just so happens that fermented foods offer some longer chain menaquinones, some lively ‘critters’ that seem to support the microbiome, and are often consumed in some cultures with health longevity such as the so-called Blue Zones. Don’t misunderstand, I don’t agree with Buetner much at all, but the cultures he cites really do have more healthy centenarians. For a really fun read, check out how Okinawan centenarians attribute their healthy longevity to feral pigs that they have trapped. Poor Dan, always seeking plants and can’t see otherwise.
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Given that calcium is the marker of dangerous plaques, and that non-calcified plaques are benign (I know, goes against the grain, doesn’t it?) let’s question those biomarkers that have been too heavily embraced. Like the various permutations of cholesterol, even the biomarkers of inflammation!
Who says that they are even pertinent? Fundamental? We’ve just all bought it and they have taken on lives of their own, even if incorrect.
Calcium dysregulation is what I believe is the shared etiological factor in all the common chronic diseases.
It is affected by many things in environment, diet, by drugs, by nutrients/hormones, but most of modern medicine sees this topic in linear ways, unable to see the multiple factors that affect calcium regulation – in tissues such as bones or arteries (good v bad deposition) and even when calcium acts as a signaling molecule.
Osteocalcin is one of about 17ish vitamin K-dependent proteins (VKDP) – they are ‘activated’ by way of vitamin K action, as carboxylation – and they all seem to share effects on calcium behavior.
Let’s look at another VKDP that really IS a known factor in cardiovascular disease: matrix gla protein (MGP).
It’s found in arteries, in endothelium, and other places. When properly activated by way of vitamin K it is dubbed carboxylated MGP, but MGP also has the possibility to be phosphorylated, so MGP can be uc-upMGP, c-upMGP, uc-pMGP, or c-pMGP. What these differences mean is still being looked at, but the really interesting thing about osteocalcin (OC) and MGP is how they are created, what factors influence their creation, and then subsequent to that, how well they are activated.
MGP is the potent anti-calcification agent currently known – when activated.
A CAC of zero represents a 15 year warranty from death by all causes.
OC in humans needs vitamin D to be created – rodents use vitamin C.
MGP needs sufficient triiodothyronine (T3, the so-called ‘active’ thyroid hormone) to be created.
I think we have totally messed up T3 synthesis and no one realizes this.
So it’s not OC, it’s MGP, and it’s not stress per se, it’s the messed up thyroid hormone that is missed in today’s idiotic endocrinology world/cardiology world…well, all of traditional medicine.
We measure serum levels of a few thyroid hormones to supposedly identify how well thyroids are working – TSH, T4, fT4, T3, fT3 – and we miss that this does NOT represent how well T3 is being created in various body tissues. If we are like rodents (seems likely) those serum levels are not representative of specific and varying tissue levels of T3, but this is just swept under the rug. No one has pursued this. Why? Because we’re stuck chasing the wrong biomarkers and we have the wrong paradigms for all these diseases.
Look into vitamin K2 and be totally amazed. Search it with these diseases. Understand what I have shared. And then learn how calcium can be dysregulated. It is dysregulated with water fluoridation. With lead exposure. With statins/warfarin/bisphosphonates (which, BTW, are given due to these incorrect biomarkers such as cholesterol/INR/t score). With all the crazy food additives which are falsely declared GRAS. Why did the Tsimane have no CAC? Because they’ve avoided all these toxins in which we are immersed and so they have the one true biomarker that really tells something profound: CAC = 0.
Screw inflammation. Screw cholesterol. Screw all those and learn how getting more vitamin K, and not interfering with K actions, makes for less insulin resistance, less, CVD/CHD, less CAC, less obesity, less cancer, etc.
Heck, a guy with HCC quit responding to the traditional way of treating it so he was put on a vitamin K2 analogue. His liver was cured. All his metastasizes went way. He had what is called a ‘complete response.’ Don’t know about that? Look it up on pubmed. Look up all I have claimed. It’s all there and traditional medicine is missing this.
Oncology is equally misguided, too.
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Cynthia,
I agree to most of what you write but I think an important point ((or two) is left out.
Modern medicine is not here to cure disease. I am not sure why we assume that it’s job is to cure all diseases. Its job is to medicate symptoms, and in some cases, such as surgical intervention or antibiotics of a life-threatening infection, it may have the tools to cure. But let’s face it: modern medicine is a money-making industry, employing millions of doctors, nurses, hospital staff, all kinds of administration, pharmacies, scientists whose job is to find medicines–not cure but medicines that treat the symptoms.
If any research ever found a cure for all/most of modern “diseases”, we are talking about the collapses of the biggest industries and millions of people in the unemployment lines! It is not that the scientists don’t know that low fat and high carbs–and especially sugar–processed foods, seed oils, and even “natural” or artificial sweeteners–is bad for us. They know it! But if they told the public that, they would lose their jobs.
Scientists must be able to publish to get tenured. It doesn’t matter what they publish, but it must be published in a “good journal”. So they write trash, repeating bad science, because they know it will publish.
So we need to stop criticizing those who cannot change the system and must start focusing on those who can. Who can change the system? You and I and other shoppers who spend their money where it best suits their health. You mention vitamin K2. I need not be amazed since I have taken it for ages, but I no longer need to because my food is mostly animal products. I eat no grains, no processed foods, no seed oils, so sweeteners of any kinds. I eat only animal products, including dairy, and some fruits. Animal products are full of K2. I have never had trouble with my bones, my CAC is 0, and my DEXA was great with no reduction in bone density.
So I know what’s good for me. And my job is to make an impression on other shoppers so they can “vote with their purchases” and since producers produce what they can sell, we can change the market to our advantage. There is a store that started out as vegan, then turned to vegetarian. As I started to shop there, I kept on asking about meat, especially beef and bacon. And guess what: now they have the best NZ pasture raised grass fed organic beef and they also sell bacon.
Changes are made at the level of the shopper. Demand drives the market. So stop pushing from above and start pushing from the bottom and educating people. What you posted here is not educating but blows everyone over after the 2nd sentence and they close the book… this is no way to get your message though such that people listen and/or read. 🙂
Best wishes,
Angela
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Re: “Changes are made at the level of the shopper. Demand drives the market. So stop pushing from above and start pushing from the bottom and educating people.” I can only agree 100% and applaud this. Power is in the hands of each individual. But from what I’ve seen so far, way too many don’t see it that way, don’t care, or love to succumb to what the shepherds of their herd tell them to do. But then again, due to the growing amount of individuals who relentlessly keep pushing from the bottom, maybe this could gradually change in a few centuries ☺️ 😈
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Great to hear from your Roald! 🙂
I agree… a few centuries, by which time there will be no humans on the planet, so might as well. 😉 Until then: it is a Darwinian evolutionary world out there and those who self-destruct won’t be here to reproduce. We cannot save them all. We can take the to the river but cannot make them drink…
And those of us who do embrace what truly is a healthier life for humans will live healthy and happy, for as long as humans are living on this planet. I am kind of happy that I am old. Selfishly, I don’t want to see the total destruction of the planet as vegans and the SAD dieters are doing the destruction now with all the major processed food industries catering to them. They blame the cows but it is actually them. I hope to die before there is no more land to feed to animals.
Stay safe and healthy,
Ang
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Great work, Angela. I was really interested by your comments on the Tsimane and read Reference 2. I could not see that Ref 2 goes so far as you say: it indeed reports low CAC levels combined with high inflammation but it provides no evidence of CAC-free atherosclerosis.
Your argument remains interesting but surely Ref 2 neither confirms nor contradicts it. Do you have a different view?
Jonathan
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Thanks Jonathan. You find some sentences on page 7 and 8 that, combined, can be used to interpret this paper as I did:
“This low prevalence and extent of CAC exists in the presence of low HDL, a known coronary artery disease risk factor. In the Tsimane, the average HDL was 1·0 mmol/L. This finding might highlight a differential weight to LDL versus HDL cholesterol for CAC” formation… In this study, a high inflammatory burden was observed in the Tsimane with a low prevalence of CAC for all inflammatory markers… The current study used single measures of hs-CRP and other inflammatory biomarkers, previous work by the THLHP showed strong consistency in immune activation across multiple time points, suggesting much of the increased inflammation among Tsimane is chronic.30 Hs-CRP was marginally associated with CAC presence, but other inflammatory markers such as erythrocyte sedimentation rate, neutrophil count, interleukin 5, and interleukin 10 were noted to be inversely proportional to CAC. These findings run counter to previous industrialised population studies, for which the opposite has been found.” (first half page 7, rest page 8)
And while these alone may not fully support my statement, with this sentence it does: “Our study is not without limitations. We employed CAC
scoring as a direct measure of coronary atherosclerosis, but its non-contrast nature precludes assessment of noncalcified plaque constituents.” (page 8)
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Thank you for your detailed reply, Angela. It would be interesting to inspect the arteries of the Tsimane for confirmation, as I do think you could be onto something.
I do congratulate you on your original thinking and fascinating website. You are doing a great public service that I hope brings you much satisfaction and pride. Well done indeed!
It is extraordinary that the medical establishment steadfastly stands by falsehoods like the LDL theory or the benefits of carb-based diets, when the data don’t support the falsehoods. That said, high carb diets as such aren’t necessarily unhealthy: the Tsimane experience proves that. It’s complicated …
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Thanks Jonathan. 🙂 I agree on both counts. It woudl be interesting to do a study like that but because the finding are then no longer hypotheses–deductive reasoning like I made and they hinted at in the paper–the findings will then stand up against the current dogma. There are two problems with that:
1) when findings come in the face of 99.99999999999% of the published “research”, publishing in a journal that people read and journalists take to “new flash” that then spreads like wildfire are zero. Look at our current experience. One journal published that red meat is not harmful and had to do so in 5 articles in the same journal to be able to withstand the attacks for retraction. And the findings are not carried by newsflash like they would have been had they found the opposite! Sensationalism only pays off if someone gets paid! And here we connect to the 2nd point,
2) when something shows (proves) that there is no need to treat most anyone with high cholesterol because high cholesterol and even plaques may not be the causes of heart disease (but perhaps the symptoms), and statins don’t save lives–and they don’t; none of us gets out of here alive and they only lengthen lifespan by 3-4 days after 10 years of statin use, so pointless–then there are not funds for such research.
So, as you see, the study you recommend, as great as it is, could not be completed.
In terms of carbs: I just heard a sentence in a lecture somewhere that grabbed my attention: “it’s not what we do that matters but what we don’t do”. To translate this to the Tsimane experience: int’s not that they eat a lot of carbs, some meat and fat. It’s what they don’t eat that makes the difference. They don’t eat any refined carbs, processed foods, industrialized processed seed and vegetable oils (this is the real killer by the way). I recommend you watch this video: https://www.youtube.com/watch?v=pHnPinYI2Yc
Let’s see if I can embed:
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For the first time in over 70 years I had a run in with very severe migraines a few months ago and was able to trace it down to the tomatoes on the BLTs. I had not eaten any tomatoes for about 6 months as avoiding nightshades and then I bought some of the plum , which were easy to remove the skins and the seeds to get out the suspect lectins. No problems for about a week and then got sloppy about removing the seeds and skins and bought varieties which were much more difficult to do this. After about three weeks of this the migraines started and got really severe. About 2 or 3 days after suspending all tomatoes the migraines subsided and then disappeared. I can’t say it was the seeds, the α-tomatine in the tomatoes or what, for sure. I found a pretty decent discussion on the nightshades:
“The largest series of solanine poisoning
involved an English day school where 78 schoolboys developed
diarrhea and vomiting after eating potatoes stored since the summer
term.29 Symptoms began 7-19 hours after ingestion with vomiting,
diarrhea, anorexia, and malaise. Of the 78 boys, 17 were admitted to the
hospital. Other symptoms included fever (88%), altered mental status
(drowsiness, confusion, delirium) (82%), restlessness (47%), headache
(29%), and hallucinations (23%). Three boys were seriously ill with
hypotension, tachycardia, and stupor out of proportion to fluid and
electrolyte imbalance. These boys were discharged 6-11 days after
admission, and they had nonspecific symptoms and visual blurring for
several weeks after release from the hospital.
Fatalities from solanine poisoning are not well documented in the”
https://www.ncbi.nlm.nih.gov/pubmed/19446683
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Thanks for your comment Fred. While solanine poisoning may cause severe distress and extreme headache. migraine is not a headache. Migraine may not even come with a pain in the head. Migraine is a very specific condition with a different brain from the norm, with channelopathy, hyper sensitive alert brains with sensory organs with much more neurons than normal and with several fold increase of connection. A migraine brain is physiologically different from a regular brain. So unless you have a migraine brain, you cannot experience migraines–you can experience headaches.
A headache may be much stronger than a migraine headache. Migraine headaches are not the strongest headaches–though they come close. Cluster and thunderclap are two headaches that are much stronger.
I suspect what you had were severe headaches but not migraines. 🙂
Thanks,
Angela
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Fascinating explanation of the ‘How & Why’. I’d love think you’ve got it.
Thank you !
There is a difference between how we react to happy stress…and horrible stress.
The former is… like taking off on my First Solo Flight, and the thought was “This is going to be FUN”
Horrible stress is standing up in front of an audience and realizing a zip is undone, and for the next 40 minutes…
I’m also convinced that *mis-handled* stress – or ‘strain’ as Dr Kendrick calls it, is pivotal to CVD.
In my case, CABG x5 very much so. Not only but also, my life history ticks too many boxes for Good cardiac health… eg, bullied at middle-High school, parents split when young, no siblings or extended family, too many shifts of residence to keep friends and inclination towards depressive episodes Plus my working life was rotating shifts, in a job I had no great passion for.
Don’t forget the T2 Diabetes / obesity /fitness deficiency…
Then, 12 months of constant stress, personal, financial and “legal”… resulting in loss of weight control / A1c regulation and self-image in a massive unending depression…. It’s no wonder – with hindsight – that my heart did it’s best to end it all for me !
Proverbs Ch 17 verse 22 says it all – and notice the inclusion of…. bones !
“A joyful heart is good medicine, But a broken spirit dries up the bones.”
Blue Zones the world over, have close personal & social support as the Common Factor, with ‘wholesome’ diets coming in after. – They vary enough to put them in second place.
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Glad you are coming around. Most everything broken can be repaired–though they may never look or behave like new, they will work just fine. 😉 Enjoy your new life and recovery!
The “Blue Zone” is all fake… none of what they labeled as “Blue Zone” fits the mold today and some never fit the mold in the past (Like in Japan or even in Loma Linda, which is a stone throw away from where I live, and where I almost ended up doing some research. Including that even mustard is forbidden for its “excitatory effects”, it is a horrible vegan-special diet with more restrictions than a standard vegan. What keeps people live longer (or used to.. not anymore) is the strong social-community-like nature of Loma Linda.
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Yesterday night I asked you about a new drug for T2D called Rybelsus which was recently approved by the FDA. But my message isn’t visible anymore. So I sent this one.
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Sorry, I have not yet been online since yesterday evening. Trying to finish writing a book, so I turned off all my online toys. 😉 I read both emails (I get an email when I get a message posted) just now.
It is a GLP-1 drug, glucagon-like peptide 1, receptor agonist, meaning they increase glucagon-like peptide. There is a pretty bad safety record for these drugs when injected–this is the first one that is by a different mechanism; not sure what it is. Whatever it is, it is making T2D worse by forcefully reducing the symptoms, which is high blood glucose… it is like placing your broken arm on a rack and constantly hit it with a bat, while you are drugged to not feel the pain.
These drugs are all misguided in that they only remove the symptom but to do so, they actually make the condition worse.
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Apart from the “money thing”, why the heck is stuff like this brought to the consumer? Are the “experts” thát stupid?
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Money talks. No one cares about curing people. Keeping them dependent on drugs is key.. right? So smart people because they go home with pockets full of money.
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Like I said b4, this also confirms my distrust in whatever authority is sitting in the drivers seat. Time for those people to rot in hell, I’d say.
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I couldn’t agree with you more!
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Rybelsus for T2D is FDA approved now. Your take on this?
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Re: “But stress on its own is also causing the release of osteocalcin……..” Negative as well as positive stress?
Talking about negative stress. I’m one of those who, for as long as I can remember, is living with it on a daily basis. Seems to me it’s based on my from childhood on developed and now ingrained anger with moron authorities hypocritically pushing their hidden agendas, as well as with their opportunistic lackeys, ignorant supporters, and indifferent followers. And yet………even after multiple visits to cardiologists triggered by a shitload of times I had all the classical symptoms of having a heart-disease/attack, I always came out clean. In my twenties a professor once told me: “Mister Michel, we can go on and on, but there’s nothing wrong with your heart.” Being now in my seventies, I’m told the same thing 😛
Note: As a long time online friend I feel I also have to tell you, that since last month my stress level has increased exponentially. Why is that? Because Lucitta died. I know you’re extremely busy, but if you want to know more about the latter, then, because I know the 2 of you are friends there, go to her FB page. Or mine for that matter. On both you can find several entries regarding her death.
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OMG Roald, I am so sorry! I have been too busy and didn’t visit her FB page. My deepest condolences to you and Vanessa! ❤ I have known that she was ill and all I can say is that at last she is in no pain. ❤ That won't heal your sorrow but at least her suffering is over. She was a wonderful person from the few times we exchanged words. She will be missed. ❤
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Thx. It’s extremely hard to accept she’s gone. Trying now to find out what to do with the rest of my time. Currently I’m devouring a cocktail consisting grief, desperation, anger, hopelessness, aggression, and other foul ingredients.
Still, what’s your take on my stress story?
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I think what you are going through is totally normal and I would not call it an unnatural stress story. I would think that you need to mourn the best way you can, just be sure you do, because otherwise the pain won’t leave. I have not lost anyone that close to me in my life, so I cannot even imagine what you are going through now. I am not sure what I would do so I cannot even recommend anything other than change your lifestyle from what you had before. Change what you do and when you do it so that you are not reminded of little things you always did together. That’s what I would do. ❤
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I see your point. It makes sense too. Given the way we lived together, also the real estate we own, all the stuff coming with all that, it will take a lot of time to organize/change same. And then there’s this too……. I don’t want to let her go 🎎
The other thing I was asking your opinion about was related to that osteocalcin thingy, as stress didn’t do to me what was suggested by the article you shared.
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You have no choice but to let her go because you have a future to think of. How you feel now is transient–regardless how long it lasts. ❤
In terms of stress and how it affected you. Not sure I understand what you mean: do you mean the fight-or-flight?? I think that there are several types of stresses and it is not clear that fight-or-flight and/or osteocalcin is part of each type. I don't suppose that the stress released by skydiving for the first time is the same experience as getting a first job, or having a loved one die, or getting your first new car. Each of these is a stress but each is very different in what they activate, plus they differ among people.
For example, when I was teaching in the university, I often had classes of several hundred in huge lecture halls and sometimes those lecture halls were filled with faculty to whom I lectured. The stress I felt totally fit me–I got a "high" from that stress. Yet pull a few typical people off the street and place them into that situation and watch some faint from stress. Feeling happy and looking forward to public speaking would have a very different stress response than feeling scared of public speaking. Same activity, different stress response.
So I think there is a lot more to this that none of the articles I discussed covered. Plus, in some situations, fight-or-flight exists without us actually being conscious of it. Migraine is very typical for that. I discuss this in my book. The first step in migraine is a fight-or-flight but few of us actually feel the fight-or-flight.
However, we may have its symptoms only we call these something else, even though they are all part of fight-or-flight: a sudden urge of a bowel movement out of regular timing and much bigger, a sudden urge to frequent urination, a bit faster heart rate than usual, being a bit out of breath perhaps, maybe a slight dizziness, a bit of nausea and maybe even vomiting, and many more. These are all symptoms of fight-or-flight without feeling anxiety. So you may have had the fight-or-flight without discovering it.
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Yes, I too can flourish under positive stress. That’s why I asked: “Negative as well as positive stress?”
Re: “Could it be that the real cause of CVD is stress?” & “…..osteocalcin, which then is just very happy to stick to wherever it can, causing calcification of atheroma.” Seems (well….um…..up till now) not to have happened in my case 😛
Re: “fight-or-flight”. There’s also “freeze” ⛄️
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I suppose CVD takes some time to develop and probably there are genetic factors mixed in there based on our reactions.
Yes, I am sure it is extremely hard to accept that she is gone. I don’t know what to recommend since I have not had the experience–I don’t have the right to recommend. Your body and mind will tell you how to advance. ❤
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Oh I’m so sorry! i wondered where you’d gone.
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BRILLIANT piece, thank you!!
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I’ve heard the same line where stress is the key trigger of CVD from Dr. Malcolm Kendrick. Thanks for another great post!
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Yes and in a recent post one of the replies was from someone looking at calcium metabolism.
I spent most of my life suffering from reactive hypoglycemia. A lack of Phase 1 insulin means my glucose spikes on eating carbs, then the Phase 2 turns up and knocks it back down again but fails to shut off and the rapid drop in glucose releases counterregulatory hormones including cortisol, epinephrine and norepinephrine which explains my mood symptoms and reacting as if |I was under stress when I wasn’t. All gone thanks to a low carb/keto diet. Maybe one more mechanism where diabetes is a cardiovascular risk.
I came across osteocalcin before in the context of diabetes also. \now to read these papers . . .
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Many of the migraineurs I work with have reactive hypoglycemia. To recover from that, I place them on the carnivore diet. It seems to work very well for most–not all so far.
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It’s amazing what you can see in retrospect! I used to get migraines, but they were comparatively mild and uncommon, so I lived with them, On the other hand I never had “normal” headaches, ie. without visual and sometimes aural disturbances.
Now I realise they occurred in the afternoon or evening a few hours after eating too many carbs. Yet another symptom that went away once I nailed my blood glucose.
Ok I’ve read your references, fascinating stuff! I only read one of them before. This one
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6213520/
looks to have some good links too.
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Thanks! Great that your migraines responded so well. For most migraineurs–particularly those on dozens of brain numbing drugs–it is not that easy.
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