Oreo Cookie Treatment Lowers LDL Cholesterol More Than High-Intensity Statin therapy

[Todd Allen]

https://www.mdpi.com/2218-1989/14/1/73

Quote

3. Results

The subject’s baseline BMI was 20.8 kg/m² with LDL-C 384 mg/dL. Oreo supplementation at 12 cookies/d (100 g added carbohydrate) decreased LDL-C to 308 mg/dL during the first week. During this time, β-HB one hour after waking, before the first ketone dose, remained at 0.3–0.7 mM, with an average of 0.5 mM, with a drop to 0.2–0.3 mM in the second week consistent with prolonged and gradual repletion of hepatic glycogen over the first week. After the second week of Oreo supplementation, the subject’s LDL-C dropped to 140 mg/dL (day 14), with repeat tests on subsequent days confirming LDL-C 129 mg/dL (day 15) and 111 mg/dL (day 16). Thus, 16 days of consuming 12 Oreo cookies/d decreased the subject’s LDL-C by 273 mg/dL, a 71% drop, and returned his LDL-C into the ‘normal’ reference range (Figure 2, Table 2), with a continued downtrend towards his pre-KD level of 95 mg/dL. The subject gained 1.5 kg during the Oreo arm. BMI returned to baseline (20.8 kg/m²) after ad libitum consumption of a KD during the washout period.

 

Treatment with 20 mg/d rosuvastatin daily ultimately lowered the subject’s LDL-C from 421 mg/dL to 284 mg/dL at 4 weeks, with a plateau in LDL-C to 294, 284, and 295 mg/dL on weeks 3, 4 and 5. There was a moderate increase in LDL-C to 346 mg/dL after the 6th week, during which daily step count was increased from ~10,000 steps/d to ~20,000 steps/d. Thus, peak LDL-C reduction on high-intensity statin therapy was less than half that of the Oreo supplementation, despite 6 weeks of the statin intervention. The only notable side effects of the statin treatment were myalgias with mildly elevated creatine kinase to the mid 300s U/L (risk factors for which, in this case, include lower BMI and physical activity [10]) starting at week 3, through which the subject persevered.

 

[Dean Pomerleau]

Nice find Todd. It looks like the subject was successful at reversing his ketogenic diet-induced problem with high cholesterol via diet alone. Good for him! He probably could have done even better by eating healthy carbs rather than Oreos. 😀

[Ron Put]

18 hours ago, Dean Pomerleau said:

It looks like the subject was successful at reversing his ketogenic diet-induced problem with high cholesterol via diet alone.

LOL. I saw a couple of interviews on this, and I've been keeping an eye on this citizen science project. I am still not entirely sure what exactly this focus on supposed "lean-mass hyper-responders" is trying to prove, but the keto tribe is super excited about it.

[TomBAvoider]

It looks like the subject was successful at reversing his ketogenic diet-induced problem with high cholesterol via diet alone.

Before we laugh too much, we should note one thing: the subject did not change his ketogenic diet in any way, and added a sleeve of oreos on top of his usual diet. 

So unless we believe that the ketogenic state by itself causes those lipid aberrations, (i.e. the very low levels of carbohydrates in the diet alone) rather than the other ingredients of the diet, such as high levels of fat (specifically saturated fat) and animal proteins, we can't say that the subject "corrected" his diet by adding some (rather unhealthy!) carbohydrates in the form of oreo cookies on top of his usual "unhealthy" diet. Btw., oreo cookies in addition to having a ton of simple sugars, also have salt and saturated fat as the biggest SFA, so yeah, not something you'd think would lower cholesterol, quite the opposite, yet here we are.

It's exactly the same crap diet, only now you've added a bunch of awful ultra processed high extra calorie snack in the form of oreos. Really, does not qualify as better than before from the point of view of decreasing cholesterol. Nothing in that diet composition, the mere addition of a terrible junk food would indicate a cholesterol win.

The study is intentionally provocative, but well designed. He is testing the hypothesis behind how the LMHR phenotype works. If the hypothesis is correct, then the addition of the oreos  - in all their nutritional abomination - should lower LDL. It did. Score one for the LMHR team. The fact that the standard of care and treatment of hyperlipidemia, a high dose statin (20mg/d rosuvastatin), when added with the same ketogenic diet (in place of the oreos) brought down the LDL dramatically less effectively than the oreos simply underscores that our current consensus understanding of lipid metabolizm is profoundly inadequate, and wrong in some critical aspects.

I am not inclined to jeer at the LMHR crowd (note: these folks are a small subset of the keto advocates!). The are on to something, at least insofar as telling us that the currently accepted lipid model is wrong and incomplete.

[Ron Put]

Jokes aside, there are many issues with this "study" in addition to the fact that it is a single subject, and numerous unaccounted-for confounders.

The way I see this, this is just as well anticipated by the conventional lipid wisdom and this is why I am a bit puzzled by the excitement.

Basically, the reduction in LDL-C can be explained as due to an abrupt dietary addition that alters microbiome composition, and changes lipid metabolism, insulin secretion, and energy utilization.

I just looked and Oreos have either palm or canola oil and based on the saturated fat content, I assume in this case it's mostly palm oil. However, there is evidence that palmitic acid from plant sources is less atherogenic than that from animal sources. Plant saturated fats also contain various antioxidants and other factors that may account for the drop of LDL-c compared to animal-derived fats.

There was also an increase of monounsaturated fats and a slight fiber increase, in addition to the sugars, and the overall effect may account for the changes in LDL-c.

It is also a very short-term test and I don't see why long-term the risks of such dramatic elevation of LDL-c would be different than those suggested by the current model.

Unusual genetics may also matter in this n=1 test. For all we know the guy may carry some Inuit mutations 🙂

[Todd Allen]

On 1/25/2024 at 1:12 AM, TomBAvoider said:

The study is intentionally provocative, but well designed. He is testing the hypothesis behind how the LMHR phenotype works. If the hypothesis is correct, then the addition of the oreos  - in all their nutritional abomination - should lower LDL. It did. Score one for the LMHR team. The fact that the standard of care and treatment of hyperlipidemia, a high dose statin (20mg/d rosuvastatin), when added with the same ketogenic diet (in place of the oreos) brought down the LDL dramatically less effectively than the oreos simply underscores that our current consensus understanding of lipid metabolizm is profoundly inadequate, and wrong in some critical aspects.

You got to the heart of it, nicely summarized.  It is very widely assumed that lower LDL is healthier and thus things which lower LDL are intrinsically good and those which raise LDL are bad.  But then how does adding oreos to a diet still rich in animal sourced saturated fats result in a dramatic lowering of LDL to within range from FH levels?

While this is the only case I know of testing oreos I expect a great many people could produce similar results if they cared to try it.  Myself and many others find the biggest levers to raise LDL are carbohydrate restriction, increasing leanness and recent caloric deficit.  I suspect it is actually smaller average adipocyte size rather than body fat percentage or muscle mass increasing LDL volatility in response to carbohydrate restriction/intake.  Myself whenever I do a phase of rapid weight loss I can spike my LDL but when I maintain weight LDL drifts slowly down and it plummets when I regain any fat.  Changes in diet such as swapping in coconut oil or beef suet for olive oil show no power to raise or sustain my LDL compared to actively reducing body fat and restricting carbohydrates.

[Dean Pomerleau]

42 minutes ago, Todd Allen said:

It is very widely assumed that lower LDL is healthier and thus things which lower LDL are intrinsically good and those which raise LDL are bad.

Seems like a straw man. Elevated cholesterol uptake by cancer cells [1] often results in reduced blood LDL cholesterol in people with cancer [2]. But like Oreos, I don't think anyone would claim cancer is "intrinsically good" because it can lower your LDL cholesterol.

--Dean

--------------------

[1] AUTHOR=Halimi Hossein, Farjadian Shirin

     
TITLE=Cholesterol: An important actor on the cancer immune scene  
    
JOURNAL=Frontiers in Immunology     
    
VOLUME=13      
    
YEAR=2022   
        
URL=https://www.frontiersin.org/articles/10.3389/fimmu.2022.1057546     
      
DOI=10.3389/fimmu.2022.1057546    
    
ISSN=1664-3224   

ABSTRACT=Based on the structural and signaling roles of cholesterol, which are necessary for immune cell activity, high concentrations of cholesterol and its metabolites not only trigger malignant cell activities but also impede immune responses against cancer cells. To proliferate and evade immune responses, tumor cells overcome environmental restrictions by changing their metabolic and signaling pathways. Overexpression of mevalonate pathway enzymes and low-density lipoprotein receptor cause elevated cholesterol synthesis and uptake, respectively. Accordingly, cholesterol can be considered as both a cause and an effect of cancer. Variations in the effects of blood cholesterol levels on the outcome of different types of cancer may depend on the stage of cancer. However, positive effects of cholesterol-lowering drugs have been reported in the treatment of patients with some malignancies.

-----------

[2] 

1. Cancer Epidemiol Biomarkers Prev. 2009 Nov;18(11):2814-21. doi: 
10.1158/1055-9965.EPI-08-1248. Epub 2009 Nov 3.

Prediagnostic total and high-density lipoprotein cholesterol and risk of cancer.

Ahn J(1), Lim U, Weinstein SJ, Schatzkin A, Hayes RB, Virtamo J, Albanes D.

Author information:
(1)Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, 
Bethesda, Maryland 20892, USA.

Comment in
    Cancer Epidemiol Biomarkers Prev. 2009 Nov;18(11):2805-6.

BACKGROUND: Circulating total cholesterol has been inversely associated with 
cancer risk; however, the role of reverse causation and the associations for 
high-density lipoprotein (HDL) cholesterol have not been fully characterized. We 
examined the relationship between serum total and HDL cholesterol and risk of 
overall and site-specific cancers among 29,093 men in the Alpha-Tocopherol, 
Beta-Carotene Cancer Prevention (ATBC) Study cohort.
METHODS: Fasting serum total and HDL cholesterol were assayed at baseline, and 
7,545 incident cancers were identified during up to 18 years of follow-up. 
Multivariable proportional hazards models were conducted to estimate relative 
risks (RR).
RESULTS: Higher serum total cholesterol concentration was associated with 
decreased risk of cancer overall (RR for comparing high versus low quintile, 
0.85; 95% confidence interval, 0.79-0.91; P trend <0.001; >276.7 versus <203.9 
mg/dL), and the inverse association was particularly evident for cancers of the 
lung and liver. These associations were no longer significant, however, when 
cases diagnosed during the first 9 years of follow-up were excluded. Greater HDL 
cholesterol was also associated with decreased risk of cancer (RR for high 
versus low quintile, 0.89; 95% confidence interval, 0.83-0.97; P trend = 0.01; 
>55.3 versus <36.2 mg/dL). The inverse association of HDL cholesterol was 
evident for cancers of lung, prostate, liver, and the hematopoietic system, and 
the associations of HDL cholesterol with liver and lung cancers remained after 
excluding cases diagnosed within 12 years of study entry.
CONCLUSION: Our findings suggest that prior observations regarding serum total cholesterol and cancer are largely explained by reverse causation. Although chance and reverse causation may explain some of the inverse HDL associations, we cannot rule out some etiologic role for this lipid fraction.

DOI: 10.1158/1055-9965.EPI-08-1248
PMCID: PMC3534759
PMID: 19887581 [Indexed for MEDLINE]

[Todd Allen]

6 hours ago, Dean Pomerleau said:

Seems like a straw man. Elevated cholesterol uptake by cancer cells [1] often results in reduced blood LDL cholesterol in people with cancer [2].

On 1/23/2024 at 4:25 PM, Dean Pomerleau said:

Nice find Todd. It looks like the subject was successful at reversing his ketogenic diet-induced problem with high cholesterol via diet alone. Good for him! He probably could have done even better by eating healthy carbs rather than Oreos.

Perhaps I should have spelled it out more clearly but I was speaking about the domain of foods raising or lowering LDL.  Nick used oreos because they do not have a health halo.  If he chose oatmeal or goji berries people would not have found the result as striking.  Note, never in Nick's paper does he characterize high LDL as a problem or lowering it with oreos as desirable.  Yet you jumped to those conclusions despite knowing the association of low cholesterol and some cancers.

 

On 1/25/2024 at 2:08 PM, Ron Put said:

Plant saturated fats also contain various antioxidants and other factors that may account for the drop of LDL-c compared to animal-derived fats.

There was also an increase of monounsaturated fats and a slight fiber increase, in addition to the sugars, and the overall effect may account for the changes in LDL-c.

Fortunately we have Ron leading us down the path of oreos possibly being yet another vegan superfood as a handful of oreos and their uber healthy refined plant fats can over power the effects of a diet still based on vast quantities of saturated animal fats.  Thankfully we don't have to fear Nick achieving his results through oreo induced cancer.

[Dean Pomerleau]

1 hour ago, Todd Allen said:

Yet you jumped to those conclusions despite knowing the association of low cholesterol and some cancers.

An association ascribed to reverse causation, as discussed in [2] above. Also see this review:

https://aacrjournals.org/cebp/article/18/11/2805/67526/Cholesterol-and-Cancer-Answers-and-New

[Todd Allen]

3 hours ago, Dean Pomerleau said:

An association ascribed to reverse causation

Exactly!  The oreos caused the cancer which lowered his LDL.  And thus his risk of dying from CVD is reduced.  Problem fixed!

[Dean Pomerleau]

5 hours ago, Todd Allen said:

Exactly!  The oreos caused the cancer which lowered his LDL.  And thus his risk of dying from CVD is reduced.  Problem fixed!

LOL. 

[Todd Allen]

7 hours ago, Dean Pomerleau said:

LOL.

Yes, I was being facetious.  Although my desire was to be sarcastic and ridicule your position.  You acknowledge that LDL can drop for a bad reason: cancer.  I assume you are aware LDL can drop for other bad reasons too.   You seem to believe oreos are an unhealthy food choice.  And yet you jumped to the conclusion that Nick's drop in LDL was a good thing despite no other positive data suggesting an improvement Nick's health from the intervention which lowered his LDL.

[Ron Put]

19 hours ago, Todd Allen said:

Fortunately we have Ron leading us down the path of oreos possibly being yet another vegan superfood as a handful of oreos and their uber healthy refined plant fats can over power the effects of a diet still based on vast quantities of saturated animal fats.

While I appreciate the humor, you seem to miss the point of my post.

This whole exercise is rather silly, IMO, given the preponderance of the evidence for the detrimental long-term outcomes of high-fat diets. It is well established that while in the short-term keto improves insulin sensitivity, in the long-term it results in insulin resistance. Much of the results can be explained by it:

1. Since long-term ketosis generally results in increased insulin resistance, when carbs are reintroduced, in any form, even as Oreos, they stimulate significant insulin release which promotes glucose uptake by cells and reduces the release of fatty acids from adipose tissue, lowering the availability for liver cholesterol synthesis.

2. Insulin also triggers reduced lipolysis AND reduced liver lipogenesis, so when Oreos reintroduce carbs and insulin levels shoot up, this would lead to a reduction in the production of LDL-c.

3. Insulin also boosts the expression of LDL receptors on liver cells and it can significantly increase the clearance of plasma LDL-c.

4. To boot, the Oreos introduction would significantly increase enzymes like lipoprotein lipase, which breaks down triglycerides and drops plasma VLDL, which then drops LDL-c.

Then there is the other point I made above, which is that what is substituted by the Oreos matters. Oreos may be bad, but presumably, their profile looks great when compared to fat-dripping bacon.

Nothing in this "study" proves to me that somehow high LDL-c is a good thing, or at least that it doesn't matter in the long run.

Edited February 2 by Ron Put

[Dean Pomerleau]

1 hour ago, Todd Allen said:

And yet you jumped to the conclusion that Nick's drop in LDL was a good thing despite no other positive data suggesting an improvement Nick's health from the intervention which lowered his LDL.

Todd, I think you missed the sarcasm in my own initial response to you posting this study. Of course I don't believe Nick was doing himself a favor by dumping a buttload of Oreos into his high fat keto diet. I don't know what to make of the fact that Oreos dropped his crazy high LDL more than statins and frankly I don't really care. Garbage in, garbage out, as far as I can tell.

I don't consider a keto diet to be a good option except perhaps for people with unusual health problems like you, or for those whose glucose metabolism is seriously impaired. And for the latter, I think there are healthier & better (for the planet) options, like a whole food plant-based diet. 

But It's a free country and I'm strongly in favor of self-experimentation. Perhaps Nick and others like him will revolutionize our understanding of human nutrition. But I'm not holding my breath and this study seems more like a joke destined for an Ig Noble Award rather than useful science.

[Dean Pomerleau]

I wrote:

34 minutes ago, Dean Pomerleau said:

frankly I don't really care. Garbage in, garbage out, as far as I can tell.

By analogy: I'd feel the same way about a well-controlled study with many subjects that demonstrated conclusively that two shots of whiskey a day reduced arterial stiffness among heavy smokers. Big wup. It's better to adopt neither of those practices, despite the fact that one might mitigate some detrimental aspect of the other.

[Todd Allen]

2 minutes ago, Ron Put said:

Nothing in this "study" proves to me that somehow high LDL-c is a good thing, or at least that it doesn't matter in the long run

That was not the point of the study.  The point was as TomBAvoider described, the mainstream understanding of lipid metabolism as embraced by the pharma driven health care system would not have predicted this result.  The result however is in alignment with the lipid energy model hypothesis put out by Dave Feldman and associates.  Our choices are made based on our conceptual frameworks or models of reality.  It is import to investigate when our models fail to predict testable outcomes.  Medical and especially nutritional "science" far too often dismiss failures of their models to make predictions as paradoxes.  Science riddled with paradoxes is not science.

[Todd Allen]

27 minutes ago, Dean Pomerleau said:

I don't know what to make of the fact that Oreos dropped his crazy high LDL more than statins and frankly I don't really care.

Yes you have long and repeatedly made your preference for ignorance and dogma versus science abundantly clear.

[Dean Pomerleau]

2 minutes ago, Todd Allen said:

Yes you have long and repeatedly made your preference for ignorance and dogma versus science abundantly clear.

LOL. You left out the part where I said I'm in favor of self-experimentation and that there is a (slim) chance this sort of investigation might teach us something interesting (or even more unlikely, useful) about human nutrition. 

[mccoy]

I've been listening to some discussions with Nick Norwitz even before his Oreo experiment.

The very basic point that Norwitz and the LMHR researchers noticed is that, in lean subjects who suffered inordinate cholesterol elevation because of a keto diet, the addition of carbs in sufficient quantities, let's say 50-100 grams per day (any carbs, not just cookies), tends to reverse the increasing trend.

Of course that also decreases the ketone concentrations and the diet is no more a keto diet, at most a low carbs regime.

The cause of this bizarre mechanism is unknown, although there are some speculations.

Dom D'agostino also suffers from very elevated cholesterol, ditto for Ken Ford, the host of Stem Talk. The latter said in a podcast with D'agostino: 'Apparently, there is not such a thing as a free lunch', that is, it seems to be impossible to enjoy the (individual) benefits of keto diet without a deleterious increase of cholesterol in the blood.

What Nick Norwitz did is confusing, he did it to receive more attention, but he should have better not. He should have done the experiment with healthy carbs, like bananas, dried fruit, honey, even whole cereals, or with aseptic clinical food as glucose solution. He gained an audience but did not deliver what he wanted.

Last but not least, and very interesting, Norwitz tried a keto-vegan diet with only PUFAs to see if cholesterol elevation could have been avoided without the ingestion of saturated fats. To no avail. The surge in cholesterol seems to be directly related to the plunge in carbs in the system, at least in some people, even though Peter Attia says that substituting animal fats with EVOO (monounsaturated fats) will decrease  cholesterol in hyperresponders. Of course Norwitz' reports are all very anecdotal. There are no trials with hyperresponders and substitions of SAFAs with PUFAs, nor of addition of carbs (which seems a pretty common phenomenon though).

Edited February 3 by mccoy

[Ron Put]

On 2/2/2024 at 10:09 AM, Todd Allen said:

That was not the point of the study.  The point was as TomBAvoider described, the mainstream understanding of lipid metabolism as embraced by the pharma driven health care system would not have predicted this result.  ... Our choices are made based on our conceptual frameworks or models of reality.  It is import to investigate when our models fail to predict testable outcomes.

Todd, I am still not clear why this is such an unpredictable result. Maybe I am missing something, but I posted above several rather plausible, IMO, reasons for the reduction in cholesterol upon reintroduction of carbs. I will repeat them here because I am curious why you or Tom don't believe that such potential mechanisms are valid:

1. Since long-term ketosis generally results in increased insulin resistance, when carbs are reintroduced, in any form, even as Oreos, they stimulate significant insulin release which promotes glucose uptake by cells and reduces the release of fatty acids from adipose tissue, lowering the availability for liver cholesterol synthesis.

2. Insulin also triggers reduced lipolysis AND reduced liver lipogenesis, so when Oreos reintroduce carbs and insulin levels shoot up, this would lead to a reduction in the production of LDL-c.

3. Insulin also boosts the expression of LDL receptors on liver cells and it can significantly increase the clearance of plasma LDL-c.

4. To boot, the Oreos introduction would significantly increase enzymes like lipoprotein lipase, which breaks down triglycerides and drops plasma VLDL, which then drops LDL-c.

5. Abrupt dietary change also rapidly changes the composition of the gut microbiome and that can potentially have a significant effect as well.

All of the above potential explanations can fit within the current model and do not require the miracle of the lipid energy model, which against good evidence presumes no long-term deleterious effects of high-fat consumption and an essentially permanent state of ketoses.

[TomBAvoider]

Perhaps it's not very clear - or maybe it is - but the point of this n1 rat experiment wasn't to assess how healthy or not was a ketogenic diet. It wasn't whether high/low LDL is healthy/unhealthy. It was strictly - "LDL goes up and down in ways our consensus understanding does not account for". 

Since long-term ketosis generally results in increased insulin resistance, when carbs are reintroduced, in any form, even as Oreos, they stimulate significant insulin release which promotes glucose uptake by cells and reduces the release of fatty acids from adipose tissue, lowering the availability for liver cholesterol synthesis.

I don't know about this. My general understanding of cholesterol de novo synthesis by hepatocytes is based on this. In the LMHR phenotype, the LM stands for Lean Mass. These are by definition low adipose tissue carriers. If the the liver producing high levels of LDL was dependent on fatty acids released from adipose tissue, then there's not much adipose tissue to work with in LMHR to gain such sky high LDL production. Meanwhile we see in cases of FHC that the levels of LDL are not dependent on adipose tissue - how fat or skinny the FHC individuals are - but on genetic defects in LDL receptors. It's a LDL clearance issue, not that there isn't enough substrate of fatty acids from adipose tissue to synthesize cholesterol. Of course, there are many reasons for hypercholesterolemia, including excess ROS production in mitochondria and so on, but in this case we are talking about truly extremely high LDL levels, so not for example age-related LDL elevations (where mitochondrial ROS overproduction is the mechanism).

The thing that makes this notworthy is the sheer level of effect - if the conventional understanding of lipid metabolism were correct, then Rosuvastatin should have been immensenly more effective at lowering LDL than oreo cookies. Yet, that's not what has happened - quite the opposite. That tells us very clearly, that the mechanisms - the levers of action if you will - that are affected by statins are not the operative ones here - statins both limit synthesis of LDL and clear LDL from the blood. What do you imagine oreo cookies do - if you say "limit synthesis of LDL" by the purported mechanisms you enumerated then you are saying that oreo cookies limit LDL synthesis dramatically more effectively than statins... highly implausible! Btw. don't forget two crucial points - in general, statins are FAR MORE effective at reducing LDL levels than lifestyle/diet interventions, so ascribing such powers to oreos (i.e. dietary intervention) compared to a statin is not plausible. The other crucial point, far more devastating, is the other difference between these two interventions - one was magnitude (which we discussed so far, i.e. oreos lowered LDL far more dramatically than rosuvastatin) and the other was speed - the oreas worked dramatically faster - it took rosuvastatin to lower LDL (poorly!) dramatically LONGER to achieve those pitiful results. 

Again, the argument here is not whether ketogenic diets are healthy or not, but rather "how does a full picture of lipid metabolism in humans look like". Clearly, the standard model is very lacking. Which is a separate issue from "are high/low levels of LDL healthy/unhealthy". 

Personal disclosure: I have had life-long high LDL, from as far back as it was measured (1980's). My diet was not great until my 40's and my transition to a CR diet. I cleaned up my diet - still high LDL. I then laser-focused on lowering my LDL through lifestyle, diet and supplement regiments - and believe me, I did everything in my power in those interventions - my LDL remained stubbornly high. I finally threw in the towel and got on 10mg/day atorvastatin in 2018. At first my LDL levels plunged into the 70's. I was beyond thrilled. Then every year afterwards it started creeping back up - even as I kept everything else constant (except increased my exercise levels!). By last year, it was again a dramatic situation - LDL levels almost back to the previous high levels. I was heartbroken (yes, bad pun, sorry!). In some respects I resemble LMHR - my HDL is generally high (ranging from high 70's - this year 87 - to 105); my triglycerides, generally low (50's). My LDL high. Yet, I get these results on almost the opposite of the ketogenic diet - I'm a pescatarian, and other than fish, generally plant based, high fruit low fat diet (except for a tiny bit of EVOO), with nuts and flaxseed supplying my fatty acids. Metric tons of fiber (truly epic amounts, lol). Again - not ketogenic by any stretch of imagination.

Why am I mentioning my personal data - because I checked for my Lp(a) - it is catastrophically high 78 mg/dL. High ApoB (flagged by the lab) and sky high Lp(a), which is the very worst kind of lipoprotein, extremely artherogenic. Fearing the worst, but wanting to know where I stand, my doctor agreed that I should go in for a CAC scan. I went in (tested at UCLA) with a sense of doom, expecting the technicians operating the scanner to march in and tell me that given my CAC score, I am considered dead and should immediately take an uber to the nearest cemetary. 

The result came in the next day: zero score. My heart arteries are clear of ANY calcification. Impossible! I wanted to call the lab and ask them to please get my results, because clearly they mixed them up with someone else. I mean - consider: lifelong high LDL, some of the very worst Lp(a) levels known to humanity, unremarkable  (read: poor) heart health-diet/lifestyle up to my 40's. On a statin only for the past 5.5 years (and btw., statins if anything can ELEVATE your CAC score, because the calcium stabilizes the plaque). What are the odds that I would have a ZERO score - which also, according to MESA is *unusual* for my age group as the majority have some calcification... I have actually less calcification than appearing for the majority of my cohorts (who have better lipid profiles). Also, my artery width was stellar (29mm - my best friend, a lifelong health freak had it worse by 1mm, lol). I have been slim all my life though. 

So the question is: just going by what we know about atherosclerosis and lifelong lipid profiles, I should be in a vat somewhere in a medical school as an example of what bad lipid profiles can do to a human body. And yet my CAC score is to be envied at my age - as my cardiologist admitted, he doesn't know what to do with me - my lipids are clearly bad, but what to do about them, since as he put it, my CAC score is "a stone cold zero"... more statin? pcsk9i? bempedoic acid? Will that get me to "minus" since zero is already taken?

My point here is: there's a lot we don't know about how lipids work in the human body. By rights, I should have extensively calcified arteries. We have FHC folks walking around with stratospheric levels who live to a ripe old age - according to conventional models an impossible feat. And yet. If there is one thing clear, it's that we simply don't have a complete picture of lipid metabolism - and the LMHR case is just one more example of this. YMMV.

[IgorF]

hm, based on experiment description it seems that the experiment was about

- a study of a complex non-linear system (energy pressure on carb/triglies metabolic networks is very complex and is far far away from linear models used in big groups statistical studies) taken in

- a person on a let's be honest - a diet that is far from being usual and long-term adopted by our species

- with a special condition (ulcerative colitis) that in the age described is very suspicious from immune system perspective (age and lifestyle) and given the timeframe of this codition is definitely about gut microbiota deformity (that on its own is a complex non-linear system we will probably never have tools to study due to math apparatus we have now)

 

maybe a bad analogy but picking e.g. a so called "logistic map" (https://en.wikipedia.org/wiki/File:Logistic_map_animation.gif) as a simple model it seems like a "lucky man's case" - he was able to decrease the factor that creates a pressure and the system's behavior changed back to a linear area

those who are for various reasons not lucky can move to the area of unpredictability without a chance to return (e.g. td2 that do not react on complete diet changes etc); some people are lucky enough (do not have broken feedbackloop controls yet) to go into a bad state but return to normal with a proper care/control

 

br,

Igor

[mccoy]

Tomb, your lipids situation is an unusual but surely not an unknown one. In one of his podcasts, Tom Dayspring suggests some 'unknwon protective factors' which prevent atherosclerosis in some individuals with very high cholesterol and ApoB levels. The issue is often raised by the keto people: this guy, this gal, 500 TC and they exhibited CAC score= 0. What doctors say about cholesterol is a hoax!

Of course, the above reasoning is delusional.

The law which governs the increase of risk of atherosclerosis with the increase of ApoB and cholesterol i general is a probabilistic one. I am always amazed at how people do not consider (or choose not to, or simply do not understand) that risk is described by probabilistic functions.

The studies detect that when cholesterol is very high, the risk of atherosclerosis increases by various ratios, in a dose dependent fashion. An increase of risk though does not mean that 100% of the individuals with higher cholesterol will develop an atherosclerotic stage.

For example, in the subgroup with a 95th percentile of the blood ApoB values, let's say ApoB 180 mg/dL, there will be some percentage of individuals, let's say 5%, with a zero CAC score, whereas the expected value, or mean, which represents the majority of people, will include for example 80% of people within a one standard deviation width.

 

[mccoy]

11 minutes ago, IgorF said:

maybe a bad analogy but picking e.g. a so called "logistic map" (https://en.wikipedia.org/wiki/File:Logistic_map_animation.gif) as a simple model it seems like a "lucky man's case" - he was able to decrease the factor that creates a pressure and the system's behavior changed back to a linear area

those who are for various reasons not lucky can move to the area of unpredictability without a chance to return (e.g. td2 that do not react on complete diet changes etc); some people are lucky enough (do not have broken feedbackloop controls yet) to go into a bad state but return to normal with a proper care/control

I see it from a simpler perspective, maybe I'm missing something (?): as a consequence of a keto diet, Norwitz experienced a very high increase in LDL (a commonly noticed occurrence-anecdotally). When he ceased restricting carbs (by ingesting oreos), the LDL went down. Hence, he was cured by the anomaly simply adopting a moderate-carbs regimen. For reasons yet unknown.

Oreos have nothing at all to do with the anecdote, and in my opinion he had a very bad idea of illustrating an interesting biological phenomenon by introducing a hugely confounding factor: Oreos, that is junk food: what does that mean?

Edited February 4 by mccoy

[Todd Allen]

18 hours ago, Ron Put said:

but I posted above several rather plausible, IMO, reasons for the reduction in cholesterol upon reintroduction of carbs. I will repeat them here because I am curious why you or Tom don't believe that such potential mechanisms are valid:

You started with a statement about people becoming insulin resistant on a ketogenic diet.  I believe practically the polar opposite and that LMHRs are in general exquisitely insulin sensitive.  Our viewpoints are so completely divergent that discussion is pointless.  Is it even possible for either of us to provide sources or evidence for our beliefs that the other is likely to accept or even seriously consider?  The years of covid have left me jaded about the value of discussing strongly held divergent views.  It generates a poor return on the invested time and energy.