@pmiguel You’re mixing up LDL-P and LDL-C. this review is disputing the proposed causal link between LDL-C (amount of cholesterol contained in LDL particles) and CVD. Ron Krauss as you correctly said was talking about the proposed causal relationship between LDL-P (number of LDL particles) and CVD which is widely supported among experts.

@rhonda this is a really poor study. Or at least the conclusions drawn from it and trumpeted through the media are poorly supported by the study.

Take a look here: http://www.fathead-movie.com/index.php/2019/02/18/pushups-and-heart-attacks-the-usual-harvard-nonsense/

Basically the ability to do some number of push-up stratifies the firefighters into age groups. When age is accounted for there is significant differences between only two groups. This presumably disappears when smoking is taken into account since the authors didn’t do that test. (Although they did collect the smoking status of the participants.)

Wow FP, this is even more bizarre than the Ginger Exosome-like Nanoparticles paper I posted: linked text The Ginger ELNs protect mice from DSS-induced colitis through interactions with Lactobacillus rhamnosus. Ginger is a root and so it would be expected that it would communicate with bacteria. But Grape ELNs do this directly?

…we show that the cells targeted by grape exosome-like nanoparticles (GELNs) are intestinal stem cells whose responses underlie the GELN-mediated intestinal tissue remodeling and protection against dextran sulfate sodium (DSS)-induced colitis.

Why does a plant do this?!?

This paper is covered in a This Week in Microbiology episode: http://www.microbe.tv/twim/twim-190/ which is easier to understand than the paper…

Discussion of this review by hard-core virologists in the most recent episode of the podcast This Week in Virology: http://www.microbe.tv/twiv/twiv-519/

Here is a good article: https://www.technologyreview.com/s/611713/researchers-find-way-to-mimic-clinical-trials-using-genetics/ Although only tangentially related to your question, it can give you some useful background.

My advice is that you probably should get some more information. I think there is reasonable consensus that it is the LDL particles themselves – that is, the number of them – that confers risk. Not the amount of cholesterol they carry. So getting an actual LDL-P number assay done (NMR) would be helpful.

Past this, if your LDL-C is very high, then your LDL-P will almost certainly be high also. Whether you choose to use statins or not should be a discussion between you and your doctor. Otherwise what is the point of having a doctor?

Link is to a news release. Here is a link to the full paper: https://pubs.acs.org/doi/full/10.1021/acs.chemrestox.8b00047

@rhonda, I would have concerns that the residual TiO2 might be worse than the BPA. Report: https://news.utexas.edu/2018/06/20/link-found-between-type-2-diabetes-and-common-white-pigment on a paper: https://pubs.acs.org/doi/full/10.1021/acs.chemrestox.8b00047 Previous studies showed TiO2 inhale or ingested ended up in the blood stream where it was phagocytosed. From the paper: “By binding to and activating the NLRP3(NALP3) inflammasome,(12,31−33) a macromolecular complex found in macrophages, neutrophils, platelets, and microglia, the TiO2 crystals cause inflammatory cascades leading to death of proximal cells.” Furthermore, the paper itself reported an association of TiO2 crystals in the pancreases of type 2 diabetics, but not in non-diabetics. Small study – but all 8 T2D pancreases examined had the crystals whereas none of the 5 non-T2D pancreases did.

Trying to wrap my head around the research paper. Here if you can get through the paywall: DOI: 10.1210/en.2017-00752 From the abstract: We investigated the role of nuclear factor erythroid 2–related factor 2 (Nrf2) in renin-angiotensin system (RAS) gene expression in renal proximal tubule cells (RPTCs) and in the development of systemic hypertension and kidney injury in diabetic Akita mice. We used adult male Akita Nrf2 knockout mice and Akita mice treated with trigonelline (an Nrf2 inhibitor) or oltipraz (an Nrf2 activator). …

So, if I understand correctly, these are type 1 diabetic mice. Directly activating Nrf2 using oltipraz in these diabetic mice resulted in hypertension and kidney damage.

I’m not sure how generally we want to interpret these results. Although if you are a type I diabetic with uncontrolled hyperglycemia you would probably want to keep an eye on your blood pressure in the unlikely event you were taking oltipraz.

What about sulfurophane? No idea. Not covered in this paper.

Well, okay, since we are basically stumbling around in a dark room trying to figure out what is happening, let’s take the worst possibility – that sulfurophane acts as a Nrf2 activator in exactly the same mode as oltipraz. In that case don’t use either if you are hyperglycemic. Get your hyperglycemia under control before inducing Nrf2 in your kidneys.

Although, chances are that oltipraz and sulfurophane are doing 10 other things beside dis-inhibiting Nrf2 and some of these 10 other things mitigate or aggravate damage-causing processes in some kidney cells in the presence of hyperglycemia.

If you are doing Time Restricted Eating, you are already spacing out the sulfurophane. I’m not sure what sulfurophane’s half-life is, though.

A news report about this paper was posted to Steve Gibson’s grc.health news group. Although it has this undercurrent of “auto-immunity”, it doesn’t really seem to be about that. Or at least not in the typical sense one sees the immune system invoked.

This appears actually to be a metabolic hack that involves triggering a set of immune cells in the blood of T1D patients given the vaccine to use glycolysis non-aerobically in non-hypoxic conditions. That is, “aerobic glycolysis”. These cells then apparently become a sink for sugar, fermenting it to lactic acid or otherwise shunting it off into other pathways. As a result the T1D patents given these vaccinations dropped their A1C’s from 7 to 6.

A few oddities about this process. (1) the drop in A1C occurs 2-3 years after the vaccinations but then seems durable – still in effect 5 years later and (2) it doesn’t impact the production of insulin by the pancreases of the patients. The patients are still diabetic, they just have better blood sugar control.

If you go into the paper understanding that it really is a metabolic hack that causes the drop in A1C’s it is much easier to understand. That said, BCG vaccination has also been used to treat a type of bladder cancer and multiple sclerosis. The latter presumably must be through actual immuno-modulation, right?

Is there any indication what minimum level of beta-hydroxybutyrate would be necessary for this protection. That is could this be achieved by just taking a couple of grams of an exongenous beta-hydroxybutyrate salt.

From the paper: “Cellular quiescence is a crucial process for maintaining the stemness of embryonic stem cells (ESCs) through inducing autophagy. We did not show sufficient results to prove β-HB induces autophagy and autophagy-dependent cellular quiescence (An et al., 2014, García-Prat et al., 2016). However, we predict that β-HB can induce autophagy in vascular cells, as well as ESCs, based on our observations of AMPK activation and mTOR inhibition by Oct4 upregulation after treating with β-HB in vascular cells. ”

@rhonda – is this enough to make you consider a ketogenic diet? Since I started ~8 hour TRE, I have no difficulty maintaining >2mM BHB fasted most mornings of the week.

BTW, @RadioheadKush Peter Attia recommended this critique of the study:

http://www.zoeharcombe.com/2018/08/low-carb-diets-could-shorten-life-really/

It would be good to see Rhonda’s view on this, I’ve noticed a number of studies on mice with ketogenic diets that come to the same conclusion as this study. The key failure point for me is that fat is not a natural diet for mice, does the study have any relevance for humans or is it designed for failure?

Meh. Hazard ratios below 2 – probably just looking at statistical noise. Although extremely high or low carbohydrate consumption might have been a marker for lower overall interest in ones personal health.

Pmiguel. Excellent content. Thankyou. I on the have followed a ketogenic diet for the past 3 years. I test ketones regularly out of interest, I do not aim at raising ketones, I find following a real food diet, limiting white carbs keeps me in the low nutritional ketosis range approx 0.5 to 0.8mmol quite easily. Sleep effects it, type of exercise effects it. High intensity resistance training or metabolic conditioning circuits knock me out of ketosis, to drop back in later in the day, steady state endurance for an hour will drop me back in if I am out after a cheat meal.

Eating a sugary cake will make me lie down and be lazy for a couple of hours after, however if I have new potatoes in a meal it has no effect.

I started the diet 3 years ago, lost 30lbs in 2 months. Whilst reducing exercise incidently.

I still eat the same way (I am a monotonous creature of habit with meals) and in the following years my weight has regained 20lbs. However my fat percentage has not increased. It is currently 9.7% via dexa. Interestingly my muscle mass has been increasing from when my bodyweight hit its lowest %. I practice bodyweight callisthenics each day as the stimulus. For me, a ketogenic diet has been excellent.

Here you go: this is a much better study. Clearly not “pro-KD” by any means. (This is 2010, the pro-KD camp would be a very tiny minority at this point.) The authors still seem to believe there is something bad about the effects of the KD, but at least they looked into and found that these “negative” effects were “rapidly reversed upon cessation of the diet”.

Again, Virta Health’s success reversing T2D using KD as well as studies showing increased average lifespan of mice fed a KD – as long as they were not allowed to become obese eating it – indicate the effect described are not ultimately harmful.

Discussed in another thread, but this letter to the editor politely (but completely) refutes “Impaired glucose tolerance in rats fed low-carbohydrate, high-fat diets” link: https://doi.org/10.1152/ajpendo.00208.2013

which, I think, is often the source of the “KD leads to T2D” meme. The meme seems absurd given Virta Health’s success in reversing T2D. But absurdity is no bar to meme propagation…

Hi pmiguel, many thanks for taking the time to review the study and article, and also for your insight.after reading the study at source thanks to your link I totally agree with you, I should be less naive when reading press releases in future, it’s interesting that a number of UK newspapers published similar articles denouncing a ketogenic diet on the back of this study yesterday, after reading the study it’s evident the articles are disingenuous. I wonder what is the agenda for someone to feed a flawed analysis to multiple national press outlets to discredit a diet that has immediate weight loss benefits when the lay person tries it.

Hi Magonrag, I think the medicalxpress.com coverage of this paper: https://physoc.onlinelibrary.wiley.com/doi/full/10.1113/JP275173 is poor. Actually it is probably just click-bait. The paper itself doesn’t promote the perennial canard “KD makes you T2D!” After a cursory look at it, I think it is looking at the metabolic differences between a KD and the so-called HFD. Of course mice aren’t just tiny humans and this isn’t their natural diet. But neither is mice chow. And very few human eat anything approximating a natural diet.