New from Japan: Five Tips to Surviving Foundation Japanese

From Grace Under Pressure

"Five Tips to Surviving Foundation Japanese"

My daughter got a job writing for the school website. This is her first post.

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Thoughts on "Cardiolipin Synthesis in Brown and Beige Fat Mitochondria Is Essential for Systemic Energy Homeostasis"

Interesting confirmation of a core mitochondrial functional role for cardiolipin, and some interesting observations about cold-adaptation.

Get used to shivering! 

"However, the ability of adipose tissue to expend energy is a dynamic process that continues to increase with prolonged cold exposure, only reaching maximal capacity after several weeks (Cannon and Nedergaard, 2004)."

And clearly staying warm is overwhelmingly dependent on fat metabolism.

"However, the enrichment of lipid metabolism proteins far eclipsed that of proteins involved in all other metabolite pathways from 3 days to 3 weeks of cold exposure (Figure 1B)."

This likely explains why overweight people or inactive people have such a problem staying warm. Fat-burning capacity is dependent on stimulus, and while this doesn't show it, it likely atrophies like every other function of the body. Use it or lose it.

One of the key questions around cardiolipin and omega-6 fat intake is: what is a cardiolipin supposed to look like? This is more evidence that they're not supposed to be saturated with linoleic acid, leaving them uniquely susceptible to oxidizing and producing toxins like HNE as they damage mitocondrial function.

"Newly synthesized CL is characterized by shorter, more saturated acyl chains, which can be remodeled by phospholipases, and acyltransferases through monolysocardiolipin (monolysoCL) intermediates to generate a diverse pool of CLs."

It shouldn't surprise that CL is produced in an ideal state. Why it so readily takes up linoleic acid is an interesting question...

The paper also claims that energy production in brown-fat adipocytes (fat cells) controls systemic glucose homeostasis and therefore type 2 diabetes.

I'm a little more skeptical of that claim, as I looked into the connection between mitochondrial dysfunction and diabetes, and it's not as clear as I would like it to be. If this was a clear mechanism, then it would suggest that people living in warm climates that never experience a need for cold thermogenesis would be more susceptible to diabetes, and we really don't see that.

They get it when the industrial diet is introduced, same as everyone else on the planet.

New from Japan: ‘Kao’ versus ‘Cow’ and Other Misunderstandings

From Grace Under Pressure

"‘Kao’ versus ‘Cow’ and Other Misunderstandings"

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LDL Cholesterol: You Aren't Always What You Eat, or Roundabout Ways to Improve Your Diet

Sometimes you read these papers and shake your head.

"Lowering Dietary Saturated Fat and Total Fat Reduces the Oxidative Susceptibility of LDL in Healthy Men and Women"

The troll who pointed me to this was trying to argue that this invalidated the claim that omega-6 polyunsaturated (n-6) fats are important in cardiovascular disease (I gather), since lowering saturated fat (see the title) lowered oxidation.

Oddly enough, he was almost right, but not quite.

Fat components

The intervention was to have fixed protein (15%), but a variable rate of saturated fat (SFA), to be replaced by carbohydrate (CHO), and fixed rates of monounsaturated and polyunsaturated fats (MUFA and PUFA, respectively). And they did a good job of detailing what the diet included, right down to the individual fats.

However you have to go to a different study to find all the details ("Effects of Reducing Dietary Saturated Fatty Acids on Plasma Lipids and Lipoproteins in Healthy Subjects")

To sum the variation, SFAs were 16%, 9%, and 5%; and CHO was therefore 48%, 55%, and 59%. MUFA was 14%, and PUFA was 7%.

The diet part of it seems to have been very well done, indeed. If you want some idea from where the food may have come, may I introduce you to their sponsors?

"The DELTA Investigators express thanks to the following contributors: AARHUS, Bertolli, USA., Best Foods, Campbell Soup Company, Del Monte Foods, General Mills, Hershey Foods Corp., Institute of Edible Oils and Shortenings, Kraft General Foods, Land O'Lakes, McCormick Incorporated, Nabisco Foods Group, Neomonde Baking Company, Palm Oil Research Institute, Park Corporation, Procter & Gamble, Quaker Oats, Ross Products Division/Abbott Laboratories, Swift-Armour and Eckrick, Van Den Bergh Foods, Cholestech, Lifelines Technology Incorporated."

Wow.

The troll was almost right because LDL oxidation did indeed go down in this study. But it went down for a reason that I wouldn't have expected, and which leaves me somewhat perplexed to explain mechanistically. 

The paper goes on ad nauseum along these lines:

"Convincing evidence suggests that oxidative modification of LDL plays an important role in the pathophysiology of atherogenesis (Steinberg 1997). In recent years, numerous molecular mechanisms have been proposed to explain the different oxidation pathways that lead to modification of LDL (Steinberg 1997). 

"One of the earliest steps in the generation of oxidatively modified LDL is the peroxidation of its polyunsaturated fatty acids (PUFA).3 The oxidative breakdown products of these fatty acids, such as malondialdehyde [MDA] and 4-hydroxynonenal [HNE], form covalent bonds with apolipoprotein B (apo B)..."

Yeah, yeah. Old news (the paper is from 2000), but here's where it gets odd:

"The results of the present study also show that LDL composition (LDL quality) affects susceptibility to oxidation. [It] was inversely correlated with the quantity of LDL oleic acid (r = −0.29, P < 0.01), and positively correlated with the quantity of LDL linoleic acid (r = 0.23, P = 0.04) and the 18:2-to-18:1 ratio (r = 0.52, P < 0.001). The oxidation rate was positively correlated with the 18:2-to-18:1 ratio (r = 0.24, P = 0.03)."

To lower n-6, cut SFA?

What?

So lowering SFA indeed made the LDL more resistant to oxidation. But it did so by lowering n-6 and raising MUFA in the LDL! SFA was basically unchanged.

A little Lipidology 101, MDA and HNE, mentioned above, aren't made from SFA, they're made from PUFA, and HNE is made exclusively from n-6. MDA and HNE pretty much are oxidized LDL. So you're not getting oxidized LDL from SFA in the body. It just won't happen.

Of course the authors don't mention that little fact. More below.

For some reason I am unable to explain, lowering SFA (16:0, palmitate in the chart) in the diet lowered n-6 (18:2, linoleate) in the LDL, and increased MUFA (18:2, oleate), protecting LDL from oxidation. SFA stayed  the same, basically.

My best guess is that it was the increased CHO in the diet (is this what's behind the Japanese diet, which is low in SFA and high in CHO?) but it is just a guess.

"In the present study, the ratios of 18:2 to 18:1 and PUFA to MUFA in the LDL from subjects when they consumed the Step-1 and Low-Sat diets were significantly lower than they were in the LDL from subjects when they consumed the AAD. Linoleic acid (n-6) in LDL from subjects when they consumed the Low-Sat diet also was significantly lower compared with those from subjects when they consumed the AAD. "

The first citation for this paper is:

"Oxidation of low-density lipoproteins: intraindividual variability and the effect of dietary linoleate supplementation"

"LDL oxidized faster after the linoleate diet than after the oleate diet... and produced more conjugated diene [that's bad] in proportion to the increase in LDL linoleate."

Here's where we get to the shaking my head part.

Why in blazes wouldn't you reduce the thing that is actually capable of causing the harm, as your first cite shows, and as your own study shows, is the source of the problem? Why keep n-6 flat and reduce something else, which through some round-about effect, lowers what you need to lower, the n-6?

Just lower the n-6 and you reduce the susceptibility for oxidation! They cite other papers that have done exactly that!

This study was done in 2000, did I mention that?

Think of the progress we would have made if they'd actually done what any engineer reading this paper would have told them to do. 

"N-6 converts to these toxins? You're proved that? Why not reduce the n-6?"

Let's not get too into conspiracies here, but on the face of it this study is clearly little more than a misleading advertisement for the sponsors listed above, who are forced to follow the United States Dietary Guidelines and replace saturated fats with the n-6 fat that their own research claims is harmful.

---

This post started with a twitter troll who cited the first-mentioned study:

I unblocked you and looked at your study. Declining oxidation in LDL tracks w/ declining n-6 LA content in LDL, while SFA flat and MUFA went up.

Interactions between FA is a fascinating topic, & may be due to CHO, but reinforces n-6 claim for LDL.

Figure things out, you said? pic.twitter.com/qSCu2qDkSF

— Tucker Goodrich (@TuckerGoodrich) April 26, 2018

Breakfast with Low-Carb Dr. Tro Kalayjian

I'm the one with the bunny ears.

I had breakfast with Dr. Tro this morning in poverty-stricken Greenwich, Connecticut this morning, where I believe he treats gunshot wounds or stabbing victims, or something. Or maybe broken fingernails from Ferraris. Not too clear on that, actually...

He's a fascinating guy, he was morbidly obese (see pic below) until he decided to commit to a low-carb and then zero-carb (carnivore) diet. After initially thinking the whole notion of "fat adaption" was nonsense, he became a convert after discovering how it worked himself, with guidance from a bunch of folks, including (I hope) yours truly.

You'd never guess he was ever anything but lean and healthy. It's really quite remarkable.

He seems like he's got all the motivations to make an excellent, scientific doctor (which is not an easy thing!), and I hope he goes ahead and opens the practice we were discussing. He wants to help people with obesity, and show them how to "get off all their pills", so two thumbs up for that!

We also discussed training; if people can rebuild tendons and ligaments in the middle of life, which is a project we're both working on; and dreadful doctor-run blogs.

And a bunch of other stuff. See his post below and the replies, including my attempt to follow-up on some of our discussion points.

Had an excellent chat with @TuckerGoodrich
Talked about gluconeogensis, seed oils, chronic biochemical stress, dose response of exercise and so much more... dude is smart!
Still got him with the bunny ears😜https://t.co/h6oLqwe3Ys pic.twitter.com/wkBT7DorPK

— Low Carb Dr. T (@TroKalayjian) April 26, 2018

Some nutritionist online told me that the #Keto diet is only good for losing water weight

I am so glad that I lost 145lbs of water in these past 2 years...

🤔#Ketogenic #lowcarb #lchf #jerf pic.twitter.com/1ZIT6pYYkD

— Low Carb Dr. T (@TroKalayjian) April 8, 2018

How Much Carbohydrates Should Humans Eat?

"Abstract: In the past, attempts have been made to estimate the carbohydrate contents of preagricultural human diets. Those estimations have primarily been based on interpretations of ethnographic data of modern hunter-gatherers. In this study, it was hypothesized that diets of modern hunter-gatherers vary in their carbohydrate content depending on ecoenvironments.

"Thus, using data of plant-to-animal subsistence ratios, we calculated the carbohydrate intake (percentage of the total energy) in 229 hunter-gatherer diets throughout the world and determined how differences in ecological environments altered carbohydrate intake. We found a wide range of carbohydrate intake (≈3%-50% of the total energy intake; median and mode, 16%-22% of the total energy). Hunter-gatherer diets were characterized by an identical carbohydrate intake (30%-35% of the total energy) over a wide range of latitude intervals (11°-40° north or south of the equator).

"However, with increasing latitude intervals from 41° to greater than 60°, carbohydrate intake decreased markedly from approximately equal to 20% to 9% or less of the total energy. Hunter-gatherers living in desert and tropical grasslands consumed the most carbohydrates (≈29%-34% of the total energy). Diets of hunter-gatherers living in northern areas (tundra and northern coniferous forest) contained a very low carbohydrate content (≤15% of the total energy).

"In conclusion, diets of hunter-gatherers showed substantial variation in their carbohydrate content. Independent of the local environment, however, the range of energy intake from carbohydrates in the diets of most hunter-gatherer societies was markedly different (lower) from the amounts currently recommended for healthy humans."

"Diets of modern hunter-gatherers vary substantially in their carbohydrate content depending on ecoenvironments: results from an ethnographic analysis"

"How fast can we run?"

"Marathon-ready Daniel Lieberman offers evolutionary perspective on Bannister 4-minute mile, human speed limits, and ‘Man Against Horse’".

"...He did talk about the kinds of shoes that he wore back in the day, and was fascinated by — and not particularly approving of — how running shoes had gotten so built up. He, like any fast miler, was a forefoot striker. We published a few years later the paper in which we made the argument that, essentially, prior to shoes pretty much everybody ran the way Bannister ran. He felt that was clearly the best way to run.

"I remember him describing how he had his shoes made by a cobbler in London. You couldn’t go to a shoe store back then and buy a pair of running shoes. He basically had to have his shoes custom made. I remember he discussed how hard it was to get the right kind of material — light but durable enough not to fall apart...."

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