I know full well that this is not the sort of post most people love.
I also know full well that the only thing that makes me a blogger people pay attention to is that lacking some fundamentals of sciences, I nonetheless have a keen sense of contradictions, posturings, logical fallacies, diversions, syntheses, and integrations. A is A.
For over a year now, I and several collaborators collectively known as “Duck Dodgers” have engaged in a dispute with Mike Eades—a dispute that he has no time for, except to take a lot of time reminding everyone how little time he has. In spite of everyone having their own opinions on how I ought to conduct my affairs, not a single vowel of an alphabetic integration—mixed with consonants of discord—means a runny shit to me. It’s my blog: there’s the door.
…A lot of time recently has been spent in Eades’ comment section—330 of them and counting—and much of it reads like some of my own comment threads. You’re perfectly free to not care a wit about it; but I do, and I disagree with all notions that I ought not take this with the utmost of seriousness. It’s extremely serious to me, and it goes way beyond the Inuit and Ketosis. There’s the door.
It goes to basking in the comfort of sycophants. A man who would take it easy long-term defending basic dogma, rather than embrace new discovery, knowledge, and understanding: synthesize and integrate them.
We’re dealing with a basic Guru.
“If you meet the Buddha, kill him.” — Linji
So Eades decided to put Duck Dodgers in his place; this, after promising for a year or more to “don’t worry, an answer is coming right up. It’s just basic biochemistry.” …If you’re unfamiliar with the background, there’s plenty of link fodder to go chasing after if you’re better than demanding to be fed with spoons. You can start here.
Basic-psychologically, Eades has gone all in on his necessary delusion that none of “Duck Dodgers” understand basic biochemistry. (It’s really advanced biochemistry; but this is the sort of characterization basic Gurus deal in for basic Guru-reasons.)
March 3, 2015 at 4:09 pm
What’s uncoupling? If you don’t know, you shouldn’t be throwing the term around.
This isn’t a debate between Peter and me, it’s between you and me. You’ve made it personal, and now when you’ve been caught in a bunch of BS showing how clueless you are about the very fat burning (for heat, as I recall) you’ve been touting, you try to foist the whole thing off as a disagreement I have with Peter.
Just so you’ll know, fats are burned in the mitochondria. They have to get in there somehow, which they do by riding in on carnitine. Attaching the fatty acid to the carnitine requires the enzyme CPT1 (and CPT2 to get through the inner mitochondrial membrane, but the CPT1 is the rate limiting enzyme). So if all Eskimos have CPT1 deficiencies, how do they get the fat in their mitochondria to burn for heat as you suggest? And if the CPT1 deficiency is widespread, how do Eskimos burn fat if they can’t get it into the mitochondria where fat is oxidized? Unlike glucose, fat can’t be burned other than in the mitochondria.
Only once the fat is burned can there be uncoupling. Uncoupling is involved in the electron transport chain, which basically consumes energy (thrown off by fat oxidation) to creates an electrochemical gradient across the inner mitochondrial membrane. This gradient is what ends up powering the turbine-like crank to make ATP. So you’ve got the electron transport chain coupled with oxidative phosphorylation, which is the process of making ATP. Uncoupling occurs when the energy required to create the electrochemical gradient is somehow dissipated and ends up not being used to create ATP. In other words the process of creating the gradient is uncoupled from the process of producing ATP.
Would you care to speculate as to how this uncoupling occurs? Or what the end result is?
Or do you need another round of basic biochemistry instruction so you’ll know the answers to those questions?
Notice how he’s finally and thoroughly detailed how the Inuit are in perpetual ketosis, so keto-adapted that neither ketones nor their by-products can be detected in Eskimo, how they eat high fat, moderate protein year round, don’t need fat for lamps, cooking, or dogs, etc.
Here’s the thing. The Duck Dodgers had been chewing on the questions Eades posed for about a day. When dealing with the CPT1a mutation and FFA oxidation a-la Eskimo, there are papers that both answer and raise questions. It’s a bit beyond basic. But because Eades is basically most of all concerned with the basic integrity of basic low-carb dogma, he basically missed important distinctions.
Even basic veterinarian Peter seems to take it that way (but all of it prefaced as basic speculation), as he’s basically unblessed with Mike’s basic certitude of all being basically settled on the basic basis of basic biochemistry. Sometimes though, advanced thinking is required. Peter wrote:
This is not quite so simple.
Uncoupling is one component. Uncoupling respiration generates heat. There might just be a positive advantage to running your metabolism fairly uncoupled in a very low temperature environment. Elevated FFAs are completely essential to uncoupling and heat generation. Limiting fatty acid removal from the cytoplasm to the mitochondria might be a facilitator of uncoupling. It’s FFAs on the cytosolic side of UCPs which facilitate proton translocation. Having a higher level of cytoplasmic FFAs at a given level of plasma FFAs might give an advantage over the normal level of uncoupling seen under near ketogenic diet conditions.
Fortunately, we have Dr. Eades to basically brush it all aside.
Well sure. When everything hinges on proclamations of “just basic biochemistry,” then everything’s a nail, as they say.
Whereas, there’s way, way more abnormal identifications that require integration (vs. “interpretation”) at that post. Like this from Peter, once again:
The paper itself is largely an account of the detective work involved in pinning down a specific mutation which has been positively selected for in a Siberian population living in the Arctic. The same mutation is also present in non related groups inhabiting the Arctic areas of northern America. The mutated gene is very common and frequently homozygous. It puts a leucine in the place of a proline in CPT-1a, the core enzyme for getting long chain fatty acids in to mitochondria. Putting a leucine where there should be a proline means the protein is basically f*cked. The mutation is linked, not surprisingly, to failure to generate ketones in infancy and can be associated with profound hypoglycaemia, potentially causing sudden death.
In his haste to brush up on his basic understanding of CPT1a, Eades seems to have only accounted for 70’s-era basic biochemistry—where all carnitine palmitoyltransferase were about the same. The thing is: they aren’t. In fact, they all do different things, and the Eskimos only had a deficiency in CPT1a. It’s what you call a basic critical distinction.
The mutation that causes a deficiency in the Mark 1, Mod A form is more prevalent along coastal regions where polyunsaturated fatty acid intake was high (i.e., seafood). The Eskimos were known to be strong, intelligent, and could generate their own heat (they felt warm to the touch). To be an autosomal recessive mutation, it must be highly selective, since it causes hypoketotic hypoglycemia: low blood ketones and low blood sugar. Which, in practical day-to-day living, means: difficulty fasting. Another basic critical distinction. For example, in Pic = 1,000 style: Mouse white adipocytes and 3T3-L1 cells display an anomalous pattern of carnitine palmitoyltransferase (CPT) I isoform expression during differentiation.
Notice how CPT1b is highly active in Brown Adipose Tissue (BAT)?
So, leaving basic biochemistry to Dr. Eades, how about we get into some speculative advanced shit? Keep in mind that it requires only that you can think, spot contradictions, syntheses, and integrations—connections. You don’t need a degree and you haven’t to have passed a test on a bunch of shit you had to memorize but never truly understood, integrated, or connected to actual observations. In that same comment thread, Eades spurns Googling. Well of course. All Gurus hate Google—except for themselves.
This is by no means exhaustive “Duck Dodgers.” Just basic bullets representing a bit of basic chewing on possible contradictions between basic biochemistry and what has been more recently discovered, enlightened, or understood, demanding integration and synthesis. We call this advanced biochemistry; or, basic thinking. It’s not exhaustive, just basically a culling of a bunch of emails with ideas Duck Dodgers collectively tosses around.
- Brown fat, where thermogenesis takes place, has CPT1b, not CPT1a.
- The Eskimo genetic mutation we’re dealing with here involves CPT1a, not CPT1b, or even CPT1c.
- CPT1a is primarily associated with liver cells
- CPT1b is primarily associated with brown fat, skeletal, and heart muscle cells
- CPT1c is primarily associated with brain cells.
- Infants in general have lots of brown fat. Eskimo infants are at the greatest mortality risk for the CPT1a mutation. Is FFA oxidation via CPT1b in brown fat what primarily gives them a chance vs. ketones, that aren’t produced as normal in the liver? Do Eskimo adults retain more brown fat than humans in temperate climes?
- Consider basic bears. Basically, they’re enormous mammals that live in frigid to fucking cold environments, such that there’s only enough food in late spring, summer and fall to feed them for an entire year. So they have adapted to hibernation for 6-7 months. They don’t do ketosis, even in a 7-month fast-hibernation.
- Bears and other hibernating mammals have lots of brown fat.
- Does the CPT1a mutation protect Eskimos from excess production of methylglyoxal that specifically targets mitochondria, and inhibits manganese superoxide dismutase, since FFAs aren’t getting into the liver to produce acetone, a precursor to methylglyoxal?
- How about CPT1a residual enzyme activity on cultured skin fibroblasts? Well, in people with a CPT1a deficiency, the residual activity is 1-5%, but in Inuit with the myopathic phenotype, the activity is 15-25%. All CPT1a abnormality is not created equal.
- Or…Brown Adipose Tissue (BAT) is a clue is a clue; thyroid is a clue; mitochondrial DNA is a clue; high N-3 PUFA matters. Gut flora? Rotten meat and blueberries? All that together?
There’s a lot more, but let’s jump to a couple of studies for basic fun.
Arctic populations live in an environment characterized by extreme cold and the absence of plant foods for much of the year and are likely to have undergone genetic adaptations to these environmental conditions in the time they have been living there. Genome-wide selection scans based on genotype data from native Siberians have previously highlighted a 3 Mb chromosome 11 region containing 79 protein-coding genes as the strongest candidates for positive selection in Northeast Siberians. However, it was not possible to determine which of the genes might be driving the selection signal. Here, using whole-genome high-coverage sequence data, we identified the most likely causative variant as a nonsynonymous G>A transition (rs80356779; c.1436C>T [p.Pro479Leu] on the reverse strand) in CPT1A, a key regulator of mitochondrial long-chain fatty-acid oxidation.
Remarkably, the derived allele is associated with hypoketotic hypoglycemia and high infant mortality yet occurs at high frequency in Canadian and Greenland Inuits and was also found at 68% frequency in our Northeast Siberian sample.
We provide evidence of one of the strongest selective sweeps reported in humans; this sweep has driven this variant to high frequency in circum-Arctic populations within the last 6–23 ka despite associated deleterious consequences, possibly as a result of the selective advantage it originally provided to either a high-fat diet or a cold environment.”
Shorter American Journal of Human Genetics: Ketosis is shit. Need something better, like brown fat. Wouldn’t it be deliciously ironic if, in the end, it turns out that the primary justification for the purported “magic” of ketogenic diets—the Eskimo—were genetically dumped from that ability thousands of years ago for various reasons? I adore iconoclasm above all else.
Only in error does one attain certainty. And only in the relentless pursuit of honestly integrated understanding does one attain error. — Me
Here’s something new, from January, 2015:
- Adipose fatty acid oxidation (FAO) is required for cold-induced thermogenesis
- Adipose FAO is required for agonist-induced thermogenic gene expression
- Loss of adipose FAO does not alter body weight
- Adipose FAO is required for high-fat-induced oxidative stress and inflammation.
To understand the contribution of adipose tissue fatty acid oxidation to whole-body metabolism, we generated mice with an adipose-specific knockout of carnitine palmitoyltransferase 2 (CPT2A−/−), an obligate step in mitochondrial long-chain fatty acid oxidation. CPT2A−/− mice became hypothermic after an acute cold challenge, and CPT2A−/− brown adipose tissue (BAT) failed to upregulate thermogenic genes in response to agonist-induced stimulation. The adipose-specific loss of CPT2 resulted in diet-dependent changes in adiposity but did not result in changes in body weight on low- or high-fat diets. Additionally, CPT2A−/− mice had suppressed high-fat diet-induced oxidative stress and inflammation in visceral white adipose tissue (WAT); however, high-fat diet-induced glucose intolerance was not improved. These data show that fatty acid oxidation is required for cold-induced thermogenesis in BAT and high-fat diet-induced oxidative stress and inflammation in WAT.
It has a cool image too.
Notice how you don’t need CPT1a to generate body heat through thermogenesis? Lacking CPT1a preferentially shunts FAs to brown fat cells.
I ferociously enjoy all of this on a number of levels. First and foremost is that I’m integrating new understandings and insights with virtually every email exchanged between The Duck Dodgers. Second, I appreciate my role as the primary publisher of the distillation of an amazingly vibrant collaboration.
Our chief aim is always to get a bit more right by identifying and setting aside that which is obsolete, in spite of its Newtonian usefulness for its time. We don’t wait impatiently on asymptotes, but rather embrace their nature of getting ever closer.
As to Dr. Eades, well, I’ve just seen too much to be able to give him a pass and chalk it up to too busy, but trust me it’s basic. Just hours ago, this:
That was the first paper I read. Do you just have the abstract? The entire paper is filled with weasel words, which tells me that authors are speculating about everything. Which they ultimately end up saying.
I’ve seen it so many times since I first began reading him in 2007. There’s so many ways to unpack that, other than the way I used to do, which was to think “thanks Mike for showing me The Way, The Truth, and The Light.”
My path towards understanding how he always—100% of the time—has some fatal-flaw problem with studies that contradict low-carb dogma—while regularly adoring nonsense from Phinney, Volek***—and other papers that seem to only primarily reference Phinney and Volek—came courtesy of Anthony Colpo. See, I actually read The Fat Loss Bible, a book that goes into excruciating detail over every single metabolic ward study comparing different dietary regimes.
And guess what? There’s really not a dime’s worth of difference in terms of fat loss. It really is predominantly about CICO. It just is. I use the term predominantly rather than all, because I do think that real food that includes sane levels of fat and is low in refined forms of sugar helps one better eat an appropriate amount, and not too much too often.
And then I think back at the exchange of blog posts between the two and for the most part, Anthony is quoting studies (like The Duck Dodgers) while Dr. Eades dazzles with basic biochemical medical pathways, since none of the studies can be trusted.
And now it’s the same thing all over again, here.
To close by drawing an analogy, Eades’ methods parallel those of constitutional law. In our legal system, we begin with a constitution and three branches of federal government. Two of them are legislative, and one—the Supreme Court—is judiciary. So, two branches composed of politicians making laws, and the Supreme Court is supposed to make sure they pass muster with the constitution. Basic stuff.
Only, that’s not how it works. How it works is that politicians need to be elected and re-elected, and promissing the best and most bread & circuses is the prime means by which that’s accomplished. Members of the high court are also appointed by these politicians and the chief way a judge gets a look is in the record of decisions and opinions whereby the constitution gets “interpreted” in a way that makes politically motivated laws promising the best and most bread and circuses constitutional.
So, rather than just read and understand the plain English in which the constitution was written, it requires constant interpretation.
Now, note how very often Eades writes of the need to “interpret” various studies “properly.” What this means is that either they are by Phinney, Volek—or by someone primarily referencing them—and they’re constitutional, or, they’re not; and if in contradiction to the constitution, require dismissal or interpretation as needs arise. I’m more of a “common law” guy. Post it, see how it floats, go with it or drop it.
Essentially, what the LC community is up to is the establishment of echo-chambers similar to the low-fat, cholesterolphobes, and statin pushers.
*** For a current example, see in that comment thread where Eades touts all the marvelous athletic performance by athletes doing keto diets and specifically cites Phinney.
Phinney did all the early work on the ketogenic diet and athletic performance. I know him well and have had many discussions with him about it. And heard him speak on his early experiments numerous times. When he did this work, he was trying to disprove the Atkins diet. Didn’t turn out that way.
(Reminds me of the fundie born-agains telling me when I was a kid that “30 scientists set out to disprove the Bible and ended up accepting Jesus as their personal Lord and Savior.”)
Anthony Colpo just recently demolished that worthless bullshit study of Phinney’s once again. Dogma Destruction: Phinney’s Dodgey Ketogenic Cyclist Study Revisited.