Tuesday, April 26, 2016

Dave Asprey and Dr Veech

Dave Asprey has a very interesting extended discussion with Dr Veech on his Bulletproof website, mostly about ketones but also about the history of biochemistry and a number of other subjects. Dr Veech is very pro ketones while being surprisingly anti high fat diets, an interesting combination and clearly far from my own perspective. Much of the interview is simply fascinating in its own right but I'd just like to talk about the aspects with which I disagree. As one must.

Exclusive: Interview with Ketone Expert Dr. Richard Veech

The section of interest is around one hour five minutes in to the discussion. For those who would like some flavour of Dr Veech's uncomfortable stances on a fat based diet, cardiologists and cholesterol you can grind your teeth through the ten minutes leading up to that point. It's pretty obvious that Dr Veech has a lot of reading to do on cholesterol and cardiovascular health, should he so wish.

I had to correct a few relatively minor typos, nothing to do with what was said, just how it got written down, so I've put up the original text followed by my edited version. I've listened to this section three times now and I think my modified transcript is correct:


Dr. Veech: However, when you’re burning fat, you’re going through beta-oxidation. One reducing equivalent goes to NAD and one goes to pflavo protein. You’ve already lost 1/3 of your ATP in that step. Go back to your lennature Lehninger, beta-oxidation, you do one NADH, you do one NADH, you do one pflavo protein. You do that to keep from blowing the mitochondria up.

Tidied up:

Dr. Veech: However, when you’re burning fat, you’re going through beta-oxidation. One reducing equivalent goes to NAD and one goes to flavo protein. You’ve already lost 1/3 of your ATP in that step. Go back to your Lehninger, beta-oxidation, you do one NADH, you do one flavo protein. You do that to keep from blowing the mitochondria up.

I sold my copy of the biblical Lehninger at the end of my second year at vet school when we finished biochemistry as a subject in its own right. I have to say I really enjoyed the book. I also midnight question-spotted the urea cycle for my biochemistry written exam and it came up. Yeaha!

Sooooooo. Yes, beta oxidation (of saturated fats) does indeed yield one FADH2 which is embedded in a flavoprotein as well as generating an NADH. Electron transporting flavoprotein (ETF), which docks with ETF dehydrogenase, reduces the CoQ couple and omits pumping the four protons which could have been pumped had a second NADH been generated instead. My back-of-an-envelope calculations suggest an NADH could have been generated instead of the FADH2. This does indeed waste a four protons worth of the ATP which might have been generated.

And yes, the FADH2 is generated to stop damage to our mitochondria. So fats are bad?

With some slight discomfort I have to re-cite (yet again) the Protons thread. The whole point of generating inputs which reduce the CoQ couple is to drive reverse electron flow through complex I. Low levels to trigger insulin signalling, high levels to resist insulin signalling. H2O2 is the second messenger.

The waste of proton pumping by supplying FADH2 at the CoQ couple is offset by it being used to regulate the system. This applies to mitochondrial glycerol-3-phosphate dehydrogenase, driven by glycolysis, or ETFdh driven by beta oxidation of saturated fats. Both initially assist insulin signalling and, as substrate throughput increases, they facilitate resistance to the signal from insulin to accept more calories.

Another sooooooo. FADH2 is, I agree, wasteful but more importantly it also drives reverse electron flow through complex I. And undoubtedly you can have too much of a good thing. Waaaay back in the early Protons posts I spent a lot of time looking at FADH2:NADH ratios and decided that somewhere around palmitic or stearic acids there was a maximum healthy FADH2:NADH ratio, somewhere around 0.48. At that time Dr Speijer was kind enough to supply his paper looking at the development of the peroxisome in LECA, the Last Eukaryote Common Ancestor (not to be confused with LUCA, of the hydrothermal vents).

One major function of peroxisomes is to deal with very long chain fatty acids using a beta oxidation version which does not generate FADH2. Problem solved, no need to blow a gasket in our mitochondria. In fact the peroxisomes shorten VLC fatty acids to octanoate, much beloved of Dave Asprey and Dr Veech.

Minor aside: How might you explode your mitochondria if Dr Veech's concerns were correct re FFAs and his idea about FADH2 being used to reduce the supply of pumped protons from complex I? There is a technique to completely flood your mitochondria with NADH. It's called beta-hydroxybutyrate, particularly if supplied in large amounts from ketone esters. This enters the mitochondria using the monocarboxylate transporters, generates NADH as it converts to acetoacetate then goes on to generate three more NADHs from each of the two acetyl-CoA entering the TCA. These NADHs are potentially capable of pumping membrane popping numbers of protons through complex I, without concerning Dr Veech. And without actually doing any damage, that I can tell. End aside.

Next minor aside: Free fatty acids are not going to explode your mitochondria: Under ketogenic high fat eating there is a combination of elevated free fatty acids (happy happy), low insulin (so no loss of FFAs through insulin induced triglyceride formation), plenty of ATP in the mitochondria to allow uncoupling proteins to function (UCPs must have generous ATP on their mitochondrial matrix end to allow them to function) and those ad lib FFAs are necessary and available to actually carry the protons through the uncoupling proteins. FFAs are essential for uncoupling, no FFAs = no uncoupling, pax mtG3Pdh. FFAs = uncoupling = no exploding mitochondria. End second aside.

I'm left here with my view of a healthy metabolism as one based around beta oxidation of saturated fatty acids. Ketones as they happen, no stress. Nothing originating from the discussion has budged my entrenched position in the least, interesting though it has been to listen to.



raphi said...


However, i will need the TCA cycle open next to me & a calculator to ingrain this post.

Fat phobia cuts so deep, it never ceases to surprise me - i'd have never guessed this by Veech!

Unknown said...

So glad you went back to look. I hope you continue on this proton path. It is where the pot of gold lies Peter.

Puddleg said...

With some very heavy irony, increased beta-oxidation in muscle is suggested as a means to avoid statin side effects in this paper, because statins, if lactones are formed in the gut, muck up complex III.

bill said...

You're right. I did grind my teeth
a bit listening to him scaremongering.

Passthecream said...

Not sure if this comment belongs on the previous ketone post or this one, they overlap. I recently bought some purified c-nut oil. It is an almost odourless clear liquid at room temp supposedly containing a higher level of mct's.

Gulped about 75 ml, neat, and fairly soon afterwards experienced what seemed to be a reactive hypo. Reading around i soon discovered this is quite common from coconut oil. I suppose because it quickly converts to ketones which trigger insulin which in turn supresses ffa and shaky-crazy hunger results. More quickly and strongly with this purified version it seems.

I am t2d and i aim to be running on fat if at all possible although i find it difficult to generate high levels of either bohb or aca. Must be running on something since I'm not losing much weight but i don't eat much cho and tag levels are low.

Wooo wrote some good ideas about this after her experiments with ketone salts. Partic this:

' in normal metabolism (starving or a deep keto diet) you can never end up in a situation where ketogenesis is so much that it inhibits FFA beta oxidation (which is *vastly* more important to energy needs of body in keto adapted people!) . However, if you have a crappy keto and you drink ketone salts, this is suddenly VERY POSSIBLE. Especially if your metabolism sucks and your FFA oxidation rate is low because of that.'

So maybe ketone salts are fine to consume if you're not already fat adapted/ketone producing or diabetic with damaged metabolism but otherwise they seem a bit like glucose in their outcome. This might explain Veech's fat phobia too, in the context of liberal dosing with ketone salts, misguided as it is.


Passthecream said...
This comment has been removed by the author.
Passthecream said...
This comment has been removed by the author.
raphi said...

I listened to the interview this morning. if i heard correctly (the audio is a bit choppy), Veech seemed to be relaying the worries of the Mayo cardiologists about climbing cholesterol/LDLc on ketogenic diets. He also disparagingly mentioned Merck's interest in profiting from statins.

Now, even if he doesn't agree with those concerns and was simply relaying those hold by other medical professionals, that's still no excuse to avoid explicitly coming down hard on the veracity of the fat-cholesterol-CVD connection...especially for someone in his position! He should know better.

At least im happy he told Dave Asprey (in a roundabout way) that the problems Asprey encountered on his 'ketogenic all-meat diet' was likely due to failing to do what the Eskimos actually did...

WilliamS said...

Peter, IIRC not very long ago you said that in the context of living a life, and limiting carbs as you do, restricting protein as well wasn't a practical option for you. But now you seem to be doing so. I'm curious what may have changed your thinking.

I find Ron Rosedale's arguments for protein restriction compelling, but Bill Lagakos seems right to say that while Rosedale's mechanistic arguments are convincing there is no data on real outcomes in humans to back them up.

altavista said...

That's cute, but does it all this really matter? If you're from Europe and under 70ish, forget about it.



Peter said...

William, yes, a lot of things have changed in the last year or so, especially retiring. Probably worth a post some time. Ultimately I have pretty well given up breakfast and so don't manage so many eggs. They tend to get grouped in to 12 or so yolks about once a week, more cream in general and still a fair amount of 90% cocoa choc...

altavista, your post puzzles me. Do you mean that the radiation hormesis benefits mean that minimising mTOR doesn't matter? Or are you worried about radiation exposure?Each to their own.


altavista said...

Congrats on your retirement.
I was just venting my frustration with it all. If reindeers have 8,000 becquerels/kg after 30 years, is a perfect understanding of mTor really going to have an impact on our health? Rant off.

Peter said...

Are the reindeer sick?



WilliamS said...

Would be great to hear your thoughts sometime about the evidence supporting protein restriction. It makes sense to me mechanistically, and I try to do it, but it would seem to have vastly less supporting human data than carb restriction. And it can be challenging when the cream and ghee containers aren't handy.

Galina L. said...

Yesterday I was chatting with a fellow customer in an ethnic Eastern European store. She lives half of year in Florida, but in May moves back to her native Latvia for 6 months to escape Floridian heat. She takes her cat everywhere, that cat refuses to eat anything but beef. The cat routinely grows fatter while living in US, but gets leaner in Riga. Go figure.I hope my comment is not complitely out of the main theme of discussion. It is not easy to pay attention to the quality of protein while living in US. Cheap meat in US is so tempting to buy and it tastes great. I try to get more of lamb and quality beef, but often just can't resist prices.

Boundless said...

re: …cat refuses to eat anything but beef. The cat routinely grows fatter while living in US, but gets leaner in Riga.

How are cattle raised and finished in Lativa? If they are usually pastured, vs. the feedlot process used in the US, then we have multiple suspects:
• fatty acid profile is inflammatory in US
but it could also be:
• second hand growth hormones
• second hand antibiotics

altavista said...

Peter, I'm all for counterintuitive solutions, but curing cancer by 97% when they cant count mSv - Sv properly? Not to mention ingesting glowing food is different delivery method than full-body low dose.

"The Institute was established in 1968, with primary responsiblity for nuclear weapons development. INER's current primary missions are to advance nuclear technologies, assure nuclear safety and promote the well-being of the people in Taiwan"

Galina L. said...

Sorry, guys, for reporting a random chat with a stranger. As far as I know rules for beef production in Latvia should be the same as in any European country.

Peter said...

Galina, that's possibly the answer. Much of USA beef is not considered fit for human consumption in Europe... Some is now imported to the UK but only if not growth promoter treated. I wonder if we check that or just take the exporter's word for it?


Galina L. said...

Wiki said that "The EU did not impose an absolute ban. Under veterinary supervision, cattle farmers were permitted to administer the synthetic versions of natural hormones for cost-reduction and possibly therapeutic purposes, such as synchronising the oestrus cycles of dairy cows." On a positive side, hardly anyone follows the same diet as that freaky cat.

Peter said...

So we still buy the "jab a hormone, make a buck" stuff.... Sigh.


Passthecream said...

Lehninger fifth ed, free download, all 1294 pages.


Rattus said...

Peter, do you think that in the former quantities of egg yolks you were eating [around 6 every morning) along with the high quantities of dairy fat that constitute most of this kind of diet, that omega 3-6 balance could become somewhat of an issue?

Malcolm said...

Peter, I'd be interested if you would post another "what do I eat" blog at some point. Perhaps this one could be more about what quantities of each macro, type of fat, vitamins etc etc you think the average (reasonably healthy) person should eat? Or just an update of what you personally eat, obviously the format is up to you.