Fasting, autophagy, and fat supplementation

(Michael Wallace Ellwood) #95

Sorry @richard this may be a bit off-topic for the original post, but your mentioning NEFAs reminds me of something I still haven’t fully got my head around, despite having studied LCHF diets, and more recently keto, for some time.

I believe that NEFAs and FFAs (Free Fatty Acids) are one and the same thing, and Wikipedia has just reminded me that the “free” does not mean that they are literally free-floating in the bloodstream, because they still need a “transport protein” (Wikipedia mentions albumin, but I think it could be other things (chylomicrons, or example?).

Anyway, these NEFAs or FFAs are, in principle, available for metabolism, i.e. are available as fuel. One of the things I learned (or thought I had learned) from Gary Taubes’ magnum opus “Good Calories, Bad Calories” (on my many readings/re-readings of it, over several years) was that the presence of FFAs in the bloodstream was a good thing, from the LCHF point of view.

However, from time to time, I see things from more mainstream sources implying that a lot of FFAs in the bloodstream is a bad thing.

Here, for example:

Would you care to comment / clarify my thinking in this area @richard?
Thank you!

(Richard Morris) #96

Yep, same thing. The esterification of fatty acids just means they have been bonding to an ester to make an acylglycedride - and usually we have 3 bonded to a glycerol make a triglyceride. It’s the storage form of fatty acids, and the NEFA form is the ready fuel version.

Non-esterified fatty acids aren’t as you say freely roaming as they have to be ported about by proteins. So Non-esterified fatty acids is a more accurate description than Free fatty acids.

Our fat burning cells get them from 3 places;

From inside massive lipoprotein particles called chylomicrons carrying triglyceride from the gut … will dock with the cell and they will use an enzyme called lipoprotein lipase to break a triglyceride into it’s 3 NEFAs and they are transported into the cell.

From inside Low density lipoproteins carrying fat from the liver, much the same process happens to extra a triglyceride out.

Finally when energy in circulation drops, fat cells release NEFAs bound to sheets of protein called albumin and that also carries the NEFAs through the circulation to any consumers. When glucose comes into the system, insulin goes up and that inhibits healthy fat cells from releasing NEFAs into the blood stream. When insulin drops, the fat cells start releasing NEFAs again. That is the daily switch between the fed and fasted state. Insulin going up or down based on when you eat determines if health fat cells release energy.

That is the one Gary Taubes was talking about, when he talks about NEFAS in circulation it’s the supply of energy from adipose when glucose is low, to a system that is good at burning fat. That is pretty much Keto perfection in a nutshell.

The problem identified in that paper is a description of what happens when the adipose no longer can store any more energy - which is adipose insulin resistance. The pancreas produces more insulin when there is fat in circulation (to try to get NEFAs out of circulation) when glucose is about - that’s one of the drivers of increasing pancreatic over production of insulin, NEFAs and Glucose both in circulation.

Why this is a problem, we have to go down to the level of the cellular consumers of that energy. We have a switch at the mitochondria in our cells where insulin inhibits us being able to quickly get fats in to be burned (the carnitine shuttle). When we have both NEFAs AND glucose (and therefore insulin) in abundance then we burn the glucose and the NEFAs build up in lipid droplets in our cells. Eventually that interferes with the ability to get glucose transports to the cell wall … and that is cellular IR in action.

I could be wrong about all that … but that is my understanding. Hope it’s helpful.

(Michael Wallace Ellwood) #97

Wow, thanks for such a rapid and comprehensive reply!

Will have to re-read (especially the last 2 paras) a few times to make sure I’ve got my head around it, but yes, very helpful thanks Richard.

(Julian Broaddus) #98
(Over Comer) #99

I just found this thread on this forum and I must say it is the most well-informed, comprehensive, and scientifically based discussion around. Perhaps someone could help me. I am a rather obese (50# overfat) menopausal woman who is extremely metabolically healthy. I have great cholesterol levels, FBGL in the mid 80’s, excellent blood pressure, and ALL extensive blood work was normal except slightly low white blood cell count and slightly low body temperature. However, I and my mother and sister ALL have slightly lower body temperature for all of our lives. My white cell count has ALWAYS been slightly low for years and years. I rarely if ever get ill. No allergies or autoimmune issues. I have been getting migraines for many years. Sometimes very severely. I have had MRI’s, blood work and ALL are negative. In saying ALL of that, I want to try fasting for several reasons: religious, weight loss, autophagy, and to deal with a binge eating disorder that occured after a long deployment. I made a 24 hour fast with no hunger or temptation issues. I DID vomit, get a migraine, and had diarrhea. I suspect that was lack of caffeine from reduced coffee intake. For those of you who are still with me :yum: my question is this: I REALLY want to induce autophagy without losing lean body mass, yet in a talk by Dr. Stephen Phinney he emphasized that LBM would decrease at fasts over 48 hours. That was actually the longest I planned to fast anyway but will I be able to induce autophagy in that short of time period given that I am probably NOT fat adapted and am a carb burner? I have other questions regarding hormone regulation specifically thyroid, leptin, the hypothalamus and pituitary but I shall save them for later. Thanks to anyone who would answer this long post!!

#100

There’s a great thread about Dr. Phinney and fasting here. Lets just say there is much disagreement with his extrapolation of numbers.

#101

Dr. Jason Fung’s main purpose for fasting is to reduce insulin and this is accomplished by avoiding foods that raise it such as carbs and then protein which is stimulated at only 50% of the rate that carbs stimulate insulin. Fat has an absolutely minimal effect on insulin which is on par with the gut-stretching effect of eating rocks raising insulin, but it is possible to over-consume fat to some degree that it affects insulin if someone is Insulin Resistant (IR).

Dr. Ron Rosedale’s take on reducing protein and indirectly on fasting (which would inherently reduce it) is to avoid stimulating MTOR (Mechanistic/Mammalian Target of Rapamyocin) because it is growth pathway and is the opposite of autophagy.

Autophagy is mainly stimulated by the absence of carbohydrates and the absence of protein, where the body is primed to start scavenging from itself as cleanup, so consuming fat for the body’s basic energy requirements would be “fat-fasting” and you can find talks by Dr. Valter Longo for more details on his Fasting Mimicking Diet (FMD), but many people have inferred that eating some fat, and perhaps fiber-carbohydrates from things such as avocados with absolutely minimal amounts of protein will still allow the body to enter autophagy.

The main problem with a general recommendation for fat-fasting is some people over-indulge in adding fats to coffee/tea for example, or they add sweeteners of some kind that stimulate insulin. I’ve personally tested my response to sucralose and I’ve indirectly determined that it releases insulin, so I can’t use it during any fasting that attempts to do anything more than just reduce calories, which is not my main goal since I fat-fast for autophagy and to maintain my T2DM reversal.

I’ve recently started experimenting with including AMPK Activators such as berberine to my fat-fasting regime, and so far I like the results.

There may be other objective criteria such as fasting insulin levels, but the closest thing I have is the Glucose Ketone Index (GKI) where anything under a ratio of 1:1 is considered an excellent fasting indicator and even before adding berberine my fat-fasting GKIs have always been under 1.0 and adding berberine has only improved them.

(Woody Dailey) #102

I realize this is a rat study but it’s still interesting. As I read it it may make
a big difference just what fatty acids are being burned during your fast. It
might be interesting doing a fat fast that used a lot of monounsaturated fat.

(David Cumming) #103

thanks for this explanation - I’m having trouble understanding completely, but it seems like a sound explanation. It’s does seem counter intuitive to me since we evolved an ability to store energy as fat for later use but then we also evolved to have a limit on how much of that fat we could use when we weren’t eating and needed it. Maybe it’s just me, but that doesn’t seem like a very elegant design.
I suppose burning protein/muscle (because your fat doesn’t give you enough fuel) would make sense in order to lower your BMR but it would make it increasingly harder to score your next kill. But I guess our species made it so it must work somehow :slight_smile:

(Richard Morris) #104

Yes limiting energy access to just 1% per day may sound like a poor evolutionary strategy, but it does mean that you have 3 months of energy. Maybe that’s the survival benefit. You can’t use all of it immediately.

It does seem that left to it’s own devices our bodies don’t appear to optimize for leanness but some adequate comfortable amount of body fat - I mean in the absence of a derangement due to modern sugars and starches.

(Gabe “No Dogma, Only Science Please!” ) #105

Very interesting thread, especially the link someone provided to Steve Phinney’s comments about fasting. It sounds to me as if fasts of <=48 hours are fine per Phinney; beyond that, he doesn’t approve.

Can anyone confirm that that’s their understanding?

(Chris W) #106

I’ve seen one of the presentations that Dr. Phinney speaks about fasting and yes, he seems to draw the line at about 48 hours as the limit of fasting that he can support with reservations. His primary concern seems to be with older patients since any loss of lean body mass is so difficult to rebuild as you get older.

(Gabe “No Dogma, Only Science Please!” ) #107

So basically what you’re telling me is I should start lifting while I’m still under age 40?

(Chris W) #108

I wouldn’t necessarily put a number to the age. Dr Phinney was likely been referring to patients in general and perhaps the generalization that many older patients may be less inclined to take up lifting or high intensity activity of any sort. After losing some LBM, which I believe was due to dropping protein too low for a while, I was able to restore it by increasing my protein a bit and stepping up my resistance and interval training a bit, and I am 52.

(Ty Belshe) #109

Here is a very recent video on autophagy from an expert in the field, Dr. Guido Kroemer, being interviewed by Dr. Rhonda Patrick:


It seems in humans it may take around 3 days of fasting to kickstart the process of autophagy and it’s unknown wether fat intake works against the process, a lot of people speculate it doesn’t however we don’t know definitively.
(G. Andrew Duthie) #110

Just watched that the other day. Good video, and I really like the way they provide on-screen definitions of many of the terms used. Wish that more health/science videos did the same. Would make the material more approachable for a wider audience.

(Robert) #111

I’ve listed to her podcasts and watched them and completely agree that the video’s are nice with the definitions/references to studies that she provides! If you’ve watched/listened to a few of her more recent podcasts, she does seem to be striving to determine the period after which autophagy benefits begin.

#112

Does this time frame take into consideration whether one starts a fast already keto adapted? This would be an interesting and useful parameter to know.

(G. Andrew Duthie) #113

I think the simple answer is…we don’t know.

Given what we do know, it probably varies from person to person. But even that is speculation.

#114

Thanks. So true about so much of this WOE.