haidut

Member
Joined
Mar 18, 2013
Messages
17,435
Location
USA / Europe
Just a quick post in response to some of the hate mail I keep getting on a daily basis in regards to the body's discriminatory treatment of various fat types. According to various proponents of keto diets, fasting, etc the organism has no preference for one type of fat or another in terms of oxidation or storage. As such, the claim is that body fat stores have a composition reflected by a person's diet. Since the Western diet contains more SFA/MUFA than PUFA, the argument of the keto crowd is that if lipolysis is detrimental it is due mostly to the effects of SFA and MUFA, not PUFA.

Well, as the studies below show, that is not the case. Apparently, SFA are not only resistant to esterification (and thus storage) but are also oxidized as quickly as pyruvate (the glucose pathway). PUFA/MUFA, on the other hand, are readily esterified/stored and thus become the predominant fat found in fatty tissues, while at the same time being oxidized at only 1/5 the rate of pyruvate. This means that if PUFA consumption in the diet reaches a certain percentage of total fat consumed, and the total fat consumed exceeds the oxidation capacity of that specific person, the fat stores of a person will likely consist predominantly of PUFA (and maybe 5%-10% MUFA) and only trace amounts of SFA. Thus, during lipolysis the FFA being dumped in the blood will be predominantly PUFA and due to their slow rate of oxidation this will result in an extended inhibition of glucose oxidation as a result of the Randle cycle. If that was not bad enough, due to the slow rate of oxidation and high rate of esterification, if lipolysis exceeds a certain limit, there will be more FFA (PUFA) in the bloodstream than tissues can oxidize. Since one of the roles of the liver is to protect tissues from excessive lipid exposure, most of the excess PUFA that cannot be oxidized/excreted will end up as triglycerides in the liver, resulting in the infamous NAFLD. This is actually a lesser of two evils, because if the liver cannot cope with the flood of PUFA due to extreme lipolysis, then ketoacidosis (and even death) may result due to FFA blocking both insulin release and its action. If the liver is healthy enough to cope with the flood of PUFA and that process continues for some time, the interaction of PUFA with iron (a good portion of which is stored in the liver) will result in lipofuscin formation affecting the entire body, and liver-centric fibrotic changes that lead to NASH, then cirrhosis and eventually liver cancer (HCC). In addition, the extra PUFA floating around that the liver could not excrete or store within itself leads to all sorts of degenerative changes in organs, including kidney failure, brain atrophy, gonadal suppression, adrenal overactivation, etc as well as the well-known inflammatory cascades through COX/LOX pathways. All of these pathological changes are readily visible in patients with type II diabetes on an ongoing basis. In addition, blood samples from diabetic patients readily demonstrates the predominance of PUFA in the FFA fraction of the sample.

Type 2 diabetes associated changes in the plasma non-esterified fatty acids, oxylipins and endocannabinoids. - PubMed - NCBI

"...Further, epoxides and ketones of eighteen carbon polyunsaturated fatty acids were elevated >80% in diabetes and strongly correlated with changes in NEFA, consistent with their liberation during adipose lipolysis. Endocannabinoid behavior differed by class with diabetes increasing an array of N-acylethanolamides which were positively correlated with pro-inflammatory 5-lipooxygenase-derived metabolites, while monoacylglycerols were negatively correlated with body mass. These results clearly show that diabetes not only results in an increase in plasma NEFA, but shifts the plasma lipidomic profiles in ways that reflect the biochemical and physiological changes of this pathological state which are independent of obesity associated changes."

None of this is even remotely theoretical, as many other recent studies I have discussed in this blog have already confirmed that increased fatty acid oxidation drives most of the organ failures seen in diabetic patients. While kidney failure is the most-often cited example of lipolysis-induced organ failure, the destruction of the beta-cells in the pancreas, dementias, movement disorders (Parkinson, Huntington, etc), CVD, osteoporosis, hypogonadism, etc have all been tied to excessive (or prolonged) FFA exposure. In light of the studies discussed in this blog, I think we can safely reclassify all of these pathologies as due to PUFA exposure/overload.

The takeaway of this post is the following. If a person consumes a diet high on fat (e.g. >15% of daily calories) with a PUFA fraction above a certain critical level (I suspect that number is around 10% of total fat), over time their fat stores will increase and will be composed predominantly of PUFA. In addition, any time such a person is exposed to stress, fasting, exhaustive exercise, infection, or really any other event that results in increased lipolysis their bloodstream will be flooded with FFA consisting mostly of PUFA. This elevated lipolysis (if maintained chronically) will at best result in liver disease and at worst in all the degenerative changes seen in conditions such as diabetes, CVD, neurodegenerative diseases and even cancer. As such, fasting and/or exhaustive exercise are one of the worst things an overweight person can do as it will only lead to a prolonged PUFA exposure and the resulting suppression of glucose oxidation, increased inflammation and ultimately severe chronic disease. A healthy approach to this problem for an obese/overweight/diabetic person would be to (1) lower total fat intake; (2) ensure SFA/PUFA ratio is as high as practically possible; (3) protect the liver and other organs from excessive lipolysis (niacinamide, aspirin, vitamin E); (4) support hormonal environment that resists weight gain (e.g. keep cortisol/estrogen at bay and pregnenolone/progesterone/DHEA/T/DHT at optimal levels). If these guidelines are followed, over time the muscles should be able to oxidize the stored PUFA and the liver should be able to glucuronidate whatever the muscles cannot handle.

Molecular Mechanisms and the Role of Saturated Fatty Acids in the Progression of Non-Alcoholic Fatty Liver Disease

"...Although there is no definitive mechanism explaining how SFAs induce ER stress, increasing evidence points to disordered phospholipid metabolism as one initiating factor. Unsaturated fatty acids are readily incorporated into inert TGs, but excess SFAs remain largely unesterified [28]. Recent literature suggests that these free SFAs are rapidly assembled into saturated phospholipid species that are subsequently integrated into ER membrane bilayers [46]."

Hepatic β-Oxidation and Regulation of Carnitine Palmitoyltransferase (CPT) I in Blunt Snout Bream Megalobrama amblycephala Fed a High Fat Diet

"...This previous study showed that SFA and MUFA levels are strongly reduced, while PUFA accumulates, in blunt snout bream fed a 15% fat diet [9]. SFA and MUFA in fish are preferentially used as oxidation substrates through the mitochondrial pathway, whereas this is not the case for PUFA [45]. Thus, it is predicted that decreased FA oxidation will not only affect lipid levels, but also the FA content of the liver."

https://www.researchgate.net/public...ynchus_mykiss_Walbaum_red_muscle_mitochondria

"...Beta-oxidation was studied in red muscle mitochondria of 10 major fatty acids that are acquired in the diet and occur in the fat depots of rainbow trout (Oncorhynchus mykiss Walbaum). The mitochondria were isolated by fractional centrifugation and the fatty acids were added as coenzyme A esters in the presence of carnitine. The fatty acids could be separated into roughly three groups in relation to their oxidation rates. Two fatty acids (14:0 and 16:0) were oxidized as rapidly as pyruvate. Another six acids (16:1 n − 7, 18:0, 18:1 n − 9, 20:1 n − 9, 22:1 n − 9 and 22:6 n − 3) were oxidized at about three-quarters to one-half the rate of pyruvate. The two essential fatty acids (18:2 n − 6 and 18:3 n − 3) had a slow oxidation rate, about one-fifth of that of pyruvate. The liver mitochondria from rainbow trout oxidized 18:0, 18:1, 18:2, and 18:3 at the same rate, 70–80% of that of pyruvate. These results show that rainbow trout red muscle discriminates between fatty acids used in energy production and essential fatty acid precursors, as indicated by the low β-oxidation rate of the latter acids."
 

Jem Oz

Member
Joined
Jun 13, 2016
Messages
370
I'd love to know how a keto fiend responds to this.

Meanwhile, I know this topic has been covered, but @haidut you mention for the overweight person the importance of aspirin and niacinamide to protect against excessive lipolysis. However these substances interfere with and even prevent weight loss. I remember you yourself saying if you needed to lose weight you would avoid niacinamide. Would Vit E be enough, if one were actively losing weight? Is a period of poor health essentially unavoidable if one wants to shed the pounds? (for the greater good).
 

boris

Member
Joined
Oct 1, 2019
Messages
1,906
You can lose fat without fat burning. In a well working metabolism you will excrete excess bodyfat in the urine over time.

"To keep the metabolic rate up, you recommend to block lipolysis in favour of glucose oxidation. By preventing the liberation and metabolism of fatty acids (i.e. lipolysis), how does one lose excess stored fat?"

Answer from RP on 4/15/15: The liver can gradually excrete it in the urine as a toxin.
 

Jem Oz

Member
Joined
Jun 13, 2016
Messages
370
Interesting. I guess the only exception to this advice would be if you were actively trying to deplete stored pufa?
 

haidut

Member
Thread starter
Joined
Mar 18, 2013
Messages
17,435
Location
USA / Europe
I'd love to know how a keto fiend responds to this.

Meanwhile, I know this topic has been covered, but @haidut you mention for the overweight person the importance of aspirin and niacinamide to protect against excessive lipolysis. However these substances interfere with and even prevent weight loss. I remember you yourself saying if you needed to lose weight you would avoid niacinamide. Would Vit E be enough, if one were actively losing weight? Is a period of poor health essentially unavoidable if one wants to shed the pounds? (for the greater good).

I think aspirin and niacinamide prevent "excessive" lipolysis but not baseline one. My difficulty with losing weight back in the day was due to elevated cortisol/prolactin, and I mistakenly ascribed the blame to aspirin/niacinamide. Once the cortisol was lowered with cyproheptadine, the aspirin/niacinamide did not cause any more issues.
But as far as your question goes - yes, vitamin E should also help block excessive lipolysis and may also directly deactivate linoleic/linolenic acids in the blood.
 

Jake sullivan

Member
Joined
Oct 3, 2016
Messages
138
Age
24
Its sometimes concerning because Peat says that by the time a person is 30, even a little consumption of PUFA leads to the accumulation of it due to the fact it preferentially stores, now i think the goal here of everyone on the forum including myself is to not only prevent PUFA from accumulating, but also reduce/deplete it as much as possible, sometimes with some of the information and quotes from Peat floating around it almost makes it seem like an inevitable/impossible task or a process of nature,

But im assuming if one were to do a fat free diet/pure hydrogenated coconut oil or MCT as the fat source, or at LEAST keep PUFA/fat intake at a certain percentage that would also produce the same results? Theres a few quotes floating around on here where Ray apparently speculated around 0.5G per day would be low enough to keep it from accumulating with age and also low enough to oxidize safely/turnover the small amount of PUFA that does get stored since it’s minimal and the higher SFA in the tissues will run a higher metabolic rate to oxidize PUFA off even faster i assume,

Novody wants to feel like their situation and efforts of PUFA depletion are futile, does anyone have any thoughts on what the average baseline consumption of PUFA would need to be reduced to in order to stay in a depleting/reducing state of total PUFA stores???
 

Maljam

Member
Joined
Jul 8, 2020
Messages
696
Its sometimes concerning because Peat says that by the time a person is 30, even a little consumption of PUFA leads to the accumulation of it due to the fact it preferentially stores, now i think the goal here of everyone on the forum including myself is to not only prevent PUFA from accumulating, but also reduce/deplete it as much as possible, sometimes with some of the information and quotes from Peat floating around it almost makes it seem like an inevitable/impossible task or a process of nature,

But im assuming if one were to do a fat free diet/pure hydrogenated coconut oil or MCT as the fat source, or at LEAST keep PUFA/fat intake at a certain percentage that would also produce the same results? Theres a few quotes floating around on here where Ray apparently speculated around 0.5G per day would be low enough to keep it from accumulating with age and also low enough to oxidize safely/turnover the small amount of PUFA that does get stored since it’s minimal and the higher SFA in the tissues will run a higher metabolic rate to oxidize PUFA off even faster i assume,

Novody wants to feel like their situation and efforts of PUFA depletion are futile, does anyone have any thoughts on what the average baseline consumption of PUFA would need to be reduced to in order to stay in a depleting/reducing state of total PUFA stores???

Under 4g a day of PUFA is the most repeated amount around here. I wouldn't overly stress about it, as long as you aren't eating fast food daily and sourcing your own food it becomes second nature. Peat has also said recently in the Patrick Timpone interview that the liver can deal with small amounts of PUFA. I don't think you would even be able to manage under 0.5g outside of a laboratory or giving yourself serious orthorexia, not sure where you have read that. Just relax and don't eat any vegetable oils.
 

Spartan300

Member
Joined
Feb 4, 2018
Messages
474
I think aspirin and niacinamide prevent "excessive" lipolysis but not baseline one. My difficulty with losing weight back in the day was due to elevated cortisol/prolactin, and I mistakenly ascribed the blame to aspirin/niacinamide. Once the cortisol was lowered with cyproheptadine, the aspirin/niacinamide did not cause any more issues.

@haidut What dose/duration did you use cypro for and did it effect libido?
 
Similar threads
Thread starter Title Forum Replies Date
haidut Cholesterol And SFA Are Anabolic; PUFA/MUFA Akin To Chemical Castration Scientific Studies 27
P Different Effect Of MUFA Vs SFA On Tissues PUFA Content Articles & Scientific Studies 3
A Effects Of SFA, PUFA, MUFA, And CH On Glucose-Insulin Homeostasis Scientific Studies 3
haidut MUFA & PUFA increase inflammation; SFA decreases it Scientific Studies 5
GreekDemiGod Human studies showing androgenic benefits of SFA? Ask For Help or Advice 2
haidut PUFA is catabolic, SFA is anti-catabolic (anabolic) Scientific Studies 0
haidut PUFA Exacerbate, Saturated Fats (SFA) / Albumin / Calcium Ameliorate COVID-19 Scientific Studies 2
Kingpinguin PUFA Has Greater Anti-epileptic Effect Than SFA In Ketogenic Diet According To Study Scientific Studies 1
B Anti-Peat Lean Mass Increased 3x As Much With PUFA Versus SFA Debate - Anti-Peat 21
Mr. God of Cars How/why Does Eating Muffins Made With SFA Cause Visceral Fat Gain, But Not With PUFA? Metabolism 36
Jon Pufa Better For Lean Mass Than SFA? Diet 5
haidut Saturated Fats (SFA) Increase Glucose Oxidation While PUFA Decrease It Scientific Studies 82
P Difference Between Tocopherols/MTC And SFA Ester / Ethanol? Supplements 3
haidut Western Diet Or SFA Strikingly Protective Against Colon Cancer And Mortality Scientific Studies 7
haidut PUFA Cause Fatal Swelling Seen In Brain Infections; SFA Are Harmless Scientific Studies 3
haidut Topical Stearic Acid Is Metabolized Into Longer Chain SFA Scientific Studies 56
haidut PUFA Increases Alcohol Damage By Increasing Cell Fluidity; SFA Are Protective Scientific Studies 5
haidut PUFA Is Directly Catabolic (without Cortisol/estrogen), SFA Is Anabolic Scientific Studies 5
L So Is The Absolute Amount Of PUFA Important Or The Proportion Of SFA To PUFA? Diet 4
haidut PUFA Initiate & Promote The Stress Response (ACTH/cortisol), SFA Inhibit It Scientific Studies 20
W Impact Of PUFA And SFA Overfeeding On The DNA-methylation Pattern In Human Adipose Tissue Scientific Studies 1
haidut DeFibron - Liquid Methylated SFA For Lab/R&D IdeaLabs 434
Milena SFA Causes More Liver And Visceral Fat Accumulation Than PUFA Scientific Studies 6
L Bacteria Can Hydrogenate PUFA Into SFA Digestion, Gut Flora 59
haidut DHEA (and Other Androgens) Deplete EFA (PUFA) And Increase SFA Scientific Studies 10
J Carb / SFA / PUFA intake: LDL & Glycation Diet, Recipes 14
encerent Should MUFA's Be Avoided As Well? Diet 2
haidut PUFA And MUFA Are Strong Inhibitors Of 5-AR, Saturated Fatty Acids Are Not Scientific Studies 54
haidut PUFA Activates NF-kB, MUFA Does Not Scientific Studies 4
Gabriel What's Your Opinion About MUFAs And MUFA-rich Foods? Fats 3
F Confused On Ray Peat View On Fats [MUFA] Fats 27
jamies33 Theory: PUFA Preferentially Stored Vs Burned Is Genetic (or At Least Can Differ Between People) Polyunsaturated Fats, Seed Oils 1
ecstatichamster Studies? Where Is Evidence PUFAs Are Preferentially Stored Not Burned? Science 25
Drareg Human Aging-associated DNA Hypermethylation Occurs Preferentially At Bivalent Chromatin Domains Scientific Studies 2
haidut DHEA Is Preferentially Converted Into DHT In Humans Scientific Studies 22

Similar threads

Top