Nov 2018: Dr. Peat Talks About Cholesterol Esters Causing Aging

gabys225

Member
Joined
Sep 15, 2013
Messages
121
Does anyone know how we'd go about using lidocaine? It's easy to get on Ebay (for veterinary use of course) with just ethanol and propylene glycol as the inactives. Pretty low molecular weight too so maybe a little transdermal would be ideal?
 

Light

Member
Joined
Oct 5, 2018
Messages
304
The characteristic opacity of aged skin is the result of an accumulation of layers of dead cells on the surface. While the vital underlying skin cells contain much less cholesterol than normal, the inert cells contain an increased amount of choles- terol sulfate. When the skin’s free cholesterol content is increased experimentally, the skin regains its ability to shed the dead superficial cells. When it’s lowered experimentally, as with a statin, the skin takes on the structure and appearance of old skin. Aging seems to be a state of cholesterol starvation.
Hamster, where's that from?
How was free cholesterol increased in the skin? Was it increased in general in the body? Was it topical? Is this from a human study?

I as a recipient of Kobayashi Award
WTF?! What's your background man? (sorry if you've answered it before...)

cerebellar and pineal neurosteroids and their biological actions on the growth and survival of Purkinje cells during development
Only during development? What happens in adulthood?
And do you know of its effects in the spinal cord, if any?
 

haidut

Member
Forum Supporter
Joined
Mar 18, 2013
Messages
19,798
Location
USA / Europe
Saturated fats aren’t superior. It’s more complicated than a black or white situation based from Petri dish studies.

It goes well beyond Petri dishes. The effects of SFA vs. PUFA on CVD have been tested on multiple animal models, including primates (and even humans) and the evidence is pretty conclusive. The easy perodixation of PUFA is the minor issue. The major one is PUFA being the main precursor to inflammatory mediators like prostaglanding and leukotrienes, as well as promoting cortisol, estrogen, serotonin and NO. SFA have largely the opposite of those effects. CVD is an inflammatory disease, just like all other chronic ones and as such the role of PUFA is pretty clear. Even Wikipedia has caught up with the issue.
Polyunsaturated fat - Wikipedia
"...Contrary to conventional advice, an evaluation of evidence from 1966-1973 pertaining to the health impacts of replacing dietary saturated fat with linoleic acid found that participants in the group doing so had increased rates of death from all causes, coronary heart disease, and cardiovascular disease.[10]"
 

haidut

Member
Forum Supporter
Joined
Mar 18, 2013
Messages
19,798
Location
USA / Europe
That's because it is.

I think Sour is just a troll. If somebody is that contrarian to everything we are discussing on the forum then why be here??? Either a troll or a paid agent provocateur.
I would not waste time with him/her.
@haidut curious about fatty acid esters like the SFA esters. How come they are beneficial vs. Cholesterol esters?

Most SFA esters are easily metabolized back into their SFA + ester components but I don't think the same happens with cholesterol. Also, there are many studies with SFA esters on mammals showing their beneficial effects while studies with the cholesteryl esters are invariably negative.
 

GAF

Member
Joined
Dec 28, 2014
Messages
789
Age
67
Location
Dallas Texas
Most SFA esters are easily metabolized back into their SFA + ester components but I don't think the same happens with cholesterol

Classification and cause
Lysosomal acid lipase deficiency is a genetic disease that is autosomal recessive. It is an inborn error of metabolism that causes a lysosomal storage disease.[3] The condition is caused by a mutation of the LIPA gene, which is responsible for the gene coding of the lysosomal lipase protein (also called lysosomal acid lipase or LAL), which results in a loss of the protein's normal function.[2] When LAL functions normally, it breaks down cholesteryl esters and triglycerides in low density lipoprotein particles into free cholesterol and free fatty acids that the body can reuse; when LAL doesn't function, cholesteryl esters and triglycerides build up in the liver, spleen and other organs.[3][4] The accumulation of fat in the walls of the gut and other organs in leads to serious digestive problems including malabsorption, a condition in which the gut fails to absorb nutrients and calories from food, persistent and often forceful vomiting, frequent diarrhea, foul-smelling and fatty stools (steatorrhea), and failure to grow.[3]


It appear to me that a shortage or some malfunctioning of this pancreatic enzyme is THE ISSUE in heart disease and liver disease and nearly every other fatty problem in the human body. The genetic explanation may be true in infants but I doubt it's the issue in everyone else. Something blocks the production or inactivates this enzyme as we age and bad things happen. It's up to us to solve the mystery because big pharma would not be interested in doing so.
 

Risingfire

Member
Joined
May 10, 2016
Messages
1,063
In addition to progesterone and lidocaine mentioned in the newsletter, pregnenolone may help as well. The study below suggests pregnenolone could be a competitor for the ACAT enzyme that creates cholesteryl esters and as such inhibit the formation of those esters, as pregnenolone had 50-100 fold higher affinity for ACAT than cholesterol does. So far there is no evidence that pregnenolone esters are harmful and at least one of them (pregnenolone sulfate) is known to serve as the long term storage form of pregnenolone.
Cellular Pregnenolone Esterification by Acyl-CoA:Cholesterol Acyltransferase
"...Pregnenolone (PREG) can be converted to PREG esters (PE) by the plasma enzyme lecithin: cholesterol acyltransferase (LCAT), and by other enzyme(s) with unknown identity. Acyl-CoA:cholesterol acyltransferase 1 and 2 (ACAT1 and ACAT2) convert various sterols to steryl esters; their activities are activated by cholesterol. PREG is a sterol-like molecule, with 3-β-hydroxy moiety at steroid ring A, but with much shorter side chain at steroid ring D. Here we show that without cholesterol, PREG is a poor ACAT substrate; with cholesterol, the Vmax for PREG esterification increases by 100-fold. The binding affinity of ACAT1 for PREG is 30–50-fold stronger than that for cholesterol; however, PREG is only a substrate but not an activator, while cholesterol is both a substrate and an activator. These results indicate that the sterol substrate site in ACAT1 does not involve significant sterol-phospholipid interaction, while the sterol activator site does. Studies utilizing small molecule ACAT inhibitors show that ACAT plays a key role in PREG esterification in various cell types examined. Mice lacking ACAT1 or ACAT2 do not have decreased PREG ester contents in adrenals, nor do they have altered levels of the three major secreted adrenal steroids in serum. Mice lacking LCAT have decreased levels of PREG esters in the adrenals. These results suggest LCAT along with ACAT1/ACAT2 contribute to control pregnenolone ester content in different cell types and tissues."
Would you suggest taking lidocaine orally? Would you suggest orally for progesterone?
 

haidut

Member
Forum Supporter
Joined
Mar 18, 2013
Messages
19,798
Location
USA / Europe
Lowering blood cholesterol VIA DRUGS or PUFAs. You make it sound like higher cholesterol is superior than normal cholesterol.

I gave you a link with evidence.
Classification and cause
Lysosomal acid lipase deficiency is a genetic disease that is autosomal recessive. It is an inborn error of metabolism that causes a lysosomal storage disease.[3] The condition is caused by a mutation of the LIPA gene, which is responsible for the gene coding of the lysosomal lipase protein (also called lysosomal acid lipase or LAL), which results in a loss of the protein's normal function.[2] When LAL functions normally, it breaks down cholesteryl esters and triglycerides in low density lipoprotein particles into free cholesterol and free fatty acids that the body can reuse; when LAL doesn't function, cholesteryl esters and triglycerides build up in the liver, spleen and other organs.[3][4] The accumulation of fat in the walls of the gut and other organs in leads to serious digestive problems including malabsorption, a condition in which the gut fails to absorb nutrients and calories from food, persistent and often forceful vomiting, frequent diarrhea, foul-smelling and fatty stools (steatorrhea), and failure to grow.[3]


It appear to me that a shortage or some malfunctioning of this pancreatic enzyme is THE ISSUE in heart disease and liver disease and nearly every other fatty problem in the human body. The genetic explanation may be true in infants but I doubt it's the issue in everyone else. Something blocks the production or inactivates this enzyme as we age and bad things happen. It's up to us to solve the mystery because big pharma would not be interested in doing so.

Both cortisol and estrogen, which rise with age, block pancreatic function. Elevated FFA also do, especially if they are PUFA. I guess the easiest thing would be to supplement with some digestive enzymes and pregnenolone/progesterone could help with the cortisol/estrogen and also by competing with cholesterol for esterification.
 

GAF

Member
Joined
Dec 28, 2014
Messages
789
Age
67
Location
Dallas Texas
When looking at bottles of Digestive Enzymes, the ingredients just include "Lipase". I wonder if anyone knows if oral lipase capsules can turn into LAL thru some magical body process. Do we have any pancreas scientist experts on this forum?
 

Mito

Member
Joined
Dec 10, 2016
Messages
2,554
The major one is PUFA being the main precursor to inflammatory mediators like prostaglanding and leukotrienes, as well as promoting cortisol, estrogen, serotonin and NO. SFA have largely the opposite of those effects. CVD is an inflammatory disease, just like all other chronic ones and as such the role of PUFA is pretty clear.
Interleukin-1 Beta as a Target for Atherosclerosis Therapy: The Biological Basis of CANTOS and Beyond
Condensed Abstract
Inflammatory pathways drive atherogenesis and link traditional risk factors to atherosclerosis and its complications. Interleukin-1 beta (IL-1β) has emerged as an actionable mediator in prevention of recurrent cardiovascular events. Intrinsic vascular wall cells and lesional leukocytes alike can produce this pro-inflammatory cytokine. Local stimuli in the plaque boost the generation of active IL-1β through the action of a molecular assembly known as the inflammasome. Therapies that interfere with IL-1 action can improve cardiovascular outcomes, ushering in a new era of anti-inflammatory therapies for atherosclerosis. Biomarker-directed application of anti-inflammatory interventions promise to personalize allocation of therapy for our cardiovascular patients.”
Interleukin-1 Beta as a Target for Atherosclerosis Therapy: The Biological Basis of CANTOS and Beyond
 

haidut

Member
Forum Supporter
Joined
Mar 18, 2013
Messages
19,798
Location
USA / Europe
Interleukin-1 Beta as a Target for Atherosclerosis Therapy: The Biological Basis of CANTOS and Beyond
Condensed Abstract
Inflammatory pathways drive atherogenesis and link traditional risk factors to atherosclerosis and its complications. Interleukin-1 beta (IL-1β) has emerged as an actionable mediator in prevention of recurrent cardiovascular events. Intrinsic vascular wall cells and lesional leukocytes alike can produce this pro-inflammatory cytokine. Local stimuli in the plaque boost the generation of active IL-1β through the action of a molecular assembly known as the inflammasome. Therapies that interfere with IL-1 action can improve cardiovascular outcomes, ushering in a new era of anti-inflammatory therapies for atherosclerosis. Biomarker-directed application of anti-inflammatory interventions promise to personalize allocation of therapy for our cardiovascular patients.”
Interleukin-1 Beta as a Target for Atherosclerosis Therapy: The Biological Basis of CANTOS and Beyond

Thanks.
I am beginning to suspect the cholesterol strawman was invented deliberately to keep people distracted from the real cause (inflammation) and what drives inflammation. The cholesterol hypothesis came long before statins were even conceptualized, so there must have been some other impetus to propose this ruse. And that something was sales of omega-6 and omega-3, which are the main byproducts of the agricultural and maritime industries. Those industries were the dominant ones in most Western countries at the turn of the 20th century when the cholesterol ruse first started, and to this day are some of the most heavily subsidized ones.
 

High_Prob

Member
Joined
Mar 23, 2016
Messages
391
δ-Tocopherol Reduces Lipid Accumulation in Niemann-Pick Type C1 and Wolman Cholesterol Storage Disorders



δ-Tocopherol Reduces Lipid Accumulation in Niemann-Pick Type C1 and Wolman Cholesterol Storage Disorders


Next Section
Abstract
Niemann-Pick disease type C (NPC) and Wolman disease are two members of a family of storage disorders caused by mutations of genes encoding lysosomal proteins. Deficiency in function of either the NPC1 or NPC2 protein in NPC disease or lysosomal acid lipase in Wolman disease results in defective cellular cholesterol trafficking. Lysosomal accumulation of cholesterol and enlarged lysosomes are shared phenotypic characteristics of both NPC and Wolman cells. Utilizing a phenotypic screen of an approved drug collection, we found that δ-tocopherol effectively reduced lysosomal cholesterol accumulation, decreased lysosomal volume, increased cholesterol efflux, and alleviated pathological phenotypes in both NPC1 and Wolman fibroblasts. Reduction of these abnormalities may be mediated by a δ-tocopherol-induced intracellular Ca2+ response and subsequent enhancement of lysosomal exocytosis. Consistent with a general mechanism for reduction of lysosomal lipid accumulation, we also found that δ-tocopherol reduces pathological phenotypes in patient fibroblasts from other lysosomal storage diseases, including NPC2, Batten (ceroid lipofuscinosis, neuronal 2, CLN2), Fabry, Farber, Niemann-Pick disease type A, Sanfilippo type B (mucopolysaccharidosis type IIIB, MPSIIIB), and Tay-Sachs. Our data suggest that regulated exocytosis may represent a potential therapeutic target for reduction of lysosomal storage in this class of diseases.

Introduction
Niemann-Pick disease type C (NPC)3 is caused by mutations in either the NPC1 or NPC2gene, encoding two distinct lysosomal cholesterol-binding proteins (1, 2). The NPC cellular phenotype is characterized by lysosomal accumulation of unesterified cholesterol and other lipids, resulting from impaired cholesterol export from the late endosomal and lysosomal compartments (2, 3). Wolman disease is caused by mutations in the gene encoding lysosomal acid lipase (LAL). Deficiency of LAL function results in two distinct disease phenotypes that accumulate both cholesteryl ester and triglycerides. The early onset form is known as Wolman disease, and the late onset form is known as cholesteryl ester storage disease (3, 4). Enlarged lysosomes are a common cellular phenotype for both NPC and Wolman diseases.

Cholesterol is an essential component of cellular membranes and is central to maintaining both membrane integrity and fluidity as well as regulating membrane protein function, cell signaling, and ion permeability (5). In addition, cholesterol is the precursor molecule for synthesis of cellular components such as bile acids, oxysterols, and steroid hormones. Cholesterol homeostasis is tightly regulated at both the cellular and whole-body levels (6). Although the homeostasis of serum and tissue cholesterol has been well defined, many details of intracellular cholesterol regulation and trafficking are yet to be elucidated. Esterified cholesterol contained in low density lipoprotein (LDL) enters a cell via endocytosis. Upon LDL entry into the late endosome/lysosome, LAL hydrolyzes fatty acyl chains from cholesteryl esters to liberate unesterified cholesterol that is transported out of the late endosome/lysosome involving NPC1 and NPC2 proteins (6,,8). The precise mechanism and pathway of cholesterol trafficking from the lysosome remain unclear, although it has been established that unesterified cholesterol moves to the endoplasmic reticulum for re-esterification or utilization by the cell and to the trans-Golgi network and/or plasma membrane for efflux from the cell (5, 9).

Currently, there are no Food and Drug Administration-approved therapies for either NPC disease or Wolman disease. However, miglustat, originally approved as a substrate reduction drug for Gaucher disease, has been approved in the European Union for the treatment of NPC1 disease by the European Agency for the Evaluation of Medicinal Products. Therapeutic strategies that have been explored include reduction of lysosomal lipid burden, augmentation of mutant protein expression, or replacement of mutant proteins in lysosome (10). Enzyme replacement therapy, which has been successfully used to treat selected lysosomal storage diseases, was studied in the mouse model of Wolman disease but is not clinically approved (11). A protein replacement therapy, similar to enzyme replacement therapy, would in theory be possible for NPC2 disease, but it is not feasible for NPC1 disease because NPC1 is an integral membrane protein. A phenotypic screen of a compound collection recently identified compounds that reduced filipin staining in NPC1 fibroblasts (12), and several laboratories have reported lead compounds, including 2-hydroxypropyl-β-cyclodextrin and histone deacetylase inhibitors, that reduce cholesterol accumulation (12,,15). A recent report revealed that cyclodextrin's mechanism of action to reduce cholesterol accumulation in NPC1 mutant cells is through induction of exocytosis (16). Here we report the identification of δ-tocopherol (δ-T) in a phenotypic screen of an approved drug library that significantly reduces lysosomal cholesterol accumulation in NPC1 fibroblasts. Following δ-T treatment, the enlarged acidic endosomal/lysosome compartment was dramatically reduced, and the pathological phenotype of NPC1 cells, as determined by ultrastructural analysis, was alleviated. Similar effects of δ-T were also observed in Wolman fibroblasts. The mechanism of action for δ-T was linked to increase in cytosolic Ca2+, correction of the lysosomal Ca2+ deficiency, and enhancement of lysosomal exocytosis. The effect of δ-T also extended to patient-derived fibroblasts from other lysosomal storage diseases, including Batten (CLN2), Fabry, Farber, Niemann-Pick disease type A, NPC2, Sanfilippo type B (MPS IIIB), and Tay-Sachs. The results indicate that the enhancement of lysosomal exocytosis may represent a new therapeutic strategy for drug development that may be widely applicable to lysosomal storage diseases.



DISCUSSION
Exocytosis is a housekeeping function responsible for the secretion of hormones, cytokines, and neurotransmitter in secretory cells. In response to a transient increase of cytosolic Ca2+, secretory vesicles move toward the plasma membrane, fuse with the membrane, and then expel the luminal contents into the external cellular environment. Exocytosis in nonsecretory cells plays an important role in plasma membrane repair (31), bone resorption (30), cycling/recycling proteins to plasma membrane (32), pathogen invasion (33), neurite outgrowth (34), and cellular clearance (29, 35). Lysosomes, which are the most important exocytic organelle in nonsecretory cells, release their contents in response to a transient rise in cytosolic Ca2+ or ionomycin (29). A recent paper reported that lysosomal exocytosis is regulated by the bHLH-leucine zipper transcription factor EB, and overexpression of transcription factor EB reduces the storage materials in cell-based disease models (30). Regulated exocytosis may be operative in vivo because lysosomal contents have been found in extracellular fluids, blood, and urine in certain patients with lysosomal storage diseases (35). Thus, targeting lysosomal exocytosis may be a useful strategy to mitigate the lysosomal burden in storage diseases.

In this study, we show that δ-T, a minor vitamin E species, appears to exert its effect in NPC1 and Wolman fibroblasts through stimulation of lysosomal exocytosis. Translating these cell-based results to the in vivo use in animal models and patients poses a challenge with respect to its unfavorable pharmacokinetics. In comparison with α-T, which is present at 20–40 μM in human plasma, the highest among eight vitamin E isoforms, the δ-T plasma concentration in humans is <1 μM (36,,39). Contributing to the low plasma concentration of δ-T is its rapid oxidation by the P450 enzyme CYP4F2 (40). The brain concentration of δ-T in mice was under 1 μM after a 4-week treatment with 1.67 g/kg of diet/day δ-T (49). By contrast, α-T, unique among the vitamin E isoforms, is stabilized in plasma by α-tocopherol transfer protein (41). Nonetheless, α-T is far less potent than δ-T in reducing storage in NPC1 and Wolman fibroblasts and, even with a dietary supplement, may not reach the required plasma concentration for this pharmacological effect (36, 38). In the Npc1−/− mouse model, treatment with α-T provided a functional benefit, although it did not prolong survival (42). This could be due to low plasma and tissue concentrations of α-T in the mouse that are insufficient for the activity of cholesterol reduction. Therefore, the insufficient therapeutic concentrations in plasma and brain limit the use of δ-T and α-T in the animal model study as well as in clinical use to treat patients. To explore the potential effect of δ-T in vivo, chemical optimization of its pharmacokinetic properties will be required.

Although the antioxidant capacity of vitamin E is frequently thought to be its primary biological function, a number of non-antioxidant functions have been proposed. These include regulation of enzyme function, cell signaling, cell proliferation, and neuroprotection (43, 44). Vitamin E contains a chromanol ring with a hydroxyl group that is responsible for its antioxidant effect and a 13-carbon hydrophobic phytyl side chain that inserts into the plasma membrane (45). α-T, the major vitamin E isoform in human plasma, prevents apoptosis induced by 7-ketocholesterol, one of the cholesterol oxidation products in neuronal cells that is markedly increased in NPC1 disease (46). α-T has also been shown to stimulate mast cell degranulation, a secretory form of exocytosis (47). This effect of α-T was not mediated by an up-regulation of genes for proteins involved in vesicular transport (e.g. Nsf, Cplx2, Snap23, and Stx3) but through the direct interaction of α-T with the plasma membrane (47). The pretreatment requirement of α-T for these reported pharmacological effects may be explained by the time necessary for the incorporation of α-T molecules into the plasma membrane and for the subsequent transfer of incorporated α-T molecules to other cellular organelles and compartments.

A specific target protein for δ-T has not been found or implicated. In lysosomal storage diseases, the accumulation of lipids in lysosomes impairs cellular lipid trafficking, which could directly impact plasma membrane fluidity and dynamics. It is possible that the incorporation of δ-T in the plasma membrane and the subsequent alteration of membrane physical status, such as lipid fluidity, plays a critical role in the effect of δ-T on reduction of cholesterol and other lipid in the lysosome. The increase of intracellular Ca2+ and subsequent lysosomal exocytosis by δ-T support a mechanism of action mediated through the favorable change in membrane physical status. Thus, further studies on membrane biophysics and the function of membrane protein as affected by δ-T are necessary to elucidate the precise mechanism of action.

Based on the above data, we have proposed a model for the pharmacological effect of δ-T on the reduction of lipid accumulation in cells from patients with lysosomal storage diseases. Under normal conditions, cellular cholesterol derived from either LDL endocytosis or de novo synthesis is mobilized from lysosomes through a LAL-NPC2-NPC1-dependent pathway for distribution to the trans-Golgi and endoplasmic reticulum. We hypothesized that a minor, low flux cholesterol trafficking pathway, such as lysosomal exocytosis, may also exist because the cholesterol accumulation in NPC1 cells can be corrected following culture in lipoprotein-deficient serum for 5–6 days (48). Deficiency in function of the NPC1 protein disrupts the LAL-NPC2-NPC1-dependent pathway for cholesterol trafficking, resulting in impaired cholesterol efflux and lysosomal accumulation of cholesterol and other lipids. When the NPC1-deficient cells are treated with a high concentration of δ-T, the enhanced lysosomal exocytosis reduces lysosomal accumulation of cholesterol and other lipids, although the defect in the LAL-NPC2-NPC1-dependent pathway is not corrected. However, given the complexity of its mechanism of action, other intracellular pathways may be involved in the vitamin E function that merit further study.

In conclusion, we have demonstrated that δ-T reduces cholesterol accumulation and alleviates cellular phenotypes in NPC1 and Wolman cells. Our data suggest that the pharmacological effect of δ-T may be mediated by stimulating an increase in cytosolic Ca2+ that enhances lysosomal exocytosis. This mechanism appears to be independent of either the mutant enzyme or the storage material because we found that δ-T alleviated the lysosomal storage phenotype in other fibroblasts derived from patients with Batten (CLN2), Fabry, Farber, Niemann-Pick disease type A, Sanfilippo type B (MPS IIIB), and Tay-Sachs diseases. Although utilization of δ-T directly as a therapeutic agent is at present limited by its inability to achieve adequate plasma and brain concentrations in both animals and humans, structure optimization to improve its pharmacokinetic properties and increase its plasma and tissue concentrations could lead to the development of a new class of drugs for the treatment of lysosomal storage diseases.
 
J

jb116

Guest
I think Sour is just a troll. If somebody is that contrarian to everything we are discussing on the forum then why be here??? Either a troll or a paid agent provocateur.
I would not waste time with him/her.


Most SFA esters are easily metabolized back into their SFA + ester components but I don't think the same happens with cholesterol. Also, there are many studies with SFA esters on mammals showing their beneficial effects while studies with the cholesteryl esters are invariably negative.
Thank you
 

tankasnowgod

Member
Joined
Jan 25, 2014
Messages
8,131
Thanks.
I am beginning to suspect the cholesterol strawman was invented deliberately to keep people distracted from the real cause (inflammation) and what drives inflammation. The cholesterol hypothesis came long before statins were even conceptualized, so there must have been some other impetus to propose this ruse. And that something was sales of omega-6 and omega-3, which are the main byproducts of the agricultural and maritime industries. Those industries were the dominant ones in most Western countries at the turn of the 20th century when the cholesterol ruse first started, and to this day are some of the most heavily subsidized ones.

I don't know if you've ever read Anthony Colpo's book "The Great Cholesterol Con," but there are three chapters that deal with this very issue. Chapter 10 "Money, Politics, and Cholesterol" Chapter 11 "Creating a 'Consensus'" and Chapter 12 "If We Want Your Opinion, We'll Give It To You!"

He specifically talks about that infamous Time Magazine with "Cholesterol: And Now The Bad News...." on the cover, and the Consensus Development Conference in Bethesda Maryland in 1984, and how it was clearly pre-planned agenda, to spread the idea of Cholesterol being bad. He also discusses how the Vegetable Oil industry profited off this "Consensus" before statins.
 

Light

Member
Joined
Oct 5, 2018
Messages
304
I guess the easiest thing would be to supplement with some digestive enzymes and pregnenolone/progesterone could help with the cortisol/estrogen and also by competing with cholesterol for esterification.
Would progesterone also reverse existing cholesteryl esters, or only slow down their production?
 

Koveras

Member
Joined
Dec 17, 2015
Messages
720
@haidut @ecstatichamster @lampofred @Hugh Johnson @jamies33 @yerrag @Mito

Maybe this is one of the larger, currently unsung, benefits of sulfur amino acid restriction (SAAR, =methionine+cysteine restriction) with respect to longevity and healthspan

Low sulfur intake > less substrate for cholesterol sulfation

On top of that, SAAR diets tend to lower stearoyl-CoA desaturase-1 (SCD1) activity, lowering the endogenous synthesis of unsaturated fatty acids > less substrate for cholesterol esterification to unsaturated fats
 

Hugh Johnson

Member
Joined
Mar 14, 2014
Messages
2,648
Location
The Sultanate of Portugal
@haidut @ecstatichamster @lampofred @Hugh Johnson @jamies33 @yerrag @Mito

Maybe this is one of the larger, currently unsung, benefits of sulfur amino acid restriction (SAAR, =methionine+cysteine restriction) with respect to longevity and healthspan

Low sulfur intake > less substrate for cholesterol sulfation

On top of that, SAAR diets tend to lower stearoyl-CoA desaturase-1 (SCD1) activity, lowering the endogenous synthesis of unsaturated fatty acids > less substrate for cholesterol esterification to unsaturated fats
Perhaps, but it's too much trouble for a dubious gain.
 

haidut

Member
Forum Supporter
Joined
Mar 18, 2013
Messages
19,798
Location
USA / Europe
Would progesterone also reverse existing cholesteryl esters, or only slow down their production?

I don't know, but progesterone increases metabolism and lowers inflammation, and that is protective even if the esters cannot be broken down.
 
Last edited:

haidut

Member
Forum Supporter
Joined
Mar 18, 2013
Messages
19,798
Location
USA / Europe
I don't know if you've ever read Anthony Colpo's book "The Great Cholesterol Con," but there are three chapters that deal with this very issue. Chapter 10 "Money, Politics, and Cholesterol" Chapter 11 "Creating a 'Consensus'" and Chapter 12 "If We Want Your Opinion, We'll Give It To You!"

He specifically talks about that infamous Time Magazine with "Cholesterol: And Now The Bad News...." on the cover, and the Consensus Development Conference in Bethesda Maryland in 1984, and how it was clearly pre-planned agenda, to spread the idea of Cholesterol being bad. He also discusses how the Vegetable Oil industry profited off this "Consensus" before statins.

Interesting, thanks. I think I can find this book as PDF so I will take a look at those chapters.
 

Similar threads

Back
Top Bottom