Jonasㅤㅤ
Luminary
- Joined
- Sep 3, 2023
- Posts
- 6,666
- Reputation
- 21,431
How to manage your cholesterol effectively - The last secret about longevity
What is cholesterol?
Disclaimer: For the sake of this thread, I want you to forget everything you’ve ever heard about cholesterol.
Cholesterol is a fatty substance essential for many processes in the body and is found in every animal cell.
Managing your cholesterol is extremely important. Cardiovascular diseases remain the leading cause of death worldwide.
The Role of cholesterol in the body
Now unlike DHT after puberty, cholesterol is quite important and you should think twice before nuking it to the ground.
Cholesterol is required to build and maintain membranes and helps in regulating their fluidity. It also affects substrate presentation and plays a major role in the epidermis and has its own signalling pathways.
The most important aspect of cholesterol though is the steroidogenesis, the process by which many sex hormones including testosterone and adrenal gland hormones are synthesized.
I'm sure you've seen this image before.
There are a few studies claiming there is a weak correlation between dietary cholesterol and total testosterone levels.
This study suggests that HDL levels are correlated with androgen levels.
And this one suggests the opposite.
It is only logical that cholesterol affects hormone levels via the steroidogenesis pathway. Though additional dietary cholesterol intake may not result in increased testosterone levels.
Additionally the body compensates for dietary cholesterol intake by reducing its own cholesterol production.(1)
Unlike what many believe dietary cholesterol doesn't cross the blood-brain barrier.
The brain produces its own supply via astrocytes.(2)
What does this tell us?
Cholesterol isn't bad at all. The dose makes the poison. The thing is, you can't know if it is the poison without getting a blood test.
Stay better safe than sorry. Use this table as a general guide.
Additionally you can use Apob/ApoA as guidance, since all those values correlate with eachother.
Atherosclerosis
Atherosclerosis is a progressive disease marked by the accumulation of lipids and fibrous elements in the large arteries in response to oxidative stress.(3)
Let me make it more clear: There are multiple factors contributing to atherosclerosis.
Gene polymorphisms heavily influence whether your body can effectively clear LDL cholesterol.
I checked my genome and found a mutation in the LDL-R
Apart from that obviously LDL and HDL levels directly influence the risk of developing atherosclerosis. Oxidative stress is a heavily underestimated factor too.
The best way to mitigate the risks would be decreasing all of those factors.
This is where the real thread starts.
Effective ways to reduce your risk of developing atherosclerosis
Low bodyfat%
It may not look healthy to normies, but being at a low bodyfat% in general is extremely healthy while being the biggest Looksmax simultaneously.
It can improve your lipids naturally without pharmacological intervention.(4)
Exercise
Be it aerobic exercise or strength training, just be the fuck in shape and move.
This will also manage your blood pressure naturally.(5)
Antioxidants
To mitigate the oxidative stress aspect of atherosclerosis you should eat a balanced, non-processed diet. It is fucking simple.
Extremely beneficial antioxidants include coQ10, OPC and NAC just to name a few.
Quit smoking
Smoking is one of the worst things you could do for your lipids and health in general.
There are three primary ways in how smoking affects coronary heart disease.(6)
1. Carbon monoxide promotes atherogenesis by damaging the endothelium and reducing oxygen delivery.
2. Nicotine stimulates the adrenergic system, leading to increased blood pressure and myocardial oxygen demand.
3. Smoking disrupts the lipid metabolism resulting in higher LDL and lower HDL cholesterol levels.
Also keep in mind smokers usually maintain a lower bf%, meaning smoking completely negates the benefits of being at a low bf% in the first place.
There are countless other risks associated with smoking. If you insist on continuing, don’t call yourself a Looksmaxxer.
Pharmacology
Now that we covered the water topics let's discuss the real shit. This is for you if you want to take your longevity protocol to the next level.
Statins
Ezetimibe
Obicetrapip
PCSK-9 inhibitors
SR9009
Retatrutide
Bempedoic acid
What is cholesterol?
Disclaimer: For the sake of this thread, I want you to forget everything you’ve ever heard about cholesterol.
Cholesterol is a fatty substance essential for many processes in the body and is found in every animal cell.
Managing your cholesterol is extremely important. Cardiovascular diseases remain the leading cause of death worldwide.
The Role of cholesterol in the body
Now unlike DHT after puberty, cholesterol is quite important and you should think twice before nuking it to the ground.
Cholesterol is required to build and maintain membranes and helps in regulating their fluidity. It also affects substrate presentation and plays a major role in the epidermis and has its own signalling pathways.
The most important aspect of cholesterol though is the steroidogenesis, the process by which many sex hormones including testosterone and adrenal gland hormones are synthesized.
I'm sure you've seen this image before.
There are a few studies claiming there is a weak correlation between dietary cholesterol and total testosterone levels.
This study suggests that HDL levels are correlated with androgen levels.
And this one suggests the opposite.
It is only logical that cholesterol affects hormone levels via the steroidogenesis pathway. Though additional dietary cholesterol intake may not result in increased testosterone levels.
Additionally the body compensates for dietary cholesterol intake by reducing its own cholesterol production.(1)
Unlike what many believe dietary cholesterol doesn't cross the blood-brain barrier.
The brain produces its own supply via astrocytes.(2)
What does this tell us?
Cholesterol isn't bad at all. The dose makes the poison. The thing is, you can't know if it is the poison without getting a blood test.
Stay better safe than sorry. Use this table as a general guide.
Additionally you can use Apob/ApoA as guidance, since all those values correlate with eachother.
Atherosclerosis
Atherosclerosis is a progressive disease marked by the accumulation of lipids and fibrous elements in the large arteries in response to oxidative stress.(3)
Let me make it more clear: There are multiple factors contributing to atherosclerosis.
Gene polymorphisms heavily influence whether your body can effectively clear LDL cholesterol.
I checked my genome and found a mutation in the LDL-R
Apart from that obviously LDL and HDL levels directly influence the risk of developing atherosclerosis. Oxidative stress is a heavily underestimated factor too.
The best way to mitigate the risks would be decreasing all of those factors.
This is where the real thread starts.
Effective ways to reduce your risk of developing atherosclerosis
Low bodyfat%
It may not look healthy to normies, but being at a low bodyfat% in general is extremely healthy while being the biggest Looksmax simultaneously.
It can improve your lipids naturally without pharmacological intervention.(4)
Exercise
Be it aerobic exercise or strength training, just be the fuck in shape and move.
This will also manage your blood pressure naturally.(5)
Antioxidants
To mitigate the oxidative stress aspect of atherosclerosis you should eat a balanced, non-processed diet. It is fucking simple.
Extremely beneficial antioxidants include coQ10, OPC and NAC just to name a few.
Quit smoking
Smoking is one of the worst things you could do for your lipids and health in general.
There are three primary ways in how smoking affects coronary heart disease.(6)
1. Carbon monoxide promotes atherogenesis by damaging the endothelium and reducing oxygen delivery.
2. Nicotine stimulates the adrenergic system, leading to increased blood pressure and myocardial oxygen demand.
3. Smoking disrupts the lipid metabolism resulting in higher LDL and lower HDL cholesterol levels.
Also keep in mind smokers usually maintain a lower bf%, meaning smoking completely negates the benefits of being at a low bf% in the first place.
There are countless other risks associated with smoking. If you insist on continuing, don’t call yourself a Looksmaxxer.
Pharmacology
Now that we covered the water topics let's discuss the real shit. This is for you if you want to take your longevity protocol to the next level.
Statins
General info
Let’s cover this first. It’s the primary normie method for lowering cholesterol and LDL levels.
They’re also the best-selling pharmaceuticals ever in history so if you’re skeptical about biased/manipulated studies, this is one of the first compounds you should question.(7)
Statins are generally less effective in treating individuals with genetic disorders such as familial hypercholesterolemia.
Mechanisms of action
Statins work by inhibiting HMG-CoA reductase, an enzyme involved in a key step of the cholesterol synthesis pathway.
They also increase LDL receptors in the liver meaning more LDL can be removed from the bloodstream.
Benefits
Reduction in C-Reactive protein, tumornecrosis factor alpha and interleukins.
Statins also slightly activate PPARα via overexpression of COX-2.
Side effects
We can differentiate between two groups of statins:
Hydrophilic statins: Won't cross the blood-brain barrier, more inflammation.
Examples: Rosuvastatin and pravastatin.
Lipophilic statins: Crosses the blood-brain barrier, less inflammation.
Examples: Pitavastatin, atorvastatin and simvastatin.
Besides that statins have a ±10% risk of diabetes in men.(8)
Recommendation
The best statins by far are pitavastatin and rosuvastatin as they have the best side effect profile.
Pitavastatin
A study shows that pitavastatin reduces total cholesterol by 21%, LDL-C by 31% and increases HDL-C by 14% and 25% at 12 and 104 weeks.(9)
Dosage: Take 1-4mg daily.
Rosuvastatin
This is by far one of the best statins besides pitavastatin in terms of side effect profile and effectiveness.
Dosage: You can take anything from 5 to 40mg. Even a low dosage of 5mg seems to be quite effective.(10)
Let’s cover this first. It’s the primary normie method for lowering cholesterol and LDL levels.
They’re also the best-selling pharmaceuticals ever in history so if you’re skeptical about biased/manipulated studies, this is one of the first compounds you should question.(7)
Statins are generally less effective in treating individuals with genetic disorders such as familial hypercholesterolemia.
Mechanisms of action
Statins work by inhibiting HMG-CoA reductase, an enzyme involved in a key step of the cholesterol synthesis pathway.
They also increase LDL receptors in the liver meaning more LDL can be removed from the bloodstream.
Benefits
Reduction in C-Reactive protein, tumornecrosis factor alpha and interleukins.
Statins also slightly activate PPARα via overexpression of COX-2.
Side effects
We can differentiate between two groups of statins:
Hydrophilic statins: Won't cross the blood-brain barrier, more inflammation.
Examples: Rosuvastatin and pravastatin.
Lipophilic statins: Crosses the blood-brain barrier, less inflammation.
Examples: Pitavastatin, atorvastatin and simvastatin.
Besides that statins have a ±10% risk of diabetes in men.(8)
Recommendation
The best statins by far are pitavastatin and rosuvastatin as they have the best side effect profile.
Pitavastatin
A study shows that pitavastatin reduces total cholesterol by 21%, LDL-C by 31% and increases HDL-C by 14% and 25% at 12 and 104 weeks.(9)
Dosage: Take 1-4mg daily.
Rosuvastatin
This is by far one of the best statins besides pitavastatin in terms of side effect profile and effectiveness.
Dosage: You can take anything from 5 to 40mg. Even a low dosage of 5mg seems to be quite effective.(10)
Ezetimibe
Ezetimibe inhibits the absorption of dietary cholesterol. You can expect a reduction of around 30% in total cholesterol.
It can improve nonalcoholic fatty liver disease. Besides that ezetimibe reduces c-reactive protein.(11)
It doesn't affect fat-soluble vitamins unlike popular belief.(12)
Ezetimibe monotherapy isn't as effective as combining it with another compound like statins.
Dosage: 5-10mg once daily.
It can improve nonalcoholic fatty liver disease. Besides that ezetimibe reduces c-reactive protein.(11)
It doesn't affect fat-soluble vitamins unlike popular belief.(12)
Ezetimibe monotherapy isn't as effective as combining it with another compound like statins.
Dosage: 5-10mg once daily.
Obicetrapip
Obicetrapip is the first CETP inhibitor that effectively manages lipids without being utter garbage. It is significantly better than torcetrapib, dalcetrapib and evacetrapib combined.
The compound is quite new and already showed promising results. Besides that it improves alzheimer's disease.
"LDL-C decreased from baseline to week 12 by 63.4%, 43.5%, and 6.35% in combination, monotherapy, and placebo groups, respectively (p<0.0001 vs. Placebo)."(13)
Both active treatments also significantly reduced concentrations of non-HDL-C, apolipoprotein B, and total and small LDL particles. Obicetrapib was well tolerated and no safety issues were identified.(13)
Combining it with another compound would be a good choice as with ezetimibe.
Dosage: 5-10mg daily.
The compound is quite new and already showed promising results. Besides that it improves alzheimer's disease.
"LDL-C decreased from baseline to week 12 by 63.4%, 43.5%, and 6.35% in combination, monotherapy, and placebo groups, respectively (p<0.0001 vs. Placebo)."(13)
Both active treatments also significantly reduced concentrations of non-HDL-C, apolipoprotein B, and total and small LDL particles. Obicetrapib was well tolerated and no safety issues were identified.(13)
Combining it with another compound would be a good choice as with ezetimibe.
Dosage: 5-10mg daily.
PCSK-9 inhibitors
This is one of the best pathways to improve your lipids drastically.
PCSK-9 inhibitors are fully humanized monoclonal antibodies that prevent the enzyme PCSK-9 from binding to LDL receptors in the liver. This leads to an upregulation in receptors leading to a reduction in LDL.
The apolipoprotein B autoantibody and anti-PCSK9 antibody reduced the level of LDL and plaques in animal studies.(14)
Dosage: Alirocumab and evolocumab are injected subcutaneously every 2 to 4 weeks. Sourcing is extremely hard and you are better off trying to get a prescription.
Here is my personal alirocumab.
It is extremely expensive, so try to have the cost covered by your health insurance.
PCSK-9 inhibitors are fully humanized monoclonal antibodies that prevent the enzyme PCSK-9 from binding to LDL receptors in the liver. This leads to an upregulation in receptors leading to a reduction in LDL.
The apolipoprotein B autoantibody and anti-PCSK9 antibody reduced the level of LDL and plaques in animal studies.(14)
Dosage: Alirocumab and evolocumab are injected subcutaneously every 2 to 4 weeks. Sourcing is extremely hard and you are better off trying to get a prescription.
Here is my personal alirocumab.
It is extremely expensive, so try to have the cost covered by your health insurance.
SR9009
SR9009 (Stenabolic) is an agonist of Rev-Erbα/ß along with SR9011 and other synthetic Rev-Erbα/ß ligands. It is being used to boost mitochondrial activity and fat metabolism. It can also have a positive impact on your circadian rhythm, endurance and inflammation.
You can see a few benefits of agonizing this pathway below.
You should use this compound ideally for the lipid aspect, in conjunction with the tons of other benefits. If you're trying to negate some side effects of PEDs, you should look into SR9009/SR9011 as well.(15)
Dosage: 10-40mg.(16)
You can see a few benefits of agonizing this pathway below.
You should use this compound ideally for the lipid aspect, in conjunction with the tons of other benefits. If you're trying to negate some side effects of PEDs, you should look into SR9009/SR9011 as well.(15)
Dosage: 10-40mg.(16)
Retatrutide
Retatrutide is a godsent molecule. It is a triple agonist of GLP-1, GIP and the glucagon receptor.
You can expect an inprovement in insulin sensitivity, increased energy expenditure, appetite supression and barely any side effects.
It also can support lipids drastically.
"apoB was reduced by up to 19.6% and 24.2% at 24 and 48 weeks"(17)
"At 48 weeks, the drug reduced triglycerides and apoC-III levels by up to 40.6% and 38.0%"(17)
"Retatrutide also reduced the number of total and highly atherogenic small LDL particles (LDLP)"(17)
Retatrutide is by far one of the best compounds for literally anything, be it Looksmaxxing or just general health.
Dosage: Anything between 4-8mg weekly is a good effective dose. Dosages above 8mg have extreme diminishing returns in terms of effectiveness. You can split the dosage to twice a week.
You can expect an inprovement in insulin sensitivity, increased energy expenditure, appetite supression and barely any side effects.
It also can support lipids drastically.
"apoB was reduced by up to 19.6% and 24.2% at 24 and 48 weeks"(17)
"At 48 weeks, the drug reduced triglycerides and apoC-III levels by up to 40.6% and 38.0%"(17)
"Retatrutide also reduced the number of total and highly atherogenic small LDL particles (LDLP)"(17)
Retatrutide is by far one of the best compounds for literally anything, be it Looksmaxxing or just general health.
Dosage: Anything between 4-8mg weekly is a good effective dose. Dosages above 8mg have extreme diminishing returns in terms of effectiveness. You can split the dosage to twice a week.
Bempedoic acid
Bempedoic Acid is an oral prodrug that inhibits ATP citrate lyase, which is involved in the liver's biosynthesis of cholesterol upstream of HMG-CoA reductase, the enzyme that is blocked by statins.
"At week 12, bempedoic acid reduced the mean LDL cholesterol level by 19.2 mg per deciliter (0.50 mmol per liter)."(18)
Dosage: 180mg daily.(19)
"At week 12, bempedoic acid reduced the mean LDL cholesterol level by 19.2 mg per deciliter (0.50 mmol per liter)."(18)
Dosage: 180mg daily.(19)
@chadisbeingmade @Clavicular @Orc @Eltrē @Magnum Opus
