How to increase HDL # and HDL cholesterol levels
Sources of HDL
HDL are the smallest and most heterogeneous of the plasma lipoproteins. They can be formed in three ways:
(i) from intravascular lipolysis of triglyceride-rich lipoproteins (chylomicron & VLDL)Sources of HDL
HDL are the smallest and most heterogeneous of the plasma lipoproteins. They can be formed in three ways:
(ii) from intestinal mucosal cells
(iii) by the liver.
Lipolysis
When large triglyceride-rich lipoproteins undergo lipolysis at the capillary endothelium, the excess surface lipids of these particles are sloughed off as nascent discoidal HDL which are rich in phospholipids and contain little apolipoprotein. They also contain a surface enzyme called lecthin:cholesterol acyltransferase (LCAT). These discoidal structures can absorb free excess cholesterol off surfaces of rbcs and epithelial cells of the intima.
When large triglyceride-rich lipoproteins undergo lipolysis at the capillary endothelium, the excess surface lipids of these particles are sloughed off as nascent discoidal HDL which are rich in phospholipids and contain little apolipoprotein. They also contain a surface enzyme called lecthin:cholesterol acyltransferase (LCAT). These discoidal structures can absorb free excess cholesterol off surfaces of rbcs and epithelial cells of the intima.
Intestines
The intestinal mucosa also secretes nascent HDL into lymph and they travel via the lymphatics, out through the jugular vein, into the general circulation. They then mature in the peripheral circulation by cholesterol uptake and subsequent LCAT action (these reactions are concerted).
States of cholesterol
Cholesterol exists in the body in two states, the active form is free cholesterol (FC) and the non active or storage form is the esterified form, cholesteryl esters (CE).
LCAT activity in blood
LCAT is present on the HDL surfaces. LCAT serves to catalyse the conversion of FC to CE.
Fates of cholesterol in HDL
FC and CE have different water preferences or polarity. FC is more polar than CE, which means FC is more likely to remain at the HDL surface while CE has to go somewhere. Where should CE go? CE will most likely enter the HDL core. This means as soon as FC is converted to CE by LCAT, the CE formed rapidly goes inside HDL. What is the result of CE entering into HDL core?
Outcome of LCAT activity: Impact on HDL size
From basic chemistry, we know CE is a larger molecule compared to FC. So when CE enters the HDL core, it will cause the HDL to swell or increase in size, ie HDL become larger particles. Is there a limit to how big HDL can get? Yes, definitely. Science is about exact numbers. So there is a limit to how big HDL can be.
Fates of HDL
What happens when HDL are as big as they can be? There are two possibilities that can happen - 1) big HDL (known as HDL2) can deliver their contents to the liver, and 2) they can transfer their contents to large atherogenic lipoproteins (chylomicron, VLDL, IDL) via an exchange mechanism (CE is exchanged for triglycerides, TG). This second route (CE exchange for TG) is part of the reverse cholesterol transport.
States of cholesterol
Cholesterol exists in the body in two states, the active form is free cholesterol (FC) and the non active or storage form is the esterified form, cholesteryl esters (CE).
LCAT activity in blood
LCAT is present on the HDL surfaces. LCAT serves to catalyse the conversion of FC to CE.
Fates of cholesterol in HDL
FC and CE have different water preferences or polarity. FC is more polar than CE, which means FC is more likely to remain at the HDL surface while CE has to go somewhere. Where should CE go? CE will most likely enter the HDL core. This means as soon as FC is converted to CE by LCAT, the CE formed rapidly goes inside HDL. What is the result of CE entering into HDL core?
Outcome of LCAT activity: Impact on HDL size
From basic chemistry, we know CE is a larger molecule compared to FC. So when CE enters the HDL core, it will cause the HDL to swell or increase in size, ie HDL become larger particles. Is there a limit to how big HDL can get? Yes, definitely. Science is about exact numbers. So there is a limit to how big HDL can be.
Fates of HDL
What happens when HDL are as big as they can be? There are two possibilities that can happen - 1) big HDL (known as HDL2) can deliver their contents to the liver, and 2) they can transfer their contents to large atherogenic lipoproteins (chylomicron, VLDL, IDL) via an exchange mechanism (CE is exchanged for triglycerides, TG). This second route (CE exchange for TG) is part of the reverse cholesterol transport.
Liver
The liver secretes small spherical HDL and is the major producer of such HDL during fasting.
HDL cholesterol levels in blood
Other than normal HDL, why do we see cases of low HDL? Cases of high HDL? What can possibly lead to low HDL? What can possibly cause HDL to be elevated in blood?
HDL metabolism wrt size distribution
From research we understand that the lipoprotein particles are constantly in a dynamic state. This means their numbers and forms constantly change with time. The collection of HDL particles at time A may differ from HDL particles at time B in the same individual. How can this be? These lipoprotein particles are constantly being shaped and re-shaped by enzymes which are part of HDL metabolism. There are also other factors such as nicotine, and hormones that affect HDL numbers and size distribution. What this means then is if I take a blood sample from two people of the same age and BMI but of opposite sex, I will not get the same HDL profile for both of them. Each HDL profile will be different not only because of gender but also hormones and other factors.
Causes of low HDL cholesterol in blood
Factors known to reduce HDL levels are being sedantary, ie not moving much and not using the skeletal muscles.
Causes of high HDL cholesterol in blood
Factors known to increase HDL levels are intense physical activity and non smoking Different scientists have different interpretations of physical activity levels. Asking two people of the same physical strength to do the same set of exercises may give different levels of HDL in the long run, let's say in three months. Quit smoking instantly raises HDL levels in blood.
Causes of high HDL cholesterol in blood
Factors known to increase HDL levels are intense physical activity and non smoking Different scientists have different interpretations of physical activity levels. Asking two people of the same physical strength to do the same set of exercises may give different levels of HDL in the long run, let's say in three months. Quit smoking instantly raises HDL levels in blood.
HDL matrices and rubrics
What statements (hypotheses) can we draw from such manipulations?
# of HDL in blood reflects the synthetic activities of lypolysis, intestines and liver.
Small HDL (known as HDL3) are not favoured and regarded as less healthier.
Larger HDL (known as HDL2) are favoured and regarded as healthier.
The ratio of HDL2/HDL3 should be higher in healthier individuals
The ratio of HDL3/HD2 should be lower in healthier individuals.
It is safer to have more HDL2 than HDL3.
It is less safe to have more HDL3 than HDL2.
# of HDL will reflect HDL cholesterol levels in blood.
High # of small HDL may give normal or low HDL levels in blood.
High # of large HDL may give normal or high HDL levels in blood.
Low # of small HDL will necessarily give low HDL levels in blood.
Low # of large HDL will give normal or low HDL levels in blood.
HDL cholesterol lab test (analysis)
We sometimes forget that HDL is a double-step lab test, which means it is subject to more errors than a straight forward one-step test. HDL cholesterol is determined in the supernatant fluid after all other lipoproteins have been removed by chemical precipitation. Chemical precipitation is a tricky step to do in the routine lab. Sometimes it works alright, other times it is a total failure! Even the best lab technologist will introduce an error in the chemical precipitation step before the supernatant is harvested for chemical analysis to determine (HDL) cholesterol content.
After the chemical precipitation, the supernatant is analysed just as for cholesterol test. A cholesterol test is easy to do but an error can easily slip in at analysis time. We have to remember HDL cholesterol is a tiny value. One small error can easily give a false value.
Conclusion
In conclusion, if a HDL cholesterol value is LOW, I would suspect a technical or lab error first. If a repeat still shows a LOW HDL cholesterol value, then exercise is the way to go. HDL levels in blood are sensitive to physical activity and nicotine. Increase physical activity will increase HDL levels in blood. Since HDL are increased with intense physical activity (with much skeletal muscle involvement), I would say an intense physical training may be needed to raise HDL levels in some individuals who have a hard time raising their HDL levels.
Whether we fast or not, HDL are always produced by the body. Intravascular lipolysis and intestinal mucosa when combined produce quite a substantial amount of HDL and these sources are a bit more significant in the postprandial state (fed state). Otherwise the liver is a source of HDL.
Whether we fast or not, HDL are always produced by the body. Intravascular lipolysis and intestinal mucosa when combined produce quite a substantial amount of HDL and these sources are a bit more significant in the postprandial state (fed state). Otherwise the liver is a source of HDL.
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