Mitra
03-09-2006, 05:05 AM
I've lowered my cholesterol but...
Why is my LDL still high?
Gabriel E. Guzmán, Ph.D.
Those of us who follow a low-carbohydrate diet (“low-carb” diet) can tell you the countless benefits we’ve experienced. Ranging from controlled (and normal) blood sugar levels and blood pressure to weight loss an improvement, even elimination of snoring. But what can we tell you about our cholesterol levels, if they have been high before we started a low-carb diet? We would tell you how we’ve managed to lower our cholesterol levels to call then “normal”. However, even though our total cholesterol decreases with time and stabilizes around physiologically acceptable levels, some will add this to their response: “…but my LDL is still high”, or “… my LDL has gone up and my doctor wants to put me on cholesterol-lowering drugs…” Why does that happen? Is that the forever-sought proof that low-carbohydrate diets don’t work?
The answer to the second question is easy: not in the least! In fact, recent studies comparing carbohydrate-restricted diets with a standard low-fat/low calorie approach show that those on a “low-carb” diet improved their cholesterol levels significantly more than those in the standard diet. Interestingly, and as it frequently happens among scientists, since the results were opposite to what they expected, they called them “paradoxical”.
Reviewing the way the body makes cholesterol, sort of biochemistry 101, we find that there may not be a paradox at all… only a wrong hypothesis to begin with. This leads to the second question: why do LDL-cholesterol levels (and sometimes total cholesterol levels as well) increase while on a “low-carb” diet?
A fully detailed answer may consume the space dedicated to this contribution, and it may be impossible to avoid the technical language associated with the dynamics of cholesterol metabolism. However, a less formal answer can help to grasp why a “low-carb” diet is effective to lower and control cholesterol levels. For this, it may help to think of cholesterol in two ways; how it is made in the body, and how the body handles it. It’s also helpful to establish some premises that are normally ignored by the experts. First, most of the cholesterol you measure in your blood is made by your own liver cells and only about 25% of it comes from dietary sources. In fact, we need it! Second, the “raw material” for cholesterol (something called “Acetyl CoA”), although it can be produced from fat metabolism, doesn’t really come from that fat only. In other words, just because fat metabolism produces Acetyl CoA, doesn’t mean that cholesterol will necessarily be made. Third, carbohydrate metabolism provides not only with cholesterol’s raw material, but also with the necessary hormonal stimulus to initiate cholesterol synthesis inside the cells. That’s a fundamental difference between the hormonal response to food that may be higher in fat but with minimum carbohydrate and the response to carbohydrate-laden food. With that in mind, perhaps it’s easier to explain the effect of carbohydrate restriction on cholesterol levels.
The most important effect of carbohydrate restriction is the reduction in insulin levels. A “high- carb” diet encourages the constant release of insulin to levels that are more than enough to cope with the disposal of excessive blood sugar, at least up to a point where is no longer enough.
Before that happens, constant hyperinsulinemia, although deals with excess blood sugar, also stimulates other processes in the body, including cholesterol and fat synthesis. Statin drugs, used to lower LDL-cholesterol levels, do their work by inhibiting a key enzyme in the machinery that makes cholesterol in the cells. Think of this enzyme as the one that “decides” if cholesterol is made or not, even if the raw materials are present. It turns out that insulin promotes the activity of this enzyme. If at this point you’re thinking “so… why not shutting down that enzyme by reducing insulin levels?” You’re right! That is a very plausible mechanism by which a “low- carb” diet reduces cholesterol levels. By shutting down the cholesterol-making machinery inside the cells, they “starve” of cholesterol and respond by catching whatever cholesterol they can from the blood. Cells do that by making more “LDL-receptors” and exposing them in their membranes to capture any LDL-bound cholesterol circulating in the blood, thus reducing its levels in circulation. That is also how statin drugs work. So, here you have it, a “low-carb” diet may very well be your “statin-replacement” diet-therapy! This addresses the part on how cholesterol is made and how “low-carb” helps to control it, but still doesn’t explain why LDL levels seem to increase. After all, isn’t LDL-cholesterol the villain in the cardiovascular disease drama?
Since cholesterol is not water soluble, just as other lipids, it must be transported throughout the body packed in special carriers that are water-soluble. Depending on where cholesterol needs to go, so the lipoprotein that will carry it. For example, when dietary cholesterol is carried from the intestine to the liver, it’s transported in “chylomicrons”. When it needs to go from the liver to other tissues, it is transported in LDL particles and it’s called LDL-cholesterol, and that’s the number the clinician is interested in order to make a decision whether or no to prescribe cholesterol-lowering drugs.
Assuming that the diet contains no cholesterol, as is the case in a diet that restricts fats, the body makes it. If, in addition, the diet contains excess carbohydrates, enough to cause constant hyperinsulinemia, then the cholesterol-lowering machinery is always on and cholesterol is continuously packed in LDL particles to be sent out to the tissues. But cholesterol is not the only lipid being carried in LDL particles; they also contain triglycerides, and lots of them. Think of LDL particles as the shuttles that “deliver” cholesterol and triglycerides to other tissues. It is now recognized that not all LDL particles are made in the same way; some of these particles are small and dense, others are large and light. In fact, there are at least seven subtypes of LDL particles that differ in size. There is mounting evidence that links the small, dense LDL particles to increased risk of cardiovascular disease. But what determines the type of LDL particle found at a given time in circulation?
Recent studies have shown that diabetics have a large amount of the small sized particles, which are atherogenic and known to be a more significant risk of coronary artery diseases. Research has also shown the importance of triglycerides to cardiovascular disease, indicating that the risk increases with increasing levels of triglycerides. It is also been recently established that triglycerides correlate independently with the small sized LDL particle. Finally, it is also well known that when triglycerides fall (for example by fibrate therapy), LDL-cholesterol may rise, but just which type of LDL? From these studies we can’t get the answer. However, a recent study comparing diabetics and healthy individuals, analyzing the LDL particle subtype, found that diabetics had more small LDL particles than healthy individuals, and size particle was correlated with triglycerides levels. It would seem that the more triglycerides, the more small size LDL particles, the higher the risk of coronary artery disease. Thus, it’s “how much”, but “which type” of LDL-cholesterol particle what matters. Unfortunately, the way LDL-cholesterol is obtained in the clinic is not by actually measuring it directly, but by using a formula first proposed in 1972 known as The Friedewald Formula.
A recent review of the limitations and pitfalls of the Friedewald formula exposed “the Achilles heels” of the very method used today by medical practitioners to decide on the prescription of cholesterol-lowering drugs, despite the associated risks. As it turns out, the formula is useful only when triglycerides are not too high or not too low. In fact, the mathematical method of calculating LDL-cholesterol can introduce unacceptable errors in as many as 40% of subjects with triglycerides levels in the range in which results are routinely reported from clinical laboratories. The source of the error is out of the scope of this article, but suffice to say that such errors can bedevil clinical assessment.
So, when a person on a “low-carb” diet notices an increase in LDL-cholesterol (as reported by the laboratory), one has to wonder just how much of that is real and how much is an artifact of the calculation. Unless the actual type of LDL-particle and the relative amount within the total LDL particles is established, the calculated LDL value is meaningless and can’t really say anything regarding the benefits (or lack thereof) of a low-carbohydrate diet.
All this, put together on a big canvas, paints the following picture: A low-carbohydrate diet effectively lowers insulin levels, which results in a decrease in cholesterol production by controlling the activity of the key enzyme involved in cholesterol synthesis. This results in the decrease of circulating cholesterol in a manner similar to that attributed to statin drugs. A decrease in excess insulin levels also reduces triglycerides levels, which in turn reduces the amount of small sized LDL particles, possibly increasing the amount of large sized particles, not associated with risk of cardiovascular disease.
So, if you’re following a “low-carb” diet and your lab tests come back with an LDL value apparently high, remember that it is the type of particle what gives the most information. Moreover, before worrying about the LDL-cholesterol number, check the numbers next to “Triglycerides” and “HDL-cholesterol”. Those are the numbers that can tell you what’s happening in your quest for better health.
References
Westman EC et al. 2003. A review of Low-carbohydrate Ketogenic Diets. Current
Atherosclerosis Reports 5:476-483.
Sniderman AD et al. 2003. Triglycerides and small dense LDL: the twin Achilles heels of the
Friedewald formula. Clinical Biochemistry 36:499-504.
Woochang L et al. 2003. Low-density lipoprotein subclass and its correlating factors in
diabetics. Clinical Biochemistry 36:657-661.
Brehm BJ et al. 2003. A randomized trial comparing a very low carbohydrate diet and a calorie-
restricted low fat diet on body weight and cardiovascular risk factors in healthy women. Journal
of Clinical Endocrinology and Metabolism 88:1617-1623.
Eades MR and MD Eades. 2000. The Protein Power LifePlan. Warner Books, Inc. New York.
434 pp.
Why is my LDL still high?
Gabriel E. Guzmán, Ph.D.
Those of us who follow a low-carbohydrate diet (“low-carb” diet) can tell you the countless benefits we’ve experienced. Ranging from controlled (and normal) blood sugar levels and blood pressure to weight loss an improvement, even elimination of snoring. But what can we tell you about our cholesterol levels, if they have been high before we started a low-carb diet? We would tell you how we’ve managed to lower our cholesterol levels to call then “normal”. However, even though our total cholesterol decreases with time and stabilizes around physiologically acceptable levels, some will add this to their response: “…but my LDL is still high”, or “… my LDL has gone up and my doctor wants to put me on cholesterol-lowering drugs…” Why does that happen? Is that the forever-sought proof that low-carbohydrate diets don’t work?
The answer to the second question is easy: not in the least! In fact, recent studies comparing carbohydrate-restricted diets with a standard low-fat/low calorie approach show that those on a “low-carb” diet improved their cholesterol levels significantly more than those in the standard diet. Interestingly, and as it frequently happens among scientists, since the results were opposite to what they expected, they called them “paradoxical”.
Reviewing the way the body makes cholesterol, sort of biochemistry 101, we find that there may not be a paradox at all… only a wrong hypothesis to begin with. This leads to the second question: why do LDL-cholesterol levels (and sometimes total cholesterol levels as well) increase while on a “low-carb” diet?
A fully detailed answer may consume the space dedicated to this contribution, and it may be impossible to avoid the technical language associated with the dynamics of cholesterol metabolism. However, a less formal answer can help to grasp why a “low-carb” diet is effective to lower and control cholesterol levels. For this, it may help to think of cholesterol in two ways; how it is made in the body, and how the body handles it. It’s also helpful to establish some premises that are normally ignored by the experts. First, most of the cholesterol you measure in your blood is made by your own liver cells and only about 25% of it comes from dietary sources. In fact, we need it! Second, the “raw material” for cholesterol (something called “Acetyl CoA”), although it can be produced from fat metabolism, doesn’t really come from that fat only. In other words, just because fat metabolism produces Acetyl CoA, doesn’t mean that cholesterol will necessarily be made. Third, carbohydrate metabolism provides not only with cholesterol’s raw material, but also with the necessary hormonal stimulus to initiate cholesterol synthesis inside the cells. That’s a fundamental difference between the hormonal response to food that may be higher in fat but with minimum carbohydrate and the response to carbohydrate-laden food. With that in mind, perhaps it’s easier to explain the effect of carbohydrate restriction on cholesterol levels.
The most important effect of carbohydrate restriction is the reduction in insulin levels. A “high- carb” diet encourages the constant release of insulin to levels that are more than enough to cope with the disposal of excessive blood sugar, at least up to a point where is no longer enough.
Before that happens, constant hyperinsulinemia, although deals with excess blood sugar, also stimulates other processes in the body, including cholesterol and fat synthesis. Statin drugs, used to lower LDL-cholesterol levels, do their work by inhibiting a key enzyme in the machinery that makes cholesterol in the cells. Think of this enzyme as the one that “decides” if cholesterol is made or not, even if the raw materials are present. It turns out that insulin promotes the activity of this enzyme. If at this point you’re thinking “so… why not shutting down that enzyme by reducing insulin levels?” You’re right! That is a very plausible mechanism by which a “low- carb” diet reduces cholesterol levels. By shutting down the cholesterol-making machinery inside the cells, they “starve” of cholesterol and respond by catching whatever cholesterol they can from the blood. Cells do that by making more “LDL-receptors” and exposing them in their membranes to capture any LDL-bound cholesterol circulating in the blood, thus reducing its levels in circulation. That is also how statin drugs work. So, here you have it, a “low-carb” diet may very well be your “statin-replacement” diet-therapy! This addresses the part on how cholesterol is made and how “low-carb” helps to control it, but still doesn’t explain why LDL levels seem to increase. After all, isn’t LDL-cholesterol the villain in the cardiovascular disease drama?
Since cholesterol is not water soluble, just as other lipids, it must be transported throughout the body packed in special carriers that are water-soluble. Depending on where cholesterol needs to go, so the lipoprotein that will carry it. For example, when dietary cholesterol is carried from the intestine to the liver, it’s transported in “chylomicrons”. When it needs to go from the liver to other tissues, it is transported in LDL particles and it’s called LDL-cholesterol, and that’s the number the clinician is interested in order to make a decision whether or no to prescribe cholesterol-lowering drugs.
Assuming that the diet contains no cholesterol, as is the case in a diet that restricts fats, the body makes it. If, in addition, the diet contains excess carbohydrates, enough to cause constant hyperinsulinemia, then the cholesterol-lowering machinery is always on and cholesterol is continuously packed in LDL particles to be sent out to the tissues. But cholesterol is not the only lipid being carried in LDL particles; they also contain triglycerides, and lots of them. Think of LDL particles as the shuttles that “deliver” cholesterol and triglycerides to other tissues. It is now recognized that not all LDL particles are made in the same way; some of these particles are small and dense, others are large and light. In fact, there are at least seven subtypes of LDL particles that differ in size. There is mounting evidence that links the small, dense LDL particles to increased risk of cardiovascular disease. But what determines the type of LDL particle found at a given time in circulation?
Recent studies have shown that diabetics have a large amount of the small sized particles, which are atherogenic and known to be a more significant risk of coronary artery diseases. Research has also shown the importance of triglycerides to cardiovascular disease, indicating that the risk increases with increasing levels of triglycerides. It is also been recently established that triglycerides correlate independently with the small sized LDL particle. Finally, it is also well known that when triglycerides fall (for example by fibrate therapy), LDL-cholesterol may rise, but just which type of LDL? From these studies we can’t get the answer. However, a recent study comparing diabetics and healthy individuals, analyzing the LDL particle subtype, found that diabetics had more small LDL particles than healthy individuals, and size particle was correlated with triglycerides levels. It would seem that the more triglycerides, the more small size LDL particles, the higher the risk of coronary artery disease. Thus, it’s “how much”, but “which type” of LDL-cholesterol particle what matters. Unfortunately, the way LDL-cholesterol is obtained in the clinic is not by actually measuring it directly, but by using a formula first proposed in 1972 known as The Friedewald Formula.
A recent review of the limitations and pitfalls of the Friedewald formula exposed “the Achilles heels” of the very method used today by medical practitioners to decide on the prescription of cholesterol-lowering drugs, despite the associated risks. As it turns out, the formula is useful only when triglycerides are not too high or not too low. In fact, the mathematical method of calculating LDL-cholesterol can introduce unacceptable errors in as many as 40% of subjects with triglycerides levels in the range in which results are routinely reported from clinical laboratories. The source of the error is out of the scope of this article, but suffice to say that such errors can bedevil clinical assessment.
So, when a person on a “low-carb” diet notices an increase in LDL-cholesterol (as reported by the laboratory), one has to wonder just how much of that is real and how much is an artifact of the calculation. Unless the actual type of LDL-particle and the relative amount within the total LDL particles is established, the calculated LDL value is meaningless and can’t really say anything regarding the benefits (or lack thereof) of a low-carbohydrate diet.
All this, put together on a big canvas, paints the following picture: A low-carbohydrate diet effectively lowers insulin levels, which results in a decrease in cholesterol production by controlling the activity of the key enzyme involved in cholesterol synthesis. This results in the decrease of circulating cholesterol in a manner similar to that attributed to statin drugs. A decrease in excess insulin levels also reduces triglycerides levels, which in turn reduces the amount of small sized LDL particles, possibly increasing the amount of large sized particles, not associated with risk of cardiovascular disease.
So, if you’re following a “low-carb” diet and your lab tests come back with an LDL value apparently high, remember that it is the type of particle what gives the most information. Moreover, before worrying about the LDL-cholesterol number, check the numbers next to “Triglycerides” and “HDL-cholesterol”. Those are the numbers that can tell you what’s happening in your quest for better health.
References
Westman EC et al. 2003. A review of Low-carbohydrate Ketogenic Diets. Current
Atherosclerosis Reports 5:476-483.
Sniderman AD et al. 2003. Triglycerides and small dense LDL: the twin Achilles heels of the
Friedewald formula. Clinical Biochemistry 36:499-504.
Woochang L et al. 2003. Low-density lipoprotein subclass and its correlating factors in
diabetics. Clinical Biochemistry 36:657-661.
Brehm BJ et al. 2003. A randomized trial comparing a very low carbohydrate diet and a calorie-
restricted low fat diet on body weight and cardiovascular risk factors in healthy women. Journal
of Clinical Endocrinology and Metabolism 88:1617-1623.
Eades MR and MD Eades. 2000. The Protein Power LifePlan. Warner Books, Inc. New York.
434 pp.