A recent study published in the online journal Lipids in Health and Disease demonstrates that low-carbohydrate diets act in much the same way statin drugs do to reduce cholesterol.
Before we delve into what this study shows, let’s take a moment and discuss the synthesis of cholesterol in the body.
Although every cell can make cholesterol, most is made in the liver and small intestine. The fact that every cell can make cholesterol should at least imply that cholesterol is a pretty important molecule, which indeed it is. Most of the cholesterol in the body is made in the cells, but about 15 percent of it comes from the diet.
When a cell needs cholesterol it has two places from which to get it: it can make it and/or it can get it from the blood. Usually it does both. If the cell makes cholesterol it goes through the multi-step process shown above. If the cell wants to get cholesterol from the blood, it synthesizes little protein structures called LDL receptors that it sends to the surface of the cell. Once on the surface of the cell these receptors bind to LDL-cholesterol in the blood and transport it into the interior where the cholesterol is released for use by the cell.
As in all synthesis pathways there is a single reaction in the long chain of reactions that is the rate-limiting one, the reaction that determines the overall output of the pathway. In the case of cholesterol synthesis this reaction is the step shown in the diagram below in which hydroxymethylglutaryl-CoA (HMG-CoA) is converted to mevanolate, catalyzed by the enzyme HMG-CoA reductase.
Scientists have known for years that the enzyme HMG-CoA reductase is the rate-limiting enzyme in the 
entire cholesterol synthesis cascade. They figured that if they could design a drug that would interfere with this enzyme, they would have a drug that would lower cholesterol. The class of drugs ultimately developed to perform this task are the statins. Statins are a type of drug called HMG-CoA reductase inhibitors.
When statins (or anything else) inhibit HMG-CoA reductase, the cells can’t make the cholesterol they need to function properly so they resort to the other method and synthesize many LDL receptors that are dispatched to the surface to harvest LDL-cholesterol from the bloodstream. The LDL-cholesterol extracted from the blood means there is less in the blood and levels measured are lower, which is why statins reduce LDL-cholesterol levels.
Now that we’ve had the briefest of primers on cholesterol synthesis, let’s look at this enlightening study. It would seem that if people eat a lot of cholesterol – as they usually do on low-carb diets – that cholesterol levels would go up. But it has been shown that in people following low-carb diets this doesn’t really happen. Why is this the case? That’s what the researchers who did this study wanted to find out.
Subjects were randomized into two groups, both of which consumed low-carb diets (10-15% energy from carbs, 30-35% from protein and 55-60% from fat) for 12 weeks. The groups differed in that one group was given an extra 640 mg per day of cholesterol in the form of eggs while the other group was given an egg substitute containing no cholesterol.
At the end of the intervention, there were no changes in plasma total of LDL cholesterol (LDL-C) compared to baseline or differences in plasma total of LDL-C between groups.
Mononuclear cells were taken from the blood of these subject, then RNA was extracted from these cells. The researchers then used the polymerase chain reaction to determine the amount of messenger RNA (mRNA) for both HMG-CoA reductase and the LDL-receptor protein. (If you need to brush up on mRNA and protein synthesis, take a look at the video in this post from about a year ago.) In short, mRNA correlates with the amount of a specific protein being synthesized – if mRNA is high, then a lot of this protein is being made.
When researchers measured the mRNA they discovered that in those subjects consuming the extra cholesterol there was a significant decrease in the amount of HMG-CoA reductase mRNA ( which means a decrease in the amount of HMG-CoA reductase being made) and a decrease in the amount of LDL-receptor mRNA. The subjects consuming the lesser amounts of cholesterol had the opposite findings – they made more HMG-CoA reductase and more LDL receptors.
What does this all mean? It means that a low-carbohydrate diet allows the body to regulate cellular cholesterol levels over a wide range of dietary cholesterol levels by changing the cellular synthesis and uptake. And it does all this by acting in much the same way that statins do, but without all the side effects.
Another interesting finding in this study is that the group who ate the extra cholesterol had a 21% increase in HDL-cholesterol levels while the group consuming the lower amount of cholesterol had no HDL-cholestrol increase over baseline.
The take-home message from this study is that you don’t really have to worry about the extra cholesterol you might be getting in your low-carb diet. Your body will deal with it nicely. And if you want to go up on the cholesterol by, say, eating a few more eggs, not only will your body compensate, but it will throw in some extra HDL in the bargain.
In short, don’t worry about your cholesterol on a low-carb diet.
Sir Hola and HNY and all the rest of it.
Now seriously can a body chew up more than 1-2 pounds of fat per week or is that the max ?
I’ve read so many seemingly conflicting thangs and am curious if the 1-2 pounds is verbatim fact or not.
Sinc.
Hey Simon–
HNY and all that back to you.
A pound of fat contains about 3500 calories of stored energy. If you create a caloric deficit of 7,000 calories in a week, you should drop two pounds of fat. If you create a 10,000 calorie deficit, you should drop about three pounds of fat. You have to remember that weight loss is different from fat loss in that other things than fat – water, muscle mass, etc. – have weight, so when you lose weight, that weight is composed of all those things, not just the fat. It’s fairly easy to lose 3-5 pounds per week early on on a low-carb diet, but I would imagine that of that 3-5 pounds about 1-2 would be fat.
Cheers–
MRE
This is lucky since for the last three years I have consumed, each day without fail… 5 organic free range eggs (fried in water using a pan with a lid), 5 sausages (good quality organic pork) and a tin of peeled tomatoes. From start to finish, getting stuff out the fridge, etc, cooking time is no more than 12 mins on average including some coffee. Steaming fast in a frying pan really helps, so i recommend a pan with a lid.
Oh, and it tastes really good!
I’ll bet it tastes great!
And, if one reads enough on the subject (Uffe, Malcolm, etc.) by and large one need not worry about their cholesterol level at all.
Agreed. But it’s nice to know how it all works.
Cheers–
Mike
Another point on the board for the low-carb lifestlye!
I have a question for you that i find is hardly addressed. It concerns people who have suffered majorily as a result of consuming high carbs for many years. Take, for example, a person who has had a heart attack as a result of a high blood triglyceride level. If i am correct, these people are often prescibed meds like statins and aspirin. Now, this is something i’ve often wondered about: if we know that low-carb diets are effective in improving health parameters associated with heart disease, could a person who has had a heart attack decline the meds and instead follow a diet high in fats, low in carbs and moderate in protein, such as the diet discussed in the abovementioned study you cited? Or is it a case of where, if you’ve had a heart attack you are confined to a life of meds?
I hope this query doesn’t breach your recent comment about ‘medical issues’.
In my opinion, switching to a low-carb diet will help people who already have these disorders.
Cheers–
MRE
Thanks so much for explaining this and helping those of us who haven’t studied medicine understand what it all means!
Glad to help.
Best–
MRE
Dr. Eades,
I thought i would draw your attention to the latest study by Mark Mattson on IF. It is kind of disheartening to say the least:
http://ifdiet.blogspot.com/
The study was titles “Impact of reduced meal frequency without caloric restriction on glucose regulation in healthy, normal-weight middle-aged men and women.” Essentially, they divided the subjects into a 3-meal-per-day group, and a 1-meal-per-day group. For 2 months the participants did this, and the researchers discovered that “Subjects consuming a single large daily meal exhibit elevated fasting glucose levels and impaired morning glucose tolerance associated with a delayed insulin response”.
The same group of doctors conducted a study 7 months earlier, and found “when consuming 1 meal/d, subjects had…a significant increases in blood pressure and in total LDL”.
This just didn’t happen for me. My LDL went up from 70 to 170 off a statin while on a low carb diet. This is the second time I’ve tried it to no avail.
You need to get your LDL particle size checked. Or at least your APO B. Only then can you tell if this is a problem – and only then if you’re a believer in the lipid hypothesis.
There is a major rebound effect when many people go off statins, so going off a statin then onto a low-carb diet doesn’t really give an accurate representation of what’s going on.
Cheers–
MRE
Interesting find, Mike. I think in PP you pointed out that insulin is a potent stimulator of that HMG CoA enzyme, while glucagon has an inhibitory effect. So perhaps with the low-carb diet as the ‘background’ condition, cholesterol synthesis was rather restrained to begin with, and was easily adjusted to suit the level of incoming dietary cholesterol.
That’s the way I would call it.
Cheers–
MRE
Is this dietary cholesterol effect independent of the carb content of the diet, or does this only happen on a low-carb diet?
The studies in which saturated fat drives up cholesterol levels used a standard diet, which is a high-carb diet.
Cheers–
MRE
So if we aren’t enamored of the lipid hypothesis, then this research is pretty much meaningless. And if we believe there is some link between cholesterol and heart disease, then we still don’t know that LC exerts positive effects through the mechanism described, because they didn’t do the high carb control. Could be that any dietary cholesterol will inhibit experession of the enzyme, and maybe the difference in blood levels is via turnover rather than synthesis.
Goddit..thanks much.
It’s what i reckoned.
Does yr Mrs make rillettes..actually we might have had this conver some time ago.
Dementia aged 42
OH yes and BTW PLEASE get yerself a copy of The Limerick, the Famous Paris edition.
We did indeed go over the rillettes about a year ago.
And I have a copy of The Limerick, but I don’t know if it’s the famous Paris edition or not. Send me a link.
Maybe I should work on a limerick about Anthony Colpo.
Let’s see…
There was once a young prat from down under
Who tried to tear laws of thermodynamics asunder
Not a bad start.
Cheers–
MRE
Looking at Wikipedia: http://en.wikipedia.org/wiki/HMG-CoA_reductase
It seems that “HMG-CoA reductase is active when blood glucose is high”.
Hmmm… would that happen on a high carb, or a low carb diet?
You tell me. Insulin stimulates HMG-CoA reductase, so that should tell you all you need to know.
Cheers–
MRE
There is no such thing as a single rate-limiting reaction in a biochemical pathway. Modern control theory (at least it was modern when I took biochem in 1983) shows that there are multiple feedback/feedforward controls at work in every biochemical pathway. Basically, “everything affects everything else”. The idea that increased dietary intake leads to decreased synthesis, sounds plausible. Doesn’t seem to work the same way when you aren’t on a low carb diet though. It would be interesting to see the same experiment done on people consuming a high carb diet. I suppose you would see their cholesterol level go up and their ratio affected in a bad way.
Personally I think the study was improperly focused in on one particular enzyme, and even though the result fits with the simplistic story, I wouldn’t take it as proof that this is what is going on.
I do believe that LC improves circulatory health by preventing inflammation. To what extent lipid profiles play into this, I am not entirely sure. If cholesterol is indeed a “band-aid” that helps internal “sores” scab over, it would seem that removing the sore is far more important than how much band-aid is floating around. Even the correlations between cholesterol and circulatory problems in the general population haven’t been all that convincing. Trying to show that LC exerts effects through cholesterol levels, is giving needless credence to a poor theory.
I’m just reporting the study. I didn’t design it. I, too, believe that LC improves circulatory health by preventing or decreasing inflammation among other things. But so many people are focused on lipids, and it is nice to show that LC improves them too.
And in other studies with higher carb diets increased saturated fat intake does run up LDL-cholesterol to some extent. It was those studies that got us launched off into the lipid hypothesis.
Cheers–
MRE
I just couldn’t fail to link you to this one from Dr. Howard Brody’s blog. It’s all about “Dr.” you-know-who of Lipitor marketing fame (I’d say infamy) who, according to this blog piece was really just a biomedical researcher with no clinical experience of every treating patients (and barely able to get a medical degree). And the suffering of the unfortunate individuals who ended up with the artificial device he “invented?” If this info is accurate……well, Jesus wept again. http://brodyhooked.blogspot.com/
I wonder how can Pfizer’s DTC marketing of their product using “him” as their shill be viewed as anything other than fraud?
W
How indeed?
MRE
I low carb to lose weight (40 lbs so far) and to reduce inflammation. I’m still on statins because supposedly those help with inflammation. Can you address how low carb helps (or doesn’t) inflammation?
Hi Johanna–
That’s a big question, bigger than I can address in the comments. But I can say that numerous studies have shown an increase in inflammation with high carb diets.
Cheers–
MRE
How long does it take for someone eating low carb to have the beneficial cholesterol effects? Also, can you think of any reason for someone eating very low carb to have high triglycerides?
I’ve had patients have substantial lipid improvements within 10 days. I’ve never seen it before that, but I’ve never checked before at least 10 days. Without knowing the patient or the patient’s history, I can’t think of any reason that a very-low-carb diet wouldn’t result in triglyceride lowering.
Cheers–
MRE
Hi,
Thanks for such an interesting post. I think it has been worth it so far for me taking less carbohydrates nowadays especially during dinner. I understand Policosanol from sugar cane extract in the product Bios Life helps to reduce the cholesterol produced by the liver as well.
Not substantially, in my opinion.
Cheers–
MRE
Thanks for this Doc. From what I’ve read though I don’t worry too much about cholesterol anyway.
by the way, interesting study I just read that a low fat intake was associated with more injuries in runners. I’ve written about it here:
http://conditioningresearch.blogspot.com/2008/01/eating-more-fat-protects-runners-from.html
Hey Chris–
Thanks for the link. I remember back in the old days when NFL players didn’t get hurt all that often, then some started following low-fat diets to keep their weight down, and the injuries ran rampant.
Cheers–
MRE
If that same study would have been done with the subjects eating 30-40% carbs, what would you expect the rise in cholesterol to be in the group eating eggs compared to the group eating egg substitute?
Can you think of any type of person who really needs more than about 15% carbs or more than about 80grams daily? Maybe a young extremely active person? I think you wrote before that most people can get all the benefits of a low carb diet with about 60g daily (Groves and Lutz also recommend something around that number).
Thanks
Yep, I would expect an increase with a higher carb diet. That’s what most of the studies have shown.
I can’t think of anyone who would physiologically benefit from more than 15% carbs: hedonistically, however, is another situation.
Cheers–
MRE
As always thank you for these very interesting posts, doc.
While browsing another blog, I came across this link on the comments:
http://www.opinions3.com/how_it_really_works.htm
It’s an article by Liz Pavek. It’s well written but I think it may have some misinformation regarding cholesterol medications.
“then they take cholesterol-lowering drugs that force the body to make its own cholesterol by preventing the body from utilizing any from dietary sources. ”
There are some cholesterol-lowering drugs that may work that way, but not statins. The way I understand it, statins block the production of the body’s cholesterol, and the body is forced to get it from the blood via the LDL-receptors.
Off topic, I found a picture of “modern-day David” and pasted the original next to it for added effect. I’m not sure the image tag will work, but if it doesn’t here’s a direct link.
[IMG]http://i66.photobucket.com/albums/h267/mtflight/health/david.jpg[/IMG]
http://i66.photobucket.com/albums/h267/mtflight/health/david.jpg
Hey Alex–
You’re on the money with your analysis of how statins and non-statins work. Statins do work by inhibiting HMG-CoA reductase.
Thanks for the image of David. It’s terrific. I’ve got to figure out how to use it to great effect.
Cheers–
MRE
So low-carb breaks the cholesterol-synthesis chain, and it does it at the same place as statins.
Then does low-carb potentially have some of the same side effects as do statins? In particular, if they both equally shut down synthesis of mevanolate, then aren’t they both equally shutting down production of CoQ10 (ubiquitin)? If not, why not?
I’ve been low-carbing for 4+ years. Should I then be taking a CoQ10 supplement?
David
Hi David–
No, it doesn’t have the same effect that statins do. Statins reduce the level of the enzyme all the time, whereas the insulin and glucagon in the diet do it whenever appropriate.
Cheers–
MRE
Is there a study that shows a correlation between LC and changes in cholesterol levels? From what I’ve heard anecdotally on the LC websites, it seems that at least the gross levels of total cholesterol and LDL don’t tend to respond uniformly. At least not like triglycerides which seem to really decrease dramatically in the majority of people. I’ve heard of many instances where ratios seemed to improve even though total cholesterol remained elevated or even increased a bit. Just wondering if there is any consensus yet on what blood lipid effects you might expect. I’m sure it is going to depend on body fat and rate of fat loss. You would think it was common sense that when fat stores are being broken down and mobilized, there might be some transient increase. Though it would seem that triglyceride catabolism more than keeps up with this as those levels decrease early in the process of doing LC.
There are numerous studies showing decreases in total and LDL-cholesterol levels with low-carb diets. But the data in most of these studies shows that there is not a uniform response in these numbers across all subjects whereas a lowering of triglycerides is a uniform finding. What does seem to be a uniform finding is that even when LDL-cholesterol levels don’t decrease (or even increase) the particle size either doesn’t change or gets larger. With low-fat diets the opposite holds. Uniformly LDL falls to some extent, but particle size always gets smaller.
Cheers–
MRE
dr. mike! just catching up with all your posts – keep these statin posts coming!
building off another comment above, re: “rebound effect” when going off statins. are there any (good) studies you can point me to effects of quitting statins abruptly? more importantly, any studies linking this “rebound effect” and actual mortality (i.e., not just higher total cholesterol)?
finally, if someone is following LC – goes off statins – what is your expectation for the length of this rebound? could this be as short as 10 days (as you mentioned above – re: improvement time for lipids)?
Hi ec–
I don’t really know the answer to your question. Usually when I took patients off statins I didn’t recheck their bloodwork for six weeks, and by then the rebound effect was pretty much over. I would imagine the effect lasts for a week to 10 days, but I don’t know for sure.
Best–
MRE
I’m a bit confused as to why BOTH the LDL receptors and HMG-CoA were down-regulated in the EGG group. I would have imagined an uptick in LDL-R concomitant with less being made inside the cell. Do cells just need less receptors to garner the same amount of cholesterol in this case? Any insight is greatly appreciated.
Because the cells have plenty of cholesterol available to them so they don’t have to make more or go out and drag it in. If the cells are deficient, they can get it two ways: they can make it and/or they can go out and pull it in with LDL receptors. If the cells contain plenty they don’t need to do either, and so they don’t activate the machinery to do so.
Cheers–
MRE
Would you kindly explain why BOTH the LDL receptors and HMG-CoA were down-regulated in the EGG (higher cholesterol) group. I’m guessing the cell’s needs remain constant…so do they just require less receptors to garner the same amount of cholesterol? Your insight is greatly appreciated, as always.
You’re correct. Because the cells have plenty of cholesterol available to them so they don’t have to make more or go out and drag it in. If the cells are deficient, they can get it two ways: they can make it and/or they can go out and pull it in with LDL receptors. If the cells contain plenty they don’t need to do either, and so they don’t activate the machinery to do so.
Cheers–
MRE
True or false: Most cholesterol under normal conditions is manufactured in extrahepatic tissues.
True
False
Explanation:
Most cholesterol under normal conditions is manufactured in extrahepatic tissues, and the principal and essential task is to move cholesterol to the liver for excretion as bile acids and unaltered cholesterol. The liver is the only organ that can excrete the cholesterol in these forms and in quantities necessary to maintain balance between excretion and the combined effects of dietary absorption and synthesis. It is believed that virtually all cells can synthesize sufficient cholesterol to meet the basic needs for normal function.
Okay, I’m confused. My LDL recently was 151, and my (Internal Med) doc wants to put me on a statin. I said no.
I spoke to a cardiologist the other day, asking about the difference between the fluffy and dense LDL sizes, and why a statin? Her response was that the statin helps repair the endothelium, thus preventing the particles from adhering to the arterial walls, regardless of whether they’re dense or fluffy.
Can you comment on this? I’m now concerned as to whether the statin might help, after all.
Also, she suggested I talk with an endocrinologist in regards to Metformin and increasing insulin sensitivity, which might have some success in helping Metabolic Syndrome pre-diabetics lose weight. Thoughts?
First, you’ve got to understand that randomized, placebo-controlled studies (the only kind that really count) have shown no benefit in terms of longevity for women taking statins. Period. End of story. It didn’t matter if the women were young or old or if they had already been diagnosed with heart disease or not, statins didn’t make them live longer.
Statins may or may not “repair endothelium,” but it doesn’t matter because the data show that the drugs don’t make women live longer, which is the real issue. I suspect that the idea that these drugs repair the endothelium is an ad hoc hypothesis to somehow counter the idea that the drugs don’t work in terms of increasing longevity.
There is some evidence that Metformin does increase insulin sensitivity and that, consequently, it can help with weight loss. Metformin is one of the very few drugs that I use in my practice, but I try dietary changes first.
This answers my question indirectly. I don’t need to take the statin. Why worry about a conflict with low carb diet.
I would like to know what is going to happen if I eat a low carb diet to lose weight and still take the statin my physician thinks it is important that I take.
I doubt it will affect your low-carb diet one way or another. I think the problems with statins don’t revolve around diet as much as they do other issues. You should discuss with your physician.