Significance of VERY low cholesterol?

[Guest guest]

I have a patient in clinic with very low cholesterol - total is 105.

I can't remember the HDL/LDL ratio (have to look it up), but I recall

it being favorable.

I'm well aware of the many essential roles of cholesterol in health.

I'm also aware of many studies, such as Framingham, J-Lit and the

Honolulu Heart Program, which indicate increased mortality with

cholesterol levels under 180mg/dl.

What do you think the clinical significance of a cholesterol level

this low is? And, since diet has minimal impact on cholesterol

levels, how would someone who actually wanted to raise their

cholesterol levels do it?

Chris

[Guest guest]

Chris

HDL is 58 and LDL is 35 in this patient. TGL is 45.

K.

[Guest guest]

--- " chriskjezp " <chriskresser@...> wrote:

> I have a patient in clinic with very low cholesterol - total is 105.

> I can't remember the HDL/LDL ratio (have to look it up), but I

> recall it being favorable.

>

> I'm well aware of the many essential roles of cholesterol in health.

> I'm also aware of many studies, such as Framingham, J-Lit and the

> Honolulu Heart Program, which indicate increased mortality with

> cholesterol levels under 180mg/dl.

>

> What do you think the clinical significance of a cholesterol level

> this low is? And, since diet has minimal impact on cholesterol

> levels, how would someone who actually wanted to raise their

> cholesterol levels do it?

K, in case you didn't know, Dr Mercola has very low cholesterol

and mentions it in some of his articles. Here's an example:

http://articles.mercola.com/sites/articles/archive/2001/08/08/suicide.aspx

=========================================

Unfortunately, many people have low cholesterol who are not taking

medications. I am one of them. This is largely due to my having beta

thallasemia which is a genetic defect in the size of red blood cells

that is also associated with a low cholesterol.

Yes, my risk for heart disease is quite low, but the risk for the

other diseases mentioned above is clearly elevated.

It seems that low cholesterol in many individuals is related to a non

optimized gall bladder and liver function. However, I have yet to

learn of an effectively consistent approach to normalize this issue.

=========================================

FWIW,

[Guest guest]

> I have a patient in clinic with very low cholesterol - total is 105.

> I can't remember the HDL/LDL ratio (have to look it up), but I recall

> it being favorable.

Interesting. The only time I ever got mine tested it was 106. I was

vegan at the time, but even most vegans have much higher cholesterol

than that.

> I'm well aware of the many essential roles of cholesterol in health.

> I'm also aware of many studies, such as Framingham, J-Lit and the

> Honolulu Heart Program, which indicate increased mortality with

> cholesterol levels under 180mg/dl.

I haven't looked at all these studies, but the mainstream explanation

is that a drop in cholesterol with age indicates certain diseases that

lower cholesterol levels. I have not looked into this claim to make

sure it checks out. In Framingham, no one with a cholesterol level

under 150 has ever had heart disease, but I'm not sure what their

risks are for cancer and other diseases.

> What do you think the clinical significance of a cholesterol level

> this low is?

It's hard to say. On the one hand, there are a number of studies in

the modern western world showing that low cholesterol levels are

associated with adverse effects. On the other hand, the primitive

groups we are all trying to emulate almost universally had very low

cholesterol levels and the Masai, who are often invoked in

contradiction to the idea that cholesterol and fat in foods cause

heart disease, have the lowest cholesterol in the world. Still,

their's averages around 130, which is higher than this patient's.

SLOS carriers have a defect in cholesterol synthesis and an increased

risk of suicide:

http://www.cholesterol-and-health.com/Foods-High-In-Cholesterol.html#essential

> And, since diet has minimal impact on cholesterol

> levels, how would someone who actually wanted to raise their

> cholesterol levels do it?

Diet doesn't have _no_ impact on cholesterol levels. They could try

eating more fruit for the fructose, and very large amounts of

cholesterol. More will probably be absorbed if they spread it out

over various meals. The current treatment for SLOS is cholesterol

supplements (they used to use cream and egg yolk-based diets, which

helped, but the food cholesterol isn't absorbed as well because of

their bile acid deficiencies).

Chris

[Guest guest]

Thanks for your reply. I just found out that this patient is indeed vegan. I

suspect that their

cholesterol levels may increase if they shift their diet to include more animal

products,

especially those high in cholesterol (egg yolks, liver, shrimp, etc.)

How does fructose raise cholesterol?

Chris

[Guest guest]

> I haven't looked at all these studies, but the mainstream explanation

> is that a drop in cholesterol with age indicates certain diseases that

> lower cholesterol levels. I have not looked into this claim to make

> sure it checks out. In Framingham, no one with a cholesterol level

> under 150 has ever had heart disease, but I'm not sure what their

> risks are for cancer and other diseases.

Forgot to mention that Colpo and others (Ravnskov, etc.) have criticized the

study done by

Ibarren et al. that attempted to " prove " this notion (that the increased

mortality risk of low

cholesterol with age is due to an underlying disease). I'll have to dig around

and find the

information, but in short I was not convinced that the low cholesterol

concentrations and

consequent increase in mortality were due to an underlying condition. Perhaps

in some

cases, but not all.

I'm cautious when comparing markers like cholesterol in modern, industrialized

countries

with populations like the Masai. There are so many potential confounding

factors, such as

exposure to environmental toxins, stress and cultural practices (proven by

Marmot's

studies indicating that Japanese emigrants who abandon their traditions have

much higher

rates of CHD than those that retained them), antioxidant intake, PUFA intake,

etc. etc.

Since cholesterol has so many vital functions in the body, I tend to think that

a level as low

as 100 is probably not ideal. I think we'd need more studies on this to be

sure, but since

everyone's been focused on high cholesterol for so long there isn't much data

here.

Chris

[Guest guest]

Hi

> How does fructose raise cholesterol?

I'm not positive of all the details, but all carbohydrates will raise

cholesterol levels in excess of that needed to restore glycogen levels

becuase they provide the basic substrate for cholesterol synthesis,

acetyl CoA. Fructose is retained by the liver much more than glucose

and a much greater proportion of it is converted to triglycerides, so

the same is probably true of its conversion to cholesterol. I think I

actually read this in one of Ray Peat's articles, but it makes sense.

Chris

[Guest guest]

Hi

> Forgot to mention that Colpo and others (Ravnskov, etc.) have criticized the

> study done by

> Ibarren et al. that attempted to " prove " this notion (that the increased

> mortality risk of low

> cholesterol with age is due to an underlying disease). I'll have to dig

> around and find the

> information, but in short I was not convinced that the low cholesterol

> concentrations and

> consequent increase in mortality were due to an underlying condition.

> Perhaps in some

> cases, but not all.

Cool. I'm going to go through their books again to write reviews but

haven't had the time yet. If you find the criticism, I'd be

interested as I don't remember what the critique is (or what the

evidence presented by Ibarren is either).

> I'm cautious when comparing markers like cholesterol in modern,

> industrialized countries

> with populations like the Masai. There are so many potential confounding

> factors, such as

> exposure to environmental toxins, stress and cultural practices (proven by

> Marmot's

> studies indicating that Japanese emigrants who abandon their traditions have

> much higher

> rates of CHD than those that retained them), antioxidant intake, PUFA

> intake, etc. etc.

I agree with all of that. It may be that a level is very harmful here

and not for them, but then we have to ask why that is. It just shows

that the low levels are not *inherently* bad.

> Since cholesterol has so many vital functions in the body, I tend to think

> that a level as low

> as 100 is probably not ideal. I think we'd need more studies on this to be

> sure, but since

> everyone's been focused on high cholesterol for so long there isn't much

> data here.

I think it probably is too, because there are associations with

suicide and other mental issues at levels that are much higher than

that. Also, even the Masai don't have average levels anywhere near

that low (they are more around 130).

Chris

[Guest guest]

> Cool. I'm going to go through their books again to write reviews but

> haven't had the time yet. If you find the criticism, I'd be

> interested as I don't remember what the critique is (or what the

> evidence presented by Ibarren is either).

Iribarren (sorry, I mis-spelled his name before) did a big study in

San Francisco that followed 100,000 people for 15 years. At the end

of the study those with low cholesterol had been admitted to the

hospital more frequently for an infectious disease than those with

high cholesterol.

Iribarren's analysis was that the infections were responsible for the

low cholesterol, and not the other way around. He said this in spite

of the fact that when cholesterol levels were measured (at the

beginning of the study), those with low cholesterol had no evidence at

all of infection. None whatsoever. Rather than reach the more

obvious conclusion (that low cholesterol predisposes to infection),

Iribarren's theory is that those patients with low cholesterol

actually had " sub-clinical " levels of infection that couldn't be

detected by tests.

To me this is another case of the cart leading the horse. When

confronted with data that challenge his underlying assumption (that

low cholesterol is healthy), rather than modifying the underlying

assumption a new and in my mind, far less likely, hypothesis is

created that maintains the original hypothesis.

I'm not at home and can't remember where I read the full analysis by

Ravnskov, but here's a short snippet from Ravnskov's article on the

Benefits of High Cholesterol on the WAPF site:

" Many studies have found that low cholesterol is in certain respects

worse than high cholesterol. For instance, in 19 large studies of more

than 68,000 deaths, reviewed by Professor R. s and his

co-workers from the Division of Epidemiology at the University of

Minnesota, low cholesterol predicted an increased risk of dying from

gastrointestinal and respiratory diseases.3

Most gastrointestinal and respiratory diseases have an infectious

origin. Therefore, a relevant question is whether it is the infection

that lowers cholesterol or the low cholesterol that predisposes to

infection? To answer this question Professor s and his group,

together with Dr. Iribarren, followed more than 100,000 healthy

individuals in the San Francisco area for fifteen years. At the end of

the study those who had low cholesterol at the start of the study had

more often been admitted to the hospital because of an infectious

disease.4,5 This finding cannot be explained away with the argument

that the infection had caused cholesterol to go down, because how

could low cholesterol, recorded when these people were without any

evidence of infection, be caused by a disease they had not yet

encountered? Isn´t it more likely that low cholesterol in some way

made them more vulnerable to infection, or that high cholesterol

protected those who did not become infected? Much evidence exists to

support that interpretation. "

Chris

[Guest guest]

> Most gastrointestinal and respiratory diseases have an infectious

> origin. Therefore, a relevant question is whether it is the infection

> that lowers cholesterol or the low cholesterol that predisposes to

> infection? To answer this question Professor s and his group,

> together with Dr. Iribarren, followed more than 100,000 healthy

> individuals in the San Francisco area for fifteen years. At the end of

> the study those who had low cholesterol at the start of the study had

> more often been admitted to the hospital because of an infectious

> disease.4,5 This finding cannot be explained away with the argument

> that the infection had caused cholesterol to go down, because how

> could low cholesterol, recorded when these people were without any

> evidence of infection, be caused by a disease they had not yet

> encountered? Isn´t it more likely that low cholesterol in some way

> made them more vulnerable to infection, or that high cholesterol

> protected those who did not become infected? Much evidence exists to

> support that interpretation. "

I definitely agree with Ravnskov here. The interpretation you

supplied from Iribarren (sp?) is, if accurately portrayed, pretty

ridiculous. I think it would be reasonable to suggest this if we were

looking at drops in cholesterol from baseline over time, but not when

looking at low baseline cholesterol in a prospective study. Of

course, the " subclinical infection " has to be considered, but to

suggest that it is more likely or reasonable than low cholesterol

predisoposing to infection seems simply absurd.

Chris

[Guest guest]

I found the article:

http://qjmed.oxfordjournals.org/cgi/content/full/96/12/927

Interesting food for thought.

Chris

[Guest guest]

> Iribarren (sorry, I mis-spelled his name before) did a big study in

> San Francisco that followed 100,000 people for 15 years. At the end

> of the study those with low cholesterol had been admitted to the

> hospital more frequently for an infectious disease than those with

> high cholesterol.

It looks like this is a different and more important analysis by the

same author:

http://circ.ahajournals.org/cgi/content/full/92/9/2396

I don't have time to read the full text (which is free at this link)

at the moment, but if the abstract is accurate, the evidence is quite

a bit more compelling than what you've described. People whose

cholesterol dropped were at increased risk for all-cause and various

specific mortalities, but those whose cholesterol was stable were not

at an increased risk, whether it was low or middle.

Chris

[Guest guest]

From a quick scan of the article, Iribarren is defining " low "

cholesterol as <180mg/dl. That's certainly lower than average, but

perhaps not low enough to be pathogenic.

In any event, this article seems to support the growing understanding

that while cholesterol is involved in the disease process, it's a

relatively minor (and often peripheral) contributor - whether high or

low.

In heart disease, high LDL is a risk factor for some populations - but

probably because it increases the potential for ox-LDL. (However,

Colpo points out studies in his book where ox-LDL was lowered and

total LDL stayed the same, or even increased, and CHD events were

reduced). High LDL can also simply be a marker for stress, infection

and inflammation.

On the other hand, Iribarren's study suggests that falling LDL can be

a marker for cancer and other non-cardiovascular diseases. This

particular study indicates that stable low choletsterol " was not

associated with significantly increased mortality risk, although some

marginal risk existed owing to an association of very low TC with

fatal hemorrhagic stroke. "

Two things about this: I believe Ravnskov has analyzed this study and

pointed out that there was an increased mortality risk with stable low

cholesterol, but it wasn't significant. You have pointed out

elsewhere that the lack of statistical significance may simply mean

that the study wasn't powerful enough to achieve significance. This

study followed 6,000 men, whereas the other three studies mentioned in

Ravnskov's article followed 70,000, 100,000 and 120,000.

Then of course we have the findings that low cholesterol increases the

risk of violent death, suicide and antisocial & violent behavior.

There are also studies that indicate a link to depression, due to

cholesterol's role in serotonin uptake in the brain.

Add to that the clear physiological roles of cholesterol in the body,

and I think one can still make a relatively strong case that

persistent low levels of cholesterol (not sure what the cut-off for

" low " would be is) are not ideal in modern, Western populations.

Chris

[Guest guest]

Another interesting tidbit. The Honolulu Heart Program Study was one of those

that showed

increasing mortality with low cholesterol levels. Iribarren suggested that this

was due to the

presence of an undiagnosed or " subclinical " disease that was lowering

cholesterol.

The authors of the HHP responded thusly:

" iribarren and colleagues suggested that a decline in serum cholesterol might

occur over a

decade before diagnosis of a disease, and such long-term morbidity could be

attributable to

chronic subclinical infections with Hepatitis B, or to chronic respiratory

diseases..

....our data suggest that those individuals with a low serum cholesterol

maintained over a

twenty year period will have the worst case outlook for all-cause mortality.

Our present analysis suggests that Iribarren's hypothesis is implausible and is

unlikely to

account for the adverse effects of low cholesterol over twenty years. "

Chris

[Guest guest]

I'm researching the same thing regarding Autism. Here's an article which

might be of benefit for you:

http://www.greatplainslaboratory.com/cholesterol/web/

Sharon

On Tue, Mar 4, 2008 at 12:01 PM, chriskjezp <chriskresser@...> wrote:

>

>

> I have a patient in clinic with very low cholesterol - total is 105.

> I can't remember the HDL/LDL ratio (have to look it up), but I recall

> it being favorable.

>

> I'm well aware of the many essential roles of cholesterol in health.

> I'm also aware of many studies, such as Framingham, J-Lit and the

> Honolulu Heart Program, which indicate increased mortality with

> cholesterol levels under 180mg/dl.

>

> What do you think the clinical significance of a cholesterol level

> this low is? And, since diet has minimal impact on cholesterol

> levels, how would someone who actually wanted to raise their

> cholesterol levels do it?

>

> Chris

>

>

>

--

Deut 11:15 He will put grass in the fields for your cattle, and you will

have plenty to eat.

Check out my blog - www.ericsons.net - Food for the Body and Soul

[Guest guest]

> From a quick scan of the article, Iribarren is defining " low "

> cholesterol as <180mg/dl. That's certainly lower than average, but

> perhaps not low enough to be pathogenic.

That is a good point, although it does not discount the apparent association

with the drop. In other words, if he redefined it, maybe that could show that

both are important.

> In any event, this article seems to support the growing understanding

> that while cholesterol is involved in the disease process, it's a

> relatively minor (and often peripheral) contributor - whether high or

> low.

Well, I don't think we can yet quantify the contribution of ox-LDL with any

confidence, but certainly the total concentration of LDL is of minor and

secondary importance IMO.

[snip]

> On the other hand, Iribarren's study suggests that falling LDL can be

> a marker for cancer and other non-cardiovascular diseases. This

> particular study indicates that stable low choletsterol " was not

> associated with significantly increased mortality risk, although some

> marginal risk existed owing to an association of very low TC with

> fatal hemorrhagic stroke. "

I forgot to mention earlier, that low cholesterol has been clearly associated

with hemorrhagic stroke, as has a low consumption of animal protein and fat.

However, it appears to be only important in people with high blood pressure when

it is segregated according to BP.

> Two things about this: I believe Ravnskov has analyzed this study and

> pointed out that there was an increased mortality risk with stable low

> cholesterol, but it wasn't significant. You have pointed out

> elsewhere that the lack of statistical significance may simply mean

> that the study wasn't powerful enough to achieve significance. This

> study followed 6,000 men, whereas the other three studies mentioned in

> Ravnskov's article followed 70,000, 100,000 and 120,000.

Not only that, but as you pointed out, the effect may have been diluted by the

category definition. In other words, if the mortality increased below 160, then

making " low " below 180 would dilute the effect by including lots of people who

should be in the " middle " group to the point where the magnitude becomes smaller

and loses statistical significance.

> Then of course we have the findings that low cholesterol increases the

> risk of violent death, suicide and antisocial & violent behavior.

That's true, but there is correlation/causation iffiness here too. I suspect it

is causal just because cholesterol is so important to the brain. However, just

as Ravnskov points out that the " high cholesterol " folks in the studies are

mostly people with familiar hypercholesterolemia, which is a genetic defect in

the LDL receptor, and when you exclude them, the correlation often disappears,

the same could be said of folks with low cholesterol, many of whom probably are

carriers of the SLOS gene (1-3%), who have not only low cholesterol, but a

buildup of 7-dehydrocholesterol, which might be toxic. And to my knowledge,

there are not cholesterol-boosting therapies that have been shown to attenuate

or eliminate the increased risk of suicide or violent behavior. That said,

again I suspect it is causal but I'm just pointing out that we have to apply the

same criticisms to both sides.

> There are also studies that indicate a link to depression, due to

> cholesterol's role in serotonin uptake in the brain.

> Add to that the clear physiological roles of cholesterol in the body,

> and I think one can still make a relatively strong case that

> persistent low levels of cholesterol (not sure what the cut-off for

> " low " would be is) are not ideal in modern, Western populations.

I'm not familiar with cholesterol's role in seratonin uptake, but cholesterol is

actually the limiting factor for synapse formation, so it would be surprising if

low brain cholesterol cholesterol were not associated with poor mental

functioning -- though blood levels and brain levels seem to be segregated and

the brain seems to rely almost entirely on endogenous synthesis. I agree with

you that it seems the modern western requirement is higher, but I still think

the reasons why that might be need a LOT more hashing out before it really makes

sense on more than a vague intuitive basis.

Chris

[Guest guest]

> Our present analysis suggests that Iribarren's hypothesis is implausible and

> is unlikely to

> account for the adverse effects of low cholesterol over twenty years. "

While I think he may have shown that a drop in cholesterol is indeed

indicative of harm, it seems like he's probably grasping at straws

here to try to avoid the conclusion that cholesterol can get too low.

Chris

[Guest guest]

> I'm not familiar with cholesterol's role in seratonin uptake, but cholesterol

is actually the

limiting factor for synapse formation, so it would be surprising if low brain

cholesterol

cholesterol were not associated with poor mental functioning -- though blood

levels and

brain levels seem to be segregated and the brain seems to rely almost entirely

on

endogenous synthesis. I agree with you that it seems the modern western

requirement is

higher, but I still think the reasons why that might be need a LOT more hashing

out

before it really makes sense on more than a vague intuitive basis.

>

I can't find the exact study I was referring to, but I did find a summary of it

by Dr. Weil of

all people:

" One of the Duke researchers, psychologist Suarez says that some evidence

suggests that having low cholesterol alters the way brain cells function and

that brain cells

with low levels of cholesterol may have fewer than normal receptors for the

mood-

elevating neurotransmitter serotonin which could lead to depression by

preventing the

cells from receiving and using this vital brain chemical. "

I think that relationship between cholesterol and serotonin in the brain is not

completely

clear yet; but I have seen a few studies now that indicate a link between low

cholesterol

and anxiety/depression. The authors of all of those studies suggested that

serotonin was

the underlying mechanism.

Chris

[Guest guest]

> " One of the Duke researchers, psychologist Suarez says that some

> evidence

> suggests that having low cholesterol alters the way brain cells function and

> that brain cells

> with low levels of cholesterol may have fewer than normal receptors for the

> mood-

> elevating neurotransmitter serotonin which could lead to depression by

> preventing the

> cells from receiving and using this vital brain chemical. "

Well if I could throw out a guess, I would say that the receptors

probably need to be stabilized by lipid rafts, which are very rich in

cholesterol and basically are involved in anchoring and arranging

protein organization in membranes. Certain proteins seem to require

them specifically.

Chris

[Guest guest]

I would like to take a stab at this one. Fructose raises insulin, the

master hormone, which controls cholesterol, especially triglycerides,

hence processed carbs even ones that aren't sweet can raise

cholesterol, high fructose corn syrup, oy vey!!! Anyway as we all know

it's not the saturated fat. Over on my lowcarb high fat list there are

people who routinely report cholesterol in the 130s, these are folks

who eat < 30 or so carbs a day.

Dora

> How does fructose raise cholesterol?

>

> Chris

>

[Guest guest]

>

> I would like to take a stab at this one. Fructose raises insulin, the

> master hormone, which controls cholesterol, especially triglycerides,

> hence processed carbs even ones that aren't sweet can raise

> cholesterol, high fructose corn syrup, oy vey!!! Anyway as we all know

> it's not the saturated fat. Over on my lowcarb high fat list there are

> people who routinely report cholesterol in the 130s, these are folks

> who eat < 30 or so carbs a day.

>

Well, I question whether cholesterol in the 130s is something to shoot for.

Take a look at

the other posts in this thread to see why.

K.

[Guest guest]

I understand that cholesterol is protective against cancer and et

al. My point was the roll of fructose in raising cholesterol to

healthier level.

- In , " chriskjezp "

<chriskresser@...> wrote:

>

> --- In , " Dora " <adorablemama@>

wrote:

> >

> > I would like to take a stab at this one. Fructose raises

insulin, the

> > master hormone, which controls cholesterol, especially

triglycerides,

> > hence processed carbs even ones that aren't sweet can raise

> > cholesterol, high fructose corn syrup, oy vey!!! Anyway as we

all know

> > it's not the saturated fat. Over on my lowcarb high fat list

there are

> > people who routinely report cholesterol in the 130s, these are

folks

> > who eat < 30 or so carbs a day.

> >

>

> Well, I question whether cholesterol in the 130s is something to

shoot for. Take a look at

> the other posts in this thread to see why.

>

> K.

>