Do Animal Models Support Cholesterol Theory?

[ofonorow]

Studies have shown that cholesterol is thrombogenic, and the link between cholesterol and atherosclerosis is supported by animal models. Nonetheless, whether there is a direct causal link is a moot point, considering that lowering cholesterol has been shown to reduce the risk of heart disease.

What animal models? I submit that the only animal model known to occur in nature which creates a lesion similar to the human is the guinea pig. This was noticed and first published in 1950. It is possible to create "fatty streaks", in other species with a very high cholesterol diet, but these lesions seem to bear little relation to CVD in humans. (There are clever (non cholesterol) methods known that will create human-like lesions, such as restricting vitamin B6 or copper in the diet of apes.)

By the way, perhaps the strongest animal models of which you speak have been created in recent years through genetic engineering. Mice which have been genetically altered so they cannot produce their own vitamin C rapidly develop atherosclerosis of the aorta.
http://www.pubmedcentral.nih.gov/articl ... d=10639167

Furthermore, I believe that the now often repeated claim that lowering cholesterol has been "shown to reduce the risk of heart disease" is an outright lie, unless clarified to some particular sub group on the basis of some limited study. On what do you base this statement?

Note that it has been reliably shown that increasing vitamin C intake lowers total cholesterol, so I can understand medicine's confusion. When increased vitamin C supplementatio is reducing the "risk of heart disease", a side-effect is lowered cholesterol.

[Dolev]

the now often repeated claim that lowering cholesterol has been "shown to reduce the risk of heart disease" is an outright lie

One person made a statement which was repeated to the next person with embellishments. The second person wrote an article read by 20 people and each told 3 others who each told 5 others, one of whom wrote an article read by 104 people who each told...

Just like a computer virus.

[godsilove]

What animal models? I submit that the only animal model known to occur in nature which creates a lesion similar to the human is the guinea pig. This was noticed and first published in 1950. It is possible to create "fatty streaks", in other species with a very high cholesterol diet, but these lesions seem to bear little relation to CVD in humans. (There are clever (non cholesterol) methods known that will create human-like lesions, such as restricting vitamin B6 or copper in the diet of apes.)

By the way, perhaps the strongest animal models of which you speak have been created in recent years through genetic engineering. Mice which have been genetically altered so they cannot produce their own vitamin C rapidly develop atherosclerosis of the aorta.
http://www.pubmedcentral.nih.gov/articl ... d=10639167

Obviously, animal models do not not completely mimic the same pathology as in humans. (Just think of various animal models for mental illnesses) They are however useful to establish proof-of-concept, and to investigate specific molecular and genetic pathways that cannot be experimented on with human subjects. Often, the entire disease process cannot be simulated in a specific animal model; but a specific component of it, e.g. plaque rupture can be mimicked.

The example of the GULO-knockout mouse is quite interesting; nonetheless, upon reading the paper I don't see any indication that the aortic lesions in these mice resemble those found in atherosclerotic humans, nor that is meant to be a model for heart disease.

It might interest you to know that mice models used to study atherosclerosis include apo-E and LDL receptor knockouts.

Furthermore, I believe that the now often repeated claim that lowering cholesterol has been "shown to reduce the risk of heart disease" is an outright lie, unless clarified to some particular sub group on the basis of some limited study. On what do you base this statement?

It's based on multiple, large randomized clinical trials, meta-analyses that systematically review these studies, as well as long term observational studies. I think it's fairly well established that lowering cholesterol (primarily through the use of statins) can reduce the risk of heart disease, although to varying degrees in different subgroups.

Note that it has been reliably shown that increasing vitamin C intake lowers total cholesterol, so I can understand medicine's confusion. When increased vitamin C supplementatio is reducing the "risk of heart disease", a side-effect is lowered cholesterol.

Placebo-controlled trials strongly suggest that the benefit is independent of vitamin C intake. Furthermore, I'd be very intrigued by any RCTs showing that ascorbic acid lowers cholesterol as effectively as statins.

[DonHarry]

No one is denying that statins lower cholesterol - they do, very well. The point is, as Dr Fonorow mentioned, is there a benefit to reducing a symptom instead of attacking the cause? Vitamin C lowers cholesterol, but only as a side effect of resolving the cause. Only if you believe (The ever modified) cholesterol hypothesis does it make sense to block cholesterol production.

[ofonorow]

I'd be very intrigued by any RCTs showing that ascorbic acid lowers cholesterol as effectively as statins.

viewtopic.php?f=9&t=152

This thread is devoted to the large number of experiments by Emil Ginter on both guinea pigs and humans, and provides an overview. The Ginter work was referenced and discussed by Pauling in 1970 (long before statins) in HOW TO LIVE LONGER...

[godsilove]

No one is denying that statins lower cholesterol - they do, very well. The point is, as Dr Fonorow mentioned, is there a benefit to reducing a symptom instead of attacking the cause? Vitamin C lowers cholesterol, but only as a side effect of resolving the cause.

This has been addressed in a different thread - the evidence indicates that lowering cholesterol does decrease one's risk of CV events and mortality. It's just a question of who benefits more - those with previous CV events tend to benefit more, men tend to benefit more than women, middle-aged folks tend to benefit more than the elderly, etc.

Only if you believe (The ever modified) cholesterol hypothesis does it make sense to block cholesterol production.

That the "cholesterol hypothesis" is always being modified does not worry me. To the contrary, it encourages me. It's a characteristic of the scientific process - ideas should be constantly revised and updated based on accumulating evidence; aspects of a theory that are corroborated are kept, while those that are falsified or better explained by a different theory should be discarded.

[godsilove]

I'd be very intrigued by any RCTs showing that ascorbic acid lowers cholesterol as effectively as statins.

viewtopic.php?f=9&t=152

This thread is devoted to the large number of experiments by Emil Ginter on both guinea pigs and humans, and provides an overview. The Ginter work was referenced and discussed by Pauling in 1970 (long before statins) in HOW TO LIVE LONGER...

Unfortunately, we cannot establish that ascorbic acid lowers cholesterol as effectively as statins going simply by titles of papers without the abstracts.

I've briefly skimmed through the abstracts involving human clinical trials - the first one caught my eye, although I'm unable to track down the full paper. Have you been able to get a hold of it? The abstract does not give any indication of what kind of cholesterol reductions are seen with ascorbic acid treatment.