I've had no success lowering my very high LDL(350), can't tolerate statins..supposedly have combination of large and small LDL, 20-40% blockages per cardiac cath.My HDL (80), Trig.(70)are good, but still concerned since already show athrosclerosis. I'm 55, 100 lbs., and have had high LDL since a teen. Any suggestions? Thanks!

Isn't inflammation the root cause of atherosclerosis ? Isn't cholesterol's role in heart disease only that it happens to be used as the material, with which the body repairs the lesions caused by inflammation ?

excellent post. 1. if statins not preferred way to go for small LDL, what is- Niacin and elimination of grains? 2. How is it possible that a VAP test showed large Pattern A(by small margin)and two years later NMR shows nearly 100% small dense Pattern B?  Is one test better than the other? 3. Do genetics overwhelmingly determine pattern size?  I have eliminated all grains,sugars, starchy veggies to see if i can get my LDL to be large and fluffy.  Thank you.

I am an example of someone with "normal" cholesterol and CAD. I was only 54 years old when my LAD blocked. I went on to bypass as I reblocked after each stent.

In the past few years I have been looking into many of the other factors may have contributed to my  health problems and trying to optimize my health. Yes, coromary heart disease is so much more than elevated cholesterol.

No it doesn't!

Hi Dr Davis,

Excellent post. The value of total cholesterol is irrelevant. While there is a VERY slightly higher cholesterol level in heart attack patients, the overlap with the normal population is such as to make total cholesterol level meaningless. Once it's meaningless and you can then look back to the initial work of Ancel Keys, who appears to have been the primary architect of the lipid hypothesis, and you can see it is based on this now clearly meaningless measurement.

The very slight increase in TC in cardiac patients is explicable by the fact that glycation of the apoA particle inhibits its attachment to the LDL receptor. I would expect this to produce a slight rise in TC. You then have to pose the question as to which does most damage: persisting apoA containing particles due to glycation of their surface protein, or glycation of all of the body proteins by the same hyperglycaemia that affected the apo A protein. Using HbA1c as a marker of hyperglycaemia there is a reasonable correlation with CVD even within "normal" HbA1c levels in the EPIC study. Whole grains = hyperglycaemia. Hyperglycaemia = apoptosis of vascular endothelium. What more do you need for vascular damage?

So, as the lipid hypothesis is based on TC and should have been stillborn or drowned at birth, where does particle size come in? We have the situation of good (HDL) cholesterol and bad (LDL) cholesterol to explain why TC is useless. Then we get good LDL (large fluffy) and bad LDL (small dense) to explain why total LDL (by calculation) is utterly useless too. We even now have good and bad HDL. Never mind good (small) VLDL and bad (large) VLDL to explain why some triglycerides are better/worse than others.

Ultimately small dense LDL, large VLDL and HDL3 are strong markers of the metabolic syndrome. Hyperinsulinaemia and insulin resistance are the cornerstones of metabolic syndrome according to Reaven, who largely popularised the concept. The lipid changes are easily viewed as a consequence, not a cause, of metabolic syndrome. It is undoubtedly believable that sdLDL is stickier/more oxidisable than other lipoproteins, but that becomes unimportant if it's not there in the first place, ie no metabolic syndrome. This would, simply, explain why reducing wheat products works to reduce sdLDL, unless they are replaced by equally insulinogenic "wheat free" comparable junk foods based on non wheat sugar sources. If it turned out that purple spotted LDL, induced by eating blackberries, was stickier than sdLDL we would no doubt have a drive to eliminate blackberries or (more likely) develop a drug to remove the purple spots.

Following your blog gives me the distinct impression that one day you really could become a cholesterol skeptic. Stranger things have happened.

Peter

Anonymous and Steve - I stronly believe in a propper low carb (note that I say LOW carb, and not NO Carb) way of eating. I would really like to suggest some awesome reading material. It is from dr. James E Carslon who wrote the book "Genocide. How your doctors dietary ignorance will kill you!!!". In the book he explains amongst other things the actual benefits of dietary cholesterol and how a low-carb way of eating will increase the ldl-particle sizes and bring down the triglycerides and dangerous VLDL.

From a recent personal answer I got from him, he explained to me the benefits of adding dietary cholesterol from a biochemical point of view. I hope this helps in understanding that a correct dietary change can help.

Here is what he said :

OK, so what are the benefits of adding cholesterol to the diet? It's not only fascinating, it'll blow your mind. When we eat cholesterol containing foods, the cholesterol in the food we consume actually binds to an enzyme called HMG CoA reductase and inhibits its function. This enzyme is what's known as the rate limiting enzyme in cholesterol biosynthesis. This means that once this enzyme does what it's supposed to do, cholesterol will be made no matter what. By inhibiting the enzyme's function, choilesterol cannot be made. So eating cholesterol actually inhibts its own production.
But wait, it gets even better.

The cholesterol in the foods we eat is what's referred to as fat soluble, or lipophilic (or fat loving). Since cholesterol is lipophilic, it diffuses through not only the outer cell membrane, but the cell's=2 0nucleus membrane and attaches the the DNA. Guess where it attaches to on the DNA? It attaches to the sites on DNA WHERE HMG Co A IS MADE!!!!! That's right, so not only does the cholesterol in the food we eat attache and inhibit the function of the enzyme already present to make cholesterol; the cholesterol in the foods we eat also prevents the production of the enzymes needed to make itself. In biochemical speak, this is known as negative biofeedback.

Eat more cholesterol, make less cholesterol. By the way, the only thing I've seen in eighteen years considerably raise the good cholesterol known as the HDL, is the consumption of more cholesterol. So EAT MORE CHOLESTEROL IT"S GOOD FOR YOU!

Inflammation is essentially the cause of heart disease isn't it?
I'm not medically trained, but I assume small particle LDL is a signifier of crammed, broken up large particles - perhaps a long time accumulation of what was once sent to the skin hoping to be converted to D by UVB but didn't(there is a study that says British gardeners have lower cholesterol in the Summer which seems very interesting).
The fact that statins work (albeit with alarming side effects), and that according to a Spanish study, that atorvastatin raises vitamin D some degree shows the problem isn't really cholesterol. That is erroneous cholesterol readings are the 'symptom' of either vitamin D deficiency or associated things that domino on to the ability for the heart to succomb to heart disease. As a rule I still think the general cholesterol hypothesis is a farce, not just because of the way the products are marketed but because it's only looking at one station on the tube system. 'High cholesterol causing heart disease' might be better termed as 'low vitamin D causes heart disease' because that's perhaps the root, or at least one root.

Dr. Davis,

First let me say a big thank you for your blog.  I follow your's, Jimmy Moore's and the Drs. Eades' blogs closely.  As a result of reading your book and blot, I just had my first heart scan at age 50, and was vert happy to hear zero calcium score.

I do low carb nutrition (~50g/day), so my triglycerides were very low (28).  I've read that all LDL will be large with triglycerides that low (below 70).  Can you confirm that?  Would I be wasting my money on blood work to determine particle size?  HDL is 62, LDL 136.

Steve L.

Simple cholesterol measurement also ignores the presence of other factors that lead to heart disease, like lipoprotein(a) and vitamin D deficiency.

Conventional total and LDL cholesterol do not distinguish between large and small particles, nor reveal the presence of other hidden patterns. An LDL cholesterol of 150 mg/dl, for instance, may contain 100% large LDL--a relatively good situation that by itself is unlikely to cause heart disease, or it might contain 100% small LDL--a very bad situation that is likely to cause heart disease. Just knowing that LDL is 150 mg/dl tells you almost nothing. In 2008, most people have some mixture of the two, particularly with the proliferation of "healthy whole grains" in the American diet, foods that trigger formation of small LDL.

I'm looking for heart disease info that isn't related to cholesterol OR grain intake, because my cat has it--cats are obligate carnivores, and therefore do not take in grains unless fed commercially-prepared foods.  Mine do not--I make their food from scratch, using a UC Davis vet-designed diet recipe.  Cholesterol levels aren't a concern either, although I now know to have the SIZE of cells examined, as well as vitamin D levels checked.  As for anti-inflammatories, fish oil is part of the diet recipe.

I'm going back to the vet for more blood work (now that I have more clues).

Statins Do Not Decrease Small, Dense Low-Density Lipoprotein
Free full text at link.
In an observational study, we examined the effect of statins on low-density-lipoprotein (LDL) subfractions.
Using density-gradient ultracentrifugation, we measured small, dense LDL density in 612 patients (mean age, 61.7 ± 12.6 yr), some with and some without coronary artery disease, who were placed in a statin-treated group (n=172) or a control group (n=440) and subdivided on the basis of coronary artery disease status.
Total cholesterol, LDL cholesterol, apolipoprotein B, and the LDL cholesterol/apolipoprotein B ratio were significantly lower in the statin group. However, the proportion of small, dense LDL was higher in the statin group (42.9% ± 9.5% vs 41.3% ± 8.5%; P=0.046) and the proportion of large, buoyant LDL was lower (23.6% ± 7.5% vs 25.4% ± 7.9%; P=0.011). In the statin group, persons without coronary artery disease had higher proportions of small, dense LDL, and persons with coronary artery disease tended to have higher proportions of small, dense LDL.
Our study suggests that statin therapy—whether or not recipients have coronary artery disease—does not decrease the proportion of small, dense LDL among total LDL particles, but in fact increases it, while predictably reducing total LDL cholesterol, absolute amounts of small, dense LDL, and absolute amounts of large, buoyant LDL. If and when our observation proves to be reproducible in subsequent large-scale studies, it should provide new insights into small, dense LDL and its actual role in atherogenesis or the progression of atherosclerosis.

The imprecision and uncertainty of conventional total and LDL cholesterol has provided ammunition for some to discount the entire cholesterol concept. And they are right to a degree: cholesterol by itself is indeed a lousy predictor of heart disease. But small LDL is a very reliable predictor of potential for heart disease. Dismissing the entire concept because the standard measurement stinks is not right, either.

For years I suffered from high cholesterol and was almost permanently on statin medication. I come for a family with a strong history of heart disease and I personally believe that high cholesterol can cause heart disease. Thankfully I now have my cholesterol under control but it has been hard work, and I done it the natural way, as I suffered from the side effects statins cause.

How To Lower Cholesterol Without Medication

About eighty percent of our cholesterol is produced by the liver and the rest depends on our diet. Foods such as red meat and butter are rich in cholesterol where as those from plant origin have very little or no cholesterol at all. The control of cholesterol in our body is done by the liver. I think,more can be found out from:
http://www.heart-consult.com/articles/how-cholesterol-affects-heart

exactly!!!!!

You are probably right that most people should increase their omega-3 intake.  However, all of fish oil pills (and the liquid) that I see have moderate-to-high doses of vitamin E.  So your recommendation appears require supplementing with large doses of vitamin E (in addition to the fish oil); do you think this is a cause for even mild concern?

What about all those CVD-free populations that don´t eat any fish (e.g. Masai)? Obviously fish (oil) is not necessary to be healthy.

What a range - but must remember that both fish oils omega 3 and omega 6 important herbal supplements.

I think that it is extremely difficult to separate the benefits of one nutrient from the effects of one's overall diet and supplement regimen.
Maintaining a low omega 6 to omega 3 ratio has been shown to be very important.
I have taken 3 standard Sam's/Costco capsules (total EPA+DHA=900 mg) for many years,along with an overall regimen not unlike Dr Davis's recommendation.
My guess is that an ounce of early prevention is probably worth a pound of later reversal, but perhaps I am simply in the lucky 50%.

FWIW my HDL at the outset was in the low 30's @ age 40, now runs about 50, @ age 72. CTA scan 1 year ago: "no detectable plaque"
My Father died of second MI @ age 76.
Over the years most of us "preventers" have had to read the studies, and take our "shot in the dark" with our supplements.

Dr Davis, I can't over emphasize the value and encouragement of receiving feedback from you and your patients on the frontline. Please keep up (and promulgate) this excellent work.
MikeV

Is there a reason to eat those omega 3 eggs if you think you're getting enough 3 from fish oil?

Since omega-3 fats are polyunsaturated that renders them prone to peroxidation.  Evidence indicates fishoil improves lipid profile, but at what cost?

I hope that you (Dr Davis) realize that fish oil decreases clotting time. At what point does that come into play as being an undesirable side effect? If it takes longer than 5 or 10 minutes to stop a cut from bleeding, is that too long? What about occult internal bleeding or hemorrhagic stroke? I think this needs to be addressed. In addition many people take aspirin, more than the 81 mgs that is recommended. NSAIDS affect clotting, Vitamin E in larger doses can affect clotting, some herbs affect clotting. While I understand that the cardiovascular effects are desirable, I question the clotting issue.

I can see why fish oil might seem beneficial to folks who eat the SAD, in a similar way the epi studies indicate eating whole grains trumps refined grains (I think the evidence indicates that no grain is better whole grain).  Fish oils make a crummy standard diet less damaging, so it seems like a great idea.  

But what about if one avoids industrial foods and the sources of omega 6 PUFA in the first place?  Why supplement with omega 3 if there is no need to offset the omega 6 FAs?  Why purposely raise intake of intake any unstable PUFAs, including omega 3s (fish oil).

There are considerable concerns about PUFAs consumption in general, particularly cancer.  

I have greatly reduced or eliminated the most common sources of omega 6 FA (minimal or no grain,  industrial veg oils, or grain-fed meat/dairy/poultry).  Instead, I stick to pastured animal foods and traditional fats that are predominately naturally saturated or monosaturated (unless the PUFAs are in the original intact food, such as nuts, fish, etc.).  

So if I supplement with fish oil omega 3s (or any concentrated non-food source), I could actually be overloading on omega 3 PUFA intake in relationship to my low omega 6 intake.  

I've been mulling this over for some time, trying to reconcile the differences in views.  Then Peter's post on Hyperlipid showed up today.  Could this be the interpretation that explains my reluctance on the fish oil supplementation?

http://high-fat-nutrition.blogspot.com/2008/08/age-rage-and-ale-vldl-degradation-and_25.html

Dr. Davis, I know you are busy, and I'm not trying to create waves, but since you do advocate fish oil supplementation, I wonder if you can review Peter's post and explain if you have a different interpretation.  

On the fish oil issue, I just haven't been able to decide my best course of action, other than holding off on supplementation until I am more confidently sure of my understanding of what more omega 3 might or might not do for me and my family (not on the SAD).

A recent review published in the American Journal of Clinical Nutrition by Dariush Mozaffarian of Brigham and Women's Hospital and Harvard Medical School concluded that omega-3 fish oil fatty acids EPA and DHA help prevent heart disease, but that the benefits only extent to taking 250 mg/day. This conclusion was based on the convergence of data from prospective cohort studies and randomized clinical trials.

This is from Chris Masterjohn´s newsletter.

Yes, I've been reading Chris Masterjohn's interpretations of the PUFA and cholesterol literature, too (among others).  Gotta love the access the web gives us, eh?  Though it does give us a lot to ponder...still, I feel better about sifting through some contradictory ideas or ones that don't quite fit the puzzle vs. just accepting the conventional info spooned out to me and burying my head in the sand, like too many do.

Sven,

Mozzafarian is misinformed about a lot of things -- he wrote a letter once advising against EBT heartscans (low rad, no dyes, low maintenance) for the general population (he's kinda right -- health insurance may not be able to 'afford' an EBT for 'everyone' however on the flip side, if prevention of expensive procedures and hospitalizations (and optimal health) were goals of health insurance, then eventually they cannot NOT afford to offer EBT to everyone.  

Darius is young... give him time -- he has done some wonderful research and I believe he's on the right track.

He was my chief resident on my Internal Med rotation at Stanford, as a pharmacy clerkship student.  My classmates (male and female) all drooled after him... Some thought he was a blond, hazel-eyed Persian god. Very kind, humble, hard worker (despite family wealth) and smart too!  

-G

Sven,

Mozzafarian is misinformed about a lot of things -- he wrote a letter once advising against EBT heartscans (low rad, no dyes, low maintenance) for the general population (he's kinda right -- health insurance may not be able to 'afford' an EBT for 'everyone' however on the flip side, if prevention of expensive procedures and hospitalizations (and optimal health) were goals of health insurance, then eventually they cannot NOT afford to offer EBT to everyone.  

Darius is young... give him time -- he has done some wonderful research and I believe he's on the right track.

He was my chief resident on my Internal Med rotation at Stanford, as a pharmacy clerkship student.  My classmates (male and female) all drooled after him... Some thought he was a blond, hazel-eyed Persian god. Very kind, humble, hard worker (despite family wealth) and smart too!  

-G

BETTER THAN STATINS

Keep up the good work folks.
More vindication from Europe.

http://www.iht.com/articles/2008/08/31/healthscience/fishoil31.php

Mike V

"What about all those CVD-free populations that don´t eat any fish (e.g. Masai)? Obviously fish (oil) is not necessary to be healthy"
thye eat a lot of grass fed animals and their organ and drink their blood all high im omega 3

Dr. Davis,

Just came across your blog recently--fascinated by it. Learning a lot. Question: Have you had any experience with Neptune Krill Oil? The DHA and EPA in it is supposedly naturally bound to naturally-occurring phospholipids (the composition of our all our cell membranes), which makes its bioavailability and assimilation so much higher. Consequently, so much less is needed for a therapeutic dose.

There are also several clinical trials (even though they are small) with really amazing results.

Check it out and please let me know what you think.

http://neptunebiotech.com/

I keep reading about getting toxic dose of Vit A with taking high doses of fish oils.  The vegetarian option only seems to have DHA and no EPA.  Sugestions?

Dr. Goldstrich has proven especially adept at understanding how to incorporate new findings from clinical studies in our framework of coronary atherosclerotic plaque management strategies.