"But too much is not good either. Some participants in Track Your Plaque, for instance, have experimented with very high doses of EPA + DHA in the 9000-10,000 per day range and witnessed dramatic increases in LDL."

So what?

Wolf, Sears, and Poliquin recommend a high fish oil dose of 0.5g-1.9g EPA/DHA per 10lbs BW; this generally equates to 9-10g range.  All three have had amazing success with sedentary, chronically ill individuals and elite level athletes.

I believe you yourself have stated in the past that fish oil causes a shift from VLDL and IDL to large particle LDL---a benign, if not beneficial action.

So is the raising of LDL in high dose fish oil even a concern?  Some clarification on this would be appreciated.

Gosh... what an ODD response to fish oil! *wink* Do you actually believe it?  The reports would be contrary to the literature.  At least fish oil would have a strong role in stabilizing plaque and prevents soft ruptures in growing plaque (just like the Tokelau and Masai, high carb H-G societies)!

Nowhere in the literature that I can find reports omega-3 increases dense LDL. Perhaps there is a TYP program-omega3 interaction? Or perhaps this only occurs in those who take high-dose statins and fail to convert to Pattern A (due to the overstatination phenomenon, as reported by researchers where TG <  150)) and complain annually about their EBCT plaque progression 10-25%??  I have tried to admonish the statin overuse but apparently that doen't go over well with this individuals as you are aware. Oh well.

I have noticed that in the summers people's HDLs drift down.  Have you Dr. Davis in your practice?  I suspect a strong fruit-effect on splaying out dense LDL. Thoughts?

IMHO many on the TYP members consume WAY way way too much grains, orange juice, oat bran, oatmeal, FRUITY SHAKES (e.g. JJ) and consume several servings of fruit all day (e.g Jeg). Do you think this may play any part of complaints related to higher dense LDL?  My first thoughts are ALWAYS... diet.  

Your observastions are always UNIQUE!!  Thank you putting the highlights on the omega-3 index and the role of n-6 to n-3 on inflammation, the root cause of CAD!  You are certainly the biggest quantum EVOLVER.

http://drbganimalpharm.blogspot.com/search/label/Evolver

Gosh... what an ODD response to fish oil! *wink* Do you actually believe it?  The reports would be contrary to the literature.  At least fish oil would have a strong role in stabilizing plaque and prevents soft ruptures in growing plaque (just like the Tokelau and Masai, high carb H-G societies)!

Nowhere in the literature that I can find reports omega-3 increases dense LDL. Perhaps there is a TYP program-omega3 interaction? Or perhaps this only occurs in those who take high-dose statins and fail to convert to Pattern A (due to the overstatination phenomenon, as reported by researchers where TG <  150)) and complain annually about their EBCT plaque progression 10-25%??  I have tried to admonish the statin overuse but apparently that doen't go over well with this individuals as you are aware. Oh well.

I have noticed that in the summers people's HDLs drift down.  Have you Dr. Davis in your practice?  I suspect a strong fruit-effect on splaying out dense LDL. Thoughts?

IMHO many on the TYP members consume WAY way way too much grains, orange juice, oat bran, oatmeal, FRUITY SHAKES (e.g. JJ) and consume several servings of fruit all day (e.g Jeg). Do you think this may play any part of complaints related to higher dense LDL?  My first thoughts are ALWAYS... diet.  

Your observastions are always UNIQUE!!  Thank you putting the highlights on the omega-3 index and the role of n-6 to n-3 on inflammation, the root cause of CAD!  You are certainly the biggest quantum EVOLVER.

http://drbganimalpharm.blogspot.com/search/label/Evolver

My EFA results showed an Omega3 index of 11.7% and a Omega 6:3 ratio of 2.3/1. I supplement with 1600mg EPA and 800mg DHA daily. I follow a low carb (high fat) I can't afford to eat "grass fed", but I do avoid processed foods whenever possible and my dietary fats are from coconut oil, lard, beef tallow, butter, olive oil and small amounts sesame oil. The Omega 3 Index test was a bit pricey, but...it did give me some comfort that I am on the right track.

For those who witnessed an increase in LDL, what was the profile of small, dense VLDL vs large, fluffy VLDL reflected in the increase?

Also, first-time commenter. Thank you for a great, informative blog.

"But too much is not good either. Some participants in Track Your Plaque, for instance, have experimented with very high doses of EPA + DHA in the 9000-10,000 per day range and witnessed dramatic increases in LDL."

I'm hoping (and wondering if...) that while those diligent enough to take that high a dose of omega-3's may have higher measured LDL levels, they indeed have much larger, fluffier particles now than when they began the megadosing.  That would be something marvelous to hear.
Good stuff here, as usual!
-Adam

If one's LDL's raise dramatically on omega-3's, without the corresponding increase in hdl, or decrease in trigs, is it better to lower the omega 3's?

Ex:

pre-omega
tc 240
hdl 45
ldl 165
tg 70

during 2000mg omega-3's
tc 320
hdl 58
ldl 240
tg 90

Also, the pattern size of the ldl's are type a with a low carb, no grain diet.

I'd very much like to know what subfraction of LDL was elevated in the TYP followers on 9,000 plus omega 3's a day.  My experience is that large fluffy LDL increases but not small dense.

What about lipid peroxidation on high dose of fish oil?

The form of LDL that increases depends.

It seems to depend on the genetic basis for small LDL. In other words, if the triggers of small LDL have been removed along with other efforts aimed at reducing small LDL like niacin, and there is no genetic basis for small LDL, then large LDL increases.

If small LDL is genetically programmed (a lot more common than many think), then small LDL can increase explosively.  

Having performed many thousands of lipoprotein panels, the latter situation in which small LDL increases is worrisome.

I am unsure of the implications of the first situation. Sure, we can extrapolate and speculate that it might not be related to increased risk. But I am not willing to gamble someone's health and life on pure speculation with no human data.

The only references to an increase in LDLC with fish oil supplementation is from WS Harris who authors 95% of the omega 3 index studies including a 2008 review which concludes that the omega 3 index is superior to omega 3/omega 6 ratio.  When 95% of literature comes from one man who promotes a pricey lab test I can't help but wonder if he gets part of the profits. I have no data to say he does though.

He has two 1997 publications,one showing that Omnacor given at 4 g epa/dha a day raised ldlc by 10%. 1997 was the predawn era of advanced lipids.  In his second publication individuals with severe hypertriglyceridemia (baseline fasting levels on statins of 500 to 2000) did have a 32% rise in LDLC.  
Harris has ties to Big Pharma (the maker of Lovasa/Omnacor) and to Monsanto.
Data that I can easily access ascide from Harris shows effecacy of fish oil supplementation up to 4 grams of epa/dha a day.  5 grams a day for plaque stabilization/ antiinflammatory effect.  9 or 10 grams a day only in obese heart failure patients.  
My bottom line:  if your baseline tg's are 500-2000, watch out for your ldlp on high dose fish oil.  If you are an obese heart failure patient, lose weight.

I believe that when people use theraputic levels of fish oil (more than 3gm EPA=DHA)  they should follow their omega profile and lipoprotein analysis closely.  It is possible to push the eicosanoid synthesis pathways toward the arachadonic acid side depending on your diet.   Once you know your optimal dose, then you can adjust it up in certain circumstances.  I attended a football tailgate and found some of the mixed nuts were cooked in soy oil, so I took an extra dose of fishoil when I got home to compensate.

Thanks for your thoughts on this.  Regarding LDL particle size, how dependable would TG/HDL ratio be?  Sears indicates a ratio less than 2 indicates large benign LDL.  In my own experience over the past few years, as I've increased my fish oil intake (along with a Paleo diet) my HDL has gone up, my LDL has gone up, and my TGs have decreased.

I have increased my intake of omega-3 since I answered the poll. My problem was that I couldn't take it all at once. Too much fish oil gave me a super upset stomach. Granted, it was the impure Nature Made brand sold at Walmart (34% pure). Now that I am using Omapure, I take one capsule with every meal and then one before bed time. It 6x more expensive than the Nature Made junk but I'm not getting sick from it.

Does it matter that I break up my intake over the course of the day rather than swallow four capsules all at once?

great information here, thanks all.

To follow on Dr.BG's note on statin overuse :  there is an interesting presentation of baylor college's lipidsonline.org with discussion of guidelines for statin dosage.  The presenter notes how very little value is obtained from subsequent doubling of a statin dose and the risks for side effects.

http://www.lipidsonline.org/slides/slide01.cfm?tk=82

Dr. D.  Thank you for the caution on fish oil. I take 1650mgs EPA/DHA twice per day.  Might be a good idea to cut out a dose if I eat salmon or other oily fish.

Would love to see more info on MK4/Mk7 K2 and MCFAs like coconut oil.

Hi, Mike--

While the Triglyceride/HDL ratio can serve as a useful measure of small LDL in a population, it performs poorly when applied to specific individuals. This is because small LDl, while influenced by the situation creating low HDL and high triglycerides, can also behave independently.

Small LDL is, in my view, best measured specifically.

It's pretty straightforward to end up in the middle of the pack on that poll.  But don't take gels or you'll be there all day.  One tablespoon of Carlson's Finest has 4800mg O-3's with 2400mg EPA and 1500mg DHA.  One swallow just as I'm sitting down to breakfast makes for a great start to every day.

I was told than an ApoE 4 Patient should not be on therapeutic doses of fish oil (for reasons which you have stated- raising LDL).

Dr Davis:

I would like to know which WS Harris 2008 you referenced and the reference for the females in the Harvard School of Public Health please.
I also would like to know if there was a correlation between baseline tg levels and those who experienced a more marked elevation of sd LDL on fish oil.

I guess that this is my day to ask you questions.
When you read a MDCT, do you also measure pericardial fat?
What do you think of Dr. Ding's new MESA findings re pericardial fat.  Thanks in advance.

I take 6000 units daily or more, but I also consume a few tablespoons of ground flax seed daily as well.
AND still eat fish a few times a week, especially oil rich sardines.

Homertobias:

Lots of interesting work being done on pericardial adipose tissue (PAT) and using CT imaging done in conjunction with CAC scoring to more precisely determine the relationship between PAT and the development of CAD and calcified plaques, i.e., in order to more precisely "score" the level of PAT and to determine association and/or causality with calcific lesions.

Dr. Lerber at University Hospital in Munich, Germany has observed that PAT accumulation precedes the development of calcified plaques, that increased volume of PAT are associated with reduced levels of  adiponectin and higher CRP.   So the idea is that with more precise measurements and concomittant imaging of both PAT and CAC, we might be able to better detect the presence of disease in an earlier stage.   There is also some push among those doing such research to link PAT thickness assessment with administering routine echo stress testing but this hasn't gained much traction yet other than in a small circle of folks.   The hope though is that PAT can also be used as another surrogate marker for diagnosing preclinical atherosclerosis.

But as of now, I don't think anyone who does a routine CAC scan, whether with MDCT or EBT is doing any form of assessment of PAT, at least not until there is more data on the reliability of using this as a clinical marker of disease.

Personally, I think there's a lot of interesting info that can come from this, and the idea of deposition of fat into muscle tissue and necrosis of that tissue, inflammation and the relation to levels of saturated fats consumed from dietary sources is an area that is just begging to be better researched.

Oh, and by the way, don't believe everything you read here from BG about what foods I consume, how much statin I take, or much else when it comes to me.  In fact, I'd prefer that she simply not make references to me in her writings wherever they appear.  This will obviate the need for me to continue to correct her misstatements about me, my lipids, and drug and supplement usage, as well as the fact that she continues to misrepresent that I have not achieved plaque stability and/or demonstrated regression through serial MDCT CAC scoring over a period of three years despite very low dose use of rosuvastatin.

A correction....  My serial scan scores show that I have achieved stability and optimally regression of coronary calcium.   My point is that Dr. BG continues to claim that those taking rosuvastatin at doses of ~10mg daily cannot possibly achieve regression on EBT/MCDT scanning, and that just isn't so.

I happen to be one of those whom I believe Dr. Davis was referring to with "too much of a good thing" with reference to EPA/DHA dosing.  My dose was upped from ~1-2 grams per day (of EPA/DHA) to ~10 grams based on recommendations from Dr. BG.  This occurred in or around December 2008 and continued until very recently. Based on five consecutive, quarterly NMR's and VAP's, my sdLDL-P remained at >85% of LDL-P, and my trigs went from ~40 to ~75, and, more significantly, my overall LDL-P rose from ~1000 to ~1300.   No other significant impacts were noted, other than CRP dropping to 0.7, which I attribute not to the n-3's, but instead to continued use of rosuvastatin together with combined high dosing of both boswellia and 5-Loxin and large doses of aspirin (taken specifically as an anti-inflammatory due to nerve and muscle pain from a herniated cervical disc in the month immediately prior to the last VAP testing).

The point though is that in some, excess fish oil can convert to higher trigs and higher LDL, and will not improve the concentration or ratios of sdLDL-P/LDL-P.

Yes, n=1, but I'm the n, so that's really most important to me, not what Wolf, Sears or anyone else has to say about this.  After all, what we're after is personalized medicine, not epidemiological observations that may be valid in large population studies but which may have no relevance to a particular individual.

Hi JEG,
Thanks for the references.  I am truly upset that you andBG seem to be having a cybertiff.  She has a big heart, alot of enthusiasm, alot of intelligence and makes me laugh. You are a sincere intellectual, very bright, searching for truth in medicine and are doing a good job of it.  I can learn from both of you and want to continue to do so.
As to omega 3 and dosage.  I can't seem to find any solid benefit to doses over 4g to maybe 5g per day. This seems to max out tg lowering, ldl improvement in particle size, minimal increase in hdl, bp lowering, improvement in tnf alpha, interleukin 6.  Reports on irs effect on HSCRP are conflicting.  One interesting report, Thies F, in Lancet 2003 took 188 patients scheduled for carotid endarterectomy and treated them with either DHA/EPA, sunflower oil, or placebo for an average duration of 42 days prior to surgery.  There was a significant difference in thickness of the fibrous cap over the plaque,the degree of monocyte  infiltration of the fibrous cap, percent DHA etc.  This directly addresses plaque stability.  I love it.

Homertobias,

That is a great plaque stablization article -- will have to ck out!



Jeq,

I must be correct again as indicated by the length and duration of the post!

Let me get this straight -- the lipoproteins were less than desirable for both you and JJ/Jim for the past 2008 to 2009 (you reported increased sdLDL?), yet both of you posted regression recently on BOTH of your EBCT/MDCT results....  

Gosh... I wonder if the high dose fish oil had anything to do with it?

EPA DHA get infiltrated directly locally into calcified plaque and has immense immeasurable benefits for regression BEYOND lipoproteins.  I think you have seen some them, personally IMHO.

-G

Homertobias,

That is a great plaque stablization article -- will have to ck out!



Jeq,

I must be correct again as indicated by the length and duration of the post!

Let me get this straight -- the lipoproteins were less than desirable for both you and JJ/Jim for the past 2008 to 2009 (you reported increased sdLDL?), yet both of you posted regression recently on BOTH of your EBCT/MDCT results....  

Gosh... I wonder if the high dose fish oil had anything to do with it?

EPA DHA get infiltrated directly locally into calcified plaque and has immense immeasurable benefits for regression BEYOND lipoproteins.  I think you have seen some them, personally IMHO.

-G

By the way, congratulations to you two gentleman, JJ and Jeg, for achieving regression with Pattern B! I have looked for regression in Pattern B forum posters, but turned up none. You two are the FIRST at TYP that I can find...

Do you think omega-3 had any role in your success since that appears to be the common link as well as major supplement change you guys identified?

I wonder what the omega-6:3 ratio is now off the fish oil?

By the way, congratulations to you two gentleman, JJ and Jeg, for achieving regression with Pattern B! I have looked for regression in Pattern B forum posters, but turned up none. You two are the FIRST at TYP that I can find...

Do you think omega-3 had any role in your success since that appears to be the common link as well as major supplement change you guys identified?

I wonder what the omega-6:3 ratio is now off the fish oil?

Dr. Davis,

You keep making posts about things this newcomer to the Track Your Plaque program is thinking about.

I was thinking just last night that I would soon make a post at the Track Your Plaque (TYP) forum asking about what a TYP+ Supplement program might look like.

For people like me who have already experienced cardiac events this would be a huge thing.

I've now got my blood testing done.  I appreciate your providing feedback yesterday at the forum to my posting my blood test results there.

I also had a heart scan done even though I know it's of more limited use given my cardiac history and that you basically don't recommend it.  Frankly, I disagree with you a bit on the usefulness of a heart scan with preexisting cardiac events.  I'll explain why later.

So, I'm ready to go with TYP+ Supplement Program.

I have some specific supplements in mind that aren't among the current recommended TYP Supplements.  I'll make a note of the ones you mention in this post.  I'd like your feedback on a comprehensive list to try for inclusion in a TYP+ program of supplements.

I'll make that post to the forum soon now that I know you're thinking about this already.

Dream big my friend!

I am thinking a resort off the coast of Thailand. You take a month for the treatment. Fly in to a first class medical resort - do your fast while lounging in a tropical paradise - get lots of sun lounging by the pool (aids in Vit D absorption). While you are receiving the various medical and supplement treatments for your heart disease you might want to look into getting a little "touch-up" plastic surgery  or maybe that hip replacement you've been putting off...

I bet your "instant Heart Disease" treatment, some plastic surgery and a hip replacement in total would still be less money than a cardiac cath and stenting back in the United States!

I being somewhat facetious in writing this post...but I truly believe that scenario I discribed  
will be the norm in the next 10 or 15 years - as the rest of the world becomes richer and the regulatory environment in the US and Europe slows cutting edge development i could see some fast developing nation such as Thailand assembling a team of highly skilled Doctors in order become the world leader in treat a particular disease.


Peace

Joe E O

Hi, Joe--

Interesting perspective. I hadn't thought of it in those terms. If nothing else, it would make a fascinating experience to watch.

I think that method exists since the fifties and is known as chelation therapy.

Admittedly the mix, which is often vitamin C and other supplements plus EDTA or something similar, needs to be improved with the current knowledge about amino acids etc. But it could do the job.

Diet on the other hand is unbeatable. One could spend two weeks in a resort and eat ideal meals to improve health.

Sorry, but the chelation in my experience has never worked. I personally have seen several people go through it, usually provided by shady types, with huge rises in heart scan score. Until genuine evidence suggests otherwise, chelation falls in my scam file.

Hi Dr. Davis,

I have now got my intake of Niacin up to 3g a day using Slo Niacin.  I'm wondering if I shouldn't attempt to get it higher to impact my Lp(a) number.

I'm 6' tall and at 250 pounds am a "big person".  I'm working on the weight of course.

I understand there are potential impacts on the liver.

I have been told and found in the past that Silibinin Plus from LEF and n-acetyl-cysteine work pretty well to keep liver numbers under control.

What would you think about my taking my niacin dose up to 4g a day (or even potentially higher) if I could keep my liver numbers under control.

Thanks.

I'm a big believer in going slow with niacin. It may take a year or more for it to exert full effects, including reduction of Lp(a). I am generally not in a hurry to raise doses.

I do favor periodic cycles off niacin, however, especially in people with Lp(a). In my many hundreds of patients with this disorder who take niacin for several years, there is a peculiar creep back up of Lp(a) levels back to the starting values. I believe that periodic "vacations" off niacin are necessary from the start, e.g., one month off every six months. Resume dose gradually and work with your doctor if/when you do this.

Re: liver protection. I'm only superficially familiar with those agents, and I cannot say specifically whether they spare the liver from niacin effects. Interesting idea, though. Phosphatidylcholine? The liver-sparing effects of this agent are interesting, also. But I know of no specific experience with niacin, unfortunately.

Thanks for the reply Dr. Davis,

I understand that, because you're not my doctor, you can't give me specific medical advice.

It's also true that I know of no other doctor who has more of the scientific literature and practical supplement experience than you have.

First, however, thanks for the tip on periodic Niacin vacations.

Let me then put another question to you this way...

I'd like to propose to my doctor the following to get his expert insight but before I do, having your opinion would come in handy.

Suppose I pumped up my intake of niacin to 5 grams.  After a month of that, I get a liver numbers test.  Then I begin the Silibinin Plus - N-Acetyl-Choline regimen.  Then after another month, I take another liver numbers test.

Would a scenario like that provide me with useful information for long term Lp(a) treatment without doing permanent damage to my liver?

Any suggestions for improving the idea?

One last thought...

Because Lp(a) is believed to be formed in circulation (per McCormick, Marcovina, et al), it seems to me that continuous availability of niacin in circulation is important.  So, I'm thinking 2 or 3 doses of niacin per day at 1.5g to 2.5g per dose.

Seems to me that dosing like that would be beneficial to assessing the impact of the Silibinin Plus - N-Acetyl-Cysteine regimen.

Does that make sense?

Thanks for all you do!

wccaguy--

I think that it depends on your endpoint.

If Lp(a)reduction alone is your endpoint, then raising niacin even to 5 g per day is reasonable.

However, if control of plaque growth is your endpoint, then you might make do with far less, e.g., 2000-3000 mg per day. It can vary enormously. (In fact, I have even seen an occasional person reverse without Lp(a) control, though this is unusual.)

One warning re: the frequent dosing of niacin. Far more likely to yield liver toxicity than dose is frequency. Taking niacin three times a day as SloNiacin virtually guarantees serious liver toxicity--I would strongly urge you to NOT do this. You are safest with once daily dosing of the SloNiacin preparation.

Re: liver toxicity gauged by liver function tests. Unfortunately, these are not really good tests for quantitative assessment of liver toxicity; they are rather weak, qualitative tests. So I do not believe you can make much of shifts within the normal range.

Thanks Dr. Davis for the niacin regime tips:

To sum up.

1   I will try to get my Slo Niacin dose to 5g per day in a single dose.

2   I will monitor Lp(a) test scores.

3   I will take a one month niacin vacation every six months.

Thanks again.

Your blog is very informative i must say. I like such dedicated blogs. I too write a blog on fitness and health and life. it is http://dreamfit.blogspot.com
do stop by sometime.

Dear Dr.Davis,

I just came across your site for the first time and very much like the content and layout.

I'm aware that you don't answer personal questions but am not quite sure with what one can post or comment on? I hope my post is considered acceptable and I hope you will take the time to comment briefly.

I'm in a desperate need to help my mother who had a hearth attack a month ago. She's always had a low blood pressure and considered herself to be very healthy. She is 63 and never been on any medication, no pains or complaints. And all of a sudden-a heart attack! She has had two stents put in and is on several medications-Plavix 75mg, Beloc Zok 25mg, Triatec, Sortis 40mg, Aspirin 100mg and Nexium 40mg.
I'm aware of the interactions of Plavix and Aspirin-Nexium and am terrified of the complications. She started taking a nattokinease supplement and thought that it will be better if she didn't take the Aspirin-Nexium. However after reading all your comments on natto-i feel this might not be a wise idea. I've been a regular reader of Dr.Mercola.com for many years and ordered a product called Cardioessentials from the site. I must say am not a fan of the statin drug as well but have only insisted on CoQ10 as ubiquinol of 200mg a day.
She has become more thoughtful of her diet and exercise. I know that thing rarely happen without warnings and am sure she  could have taken a better care of herself. She did gain a bit of weight lately and I know that visceral fat does come with a price on heart health! She is following a diet rich in vegetables and fruits, lean meat and fish, nuts and seeds and low in grains. She takes fish oil, flax oil an olive oil,garlic, green tea, vit C in high doses, vit E and D, ALA, vit B complex, grape seed extract and chlorella. I'm considering L-carnitine, L-arginine, taurine, lutein and NAC.

Please share a few wise words on this protocol and let me know if there is anything she is missing out on or should not be taking.
I would greatly appreciate your comment. Thanks in advance,

Lidija McLaren

Heart  disease is one of the most  dangerous disease which takes thousands of life every years all over the world. If we know its symptoms and Treatment for heart disease. We can prevent is to large extent.

Heart  disease is one of the most  dangerous disease which takes thousands of life every years all over the world. If we know its symptoms and Treatment for heart disease. We can prevent is to large extent.

This is a routine widely practised in Japanese hospitals for many diseases. They also use an IV glucose solution with electrolytes.

I am doing exactly what you suggest at the moment.

Supplements:

1/2 teaspoon of salt and 1/2 teaspoon of salt substitute (potassium chloride) dissolved in 2L of water. This provides very roughly 2g sodium and 2g potassium/day.

300mg magnesium and 800mg to prevent cramps.

A single multivitamin tablet.

A high potency B group supplement.

500mg vitamin C.

5g fish oil.

After 3 days I have never felt better in my life

This is simply whimsical at this point. I don't know if such an approach would work. But if it did, you might imagine that it would offer an opportunity--for the properly motivated--as an alternative treatment for angina, advanced coronary disease, a means to pull someone back from the brink.