Saturday, January 10, 2009

HDL2 = Quintessional Regression Particle and Ways To Maximize It

It's true. We do use some statins at TYP. Primarily they may have value until insulin resistant/hyperinsulinemia/Metabolic situations are improved via diet, hormone, vitamin D, and exercise/wt loss. Also they may have a role for FH (familial hypercholesterolemia) again until diet/lifestyles/vitamin D kick in.

Statins are by no means mandatory for regression or stabilization.

Or maximal health or lifespan extension.

In Dr. Davis' experience, in fact, a great majority of his patients experience statin intolerance and myopathy (muscle pains). Low grade muscle breakdown affects more individuals on statins than probably estimated in the literature. Most of these individuals likely have some kind of mitochondrial dysfunction and/or dietary cholesterol deficiency (and since statins BLOCK CHOLESTEROL SYNTHESIS, the drugs only exacerbate such situations). Muscles cannot function without...cholesterol and its downstream intermediaries...Including... Testosterone... Cortisol. Like 25(OH)D Calcidiol (vitamin D). Like estrogen!! Like DHEA. Like Pregnenolone.


In fact...all the HORMONES that make us what we are. Cholesterol is also a vital component of our BRAIN, myelin sheaths, nervous system, immune system and every cell's membrane.




Statins Indirectly Affect PPAR/Pleiotropy, Therefore Raise HDL2
Statins work marginally because they affect PPAR-alpha. (and other research shows PPAR-gamma as well HERE and HERE)

Recall, again, saturated fats and fish oil hit this receptor known as PPAR too. PPAR is the master controller of pleiotropic actions in our body. PPAR controls CETP reduction and PTLP maximization also.

Pleiotropic PPAR properties: endothelial function, oxidized low-density lipoprotein, inflammation, plaque stability, vascular remodeling, hemostasis/coagulation, vasomotor, cardiac muscle, anti-arrhythmic, and nervous system (brain and conduction pathways to the heart, organs, muscles)

Power up your PPAR...and you will attain immortality.




Not with statin monotherapy.
Clinical significance of pleiotropic effects of statins: lipid reduction and beyond.
Comprehensive lipid management versus aggressive low-density lipoprotein lowering to reduce cardiovascular risk.
Non-lipid effects of statins: emerging new indications.
Statin pleiotropy: fact or fiction?
Ongoing clinical trials of the pleiotropic effects of statins.
Beyond lipid lowering: the role of statins in vascular protection.
[Statins: intervention studies, facts and perspectives] "Questions still remain unanswered. To what extent do we have to lower LDL-cholesterol? What are the risks of an aggressive treatment with statins?"

In fact, a recent EBT trial by Raggi et al (2009 Atherosclerosis) lead to conclusions by leading cardiologists that LDL and LDL-reduction really have nothing to do with plaque.
Non-HDL cholesterol is strongly associated with coronary artery calcification in asymptomatic individuals.



If you have Lp(a), a toxic sticky lipoprotein that accelerates many diseases including coronary and vascular calcifications, then statins won't help you at all. In fact, anecdotally, certain high dose statins (like Lipitor) make Lp(a) concentrations higher. Studies estimate that 17-25% of the population are carriers of Lp(a). I estimate that a much greater percentage have this. In fact, all Metabolic Syndrome individuals appear to me to display very accelerated heart disease even if only a small amount of Lp(a) is present (for instance 6-20 mg/dl). What lowers Lp(a)? Everything that raises HDL2 naturally and non-synthetically. (Not statins, not Zetia, not Fibrates; Actos, a PPAR-gamma drug, a little; fish oil, fats, forgoing carbs/grains -- A LOT)
Increased lipoprotein(a) in metabolic syndrome: is it a contributing factor to premature atherosclerosis? Y E S

The below authors discuss: "bezafibrate as a pan-PPAR activator has clearly demonstrated beneficial pleiotropic effects related to glucose metabolism, insulin sensitivity and pancreatic beta cell protection. Because fibrates, niacin, ezetimibe, omega-3 fatty acids..."
Optimal management of combined dyslipidemia: what have we behind statins monotherapy?

In addition to niacin and omega-3 fats, how about other dietary fats/IF/strength training/anaerobic exercise/LC-diet?

*sigh* ....the best pan-PPAR activators...





HDL2 is Cardioprotective

We like HDL2 at TYP.

HDL2 is like wealth and health...You can never have too much balanced wealth or balanced health!

HDL2 is in fact an antioxidant and provides immunoprotection as well as cardioprotection. One of the labs ordered at TYP to assess health status is the NMR (or VAP) which separate out the lipoproteins by size and density and provide a 'count' of the absolute number of particles. The larger the particles, the better. HDL2 is one of the largest, most buoyant particles, and most desirable.

The more dense, the more deadly. Like dense fuddy-duds, we don't like dense particles. Read more at TYP here (members now; later free).

These are all good: HDL2, HDL1, LDL2, LDL1, Large-HDL, Large-LDL

Bad: sdLDL (small dense LDL), HDL3, Small-HDL, LDL3, Small-LDL



Jimmy Moore recently interviewed our beloved Dr. Davis. Jimmy's Large-LDL (and presumably HDL2's) are phenomenal!! He reported that he had virtually no small dense LDL -- it's all large -- the good stuff.

Jimmy's labs aren't dense!

Strong work Jimmy!!
http://heartscanblog.blogspot.com/2009/01/another-interview-with-livin-la-vida.html




Many things increase HDL2...


PPAR-alpha drugs, like Fibrates, do certainly hit PPAR -- but not in a natural configuation because these are synthetic/FAKE chemical entities. Fibrates artificially increase total HDL but have been shown adversely affect the particle sizing. They increase HDL3 and lower HDL2.

wtf... bad bad bad...

This explains why fibrate trials are like statin trials. So far only a very limited reduction in mortality, obstructive events and interventions have been demonstrated: approx only 15-25% reductions in CAD.

Remember, it's not the quantity of HDL you have, it's the quality of HDL subparticles -- large v. small.

You don't want... s m a l l. Or dense.

Like small muscles...where's the (sex) appeal?

What's the...point?


These researchers from Switzerland 'get it'... (sorta -- they still push pharmaceuticals *sigh*) "Recent findings suggest that the mechanism of HDL modification rather than a sole increase in HDL-C determines the efficacy of anti-atherosclerotic drug therapy. " Yes, these are my observations from the medical literature and at TYP. The ones who fail to achieve stablization or regression have VERY HIGH HDL-3 and VERY very low HDL-2. Their CAC progresses 10%+ annually and they are befuddled.
Modulation of high-density lipoprotein cholesterol metabolism and reverse cholesterol transport.
Marine lipids normalize cholesteryl ester transfer in IDDM.
Change in alpha1 HDL concentration predicts progression in coronary artery stenosis.



Statins work to regress plaque by affecting PPAR receptors in our body. Yes, LDL reduction is part of their novelty but by and large the regression pattern is secondary to its significant anti-inflammatory effects (via PPAR) and its plaque remodeling effects (via PPAR) and HDL-2 raising effects (via PPAR).

These encompass all the pleiotropic actions of PPAR.

PPAR is powerful.

(And who knows? Statins may help regress plaque by raising vitamin D blood levels as well. Yes, indeedddeeyyy, statins raise [25(OH)D] HERE and HERE.)

Statin-induced inhibition of the Rho-signaling pathway activates PPARalpha and induces HDL apoA-I.
The effects of statins on high-density lipoproteins.
Comparing the effects of five different statins on the HDL subpopulation profiles of coronary heart disease patients.




Low-Fat, Low-Muscle, and HIGH-CARBS Lower HDL2

What degrades HDL2??
--AHA Low Fat/Step 2 diet -- makes you dense, your particles, I mean--Exercise deficiency or excessiveness (eg, overtraining)
--Lack of lean muscle tissue
--Preponderance of belly/visceral fat
--Excessive insulin
--Cortisol (stress)
--Carbs carbs carbs (high carb, grain-based diet)
--Soda, fructose (esp high fructose corn syrup), excessive fruit, grains, wheat (which also triggers stress responses), processed foods, cereal, etc
--Drugs/pharmaceuticals (Zetia, Lipitor high dose, statins high dose, Fibrates: Lopid/gemfibrozil, Tricor/fenofibrate)
--Insufficient dietary cholesterol, fish oil, monoun- or saturated fat intake
--Smoking
--Excessive alcohol (2-3 or more drinks for men; 2 or more, women)


What raises HDL2?
--The paleo prescription, eg, this blog, TYP and other resources--Niacin (see below)
--Intermittent fasting
--Generation of ketone bodies (low carb, mod-high prot/fat)
--Starvation
--Exercise (avoid excessive endurance training)
--Strength/resistance training
--Reduction in belly/visceral fat
--Reduction in insulin (eliminating wheat, reducing carbs)
--Tobacco cessation
--Elimination/moderation of alcohol
--Eating protein, esp Leucine, Taurine, etc
--Vitamin D (see Dr. Davis' blog)
--Carotenoids (astaxanthin, krill oil, seafood, grassfed meat, etc)
--Fish oil/EPA+DHA: supplemention, grassfed meat/dairy; fatty fish, mackerel, tuna, herring, hamachi, trout, cod liver oil, mollusks, krill, crustaceans, etc
--[If high inflammatory state: Ultra high dose 8-10 g/day EPA DHA fish oil for 6-18mos (Goal: fatty acid profile test, omega-6 to omega-3 ratio = 1.5)]
--ALA, monounsat fats: flaxseed oil, olive oil, nuts/seeds, etc
--Casein-free butter oil (rich in phytosterols, vitamin K2, CLA, short-chain and medium-chain saturated fatty acids, EPA+DHA and a bounty of other HDL-boosting nutritional factors); organic, grassfed ghee
--Eating some saturated fats (not TRANSFATS which are toxic to HDL2)
--Eating some CHOLESTEROL (via omega-3 eggs, seafood, grassfed meat/dairy, etc)






Niacin and HDL2

Remember niacin increases HDL2 by 200-300% (and reduces HDL3) in a 18-36 mos period of time... (niacin works indirectly on PPAR too)

Crestor only increases HDL2 by 21%??


Is that why Niacin (+low dose simvastatin) resulted in a 90% reduction in mortality and heart events in the unprecedented HATS trial?
Niacin-based therapy for dyslipidemia: past evidence and future advances.
Effect of niacin and atorvastatin on lipoprotein subclasses in patients with atherogenic dyslipidemia.


May it have anything to do with HDL2 subfractions increasing by 10 - 20 xxx with Niacin Therapy vs. Statin Monotherapy??!

Ten to twenty TIMES greater HDL2 increases...WOWO.

Why do statins fail to STACK UP when compared to niacin???

Billions of dollars have been pored into research (which is great and we're all grateful) but still they fail to regress/stabilize plaque as durably and effectively as Niacin, a common B vitamin which costs $12.99 for #150 tablets at Costco.

Why does Niacin trump all statins?

Niacin trumps Crestor, gorilla-statin... which can have gorilla effects on muscle soreness and kidney failure (via increases MMP-9 in the kidneys; unless one is taking fish oil/vitamin D which reduce systemic MMPs).




Fish Oil and HDL2

Of course, Fish Oil trumps statins in regression as well.

It's a dose dependent and time dependent effect.

(is more better? sorta. depends on your inflammatory status. if you have unstabilized CAD or an autoimmune disorder or cancer, you are inflammed.)
Here is one 1999 double-blind RCT in coronary male patients where low dose ~3 g/d EPA+DHA for 3 mos then switched to low, LOW dose 1.6 g/d EPA+DHA for 21 mos showed more regression than placebo . The Germans are always advanced with CAM (complementary alternative medicine).









The effect of dietary omega-3 fatty acids on coronary atherosclerosis. A randomized, double-blind, placebo-controlled trial.

von Schacky C, Angerer P, Kothny W, Theisen K, Mudra H.
Ann Intern Med. 1999

RESULTS: Pairs of angiograms (one taken at baseline and one taken at 2 years) were evaluated for 80 of 112 placebo recipients and 82 of 111 fish oil recipients.

At the end of treatment, 48 coronary segments in the placebo group showed changes (36 showed mild progression, 5 showed moderate progression, and 7 showed mild regression) and 55 coronary segments in the fish oil group showed changes (35 showed mild progression, 4 showed moderate progression, 14 showed mild regression, and 2 showed moderate regression) (P = 0.041).

Loss in minimal luminal diameter, as assessed by quantitative coronary angiography, was somewhat less in the fish oil group (P greater than 0.1).

Fish oil recipients had fewer cardiovascular events (P = 0.10); other clinical variables did not differ between the study groups.


Below: 4.5 g/d x6wks EPA+DHA resulted in a 74% HDL2 increase with a concomitant 19% decrease of HDL3-C
Omega-3 fatty acids selectively raise high-density lipoprotein 2 levels in healthy volunteers.

Below: 4 g/day x6wks DHA only related to 29% increased HDL2 (EPA 4 g/day only reduced HDL2 6.7%) in Obese Men
Purified eicosapentaenoic and docosahexaenoic acids have differential effects on serum lipids and lipoproteins, LDL particle size, glucose, and insulin in mildly hyperlipidemic men.


Below: 4 g/day x8wks EPA+DHA induced 40% increase HDL2 and reduction in HDL3 (this condition has genetically low HDL/high TG)
An omega-3 polyunsaturated fatty acid concentrate increases plasma high-density lipoprotein 2 cholesterol and paraoxonase levels in patients with familial combined hyperlipidemia.


Below: 6 g/d EPA+DHA x12 wks increased HDL2 47.8% (reduced HDL3 6.6%)
Dose-response effects of fish-oil supplementation in healthy volunteers.





Fish Oil and Genetics

Fish oil may be even more tremendously beneficial for those with apoE4 (eg, the Alzheimer marker). ApoE4 has also been implicated in the pathogenesis of heart disease and other vascular diseases. In the below trial, low dose fish oil 0.7g/day EPA DHA, compared with higher dose 1.8 g/ day, was also effective at lower TG and raising HDL, especially in men.

Effect of sex and genotype on cardiovascular biomarker response to fish oils: the FINGEN Study.
Caslake MJ, Miles EA, Kofler BM, Lietz G, Curtis P, Armah CK, Kimber AC, Grew JP, Farrell L, Stannard J, Napper FL, Sala-Vila A, West AL, Mathers JC, Packard C, Williams CM, Calder PC, Minihane AM.
Am J Clin Nutr. 2008 Sep;88(3):618-29.

28 comments:

Jake said...

Your writing style tells me that you are a wild and crazy women. But wild and crazy in a good way-an entertaining way. You are fun to read.

I read recently that statins raise Vitamin D levels (was it here?). Will we find out in the future that only benefit of statins was that it increased the anti-inflammatory effects of Vitamin D?

Dr. B G said...

Jake,

Perhaps!

I believe what you suggest may be more provocative than my writing... *ah ha*

-G

Anonymous said...

You are so smart!! They did studies years ago on "chicken soup" and couldn't put their finger on exactly what it was that made people feel better - and I think you hit the hammer on the nail!! Which is a relief for me since me & my kids are allergic to wheat, and God-forbid it be the wheat-noodles in the soup!!! Ha Ha!!

Keep on thinking and pondering ... AND writing!! Love it! - Marisa

David said...

The Lp(a) increasing effect of statins is interesting. Does it seem to be that way with all statins, or just certain ones like Lipitor?

After my dad had his heart attack last year, the doctor (who is actually Dr. James O'Keefe, the vitamin D researcher in Kansas City) put him on 40 mg of simvastatin. But his Lp(a) was 225 nmol/L! Does simvastatin cause the same increases in Lp(a) as the other statins?

The doc walked out of the room without even suggesting any way to lower the Lp(a). He was just like, "As long as we can lower your LDL cholesterol [which was like 140-- Friedewald calculation ONLY], the Lp(a) won't matter."

As my dad was paying, I said, "We'll have to get you taking niacin to help get your Lp(a) down." It wasn't 2 seconds after I said that when the doc poked his head around the corner and was like, "Hey, for that Lp(a), you might try taking a little niacin if you want to get it down. 500 mg should be enough."

I'm upset that he's on statins when we don't even know his LDL particle sizes, and also because his Lp(a) is so high. Don't know what to do about it, because I don't think it would probably be good to just stop a drug. Don't you wish there were more Dr. Davis' scattered all over the United States? Haha.

Dr. B G said...

Hi Marisa,

You said it -- no wheat noodles in our chicken soup! Maybe all the nutrients in chicken soup can actually neutralize even noodles??

Thank you so much for your encouragement and kind words!!

-G

Dr. B G said...

David,

I wish Dr. Davis was next door :) Or at least a CLONE of him *ha haa*

Fortunately he is so accessible and if your dad had a question he could just post it at the TYP Forum! Not only would DR. Davis jump but so would his followers... ummm... I mean TYP members.

Did Dr. O'Keefe order vitamin D for your father???

I don't believe that I've noticed simvastatin causing the same thing. Perhaps only high-dse Lipitor is related to REDUCING apo A1 activity -- where as fish oil and statins (and vit D) raise this important marker.

At least now you know the reason and root cause of your father's condition. Inflammation and Lp(a). He does not have a statin deficiency. Good luck and hope he feels better soon!

-G

David said...

Yes, knowing the enemy (Lp(a) in this case) is very good indeed. Dad was in seemingly great shape when he had the heart attack. Wasn't overweight, good muscle mass, etc. Seems like classic Lp(a) to me.

Vitamin D! This is what also made me mad about O'Keefe. (forgive me while I rant. Heh) Yes, we got a vitamin D test for him, but the results weren't back yet by the time of the appointment. So without even seeing the results, O'Keefe told us that 1,000 to 2,000 IU should be more than enough! (We got the results back later. He was pretty low, and is taking 6,000 IU per day, despite the docs recommendations).

I posted a comment about this on Dr. D's blog the other day when he was talking about blood pressure meds. O'Keefe hiked up the dosage on the ACE inhibitor and beta blocker before he even looked at dad's chart or saw his blood pressure. He said that those "other things" (magnesium, CoQ10, pomegranate, cocoa, etc) weren't necessary as long as he was taking his meds, his vit D, and his fish oil (which he also didn't inquire or recommend as to dosages). "The science is Lisinopril. The science is Simvastatin." Quote unquote.

So now after following the TYP basics -- has nearly eliminated all grains, is exercising, taking fish oil, vitamin D, niacin, etc., dad's BP is down to 113/60 (from over 145/90 a few months ago) with resting heart rate at like 54 bpm. He has other side effects from the blood pressure meds, but is afraid that he shouldn't get off them in case there's some other reason they're necessary after the heart attack.

The good thing that O'Keefe said: "Grains are generally very bad." Bravo, Doc!

I think I'm going to have to get my dad on the TYP forum. What a great thing to have available, eh?

Dr. B G said...

David,

I love the TYP forum -- the energy, the bright and innovative members, the stories of empowerment (like yours) and SUCCESS, and synergy of people working to help each other in this condition. Turns out in fact there is so much to learn about other conditions too!
--testosterone replacement
--best supplements and where to buy
--best K2 available
--best Arginine palatability recipes (member named 'California' ROCKS)
--thyroid challenges ('LCL' and others frequently chime in with their thoughtful insights)

Well, I guess, O'Keefe had some redeemable qualities -- he advised at least SOME vitamin D. You have no idea that is cuts above 99% of the common physicians out there.

Low BP accompanied by dizziness is not a good idea -- can cause broken and fractured bones and disability (or worse a car accident/DUI). Consider having your father call his doc and consider dose reduction of the hypertensive agents?

Thanks for you comments!
-G

Barry in Indy said...

Hi Doc:

Thanks for sharing so much valuable info with references. I'm curious about the pleiotropic effects of statins. Specifically, are they dose-dependent? If statin pleiotropic effects are efficious at a low dose, I'm thinking many patients could easily tolerate a *low-dose* statin version of the HATS treatment protocol (90% reduction in events is amazing).

Dr. B G said...

Hi Barry,

Isn't it fascinating when we break down MOAs (mechanisms of actions) of foods and drugs?? Amazes me constantly how dynamic and complete and whole our bodies are (despite our abuses).

My observations are that the benefits only exist at low doses (but again this may not be the case for FH). Could if 'low chol' diets were not used in the clinical trials? Perhaps high dose + high chol diets would yield more impressive results? I dunno...

HDL metabolism depends on ApoB, Apo A1 and other things we may not understand fully. Crestor and other statins affect ApoB and ApoA1 differentially and at different doses. Crestor actually has the max ApoA1 benefits at 2.5mg in dose-finding trials. However, it has the most apoB benefits at the max doses -- but this is not necessarily where the max regression occurs. We don't know yet. Hopefully Nissen may find out someday (he's the Crestor-lover *ha*). Also, no one tolerates 40-80mg/day Crestor without kidney proteinuria and/or intolerable muscle/mind effects.

-G

Barry in Indy said...

It amazes me that the average dose of Simvastatin in the HATS study was 13 ± 6 mg/day. This suggests to me that if one believes that LDL lowering is not the primary efficacy effect of statin therapy, that a low dose may produce the results. As far as I'm aware, no niacin mono-therapy trials have ever achieved the same results as the Niacin+Simvastatin combo used in HATS.

All the best!

Dr. B G said...

Barry,

I have not seen any niacin mono-therapy trials. Do they exist?? So how would we know?

We use a lotta niacin at TYP (statins optional) -- and the results are nearly 98-99% mortality and event reduction.

-G

Barry in Indy said...

The Niaspan label references the Coronary Drug Project study. One of the arms is Niacin 3gm/day.

"Randomized, double-blind, fixed sample. A total of 8,341 patients were randomly assigned to six treatment groups consisting of 2.5 mg/day of conjugated estrogens, 5.0 mg/day of conjugated estrogens, 1.8 gm/day of clofibrate, 6.0 mg/day of dextrothyroxine sodium, 3.0 gm/day of niacin, or 3.8 gm/day of lactose placebo"

http://www.springerlink.com/content/g350686w77404t47/

"Mortality in the niacin group was 11% lower than in the placebo group."

Dr. B G said...

Hi Barry,

Thanks for the link! Here are other niacin + polypharmacy regimens. Few outcome studies. FATS (non-statin) and L-CAD (prava +/- niacin, cholesty) were good too -- but I can't locate the specific outcomes right now for the latter. For the FATS, niacin 1 g TID + colestid 1 g TID x2.5 yr resulted in 39% angiographic regression v. placebo and for clinical events 4% (v. placebo 19%). FATS is significant like the HATS trial with a 73% relative risk reduction.

I like the CDP you posted, but I believe it looked at mortality 15yr after the start of the trial. Patients stopped niacin after the initial 5 yrs of the trial. Reduction of 11% is not bad for stopping a drug after 5 yrs!

I am surprised also how spectacular the HATS trial results are, but they mirror Dr. Davis' experience as well (and the FATS). Perhaps there is synergism with simvastatin and niacin that has not been elucidated yet? Or could it be the vitamin D raising benefits of simvastatin? (maybe it's more exceptional than other statins in this regard??)



N Engl J Med. 1990 Nov 8;323(19):1289-98. Dodge HT et al.
Post-MI patients.

Niacin IR 4 g/day + Colestipol 10 g TID x2.5 yr = 43% HDL incr and 39% Regression (arteriographic lesions)
Lovastatin 40 mg/d + Colestipol 10g TID x2.5 yr = 15% HDL incr and 32% Regression (p=0.005)


Ann Intern Med. 2005 Jan 18;142(2):95-104. Whitney EJ et al. Angiographic-evident CAD patients.

Niacin (?dose), Gemfibrozil, Cholestryamine x30mos = 26% HDL incr and 45-50% relative event reduction and angiographic regression (% not stated in abstract)

-G

Jack C said...

The assertion that HDL3 is bad seems inconsistent with the conclusion in the study by Krauss (Pubmed 8963728, last reference in your post of Sept 3, 2009)which states 9 in part

"these results present new evidence for the possible protective role of HDL3 in the progression of coronary artery lesions."

In a brief perusal of abstracts on pubmed I found a couple of other references that ascribed beneficial effects to HDL3 (pubmed 18980242: HDL3 prevents cell death, 16505860: HDL3 has anti-atherogenic activity) but did not find any that indicated that HDL3 had detrimental effects. I would appreciate references regarding the bad effects of HDL3.

I recently ran across your site and find it entertaining and informative. I plan to get a VAP test based on what I have learned from your site.

About ten years ago I switched to a high fat, relatively low carb diet based in part of WAPF guidelines, and as a result my HDL increased from 55 to 110 and TG dropped from 130 to 60.

Butter from grass fed cows is a significant part of our energy intake. In one of your posts you recommended casein free butter oil which seems to imply that you think butter should be avoided because of the casein content. Is that your intent, and if so, what is the problem with the minor casein content of butter?

Dr. B G said...

Hi Jack C,

In individuals with chronic inflammation, I wonder how powerful their small dense HDL3 can provide antioxidative effects? I believe it depends on the apo A1 content.

Apo A1 is determined by antioxidant status, high sat fat intake and low carb intake, as well as optimal hormones (adequate estrogen, vitamin D, testosterone, progesterone, thyroid, low cortisol, etc).

No doubt HDL3 may be beneficial but for everyone? Many people I have tracked and observed have high HDL3/HDL2 ratios and even HDLs as high as yours > 100 mg/dl. They have high plaque as well -- the functionality of their HDL3 is f*cked up.

Typically inflammation, high carbs, high insulin, high cortisol, estrogen deficiency, testerone and thyroid deficiencies play a role.

In all cases I would say, a serious saturated fat deficiency played the pivotal role in the failure of the HDL3 to perform as its top potential.

I think you are bringing up interesting points -- I do concur b/c in centenarians their HDL3 is high as well as their HDL2 but often the key is that their apo A1 is high and their HDL2s are exceptionally relatively high as well. I think this lends the best functionality to the HDL3 (and reflects a generally non-oxidzied and non-inflamed state).

WAPF'ers don't appear low carb to me... soaking and fermenting both their grains and legumes!

Stunning HDLs -- reflects an excellent tribute to your evolutionary gene blueprints!!

With compromised and perforated gut linings, casein can cross and affect the immunity and also lead to casein related immune complexes which trigger auto-antibodies. A great degree of the world population cannot tolerate lactose or casein (Asians ~90% and caucasions ~50% and African Am high like Asians).

Thanks for your kind comments,
G

Dr. B G said...

BTW thanks Jack for the link -- I wasn't aware that lovastatin was ENTIRELY irrelevant and completely useless in both lowering LDL-IVb (the most atherogenically nasty component) and changing HDL3 made no diff in progression. Only baseline higher HDL-3 was associated (weakly) with less progression. Baseline -- prior to statin treatment. wtf. Seems to still support the elimination/minimization of LDL-IVb and raising HDL-2b for regression, ultimately, as you have done via low carb, high sat fat. Its funny they call it the MARS trial... where's the regression? Did they even look at HDL2 in odds ratio for less progression??! Studies like this just make me PO'd b/c their conclusions are inane.

Jack C said...

Dr. B G,

Thanks for your reply.

Regarding HDL3 being "bad": I understand that those with chronic inflammation have compromised HDL3. For those with little inflammation as indicated by low Crp and pattern A LDL particle distribution, HDL3 provides potent protection against oxidative stress and displays elevated cellular cholesterol efflux capacity, so calling HDL3 "bad" seems inappropriate.

Regarding casein: Kieth Woodford, in his book "Devil in the Milk" makes a very convincing argument that the that the primary problem with casein from milk is the peptide beta-casomorphin-7 (BCM7), and opiate found in milk from cows with the A1 deviant gene, a genetic mutation that occurred several thousand years ago. Cattle in southern Europe and other parts of the world are A2 cattle that do not have the problem mutation.

Goats, camels etc produce A2 milk. The fact that many people who consider themselves as lactose intolerant can drink goat milk with no problem suggests that their intolerance is not to lactose but to BCM7 in A1 milk, for goats milk of course contains casein and lactose.

A2 milk appears to be a problem only for those with gut dysfunction for there is an enzyme dipepdidyl peptidase4 attached to epithelial cells in the lining of the stomach and intestines which breaks BCM7 down into smaller particles. (page 216 of postscript of "Devil") Similarly, lactose intolerance seems to be largely a problem of gut dysfunction, for physiological strains of E.Coli, which are found in great numbers in a healthy gut, can break down lactose. (Pg 22, Gut and Psychology Syndrome by Dr. Natasha Campbell-McBride.)

The number of people with poor gut flora continues to grow due to the increasing use of antibiotics, birth control pills and other drugs as well as poor diet. Evidence is quite convincing that the A1 peptide BCM7 is the primary cause of type 1 diabetes, the incidence of which has increased steadily for many decades.

It seems that there is not enough casein in butter to bother anyone except those with severe gut dysbiosis. At least this seems to be the opinion of Dr. Campbell McBride who advocates removing all dairy products from the diet of those with gut dysbiosis (GAPS patients), but restoring butter to the diet once digestion has been improved.

The research regarding the detrimental effects of A1 dairy products found that the strength of correlations was improved when cheese was not included. A study not included in the book (pubmed 8675779) found that a commercial strain of lactococcus used in cheddar cheese making breaks down BCM7.

I live in Alabama where raw milk or even good pasteurized milk from pasture fed cows is not available, so I eat a LOT of raw milk cheese from pasture fed Guernsey (A2)cows (from Sweet Home Farm, Elberta). And we eat a lot of butter.

Regarding WAPF and fermented foods, the only fermented foods we eat are cheese and yogurt. Many in WAPF go for butter oil but I think it is an unneeded expense.

Jack

Dr. B G said...

Dude Jack C...

Ur a bright boy. Who r u??! That is WONDEFUL you have access to A2 dairy! I'm so jealous.

Natasha's is the next book I'm gonna read :) I'm into the GAPS diet after hearing about it from Seth Roberts and the success w/spectrum children. Trying to do the bone broth and fish bone soups... Boy you need a part time job to cook and prepare everything wonderful for our health... I'll ck out Woodford's book.

I think our ancestors from the Han mountain areas (Hakka) drank goats milk...

Raw A2 should be fine for those with un-compromised guts. Robb Wolf (who's mother has both SLE and RA and celiac) tolerates raw goats milk and cheese with no difficulties.

You are absolutely correct -- I concur the antitiotics, pharmaceuticals (pepcid, prilosec, beta-blockers, metformin, oral contraceptives, synthetic HRT, NSAIDs) and antibiotic/GH fed livestock and dairy are killing our guts and gut flora.

I agree -- I've read that modern pasteurized antibiotic fed A1 dairy is a HUGE contributor to LADA (Type 1.5) and Type 1 diabetes. T

he Type 1 increase (like celiac, MS and autism/spectrum cases) may be multifactorial. Definitely early exposure to cow milk formula and the nasty soybean oil n-6 are toxic. Vitamin D deficiency and heavy gluten triggers maybe major add'l contributors. A mother's DNA methylation status? Affected by synthetic high dose folic acid? Cyanocobalamin which doesn't exist in nature? Widespread iodine, zinc, selenium, magnesium and thyroid hormone deficiencies?

I should do a f/u post on the 'antioxidant' properties of HDL3! UR right on! How to build a bionic HDL3...? No trigs, all cholesterol and apoA1. Any other thoughts? We are built by design to be perfect... every part, parcel and particle I am finding on this scientific journey has a vital role...

Have you read Krauss' latest insighits? He thinks that small dense LDL4 and LDL3 come from a previously unknown source and pathway, outside of VLDL... perhaps dense HDL3 as well (I mean the 'bad' one not the good HDL3 *ha*)?? http://www.meandmydiabetes.com/2010/03/26/ldl-cholesterol-ron-krauss-md/

I have 2 flavors of butter oil and can't stand either (pecan and chocolate *ugg vomit*). Anyway I prefer ghee from grassfed and cloverfed cows (Purity Farms) and european style pastured fermented butter. I have to drive to Berkeley to get it... Friends of ours in Mt.Shasta belong to a CSA (co-op) and milk their cow twice weekly. They don't know if it is an A2jersey but will be doing DNA testing to see. We tried their raw cheeses made from it -- it was GREAT while we were sledding this xmas!

Thank you for your thoughtful reply and BCM7 info!

Grace

Jack C said...

Dr. B. G.

While type 1 diabetes may be caused in part by many factors, the correlation between consumption of A1 beta casein (except cheese) and type 1 is exceptionally strong.

Other health problems attributed to BCM7 in A1 milk include autism, heart disease, and many auto-immune disease such as Crohn's disease and Parkinson's.

The correlation of autism with BCM7 is also quite strong. It is now common practice to put children on "gluten free, casein free" diets as soon as autism is suspected because both contain opioid peptides (gliadomorphin in gluten, BCM7 in casein). In the "Guts" book, Dr. Campbell-McBride acknowledges the problems of casein but does not relate the casein problem to the type of milk (A1 vs A2).

Studies have found that BCM7 can effect something like 37 areas of the brain as it seems to go directly to the brain, while the opioid peptides from gluten reach the brain indirectly and only effect a few areas of the brain. This suggests that A1 milk is a greater risk for autism than gluten.

I found the two books, Devil in the Milk and Gut and Psychology Syndrome, are (sort of) complimentary.

More later on casein and butter.

Jack C.

Dr. B G said...

Jack,

I did not realize the brain effects are so profound with casomorphin/casein v. gluten peptides.

Looking forward to all your thoughts,
G

Jack C said...

Regarding A1 milk and type 1 diabetes, some interesting history: In 1993 Professor Bob Elliot from Aukland University observed that Samoan children living in New Zealand were susceptible to diabetes but children living in Samoa had a very low incidence. He discussed the matter with Dr. Jeremy Hill who brought up the possibility of milk being the cause.

Subsequent epidemiological studies showed a strong correlation between A1 milk consumption and diabetes in countries throughout the world.

A study was undertaken in New Zealand by Bob Elliot which found that 47% of the mice fed A1 milk got diabetes, but none of the mice fed A2 milk got diabetes.

New Zealand, by the way, is a major world milk producer and dominates the world milk market.

Around the year 2000, the New Zealand Dairy Board funded a major study which involved three countries (New Zealand, Canada, and UK), nine diets and nine authors. Rats (New Zealand) and mice (Canada and UK) that were bred to develop diabetes were to be used.

The first disaster was that most of the rats got infected with Clostridium and died, so the New Zealand part of the study was scratched.

In the Canadian mice, 46% of those fed A1 milk got diabetes compared to 19% of those fed A2 milk. In the UK mice, the incidence of diabetes was about the same for those on A2 milk as for those on A1 milk. When combined, the increase in diabetes due to A1 milk was said not to be significant.

In October of 2000, Dr. Jeremy Hill, one of the none authors of the study, advised the New Zealand Dairy board that the A2 milk used in the UK mice, which had shown no increase in diabetes when fed A1 milk, had been contaminated with BCM7, so the study was hopelessly screwed up. He did not advise the other eight authors however! Nor did those in the Dairy board who read his memo! So the study was published in 2002 with the erroneous conclusion that A1 milk did not increase the incidence of type 1 diabetes!

All of this was not brought out until some years later, but no retraction of the conclusions of the study was ever made. Kieth Woodford goes into great detail about all this mess which derailed much of the effort to evaluate BCM7. It does not seem that he has received the attention he deserves.

It has been hypothesized that BCM7 stimulates the body to produce antibodies to fight it, but because the amino-acid sequence of GLUT2, the glucose-transporting molecule made inside insulin producing cells of the pancreas, is identical to the back end of BCM7, the antibodies also attacks the insulin producing cells of the pancreas.

More on why I like aged cheese later.

Dr. B G said...

Jack,

Isn't it funny the science and serendipity? Woodford sounds extremely intriguing...

I did not realize BCM7 peptides resemble the GLUT2 transporters... MAKES SENSE NOW. [It resembles to me the problem with lectins in legumes -- they resember our self-produced MBL (mannose-binding lectins) -- though I need to check the chemistry on that.]

Do you like fermented cream as well? Good bacteria are so good to us aren't they?

-grace

Jack C said...

Grace,

I have not tried fermented cream and doubt that I can get it around here. One of my dairy sources, Miller's Organic Farm in Pennsylvania, has creme fraiche for just a dollar more a quart than heavy cream. I'll have to try it. They also have cultured butter which I get at times.

The local Publix grocery carries Kerry Gold Irish cultured butter. The local health food store sells Organic Valley "spring summer" cultured pastured butter, and also a Minerva (Ohio) Amish roll butter which appears from its texture to be cultured. The Minerva butter comes in two pounds (approximately)rolls in waxed paper and is surprising cheap at about $2 per pound, so I get it once in a while when feeling cheap.

Regarding cheese, the French, aka "cheese heads" consume about fifty three pounds per person per year. That is a lot of cheese. I understand they have cheese for breakfast and dessert. As cheese is very high in casein, it seems that not many French are allergic to casein. All cattle in France are A2, so no problem with BCM7. The "channel" breeds of cows, Guernsey and Jersey, originated in France. Guernsey cows are almost 100% A2 and Jersey are high in A2.

Fermented cheese has about five times as much menaquinone (K2)as butter. The "French paradox", the low rate of heart disease in spite of a diet high in fat, has be attributed to a number of causes including wine consumption and increased vitamin D due to the southern latitude. While these factors may contribute somewhat to the "paradox", I think the primary factor is the high cheese intake which provides a high menaquinone intake and good saturated dairy fats high in myristic acid.

The Rotterdam study found that over an eight year period, those in the highest terile of K2 intake had less than half the CHD mortality compared to those in the lowest tertile, and less than half the risk of severe aortic calcification. In the study, more than half of the K2 was from cheese. Average cheese consumption by the French is about the same as K2 intake of the highest tertile in the Rotterdam study.

A study in Japan found that old people like me (I an 75 years old) require higher levels of menaquinone than young people to maintain the same level of carboxylated osteocalcin. So I eat a lot of cheese. And butter and eggs.

Aged cheese is also the only dairy product that does not have to be pasteurized to be legally shipped across state lines, so it is my only legal source of the natural enzymes found in milk. (Careful cheese makers raise the cheese temperature no higher than 102 degrees F., the same temperature that the milk comes out of the cow, so enzymes are not damaged.)

Knowing all this makes great tasting cheese even better. Jack

Dr. B G said...

Hello Jack C :)

We started using cultured Kerry Gold AND Organic Pastures cultured cheese too 2 months ago. Found a great cultured goat cheese as well -- it's white, so I have reservations about the K2 and plant sterol content... The label fails to indicate if the goats were pastured... Goats were raised in the tri-valley area we live in. One patient told me his asthma was controlled as a child drinking goat milk (raw of course). Goat milk is popular in the 'blue zones' where longevity and centenarians reign... Okinawa, Belgium, Crete, to name a few. Raw goat and cow milk are also rich sources of taurine which is potently anti-inflammatory, neuroprotective, cardio-protective, and is the major bile acid for excretion of toxins.

Stan recently wrote about the recent EPIC findings -- cheese consumption in Europe (as you note -- A2 dairy) is associated with the least CAD risk.
http://stan-heretic.blogspot.com/2010/04/cheese-reduced-risk-of-incident-and.html

I like how the evidence is building for our ancient diets of rich, nutrient-dense, TASTY food... The divide between Europe and American could not be deeper... it's too bad. My husband used to travel monthly to Basel and Germany -- the food was so incredibly different he always noted. Entirely fresh, no one used refridgeration and people shopped for groceries daily.

In the short term, in America we use so many preservatives and brominated-antifungals on nutrient-poor (BCM7 A1, CLA-deficiency K2-deficient, omega-6 dense, cytokine-dense), perverted food (esp 'dairy', sliced 'cheese' and salad greens, etc) that we fail in the long term to preserve ourselves... damaging our delicate endocrine organs and vasculature beyond repair.

Thank you for your keen and astute observations!

-grace

Jack C said...

Dr. B G,
There is a small dairy nearby, Henrietta's Goat Milk, that provides pasteurized organic goat milk from pasture fed goats, but only during the time of the year when the goats are not nursing their young. I drink Henrietta's goat milk when it is available and do without the rest of the year. Sweet Home Farm where I get my cheese sells nothing but cheese.)

Dr. Natasha Campbell-McBride, in her "Gut" book, does not address the A1 vs A2 milk question, but does recommend goat milk for making yogurt, noting that in spite of higher casein content it has been shown in "clinical settings" to be better tolerated than cow milk. The topic of raw vs pasteurized milk is not addressed in the book.

Keith Woodford's book "Devil in the Milk" discusses a study by Dr. Corran McLachlan concerning the correlation between A1 milk intake and CHD mortality. (2001 Medical Hypothesis). Included in the study was a hypothesis that pasteurization, particularly for long duration such as the Holder method (30 minutes at 63 degrees C.) increased the release of BCM7 and resulted in the increased CHD mortality that coincided with the introduction of pasteurization. He further noted that the subsequent decrease in CHD mortality coincided with the abandonment of the Holder method in favor of very short high temperature pasteurization.

The Weston Price Foundation is a big advocate of raw milk and frequently publishes testimonials regarding the health benefits of raw milk. The website Realmilk.com, and offshoot of WAPF, also has a bunch testimonials about raw milk benefits. The question arose in my mind about how much of the benefit of raw milk was due to the fact that it is not pasteurized, and how much is due to the fact that a lot of raw milk comes from "channel" cows, Guernseys and Jerseys, that have a high percentage of A2 genes. In an unsuccessful effort to answer the question, I perused the various anecdotes from different sources.

Woodford, in "Devil" included an anecdote about an aquaintence who had Crohn's disease who would get explosive diarrhea after drinking "regular" A1 milk but could drink A2 milk with no problem.

I found a related anecdote on the realmilk website concerning a woman who not only had Crohn's disease, but had a son with autism. She had severe gut problems that caused continuing weight loss. Her gut problems and her sons autism were both cured by drinking raw milk and eating free range organic meat. (Stephanie Fargo, Jan 27, 2007) She was a classic example of what Dr. Campbell-McBride describes in her book: a person who passes her gut problem to her child during birth, resulting in autism in the child. The testimonial listed the name of her dairy source, who had been charged with the crime of selling raw milk (which was the reason for the testimonial). Out of curiosity, I contacted Richard Hebron and asked what kind of cows they had. His wife wrote back and said they were Jersey cows and "all A2 cows".

The answer boosted my confidence in the A2 theory somewhat.

Jack

Dr. B G said...

Hi Jack C,

It is very interesting how abandoning the Holder method changed the milk proteins in the final product. Conversely how fermentation improves immunoprotective and gut protective profiles of dairy products.

Tregs in the immune system are probably regulated by some of these probiotics and fermentation products of metabolism which ultimately strengthen our immunity against infections, autoimmune diseases, allergies and asthma (I have asthma (totally controlled now on vitamin D, adrenal help and probiotics) and continue to wonder how and why this is since my sisters don't).

T-regs in diff flavors control asthma (and probably other autoimmune dzs)

Take care and warmly,
G

trinkwasser said...

Who invented all these damn subparticles anyway? I bet it was Microsoft.

I've got my head around the LDL subtypes and now there are HDL subtypes too

Like many, I managed to double my HDL and decimate my trigs (literally) through low carbing, and further improved my HDL at the expense of LDL with more sat fats mostly from grass-fed cows and sheep and quality cheese and butter from old breed cows rather than those horrid Holsteins.

I tried dropping my statin and was amazed to find what a difference a mere 10mg simvastatin makes. Conversely niacin didn't appear to affect my lipid panel.

Now I'm wondering if it may have altered HDL particle sizes without affecting the total quantity, so I'm back on it.

Whenever I try to read Untranslated Krauss I get a headache. I suspect there's no one answer that fits everyone, you need to delve into the alternatives until you find a combination that works with your specific genes.

The interview you posted is almost understandable but makes me think that what is measured is measured because it's easy to measure rather than being relevent to disease processes, the lipids are indicators of other metabolic goings on.

"When you're on a statin we don't need to test your cholesterol again" said the nurse. Say what??? I need to know my trigs/HDL ratio thank you, see if I'm keeping a lid on my insulin resistance. I'd love to get an NMR and the various lipoproteins tested too but no chance in the UK.