Friday, August 29, 2008

HDL2b -- Age, Adiposity, Alcohol and Estrogen

The lipoprotein subfraction HDL2b is emerging as the marker for regression of plaque and longevity. Even evidence from 10-15 yrs ago revealed this remarkable relationship. Looking to centenarians, scientists often search for answers and clues to longevity and control of chronic illnesses. These Italian researchers examined the the relationship between 2 subfractions of HDL -- small dense HDL 3a and large fluffy HDL 2b. The HDL 2b subfraction appear protective (at 32.4%) compared to younger/healthy matched controls (at 23.4%) and HDL 3a, appear degenerating for longevity. The interesting thing to note is that total HDLs were similar between all groups. In other words, the HDL from traditional labs tells nothing about HDL2 or HDL2b or HDL 3a. (Here Dr. Davis rails about the failures and weaknesses of conventionalist-type medicine in their overreliance on Friedewald's equation. )
"In order to assess the role of HDL on longevity, we studied HDL subfraction distribution in centenarian women compared with a group of weight- and gender-matched healthy normolipidemic controls. We did not find any significant difference in the mean plasma lipid, apolipoprotein, and Lp(a) levels. On the contrary, in spite of similar HDL-cholesterol concentrations (1.32 +/- 0.41 mmol/l in centenarians vs. 1.32 +/- 0.25 mmol/l in controls, p = not significant), HDL2b and HDL3a levels were, respectively, significantly increased and significantly reduced in centenarians in comparison with controls (HDL2b 32.4 +/- 9.2% in centenarians vs. 23.4 +/- 7.7% in controls, p less than 0.002) and HDL3a 26.3 +/- 9.8% in centenarians vs. 34.1 +/- 7.3% in controls, p less than 0.01). HDL2b levels were significantly raised and HDL3a levels were significantly reduced in centenarians in comparison with both 'middle-aged' and 'elderly' subjects, whereas no difference for any HDL subfraction was found between the two groups of controls of different ages."

HDL Subclasses

The subclasses of total HDL are defined via absorbency of a protein stain which serves as an index of mass concentrations at intervals of 0.01 nm. We desire a reduction in CETP activity to prevent transfer of mass from HDL to VLDL (small dense LDL).

  • HDL3c (7.2 to 7.8 nm) -- plaque-builder (bad)
  • HDL3b (7.8 to 8.2nm)
  • HDL3a 8.2 to 8.8 nm)
  • HDL2a (8.8 to 9.7 nm)
  • HDL2b (9.7 to 12 nm) -- plaque-BUSTER (good)
Research that came out of the Lawrence Berkeley Labs in 1993 also reinforced how reductions of HDL2b parallels how known risks for CAD go up with age, adiposity and lack of estrogen. Williams et al studied HDL subfractions in Mormon men and women here in the Bay Area. Some Mormons kindreds did drink and smoke -- *HOLY MOLY BATMAN* don't tell the church of LDS -- and their data were excluded from relevant analyses). The alcohol factor is curious -- for women it may appear protective however for men no distinct protective benefit for HDL2b appears strong because a corollary increase in HDL3b and 3c occurs with alcohol consumption (??did that potentially negate the mild protective 2b increase?).

Here are their conclusions as they summarized:
  • HDL3b concentrations were higher after menopause than before
  • Eighty-eight percent of the increase in HDL associated with estrogen replacement (conjugated/horse hormones most likely) in postmenopausal women occurred within HDL3a (bad) and HDL2a.
  • Adult men (> or = 18 years old) had significantly higher HDL3c and HDL3b
  • Adult men had significantly lower HDL2b and HDL2a levels than younger boys (why?)
  • There were no significant differences between the HDL profiles of women and younger boys, suggesting that divergence in HDL occurs during puberty
  • Compared with the women, adult men had higher levels of HDL3c and HDL3b
  • Adult men had lower levels of HDL2b, HDL2a, and larger-diameter HDL3a particles compared with women (is this why women live longer then men??? )
  • In both men and premenopausal adult women, increasing levels of body mass index were associated with higher levels of HDL3b (bad) and lower levels of HDL2b (very very bad).

The authors noticed that "Reported alcohol intake in adult men correlated with two HDL regions: one within the HDL2b region (good) and a second within the HDL3a/2a region (bad), whereas in women the positive correlation between alcohol and HDL levels was within the HDL2b region only."

So what are the most potent things we can do to raise HDL2? We know that most of the HDL2 increases are due to HDL2b increases. HDL2 in fact is a good surrogate for the regression marker HDL2b. Studies show this -- and the TYP program reinforces this:

--Achieving normal BMI. Reducing adiposity (esp central though the above study does note that central vs. peripheral was not measured) will raise HDL2b and lower HDL3a/HDL3b/HDL3c

--Reduce your 'biological age' -- how? movement movement movement, vitamin D3, etc

--Take Niacin -- this B3-vitamin which mimics fasting and ketosis raises HDL2 100% (or occasionally get ketotic with intermittent fasting -- when you're not stressed/sleep deprived which is when Cortisol is excessively high) in trials

--Take Fish Oil -- at 'low dose' 4 g DHA per day HDL2 increases of 30% are observed (is more better? yes)

--Restrict carbohydrates (yes sirree, that includes F - R - U - I - T - S , ie, Nature's candy) and again the same researchers at Lawrence Berkeley Labs Williams, Krauss et al confirm this here. And even for you elite athletes out there -- the low HDL corresponds to CAD risk -- and carb (yes fruit) will trigger concomitant huge magnitudes of insulin eruptions and reductions in HDL2b and increases in VLDL/small LDL. The research demonstrated that here well.

--Consume a higher fat and saturated fat lauric acid (unprocessed coconut oil), caproic/caprylic and butyric acid (raw pasture raised butter oil)

--Get on Bio-idential/tx estrogen which raises HDL2b 150% (see below) (if you're lacking -- yes even men? perhaps... Post-menopausal women do apply Testosterone cream, why not vice versa?) In the study below Ethinyl Estradiol 0.1mg orally was taken by pre-menopausal women and resulted in total HDL increasing 38.3% and HDL apoA1, 25-27%. Oral estrogen sometimes worsens cholesterol for some -- transderm/topically applied are preferable for some. Are women the superior species?

Well... though what would we be without the men we stand behind?
  • The effects of estrogen administration on plasma lipoprotein metabolism in premenopausal females. Schaefer EJ, et al. J Clin Endocrinol Metab. 1983 Aug;57(2):262-7.
    PMID: 6408108


If you want plaque and a reduction in heart-protective HDL2b, follow the AHA Step I low-fat diet. The researchers are GENUISES... they repeated the same results in obese, postmenopausal women (but at least their conclusions were rationale this time).
Effects of an American Heart Association step I diet and weight loss on lipoprotein lipid levels in obese men with silent myocardial ischemia and reduced high-density lipoprotein cholesterol.Katzel LI, Coon PJ, Dengel J, Goldberg AP. Metabolism. 1995 Mar;44(3):307-14.

ENJOY! And...give a copy to your conventionalist MD... you have my need to wait for April Fool's Day or another heart attack...


donny said...

I've been wondering about niacin and longevity for a while now. My understanding is that Niacin encourages burning fatty acids as opposed to glucose. They've tried to prolong rodent lives with niacinamide, which improves blood sugar control, but it failed to prolong the lives. There was one altered form of niacinamide involving I think a ribose sugar molecule. But when you have to alter a vitamin to have a good effect, isn't there the possibility that some of the good effect comes from blocking the action of the original, unaltered vitamin? I spend most of my time kind of over my head on this stuff, so please excuse me if I've said any thing really stupid!
But nicotinic acid, on the other hand--I check this every once in a while, and I can't seem to find any longevity studies involving this. Maybe the fact that it can sometimes worsen blood sugar throws people? But if it does so by encouraging fat burning and decreasing sugar burning, causing the sort of "benign" insulin resistance you also get from a low carb, low insulin diet, it seems to me to be a pretty obvious place for researchers to look.
The other longevity study I really want to see is with a true ketogenic diet. With all the rodent studies with reduced tumour growth, reduced artherosclerosis, reduced alzheimer's-like symptoms, it just seems silly not to do this kind of study.
Low carb diet plus niacin to help keep your RQ low? They kept some worms alive longer than usual with some kind of sugar blocker. I wonder if niacin woulda worked?
That's my crank comment for the day. Thanks for blogging, it's always a good read.

Dr. B G said...


Thanks for visiting (I think). You've brought up so many good questions! I dunno... I've wondered the S A M E things!

When I take niacin (Slo-Niacin) I do feel more calm sometimes (like when I used to smoke cigs/cigars which of course is the nastiest habit on earth and everyone should consider stopping if they are currently doing so). I wonder if i'ts activation on nicotinic receptors which are ALL OVER our cholinergic/CALMING nervous system? I don't know...

Absolutely I agree (and someday I'll make a big post on it) but any modifications on 'real' food or vitamin or fatty acid molecules usually doesn't work too well in the human body (and animal models) as well. Many examples exist, ie WHI, CARET, trans-fats, etc.

Studies with niacin actually have demonstrated large antioxidant capacity and as well as reduction in cancers. An anecdotal observation (which I haven't validated yet) is that those in the HATS trial on niacin did not have cancer (compared with placebo or simvastatin only). I'm not so sure about the benefits of niacinamide yet. Some forms of niacin don't work -- probably for the reasons that you cited.

I think you're right on about the mild fasting glucoses with niacin which is similar to (?excessive) low carbing -- maybe there's a corresponding 'reflex' cortisol or liver dumping effect? Again, haven't had a chance to delve into that one yet either. You've got too many ideas! You need to start blogging!

I also wondered about ketone bodies -- these are generated from the cholesterol synthesis pathway -- unfortunately Statins block this. I wonder if they block KB production to some extent as well? then we would certainly have a niacin-deficiency...

What's RQ, may I ask?


dr j said...

Dear G,
Gee thank you so much for your post, it all seems like an onion and you and Peter at hyperlipd and Dr Davis are peeling back the layers of knowledge .. but in the end i have to ( here's a giggle)after watching my researcher , my dog on the way she approached the order and relish in eating coconut oil vs fish oil I have switched to my/our pre run breakfast being 5gm of coconut fat and 3 gm of Jarrow DHA , a fried egg in non smoke point olive oil plus 5 almonds.. its quite hard switching to saturated fats.

the other issue is... Is there an optimum body fat value that is a worthy goal ? because it seems useful to me, the layperson, as a summation of many factors that include calorie excess and hormone infuenced metabolism etc. I have set a value of 10% being my goal , but would someone with 6% say, have a better lipid profile at the level of HDL dissection that you have done in your post?

Dr. B G said...

Hey John,

What a wonderful meal -- the breakfast of TYP champions!

(My husband unfortunately is rebelling -- he thinks I'm feeding him sunscreen...(from the coconut scent))

Any reduction in body fat will improve HDL2 and particularly HDL2b. Dr. Davis does notice that sometimes initially HDL drop in the first 3-6mos with weight loss (but it may not all be HDL2). The same 'rebound' phenomenom is witnessed in children following an infection. HDL2 has powerful effects in binding gram-negative bacteria (and probably other bugs too) to negate/prevent proliferation and endotoxemia (fever, infection). Remember 'feed a fever, starve a cold...'

Change in body composition is more relevant imo than ultimately achieving some 'ideal' body fat or image. Personally 10-12% is really good for men. I think achieving appropriate lean mass (muscles) is actually more important than adiposity. But if body fat is 'high' then some downward trend needs to be happening in order for inflammation to be reduced.

I haven't quite reckoned it yet -- do people who look like the men in '300' the movie (naturally -- I'm saying without pharmaceutical assistance) do they have concomitant reduction in inflammation and dramatic rises in HDL2 and 2b?

I'm thinking... probably yeah... to look ripped and hot (the 'natural way')low carb/mod fat/mod-high protein with some intermittent fasting is the only way to go. Btw this is totally the TYP diet plan. Also the 'roids (testosterone and YAH even estrogen) released from muscle work/strength training are very very effective not only at reducing inflammation and increasing HDL2 out the roof.... but they also lower Lp(a).

Some individuals do better with higher dietary fat intake, depending on the type of baseline lipoprotein pattern exhibited, in my opinion. My TGs are naturally < 100 (even on HIGH HIGH carb) -- so I'm not one of these. I'll review my sat fat experiment some day. Or you can ask Peter -- he saved me $6k on cosmetic surgery... !! A degree of saturation of fat is HIGHLY HIGHLY HIGHLY necessary for life (and for upper body 'attributes' *wink*).

So...This is just anecdotal but those with TGs way way greater than 300-500s (even while 'low carb') probably benefit from the mod to higher fat intake more than the average person (like me -- too much sat fat just makes me... F A T ). There are some with an 'arachidonic acid' pathway malfunction. In these poor suckers, high fat may actually have deleterious effects (even if low low low carb). Why? I dunno. Our diet-gene interaction? I don't know if this is the case ALL THE TIME, but it appears so to me.

You're right... I hope we can have ways to precisely detect our optimal diet for our gene pattern some day. When we're 'result' driven though, it's pretty easy. Body fat is one good target. I'm aiming at HDL2 also. Ripped abs wouldn't hurt either, eh? Ripped abs and an Australian accent is gonna be a dangerous combination for you dude!


dr j said...

you r fun.. maybe tell ur husband that the coconut scent is important to attract the dusky maidens from Polynesia , no forget that, i want them to come my way...

This muscle cell bizo is interesting stuff as it crosses over to my doc's passion which is "mitochondria biogenesis" ( good search term in pub med). Mayo Clinic recently published 2 papers showing that old and young endurance athletes have similar Mito activity which they attribute to the cell workout.

My heart doc focuses on mito efficiency as his view is that so many reactions take place there that the factory should be fed and operated at peak performance.

BTW, only in the interests of science, I do a lot of learning from these 2 sites ( for girls)
( and for boys ) .

The reason.... is ...let me think of a reason... someone once said to me when i was getting my head together about all this, "don't listen to dietitians etc, listen to body builders, coz they are the only ones who have to walk the talk".. not bad starting advice.

thanks for your blog,
its all such fun

Dr. B G said...

Hi dr. j!

I'll check out the girl website! T-nation is COOL. I read my husband's ummm... men's health journals for scientific purposes you know... for the articles. hee

I think I'm really lucky b/c the is audience is FAR MORE SMARTER... and funnier than me!! You're the s-a-v-a-n-t... I'm more 'idiot' most days...

You're right on about the mitochondria -- those microscopic powerhouses can make us or break us... I wonder what science you work on?

dr j said...

you can't get rid of me...

Can you take a squizz at Michael's post but the comments are most interesting regarding MCT and menopause

My bias is , as you might guess, is that fats and hormone panel and age should be disclosed in the med papers.

Larry is a wonderful fella and helped me with a wonderful boy who had ADD that we love who is now playimg golf in Florida and hope to go see him one day..

Dr. B G said...


I'm glad Larry helped the golf player -- that is great! I haven't read the book yet but it sounds fantastic. I'd like to meet him too :) Going ketotic (I did not say DKA which is what traditional docs think of) has much value -- similar to intermittent fasting and reducing carbs minimally as an intermittent practice. Larry is right. Hot flashes are believed to be just an adrenaline rush (like diabetics who get hypoglycemic with drugs) to counter 'glucose starvation' in the hypothalamus in the brain.

I love krill oil. I wrote about Astaxanthin which one of the major components of krill oil. I have personally witnessed amazing improvements in BP, intolerable joint knee pain and some improvements in HDL (probably HDL2/2b subfraction). Regular fish oil EPA+DHA should not be discontinued when krill/astaxanthin is started imo.

Yes -- the type of estrogen, fats and age relative to mense is very vital to make valid conclusions.

I don't know a lot about MCTs (so THANKS for the link). Lauric acid (12C) and the below (6-10C) are medium chained triglycerides and also known as 'SATURATED' fats. These have great anti-atheroclerosis and immunomodulating benefits. Somehow they promote more ketone body production as well (a phenomenal energy source in the brain -- and people on statins may not generate enough, I speculate).

This is from the UC Davis article:

Caproic, caprylic, and capric acids
In bovine and human milk, caproic acid (6:0) is present at
1% and 0.1% of milk fat, respectively, and caprylic acid (8:0)and capric acid (10:0) are present at0.3% and 1.2% of milk fat, respectively. Goat milk contains the highest percentage of caprylic acid, at 2.7% of milk fat. These 3 fatty acids have similar biological activities. Both caprylic acid and capric acid have antiviral activity, and when formed from capric acid in the animal body, monocaprin has antiviral activity against HIV (76, 77). Caprylic acid has also been reported to have antitumor activity in mice (78). Negative effects of these fatty acids on CAD and cholesterol have not been a dietary issue.

Thanks as always!


O Primitivo said...

Lipid-lowering treatment to the end? A review of observational studies and RCTs on cholesterol and mortality in 80+-year olds. -

Dr. B G said...


OF COURSE!!! I like the DATA!!!! Thank you so much for the kind linkxxx~!

I don't believe 80 yo have a statin deficiency and neither do obese, hyperlipid children or all adults... it's a hoax and snake oil to the utmost degree!!!