Tuesday, September 23, 2008

Luminations: Coronary Luminology, Lipids, Laughs

Nakashima et al admit that "Despite the fact that millions of dollars have been spent over the last 50 years on atherosclerosis research, little is known about the development of early human atherosclerosis. There are several reasons why the research on early human atherosclerosis has not advanced. First, human atherosclerosis develops very slowly and at different rates from individual to individual, and it is difficult to distinguish between lesion initiation and progression. Second, a thickened intima is present in human arteries before atherosclerosis develops, but whether this intima forms the precursor for the later more advanced lesion is not fully understood. Third, the relationship between extracellular lipids and macrophages has not been clarified (UUUMMM... yeah hyper-reduction of human cholesterol may indeed lead to cancer -- see the SEAS trial... or J-Litt or IMPROVE-IT or hey...very SHARP mono-statinators...). It is generally believed that extracellular lipids are derived from foam cell death, but there are several examples that show that extracellular lipid occurs independently of macrophage cell death. Finally, there are no good animal models for the study of early atherogenesis. The morphological features of early atherosclerosis are different between humans and laboratory animal models, and it may be somewhat misleading to extrapolate the results obtained from animal models, to humans." (though rabbits are very cute and so are indeed are we, we aren't evolved exactly like herbivores) Thus...more Animal Pharm facts!


What we are certain of though is that HDL2 -- the large puffy HDLs -- are strongly associated with plaque regression, centenarian-lives/longevity, and cancer reduction (Michalaki et al Mol Cell Biochem. 2005 Jan;268(1-2):19-24).

How can we achieve higher HDL2, these wonderfully big ghetto-fab puff-daddies?




Cholesterol Intake on HDL2 and Reduction of Small Dense LDL

Olson et al researchers examined the effects of (!!)Cholesterol and (!!)Saturated fats on HDL2 (good) and HDL3 (bad) particle sizes.

  • Schonfeld G, Patsch W, Rudel LL, Nelson C, Epstein M, Olson RE.
    Effects of dietary cholesterol and fatty acids on plasma lipoproteins.
    J Clin Invest. 1982 May;69(5):1072-80.
    PMID: 7068846
    • ABSTRACT..... The effects of dietary cholesterol and fatty acids on low density and high density lipoproteins (LDL and HDL) were studied in 20 young men. After 2-3 wk of evaluations on ad lib. diets (Latin for eating without controls), basal diets, which consisted of 15% protein, 45% carbohydrates, 40% fat, and 300 mg/day of cholesterol, were given for 4-5 wk (Basal). The ratio of dietary polyunsaturated to saturated fatty acids (P/S) for different groups of subjects were 0.25, 0.4, 0.8, or 2.5. 750 and 1,500 mg/d of cholesterol were added to the basal diets as 3 and 6 eggs, respectively.

      RESULTS Total cholesterol and LDL cholesterol (READ: MORE SMALL DENSE LDL -- 'BAD') were lower in all subjects on the basal diets than on the ad lib. diets... Thus, both the cholesterol contents and P/S ratios of diets were important in determining LDL levels...

      On the diet with low P/S ratio (this means lowest PUFA proportion, highest S-A-T-U-R-A-T-E-D FATS), HDL2 rose (good), whereas this effect was absent on diets with high P/S ratios.

      CONCLUSION The response of LDL to dietary manipulations is consonant with epidemiologic data relating diets high in cholesterol and saturated fat to atherogenesis (NO... NOT TRUE. Mono-statinators rot...substitute the words 'carbohydrates' and 'carbohydrates' respectively...cholesterol does not kill... Carbs/whole-grains do).

      The response of HDL2, however, is opposite to that of its putative role as a negative risk factor. Further work is needed to clarify this interesting paradox (THE EDITORS LIKELY MADE THE AUTHORS PUT THIS IN... TRANSLATION, WE'RE COMPLETELY BEFUDDLED BY THESE RESULTS).





      Highest Sat Fats and Cholesterol Promote HDL2 Concordant with Regression




      In addition to showing the HIGHEST INCREASE in HDL2 and the DEEPEST DROP in HDL3, Olson et al also discovered that the highest sat-fat ratios (4:1) produced the LOWEST apo B, HIGHEST apoA-I/apoA-II and LIGHTEST FLUFFIEST LDL-CHOL (see table III, IV, V). WOW. All good things. Sounds regressive to me. Quite (accidentally) awesome for these scientists from Washington and St Louis Med Schools out in Misery. Dr. Olson also authored a quite profoundly articulate paper entitled "Is it wise to restrict fat in the diets of children?" a few years after the above sat-fat discoveries.

      Brave scientist.



      Differences Between Moderate vs. High Cholesterol Intake

      Did the authors find a clinical difference between Cholesterol intake of 750 mg/day vs. 1500 mg/day? Of course! 1500mg per day (6 eggs) of cholesterol yielded lower apo B (bad) (102 mg/dl vs. 92 mg/dl) and VLDL (very bad stuff)(68 mg/dl vs. 48 mg/dl). The best total HDLs for any of the subgroups studied was: highest sat fats and highest cholesterol 1500mg/day -- 52 mg/dl vs. 50 mg/dl (3 eggs/750mg/d). Without a doubt, the most optimal HDL2/HDL3 ratio was achieved with the highest sat fat ratio and the highest cholesterol intake 1500mg/d 6 eggs daily (see Table).


      So...

      How do we achieve higher HDL2?

      Like a little piggy, I'm laughing all the way to the market to buy cholesterol/eggs *grin*

      If we take lessons learned from these 20 young men...If our diet consists of 40% fats and our caloric intake is ~2000 cal/day -- fats could comprise approximately (0.40 x 2000) = 800 cal/day. Fats are 9 cal/g -- this amount is equivalent to about 88 grams fat total.

      (Protein 15% 75 grams; Carbs 45% 225 grams OMG -- too much carbs)

      A portion of the fat would be MUFA (monounsaturated) and small amounts PUFA (olive oil, fish oil, GLA, chocolate, nuts, nut butters, veggies, etc) and a certain ratio of saturated fats. Add also the cholesterol equivalent of 6 eggs = 1500 mg cholesterol daily. One Tablespoon of Fat contains approx 13-15 grams fat. SATURATED SFA include butter, butter oil, ghee, virgin coconut oil, MCTs, lard, egg yolks, grass-fed meat, seafood, fish, mollusks, etc.

      (using omega-3 eggs adds in lutein 8x more per egg and fabulous DHA!)
      One large AA omega-3 egg contains about 4.5 grams fat of which 1.5 grams saturated




      Individual Genetic Variations

      The Missouri authors did point out that increases in LDL varied significantly among the male subjects. Like responses to Lp(a) reduction, it appears genetics and diet-gene interaction may play a large part. In the above trial, carb intake was extremely high and as we aware carbs modulate apo B and sdLDL (and HDL2). The meat used in the trial were from a 'local meat processor' in Missouri. Perhaps back then in the 1980s, the EPA + DHA content was already depleted from common meat sources. Many factors (high carbs high carbs high carbs, no EPA DHA, Cholesterol insufficiency) exist that may explain how the baseline HDLs of these young healthy robust mid-western study participants was only in the mid-40s.

      Curiously, apo E polymorphisms and other genetic influences (like PPAR-d a g) may be major players for the optimum diet for regression and fat intake. Pang et al studied apo E patterns in Hong Kong and noticed that carriers of E2 had the best highest apo E levels compared with homozygous apo E3. Other observations were that "Apolipoprotein E (apo E) allele frequencies were: epsilon2 8.7%, epsilon3 80.4% and epsilon4 10.9% with the genotype having a significant effect on plasma apo E concentration (p less than 0.001). Lipoprotein(a) levels were higher in women than men (geometric mean 15.2 versus 10.2 mg/dL, p less than 0.05) and in women with FSH above versus below 40 IU/L (185 versus 136 mg/L, p less than 0.05)." It's not clear to me yet how to discern our apo E polymorphisms without genetic testing and what is the precise diet-gene interaction because optimally the studies would consider the effects of a no-grains/Paleo diet, and unfortunately few take this stance in the medical literature.


      Eggs on the other hand appear great! Perhaps the fox know best...
      • Effect of egg yolk feeding on the concentration and composition of serum lipoproteins in man. Beynen AC, Katan MB. Atherosclerosis. 1985 Feb;54(2):157-66.
      • The effect of egg yolk consumption on the composition of LDL and on the concentration of HDL subclasses was studied in healthy subjects.
      • Six volunteers consumed a diet low in cholesterol for 10 days and then daily added 6 egg yolks to their diet for another 10 days; the experiment was repeated 1 year later with the same subjects. Egg yolk consumption caused the cholesterol intake to increase by 1600 mg/day, and the fat intake by 7 energy % at the expense of carbohydrates; this increase was due almost exclusively to monounsaturated fatty acids.
      • RESULTS: Upon egg yolk feeding the mean level of serum total cholesterol rose by 13%; the bulk of this rise was due to LDL cholesterol, which increased by 21% (READ: REDUCTION IN sdLDL).
      • VLDL and IDL cholesterol decreased by 19 and 11% (good), and serum total triglycerides by 17% (great).
      • Marked relative increases of 35 (very good) and 36% (very very good) were seen in the cholesterol level of the HDL subfractions with densities of 1.055-1.075 g/ml (HDL1) and 1.075-1.100 g/ml (HDL2), respectively.
      • The HDL2/LDL cholesterol ratio increased by 16% (VERY VERY GOOD).
      • No change in cholesterol in HDL3 (d greater than 1.100 g/ml) was observed (GOOD!).
      • The increase in cholesterol in HDL isolated by density gradient ultracentrifugation significantly exceeded the increase in cholesterol in heparin-Mn2+ soluble HDL. This suggests the formation of apo E-containing HDL, i.e. HDLc, which has HDL density but is not soluble in heparin-Mn2+. (?translation please?...Is Krauss in the house?)
      • The composition of the LDL particles was significantly altered; the core became enriched in esterified cholesterol at the expense of triglycerides, and the ratio of core components to surface components increased by 7%. (read again: elimination of sdLDL and rise in round, puffy fluffy LDL particles *cheers!*)
        PMID: 3986015


      Cute...*laugh* I love eggs video

      10 comments:

      Stephan said...

      Great study; I am definitely going to print that out!

      Dr. B G said...

      Dude,

      Go ahead...'n GEEK-OUT!! You'll get a good laugh! But I do give these guys credit. Olson turns around his story after curious low fat studies in children.

      -G

      Doug said...

      G:

      This is fantastic and desperately needed work! The negative view of saturated fats has been so drummed into everyone's minds for so long that it is hard to keep an open mind on this subject. As you know from our discussion on the TYP forum, I got excellent results from conciously and purposely adding saturated fats to my diet, but every time I talk to a doctor they want me to take a statin because of the increased LDL-C. The constant negativity can make you doubt your course of action, but the facts, as you have been pointing out so well, show that sat fat increases the size of LDL and HDL,and that is a really good thing. Please keep up your great postings in this area, your work is fuel for our motivation and confidence!

      Dr. B G said...

      Doug,

      I love stories like yours -- regression and TYP/unconventional methods!! You ROCK!!! The value of sat fats for Lp(a) and HDL2 are pretty clear.

      Stephan has great posts also esp regarding his own experiences on his blog. This young man has (!!)PHAT/ghetto-fab fats! (When/if my HDLs exceed his I'll be posting. I'm not into cold-showers right now. May take a while -- only got off wheat/grains 2mos ago.) EVERYDAY I read about sat fats and the supposed 'harm'. Normally I'd get a rise over such retardness -- but I'm off wheat -- and it doesn't bother anymore. Glad I'm not so retarded now either...

      I can't wait to see your HDLs/HDL2b in 6-12 mos -- they'll be even more ROCKIN!! Doug you must share later!

      -G

      dr j said...

      Hi G !
      I'm back.
      great post as usual
      i remember that you are going to Bruce Ames's lab. Have you seen this great video of his lecture this Sept?
      http://video.google.com/videoplay?docid=6279555376505271736

      hullo from oz
      john

      Dr. B G said...

      Hi,

      Welcome back to oz... nice trip? :)

      Getting up to speed with hormones still -- hard to make up for 12 yrs of discoveries! And then making sense of my own lessons.

      You remembered...Terrific vid!!! I'm so grateful for your thoughtfulness.

      Dr. Ames is such a luminary. Isn't he fabulous?? Going to try not drool. But will stop as I chide him over the bread basket... heee (2nd thought, maybe I'll restrain myself on the first *date*).

      -G

      Peter said...

      Hi G,

      How do you think Kwasniewski got so much right? Working in isolation, behind the iron curtain, in the 1960s and 70s Poland, with essentially no ability to look at biochemistry in the way we do today? Clinical response rather than EBCT. But it looks more and more like he hits the nail on the head.

      On a random basis we cooked a gammon that looks like lasting 3 days, so my current six egg yolks for breakfast are being supplemented with three eggs with the gammon, and a few chips to keep the carb count up... All cooked in beef tallow of course! Now looking at lipid fractions would be an interesting exercise, but I'll settle for feeling good!

      Peter

      Dr. B G said...

      Peter,

      Well, it must take a visionary to understand and recognize a visionary like Jan K., eh? *smile* Indeed, how does one infer so many interspecies connections and amazing medical observations despite the literature being littered with Ancel Key's indoctrinated followers.

      Had to look up GAMMON -- sounds absolutely YUMMicious! Lard... tallow... all sounds good to me.

      Did you ever posted on this abstract below? It was the last link on the 'Balls' post; it was meant for you :) *haha*

      Ann Nutr Metab. 1994;38(5):270-80.
      Dietary fat quantity and composition alter colon cell kinetics in growing rats.Thornton WH Jr, MacDonald RS.
      Department of Food Science and Human Nutrition, University of Missouri, Columbia 65211.

      The effects of corn oil and beef tallow on the proliferation of colon mucosal cells in rats were investigated. In protocol 1, rats were fed diets containing 12 or 38% kJ from fat supplied by either corn oil or beef tallow. Colon crypt column cell number was examined histologically. The source of dietary fat had no effect on the number of cells per crypt column, but rats fed 38% fat had significantly fewer cells per crypt column in the proximal colon than rats fed 12%. Protocol 2 examined the effects of diets containing corn oil or beef tallow at 12, 30, or 37% kJ on the percentage of colon cells in phases of the cell cycle using flow cytometry and expression of proliferating cell nuclear antigen (PCNA). Rats fed corn oil had more cells in S phase compared to rats fed beef tallow. Rats fed 30 or 37% fat had more cells in G1 and fewer cells in G2 + M compared to rats fed 12%. Animals consuming the 12% corn oil diet or the 37% beef tallow diet had the fewest colon cells expressing PCNA, while those animals consuming the 37% corn oil diet or the 12% beef tallow diet had the greatest number of cells expressing PCNA. Based on combined interpretation of PCNA and cell cycle phases, the results suggest that diets high in saturated fat result in reduced colon cell proliferation whereas diets high in unsaturated fat do not.
      PMID: 7710262

      -G

      Anonymous said...

      G-

      You might like reading Dr. Mary Enig's, Know Your Fats. She discusses traditional diets and the health issues which arose after the abandoning of those diets.

      She mentions that all of the cells in the body need sat fat.

      A very interesting article about MCT and Alzheimer's by an MD whose husband is dealing with the disease.

      http://www.coconutresearchcenter.com:80/hwnl_5-4.htm

      M

      Dr. B G said...

      Dear M,

      Thanks for the link! I will ck it out. A few wks ago I purchased Nourishing Traditions cook book and Udo Erasmus' Fats that kill, Fats that heal. You are right -- I need to read Enig. I started Taubes (from my sister) but he's so SWEET. Can only afford to bite off small pieces at a time to savor as I spawn off many ideas from him.

      Have observed fantastic Lp(a) reduction with MCT oil of course. You are on to something! It is magical stuff.

      -G