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...). 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. How can we achieve higher HDL2?
Olson et al researchers examined the effects of (!!) cholesterol and (!!) saturated fats on HDL2 and HDL3 particle sizes.
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, 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...substitute the words 'carbohydrates' and 'carbohydrates'...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 (EDITORS LIKELY MADE THE AUTHORS PUT THIS IN... TRANSLATION, WE'RE BEFUDDLED BY THESE RESULTS).
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?" eight years ago. Brave scientist.
How do we achieve higher HDL2?
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
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 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
< 0.001). Lipoprotein(a) levels were higher in women than men (geometric mean 15.2 versus 10.2 mg/dL, p
< 0.05) and in women with FSH above versus below 40 IU/L (185 versus 136 mg/L, p
< 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, but unfortunately few take this stance in the medical literature.
Eggs on the other hand appear great! Perhaps the fox know best...
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%, and serum total triglycerides by 17%.
Marked relative increases of 35 and 36% 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%.
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...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