Keep in mind, lipoprotein metabolism is not my area of expertise, caveat emptor, as they say.
I will not address the "cholesterol con" claim that TC is irrelevant. It is bogus and not really pertinent to the discussion because TC/HDL is indeed a better predictor as you said yourself. Of course, neither LDL/HDL nor TC/HDL would be any better a marker than HDL alone if TC were irrelevant. I do not know what your stance is since you seem to concede that TC/HDL is important to some degree.
Anyway, for my answer, I will rephrase your question:
Does PUFA & MUFA improve the TC/HDL ratio and would this outweigh the putative effects on Lp(a) and oxLDL?Lipoprotein(A) and its relation to CVD as well as fatty acid intakeFirst, it remains to be seen if Lp(a) is a causal risk factor. Correlation does not mandate causation: in epidemiology detrimental changes will be very difficult to discern from positively adaptive ones. Based on the biological role of Lp(a) a protective role, at least under specific circumstances, has been suggested:
"In a similar manner, we hypothesize that under certain settings, Lp[a] acts as an acute-phase reactant and its levels are increased in plasma within the context of the genetically determined set point. In turn, we postulate that the physiological role of Lp[a] may be to preferentially bind and transport OxPLs that are derived from apoptosis and cell death, as occurs during inflammation and oxidative stress, or when OxPLs are mobilized from tissues during iatrogenic plaque rupture during PCI or during lesion regression in response to therapeutic interventions. Lp[a] may possibly even detoxify OxPL." [1]
If we entertain the notion that, yes, LP(a) is a true risk factor, then it is still a rather modest one [2]:
“In a common set of participants, the adjusted RR for CHD per 1-SD higher Lp(a) concentration was considerably weaker than the corresponding RR with non-HDL cholesterol (1.14 vs 1.66, respectively)”Keep in mind that TC/HDL is even more powerful than non-HDL cholesterol!
“Lipoprotein(a) concentration is, however, a relatively modest coronary risk factor, being only about one-quarter as strong overall as non–HDL cholesterol, although Lp(a) may become proportionally more important to CHD at very high concentrations owing to its potentially curvilinear risk relationship.”I don't know where the idea that Lp(a) is an exceptionally strong risk factor originated. Perhaps people did not notice that risk estimates successively diminished in more recent meta-analyses; that the effects may be only pronounced at extremely high Lp(a) levels or under other specific circumstances. (see [2] among others)
To play the numbers game if we wish to back up the above notion (read [2] to follow the back of the envelope calculations):
-10% SAFA, +20% LP(A); this likely overestimates the increase when replacing SAFA with fat a little but may work for CHO (see e.g. KANWU) [3, 4]. Note that not all studies find SAFA to lower Lp(a), though, many or most do.
+20%/+350% (1 SD) = 0.057 factor
Let’s use the highest estimate for mortality: Coronary death RR 1.14 (1.07-
1.22) per one standard deviation of Lp(a)
New RR: 1.013; even if we generously round a modest ~2%
Different fatty acids and the TC/HDL ratioYes, what about different fatty acids and TC/HDL? Based on the Mensink et al. meta-analysis [5] (but calculated by Mozaffarian et al. [6]):
“In short-term feeding trials, each 5%E of PUFA replacing SFA lowers low-density lipoprotein cholesterol (LDL-C) by 10 mg/dl, without an appreciable reduction in HDL-C, producing a lowering of the TC:HDL-C ratio by 0.16 [Mensink et al.]... In observational studies of adults aged 40–59 y, each 1 unit lower TC:HDL-C is associated with 44% lower risk of CHD [Prospective Studies Collaboration, my ref. 8] Based on these two sets of data, a 5%E increase in PUFA replacing SFA would be predicted, based on TC:HDL-C effects alone, to reduce occurrence of CHD by 9%” [6]
I do arrive at different, though, pretty similar results both using their data (for 40-59yo) and estimates better applicable to the population at large:
TC/HDL change when 1%E PUFA is substituted for CHO or SAFA*
-0.032 (-0.042, -0.022)
for 10E% and a 33% risk reduction** per -1.33 units TC/HDL (see [8]) we get:
-7.9% (-10.4%, -5.4%) IHD mortality
If you prefer to have all your results from one solid RCT look again at KANWU [3]. I arrive at a qualitatively similar result for
MUFA when I calculate their change in TC/HDL and use that instead of Mensinks' meta-analysis (data not shown).
Note, that these calculations are consistent w/ RCTs (Mozaffarian et al. [6]) and the epidemiology (Jakobsen et al. [7]***) and further drive home the point: TC/HDL may be the key risk factor here and PUFA really is superior to SAFA in the population at large.
Again I am comparing "worst-case" scenarios for unsaturated fatty acids (lowest conceivable risk reduction via TC/HDL lowering) with a "best-case" scenario for SAFA (largest imaginable risk reduction via Lp(a)), but, based on my data, the CIs still do not come close to overlapping.
Conclusion, positive effects on Lp(a) from SAFA do not come close to outweighing benefits to the TC/HDL ratio that unsaturated FAs show under normal circumstances.
Usually one way to counter the evidence is to dismiss Mensink et al. for analysing short-term data (e.g. Stephan from wholehealthsource.blogspot.com). However, this also massively weakens one's argument against PUFA. If adaptation to high SAFA intakes takes place, the same might be true for PUFA in regards to ALL its postulated side-effects (LP(a) and ox. stress, see below). This line of reasoning is interesting and I haven't reviewed it in any detail, but the data reviewed by Mozaffarain et al. [6] clearly refutes key aspects of this hypothesis: long term PUFA RCTs
do lead to reduced TC.
*since substitution of CHO with SAFA is neutral I used the pre-calculated table for CHO given by Mensink not the actual equations; MUFA lowers the TC/HDL ratio a little less than PUFA (not significant)
**I suppose here it would be better also to use the confidence intervals given by [8] for best accuracy but I cannot find them for the whole set in the given pdf, though, the lowest available risk estimate is -26% (70-89yo group). This is so pessimistic as to be ridiculous and would give a lower bound of -4.3% for PUFA.
***for the sake of completeness: this is the study showing MUFA to be neutral or very slightly detrimental vs SAFA; why this may be artifactual is discussed by the authors and has been addressed on this forum and elsewhere -- but this is not contrary to my point, which is simply that both PUFA and MUFA edge out SAFA
when all lines of evidence are considered. Though, some studies point towards a risk from MUFA, currently, this remains the weaker proposition IMHO.
[1] A novel function of lipoprotein [a] as a preferential carrier of oxidized phospholipids in human plasma. Bergmark C, Dewan A, Orsoni A, Merki E, Miller ER, Shin MJ, Binder CJ, Hörkkö S, Krauss RM, Chapman MJ, Witztum JL, Tsimikas S.
J Lipid Res. 2008 Oct;49(10):2230-9. Epub 2008 Jul 1.
http://www.jlr.org/c...49/10/2230.full[2] JAMA. 2009 Jul 22;302(4):412-23.
Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality. Emerging Risk Factors Collaboration
http://jama.ama-assn.../full/302/4/412[3] Atherosclerosis. 2003 Mar;167(1):149-58.
Effects of dietary saturated, monounsaturated and n-3 fatty acids on fasting lipoproteins, LDL size and post-prandial lipid metabolism in healthy subjects.
Rivellese et al.
[4] Am J Clin Nutr. 2007 Dec;86(6):1611-20.
Comparison of monounsaturated fat with carbohydrates as a replacement for saturated fat in subjects with a high metabolic risk profile: studies in the fasting and postprandial states. Berglund et al.
http://www.ajcn.org/.../full/86/6/1611[5] Mensink RP, Zock PL, Kester AD, Katan MB. Effects of dietary fatty acids and carbohydrates on the ratio of serum total to HDL cholesterol and on serum lipids and apolipoproteins: a meta-analysis of 60 controlled trials. Am J Clin Nutr. 2003; 77: 1146–1155.
http://www.ajcn.org/.../full/77/5/1146[6] Mozaffarian D, Micha R, Wallace S (2010) Effects on Coronary Heart Disease of Increasing Polyunsaturated Fat in Place of Saturated Fat: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. PLoS Med 7(3): e1000252. doi:10.1371/journal.pmed.1000252
http://clinicaltrial...al.pmed.1000252[7] Am J Clin Nutr. 2009 May;89(5):1425-32. Epub 2009 Feb 11.
Major types of dietary fat and risk of coronary heart disease: a pooled analysis of 11 cohort studies. Jakobsen et al.
http://www.ajcn.org/.../full/89/5/1425[8] Lancet. 2007 Dec 1;370(9602):1829-39.
Blood cholesterol and vascular mortality by age, sex, and blood pressure: a meta-analysis of individual data from 61 prospective studies with 55,000 vascular deaths.
Prospective Studies Collaboration et al.
Edited by kismet, 13 November 2010 - 11:41 PM.