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The Albatross -- Part One: You Want More Fat
Let's start with high-CHO [Ed.: a molecule of carbohydrate is composed of Carbon-Hydrogen-Oxygen] versus high-mono-fat diets (although NB that cutting out CHO in favor of fat increases P:C -- a subject to which we will return).
>Apart from that, there has been a
I firmly agree -- and so does Sears. PH, it's a shibboleth of critics of Sears who haven't read his books that they will suggest that the Zone involves lots of saturated fat. The Zone involves very consciously choosing the leanest protein sources one can get (excepting salmon, tuna, et al), and bringing total fat up to >=30% fat with MUFA and some n3's [n3: Omega 3 fatty acids]. Sears repeatedly warns one that SaFA (saturated fatty acid) and n6 are to be avoided. E.g.:
When you add those fat blocks, though, you must pay careful attention to the KIND of fat you eat. Just as there are favorable and unfavorable carbohydrates, there are also good fats and bad fats.
"What are bad fats? The real villain fat is AA [arachidonic acid]... Saturated fats should also be kept to a minimum. [SaFA] are found in animal protein sources and in whole-fat dairy products. You want t restrict these fats in a Zone-favorable diet because they tend to raise ... insulin resistance ... That's why I recommend low-fat animal protein sources like white meat poultry and fish -they're low in [SaFA]." -Sears, _The Zone_: 85-6.
The only way to get lower SaFA than Sears' standard plans is to go vegan -- and those wishing to do just that, may see his latest book, _The Soy Zone_ (89) (gosh, does Sears pay me for this shit?!). So, what are we left with? Cut out SaFA and n6; increase mono and n3.
>Zone gives you way-over the essential oil
There is not some evidence, but an overwhelming mountain thereof, that a diet high in mono fat is superior to one high in CHO. Compared to the high-CHO AHA/ADA and SSCN [Ed.: AHA is American Heart Assoc.], a diet quite dripping with MUFA leads to similar reductions in TC and LDL (this is likely due at least partly to reducing postprandial insulin, as insulin increases the activity of HMGCoA reductase (70)) but maintains or elevates HDL where it usually drops in AHA, and significantly lowers TG, which are ELEVATED by AHA! This latter is evidently due to increases in liver VLDL TG secretion in response to carbohydrates (20).
And note that it is a high MONOUNSATURATED FAT diet, NOT specifically an OLIVE OIL diet, that has these effects: peanut (12), high-oleic sunflower (9 b-d), macadamia nut (11), avocado (19, 19b, 23), pecan (12a), hazelnut (12b), canola (37, 37a, 37b), pistachio (12c), and almond (10a-c), MUFA sources have been tried, and they all yield essentially the same results. While there may be confounding factors in the effect -- phytochemicals in this oil or amino acid balance in that nut -- the overall effect is quite powerfully consistent. Indeed, far from being an effect unique to olive oil, one review (9a) claims that olive oil yields INFERIOR results to 2 other MUFA sources (canola and high-oleic sunflower). It might be argued that the canola results are due to the n3 content added to the MUFA (and this is almost surely a factor: see below), but this certainly cannot apply to HOSO.
Note also that it is a HIGH-mono fat diet: i.e., ~40% of an *AL* diet in nearly all these trials! Mild-fat diets which are high % MUFA fail to lower blood pressure (30), unlike the high-mono diet. And note that a diet which holds to a high-CHO, moderate-low fat program like Step I, or a truly low-fat one like step II, but replaces standard fat with MUFA from avocado (19a) or canola (35, 37x, 37y), does not cause a significant improvement in lipid profiles. It's not enough to just switch fat types. FAT MUST REPLACE CHO.
The best trial, imho (in my humble opinion), was (12), a crossover trial using AHA Step II, SAD, and high-MUFA diets from two different sources (olive oil and peanuts), all in the same trial, and clearly proved that high-MUFA, irrespective of source, yields a better risk profile than low-fat. In fact, after an extensive review of the RR associated with changes in all the tested lipids (and not including the TG:HDL ratio, which would REALLY have accelerated the difference), these authors calculated that, relative to SAD, the MUFA diets cut CVD risk by 25% (olive), 16% (peanut oil), and 21% (peanuts and peanut butter -- NB [NB is "Nota bene" -- latin for "note well". Used to call particular attention to something], this latter, with all the crap that's in commercial PB [peanut butter]!!), while the AHA Step II diet cut risk by just 12%. Now recall that lowering Calories while on high-CHO diets appears to make them LESS favorable (40) ...
High-MUFA works in normals (10, 10b, 10c, 11, 19, 37a), hypercholesterolemics (10a, 11, 15, 19, 19b, 41), autoimmune diabetes (9), and NIDDM patients (11a, 13, 14, 17, 20- 27, 32); it works for smokers (16) and nonsmokers (all other trials) alike. It lowers blood pressure, as one would expect granted the effects of a higher P:C on eicosanoid metabolism (below)(11a, 21, 25). It even improves lipids in patients already taking lovastatin (37a)! It improves glycemia in NIDDM (11a, 17, 21, 22, 24, 25, 26, 27, 32) and diabetes type I (9). (More on glycemia and the recent Why doesn't the Zone lower FBG? threads below). And then there is the evidence of protection from cognitive decline (31). Not EVERY trial yielded EVERY one of these results, but the overall pattern is clear, as per the meta-analyses and systematic reviews (18, 28, 29).
And even diets which are high in fat and low in CHO, yet are NOT specifically focused on mono fat, appear to be better for you than a high-CHO one. One trial (45) found that a diet that is high in fat (45%) with equal amounts of poly, mono, and SaFA leads to better risk profiles in healthy postmenopausal women than does a high-CHO (60%) one with equal protein (15%) content: compared tot he high-fat diet, high-CHO women had higher TG, insulin, and VLDL, lower HDL, poorer muscle insulin response, and lousier uptake of fat-soluble vitamin A (extrapolate to CoQ, E complex, etc). Likewise, another controlled trial compared hypercholesterolemics put on 4 progressively lower-fat (with relative amounts of SaFA and unSaFA held constant), higher-CHO diets (41). THE LOWER THEIR FAT INTAKE GOT, THE WORSE THEIR LIPIDS BECAME: most notably, those who started out with normal TG saw them climb, dose-dependently, on lower-fat diets. BAD!
Lower fat intake is also epidemiologically linked to greater risk of ischemic stroke (42), one of the biggest killers we know. And what PARTICULAR fat was most correlated with stroke protection? Monounsaturated fat. Likewise, an epidemiological study (62) found that red blood cell oleic acid, independently of cholesterol levels, was tied to lower AA levels -- and to reduced risk of CVD death.
Further, we may be able to infer something about the insulin resistance of individuals even in trials where glycemia were NOT tested, as the clear improvements in TG:HDL these diets induce (vs. the clearly DELETERIOUS effects induced by the high-CHO diet) may be a marker for fasting insulin. Low HDL is strongly correlated with hyperinsulinemia (60, 61), t the point where Gerald Reaven has flatly declared that Isolated low HDL cholesterol [is] An insulin-resistant state (60) and Individuals with high total cholesterol/HDL cholesterol ratios are insulin resistant (61). And not only do high TG CORRELATE with insulin resistance (59) due to insulin's stimulation of hepatic VLDL synthesis (30), but in fact a case-control study (58 ) concluded that isolated low HDL cholesterol [is] an insulin-resistant state only in the presence of fasting hypertriglyceridemia. Taken together, the Sears surrogate for insulin claim seems like a reasonable hypothesis -- and, in fact, the lead (!) author of (58 ) confirmed in PC that he tends to agre with this analysis: with regards the paper by Gaziano et al. that you mentioned, you are absolutely right. I would not be surprised if the TG/HDL ratio is a surrogate marker for insulin resistance. In which case we have even clearer evidence, from these trials, that high-CHO diets induce hperinsulinemia, and high-MUFA ones reverse it.
In fact, the mechanism posited for the lowering of TG and elevation of HDL by high-MUFA, and the reverse in high-CHO, assumes exactly this (20; cf. 81). High-CHO diets result in higher postprandial insulin response, which leads to increased TG-rich VLDL secretion. By contrast, high-MUFA does not directly stimulate insulin, and in fact BLUNTS it, because it delays gastric emptying. Thus, the difference in TG.
What then enters into the equation is the cholesteryl ester transfer protein (CETP). CETP swipes cholesteryl esters (cholesterol, as stored in lipoproteins) from HDL (high in CE density) and GIVES them to VLDL (very low in CE). It thus lowers HDL, and has the potential to elevate LDL, though from the trials it doesn't appear that it actually does so.
While both high-MUFA and high-CHO diets, for different reasons, reduce the ABSOLUTE AMOUNT of CETP (REFERENCE), the ACTIVITY of CETP is lowered by oleic acid (REF). by contrast, the increased VLDL caused by high-CHO meals actually INCREASES CETP activity, because of sheer stoichiometry: when there's more VLDL around, it tends to swipe more from HDL.
So: insulin elevates TG and lowers HDL. Higher insulin = higher TG:HDL.
Now, the Lyon trial (33, 34, 35). The trial saw reductions >75% in CV mortality rates MORE DETAILS HERE -- a more impressive result than any drug or lifestyle change yet known to the world. What did they do that controls didn't? Their protein stayed the same; their intake of fruit and veggies went up marginally while grains went down marginally; and their mono and n3 fats went up as a replacement for saturated and n6 fat, without any change in %fat compared to controls. Conclusion: the fat, not the vegetables or the butler, did it. This was not a fat-reduced diet compared to the Zone. In fact, it was 30% fat by calories -- very Zonish. Except that it was, again, AD LIB, so total fat was much HIGHER.
Also note that the Lyon trial, at this moderate fat intake, did NOT see the dramatic lipid changes noted above. Why? Presumably, because they didn't eat enough fat! See 19a, 35, 37x, 37y again. This includes their Lp(a) -- see (36). Now, imagine what could have been accomplished with an improved lipid profile resulting from higher fat intake, and resulting lower TG, higher HDL, lower insulin levels, and lower Lp(a).
Note that other work shows that a similar modification in fat pattern -- starting with a truly HIGH-mono fat diet and replacing some of the mono with ALA -- yields mildly better standard lipids than even a pure high-MUFA program (36, 37), and also lowers the highly atherogenic (almost exclusively in men, it would seem: 38, 39) and very difficult to lower lipoprotein(a). The trial which reported this latter fact (36) showed additional reductions in Lp(a) of 6.2% -- which sounds like tiddleywinks, until one realizes just how difficult it is to lower Lp(a) AT ALL (niacin does it; little else does). The Framingham study found (39a) that The odds ratio for CHD risk in men with Lp(a)-C >/=0. 259 mmol/L (>/=10 mg/dL), after adjusting for age, HDL-cholesterol, LDL-cholesterol, smoking, diabetes, blood pressure, and body mass index, was 2.293. A recent meta-analysis (103) puts the risk much lower than this and many previous studies (1.6 RR top to bottom tertile), but includes studies involving women -- who evidently aren't at significant risk from Lp(a), somehow, so it's a bit artificial. Also, they went by tertiles, which will tend to blunt any progressive risk, as compared to quartiles or quintiles.
So, as per the most cardio-protective diet known to science, we want to get > (less than) 30% fat from mono and n3 while restricting saturates and n6. Hmmm... this sounds familiar, somehow...
Here are the conclusions of a recent analysis of the Nurses Health Study (104):
Each increase of 5 percent of energy intake from saturated fat, as compared with equivalent energy intake from CARBOHYDRATES, was associated with a 17 percent increase in the risk of coronary disease ... As compared with equivalent energy from CARBOHYDRATES, the relative risk for a 2 percent increment in energy intake from trans unsaturated fat was 1.93 ...; that for a 5 percent increment in energy from monounsaturated fat was *0.81* ...; and that for a 5 percent increment in energy from polyunsaturated fat was *0.62* ... Total fat intake was NOT significantly related to the risk of coronary disease...
We estimated that the replacement of 5 percent of energy from saturated fat with energy from unsaturated fats would reduce risk by 42 percent ... and that the replacement of 2 percent of energy from trans fat with energy from unhydrogenated, unsaturated fats would reduce risk by 53 percent ...
Then there's cancer. I won't bother documenting the protective effect of n3 vs. cancer, but I WILL note that the only (case-control) studies I can find on the subject (43, 44, 46) show that higher mono fat intake is associated with lower risk of cancer (and, BTW, that higher starch intake is associated with higher risk (46)). And the Lyon study (34) gives prospective evidence that a diet that is Zonsily high in mono and ALA can cut your risk of cancer death by 61% (p<.05).
Now: if almost all of the Lyon results are attributable to getting more mono and ALA (no other changes were terribly large), in moderate, Zonish %s of an AL diet, does it really make sense to cut down on these fats dramatically on CR? I put it to you that it does not. I might cut back on my saturates and n6 intake to keep a similar % fat, however. This conclusion is reinforced both by the comparison of the Biospheran and Markovic-Zone experiences, and by the following rodent CR material, which I've previously referenced, from Weindruch and Walford, in _The Retardation..._:
> p.108ff: Data showing that a high-percentage fat diet does not
"Kubo ... found that LS's [LS is lifespan] were most strikingly prolonged by DR [DR is dietary restriction, aka CR] when moderate intakes (38% of energy as fat) and not very high fat intakes (69%...) were used." p. 59. [From the descriptor moderate, I take it that it worked better than low-fat diet as well, though this isn't specified and I don't have the original].
"High fat diets are used more efficiently than are low fat ones... Quite probably the severity of the [CR] tolerable by animals could be increased by feeding high fat diets... whether this would further increase lifespan is worthy of study [see above quote: evidently, it DOES] ...*what* (not just how much) is eaten affects metabolism." -255
On this last, efficiency point: a monkey study (47) found that higher-fat diets lowered mitochondrial metabolic rate, WITHOUT altering the state 3:state4 ratio. I had been meaning to ask Aubrey da man de Grey about this, and a related question, for MONTHS, so preparing this opus put the coal to my ass. Here is our discussion:
> in the marmoset was reduced by high fat diets irrespective of the
> dietary level of lipid saturation.
> Though it's not mentioned in the abstract, the paper also asserts that
> the state 3: state 4 ratio was not altered by the different diets. So
> there was lower metabolic rate (depending on substrate, state 3
> absolute levels went down between ~ 1/9 and ~ 1/3) with no increase in
> e- fumbling.
That doesn't absolutely follow. "Mitochondrial respiration" means the rate of respiration of isolated mitochondria (extracted from cells) in defined states (states 3 and 4), and it doesn't necessarily tell us about the metabolic rate (per unit mass, i.e. the specific metabolic rate) of the intact organism. In particular, if the state 3:state 4 ratio (normally termed the respiratory control ratio) was unaltered then state 3 respiration and state 4 respiration were both lower in isolated mitochondria, but if the fat-supplemented organism was running closer to state 3 (i.e. keeping its ADP supply higher) then the organism's specific metabolic rate (which wasn't measured) could have been unaltered.
> I also note from your book (p.17) that "ubisemiquinone exists only
> fleetingly within CoQ is interacting with Complexes I of III. However,
> its existence is ... the weak link in the chain, because it can
> spontaneously revert to ubiquinone" and thus fumble e-. I take this to
> imply that this fumbling does NOT occur (or is at least much less
> likely to occur) in the transfer of e- from FADH2 via fatty acyl CoA
> dehydrogenase to CoQ. IIRC, you actually say this explicitly somewhere
> in your corpus, though I can't find t just this minute.
> if some of the e- from fat are transferred into ETS via a less fumble-
> prone route, then shouldn't a higher-fat diet (with constant caloric
> intake) to some extent reduce mt oxidative stress and thus slow aging?
Possibly, but the effect would be slight: for each two-carbon slice of a fatty acid, only two electrons enter the electron transport chain via the fatty acyl CoA dehydrogenase, whereas eight enter via Complex I and two via Complex II. In the case of carbohydrate metabolism, if we presume that the glycerophosphate dehydrogenase pathway is not used we get a bigger ratio through Complex I, five out of six rather than four, but that's a pretty small difference.
"respiration rate declined [so much] so e- flow through Complexes I and III declined by that same amount, so the rate of e- fumbling declined by about that same amount" seems more persuasive.
> Is it at least fair to say that a higher fat diet would
> slow aging by at least 1%? Any better estimate? Or am I missing something
I think that in view of the small differences in how much each enzyme is used and the quite substantial differences in metabolic rate, it is certainly justified to explore whether highly fat-biased diets might lower metabolic rate in other primates, as well as other variations on the study you mention. I found an interesting related study in Medline: Yerboeket-van de Venne and Westerterp, Appetite 1996 Jun;26(3):287-300 found a reduction in energy expenditure from medium or high fat diet relative to low, but only in people described as "restrained eaters". This may suggest that the reduction in metabolic rate is associated with retention of the fat, i.e. weight gain, which curiously was not measured in the McMurchie study.
MR: I actually would conclude the OPPOSITE re: the fat accumulation: if the reduction in energy expenditure only happened in restrained eaters, then presumably it happens in people who are NOT gorging and getting fat, no? In any case, we CR folks are certainly restrained eaters!
Aubrey de Grey: Absolutely right - I totally zoned out there. Moreover I didn't know about the results you quote from W&W [i.e. the data which MR posted above in the PRESENT post to the CRing]. I agree with your interpretation.
Conclusion on fat: low-fat diets, eaten AL or CR, will increase your odds of CVD, cancer, maybe even accelerate aging, and ultimately kill you. Why put up with that shit? Yes, CR can make up for the risk entailed by slowing down aging, but you re still better off on a higher-fat CR diet.