RoR: Forum

The Calorically Restricted Low-Fat Nutrient-Dense Diet in Biosphere 2 Significantly Lowers Blood Glucose, Total Leukocyte Count, Cholesterol, and Blood Pressure in Humans

RL Walford, SB Harris and MW Gunion

Biosphere 2 is a 3.15-acre space containing an ecosystem that is energetically open (sunlight, electric power, and heat) but materially closed, with air, water, and organic material being recycled. Since September 1991, eight subjects (four women and four men) have been sealed inside, living on food crops grown within. Their diet, low in calories (average, 1780 kcal/day; 1 kcal = 4.184 kJ), low in fat (10% of calories), and nutrient-dense, conforms to that which in numerous animal experiments has promoted health, retarded aging, and extended maximum life span. We report here medical data on the eight subjects, comparing preclosure data with data through 6 months of closure. Significant changes included: (i) weight, 74 to 62 kg (men) and 61 to 54 kg (women); (ii) mean systolic/diastolic blood pressure (eight subjects), 109/74 to 89/58 mmHg (1 mmHg = 133 Pa); (iii) total serum cholesterol, from 191 ą 11 to 123 ą 9 mg/dl (mean ą SD; 36% mean reduction), and high density lipoprotein, from 62 ą 8 to 38 ą 5 (risk ratio unchanged); (iv) triglyceride, 139 to 96 mg/dl (men) and 78 to 114 mg/dl (women); (v) fasting glucose, 92 to 74 mg/dl; (vi) leukocyte count, 6.7 to 4.7 x 109 cells per liter. We conclude that drastic reductions in cholesterol and blood pressure may be instituted in normal individuals in Western countries by application of a carefully chosen diet and that a low-calorie nutrient-dense regime shows physiologic features in humans similar to those in other animal species.

Post 41

Thursday, March 9, 2006 - 6:02pm

Now, just a couple of posts ago, I showed that the total/HDL ratio is TWICE as predictive of CVD risk as total cholesterol is -- yet you continue on with a spiel regarding total cholesterol.

And just a few posts ago, I pointed out how this has relevance for total cholesterols in the higher range, but not much relevance at all for total cholesterols as low as mine (150 with a total/HDL ratio of 5) or as low as the Tarahumara Indians' (128 with a total/HDL ratio of ~4).

What needs to be kept in mind here is that this ratio is very difficult to change and is largely a function of heredity (and of estrogen in women). Exercise and certain dietary components (e.g., omega-3 fats) can alter it some, but the change is minimal, especially for men. Therefore, if a person's total cholesterol drops, say, from 200 to 150, chances are that his total/HDL ratio will remain more or less the same. Yet his risk of heart disease will drop dramatically. Where the predictive power of the total/HDL ratio is strongest is between two people who have the same total cholesterol, but radically different total/HDL ratios.

For example, suppose that our total cholesterols are both 200, but that your ratio is 3, whereas mine is 5. In that case, it may well be true that I am at greater risk of cardiovascular disease than you are. In other words, at a total cholesterol of 200, you may be able to avoid heart disease, because of your lower ratio, whereas I cannot. But suppose that I lower my total cholesterol to 150, while retaining the same total/HDL ratio. Now, the picture changes, because at this lower total cholesterol, I am at no greater risk than you are. All things being equal (including total/HDL ratios), there will be fewer heart attacks and less cardiovascular disease at cholesterol levels of 150 than at 200, at 200 than at 250; at 250 than at 300, and so on, which is all that the table I cited is saying.

You're not disputing the figures in that table, are you? If you aren't, then you're in agreement with me that lower total cholesterol that is due to diet reduces the risk of heart disease (all things being equal). What the first table shows is that in populations with various mean levels of total cholesterol, the incidence of atherosclerosis is rare to minimal at levels of 120 to 160, but epidemic at levels of 220 to 280. What these epidemiological studies show is that low total cholesterol is related to a very low-fat diet, and high total cholesterol, to a high-fat diet, in which case, there is no other conclusion to draw than that a low-fat diet will almost certainly lower the risk of heart disease in otherwise susceptible people.

More importantly, the study showing this doubling of predictive power [for the total/HDL ratio]-- was based on the Framingham Study.

I have no problem with this, but it doesn't negate what I am saying here.

- Bill

Post 42

Thursday, March 9, 2006 - 10:20pm

Bill, first it was a strict commune (Ornish study), and you told me it wouldn't be so bad. But now you've crossed the line, buddy -- I am not getting into that damn Biosphere bubble just in order to improve my lipoprotein profile!

;-)

You wrote ...
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Their diet, low in calories (average, 1780 kcal/day; 1 kcal = 4.184 kJ), low in fat (10% of calories), and nutrient-dense, conforms to that which in numerous animal experiments has promoted health, retarded aging, and extended maximum life span.
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Well, not actually. As this gem-of-a-study shows, you'll need a teaspoon of sugar -- to help this (caloric restriction) medicine go down ...
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Source of dietary carbohydrate affects life span of Fischer 344 rats independent of caloric restriction. J Gerontol A Biol Sci Med Sci. 1995 May;50(3):B148-54.

Calorie-restricted starch-fed rats had poorer early life survival, and no significant increase in mean life span compared to ad libitum cornstarch-fed animals (726 vs 720 days).

Mean life span of calorie-restricted sucrose-fed rats was significantly greater than that of all other groups (890 +/- 18 days). The differences in survival rates between sucrose- and cornstarch-fed animals could not be attributed to the effects of carbohydrate source on body weight, energy absorption, or on the timing and severity of the pathological lesions normally associated with aging and/or caloric restriction in this species.

These data support the hypothesis that the dietary source of carbohydrate, i.e., sucrose vs cornstarch, can significantly affect life span independently of caloric intake.
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Sure, sugar -- on an ad libitum diet -- killed the rats like flies, but it was a godsend while restricting calories. Couldn't tell you why, though.

Also, in females, that drop in HDL and that increase in triglycerides ... spells trouble ---> small, dense, LDL particles (the atherogenic lipoprotein profile). These nasty little buggers are even more important than the LDL count (a quality vs. quantity issue) ...

In diabetics ...
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Low-density lipoprotein size and subclasses are markers of clinically apparent and non-apparent atherosclerosis in type 2 diabetes. Metabolism. 2005 Feb;54(2):227-34.

The atherogenic lipoprotein phenotype is characterized by an increase in plasma triglycerides, a decrease in high-density lipoprotein (HDL), and the prevalence of small, dense low-density lipoprotein (LDL) particles.

Multivariate analysis of variance of these 10 risk parameters identified LDL particle size as the best risk predictor for the presence of coronary heart disease (P = .002). Smaller LDL particle size was associated with an increase in IMT (P = .03; cut-off >1 mm).

Within the different lipid parameters (total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, apo B, apo A-I, apo C-III, LDL particle size), LDL particle size was most strongly associated with the presence of coronary heart disease (P = .002) and IMT (P = .03).

It is concluded that LDL size is the strongest marker for clinically apparent as well as non-apparent atherosclerosis in diabetes type 2.
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In Turks ...
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Lipids, lipoproteins and apolipoproteins among turks, and impact on coronary heart disease. Anadolu Kardiyol Derg. 2004 Sep;4(3):236-45.

In the setting of a prevalence of metabolic syndrome in 3 out of 8 Turkish adults, Turks have low levels of total cholesterol (mean 185 mg/dl), LDL-cholesterol (mean 116 mg/dl), and HDL-cholesterol (mean 37 and 45 mg/dl in men and women).

The latter is associated with comparatively high concentrations of triglycerides (mean 143 mg/dl) and of apo B (mean 115 mg/dl). This suggests that small, dense LDL particles (pattern B) prevail in this population though studies are missing in this regard. In line with this notion are the high levels of total/HDL cholesterol ratio (mean 5.3 in men, 4.5 in women).

The lipid parameter that has changed strikingly since 1990 are the rising triglycerides, accompanying a similar trend in (abdominal) obesity.

On multivariate analysis, the best independent lipid predictor of coronary heart disease (CHD) risk among Turks is the TC/HDL-C ratio. A 2-unit increment of TC/HDL-C adds an excess of 68% to both the nonfatal and fatal CHD event risk.
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In Sri Lankans ...
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The recent estimates for mortality from cardio and cerebrovascular diseases (CVD) for Sri Lanka--524 deaths per 100,000--is higher than that observed in many Western economies. However, neither an excessive total fat intake nor an increase in the more traditional plasma lipid markers, total and LDL cholesterol (LDL-c) levels may fully explain the increased vulnerability to CVD in this population.

In spite of an adequate total fat intake (25 en%), the relatively low intake of PUFAs in association with a high carbohydrate diet (65 en%), appear to be resulting in similar metabolic outcomes to those of very low fat diets (VLFD, < 15 en% from fat), as reflected by high triglycerides and low HDL levels.

Metabolic abnormalities including elevated postprandial hyperlipidemia, more atherogenic lipoprotein particles, hyperglycemia with resultant hyperinsulinemia and increased oxidative stress are likely to be more relevant in such settings.
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In Caucasian community dwellers ...
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Relationship between low-density lipoprotein subclasses and asymptomatic atherosclerosis in subjects from the Atherosclerosis Risk in Communities (ARIC) Study. Biomarkers. 2004 Mar-Apr;9(2):190-202.

Using gradient gel electrophoresis, large (A), intermediate (I) and small (B) LDL size subclasses were determined in 198 cases with asymptomatic carotid artery atherosclerosis (determined by B-mode ultrasonography) and 318 controls from the Atherosclerosis Risk in Communities (ARIC) Study.

In Caucasians, Subclass B prevalence was 29.1% among cases and 14.8% among controls. The odds ratio (95% confidence interval) for Subclass B rather than Subclass A in Caucasian cases was 2.94 (1.67-5.17); the association remained significant after controlling for age, body mass index, smoking, and either plasma triglycerides or HDL-cholesterol.

A predominance of smaller LDL particles is associated with asymptomatic carotid artery atherosclerosis in Caucasians, through mechanisms that remain to be elucidated.
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In the Japanese ...
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[Role of small dense low-density lipoprotein in coronary artery disease patients with normal plasma cholesterol levels] J Cardiol. 2000 Dec;36(6):371-8.

OBJECTIVES: The relationship between plasma low-density lipoprotein (LDL) cholesterol and the risk of coronary artery disease (CAD) is known, but the other characteristics of LDL, particularly particle size and density, are unclear.

CAD patients had significantly lower high-density lipoprotein (HDL)-cholesterol and apolipoprotein A-I levels (39.3 +/- 8.8 vs 49.8 +/- 12.0, 108.1 +/- 20.6 vs 122.9 +/- 20.1 mg/dl), and higher lipoprotein (a) and apolipoprotein B levels (28.8 +/- 30.4 vs 16.8 +/- 18.8, 96.5 +/- 21.8 vs 80.2 +/- 14.9 mg/dl) than non-CAD subjects, whereas total cholesterol, LDL-cholesterol, triglyceride, remnant-like particle cholesterol and insulin levels were not increased in CAD patients compared with non-CAD subjects.

Stepwise regression analysis revealed that LDL particle size was the most powerful independent determinant of CAD (F value = 20.04, p < 0.0001). Logistic regression analysis revealed that small dense LDL phenotype [relative risk (RR) of 7.0, 95% confidence interval (95% CI) 2.4-20.1], low HDL-cholesterol (RR of 5.6, 95% CI 2.1-15.2), and increased apolipoprotein B (RR of 5.8, 95% CI 1.8-18.5) were independently associated with incidence of CAD.

CONCLUSIONS: High prevalence of small dense LDL is a leading cause of CAD with even normal cholesterol levels.
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In some men ...
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Smallest LDL particles are most strongly related to coronary disease progression in men. Arterioscler Thromb Vasc Biol. 2003 Feb 1;23(2):314-21.

We hypothesized that the association between smaller LDL particles and coronary artery disease (CAD) risk might involve specific LDL subclasses.

The average annual rate in stenosis change was 6-fold more rapid in the fourth quartile of LDL-IVb (>or=5.2%) than in the first quartile (<2.5%, P=0.03). Stepwise multiple regression analysis showed that LDL-IVb was the single best predictor of stenosis change.

CONCLUSIONS: LDL-IVb was the single best lipoprotein predictor of increased stenosis, an unexpected result, given that LDL-IVb represents only a minor fraction of total LDL.
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In some other men ...
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A prospective, population-based study of low density lipoprotein particle size as a risk factor for ischemic heart disease in men. Can J Cardiol. 2001 Aug;17(8):859-65.

BACKGROUND: The current interpretation of the increased risk of ischemic heart disease (IHD) associated with reduced low density lipoprotein (LDL) particle size is based entirely on data derived from relatively small case-control studies, with a lack of evidence from large, prospective, population-based cohort data.

PATIENTS AND METHODS: Analyses were conducted in a cohort of 2057 men who were all initially free of IHD, and who were followed up over a five-year period, during which 108 first IHD events (myocardial infarction, angina or coronary death) were recorded. LDL particle size was measured by nondenaturing gradient gel electrophoresis.

RESULTS: Cox proportional hazards analysis indicated that the relationship between LDL particle size and the risk of future IHD events was not linear. Men with an LDL particle size less than 256.0 A had a significant 2.2-fold increase in the five-year rate of IHD (P<0.001) compared with men having an LDL particle size greater than 256.0 A.

Multivariate and subgroup analyses indicated that small, dense LDL particles predicted the rate of IHD independent of LDL cholesterol, triglycerides, high density lipoprotein (HDL) cholesterol, apolipoprotein B and the total cholesterol to HDL cholesterol ratio.
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In "children, healthy men and women, pre- and postmenopausal women, patients with hypertension, type 2 diabetes, dyslipidemia and patients with positive or negative angiography findings" ...
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The plasma parameter log (TG/HDL-C) as an atherogenic index: correlation with lipoprotein particle size and esterification rate in apoB-lipoprotein-depleted plasma (FER(HDL)). Clin Biochem. 2001 Oct;34(7):583-8.

OBJECTIVES: To evaluate if logarithm of the ratio of plasma concentration of triglycerides to HDL-cholesterol (Log[TG/HDL-C]) correlates with cholesterol esterification rates in apoB-lipoprotein-depleted plasma (FER(HDL)) and lipoprotein particle size.

DESIGN AND METHODS: We analyzed previous data dealing with the parameters related to the FER(HDL) (an indirect measure of lipoprotein particle size).

RESULTS: The analysis revealed a strong positive correlation (r = 0.803) between FER(HDL) and Log(TG/HDL-C). This parameter, which we propose to call "atherogenic index of plasma" (AIP) directly related to the risk of atherosclerosis in the above cohorts. We also confirmed in a cohort of 35 normal subjects a significant inverse correlation of LDL size with FER(HDL) (r = -0.818) and AIP (r = -0.776).
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And in subjects classified as high or low risk (according to NCEP guidelines) ...
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Metabolic disorders contribute to subclinical coronary atherosclerosis in patients with coronary calcification. Am J Cardiol. 2001 Aug 1;88(3):260-4.

A Lp(a) value >25 mg/dl was found significantly more often in the NCEP higher (36.9%) compared with lower (14.3%) risk group (p <0.001). None of the laboratory measurements correlated with the calcium score or calcium score percentile rank, with the exception of a weak correlation of mean LDL peak particle diameter and calcium percentile (r = 0.14, p = 0.02).

Determination of metabolic disorders in addition to LDL cholesterol and HDL cholesterol increased the diagnostic yield from 55.1%, based on NCEP lipid criteria, to 84.1% with the addition of LDL subclass distribution, Lp(a), and total homocysteine.

We conclude that: (1) disorders of LDL subclass distribution and elevated Lp(a) occur frequently in NCEP higher risk patients with subclinical coronary artery disease and are the only identifiable disorders in lower NCEP risk patients; and (2) electron beam tomographic evaluation and determination of LDL subclass distribution and Lp(a) should be considered for incorporation into primary prevention guidelines.
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And the best solution is carb-control (low glycemic load diets) ...

If you have a pot-belly ...
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Effect of a low-glycaemic index--low-fat--high protein diet on the atherogenic metabolic risk profile of abdominally obese men. Br J Nutr. 2001 Nov;86(5):557-68.

It has been suggested that the current dietary recommendations (low-fat-high-carbohydrate diet) may promote the intake of sugar and highly refined starches which could have adverse effects on the metabolic risk profile.

As opposed to the AHA diet, the low-glycaemic index-low-fat-high-protein diet produced a substantial decrease (-35 %) in plasma triacylglycerol levels (2.00 (sd 0.83) v. 1.31 (sd 0.38) mmol/l, P<0.0005), a significant increase (+1.6 %) in LDL peak particle diameter (251 (sd 5) v. 255 (sd 5) A, P<0.02) and marked decreases in plasma insulin levels measured either in the fasting state, over daytime and following a 75 g oral glucose load.

During the pair-fed session, in which subjects were exposed to a diet with the same macronutrient composition as the AHA diet but restricted to the same energy intake as during the low-glycaemic index-low-fat-high-protein diet, there was a trend for a decrease in plasma HDL-cholesterol levels which contributed to the significant increase in cholesterol:HDL-cholesterol ratio noted with this condition.

Finally, favourable changes in the metabolic risk profile noted with the ad libitum consumption of the low-glycaemic index-low-fat-high-protein diet (decreases in triacyglycerols, lack of increase in cholesterol:HDL-cholesterol ratio, increase in LDL particle size) were significantly different from the response of these variables to the AHA phase I diet.

Thus, a low-glycaemic index-low-fat-high-protein content diet may have unique beneficial effects compared with the conventional AHA diet for the treatment of the atherogenic metabolic risk profile of abdominally obese patients.
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... and ...
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Carbohydrate restriction alters lipoprotein metabolism by modifying VLDL, LDL, and HDL subfraction distribution and size in overweight men. J Nutr. 2006 Feb;136(2):384-9.

To determine the effects of carbohydrate restriction (CR) with and without soluble fiber on lipoprotein metabolism, 29 men participated in a 12-wk weight loss intervention.

Plasma LDL cholesterol and triglycerides (TG) were significantly reduced by 8.9 and 38.6%, respectively. Similarly, apolipoproteins C-I (-13.8%), C-III (-21.2%) and E (-12.5%) were significantly lower after the intervention. In contrast plasma HDL-cholesterol concentrations were increased by 12% (P<0.05).

Changes in plasma TG were positively correlated with reductions in large (r=0.615, P<0.01) and medium VLDL particles (r=0.432, P<0.05) and negatively correlated with LDL diameter (r=-0.489, P<0.01).

We conclude that weight loss induced by CR favorably alters the secretion and processing of plasma lipoproteins, rendering VLDL, LDL, and HDL particles associated with decreased risk for atherosclerosis and coronary heart disease.
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... and ...
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Effect of a low-carbohydrate, ketogenic diet program compared to a low-fat diet on fasting lipoprotein subclasses. Int J Cardiol. 2005 Nov 15; [Epub ahead of print]

BACKGROUND: Low-carbohydrate, ketogenic diets (LCKD) are effective for weight loss, but concerns remain regarding cardiovascular risk.

Subjects were randomized to either an LCKD (n=59) and nutritional supplementation (including fish, borage and flaxseed oil), or a low-fat, reduced-calorie diet (LFD, n=60).

Compared with the LFD group, the LCKD group had greater reductions in medium VLDL (p=0.01), small VLDL (p=0.01) and medium LDL (p=0.02), and greater increases in VLDL particle size (p=0.01), large LDL (p=0.004), and HDL particle size (p=0.05).

CONCLUSIONS: The LCKD with nutritional supplementation led to beneficial changes in serum lipid subclasses during weight loss. While the LCKD did not lower total LDL cholesterol, it did result in a shift from small, dense LDL to large, buoyant LDL, which could lower cardiovascular disease risk.
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And in offspring from the initial Framingham cohort ...
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Seven LDL size peaks were identified, with the largest, LDL 1, being found in the density range 1.019-1.033 g/ml; LDL 2 and LDL 3 in d = 1.033-1.038 g/ml; LDL 4 and LDL5 in d = 1.038-1.050 g/ml; and the smallest, LDL 6 and 7, in d = 1.050-1.063 g/ml.

The prevalence of small (< 255 A), dense (d > 1.038 g/ml) LDL particles 4-7 was 33% in men, 5% in premenopausal women, and 14% in postmenopausal women. In agreement with previous reports, small, dense LDL particles were significantly (p < 0.0001) associated with increased triglyceride and apolipoprotein (apo) B levels and decreased HDL cholesterol and apo A-I levels.

In addition, the presence of LDL 3 or 4 as secondary peaks was significantly associated with higher LDL cholesterol levels, while smaller secondary LDL peaks were associated with higher triglyceride levels.

Furthermore, low saturated fat and cholesterol intakes were significantly associated (p < 0.01) with smaller LDL particles.
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Bottom line:
A little less carbs, and a little more saturated fat and cholesterol intake, appears somewhat prudent -- in many cases -- as part of a holistic, risk-reduction plan.

Ed

Post 43

Thursday, March 9, 2006 - 11:30pm

Bill,

You wrote ...
===============
And just a few posts ago, I pointed out how this has relevance for total cholesterols in the higher range, but not much relevance at all for total cholesterols as low as mine (150 with a total/HDL ratio of 5) or as low as the Tarahumara Indians' (128 with a total/HDL ratio of ~4).

What needs to be kept in mind here is ...
===============

No. What needs to be kept in mind here is that high total cholesterol is not necessarily a risk (the 'Cholesterol Hypothesis'). Your argument hinges on high total cholesterol being a risk. If it's not -- then your argument is not sound. And it's not ...

HDL trumps LDL ...
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The independent correlation between high-density lipoprotein cholesterol and subsequent major adverse coronary events. Am Heart J. 2006 Mar;151(3):755.e1-755.e6.

Adjusting for covariates, a 10-mg/dL higher initial HDL-C was associated with an 11% (95% CI 7%-14%) lower risk of coronary events. A 10-mg/dL increase in HDL-C between lipid measurements was associated with a 7% (95% CI 3%-10%) lower risk of events. Neither initial or change in triglycerides nor LDL-C predicted subsequent coronary events.
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Spaniards are chock-full of serum cholesterol -- but get LESS heart attacks ...
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Risk of ischaemic heart disease and acute myocardial infarction in a Spanish population: observational prospective study in a primary-care setting. BMC Public Health. 2006 Feb 17;6(1):38 [Epub ahead of print]

At baseline, 74% of patients were overweight, serum cholesterol over 240 was present in 35% of patients, arterial hypertension in 37%, and basal glucose over 126 in 11%. Thirty-four percent of men and 13% of women were current smokers.

During follow-up, 155 first episodes of coronary disease were detected, which yielded age-adjusted rates of 362 and 191 per 100,000 person-years in men and women respectively. Disease-free survival was associated with all risk factors in univariate analyses.

CONCLUSION: Despite high prevalence of vascular risk factors, incidence rates were lower than those reported for other countries and other periods, but similar to those reported in the few population-based studies in Spain.
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HDL trumping again ...
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Relation between on-treatment increments in serum high-density lipoprotein cholesterol levels and cardiac mortality in patients with coronary heart disease (from the Bezafibrate Infarction Prevention trial). Am J Cardiol. 2006 Feb 15;97(4):466-71. Epub 2005 Dec 22.

In multivariate analysis, the magnitude of on-treatment increment of HDL cholesterol was independently associated with a decreased risk of cardiac death (hazard ratio 1.05, 95% confidence interval 0.74 to 1.47, for tertile 1; hazard ratio 0.73, 95% confidence interval 0.50 to 1.07, for tertile 2; hazard ratio 0.65, 95% confidence interval 0.43 to 0.97, for tertile 3, compared with placebo-allocated patients, p for trend = 0.02).

Analyzing the association with change in HDL cholesterol as a continuous variable showed that the risk of cardiac mortality was decreased by 27% for every 5-mg/dl increase in on-treatment change in HDL cholesterol (p <0.001).
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LDL doesn't predict late life cardiovascular mortality ...
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Low-density lipoprotein cholesterol and mortality in older people. J Am Geriatr Soc. 2005 Dec;53(12):2159-64.

In both sexes, the association between stroke mortality and LDL-C was not significant.

CONCLUSION: This study adds to the uncertainty of the role of elevated levels of LDL-C as a risk factor for mortality in old people.
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Cholesterol drops out of the risk picture -- when examined against the marker for small LDL particles ...
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Non-high-density lipoprotein cholesterol and apolipoprotein B in the prediction of coronary heart disease in men. Circulation. 2005 Nov 29;112(22):3375-83.

BACKGROUND: Apolipoprotein B (apoB) plasma levels reflect the concentration of proatherogenic lipoproteins very low-density lipoprotein and low-density lipoprotein (LDL), whereas non-high-density lipoprotein cholesterol (non-HDL-C) levels reflect the concentration of cholesterol transported by these particles.

When non-HDL-C and LDL-C were mutually adjusted, only non-HDL-C was predictive of CHD. When non-HDL-C and apoB were mutually adjusted, only apoB was predictive; the relative risk was 4.18 (95% CI, 1.30 to 13.49; P trend =0.02) for apoB compared with 0.70 (95% CI, 0.21 to 2.27; P trend =0.72) for non-HDL-C. Triglycerides added significant information to non-HDL-C but not to apoB for CHD risk prediction.

CONCLUSIONS: Although non-HDL-C and apoB were both strong predictors of CHD in this male cohort, more so than LDL-C, the findings support the concept that the plasma concentration of atherogenic lipoprotein particles measured by apoB is more predictive in development of CHD than the cholesterol carried by these particles, measured by non-HDL-C.
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LDLs don't (significantly) predict heart attack ...
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Non-high-density lipoprotein cholesterol versus low-density lipoprotein cholesterol as a risk factor for a first nonfatal myocardial infarction. Am J Cardiol. 2005 Oct 15;96(8):1129-34. Epub 2005 Aug 29.

For LDL cholesterol, the ORs were 1.10 (95% CI 0.67 to 1.81), 0.87 (95% CI 0.52 to 1.46), and 1.45 (95% CI 0.90 to 2.35) (p trend = 0.16). Including HDL cholesterol in the model increased the ORs and strengthened the test for a trend for LDL cholesterol, whereas the ORs were decreased and the test for a trend was weakened for non-HDL cholesterol.

In conclusion, given that non-HDL cholesterol accounts for LDL cholesterol plus other atherogenic particles but does not require a fasting sample, this study suggests that non-HDL cholesterol may be at least as useful as LDL cholesterol to initially screen patients for risk of a first nonfatal myocardial infarction.
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Smoking, Dyslipidemia, and Hypertension -- but no risk from LDLs ...
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Risk factors for acute myocardial infarction among Okinawans. J Nutr Health Aging. 2005 Jul-Aug;9(4):272-6.

PURPOSE: Okinawa is well known as the leading area for longevity and people in Okinawan islands are known to have the lowest risk of ischemic heart disease (IHD).

METHODS: To assess the relative importance of risk factors for IHD among the people in Okinawa, 205 Okinawan patients who had acute myocardial infarction (AMI) and 205 age-and-gender matched control were analyzed.

RESULTS: The most important risk factor of AMI was current cigarette smoking. History of diabetes mellitus and hypertension were also independent risk factors.

Of lipid profile, lower concentrations of serum high density lipoprotein (HDL) cholesterol and higher serum triglyceride (TG) were independent risk factors while, in contrary, serum low density lipoprotein cholesterol and uric acid were not associated with AMI.

CONCLUSIONS: To effectively prevent IHD among Okinawans, smoking cessation and treatment of hypertension, diabetes, and dyslipidemia (high TG and low HDL) are important. However, lowering LDL cholesterol may be not.
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Less cholesterol and twice the cardiovascular mortality ...
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Stroke and coronary heart disease in treated hypertension -- a prospective cohort study over three decades. J Intern Med. 2005 Jun;257(6):496-502.

RESULTS: Treated hypertensive men had their blood pressure reduced with 21/15 mmHg during the first 5 years of the study and mean blood pressure levels were then rather constant. A minor reduction of serum cholesterol was also observed and a significant reduction in the prevalence of smoking.

Treated hypertensive men suffered a substantial increased incidence of cardiovascular complications that escalated during the latter course of the study. Their total incidence of stroke was doubled; they had 50% more myocardial infarctions (MIs); mortality from coronary heart disease was doubled and all cause mortality was increased by a third, compared with nonhypertensive.
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And the only robust life-extender is not a low-fat diet, but just the opposite ...
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Treatment of cholesterol abnormalities. Am Fam Physician. 2005 Mar 15;71(6):1137-42.

Reducing dietary fat can improve total cholesterol levels, but consequent reductions in cardiovascular outcomes are not well documented. The Mediterranean diet is the only dietary intervention associated with a reduction in all-cause mortality.

Treatment with cholesterol-lowering medications decreases the rate of cardiovascular events, but a reduction in all-cause mortality with these agents has been found only in patients with pre-existing coronary heart disease.
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Talking point:
The 'Cholesterol Hypothesis' is bunk.

Ed

(Edited by Ed Thompson on 3/09, 11:32pm)

Post 44

Friday, March 10, 2006 - 12:13am

Ed, all very interesting. But a 185 cholesterol is too high in my book, and the study that quoted a "normal" cholesterol level didn't specify what the authors considered normal. So I couldn't really evaluate that one. I suspect that "normal" was quite a bit higher than what I would consider acceptable, viz., 160 or below.

Just to give you a little information on my own lipid profile, total cholesterol 150; HDL 30; triglycerides 125 if I'm not consistent with my exercise. If I am, they'll drop to 75. Fasting glucose 70, and random glucose about the same, but postprandial glucose can go up to 120, if I don't include some protein with my meal. If I include adequate protein, postprandial glucose doesn't rise much above 90. Given my age (I'll be 66 in a month), my fasting glucose is exceptional, as it tends to rise as people get older. Most of the people I know who are considerably younger than myself don't have fasting glucoses under 90. But I have not been able to alter the total cholesterol/HDL ratio even with vigorous exercise. It stays consistently around 5. So, it looks like I'm stuck with that. One problem I see is with the way LDL is calculated. The formula is total cholesterol minus (HDL + 1/5 triglycerides). So the higher the triglycerides, the lower the LDL, if you use this formula. It's good to have a low LDL, but not necessarily at the expense of high triglycerides, right? So, I think this method of calculation needs to be revised.

Something I'd like to ask you: Pritikin says that overconsumption of dairy products will keep your blood cholesterol deceptively low while still allowing cholesterol to be deposited on artery walls to create blockages. He cites the Masai tribe in Africa as evidence. These people consume a diet that is largely milk and blood from the cattle they raise. Yuk! There is so much vitamin B12 and protein in this diet that the Masai grow very tall on it. As you can imagine, they are consuming more fat and cholesterol than the average American, yet their total cholesterol is only 135, and they have virtually no heart attacks. However, when Masai who've died in accidents are autopsied, it is found that their coronary arteries are even more occluded than the average American's. The reason that they don't have heart attacks is that their coronary arteries are so wide, the arteries don't close all the way, even with the extensive buildup of plaque. Their wide arteries come from all the exercise they get herding cattle from an early age. They do a tremendous amount of walking. But my question is, what do you think is the mechanism that accounts for their total cholesterol's remaining low while their atherosclerosis worsens, and what is it about the milk consumption that causes this curious phenomenon?

There is something else I'd like to discuss that's related to the issue of milk and that concerns its protein content: It turns out that human milk has only 6% of total calories as protein, whereas cows milk is much higher (I think 25%). You'd think that nature would have provided the proper proportion of protein for the baby and the calf, such that a baby is better off consuming human milk, and the calf, better of consuming cows milk. Yet, parents feed their kids cows milk. The 6% protein seems low especially for this, the child's most rapid period of growth, but it must be enough; otherwise, nature would not have set it there. And if it's enough for that exceedingly rapid stage of growth, why isn't it enough for less rapid periods of growth or for fully grown adults? And since fat should be no more than 10% of total calories to ensure against heart disease, this means that the vast majority of one's calories should come from carbohydrate -- complex carbohydrate, to be sure, but carbohydrate nonetheless.

Another interesting statistic, although I'm not sure how relevant it is to human beings, is this: When the protein in rodent feed is cut from 26 percent to 4 percent, both rats and mice live significantly longer and healthier lives. Or course, you can argue that rodents are not human beings, but in several of the studies you've cited, rodents are used as "guinea pigs". Yet you've rejected my reference to primates as evidence in studies of dietary modification. I'd say that primates are a lot closer to human beings than rodents are.

- Bill

Post 45

Friday, March 10, 2006 - 12:30am

Ed, you write

And the only robust life-extender is not a low-fat diet, but just the opposite ...
===============
Treatment of cholesterol abnormalities. Am Fam Physician. 2005 Mar 15;71(6):1137-42.

Reducing dietary fat can improve total cholesterol levels, but consequent reductions in cardiovascular outcomes are not well documented. The Mediterranean diet is the only dietary intervention associated with a reduction in all-cause mortality.

Treatment with cholesterol-lowering medications decreases the rate of cardiovascular events, but a reduction in all-cause mortality with these agents has been found only in patients with pre-existing coronary heart disease.
===============

Talking point:
The 'Cholesterol Hypothesis' is bunk.

Okay, then how do you explain the epidemiological studies I've cited, which correlate low cholesterol with absence of atherosclerosis and heart disease, and higher cholesterol with their presence? Populations with very low cholesterol due to very low-fat diets tend to have little if any heart disease; populations with very high cholesterol due to high-fat diets tend to have epidemic levels of heart disease. Yes, the Mediterranean diet and the French Paradox are noteworthy exceptions, but we know the mechanism here. It's the red wine and the resveratrol which reduces inflammation, and the olive oil, which is largely monosaturated. Otherwise, populations on high-fat diets tend to have high cholesterol levels and increased heart disease, whereas populations on low-fat diets and low cholesterols tend to have the opposite. Again, the Masai are an exception as far as their low serum cholesterol is concerned, but they consume a high-fat, high-cholesterol diet, and show the effects with extensive atherosclerosis.

- Bill

Post 46

Friday, March 10, 2006 - 3:57am

Bill,

You wrote ...
===========
Pritikin says that overconsumption of dairy products will keep your blood cholesterol deceptively low while still allowing cholesterol to be deposited on artery walls to create blockages. He cites the Masai tribe in Africa as evidence.

As you can imagine, they are consuming more fat and cholesterol than the average American, yet their total cholesterol is only 135, and they have virtually no heart attacks. However, when Masai who've died in accidents are autopsied, it is found that their coronary arteries are even more occluded than the average American's.

The reason that they don't have heart attacks is that their coronary arteries are so wide, the arteries don't close all the way, even with the extensive buildup of plaque.

But my question is, what do you think is the mechanism that accounts for their total cholesterol's remaining low while their atherosclerosis worsens, and what is it about the milk consumption that causes this curious phenomenon?
===========

It's the potassium. Potassium (from milk) keeps arteries dilated. Fruits & veggies (because of their potassium) would've been just as protective as milk here. Potassium content is a nutritional deal-breaker.

You wrote ...
===========
The 6% protein seems low especially for this, the child's most rapid period of growth, but it must be enough; otherwise, nature would not have set it there. And if it's enough for that exceedingly rapid stage of growth, why isn't it enough for less rapid periods of growth or for fully grown adults?
===========

Percentages lie here. Infants require a lot of calories (to double their body weight within 6 months). On so many body-weight adjusted calories -- the 'percentage protein' masks their tripling of adult protein needs (per kg body weight). And it throws off the requirements of adults -- when expressed as a percentage of body weight ...

===========
Higher versus lower protein intake in formula-fed low birth weight infants. Cochrane Database Syst Rev. 2006 Jan 25;(1):CD003959.

MAIN RESULTS: The literature search identified 37 studies, of which five met all the inclusion criteria. All five studies compared low (< 3.0 g/kg/day) to high protein intakes (=> 3.0 g/kg/day but < 4.0 g/kg/day).

The overall analysis revealed an improved weight gain (WMD 2.36 g/kg/day, 95% CI 1.31, 3.40) and higher nitrogen accretion (WMD 143.7 mg/kg/day, 95% CI 128.7, 158.8) in infants receiving formula with higher protein content while other nutrients were kept constant.

One study (Goldman 1969) in the post-facto analysis documented a significantly increased incidence of low IQ scores, below 90, in infants of birth weight less than 1300 grams who received a very high protein intake (6 to 7.2 g/kg/day).

AUTHORS' CONCLUSIONS: This systematic review suggests that higher protein intake (=> 3.0 g/kg/day but < 4.0 g/kg/day) from formula accelerates weight gain. Based on increased nitrogen accretion rates, this most likely indicates an increase in lean body mass. Although accelerated weight gain is considered to be a positive effect, increase in other outcome measures examined may represent a negative or ambivalent effect.
===========

Almost 3 times the accepted protein needs (when directly assessed) ...
===========
Daily requirement for and splanchnic uptake of leucine in healthy adult Indians. Am J Clin Nutr. 2001 Dec;74(6):747-55.

BACKGROUND: The 1985 FAO/WHO/UNU requirement for leucine is too low according to tracer-derived estimates of leucine oxidation and balance in adults from developed regions.

RESULTS: Mean 24-h leucine oxidation rates were 29.8, 30.6, 33.6, and 39.3 mg x kg(-1) x d(-1) at leucine intakes of 14, 22, 30, and 40 mg x kg(-1) x d(-1), respectively; daily leucine balances were -16.5, -9.0, -3.3, and 0.5 mg x kg(-1) x d(-1), respectively.

Mixed-models linear regression of balance against leucine intake resulted in a zero balance at a leucine intake of 37.3 mg x kg(-1) x d(-1). Nitrogen balances were -12.7, -17.9, -3.9, and 1.0 mg x kg(-1) x d(-1) at leucine intakes of 14, 22, 30, and 40 mg x kg(-1) x d(-1).

Regression of nitrogen balance against intake resulted in a zero balance at a leucine intake of 37.6 mg x kg(-1) x d(-1). The first-pass splanchnic uptake of leucine was 45.7% and 33.9% in the fasted and fed periods, respectively.

CONCLUSION: A tentative mean leucine requirement of 40 mg x kg(-1) x d(-1) is proposed for healthy Indian adults, as it is for Western subjects.
===========

Almost 3 times the accepted protein needs (when directly assessed) ...
===========
Lysine requirements of chronically undernourished adult Indian men, measured by a 24-h indicator amino acid oxidation and balance technique. Am J Clin Nutr. 2003 Jan;77(1):101-8.

BACKGROUND: In earlier studies with well-nourished subjects that used a 24-h indicator amino acid oxidation or balance approach, we concluded that the 1985 FAO/WHO/UNU requirement for lysine (12 mg x kg(-1) x d(-1)) was inadequate for healthy South Asian subjects and proposed a tentative requirement of 30 mg x kg(-1) x d(-1).

RESULTS: A breakpoint was not identified in the lysine intake-leucine oxidation or balance response over the range of intakes studied. Mixed-models linear regression analysis indicated a mean requirement of 44 mg lysine x kg(-1) x d(-1) (95% CI: 36, 63) for the lysine intake-leucine balance relation.

CONCLUSIONS: The mean lysine requirement in chronically undernourished men is estimated to be higher than the value of 30 mg x kg(-1) x d(-1) proposed for well-nourished individuals.
===========

Ed

Post 47

Friday, March 10, 2006 - 12:21pm

Bill,

You wrote ...
================
Okay, then how do you explain the epidemiological studies I've cited, which correlate low cholesterol with absence of atherosclerosis and heart disease, and higher cholesterol with their presence?
================

The explanation is that cholesterol -- for countries besides France, Greece, and Spain -- inversely covaried with plant-based polyphenol intake (e.g. resveratrol). It's a plant deficiency. Folks in other countries -- who had had high cholesterol -- also ate few fruits and veggies.

It was always about the fruits & veggies -- and never about the saturated fat or cholesterol intake. However, saturated fat BECAME a risk once we started eating a high glycemic load diet. The combination is deadly -- though the components aren't. Here's some research, backing this up ...

Plant-based polyphenols as deal-breakers ...
================
Polyphenols as potential therapeutical agents against cardiovascular diseases. Pharmacol Rep. 2005;57 Suppl:97-107.

Increasing evidence suggests that polyphenols from fruits, vegetables and beverages such as wine and tea may exert protective effects on the cardiovascular system. Indeed, research in the field of polyphenols points out their antioxidant and free radical scavenging properties, leading to lower low-density lipoprotein (LDL) oxidation and platelet aggregation.

These compounds are also able to modulate the generation of nitric oxide (NO) from vascular endothelium and to interfere with the mechanisms leading to inflammation and endothelial apoptosis, contributing to the prevention of the endothelial dysfunction, known to play a central role in the pathogenesis of cardiovascular diseases.
================

90% of all heart attacks ...
================
[Interheart: nine risk factors predict nine out of ten myocardial infarctions] Rev Med Liege. 2004 Nov;59(11):676-9.

INTERHEART is a standardised case-control study of acute myocardial infarction in 52 countries representing every inhabited continent. 15152 cases and 14820 controls were enrolled. Collectively, 9 factors accounted for 90% of myocardial infarctions in men and 94% in women.

These factors were 6 risk factors (dyslipidaemia characterized by high apoB/apoA1 ratio, smoking, hypertension, diabetes mellitus, abdominal obesity and stressful psychosocial factors) and 3 protective factors (daily consumption of fruits and vegetables, regular alcohol consumption, and regular physical activity).

These findings suggest that interventions targeting these 9 factors have the potential to prevent most premature cases of myocardial infarction and that these strategies should be implemented worldwide.
================

Summary: To reduce your risk, work to fix these 9 things ...

1) proatherogenic dyslipidemia
2) smoking
3) hypertension
4) diabetes
5) belly fat
6) stress
7) fruits & veggies
8) moderate alcohol
9) exercise

Number 7 takes care of numbers 1, 3, 4, and 5 -- eat 2-4 servings of fruit, and 5 servings of fibrous veggies; and the other problems will just disappear. Numbers 2, 8, and 9 take care of number 6. The missing 10th item -- required to eradicate all heart disease from planet Earth -- would be long-chain omega-3 fatty acids (such as from fish, or fish oil capsules).

81 wholes eggs per week? No problem ...
================
Dietary intake, anthropometric measurements, and blood lipid values in weight training athletes (body builders). Int J Sports Med. 1986 Dec;7(6):342-6.

The high-cholesterol intake was due to a high egg intake, which varied from 0 to 81 eggs per week. Although those athletes with a high egg intake consumed significantly more fat and cholesterol than those with a low egg intake, plasma total cholesterol levels (mean = 182.9 +/- 25.7) did not differ over the range of egg intakes.

Plasma HDL-cholesterol levels were higher and plasma triacylglycerol levels were lower at a high egg intake compared with that at a low egg intake.
================

3 steps halve your risk ...
================
Risk factors for non-fatal acute myocardial infarction in Italian women. Prev Med. 2004 Jul;39(1):128-34.

Inverse association was found with fish (OR 0.7 for >1 portion/week), vegetables (0.7 for > or = 10 portions/week), and fruit (OR 0.6 for > or = 14 portions/week), while meat, whole-grain, and diary products were unrelated. Smoking effect was stronger in combination with diabetes (OR 27.7), hypertension (OR 15.7), hyperlipidemia (OR 6.3), family history of AMI (OR 8.7), and heavy coffee drinking (OR 5.7).

CONCLUSIONS: The strongest risk factor for AMI was smoking, responsible of about 37% of cases, followed by diabetes, hypertension, hyperlipidemia, family history of AMI. Avoidance of smoking and increasing fish, vegetables, and fruit would reduce AMI risk of about 50%.
================

Half of the story:
1) smoking
2) fish
3) fruits & veggies

Just a single serving of green leafy veggies -- drops risk by 23% ...
================
The effect of fruit and vegetable intake on risk for coronary heart disease. Ann Intern Med. 2001 Jun 19;134(12):1106-14.

PARTICIPANTS: 84 251 women 34 to 59 years of age who were followed for 14 years and 42 148 men 40 to 75 years who were followed for 8 years. All were free of diagnosed cardiovascular disease, cancer, and diabetes at baseline.

Each 1-serving/d increase in intake of fruits or vegetables was associated with a 4% lower risk for coronary heart disease (relative risk, 0.96 [CI, 0.94 to 0.99]; P = 0.01, test for trend).

Green leafy vegetables (relative risk with 1-serving/d increase, 0.77 [CI, 0.64 to 0.93]), and vitamin C-rich fruits and vegetables (relative risk with 1-serving/d increase, 0.94 [CI, 0.88 to 0.99]) contributed most to the apparent protective effect of total fruit and vegetable intake.
================

Bottom line:
Heart disease is a sugar and smoking toxicity-, and an exercise, plant, and fish deficiency-disease -- and that's all that it is.

Ed

Post 48

Friday, March 10, 2006 - 9:25pm

I wrote,

Pritikin says that overconsumption of dairy products will keep your blood cholesterol deceptively low while still allowing cholesterol to be deposited on artery walls to create blockages. He cites the Masai tribe in Africa as evidence.... As you can imagine, they are consuming more fat and cholesterol than the average American, yet their total cholesterol is only 135, and they have virtually no heart attacks. However, when Masai who've died in accidents are autopsied, it is found that their coronary arteries are even more occluded than the average American's. The reason that they don't have heart attacks is that their coronary arteries are so wide, the arteries don't close all the way, even with the extensive buildup of plaque.... But my question is, what do you think is the mechanism that accounts for their total cholesterol's remaining low while their atherosclerosis worsens, and what is it about the milk consumption that causes this curious phenomenon?

Ed replied,

It's the potassium. Potassium (from milk) keeps arteries dilated. Fruits & veggies (because of their potassium) would've been just as protective as milk here. Potassium content is a nutritional deal-breaker.

Ed, I think you're missing something here. The reason that the atherosclerosis didn't create blockages was not because their coronary arteries were dilated; it's because they were actually wider, which was discovered on autopsy. The larger diameter was due to their extensive exercise, which begins in early childhood. But you neglected to answer my primary question which was what caused their serum cholesterol to remain so low, despite the high degree of atherosclerosis? Pritikin theorizes that there is something in milk that causes the cholesterol to be directly deposited in the artery walls instead of circulating in the blood, which accounts for their low serum cholesterol. I was wondering if you had heard of this or knew anything about it.

- Bill

Post 49

Friday, March 10, 2006 - 10:20pm

Ed, you wrote,

What needs to be kept in mind here is that high total cholesterol is not necessarily a risk (the 'Cholesterol Hypothesis'). Your argument hinges on high total cholesterol being a risk. If it's not -- then your argument is not sound. And it's not ...

Look, I agree that what's more predictive is LDL and the ratio of total cholesterol to HDL. I'm not disagreeing with you here. Let's define "risk." "Risk" is a probability concept; probability refers to incomplete knowledge. An event is more or less probable when you don't know all of the relevant factors bearing on its occurrence. The figures I cited show a greater correlation of high total cholesterol with heart disease than low total cholesterol, absent any knowledge of LDL and of the ratio of total cholesterol to HDL. Obviously, if you know these other numbers, then you can rule out those high cholesterols that are accompanied by low LDL and a high total to HDL ratio. But if you took all of the high cholesterols, there would be a far greater percentage of heart disease cases among them than among very low total cholesterols. So, if one has a high total cholesterol and one's LDL or total to HDL ratio is unknown, one will be at greater "risk," meaning that the "probability" of heart disease will be greater. But that probability can be reduced or eliminated with additional knowledge about one's LDL and total to HDL ratio.

Also, I asked Ed,

Okay, then how do you explain the epidemiological studies I've cited, which correlate low cholesterol with absence of atherosclerosis and heart disease, and higher cholesterol with their presence?

He replied,

The explanation is that cholesterol -- for countries besides France, Greece, and Spain -- inversely covaried with plant-based polyphenol intake (e.g. resveratrol). It's a plant deficiency. Folks in other countries -- who had had high cholesterol -- also ate few fruits and veggies.

Then you agree with me that there is a correlation between heart disease and high cholesterol; you just disagree as to what causes the high cholesterol. You're saying that it's the absence of plant-based polyphenol intake, whereas I'm saying that it's a high-saturated fat diet. I think the evidence is on my side here. Both Pritikin and McDougall stress an increase in starch; they do not emphasize fruits and vegetables. In fact, both advise against too much fruit, as it can raise triglycerides. McDougall says no more than two pieces a day, and Pritikin, no more than three, and very little dried fruit. What they do stress is whole grains, brown rice, oatmeal, potatoes, whole wheat spaghetti, whole wheat bread, and various legumes. And they get dramatic reductions in cholesterol and in LDL cholesterol on that diet. I hate to cite myself as an example, but I've always eaten a lot of fruit and veggies, because I've always thought they were good for me. I did so when I was eating a high-meat, high-fat diet, and during that time, my cholesterol was very high - 250 - at the young age of 30. At the age of 45, I switched to the Pritikin diet, but I didn't increase my plant-based polyphenol intake; I increased my starch; in fact, I even cut back on some of the veggies. Yet my cholesterol fell to 115, and my blood pressure dropped from 134/90 to 100/70. I'm not denying the anti-inflammatory properties of polyphenols, but I think this micro-component of the diet is over-rated. What's important are the macro-components - a dramatic reduction in fat of all kinds, and an emphasis on starch.

It was always about the fruits & veggies -- and never about the saturated fat or cholesterol intake.

Not true.

However, saturated fat BECAME a risk once we started eating a high glycemic load diet. The combination is deadly -- though the components aren't. Here's some research, backing this up ...

I'll agree with you that fat and sugar are a deadly combination, which is why Pritikin, McDougall and Ornish all emphasize a reduction not only in fat but also in sugar. In fact, Pritikin bans all sugar from his diet -- no honey, molasses, maple syrup, white sugar, brown sugar, corn syrup, you name it. He doesn't even allow dried fruit, except in very minute quantities.

Each starch, Ed!

- Bill

Post 50

Saturday, March 11, 2006 - 6:10pm

Bill,

You wrote ...
===================
But you neglected to answer my primary question which was what caused their serum cholesterol to remain so low, despite the high degree of atherosclerosis?
===================
Um, sorry! Anyway, I finally looked for the answer and -- like 99% of the time (with a super-sleuth, such as myself) -- I found it ...

Cow casein crams cholesterol 'cross carotid artery ...
===================
A casein variant in cow's milk is atherogenic. Atherosclerosis. 2003 Sep;170(1):13-9.

Casein is a major protein in cow's milk that occurs in several variant forms, two of which are beta-casein A1 and beta-casein A2. The levels of these two proteins vary considerably in milk dependent on the breed of cow, and epidemiology studies suggest that there is a relationship between their consumption and the degree of atherosclerosis.

Rabbits fed beta-casein A1 had a higher percent surface area of aorta covered by fatty streaks than those fed beta-casein A2 (5.2+/-0.81 vs 1.1+/-0.39, P<0.05) and the thickness of the fatty streak lesions in the aortic arch was significantly higher (0.04+/-0.010 vs 0.00, P<0.05).

Similarly, the intima to media ratio (I:M) of the balloon injured carotid arteries in A1 fed animals (0.77+/-0.07) was higher than in those that consumed A2 (0.57+/-0.04) or whey (0.58+/-0.04), but this did not reach significance. In the presence of 0.5% dietary cholesterol, the thickness of the aortic arch lesions was higher (P<0.05) in 5, 10 and 20% casein A1 fed animals compared with their A2 counterparts, while other parameters were not significantly different.

It is concluded that beta-casein A1 is atherogenic compared with beta-casein A2.
===================

Anything else you wanna' know??

;-)

Ed

Post 51

Saturday, March 11, 2006 - 6:24pm

Bill,

================
[Ed] replied,

The explanation is that cholesterol -- for countries besides France, Greece, and Spain -- inversely covaried with plant-based polyphenol intake (e.g. resveratrol). It's a plant deficiency. Folks in other countries -- who had had high cholesterol -- also ate few fruits and veggies.

Post 52

Saturday, March 11, 2006 - 7:00pm

Bill,

You quote the madmen ...
====================
What they do stress is whole grains, brown rice, oatmeal, potatoes, whole wheat spaghetti, whole wheat bread, and various legumes.
====================

These are some of the least nutritious foods (per 100 calories) ...

vitamin A
============
soybeans- 0.7
broadbeans- 2
yellow corn- 20

broccoli- 478
tuna- 1364
spinach- 3509

vitamin C
============
whole wheat bread- 0.0
broadbeans- 0.5
long-grain rice- 0.7
soybeans- 1
yellow corn- 6

asparagus- 82
broccoli- 213
cauliflower- 226

vitamin B-1
============
soybeans- 0.1
broadbeans- 0.1
long-grain rice- 0.1
whole wheat bread- 0.1
yellow corn- 0.2

asparagus- 0.4
spinach- 0.4
turkey- 0.4

vitamin B-2
============
long-grain rice- 0.01
yellow corn- 0.07
whole wheat bread- 0.08
broadbeans- 0.1
soybeans- 0.2

asparagus- 0.5
broccoli- 0.7
spinach- 1

vitamin B-3
============
soybeans- 0.2
broadbeans- 0.6
yellow corn- 1
long-grain rice- 2
whole wheat bread- 2

spinach- 5
tuna- 6
salmon- 7

vitamin B-6
============
long-grain rice- 0.01
yellow corn- 0.06
whole wheat bread- 0.08
broadbeans- 0.1
soybeans- 0.1

asparagus- 0.6
broccoli- 0.7
cauliflower- 0.9

Folic acid
============
long-grain rice- 2
whole wheat bread- 23
soybeans- 31
yellow corn- 43
broadbeans- 95

broccoli- 234
asparagus- 400
spinach- 624

Potassium
============
long-grain rice- 27
whole wheat bread- 72
yellow corn- 229
broadbeans- 245
soybeans- 297

asparagus- 1268
cauliflower- 1333
spinach- 1995

Magnesium
============
long-grain rice- 7
yellow corn- 29
whole wheat bread- 38
broadbeans- 39
soybeans- 50

asparagus- 70
broccoli- 204
spinach- 376

Zinc
============
long-grain rice- 0.2
yellow corn- 0.4
whole wheat bread- 0.7
soybeans- 0.7
broadbeans- 1

T-bone steak- 2
asparagus- 2
spinach- 3

As far as nutrition goes, grains don't hold a candle to a good steak and salad -- there's just no comparison.

Ed

Post 53

Sunday, March 12, 2006 - 12:36pm

NEWS FLASH! Ed, I'm not saying that you should eat ONLY whole grains. I'm saying that to a large extent, you should substitute them for the pound of meat that you advocate eating on daily basis. Of course, you need these other vegetables and fruits for adequate vitamin and mineral intake.

Thanks for the additional explanation. I now see what you're saying, viz., that high cholesterol by itself is not correlated with heart disease, but only high cholesterol in the absence of adequate plant intake. Gotcha! But I still don't think that all the plant food in the world can offset the cholesterol you're producing from the saturated fat in a pound of meat. Nor do I think that the diet your advocating could even come close to the Pritikin diet in terms of atherosclerotic regression. Show me the studies in which your kind of diet caused patients with coronary artery disease to show regression. And you have my permission to include other lifestyle changes, such as exercise and stress reduction techniques. :-)

Thanks also for the info on casein and atherosclerosis. I've stopped all the (non-fat) cheese I've been eating; that stuff is almost pure casein, although I must say that I've had my carotid arteries checked and that I have practically no plaque buildup, which I attribute to the (quasi)-Pritikin diet that I've been following for the last 20 years.

Ed, you're "madmen" reference to Pritikin, McDougall and Ornish is hitting below the belt, don't you think?! It makes me wonder about your objectivity. 'Course, I've wondered it about anyway! Not that you're a madman or anything! ;-)

- Bill

Post 54

Sunday, March 12, 2006 - 4:50pm

Bill,

I broke down and bought The Pritikin Program for Diet & Exercise (know your enemy). I'm 4 pages into it and already disgusted. After ole' Nate tells you about how many movie stars were already on his plan [which is dubious 'name dropping'], he writes this piece of crap ...

===============
Only a foolish or unmotivated person would voluntarily abandon its enormous rewards. -- [argument from intimidation]
===============

And this kind of "madman"-style writing is present on every page (so far). As for studies showing a slowing of atherosclerotic progression ... they're coming. It's a pleasure to do ideological battle with you, Bill.

Ed

Post 55

Sunday, March 12, 2006 - 5:23pm

Bill,

Here's data on atherosclerotic progression ...
================
Dietary fats, carbohydrate, and progression of coronary atherosclerosis in postmenopausal women. Am J Clin Nutr. 2004 Nov;80(5):1175-84.

DESIGN: Quantitative coronary angiography was performed at baseline and after a mean follow-up of 3.1 y in 2243 coronary segments in 235 postmenopausal women with established coronary heart disease.

In multivariate analyses, a higher saturated fat intake was associated with a smaller decline in mean minimal coronary diameter (P = 0.001) and less progression of coronary stenosis (P = 0.002) during follow-up. Compared with a 0.22-mm decline in the lowest quartile of intake, there was a 0.10-mm decline in the second quartile (P = 0.002), a 0.07-mm decline in the third quartile (P = 0.002), and no decline in the fourth quartile (P < 0.001); P for trend = 0.001.

This inverse association was more pronounced among women with lower monounsaturated fat (P for interaction = 0.04) and higher carbohydrate (P for interaction = 0.004) intakes and possibly lower total fat intake (P for interaction = 0.09).

Monounsaturated and total fat intakes were not associated with progression. CONCLUSIONS: In postmenopausal women with relatively low total fat intake, a greater saturated fat intake is associated with less progression of coronary atherosclerosis, whereas carbohydrate intake is associated with a greater progression.
================

And here's another way (by way of diabetes) that milk could get you all plaqued up in the arteries ...
================
Avoiding milk is associated with a reduced risk of insulin resistance and the metabolic syndrome: findings from the British Women's Heart and Health Study. Diabet Med. 2005 Jun;22(6):808-11.

The age-adjusted odds ratio for the metabolic syndrome comparing non-milk drinkers with drinkers was 0.55 (0.33, 0.94), which did not attenuate with adjustment for potential confounders. Diabetes was less common in non-milk drinkers. CONCLUSION: Individuals who do not drink milk may be protected against insulin resistance and the metabolic syndrome.
================

And here's my 'punch-line' ...
================
Ischaemic heart disease, Type 1 diabetes, and cow milk A1 beta-casein. N Z Med J. 2003 Jan 24;116(1168):U295.

AIM: To test the correlation of per capita A1 beta-casein (A1/capita) and milk protein with: 1) ischaemic heart disease (IHD) mortality; 2) Type 1 (insulin-dependent) diabetes mellitus (DM-1) incidence.

CONCLUSIONS: Cow A1 beta-casein per capita supply in milk and cream (A1/capita) was significantly and positively correlated with IHD in 20 affluent countries five years later over a 20-year period--providing an alternative hypothesis to explain the high IHD mortality rates in northern compared to southern Europe.

For DM-1, this study confirms Elliott's 1999 correlation on 10 countries for A1/capita,1 but not for B beta-casein/capita. Surveys of A1 beta-casein consumption in two-year-old Nordic children, and some casein animal feeding experiments, confirm the A1/capita and milk protein/capita correlations.

They raise the possibility that intensive dairy cattle breeding may have emphasised a genetic variant in milk with adverse effects in humans. Further animal research and clinical trials would be needed to compare disease risks of A1-free versus 'ordinary' milk.
================

Ed

Post 56

Sunday, March 12, 2006 - 7:10pm

More on 'progression' (ie. high-carbs and low-meat/fish -- speed up atherosclerotic progression) ...

2+ servings of fish per week protects diabetics from heart disease ...
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Fish intake is associated with a reduced progression of coronary artery atherosclerosis in postmenopausal women with coronary artery disease. Am J Clin Nutr. 2004 Sep;80(3):626-32.

RESULTS: Compared with lower fish intakes, consumption of > or =2 servings of fish or > or =1 serving of tuna or dark fish per week was associated with smaller increases in the percentage of stenosis (4.54 +/- 1.37% compared with -0.06 +/- 1.59% and 5.12 +/- 1.48% compared with 0.35 +/- 1.47%, respectively; P < 0.05 for both) in diabetic women after adjustments for age, cardiovascular disease risk factors, and dietary intakes of fatty acids, cholesterol, fiber, and alcohol.

These associations were not significant in nondiabetic women. Higher fish consumption was also associated with smaller decreases in minimum coronary artery diameter and fewer new lesions.

CONCLUSIONS: Consumption of fish is associated with a significantly reduced progression of coronary artery atherosclerosis in women with coronary artery disease.
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A high Glycemic Load 'causes' heart disease ...
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A prospective study of dietary glycemic load, carbohydrate intake, and risk of coronary heart disease in US women. Am J Clin Nutr. 2000 Jun;71(6):1455-61.

DESIGN: A cohort of 75521 women aged 38-63 y with no previous diagnosis of diabetes mellitus, myocardial infarction, angina, stroke, or other cardiovascular diseases in 1984 was followed for 10 y. Each participant's dietary glycemic load was calculated as a function of glycemic index, carbohydrate content, and frequency of intake of individual foods reported on a validated food-frequency questionnaire at baseline. All dietary variables were updated in 1986 and 1990.

RESULTS: During 10 y of follow-up (729472 person-years), 761 cases of CHD (208 fatal and 553 nonfatal) were documented. Dietary glycemic load was directly associated with risk of CHD after adjustment for age, smoking status, total energy intake, and other coronary disease risk factors.

The relative risks from the lowest to highest quintiles of glycemic load were 1.00, 1.01, 1. 25, 1.51, and 1.98 (95% CI: 1.41, 2.77 for the highest quintile; P for trend < 0.0001). Carbohydrate classified by glycemic index, as opposed to its traditional classification as either simple or complex, was a better predictor of CHD risk.
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No association of cholesterol and heart disease (when controlled for fiber -- read: plant -- intake) ...
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Dietary fat and risk of coronary heart disease in men: cohort follow up study in the United States. BMJ. 1996 Jul 13;313(7049):84-90.

SUBJECTS--43 757 health professionals aged 40 to 75 years free of diagnosed cardiovascular disease or diabetes in 1986.

Positive associations between intake of cholesterol and risk of coronary heart disease were similarly attenuated after adjustment for fibre intake.

Intake of linolenic acid [an omega-3 fatty acid] was inversely associated with risk of myocardial infarction; this association became significant only after adjustment for non-dietary risk factors and was strengthened after adjustment for total fat intake (relative risk 0.41 for a 1% increase in energy, P for trend < 0.01).

CONCLUSIONS--These data do not support the strong association between intake of saturated fat and risk of coronary heart disease suggested by international comparisons.
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Fats: Quality more important than quantity ...
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Dietary fat and risk of coronary heart disease: possible effect modification by gender and age. Am J Epidemiol. 2004 Jul 15;160(2):141-9.

No overall association between saturated fat and coronary heart disease was found among men.

In conclusion, the present study suggests that coronary heart disease risk relates to both the quantity and the quality of dietary fats.
====================

Saturated fats keep you alive ...
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Dietary fat intake and early mortality patterns--data from The Malmo Diet and Cancer Study. J Intern Med. 2005 Aug;258(2):153-65.

RESULTS: Women in the fourth quartile of total fat intake had a significantly higher RR of cancer mortality (RR 1.46; CI 1.04-2.04). A significant downwards trend was observed for cardiovascular mortality amongst men from the first to the fourth quartile (P=0.028). No deteriorating effects of high saturated fat intake were observed for either sex for any cause of death. Beneficial effects of a relatively high intake of unsaturated fats were not uniform.

CONCLUSIONS: With the exception of cancer mortality for women, individuals receiving more than 30% of their total daily energy from fat and more than 10% from saturated fat, did not have increased mortality. Current dietary guidelines concerning fat intake are thus generally not supported by our observational results.
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Carbs kill ...
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Effects of protein, monounsaturated fat, and carbohydrate intake on blood pressure and serum lipids: results of the OmniHeart randomized trial. JAMA. 2005 Nov 16;294(19):2455-64.

Compared with the carbohydrate diet, the unsaturated fat diet decreased systolic blood pressure by 1.3 mm Hg (P = .005) and by 2.9 mm Hg among those with hypertension (P = .02), had no significant effect on low-density lipoprotein cholesterol, increased high-density lipoprotein cholesterol by 1.1 mg/dL (0.03 mmol/L; P = .03), and lowered triglycerides by 9.6 mg/dL (0.11 mmol/L; P = .02).

Compared with the carbohydrate diet, estimated 10-year coronary heart disease risk was lower and similar on the protein and unsaturated fat diets.

CONCLUSION: In the setting of a healthful diet, partial substitution of carbohydrate with either protein or monounsaturated fat can further lower blood pressure, improve lipid levels, and reduce estimated cardiovascular risk.
====================

The bane of carbs ...
====================
Effects of protein, monounsaturated fat, and carbohydrate intake on blood pressure and serum lipids: results of the OmniHeart randomized trial. JAMA. 2005 Nov 16;294(19):2455-64.

RESULTS: Blood pressure, low-density lipoprotein cholesterol, and estimated coronary heart disease risk were lower on each diet compared with baseline. Compared with the carbohydrate diet, the protein diet further decreased mean systolic blood pressure by 1.4 mm Hg (P = .002) and by 3.5 mm Hg (P = .006) among those with hypertension and decreased low-density lipoprotein cholesterol by 3.3 mg/dL (0.09 mmol/L; P = .01), high-density lipoprotein cholesterol by 1.3 mg/dL (0.03 mmol/L; P = .02), and triglycerides by 15.7 mg/dL (0.18 mmol/L; P<.001).

Compared with the carbohydrate diet, the unsaturated fat diet decreased systolic blood pressure by 1.3 mm Hg (P = .005) and by 2.9 mm Hg among those with hypertension (P = .02), had no significant effect on low-density lipoprotein cholesterol, increased high-density lipoprotein cholesterol by 1.1 mg/dL (0.03 mmol/L; P = .03), and lowered triglycerides by 9.6 mg/dL (0.11 mmol/L; P = .02).

Compared with the carbohydrate diet, estimated 10-year coronary heart disease risk was lower and similar on the protein and unsaturated fat diets.

CONCLUSION: In the setting of a healthful diet, partial substitution of carbohydrate with either protein or monounsaturated fat can further lower blood pressure, improve lipid levels, and reduce estimated cardiovascular risk.
====================

Less carbs = less atherogenicity of LDL ...
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Weight loss associated with reduced intake of carbohydrate reduces the atherogenicity of LDL in premenopausal women. Metabolism. 2005 Sep;54(9):1133-41.

The LDL mean particle size was increased from 26.74 to 26.86 nm (P<.01), and the percent of the smaller LDL subfraction (P<.05) was decreased by 26.5% (P<.05) after 10 weeks. In addition, LDL lag time increased by 9.3% (P<.01), and LDL conjugated diene formation decreased by 23% (P<.01), indicating that the susceptibility of LDL to oxidation was decreased after the intervention.

This study suggests that moderate weight loss (<5% of body weight) associated with reduced caloric intake, lower dietary carbohydrate, and increased physical activity impacts the atherogenicity of LDL.
====================

Ed

Post 57

Sunday, March 12, 2006 - 10:24pm

I broke down and bought The Pritikin Program for Diet & Exercise (know your enemy). I'm 4 pages into it and already disgusted. After ole' Nate tells you about how many movie stars were already on his plan [which is dubious 'name dropping'], he writes this piece of crap ...

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Only a foolish or unmotivated person would voluntarily abandon its enormous rewards. -- [argument from intimidation]
===============

What argument from intimidation?? If you recognize those rewards (and he gives you the evidence for them), then what he is saying is true.

And this kind of "madman"-style writing is present on every page (so far).

Talk about the pot calling the kettle black!!! You don't think that referring to this venerable soul as a "madman" isn't an argument from intimidation as well as an argument ad hominem?! Before you criticize your opponents for committing these kinds of rhetorical fallacies, you should be careful to avoid them yourself. I think your bias is showing. "Madman" indeed!

As for studies showing a slowing of atherosclerotic progression ... they're coming. It's a pleasure to do ideological battle with you, Bill.

Excuse me, but "a slowing of atherosclerotic progression" is not exactly what I had in mind, nor is it what I said. I asked if you could produce any studies that show a regression of atherosclerotic plaque, like the ones I cited from Ornish and Pritikin. You do know the difference, don't you? It's the same as the difference between deflation, which is a fall in the average level of prices, and disinflation, which is a fall in the rate at which the average level of prices is rising.

But I'm glad that you picked up a copy of The Pritikin Program of Diet and Exercise. I have it, and it's a great book -- destined to become a classic! Now if only you would read it with an open mind, but I suppose that that's too much to ask! :-/ I feel as if, in defending Rand, I have just run into a Catholic priest who is exceedingly well versed in the Summa Theologica!

- Bill

Post 58

Monday, March 13, 2006 - 8:12am

Alright Bill, I'll admit it -- I got a little 'crazy' there. But let me tell you this: I can turn the 'craziness' off -- and become the most reasonable man that you could imagine. Don't believe me? Then simply read on ...

Bill, you make a good point about the distinction between slowed progression and regression. Yes, I do recognize the difference. But, in the general view of things, I did marshall some relevant evidence on macronutrients influencing atherosclerotic progression. I invite you to consider discussing the results of those studies with me. Here are some relevant points ...

1) A potential influence of glycemic load on CHD risk

2) A potential attenuation (by omega-3 fats and fiber/plant intake) of the previously recorded relationship "between intake of saturated fat and risk of coronary heart disease suggested by international comparisons."

3) The noted absence of any "deteriorating effects of high saturated fat intake [break] for either sex for any cause of death."

4) "In the setting of a healthful diet" -- the noted reduction in "estimated 10-year coronary heart disease risk" by a "partial substitution of carbohydrate with [break] protein."

5) The observed reversal of LDL atherogenicity after a switch to a low-carb diet.

Now, the last 4 points above seem to contradict much of what Pritikin had earlier championed (and what Ornish & McDougall currently extoll). One key finding seems to be that saturated fat (on its own) is not sufficient to initiate or propagate coronary heart disease. Now this is disturbing as this has been a fundamental 'axiom' in conventional medicine. It seems absurd on its face.

One potentially integrating theme would be to appeal to evolution for a paradigm for human nutrition. I am in that camp of thinkers who believe that that appeal would be very beneficial to progress in this scientific arena. Recent relevant research (references upon request) has revealed that early human diets were at least half meat (and/or fish) -- though a leaner (wild game) meat than we tend to eat today. The balance was mostly fruits, vegetables, and nuts/seeds.

Intriguingly, this picture of subsistence of 'early man' also explains our encephalization (our big brains). This scientific explanation is called "The Expensive Tissue Hypothesis" and it has to do with a 'trade-off' made between big guts and big brains. Apes have body-size adjusted intestines that are about twice as long as we do (helps them digest plants better than we do), and we have brains that use 3 times the adjusted metabolic energy as theirs.

Bill, I'd be interested to get your thoughts on the findings above, their relation to what has been extolled by Pritikin and others, and the potential consilience afforded by more precise investigations into early human diets. Please respond if inclined.

Ed

Post 59

Monday, March 13, 2006 - 8:16am