Transcript Document

Atherosclerosis:
1.
Lipoproteins interact with vessel wall proteoglycans
2.
This causes inflammation (so the endothelial cells secrete adhesion
molecules for monocytes (type of white blood cell that rolls along the
blood vessel wall))
3.
Monocytes migrate into the endothelial tissue and differentiate into
macrophages, which take up lipids to try to dispose of them. They
become engorged and can die.
4.
Lipids are only taken up if they are oxidized (which happens to LDL
trapped on the vessel wall)
5.
Macrophages secrete cytokines like interleukin-1 and interleukin-6
that trigger an inflammation response (recruit more white blood cells
to help dispose of all the trapped lipids)
6.
The trapped, engorged, dying macrophages leads to calcification of
the atherosclerotic lesion, and the associated inflammation increases
risk of thrombosis
Lipoproteins interact with vessel wall proteoglycans
High [LDL] means more lipid to bind to vessels
This causes inflammation (so the endothelial cells secrete adhesion molecules for monocytes (type of white
blood cell that rolls along the blood vessel wall))
Monocytes migrate into the endothelial tissue and differentiate into macrophages, which take up lipids to try to
dispose of them. They become engorged and can die.
Inflammatory/immune state of body can accelerate atherosclerosis
Lipids are only taken up if they are oxidized (which happens to LDL trapped on the vessel wall)
Smoking, reactive oxygen species. Mediated by LOX-1
Macrophages secrete cytokines like interleukin-1 and interleukin-6 that trigger an inflammation response (recruit
more white blood cells to help dispose of all the trapped lipids)
Inflammatory marker proteins (like C Reactive Protein) can be detected in
the blood
The trapped, engorged, dying macrophages leads to calcification of the atherosclerotic lesion, and the
associated inflammation increases risk of thrombosis
Prostaglandins mediate pro-thrombotic or antithrombotic conditions in the
arteries, local inflammation events, and general inflammatory state.
Plaque rupture and resulting clot causes myocardial infarction (heart
attack)
(seeds)
(algae, grass)
Series 1
Series 2
Series 3
When dietary source of linoleic and a-linolenic acids are equal,
relative activities of D6 and D5 desaturases determines relative
amounts of these prostaglandins
Leukotrienes lead to
inflammation (asthma, heart
attack, anaphylaxis)
EPA-based leukotrienes have
much lower activity than their
arachidonate-derived
counterparts
eicosapentaenoic acid
(EPA) (w-3 from marine
animals) inhibits
thromboxane synthesis
Some questions I have been thinking about:
Greenland Eskimo diet: high cholesterol, high saturated fat, no vegetables
(raw fish, blubber, marine animals), and NO heart disease…
Typical poor American child diet: sugar, soybean oil, corn oil, white
flour…and high chance of developing obesity, heart disease, and diabetes.
Does inflammation play a role in health?
We have a protein called C reactive protein. It is secreted as a result of
inflammatory stimuli, IL-6, IL-1, so reflects the inflammatory state of the body.
CRP levels are measured along with cholesterol levels to diagnose risk of
heart disease.
It seems that CRP also has a role in CAUSING inflammation in the presence
of oxidized LDL.
hsCRP
(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:1222.) 2008 American Heart Association, Inc.
The Time for Cardiovascular Inflammation Reduction Trials Has Arrived. How Low to Go for hsCRP?
Paul M Ridker From the Center for Cardiovascular Disease Prevention, Brigham and Women’s Hospital, Harvard
Medical School, Boston, Mass.
That inflammation plays a fundamental role in atherothrombosis and that hsCRP is a clinically
effective predictor of risk is no longer controversial.24 If anything, from an epidemiological
perspective, the attributable risk of coronary heart disease associated with inflammation is as large
as that associated with hyperlipidemia. It would thus appear that the time for randomized trials
directly testing the inflammatory hypothesis of atherothrombosis has arrived.
High-Sensitivity C-Reactive Protein and Coronary Heart Disease in a General Population of Japanese: The
Hisayama Study
Hisatomi Arima, Michiaki Kubo, Koji Yonemoto, Yasufumi Doi, Toshiharu Ninomiya, Yumihiro Tanizaki, Jun Hata,
Kiyoshi Matsumura, Mitsuo Iida, and Yutaka KiyoharaArterioscler. Thromb. Vasc. Biol. 2008 28: 1385-1391. [Abstract]
[Full Text] [PDF]
The lower the hsCRP level, the lower the risk of atherothrombosis (heart attack), and the protective
levels of hsCRP were much lower than those found in the Women’s Health Study to be protective
(the American “healthy” diet still has a ways to go to be healthy).
The atheroma is preceded by a fatty streak, an accumulation of lipid-laden cells beneath the endothelium.3 Most of
these cells in the fatty streak are macrophages, together with some T cells. Fatty streaks are prevalent in young
people, never cause symptoms, and may progress to atheromata or eventually disappear
Hansson GK. Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med. 2005; 352:
1685�1695.[Free Full Text]
Studies in animals and humans have shown that hypercholesterolemia causes focal activation of
endothelium in large and medium-sized arteries. The infiltration and retention of LDL in the arterial intima
initiate an inflammatory response in the artery wall13,14 (Figure 2). Modification of LDL, through oxidation
or enzymatic attack in the intima, leads to the activation of endothelial cells
Bacterial endotoxins, apoptotic cell fragments, and oxidized LDL particles are all taken up and destroyed
through this pathway. If cholesterol derived from the uptake of oxidized LDL particles cannot be mobilized
from the cell to a sufficient extent, it accumulates as cytosolic droplets. Ultimately, the cell is transformed
into a foam cell, the prototypical cell in atherosclerosis.
Inhibition of the receptor pathways mediating the uptake of oxidized LDL prevents atherosclerosis
(EVEN IF HIGH LDL LEVELS!!!!!). Opposing this, stimulation of the oxLDL receptor with C reactive
protein accelerates oxLDL uptake and atherosclerotic progression.
Inhibition of cytokines mediating the inflammatory response to uptake of oxLDL eliminates atherosclerosis
(EVEN IF HIGH LDL LEVELS!!!!!).
(Peptido)leukotrienes promote vascular inflammation (but leukotrienes based on
marine lipids (w-3) are far less active!!!!!!!).
Oxidized LDL receptor LOX-1 binds to C-reactive
protein and mediates its vascular effects.
Fujita, et al. Clinical Chemistry Feb. 2009
Acute inflammation increases CRP ~1000-fold (300mg/L). Low levels (highsensitivity CRP) reflect long-term, chronic inflammation
CRP appears to function to enhance removal of foreign bodies (bacterial,
apoptotic remnants, oxLDL). It apparently binds the oxidized
phosphorylcholine on oxLDL…
C-reactive protein (CRP) is an acute-phase protein that binds specifically to
phosphorylcholine (PC) as a component of microbial capsular polysaccharide
and participates in the innate immune response against microorganisms. CRP
elevation also is a major risk factor for cardiovascular disease
Their Results:
LOX-1 binds CRP (0.3mg/L, below recommended concentrations), and
mediates its biological effects…
Evidence in the paper is pretty clear that the binding occurs. They give
good evidence for the mechanism for CRP accelerating the progression
of atherosclerosis, which clarifies something that is not well understood
in the field.
1: Atherosclerosis. 2008 Sep 2. [Epub ahead of print] Links
Reduction in dietary omega-6 polyunsaturated fatty acids: Eicosapentaenoic acid plus docosahexaenoic acid
ratio minimizes atherosclerotic lesion formation and inflammatory response in the LDL receptor null mouse.
Wang S, Wu D, Matthan NR, Lamon-Fava S, Lecker JL, Lichtenstein AH.
Cardiovascular Nutrition Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts
University, 711 Washington Street, Boston, MA 02111, United States.
Dietary very long chain omega (omega)-3 polyunsaturated fatty acids (PUFA) have been associated with
reduced CVD risk, the mechanisms of which have yet to be fully elucidated. LDL receptor null mice (LDLr-/-)
were used to assess the effect of different ratios of dietary omega-6 PUFA to eicosapentaenoic acid plus
docosahexaenoic acid (omega-6:EPA+DHA) on atherogenesis and inflammatory response. Mice were fed high
saturated fat diets without EPA and DHA (HSF omega-6), or with omega-6:EPA+DHA at ratios of 20:1 (HSF
R=20:1), 4:1 (HSF R=4:1), and 1:1 (HSF R=1:1) for 32 weeks. Mice fed the lowest omega-6:EPA+DHA
ratio diet had lower circulating concentrations of non-HDL cholesterol (25%, P<0.05) and
interleukin-6 (IL-6) (44%, P<0.05) compared to mice fed the HSF omega-6 diet. Aortic and elicited
peritoneal macrophage (Mvarphi) total cholesterol were 24% (P=0.07) and 25% (P<0.05) lower,
respectively, in HSF R=1:1 compared to HSF omega-6 fed mice. MCP-1 mRNA levels and secretion were 37%
(P<0.05) and 38% (P<0.05) lower, respectively, in elicited peritoneal Mvarphi isolated from HSF R=1:1
compared to HSF omega-6 fed mice. mRNA and protein levels of ATP-binding cassette A1, and mRNA levels of
TNFalpha were significantly lower in elicited peritoneal Mvarphi isolated from HSF R=1:1 fed mice, whereas
there was no significant effect of diets with different omega-6:EPA+DHA ratios on CD36, Mvarphi scavenger
receptor 1, scavenger receptor B1 and IL-6 mRNA or protein levels. These data suggest that lower omega6:EPA+DHA ratio diets lowered some measures of inflammation and Mvarphi cholesterol accumulation, which
was associated with less aortic lesion formation in LDLr-/- mice.
IL-6 is inflammatory marker
The hot topic in fats today is the ratio of 6s to 3s, and the effect of that ratio on our
health. The typical American diet has too much omega-6 and not nearly enough
omega-3.
Studies have shown these essential oils are critical to healthy skin, nerve cells, and
brain function, including prevention of depression. We also know that Omega-3s are
important to the proper development of the fetus and infant. Omega-3s can reduce the
clotting factors that precipitate stroke and heart disease, and they can lower the LDLs
while increasing HDLs in our cholesterol levels. This essential fatty acid is also known
to be effective in treatment of inflammatory diseases such as arthritis and allergies.
Inadequate Omega-3s, and or excess Omega-6s in relation to 3s can contribute to a host
of other chronic diseases as well, such as cancer, obesity, insulin resistance and
diabetes.
Omega-3s in beef that feed on grass is 7% of the total fat content, compared to 1% in
grain-only fed beef.
Grain-fed beef can have an omega-6 to omega-3 ratio higher than 20:1, well exceeding
the 4:1 ratio where health problems begin to show up because of the essential fatty acid
imbalance. Grass-fed beef can have an omega-6 to omega-3 ratio of 1:1.
TABLE I - Chemical Composition (per 100 g) of Raw Chicken and Beef
Beef cuts
Semimembranosus
Biceps femoris
Dark chicken meat
Moisture (g)c
74.48 ± 1.08
72.48 ± 1.57
Protein (g) c
21.17 ± 0.16
20.97 ± 0.04
Fat (g) c
3.08 ± 0.07
8.75 ± 1.12
4.08 ± 0.60
Cholesterol (mg)g
51.97 ± 1.40
63.02 ± 3.62
QuickTime™ and a
decompressor
are needed to see this picture.
77.49 ± 1.04
18.83 ± 0.09
80.30 ± 2.83
Chicken meat is a significant source of polyunsaturated fat. Chickens that
forage for insects and eat clover and other greens have better w-6: w-3 ratios
in their meat and eggs. Organic, free range, natural, cage free chickens still
live in warehouses with thousands of other chickens and eat grain (and
whatever else the food manufacturer wants to put in there, like other animal
byproducts, recently DHA, etc.).
Cattle lose their w-3 fatty acids soon after being sent to the feedlot to eat
sugar and grain until slaughter. Cows evolved to eat grass (ruminant
digestion), but humans have been fattening them on grain as long as we have
had grain to feed them. Modern industrial agriculture simply goes to extremes
with the grain-fed process.
Monsanto bred Round-up Ready Soy with almost no w-3, since it is prone to
oxidation (goes rancid). Soybean oil is about 60% polyunsaturated, with up to
a 60:1 ratio of w-6:w-3. Soybean oil is used in many restaurants and
processed food, since it is the oil we produce on our factory farms.
Olive oil has a 3:1 up to 10:1 ratio of w-6:w-3, which is borderline okay, but it
is only about 10% polyunsaturated.
Discussion points:
What is the biggest source of w-6 fat in our diets?
Where can we get w-3 fats?
What is nutritionism?
Are we practising nutritionism by obsessing about w-3 fats?
Eating plenty of grass-fed beef is a good solution, right?
Before the modern food era -- and before nutritionism -- people relied for guidance
about what to eat on their national or ethnic or regional cultures.
Where can we seek guidance on our food?
Jeff’s Wednesday food intake and PUFA analysis: the peanut butter contributes the most to the high w-6:w-3 ratio!!
Breakfast:
Oatmeal, blueberries, 50mL whole milk, 1Tbsp butter (88% of 15g plus 4% of 50g = 13.2g+2g = 15.2g total butterfat)
Bufferfat is ~3% w-6, so 3% of 15.2 = 0.46g w-6
Butterfat is ~1% w-3, so 1% of 15.2 = 0.15g w-3.
Lunch:
2 peanut butter sandwiches, 1 apple
1Tbsp butter = 0.4g w-6, 0.13g w-3
3Tbsp peanut butter = 21g fat, and 33% of 21g = 7g w-6
Peanut oil is 0.5% w-3, giving 0.5%*22.5g = 0.11g w-3
Dinner:
150g pork sausage, salad with 1Tbsp olive oil vinaigrette, sauerkraut, potatoes, 5g lard
Sausage is ~20% fat, so 150g * 20% = 30g pork fat + 5 extra = 35g lard, which is 10% w-6 (3.5g)
W-3 is 1% of the 35g, or 0.35g
Dessert:
8oz hot chocolate
200mL whole milk (4% of 220g =8.8g butterfat*3% = 0.26g w-6)
8.8g * 1% = 0.09g w-3
Total omega-6 = 0.46+7+3.5+0.26 = 11.2g
Total omega-3 = 0.15+0.11+0.35+.09=0.7g
Ratio: 16:1!!!!!!!!
Plus 1tsp fish oil (1.2g w-3), 11.2 w-6 / 1.9 w-3 = 5.8:1
Total fat for day: 15.2+45g+35g+8.8g=104g fat
Total calories: 900 fat, 1319 calories carbs (329g), 55g protein 220 calories=2340 total calories
Nutrition analysis by Eve Vodden-Thornton
B1 (thiamine)
B3 (nicotinamide)
Nutrient Total
Calories 2248.75
Pro (g) 73.63
Fat (g)
117.55
Carb (g) 245.91
Fiber (g) 26.33
Cal (mg) 644.65
Iron (mg) 19.46
Na (mg) 4126.85
Pot (mg) 3852.85
Phos(mg) 1207.13
Ash (g) 17.52
vitA (IU) 2270.32
vitC (mg) 92.42
Thia (mg) 2.33
Ribo (mg) 1.88
Nia (mg) 27.03
H2O % 39.61
satF (g) 41.4
monoF(g) 44.29
polyF (g) 15.51
Chol (mg) 212.74
Rec.
2900
63
96.67
%Rec
77.54%
116.87%
121.6%
-30
87.77%
1000
64.47%
10
194.6%
2400
171.95%
-700
172.45%
-5000
45.41%
90
102.69%
1.2
194.17%
1.3
144.62%
16
168.94%
Male 31-50
-32.22
128.49%
32.22
137.46%
32.22
48.14%
300
70.91%1
Michael Pollan describes a grass-based chicken production system in his
Omnivore’s Dilemma that humanely produces chickens and eggs that are
much healthier for you to eat (Polyface Farm, which also sells cows, pigs,
rabbits, turkeys). The USDA regulations on butchering these animals are
very restrictive, and forces farmers like Polyface to ship their animals
hundreds of miles to be slaughtered at a registered facility. Pierce County
just received funding for a mobile abattoir (slaughterhouse on wheels) that
will travel around to small farmers in Pierce, King, Kitsap and a few other
counties to enable them to slaughter their animals on-site. This is the single
biggest impediment to a return to local animal farming, and Pierce county
has one of the first of these facilities (soon) in the nation!
He also gives a philosophical discussion on the ethics of eating meat, and
one of his conclusions on the issue is that feeding our world’s fields
requires nitrogen, and one sustainable way to feed our fields is to use
manure. If we have farms that produce their fields’ fertility onsite, they
should be able to sustain themselves without chemical input or pollution.
Local farmers who are doing this include:
1. Bruce Dunlop, Lopez Island Farms, who comes to the Proctor’s Farmer’s market
(maybe this year he will only sell to you if you are on his list…)
2. Jubilee Farm east of Seattle along the Snoqualmie River near Duvall (Farmer
Erick writes wonderful newsletters online, and is a huge proponent of local
agriculture, see www.jubileefarm.org
3. Zestful Gardens, Tacoma (I get my weekly veggie box from them June1-Nov30).
4. Left-foot organics (Olympia, also runs a weekly CSA box)
Terry’s Berries, Tacoma (CSA, eggs)
Cheryl the Pig Lady in Tacoma (who supplies pigs sometimes to the Primo Grill and she visits the 6th ave and
downtown farmers’ markets),
Stokesberry Farms (in Olympia, supplies chickens to the Primo Grill, and may visit 6th ave farmers’ market)
Skagit River Ranch, sells their beef and pork at Marlene’s market S. 38th St.
Meat Shop of Tacoma (near Ft. Lewis)
Thundering Hooves, near Walla Walla, WA.
Other reading:
Michael Pollan, In Defense of Food. An expanded version of his NYTimes article
“Unhappy Meals”, about nutritionism, the problems with what we Americans eat, and
how to think about what a good diet is.
Nina Planck, Real Food. She collects an impressive amount of data on what real
dairy, meat, vegetables, etc. are, and research on how they affect our health.
Sally Fallon, Nourishing Traditions. The cookbook that challenges politically correct
nutrition. Bone broth, organ meats, traditional fermented foods, and lots of excerpts
from Weston Price’s book.