What happens to the carbs?

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Vince

Super Moderator
What happens to the carbs?

I have found a strange thing happens when I talk to nutritionists about the fate of carbohydrates in the human body. Professors, who shall be nameless, appear unable to admit how basic human physiology works. For example, they may concede a few steps here and there, but they will never, ever, admit to the following chain that I have described below.

1: Carbohydrates, such as fruit and vegetables, bread, pasta… and, of course, less complex sugars – such as the stuff we sprinkle on cornflakes, that we call ‘sugar', are all turned into simple sugars in the human digestive tract before entering the bloodstream.

2: If you keep eating carbohydrate the resultant simple sugars will, at first, be stored. The human body can pack away around 1,500 calories of sugar. However, once this limit is reached, the liver will turn the rest into fat.

3: The fat that is made in the liver is palmitic acid

4: The next step is that three palmitic acid molecules are attached to a glycerol molecule, to form a triglyceride.

5: These triglycerides will then be packed into Very Low Density Lipoproteins (VLDL) and released into the bloodstream. [Beware of confusion here. For VLDLs are also called triglycerides although, of course, they are not. VLDLs contain triglycerides but they are not the same thing – even if they are called the same thing].

6: When VLDLs reach fat cells (adipose tissue), the triglyceride is stripped out and absorbed into fat cells. Which means that VLDLs gradually shrink.

7: Once a VLDL has lost a large amount of triglyceride it becomes a new, smaller, lipoprotein, which is often referred to as ‘bad cholesterol' a.k.a. LDL (Low Density Lipoprotein).

8: LDL is taken out of the circulation, primarily, by the liver. Some LDLs are removed from the circulation by other cells around the body that need the cholesterol contained in them.

9: As can be seen, the only source of LDL is VLDL.

Here a couple of quotes from Wikipedia to confirm at least a couple of these steps:

Lipogenesis is the process by which acetyl-CoA is converted to fatty acids. The former is an intermediate stage in metabolism of simple sugars, such as glucose, a source of energy of living organisms. Through lipogenesis and subsequent triglyceride synthesis, the energy can be efficiently stored in the form of fats.

Lipogenesis encompasses both the process of fatty acid synthesis and triglyceride synthesis (where fatty acids are esterified with glycerol to form fats). The products are secreted from the liver in the form of very-low-density lipoproteins (VLDL). VLDL are secreted directly into blood, where they mature and function to deliver the endogenously derived lipids to peripheral tissues.

https://en.wikipedia.org/wiki/Lipogenesis

Excess carbohydrates in the body are converted to palmitic acid. Palmitic acid is the first fatty acid produced during fatty acid synthesis and the precursor to longer fatty acids. As a consequence, palmitic acid is a major body component of animals. In humans, one analysis found it to comprise 21–30% (molar) of human depot fat and it is a major, but highly variable, lipid component of human breast milk. https://en.wikipedia.org/wiki/Palmitic_acid

I am half tempted to leave the blog here and let you think about what all of that means for a while. However, I feel the need to make a couple of other points, in no particular order. First, I would like you to think about this fact. The form of fatty acid that the liver chooses to synthesize from sugar(s) is palmitic acid, a saturated fat. Palmitic acid is also the major component of breast milk.

Yet, despite this, we are told that saturated fats are uniquely unhealthy, and eating them leads to heart disease. Indeed, within to the very same Wikipedia article on palmitic acid we learn that: ‘According to the World Health Organization, evidence is “convincing” that consumption of palmitic acid increases risk of developing cardiovascular diseases.'

It seems that we are being asked to believe that the body naturally synthesizes a substance, palmitic acid, that actively damages our health. Not only that, but mothers choose to synthesize exactly the same form of fatty acid in their breast milk, which then increase the chances of their offspring developing cardiovascular disease.

Now just how likely does this seem…exactly? We have evolved to kill ourselves from heart disease? As Spock may have said, ‘its evolution Jim, but not as we know it.' You would think that if polyunsaturated fats were healthy, this is what the human body might choose to make. But no, we eat super healthy fruit and vegetables and then our body, in a unique and ironic twist of fate, converts them into death dealing saturated fatty acids.

Not only that, but just to rub salt into the wounds, once the liver has synthesized these death dealing fatty acid molecules it then chooses to pack them into VLDLs which have the cheek to shrink down into LDL a.k.a. ‘cholesterol' and these also kill us with heart disease (allegedly).

Of course, if you actually eat saturated fat, this gets nowhere near the liver. It is digested, packed into chylomicrons, and these very large lipoproteins enter the bloodstream directly through the thoracic duct. Which is a secret passage from the gut that opens out in one of the veins in your neck. When chylomicrons encounter fat cells, the fats/triglycerides are sucked out, and the chylomicron shrinks down to virtually nothing. Chylomicrons, however, do not convert to LDL and have nothing whatsoever to do with heart disease – even according to those who think saturated fat in the diet is deadly.

Yet, despite this knowledge we are continuously told, in all seriousness, that eating saturated fat raises our LDL levels and causes us to die prematurely of heart disease. [You may have noticed that cholesterol has hardly entered this discussion at any point.] When people ask me why I don't believe in the diet/heart hypothesis, I tend to shrug and move the conversation on.

However, if I am feeling a bit stroppy I tend to reply that ‘Even if you were to believe that a raised LDL levels causes heart disease, the current diet/heart hypothesis does not, and cannot make any sense from a biological or physiological perspective.' If you were actually looking for a substance that really could raise LDL/cholesterol levels it would have to be carbohydrates a.k.a. sugars. After all the only source of LDL is VLDL, and it is eating too much sugar that raises VLDL levels.

In short, how can it not be that carbohydrates raise LDL levels? This is what a basic understanding of lipid physiology tells us must be true. Yet, people write papers on this phenomenon in a tone of almost stunned surprise. Here for example is a paper called ‘The Effect of Dietary Carbohydrate on Triglyceride Metabolism in Humans':
When the content of dietary carbohydrate is elevated above the level typically consumed (>55% of energy), blood concentrations of triglycerides rise. This phenomenon, known as carbohydrate-induced hypertriglyceridemia, is paradoxical because the increase in dietary carbohydrate usually comes at the expense of dietary fat. Thus, when the content of the carbohydrate in the diet is increased, fat in the diet is reduced, but the content of fat (triglycerides) in the blood rises. http://jn.nutrition.org/content/131/10/2772S.full#fn-1

This author, writing for the Journal of Nutrition, finds it paradoxical that… increased dietary carbohydrate usually comes at the expense of dietary fat….but the content of fat (triglycerides) in the blood rises. Well, what did they think would happen? That carbohydrates would turn into fairies at the bottom of the garden?

Once the liver and muscles are full of sugar (stored as glycogen – a polymer of glucose) the body can do absolutely nothing else with it, but turn it into fat – through the processes I have described earlier. This is basic, incontrovertible science.
Most people who are interested in the potential benefits of the low carb high fat diet (LCHF), have tended to look at it from the perspective of helping with controlling diabetes, and promoting weight loss. I came at the LCHF diet from my own perspective, which is heart disease.

When you understand the science you find yourself looking at the diet heart hypothesis (fat in the diet raises LDL levels, which causes heart disease) and thinking. This does not make any sense at all. Yet, such is the determination of the nutritional experts to defend their position that they never, ever, talk about ‘what happens to the carbs?'

What happens to the carbs is that they are all turned into saturated fat. This then raises VLDL levels and these, in turn becomes LDL. Yet eating carbs is supposed to be healthy, and eating saturated fat is unhealthy. Go figure.
The world of nutrition is, I am afraid, nuts.
http://drmalcolmkendrick.org/
 
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Defy Medical TRT clinic doctor
Great read.

A good source of information is also Dr Deal Barnard site and book.
http://www.nealbarnard.org/

There is also another book called the China Study which is a good read.

Fats and sugars together are the issue. Low fat, high carb plant based diets do work. Problem is that people do not understand what a "carb" is. A potato is a carb a pastry is Fat and sugar.

A Pasta dinner is not bad for you but add the fat from the meat and what ever else is in the sauce and now you had something that is not as good for you. You cant have pasta without the garlic bread with butter (more fat) and dipping oil (more fat). How about that salad which is good for you then you add to it salad dressing to it, which is fat. I have pasta with vegan sauce and spinach salad with strawberries and no bread.

I do make my own bread so I know exactly whats in it.

I know a lot of high carb vegans that eat a lot of calories and are not overweight.

What is used in processed food is not "Table sugar" but high fructose corn syrup. The corn syrup is not only bad for you but makes you crave more of it. Once you take processed food out of your diet you will notice you have withdraws and crave those processed foods.

How the cells work. http://www.ncbi.nlm.nih.gov/books/NBK26882/
 

Jay

Member
FYI, 6 months ago I was told I was pre-diabetic and my total cholest was 205. I switch to a ketogenic diet...lost 15 lbs, and my ha1c dropped to 5.2 and fasting Glucose to 92. However, my total cholest went up to 312. Dr John wants me off the keto diet and back to carbs with lower amount of healthy fats. I guess for some the low carb diet will make your lipid profile improve.
 

Nelson Vergel

Founder, ExcelMale.com
I know this video is long (I saw it in 3 sittings), but it is the best given on the subject of how carbohydrates contribute to heart and metabolic disease.

 
FYI, 6 months ago I was told I was pre-diabetic and my total cholest was 205. I switch to a ketogenic diet...lost 15 lbs, and my ha1c dropped to 5.2 and fasting Glucose to 92. However, my total cholest went up to 312. Dr John wants me off the keto diet and back to carbs with lower amount of healthy fats. I guess for some the low carb diet will make your lipid profile improve.

Jay........I'm in the same boat.......Metabolic Syndrome. These days I'm more concerned with my A1C than I am my cholesterol numbers. My findings when I scoured the "cholesterol myth" is that the cholesterol numbers.....total, HDL and LDL really don't tell you anything regarding cardiovascular risk factors. Of course big pharma wants to you to scared to death of "high cholesterol" and put you on statins forever. If you have 12 mins........watch this video. I promise you it's worth your time: Statin Nation https://www.youtube.com/watch?v=Ry1Z8buyd8I
 
I am strictly Keto but I think there is room for guys like SoCalSurfer to use his way of eating.

I personally get a brain and energy boost eating Ketogenic. I don't know that a plant-based diet would do the same for me since I detest the taste of most plants. Well fruit I find tasty in most cases. Vegetables are eaten more for science reasons, haha. I honestly haven't put a piece of broccoli in my mouth and thought "**** that is some good broccoli". Whereas a Ribeye will make me salivate.

I think the important thing is for those with metabolic syndrome issues at least we have some science to back up how we are choosing to eat in order to burn fat. I've lost 80 lbs total, most of that in the first year. In the 2nd year I added TRT and started working out more and am up 20 lbs. with no increase in waist size.
 

Vince

Super Moderator
the problem I find with fruit is it's genetically modified to taste like candy, with lots of sugar. is there any difference between a ripe banana and a candy bar "sugar" wise?
 

Vince

Super Moderator
Fat is back. Quite a nice CNN headline:
CNN: Fat is back: New guidelines give vilified nutrient a reprieve
Forbes: Fat Makes A Comeback: Experts Say It's Time To Stop Limiting Dietary Fats
This comes after an article by a couple of top researchers in a the highly respected scientific journal JAMA. They urge the relevant authorities to remove any restriction on how much dietary fat to eat. Any such restriction is said to be not only useless for improving health, but actually harmful to the public health.
“I think it is crucial for all government agencies to formally state that there is no upper limit on fat,” says one of these top researchers to CNN. Very true. He also says that saturated fat is neutral for heart health. It's simply not something to worry about.
Here's the final paragraph of the JAMA article:
The limit on total fat presents an obstacle to sensible change, promoting harmful low-fat foods, undermining attempts to limit intakes of refined starch and added sugar, and discouraging the restaurant and food industry from providing products higher in healthful fats. It is time for the US Department of Agriculture and Department of Health and Human Services to develop the proper signage, public health messages, and other educational efforts to help people understand that limiting total fat does not produce any meaningful health benefits and that increasing healthful fats, including more than 35% of calories, has documented health benefits. Based on the strengths of accumulated new scientific evidence and consistent with the new DGAC report, a restructuring of national nutritional policy is warranted to move away from total fat reduction and toward healthy food choices, including those higher in healthful fats.
Fat is back. Almost all sensible people are starting to understand this. Quite a few also understand that this includes natural old-fashioned saturated fat. Butter is also back.
Do you want to eat more fat – instead of carbs – and experience the benefits? Start here
 

croaker24

New Member
The main points that I get from the new guidelines is - #1 - is to eat a primarily plant-based diet. #2 - Healthy fat is fine, based on the type/quality, but limit that saturated fat, replace your saturated fat with the good fats from nuts/seeds/fish,etc. #3 - Cut down on the red meat.

The new guidelines are not pushing low-carb or high-fat.
 

Vince

Super Moderator
The main points that I get from the new guidelines is - #1 - is to eat a primarily plant-based diet. #2 - Healthy fat is fine, based on the type/quality, but limit that saturated fat, replace your saturated fat with the good fats from nuts/seeds/fish,etc. #3 - Cut down on the red meat.

The new guidelines are not pushing low-carb or high-fat.
Because I'm a APO-E 3/3, I am very fortunate I can thrive on a high fat diet. I do get all the proper testing done, but I do believe our genes developed on a hunter gatherer diet.
 

Vince

Super Moderator
[h=2]APOLIPOPROTEIN E[/b]by Dawn Reynolds
Apolipoproteins are carrier proteins that combine with lipids to form lipoprotein particles, which have hydrophobic lipids at the core and hydrophilic side chains made of amino acids. There are several classes of lipoproteins ranging in density, from VLDL, or very low density lipoproteins, to VHDL, or very high density lipoproteins. There are nine different apolipoproteins that are found in human blood plasma, and they can act as signals, that cause lipoproteins to act on certain tissues or that activate enzymes that act on those lipoproteins (Lehninger).
Apolipoprotein E has many functions in the body. When it is synthesized by the liver as part of VLDL it functions in the transport of triglycerides to the liver tissue. It is also incorporated into HDL (as HDL-E) and functions in cholesterol distribution among cells. It is also incorporated into intestinally synthesized cholymicrons and transports dietary triglycerides and cholesterol. It is involved in lipid metabolism by mediating the receptor binding of apo-E lipoproteins to the LDL receptor. Receptor binding begins the cellular uptake of lipoproteins to be used in intracellular cholesterol metabolism (where they can be used, for example, as components of cell membranes). (Mahley)
Apolipoprotein E is synthesized in several areas of the body. Approximately three-fourths of the plasma apo-E is synthesized in the liver. Liver apo-E is produced primarily by hepatic parenchymal cells, and it becomes a component of VLDL. The brain also produces a large amount of apo-E. Approximately one-third of the liver levels of apo-E are made by astrocytes, the star-shaped branching neuroglial cells that are found in the brain. Apo-E is also synthesized in the spleen, lungs, adrenals, ovaries, kidneys, muscle cells, and in macrophages (Mahley). The apo-E synthesized from macrophages is involved in reverse cholesterol transport, local redistribution of cholesterol, and protection against the development of artherosclerotic lesions (Linton).
Apolipoprotein E (apo-E) is normally present in plasma at 5 mg/dl (Mahley). It associates with cholymicrons, VLDL, and HDL (Lehninger). It is a 299 amino acid peptide and has a molecular weight of approximately 34,000. The gene for apo-E is found on chromosome 19 and is 3.7 kb in legnth. The DNA codes for a messenger RNA that is 1163 base pairs long, thus it undergoes a great deal of posttranslational processing (Mahley).
The secondary structure can be divided into three main portions. The amino terminal end (up to residue 165) is highly ordered, the next 35 residues make up a random structure, and the carboxyl terminal portion becomes highly ordered again. The majority of the secondary structure, about 62%, is formed from alpha helices, which are amphipathic and important in lipid binding. The rest of the secondary structure is made up of beta sheets (9%), beta turns (11%), and random structure (18%). The area of the protein with the strongest lipid binding is found in the carboxyl terminal portion, from residues 202-209. The five arginine and three lysine residues between residues 140 and 160 are essential for binding to the LDL (low-density lipoprotein) lipid receptor. Receptor binding is important for cellular uptake of lipoproteins. It is believed that the receptor binding is due to the ionic interactions between the basic residues of the apo-E and the acidic residues (from aspartic and glutamic acids) of the lipid receptor (Mahley).
There are three different isoforms of apolipoprotein E: apo-E 2, apo-E 3, And apo-E 4. Apo-E 3 is the parent form and all others are compared to it. Apo-E 2 is different from apo-E 3 because a cysteine is substituted for arginine at residue 158. Apo-E 2 is associated with Type III Hyperproteinemia (where there is an excess of protein in the blood plasma) and it does not bind to the lipid receptor. In fact, apo-E 2 shows less than 2% of the normal receptor binding activity. Apo-E 4 has an arginine substituted for cysteine at residue 112. This residue is outside of the strongest lipid binding area and the substitution doesn't.affect the lipid binding ability of the apolipoprotein. Functionally, apo-E 4 still has 100% of normal receptor binding activity (Mahley).
Apoliooprotein E uses different metabolic pathways in the body. one of these pathways is endocrine-like, and involves the redistribution of lipids among cells of different organs. It takes lipids from the areas where the lipid is synthesized and distributes them to other areas where the lipids are used or stored. Another pathway in paracrine-like, where the lipids are transported among cells in the same organ or tissue. Apo- E is also involved in various pathways that are unrelated to lipid transport, such as the stimulation of lymphocytes. (Mahley)
Since apolipoprotein E is involved directly in the uptake and distribution of plasma lipids, it is natural that it has several implications for cardiovascular disease. For example, one study showed that apolipoprotein E deficiency causes high serum cholesterol and triglyceride levels and leads to premature artherosclerosis (Linton). This study used twelve apo-E deficient mice (apo-E -/-). Six of these apo-E deficient mice received bone marrow transplants from normal apo-E mice (apo-E +/+ to apoe -/-). The remaining six mice received bone marrow transplants from other apo-E deficient mice (apo-E -/- to apo-E -/-) and formed the control group. The mice were given bone marrow transplants because macrophages, which are involved in the production of apo-E, are produced from hematopoietic cells.
The post-transplant serum cholesterol levels were then measured. The researchers first looked at the apo-E +/+ to apo-E -/- mice. Two weeks after the transplant mean serum cholesterol levels had not changed in the apo-E +/+ to apo-E -/- mice. Three weeks after the transplant there was a marked decrease (the mean decrease was approximately 50%) in levels of VLDL, LDL, and LDL cholesterol. After four weeks, the cholesterol levels were measured again, and there was an even larger decrease (approximately 70%) in VLDL, LDL, and LDL cholesterol. The serum cholesterol levels of the control group (apo-E -/- to apo-E -/-) were also measured after two, three, and four weeks, and there was never any significant change in cholesterol levels.
Apolipoprotein E is very efficient at doing it's job. In the apo-E +/+ to apo-E -/- mice, the serum apo-E levels only reached 12.5% of normal levels, yet these mice were able to demonstrate significant clearance of plasma lipids. Two months after the bone marrow transplant, five mice from each group were fed a high fat, Western-type diet that contained 21% fat and 0.15% cholesterol. After three months, the mean serum cholesterol levels of these mice were measured. In the five mice from the apo-E +/+ to apo-E -/- group, the mean serum cholesterol levels were 318 +/- 76 mg/dl. In the five mice from the control group, the mean serum cholesterol levels were 1303 +/- 462 mg/dl. The mice that contained no apolipoprotein E had higher than normal serum cholesterol levels and those levels were never reduced naturally by the mice. The mice were then killed and analyzed for aortic artherosclerotic plaques. The mice from the control group had lesions in the proximal aorta. These lesions were raised and had a fibrous cap over a lipid core and had foam cells, necrosis, and extracellular lipid deposits. The mice from the apo-E +/+ to apo-E -/- group also had some artherosclerotic lesions, but they were much reduced compared to the control group and the lesions were at a very early stage with very few of the characteristics of the control group (they were not raised and didn't have a fibrous cap, foam cells, etc.). The mean lesion area per mouse was 52 times greater in the control group. The results from this study shows that apo-E has a significant affect on both plasma lipid levels and on the development of artherosclerotic lesions.
Apolipoprotein E has also been found to affect the formation of artherosclerotic lesions by inhibiting platelet aggregation. It does this when it is bound to HDL, forming HDL-E. HDL-E acts as an inhibitor of agonist induced platelet aggregation through interaction with saturable sites in the platelet surface (Desai). There is evidence that the apo-E is the active constituent of the HDL-E. HDL by itself has no inhibitory effect on aggregation, but when combined with apo-E it reduces aggregation to 26% of control levels when present at .1 mg/ml (Desai). Chemically modifying the apo-E blocks the anti-platelet action and in patients with apo-E enriched HDL (from hepatic cirrhosis) there is an enhanced anti-aggregatory effect (Riddell).
Researchers beleive that platelet inhibition occurs via the L-Arginine:Nitric Oxide pathway. Using this pathway, the vascular endothelium synthesizes nitric oxide (NO) from the terminal guanidino nitrogen atoms of L-Arginine using a soluble enzyme called NO synthase. The No then binds to soluble guanylate cyclase to produce CGMP, which has inhibitory effects on platelet aggregation. The increased levels of CGMP also decrease the amount of CAMP phosphodiesterase, the enzyme that converts CAMP to AMP. The decrease in CAMP phosphodiesterase causes an increase CAMP, and CAMP also has an inhibitory effect on platelet aggregation (Riddell). The following diagram illustrates the L-Arginine:Nitric oxide pathway and it's role in platelet inhibition:
Figure 1: L-Arginine:NO pathway it's inhibition of platelet aggregation. (Redrawn from Riddell, et al)
Evidence for the involvement of the L-Arginine:Nitric Oxide pathway in platelet aggregation comes from a study that involved the blood from healthy volunteers who had not taken drugs for 10 days prior to the study (Radomski). Platelet aggregation was induced by collagen and it was concentration dependent. The platelet aggregation was accompanied by an increase of CGMP levels. L-Arginine inhibited the platelet aggregation (this inhibition was also in concentration dependent) and enhanced the increase of CGMP levels caused by collagen. When the platelets were combined with L-MeArg (N[SUP]G[/SUP]-monomethyl-l-arginine), which is an analog of L-Arginine, there was no increase in the CGMP levels and no inhibitory effect on collagen induced aggregation.
The L-Arginine/Nitric oxide pathway acts as an intraplatelet negative feedback mechanism. Platelet exposure to hemoglobin, which acts as an inhibitor of nitric oxide actions, didn't reverse the inhibitory effects of 1-Arginine in washed platelets. It did inhibit the increase in cyclic GMP induced by 1-Arginine in platelet cytosol; however, the hemoglobin didn't penetrate the platelet surface membrane.
The most recent published study involving apolipoprotein E shows that the apo-E is an important factor in the inhibition of platelet aggregation via the L-Arginine:Nitric Oxide pathway (Riddell). This study showed that while free apo-E had little inhibitory effect, when the apo-E was complexed with a type of phospholipids (DPMC), the apo-E'DMPC vesicles (which mimic the form secreted by macrophages) inhibited platelet aggregation that was induced by ADP, epinephrine, and collagen.
This study also showed that apo-E elevated the platelet nitric oxide synthase activity and intraplatelet levels of CGMP. When the platelets were combined with threshold concentrations of ADP, the apo-E'DPMC complexes caused in increase of CGMP from basal levels of 3.7 +/- 1.1 to 33.9 +/- 3.2 pmol/109 platelets. The complexes also caused an increase in intraplatelevels of CAMP, from basal levels of 11.7 +/- 1.9 to 23.5 +/- 3.3 pmol/10 9 platelets. The increased levels of both CGMP and CAMP were concentration dependent, with the maximum levels coming from a concentration of 50 ug of protein/ml of apo-E'DPMC incubated with the platelets for 10 minutes. After incubating the platelets with the apo-E'DPMC vesicles for 10 minutes, the nitric oxide synthase was also markedly increased. Since platelets generally release very small amounts of No synthase, these levels are difficult to measure. The increase in NO synthase production was measured by the conversion of L-Arginine to L-Citrulline. The platelets incubated with the apo-E vesicles showed a four- fold increase in the formation of L-Citrulline.
The anti-platelet effects of the apo-E'DPMC vesicles was reversed with ODQ (lH-[1,2,4]oxadiazolo[4,3,-alquinoxalin-l- one). ODQ is a specific inhibitor of soluble guanylate cyclase, the enzyme that forms CGMP from GTP. The addition of ODQ lowered the inhibition of aggregation from 68.7+/- 4.4% to 7.5 +/- 8.9%.
Incubating the platelets with L-NMMA(N[SUP]G[/SUP]-monomethyl-L- arginine) or L-NAME (N[SUP]G[/SUP]-nitro-L-arginine methyl ester), both of which are amino acid analogs of L-Arginine and competitive inhibitors of NO synthase, caused blockage of the anti-platelet actions of the apo-E'DPMC vesicles. Two different inhibitors of the enzyme NO synthase, Ethyl-ITU (2-ethyl-2-thiopseudourea hydrobromide) and DPI (diphenyleneiodonium chloride, a flavoprotein inhibitor), also caused the reversal of the anti-platelet effects of apo-E. Hemoglobin, which inhibits the guanylate cyclase activity by binding to the nitric oxide formed, also inhibited the antiplatelet action of the apo-E. This study provided evidence for the mechanism of the apolipoprotein E inhibition of platelet aggregation and provided the evidence that apo-E works via the L-Arginine:Nitric Oxide pathway to cause the inhibition.
More studies need to be done to determine the clinical implications for the connection between apolipoprotein E and cardiovascular disease; however, the studies that have been done have given us a much better understanding of the mechanism of apo-E's actions. Since heart disease is the number one killer of adults, it is important that we have a clear understanding of the physiological mechanisms involved in both the cause and the prevention of cardiovascular disease. In the future, researchers may find a clinical role for apolipoprotein E in the prevention of cardiovascular disease.
[h=3]REFERENCES[/b]
Desai, K.; Bruckdorfer, R.; Hutton, R.; Owen, J. Binding of apo-E rich high density lipoprotein particles by saturable sites on human blood platelets inhibits agonist-induced platelet aggregation. Journal of Lipid Research, 1989; Vol. 30; pg. 831-840
Lehninger, Albert; Nelson, David; and Cox, Michael Principles of Biochemistry, second edition, New York, Worth Publishers, 1993
Linton, M.; Atkinson, J.; Fazio, S. Prevention of Atherosclerosis in Apolipoprotein E-Deficient Mice by Bone Marrow Transplantation Science, 1995; Vol. 267; pg. 1034-1037
Mahley, R. Apolipoprotein E: Cholesterol Transport Protein with Expanding role in Cell Biology Science, 1988; Vol. 240; pg. 622-640
Radomski, M.; Palmer, R.; Moncada, S. An L-Arginine/Nitric oxide pathway present in human platelets regulates aggregation Proc. Natl. Acad. Sci. USA, 1990; Vol. 87; pg. 5193-5197 Riddell, D.; Graham, A.; Owen, J. Apolipoprotein E Inhibits Platelet Aggregation through the L- Arginine/Nitric oxide Pathway Journal of Biological Chemistry, 1997; Vol. 272; pg. 89-95

Copyright © 1997 Dawn Reynolds and Koni Stone Back to the 1997 Table of Contents
 

Vince

Super Moderator
I thought thia was interesting :

ApoE Genotype and Coronary Artery Disease Angiographic studies of CHD patients have shown that apo E4 carriers are more often found to have disseminated and severe coronary lesions than noncarriers.[SUP]13[/SUP] The apoE genotype is reported to increase an individual carrier's differential susceptibility to future coronary artery disease (CAD) events. In larger studies and pooled analyses, apo E4 is associated with increased CAD events compared to apo E2 and apo E3. Reported CAD event risk is increased about 40% in apo E4 individuals.[SUP]32[/SUP]
A meta-analysis of clinical events in 6,355 individuals in nine observational studies

http://www.bhlinc.com/clinicians/clinical-references/reference-manual/chapter19
 

Vince

Super Moderator
This is what LabtestsOnline has to say about the test results:
What does the test result mean?Patients with ApoE e2/e2 alleles are at a higher risk of premature vascular disease, but they may never develop disease. Likewise, they may have the disease and not have e2/e2 alleles because it is only one of the factors involved. ApoE genotyping adds additional information and, if symptoms are present, e2/e2 is diagnostic of Type III hyperlipoproteinemia (also known as familial dysbetalipoproteinemia), although diagnosis must be made in conjunction with other test results and the patient's clinical history. Patients who have ApoE e4/e4 are more likely to have atherosclerosis. Patients who have symptoms of late onset Alzheimer's disease (AD) AND have one or more ApoE e4 copies of the e4 gene are more likely to have AD. It is not diagnostic of AD, though, and should NOT be used to screen asymptomatic patients or their family members. Many people will have e4 alleles and never develop AD. Even in symptomatic patients, only about 60% of those with late onset AD will have ApoE e4 alleles.
ApoE e3 has “normal” lipid metabolism, thus no genotype impact.
 

Vince

Super Moderator
Nutrient-Gene Interactions
The Effect of Dietary Fat on LDL Size Is Influenced by Apolipoprotein E Genotype in Healthy Subjects

Juan Antonio Moreno, Francisco Pérez-Jiménez, Carmen Marín, Purificación Gómez, Pablo Pérez-Martínez, Rafael Moreno, Cecilia Bellido, Francisco Fuentes and José López-Miranda

Lipids and Atherosclerosis Research Unit, Hospital Universitario Reina Sofía, Córdoba, Spain


LDL particle size is dependent on both genetic factors and environmentalfactors such as dietary fat composition. The apolipoprotein E (apoE) genotype is a major genetic determinant of LDL size.Thus, the aim of this work was to study whether the apoE genotype interacts with the quantity and quality of dietary fat, modifying LDL size in young healthy subjects. Healthy subjects (n = 84;66 apoE 3/3, 8 apoE 4/3, 10 apoE 3/2) were subjected to 3 dietary periods, each lasting 4 wk. The first was an SFA-enriched diet(38% fat, 20% SFA), which was followed by a carbohydrate (CHO)-rich[SUP][[/SUP]diet (30% fat, < 10% SFA, 55% carbohydrate) or a monounsaturated fatty acid (MUFA) olive oil–rich diet (38% fat, 22% MUFA)following a randomized crossover design. At the end of each diet period, LDL particle size and plasma levels of total cholesterol,LDL cholesterol (LDL-C), HDL-C, apoB, apoA-I, and triacylglycerols were determined. LDL particle size was significantly higher(P < 0.04) in subjects with the apoE 4/3 genotype compared with those with apoE 3/3 and apoE 3/2 in the basal state. LDL size was smaller (P < 0.02) after the CHO diet than after [SUP]][/SUP]the MUFA or SFA diets. After the CHO diet, a significant increase in LDL particle size (P < 0.035) was noted with respect tothe MUFA diet in apoE 4/3 subjects, whereas a significant decrease was observed in the apoE 3/3 individuals (P < 0.043). In conclusion, a Mediterranean diet, high in MUFA-fat increases LDL particle size compared with a CHO diet, and this effect is dependent of apoE genotypes.
 
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Vince

Super Moderator
The point of the study is not that the assumption that "a diet high in saturated fat contributes to the development of CAD" in everyone. It's that depending on the type of Apo E alleles you have (3/3, 4/4, 2/2, or some other combination) that Apo E genotype will subtly define your LDL particle size and how you metabolize saturated fats. The conundrum with some folks whose Apo E genotype tends to turn dietary fat into a significant CAD risk is what to replace it with, i.e., either carbohydrate or protein. There really are no other choices. The whole point of the study is that one size does NOT fit all, and making generalizations about particular diets as being "heart healthy" cuts across all genotypes for Apo E, i.e., in some saturated fats will drive CAD, and in others not so much, and likewise, carbohydrate can lead to excess inflammation, fat storage, insulin resistance, etc., but so can large intakes of protein. Again, the issue is not that the analysis is misleading, it's that Apo E genotypes influence things in ways that make generalizations almost impossible.

From the article's conclusion:

In conclusion, our data indicate that each subject has to be examined and guided individually when dietary recommendations are made. No diet can be recommended unequivocally without knowing more about those being targeted. Even though a MUFA-rich diet increases LDL size compared with a CHO-rich diet, this effect is dependent on apoE genotypes. Thus, the replacement of a CHO diet by a MUFA diet increases LDL-size in apoE 3/3, whereas it decreases it in apoE 4/3 subjects.

That said, there is recently emerging data which demonstrates that some saturated fats (e.g., fermented cheeses for one) are quite protective, and do not contribute to the development of CAD, and may actually do quite the opposite by increasing circulating serum K-2 (of the MK-7 variety, if you eat the right cheeses). There are many who swear by organ meats such as liver, kidney, etc., but I have to say, I'm not one of them.
 
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