2007-02-24 Meeting Photos

Vitamin E and folic acid are out of fashion in preventing cardiovascular events.

Some years ago after a visit with the cardiologist, one often stopped by the drug store to pick up a bottle of vitamin E or folic acid. No more! like fashion, the trend has since reversed; most trials have shown negative results of late.

Reported in the New England Journal of Medicine (2000; 342:154) that in patients with high risk for cardiovascular events, treatment with vitamin E for a mean of 4.5 years has no effect on the cardiovascular outcome. Vitamin E and beta carotene have shown no benefits for primary prevention (i.e. in preventing the first heart attack.)

Homocysteine has atherogenic (causing ‘hardening of artery’) and prothrombotic (promoting blood clots) properties. Hyperhomocysteinemia (too much homocysteine in the blood) is a risk factor for cardiovascular disease and venous thrombosis (blood clot in the vein) Using vitamin B6, vitamin B12, and folic acid can lower blood homocysteine level. Based on the following homocysteine metabolism pathway, one can see that vitamin B6, vitamin B12, and folic acid promote "homocysteine à à cysteine pathway", thereby lowering homocysteine level.
But several trials of such approach failed to show any decrease in cardiovascular events or death. The following is the conclusion in an article on NEJM 2006;354:1578.

Treatment with B vitamins did not lower the risk of recurrent cardiovascular disease after acute myocardial infarction. A harmful effect from combined B vitamin treatment was suggested. Such treatment should therefore not be recommended.

However, those with venous thrombosis and elevated blood homocysteine level, treatments with folic acid (1 mg/day), vitamin B6 (10 mg/day), and vitamin B12 (0.4 mg/day) are recommended. And screening hyperhomocysteinemia in patients with otherwise unexplained venous thrombosis is recommended.

Certain drugs used to treat hypercholesterolemia (high blood cholesterol level), such as fibrates and nicotinic acid, can raise homocysteine levels by 30%; however, the clinical significance of this is uncertain.

With the conflicting and ever shifting data of these vitamin supplements like a fashion, the best policy is to pay attention to those well-established cardiovascular risk factors including smoking, diabetes (which is considered a coronary equivalent), dyslipidemia, hypertension, and older age. (here is another good reason to stay forever young)

The Fact and myth of Fat and Sweet

The new fad of fat: trans fat
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Talking about trans fatty acid is a fad, a hot topic among food and healthcare industry. Trans fat is a public enemy so to speak.

Lipid, oil, fat, or fatty acid can be used interchangeably. But, for the purpose of this writing, let me say "cholesterol and triglyceride are lipids" and fatty acids (or simply fats) are the key constituents of lipids. So it is safe to say all characteristics of lipids are those of fatty acids or fats.

Fatty acid is a long hydrocarbon (hydrogen-carbon) chain. If all carbons are bonded with maximal number of hydrogens possible, it is 'saturated' (with hydrogens). If not, then double bond formed between two adjacent C==C atoms, hence unsaturated. Monounsaturated implies one double bond and polyunsaturated more than one in the long hydrocarbon chain. Molecule A is saturated whereas molecule B is polyunsaturated containing 3 double bonds. Since the energy is stored in the chemical bond, saturated fatty acid stores more energy as it has more C—H bonds. (not shown)


saturated vs unsaturated fatty acid


Trans fatty acids derived from partial hydrogenation of vegetable oils. A hydrogen atom can be added to the C atom by forming a C—H, converting C==C double bond to C—C bond. In the presence of double bonds, if the two hydrogen atoms are in the same side of the double bond, it is called cis double bond, making a bend or kink (see above molecule B) Trans double bond is the one in which the two hydrogen atoms are on the opposite sides of the bond, which straightens the fatty acid chain. Most naturally occurred fatty acids are in the cis rather than in trans configuration.


Cis vs trans fatty acid


Partial hydrogenation of vegetable oil (which are often polyunsaturated with cis double bonds) converts it to one with trans double bond configuration making it straight like a saturated fatty acid. Without bending or kinking, straight chains are packed more efficiently and this translates into stability during deep-frying, long shelf life, and the semisolidity makes it more palatable. Trans fat thus finds its way into all kinds of processed foods that include deep-fried fast foods, bakery products and margarines.

Deleterious metabolic effects of trans fats and its association with increased risk for cardiovascular diseases have been well documented. It raises LDL (bad guy) and triglycerides and lowers HDL (good guy), it also promotes inflammation and causes endothelial dysfunction, both of which involve the complex processes that lead to acute cardiovascular events.

The Nurses' Health Study reveals that each 2% increase of calories from trans fat translates into a 1.93 relative risk for cardiovascular disease. (i.e. the risk is almost double)

One may argue that trans fat is at most as bad as, and can't be worse than saturated fat, given our biochemical understanding. But, this may not be the case, as the elevated lipoprotein A is associated with increased risk of cardiovascular disease, and trans fat raises it while saturated fat lowers it.

FDA required, effective January 1, 2006, that nutrition labels must indicate the content of trans fatty acids. But, the current loophole is that if a food contains less than 500 mg trans fat per serving, it can be listed as zero. One may consume multiple servings, as is often the case, (Hey! here is America--the land of the brave and abundance!) without realizing taking any trans fat. It has been reported about 30% of our calories intake comes from ‘eating out’ and the fancy, enticing, and inviting restaurant menu is not obligated to list the trans fat content.

And worse yet, many trans fat-containing foods may be simply listed as 'hydrogenated' and conveniently neglects to mention the 'taboo word'--trans fat!

notorious LDL

LDL particle


Cholesterol is a lipid, (a hydrophobic fat that can't get along with water, thus it alone can not travel in the blood stream or in body fluid) it is transported by lipoproteins (cholesterol-carrying vehicle) which is composed of about 2,000 cholesterol molecules (about 1,500 of them bound with an ester), phospholipids, and apoprotein B-100. Even though hydrocarbon chains are mostly hydrophobic, each has a hydrophilic (get along with water well) carboxylic end (COOH), even cholesterol has a hydrophilic spot. So when it is time to form a lipoprotein, all component members position themselves in a way that all hydrophobic parts hidden inside and the hydrophilic ends expose on the surface interacting with water. What an ingenious design! Glory to God! Off the journey begins in the sea of life.

Elevated LDL is associated with increased cardiovascular risk, and the LDL particle size also has its implication; the smaller the size, the more dangerous. And this goes along with my thinking that both saturated and trans fats are of straight chains, which can be packaged into smaller, denser LDL particle. (Disclaimer: This is my 'logic' thinking and assumption of why LDL particle sizes vary) Current hypothesis is that triglyceride concentration is a determinant of small dense LDL particle.




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When I 'sea' food I eat it, and you should!

Jan 27, 2007
On the Book of Genesis, the fish appeared on the 5th day of Creation when the dry land and water were separated; thus making fish the important foods for Adam & Eve from the very beginning.

Eskimo consumes lots of fish with 40% of their daily calories derived from sea foods and yet the incidence of cardiovascular disease is very low. The answer lies in the omega 3 fatty acids. Salmon is a fatty fish rich in omega 3 fatty acid and the vegetable sources include Canola oil, soybean oil, and nuts. (If I am what I eat, I am a nut!)

The first and the second carbon in the carboxylic acid end of the long hydrocarbon chain of a fatty acid are named α and β, and the last one is named ω (omega) as ω is the last Greek alphabets. ω 3 fatty acid is one, in which the first cis double bond occurs in the third carbon from the ω end. They tend to be polyunsaturated with cis double bonds configuration.





Omega 3 fatty acid
The fatty acids of interest are virtually with even number of carbons; this is probably related to the fact of how it is made or degraded. The building block is acetyl CoA, which is a 2-carbon molecule and two carbons are added each step. Likewise two carbons are taken away on each step of degradation (oxidation) of fatty acid. The fact that the cis double bond occurring at the 3rd carbon from ω end makes it possible to have the maximal double bonds. For example, docosahexaenoic acid (an omega 3 fatty acid from fish and shellfish) has 22 carbons and 6 double bonds. Of polyunsaturated fatty acids, the more double bonds the more cardioprotective. Of note, each double bond has to be 3 carbons apart.

The major benefit of taking omega 3 fatty acids is its triglyceride-lowering effect. Long chain omega 3 fatty has been associated with reduced risk of sudden death after a heart attack or among men without prior cardiovascular disease. This is attributed to its antiarrhythmic (prevent serious irregular heart rhythm) properties. The title of the NEJM article is fitting: Fish--food to calm the heart. (NEJM 2002: 346;1102) But, it has been less convincing whether it can reduce the risk of developing a heart attack.

Unfortunately it may not be this rosy. Another article (NEJM 2002: 347;1747) reported the benefit from omega 3 fatty acids may be negated by the mercury which one get from the same fish. Increased mercury level is directlty associated with the risk of heart attack.

FDA has advised pregnant women not to eat swordfish, king mackerel, tilefish, shark, or fish from locally contaminated areas. Some advocate this advice should be extended to general population.

The take home message is that one needs to keep an eye on that mercury while enjoying your fatty omega 3 fatty acids.

If you are not a seafood lover (too fishy?) take comfort in that two servings of fish a week may be enough to confer cardioprotective effects.

The current so-called 'healthy diet' recommendation calls for 25-35% of daily calories derives from fats with less than 7% coming from saturated fats, and avoid all trans fats if at all possible. It is the type of fats, not the total amount of fats consumed that makes a difference. So read the nutrition labels and indulge yourself with a hearty fatty meal, and when you sea food, eat it!