The Homocysteine and Cardiovascular Disease connection: Further Information

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The Homocysteine and Cardiovascular Disease connection: Further Information

JoAnn Guest Aug 01, 2005 16:29 PDT

 

 

http://www.willner.com/article.aspx?artid=166

 

Further Information on the Homocysteine and Cardiovascular Disease

connection.

 

A recent study in the journal, Circulation, has cast some doubt on the

exact nature of the link between homocysteine and heart disease.

 

An editorial in that publication implied that we may in fact be somewhat

premature in how we have viewed the role of homocysteine.

 

While it may be true that we do not yet have all of the facts, we need

to be careful to keep everything in proper perspective.

 

We do know that there is a connection, and we do know that increasing

the B vitamins folate, B6 and B12, with a lowering of homocysteine,

seems to be protective. It is certain worth trying for those who are at

risk.

 

What is the downside of increasing our supplement and or dietary intake

of these inexpensive and beneficial nutrients?

 

Steve Austin, N.D., wrote an insightful commentary in the Quarterly

Review of Natural Medicine 12-31-98 p. 305-307

 

His article was titled " Clouds Appear in the Relationship Between

Homocysteine and Cardiovascular Disease " .

 

Readers of this column know that numerous trials report a positive link

between serum homocysteine and coronary heart disease (CHD).

 

Likewise, there is clear evidence that folic acid and to a lesser

extent vitamins B6 and B12 lower homocysteine levels. As homocysteine

induces vascular damage both in vitro and in animal models,

it has been widely assumed that homocysteine is not simply a marker,

but rather probably a contributory agent.

 

Recently, a large (232 coronary heart disease cases) nested

(prospective) case control study by Folsom, et al. in Circulation was

" unable " to solidly confirm an independent correlation between elevated

homocysteine and cardiovascular disease (average follow up of 3.3

years).(1)

 

In that report, higher B6 status (measured as pyridoxal 5'-phosphate)

correlated strongly with protection, but dietary B6 did

not, nor did other B vitamins.

 

If the relationship between PLP and

cardiovascular protection had anything to do with homocysteine, folic

acid status should have also been linked to protection because " folate

status " is a much stronger determinant of homocysteine levels than is B6

status.

 

A skeptical editorial appeared in the same issue of Circulation.(2) In

that editorial, the follow points were made, with literature support:

 

•Myocardial infarction " increases " homocysteine, providing a different

perspective on what might be chicken and what might be egg.

 

•In vitro experiments purporting to show that homocysteine is

atherogenic are conducted at concentrations far " in excess " of what

really " occurs " in vivo.

 

•There is at least some animal evidence that B-vitamin

supplementation-induced decreases in homocysteine are not accompanied by

" improvement " in endothelial function.

 

•Several lines of research have not linked genetic defects in enzyme

activation that cause homocysteine elevations to vascular disease,

suggesting that the strong link between homocysteine and CHD may not be

" cause and effect " .

 

An hypothesis is put forward in the editorial that possibly the

inflammatory component of atherosclerosis increases demand for folic

acid, and the drop in folate status causes homocysteine to rise, but

only as a marker -- not as a " significant " player.

 

On the other hand, the editorial acknowledges that B-vitamin deficiency

might be directly linked to heart disease and treating with supplements

might be protective, though the consequent fall in homocysteine might

merely be the decline of an " uninvolved marker " .

 

There remains little question that B-vitamin supplementation lowers

homocysteine(3) -- the recent publications do not dispute that.

 

In fact, some of the recent links between B-vitamin supplementation and

reduction in heart disease(4) were acknowledged in the Circulation

editorial.

 

Other such studies, however, were ignored,(5) including the recent

intervention trial wherein B-vitamin supplementation (250 mg vitamin B6

per day and 5 mg of folic acid) given to a group with high homocysteine

levels resulted in an incidence of cardiovascular disease no higher than

in people with normal homocysteine levels(6) -- a hopeful though not

" conclusive " study.

 

What do the data from the Folsom trial really tell us?

 

A look at the fine print is actually quite different from the negative

message broadcast by the media following publication.

 

Actually, a closer look reveals that the Folsom trial found the

following:

 

•Serum pyridoxal 5' phosphate (PLP) correlated strongly and inversely

with CHD in both sexes.

 

•Homocysteine did " correlate " with CHD -- but " only " in women.

 

•Plasma folate correlated very strongly and inversely with CHD -- but

" only " in women (p=0.003).

 

•As expected, supplement use correlated strongly with reduced

homocysteine.

 

•Supplement use was high in healthy controls, but the difference did not

reach " statistical significance " .

 

•There was no correlation whatever between dietary B vitamins and CHD.

 

Circulation editorial opinions aside, what are we to glean from these

data?

 

The Folsom trial clearly supports the link between B-vitamin

supplementation and reduced homocysteine levels.

 

Further, it shows a link between serum homocysteine and CHD, but the

relationship was limited to women only.

 

It is not at all clear why there was no relationship in men. Nor is it

clear why most significant relationships in the study " softened " when

controlled for HDL and total cholesterol, smoking, and other risk

factors.

 

The stronger effect with supplements compared with food is to be

expected in that, particularly with folate, bioavailability is far

better from synthetic pills than from natural

sources.

 

Finally, the very strong link between PLP and CHD prevention requires

further investigation.

 

The idea of " normalizing physiology " by supplying B vitamins to patients

with a need for secondary prevention of coronary heart disease and with

elevated homocysteine levels will still make sense to many healthcare

professionals.

 

But only intervention trials will tell us whether such

supplementation will " actually " reduce " coronary artery disease " " risk "

in the same predictable way it lowers homocysteine.

 

Some kind of link between B vitamins, homocysteine and CHD still appears

to exist (though the current study found it only in women).

 

The question remains, however, what's chicken and what's egg?

 

Dr. Austin has been a guest on The Willner Window, and is a contributor

to Health Notes Online. He Is author of Breast Cancer: What You Should

Know (But May Not Be Told) About Prevention, Diagnosis and Treatment.,

available at Willner Chemists.

 

(1) Folsom AR, Nieto J, McGovern PG, et al. Prospective study of

coronary heart disease incidence in relation to fasting total

homocysteine, related genetic polymorphisms, and B vitamins. Circulation

1998;-98:1-7. (2) Kuller LH, Evans RW. Homocysteine, vitamins, and

cardiovascular disease. Circulation 1998;98:196-9 [editorial]. (3)

Homocysteine Lowering Trialists' Collaboration. Lowering blood

homocysteine with folic acid based supplements; eta-analysis of

randomised trials. BMJ 1998; 316:894-8. (4) Peterson JC, Spence JD.

Vitamins and progression of atherosclerosis in

hyper-homocyst(e)ineaemia. Lancet 1998; 351:1008 [research letter]. (5)

Rimm EB, Willett WC, Hu FB, et al. Folate and vitamin B6 from diet and

supplements in relation to risk of coronary heart disease among women.

 

JAMA 1998; 279:359-64. (6) de Jong SC, Stehouwer CDA, van den Berg M, et

al. Normohomocysteinemia and vitamin-treated hyperhomocysteinemia are

associated with similar risks of cardiovascular events in patients with

premature peripheral arterial occlusive disease. A Prospective study.

 

JoAnn Guest

mrsjo-

DietaryTi-

www.geocities.com/mrsjoguest/Diets

Netherlands J Med 1998; 52:S41.

 

 

 

 

AIM Barleygreen

" Wisdom of the Past, Food of the Future "

 

http://www.geocities.com/mrsjoguest/Diets.html

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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