Vitamin E and Heart Disease...
Lets Clear Up the Confusion

Today the topic of vitamin e and heart disease is a hotspot of interest. It seems almost monthly a new press report is released. But experimental findings are not clear-cut... decisive results from one clinical trial often challenge or even contradict findings from another trial. Depending upon the trial, the vitamin E and heart disease connection may be beneficial, neutral or even harmful!

How are we to understand this wealth of important, but often conflicting data? Are there any facts that can be firmly established??

As with life, so it is with science... the path to understanding is a journey fraught with many twists and turns. Discovering factual relationship between vitamin E and heart disease is a challenging but definitely worthwhile endeavor. Stay with me! You will be richly rewarded! Ready?

Lets begin by listing some benefits derived from vitamin E and heart disease studies. Then we will see how these benefits are gleaned from experimental research and clinical trials.

Vitamin E and Heart Disease...
Benefits Derived From Research and Clinical Trials

1) Vitamin E has Well-Established "Antioxidant" Function and is Vital for Protection of Your Body From Damaging Free Radicals

2) Vitamin E Protects LDL Cholesterol From Oxidation, a Key Step in the Genesis of Heart Disease.

3) Healthy Individuals May Benefit From Vitamin E Supplementation by Preventing the Initial Stages of Atherogenesis

4) Individuals With Established Cardiovascular Disease May Benefit From Vitamin E Confirmed Anti-Inflammatory Action

5) Vitamin E is Safe and Effective When Supplemented With the Full Spectrum of Anti-Oxidant Vitamins and Minerals

These benefits are real and tangible for anyone. In order to understand how you can experience them, we will examine the vitamin E and heart disease topic very carefully. But first things first. Lets start at the beginning and see how heart disease develops...

How Does Heart Disease Begin?

Atherosclerosis, or "hardening of the arteries" is a major cause of heart disease in America today. Atherosclerosis occurs when fibrous plaque, composed primarily of cholesterol, accumulates in the artery walls and eventually restricts blood flow to a vital organ. The coronary and carotid arteries supplying the heart and brain are the usual blood vessels affected. Ultimately, when arterial blood flow to the heart or brain is blocked, a heart attack or stroke results

Atherosclerosis is an "inflammatory process" and a key event triggering atherosclerosis appears to be high blood levels of low density lipoprotein (LDL), your "bad cholesterol".

Heres why...

Low density lipoproteins (LDL) particles circulate in your blood and are rich sources of cholesterol. Cholesterol and fats in general are prime targets of free radicals.

Free radicals are highly unstable molecules that seek stability by snatching electrons from any nearby molecule... proteins, fats, DNA and, of course, LDL particles. If this destructive electron snatching process called oxidation is not stopped, a vicious , runaway chain reaction occurs.

"Accumulating science now strongly indicates the oxidation of cholesterol and other fats within the LDL particle by free radicals is the key step triggering a physiological cascade of events culminating in atherosclerosis and heart disease!"

Lets break it down and see if we can make sense out of this...

Step 1)
LDL cholesterol is oxidized or denatured to a physiologically harmful state by free radicals

Step 2)
Next, these oxidized LDL particles are "captured" by immune system cells within the artery wall called "macrophages". Special "scavenger receptors" on macrophages recognize and engulf oxidized LDL... only LDL particles oxidatively damaged by free radicals. In fact, natural, non-oxidized LDL is ignored by macrophages.

As this process continues, more oxidatively damaged LDL within the artery wall is engulfed, enlarging the macrophage.

Step 3)
This enlarged macrophage morphs into what is called a "foam cell". Eventually, the cholesterol containing foam cell bursts and ruptures its contents within the artery wall, forming a "fatty streak". And a fatty streak is the immediate precursor to an artherosclerotic lesion and coronary heart disease.

So how does vitamin E fit into the picture you ask? Good question!

Lets Take a Look at The
Vitamin E and Heart Disease Connection...

Vitamiin E circulates in the blood and is the major "antioxidant vitamin" associated with LDL particles. Laboratory studies unequivocally demonstrate vitamin E inhibits and prevents oxidation of LDL. This is well-established fact. For example, oxidation of LDL can take place only after the loss of antioxidants like vitamin E, beta-carotene, lycopene and ubiqunol.

Vitamin E and Heart Disease
Journal of Lipid Research

And supplementation studies with antioxidant vitamin E reduces oxidation of LDL. Healthy volunteers receiving 268, 537, or 805 milligrams vitamin E per day for 8 weeks showed reduced LDL oxidation. But what about supplementation with vitamin E at lower doses of only 40 or 134 mgs per day?

No significant effect!

Vitamin E and Disease
The Biochemical Journal

These studies clearly prove vitamin E inhibits oxidation of LDL, very likely the key step leading to plaque build-up and heart disease.

So far, so good, right? But now we are going to throw a wrench into the picture. Are you ready?

Vitamin E and Heart Disease
What are the Clinical Findings?

However randomized, placebo controlled clinical trials have generally failed to show clear-cut benefits...

Vitamin E and Heart Disease
The HOPE Study

For example, the Heart Outcomes Prevention Evaluation (HOPE) Study was a randomized, placebo controlled trial of 6990 men and 2545 women with established cardiovascular disease or diabetes. Individuals were randomized to receive either 400 IU natural vitamin E, placebo or a drug called Ramipril. The primary endpoint was a composite analysis of Myocardial infarction (MI), stroke and mortality from cardiovascular causes. The findings?

After 4.5 years, there was no statistically significant difference in outcomes between vitamin E and placebo. However, individuals randomized to Ramipril experienced a 22 % significant reduction in the primary trial outcome.

Vitamin E and Heart Disease
The New England Journal of Medicine

Vitamin E and Heart Disease
The GISSI Study

Likewise, the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI) Prevenzione trial was conducted in men and women who have had a recent myocardial infarction (heart attack). Individuals received either 300 mg of synthetic vitamin E daily, no supplement (the control arm), or a polyunsaturated fatty acid (PUFA). And the results?

Vitamin E didn't confer any benefits compared to placebo, however the PUFA achieved a statistically significant reduction of -10 to -15% in the primary trial outcome

Vitamin E and Heart Disease

Vitamin E and Heart Disease
The CHAOS Study

In sharp contrast to HOPE and GSSI studies, individuals with advanced or established CVD showed dramatic benefit with vitamin E supplementation in the Chaos and SPACE studies.

Specifically, the Cambridge heart and antioxidant study (CHAOS), is a secondary prevention trial designed to determine if alpha tocopherol could reduce cardiovascular death inn 2002 individuals with overt clinical and angiographic evidence of cardiovascular disease. After 510 days, individuals receiving 400 0r 800 IU vitamin E / day experienced a 77% significant reduction for non-fatal myocardial infarction (heart attack).

Vitamin E and Heart Disease
The SPACE Study

And in the Space study chronic hemodialysis patients with preexisting CVD received either 800 IU natural vitamin E or placebo for 519 days. Those patients randomized to vitamin E experienced a - 54% significant reduction in adverse heart outcomes.

What Do These Trials Mean?
Is the Vitamin E and Heart Disease Connection Valid?

The totality of these and other clinical trials of vitamin E and heart disease are inconsistent.

We must take a look at differences in experimental design and approach to understand discrepancies in experimental findings. Specifically, experimental parameters must be "standardized" or applied in a uniform way in order to accurately compare results from different trials. These experimental parameters include:

1) Selection of Individuals

2) Absorption Efficiency of Vitamin E

3) Dosage and Form of Vitamin E

4) Stage of Disease

5) Nutritional Interactions

Lack of standardization or uniform application of these variables across these trials have probably confounded the results and obscured meaningful interpretations. Lets take a look and see if we can make a little sense and headway out of all this...

Vitamin E and Heart Disease Clinical Trials
#1) Selection of Individuals

Clinical trials designed to test efficacy of supplementation with vitamin E should monitor the vitamin E status of individuals at the outset of the trial and at progressive intervals during the trial. Measuring the baseline level of alpha tocopherol in the blood before and during the trial confirms....

1) Initial vitamin statusWhat is the initial vitamin status of the individual? Are blood levels normal or is the individual actually vitamin e deficient and in an position to benefit from supplementation? If baseline levels of vitamin E are not measured at the outset of the trial, we have very little frame of reference to compare subsequent measurements against.

2) Proper Monitoring of blood plasma levels of vitamin E at pre-determined intervals confirms if the vitamin is actually being digested and absorbed into bloodstream during the trial.

Unfortunately, baseline levels of vitamin E were not universally measured in all of the trials - specifically the HOPE and GSSI studies. Therefore it is not possible to confirm if successful vitamin E absorption occurred in these trials. Also digestion and absorption of vitamin E is optimal only under certain conditions...

Vitamin E and Heart Disease Clinical Trials
#2) Optimal Absorption of Vitamin E

As a fat-soluble vitamin, vitamin E is most efficiently solubilized or dissolved along with other fats provided in the diet. Therefore, digestion and absorption of vitamin E is maximized in meals that contain sufficient levels of lipid or fat. Failure to inform individuals selected for clinical trials of these requirements may also reduce amount of vitamin E absorbed into bloodstream and diminish potential therapeutic benefits. Failure to control this variable introduces more uncertainty into the outcome of these trials

Vitamin E and Heart Disease Clinical Trials
#3) Dosage and Form of Vitamin E

Equally important, the dose and form of vitamin E varied significantly between clinical trials of vitamin E:

Hope study = 400 IU vitamin E per day from natural sources

GSSI study = 300 mg per day all rac-alpha-tocopherol

ChAOS Study = 400 or 800 IU per day RRR-alpha-tocopherol from natural sources in soy oil

SPACE Study = 800 IU vitamin E per day

Once again, the lack of experimental standardization between various trials makes comparisons difficult and may prevent meaningful interpretations

Vitamin E and Heart Disease Clinical Trials
#4) Stage of the Disease

We know vitamin E is proven effective reducing oxidation of LDL, a key step leading to the initial stages of atherosclerosis. But atherosclerosis is a progressive disease. By the time atherosclerosis is advanced, extreme structural disorganization of the arterial wall or intima has occurred. The soft fatty streaks of the initial stages have enlarged with fat and hardened with minerals (especially calcium), finally being surrounded by scar tissue. This "plaque" stiffens the arteries and narrows their diameter, frequently resulting in high blood pressure.

As powerful as nutrients are, they don't perform miracles. Is it realistic to expect a simple nutrient like vitamin E to reverse the progress of advanced stages of atherogenesis? At a stage where extreme structural disorganization of the artery wall has already occurred?

But remember, in the CHAOS and SPACE studies, we discovered individuals with advanced or established CVD experiencing dramatic benefit with vitamin E supplementation. In fact, participants in the Space study experienced a 54% reduction in adverse events while Chaos participants experienced a Whopping 77% reduction in myocardial infarction

How do we explain these beneficial results? If the oxidative preventative hypothesis of vitamin E is correct, vitamins E is very effective reducing oxidation of LDL particles - at the very early stages of atherogenesis before significant plaque build-up occurs.

So how can we explain the fact that individuals with well-established CVD experienced the beneficial effects of vitamin E in Chaos and Space studies?

Is it be possible vitamin E has alternative or multiple modes of action?

In fact, accumulating science now reveals additional biofunctions of vitamin E...

Beneficial Non-Antioxidant Functions
Vitamin E and Heart Disease

Atherosclerosis is a raging inflammatory response within the blood vessels. In addition to the well known antioxidant properties of vitamin E, vitamin E inhibits many key events of inflammation

Inflammatory Events Inhibited by Vitamin E

1) Vitamin E Prevents Aggregation of Platelets

2) Vitamin E Inhibits Monocyte Adhesion to Blood Vessel Cell Walls

3) Vitamin E Reduces the Production of Collagen in Human Fibroblasts

4) Vitamin E Inhibits [LDL induced] Proliferation of Smooth Muscle Cells

"These non-antioxidant functions of vitamin E may help explain beneficial results in some of the vitamin E and heart disease studies performed in individuals with advanced cardiovascular disease such as CHAOS and SPACE."

Vitamin E and Heart Disease Clinical Trials
#5) Nutritional Interactions or "Synergy"

Optimal nutritional health is an interdependent process and depends upon balanced teamwork of many nutrients working together for maximum benefit of your body. These powerful nutrient interactions are "synergistic".

How does "synergy" relate to vitamin E and heart disease? I'm glad you asked!!

Vitamin E, Heart Disease and Free Radicals

Vitamin E protects living tissue from the harmful effects of free radicals... highly unstable molecules with unpaired electrons in their outer atomic orbital.

Free radicals do enormous damage... seeking stability by snatching electrons from other biological molecules... proteins, lipids and fats - and, of course, LDL particles!

If this destructive electron-snatching process called oxidation is not stopped, a vicious runaway chain reaction of electron snatching ensues. In the process, the natural function of these vital molecules are destroyed in your body.

This is where vitamin E enters the picture...

Vitamin E prevents and stops destructive auto-oxidative chain reactions within the LDL particle by donating its own electron to the electron-starved free radical - becoming electron deficient in the process.

At this point, if the now electron-deficient vitamin E is not reduced with an electron by another electron donor like vitamin C, vitamin E may promote chain reactions by snatching an electrons from fats, proteins and DNA.

What does this mean to you?

Vitamin E clearly requires co-antioxidants like vitamin C for proper physiological function in your body. Nutrients like vitamin C and E work together synergistically and must be properly balanced in your diet or supplement.

"Mono-supplementation with large doses of E without C and other antioxidants negates this natural synergy and may even be detrimental to your health"

If you desire optimal nutritional health, always consider a "full spectrum" or complete vitamin and mineral supplement.

Artificially designed clinical trials testing the effects of only 1 or 2 vitamins are divorced from the reality of how nutrients actually behave in your body. In many cases they are almost "pre-designed to fail" This may help explain the inconsistent and often unpredictable outcomes of many of these randomized trials... they are not properly designed.

Evaluation of vitamin E and heart disease across clinical trials are confounded by lack of standardization of numerous experimental parameters such as dosage, form of vitamin E, stage of disease, etc. Nevertheless, we can still glean a few kernels of truth from vitamin E and heart disease research:

Vitamin E and Heart Disease...
What Have We Learned?

1) Vitamin E has well-established antioxidant function and is vital for protection of living tissue from free radicals

2) Vitamin E protects LDL particles from oxidation, a key step in the genesis of heart disease.

3) Healthy individuals may benefit from vitamin E supplementation by preventing the initial stages of plaque build-up

4) Vitamin E commonly classified as an antioxidant vitamin, also has specific anti-inflammatory roles inhibiting inflammation within blood vessels. This may help explain cardiovascular benefits derived from vitamin E and heart disease supplementation studies in those individuals with advanced cardiovascular disease.

5) Individuals with established cardiovascular disease may benefit from vitamin E confirmed anti-inflammatory action

6) Vitamin E is safe and effective when supplemented with the full spectrum of anti-oxidant vitamins and minerals like vitamin C, vitamin A, iron, selenium, manganese, etc. Monosupplementation vitamin E and heart disease clinical trials utilizing high levels of only vitamin E may actually promote pro-oxidative action and should only be recommended by a physician for individuals with specific vitamin E deficiencies.