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New Markers of Cardiovascular Health |
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(READING TIPS: For fast reading, scan through the topic headings in BOLD BLACK, important conclusions in BOLD BLUE, and " Must Know " in BOLD RED. To jump to specific sections in this article, click on the respective LINKS in the Contents.)
| Before You Begin Information presented here is for general educational purposes only. Each one of us is biochemically and metabolically different. If you have a specific health concern and wish my personalized nutritional recommendation, write to me by clicking here. |
Contents
Introduction
1. Lipoprotein(a) Connection
2.
The Mitochondrial Connection
3. The Homocysteine Connection
4. The Oxidative Stress Connection
5. Normalization of Traditional
Risk Factors
Discussion
Everyone is at risk for cardiovascular
disease, the leading cause
of death worldwide. The established risk factors for heart disease, such as
serum cholesterol level, smoking, and family history, account for only one-half
to three-fourths of the cases. The remainder are a result of other factors that
promote atherosclerosis (the buildup of fatty deposits in blood vessels) such
as infections. C. pneumoniae, a bacterium that causes respiratory infection,
has been found in 70-80% of plaques taken from a heart disease patient. The
jury is still out as far as the exact mechanism of injury is concerned. However,
it has been postulated that the infection triggers the immune system's response
and inflammation within the blood vessel wall. Large-scale research to determine
mechanism is currently underway.
Efforts to determine more ways of preventing heart disease have led to the
unearthing of about 300 predictors. One of these new markers for heart disease
is male baldness. Hair loss to the crown area has been linked to a three-fold
greater risk of heart disease in men, according to a study at Harvard Medical
School by Joanne Manson, chief of the Division of Preventive Medicine at Brigham
and Women's Hospital in Boston, and her colleagues. The connection may be elevated
male hormone levels. These findings will pave the way in the coming years to
new therapies.
Four new markers will be studied
- lipoprotein(a), mitochondrial function, homocysteine, and oxidative stress
and their ramifications for the promotion of optimum cardiovascular health.
1.
Lipoprotein(a) Connection
Fifty percent of Americans have elevated serum cholesterol levels. And the increase occurs naturally as we age. In men, most of the increase occurs after about age 45. In women, most of the increase occurs after age 55, and especially after menopause. The goal for cholesterol management is to lower the blood level of bad (low-density lipoprotein, or LDL)- cholesterol and increase the level of good (high-density lipoprotein, or HDL-) cholesterol as its job is to mop up LDL-cholesterol. There is no question that lowering dietary intake of cholesterol and saturated fats prevent heart disease because it lowers blood LDL-cholesterol levels.
Cholesterol levels alone cannot explain many heart attack deaths. Autopsy studies of heart attack victims, however, show that a good percentage of heart attack victims have clean vessels and ideal lipoprotein levels. It is obvious that there are other causes for heart disease than the traditional. Indeed, researchers with the Framingham Heart Study (the decades-long study that brought us the term "risk factor") identified a relative of LDL-cholesterol called lipoprotein(a) [Lp(a)], which is now recognized as MAJOR independent risk factor for heart disease. Lp(a) fosters the deposition of cholesterol on artery walls as well as interferes with the body's means of dissolving clots. Lp(a) fosters cholesterol deposition by enhancing oxidation of LDL-cholesterol. It is the oxidized form of cholesterol that penetrates the endothelium, leading to the build up of plaque and vascular disease.
Cardiovascular Disease and Supplementation
Some researchers believe that cardiovascular
disease is primarily caused by chronic deficiencies of vitamins and other essential
nutrients with defined biochemical properties, such as coenzymes, cellular energy
carriers, and antioxidants. Chronic depletion of these essential nutrients in
endothelial and vascular smooth muscle cells impairs their ability to function
properly.
Take the effects of Vitamin
C (ascorbic acid) deficiency as an example. Humans are one of a few animals
that cannot produce ascorbate. Humans must get Vitamin C from external sources.
Deficiency of Vitamin C leads to a disease called scurvy, the symptoms of which
are caused the reduced ability of the body to make collagen, an essential component
of wound healing, bones and joints, and blood vessels. Chronic ascorbate
deficiency leads to impairment in the structure of the blood vessel walls and
tiny lesions in its inner wall. These changes are the hallmarks of early atherosclerosis.
Atherosclerotic plaques can develop as the result of an overcompensating repair
mechanism consisting of deposition of systemic plasma and local cellular response
which includes extra cellular accumulation of Lp(a) and fibrinogen/fibrin at
the site of injury. This repair mechanism is exacerbated primarily at sites
of hemodynamic stress. This explains why the most frequent clinical manifestation
of cardiovascular disease such as myocardial infarction, is the local development
of atherosclerotic plaques in coronary arteries.
As a result of confirmation in animal studies, ascorbate with other essential
nutrients is now being recommended for the prevention and treatment of cardiovascular
diseases.
Mathias Rath and colleague conducted a yearlong study to determine the effect
of a defined nutritional supplementation program on the natural progression
of coronary artery disease. He gave 55 patients with various stages of coronary
artery disease, aged 44-67, a daily nutritional supplementation program including
2,700 mg of Vitamin C, vitamin B complex, 600 IU of Vitamin E (d-alpha-tocopherol),
450 mg of L-proline, 450 mg of L-lysine, 390 mcg of folic acid, 30 mg of coenzyme
Q-10, and 450 mg of citrus bioflavinoids. Changes in the progression of coronary
artery calcification before and during the program were determined by Ultrafast
Computerized Tomography. Before the intervention, the natural progression rate
of the coronary artery calcification averaged 44% per year. However, during
the year of treatment, the progression of coronary artery calcification decreased
by an average of 15%. In a subgroup of patients with early stages of coronary
artery disease, treatment resulted in a statistically significant decrease,
with no further progression of coronary calcification. In individual cases,
reversal and complete disappearance of previously existing coronary calcification
were documented. This landmark study, published in the Journal of Applied Nutrition
(1996, 48:3), showed that coronary
artery disease could be effectively prevented and treated by natural means.
In patients with early coronary calcification, progression was halted. In individual
cases with small-calcified deposits, nutritional supplement intervention led
to the complete disappearance of the deposits.
It is postulated that the nutrients
used by Rath initiate the reconstitution of the vascular wall. Ascorbate is
essential for the synthesis and hydroxylation of collagen. L-lysine and
L-proline are important substrates for the biosynthesis of matrix protein and
competitively inhibit the binding of lipoprotein(a) to the vascular matrix.
Maintaining the integrity and physiological function of the vascular wall
is the key therapeutic target in controlling cardiovascular disease.
It
is worth noting that Vitamin C, being water-soluble, is cleared through the
body very quickly, giving it a very short half-life. To
maintain continuous
optimum levels of Vitamin C in the body, ascorbate should be taken in divided
dosages throughout the day. To overcome this problem, a fat-soluble form of
Vitamin C, ascorbyl palmitate, has been developed. It
is readily absorbed from the gastrointestinal track and finds its way to the
micro-capillaries where it stays to exerts its health enhancing properties mentioned
above.
The amount of each nutrient required to prevent the onset of disease states
is outlined in the Recommended Dietary Allowances (RDAs).
As of July 2000, the RDA for Vitamin
C is 60 mg per day. This is about the amount present in one RED and will
prevent scurvy. The amount
for optimum health however, is less well defined.
Humans, other primates, and
guinea pigs do not produce ascorbate endogenously. Guinea-pigs
fed a diet low in ascorbate, an amount equivalent to the usual human intake,
rapidly developed atherosclerotic plaques, similar to those found in humans.
When large amounts of supplementary ascorbate were given to these guinea pigs,
there was a regression in plaque formation.
Linus Pauling, two-time Nobel Laureate, postulated that Lp(a) may be the surrogate
for ascorbate in the human. Low dietary intake of ascorbate leads to weakened
blood vessels because ascorbate is required for the synthesis of collagen and
elastin, which strengthen the blood vessel wall. In the absence of sufficient
ascorbate, Lp(a) is mobilized to repair these structural defects in arterial
walls by being deposited to strengthen the tissue. However, if the plasma concentration
of Lp(a) is too high, the process goes too far. Too much Lp(a) gets deposited
in the arterial wall, and plaque formation is initiated. Dr. Pauling concluded
that the optimum intake of Vitamin C is perhaps 100 times more than the RDA.
During the last 25 years of his life (he died at age 93 from cancer), Dr Pauling
increased his own intake of Vitamin C from 50 time to 300 times the RDA, taking
3,000 mg to 18,000 mg per day. This amount is consistent with the amount of
ascorbate in animals that are capable of producing their own on a daily basis.
It is fair to say that Dr. Pauling believed that cardiovascular disease is the
general result of ascorbate deficiency.
Preventive Nutritional Supplement
Consideration:
Ascorbyl Palmitate: 200 - 400 mg
L-Lysine: 200 - 400 mg
L-Proline: 200 - 00 mg
Ascorbate: 1,000 - 3,000 mg
If you have high lipoprotein(a), the only way to bring it down is with the Pauling Therapy which consists of- high dose Vitamin C ( 4-6 grams), L-lysine (4-6 grams), L-proline (2-4 grams). L-carnitine (1500 to 3000 mg) should also be included. Your Vitamin C intake can be significantly reduced if you are taking the fat soluble form (ascobyl palmitate).
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2. The Mitochondrial Connection
Mitochondria are the energy factories of the cell. The energy currency they produce is ATP. Generation of ATP is therefore vital to cellular process. Coenzyme Q10, or ubiquinone, is a vital component in the ATP-generating process. It acts as an electron acceptor/proton donor; hence its presence in the body is fundamental to the support of cellular life. It is omnipresent in body tissues.
Coenzyme Q10 (Ubiquinone)
The body's production of CoQ10 begins to decline after age 20 to just 50% of levels by age 70. Because the function of the heart is so dependent on the energy produced with the help of CoQ10, CoQ10 is extremely important for heart health. It is also important as a powerful antioxidant and a membrane stabilizer. The range of heart conditions for which research has found CoQ10 beneficial include (1) congestive heart failure, (2) cardiomyopathies, (3) arrhythmias, (4) angina, when there is a lack of oxygen, and (5) muscular dystrophy.
Individuals with cardiac disorders have been identified as having abnormally low levels of CoQ10. Numerous long-term studies have been conducted to ascertain the efficacy of CoQ10. These studies indicate that there is a statistically significant improvement in the condition of those patients with myocardial dysfunctions such as ischemic cardio-myopathy or congestive heart failure when they take CoQ10. In an 8-year study of 424 patients with cardiac dysfunction, 58% improved by one functional class, 28% by two classes, and 1.2% by three classes. Further, overall medication requirements dropped, with 43% of the patients discontinuing between one and three drugs. Only 6% were required to add one drug. In another study on 40 patients undergoing elective coronary artery bypass surgery, pretreatment with CoQ10 at 150mg/day for seven days served as a protection against oxidative compounds.
CoQ10 also plays a vital role as an antioxidant in cellular membranes and plasma lipoproteins. It is present in all plasma membranes and in LDL-cholesterols. Studies illustrate CoQ10's protective action against the oxidative modification that makes LDL-cholesterol atherogenic. In its reduced form, ubiquinol, CoQ10 also functions as a chain-breaking antioxidant and is believed to regenerate Vitamin E.
You can get CoQ10 from your diet, although the amount of food intake is insubstantial. For example, one pound of sardines or 2.5 pounds of peanuts provide 30 mg of CoQ10.
Working synergistically with CoQ10 are two endogenous antioxidants that enhance mitochondrial function and reduce free radical damage - L-Carnitine and Lipoic Acid.
L-Carnitine and Lipoic Acid
The ability of the cell to utilize fatty acids as a source of fuel is essential for optimizing the production of ATP by mitochondria in cardiac cells to keep the heart properly functioning. L-carnitine assists in this transportation process by bringing fatty acids from the extracellular space into the mitochondria. In one double blind trial, 500 mg per day of a modified form of carnitine called propionyl-L-carnitine lead to a 26% increase in exercise capacity after six months.
Lipoic Acid is both a water- and fat-soluble antioxidant. It neutralizes free radicals in both the fatty and watery regions of cells, in contrast to Vitamin C, which is water soluble, and Vitamin E, which is fat soluble. Lipoic acid is therefore called the "universal antioxidant". It has the ability to recycle both Vitamin C and E in our body. It helps break down sugars so that energy can be produced from them through cellular respiration. In addition to serving as the bulb of the body's antioxidant network, lipoic acid is the only antioxidant that can boost the level of intracellular glutathione, a cellular antioxidant of tremendous importance. Glutathione is a water-soluble antioxidant and is essential for the optimum functioning of the immune system.
Nutritional Supplement Consideration:
Coenzyme Q10: 30 - 120 mg
L-Carnitine: 500 - 2,000 mg
Lipoic Acid: 150 - 300 mg
| Attention Because of tremendous individual variation, the use of nutritionals should therefore be personalized for your body. One person’s nutrient can be another person’s toxin. If you have a specific health concern and wish my personalized nutritional recommendation, write to me by clicking here. |
3. The Homocysteine Connection
Homocysteine is an amino acid by-product of food metabolism. It contributes to atherosclerosis, reduces the flexibility of blood vessels, and increases clotting by making platelets stickier and slows blood flow. Studies show a direct correlation between high serum homocysteine levels increases risk of heart attack and stroke.
Research has shown that folate and other B vitamins break down homocysteine. The American Heart Association currently advocates that people who are at high risk of heart disease include more folate and other B vitamins in their diet - at least 400 microgram's worth. Studies have been conducted that show very modest supplementation of Vitamin B-6 (10mg), folic acid (650 mcg), and Vitamin B-12 (400 mcg) reduce plasma serum homocysteine levels by 49.8% in men with hyper-homocysteinemia.
Nutritional supplement Consideration:
Folate: 400 - 800 mcg
Vitamin B-12: 400 - 1,000 mcg
Vitamin B-6: 5 - 20 mg
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4. The Oxidative Stress Connection
Oxidative stress by free radicals in our body contributes to cardiovascular disease. During oxidative stress, free radicals produce structural changes in serum LDL-cholesterol. These damaged LDL-cholesterol molecules are recognized as foreign to the body, and are therefore phagotized (engulfed) by macrophages (specialized white blood cells). These macrophages then fill up with lipids, forming "foam cells" that aggregate and adhere to the inner surface of blood vessels. They contribute to the development of lesions on the artery wall, initiating a cascade of events that ultimately lead to atherosclerosis.
Over the years, research has consistently shown that Vitamin E offers significant protection against cardiovascular disease. Not only does Vitamin E reduce the risk of heart attack, it also inhibits platelet aggregation, increases the survival rate of patients undergoing bypass surgery and protects against other heart ailments, including angina. In the Cambridge Heart Antioxidant Study, 2002 patients with proven coronary heart disease were given 400 to 800 IU Vitamin E in a double-blind, randomized, placebo-controlled setting. Beneficial effects were apparent after one year of treatment. Other studies have shown that 100 IU per day of Vitamin E can significantly decrease coronary artery lesion progression. 800 IU per day reduced LDL susceptibility to oxidation by 50%. Furthermore, recent studies have determined that there is a synergistic effect between alpha- and gamma-tocopherol. This combination offers a greater level of protection against oxidative damage than either one alone.
Nutritional Supplement Consideration:
Vitamin E: 400 - 800 IU (alpha- or mixed-tocopherol)
5. Normalization of Traditional Risk Factors
Optimum cardiovascular health entails controlling the well-known risk factors including elevated cholesterol levels, hypertension, and stress. Elevated cholesterol levels can be controlled through drugs or natural supplements such as fiber, niacin, and more recently, red yeast rice powder (600 mg two times a day). Control of hypertension can be accomplished through drugs and/or natural supplementation such as Hawthorne (250 mg), magnesium (400 - 700 mg), calcium (800 - 1,000 mg), and potassium from food (400 - 600 mg). Adjunct nutritional supplementation to enhance stress reduction includes antioxidant nutrients such as coenzyme Q10 (CoQ10) and Vitamin E, Vitamin B complex, and Magnesium. These antioxidants counteract the increase in oxidative stress associated with psychological stress.
Discussion
It
is obvious that the traditional risk factors such as cholesterol, hypertension,
and stress, while good markers of cardiovascular disease, do not tell the whole
story. The fact that many people develop cardiovascular disease in spite of
normal cholesterol levels, normal blood pressure values, and relatively low
stress environment imply that there are other risk factors yet to be discovered. Four such markers are explored. Standardized laboratory references have yet to be established for these new markers and may never be established due to their multi-factorial complexity of cardiovascular disease. A natural nutritional supplementation approach appears to the best available option for those who don't want to wait.
- Lipoprotein(a): Ascorbyl Palmitate 200 - 400 mg, L-Lysine 200 - 400 mg, L-Proline 200 - 400 mg, and Ascorbate 1,000 - 3,000 mg.
- Mitochondrial Function: Coenzyme Q10 30 - 120 mg, L-Carnitine 500 - 2,000 mg, and Lipoic Acid 150 - 300 mg.
- Homocysteine Axis: Folate 400 - 800 mcg and Vitamin B12 400 - 800 mcg.
- Oxidative Stress: Vitamin E 400 - 800 IU.
| Message from Dr. Lam I hope you have enjoyed reading this article. If you have areas you don’t understand, comments (good or bad), or if you have a specific health concern, feel free to write to me by clicking here. |
About The Author
Michael Lam, M.D., M.P.H., A.B.A.A.M. is a specialist in Preventive and Anti-Aging Medicine. He is currently the Director of Medical Education at the Academy of Anti-Aging Research, U.S.A. He received his Bachelor of Science degree from Oregon State University, and his Doctor of Medicine degree from Loma Linda University School of Medicine, California. He also holds a Masters of Public Health degree and is Board Certification in Anti-aging Medicine by the American Board of Anti-Aging Medicine. Dr. Lam pioneered the formulation of the three clinical phases of aging as well as the concept of diagnosis and treatment of sub-clinical age related degenerative diseases to deter the aging process. Dr. Lam has been published extensively in this field. He is the author of The Five Proven Secrets to Longevity (available on-line). He also serves as editor of the Journal of Anti-Aging Research.
For More Information
For the latest anti-aging related health issues, visit Dr. Lam
at www.LamMD.com. Feel free to email
Dr. Lam at dr@LamMD.com if you have any questions.
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