Anticoagulants
One of the primary treatments applied for patients with coronary
artery disease are anticoagulants. The aging process lends itself
to increased coagulability. The obvious consequence of hypercoagulability
is clot formation and subsequent artery occlusion. Increase in blood
viscosity can create a hemodymamic state of ischemia, with its own
set of circumstances. Ischemia is defined as low blood flow, which
may or may not have total obstruction associated with it. Ischemia
can lead to apoptosis and inflammation. Evaluation of ischemic potential
can be approached with a functional coagulation panel. This composite
of tests includes the typical PT, PTT tests and also the more comprehensive
combination of fibrinogen, prothrombin fragments one and two, thrombin-anti-thrombin
complexes, soluble fibrin monomers and platelet CD62P (Selectin)
receptors. A valuable test for evaluation of clotting is platelet
aggregation testing. Platelet aggregation occurs with the presence
of adenosine, epinephrine, collagen and thrombin. Most anti-platelet
aggregation medications work only in the presence of adenosine (aspirin
for example). This may explain why type A personalities using aspirin
still have clot formation. In contrast EDTA (ethylene diaminetetracetic
acid), inhibits aggregation to all of the substances above with
the exception of collagen. Acute phase reaction, particularly a
high c-reactive protein, is related to vascular inflammation and
or infection. Substances, such as coumadin affect prothrombin/thrombin
activation. Natural products like vitamin E and magnesium have similar
properties. Platelet hyperactivity is minimized by aspirin and similarly
by other natural products like ginkgo and ginger. Fibrinogen/fibrin
monomers can be addressed with enzymatic therapy like bromelain
and pancreatin. Natural substances, that have similar reaction to
heparin, are arginine, niacin, bromelain and papain. I have found
clinically that increased fibrinogen levels of greater than 400
mg respond quickly and effectively to Curcuma longa.
 |
Vasodilation
An important component to coronary artery disease treatment is vasodilation.
The consequence of vasodilation is improved blood flow and subsequent
increase in tissue oxygenation. The object of nitrates or nitrate
therapy, a mainstay of both acute and chronic coronary arterial
disease care is to increase blood flow to constricted blood vessels,
whether this stricture is created by plaque or by vasospasm. The
natural substance, arginine, for example, is said to increase nitric
oxide, a free radical (part of a group of compounds known as endothelial
releasing factor, EDRF) that functions as a vasodilator. Nitric
oxide has a secondary effect to potentially reduce the damage created
by homocysteine. It has been hypothesized that EDTAÕs benefit
can, to a large degree, be attributed to its release of nitric oxide.
Of course, EDTA is an excellent anti-coagulant.
Also worthy of note, cayenne pepper has excellent effects on blood
lipids, platelet activity, and vasodilatory action. As a wonderful
first aid remedy, one teaspoon of cayenne in a glass of water can
quickly relieve the discomfort of acute chest pain caused by angina.
Lipid Modulation
There are many products that effectively control dyslipidemia without
the side effects often associated with conventional medical drugs.
For elevated cholesterol, a combination of pantethine and inositol
hexacotinate can demonstrate profound improvements in one month.
For those patients with elevated triglyceride levels, L-Carnitine,
as well as EFAs, can often solve the problem. I prefer the inositol
hexanicotinate form of niacin due to its absence of the troublesome
side effects of flush and liver irritation. Its mechanism of action
is similar to all niacin compounds to reduce plasma triglycerides,
VLDL, LDL synthesis and total cholesterol. Pantethine is the active
hormone of pantethenic acid. It is considered to be one of the most
important parts of coenzyme A (CoA) that transports fats to and
from the cells. It has a potent effect on cholesterol as well as
triglycerides. L-Carnitine is synthesized from lysine with the help
of methionine. It improves triglyceride levels, total cholesterol
and increases HDL. The n-3-polyunsaturated acids in large enough
doses have been shown to be helpful in many studies. The DART study
and most recently the GISSI study (published in The Lancet) are
good examples. The role of omega-3 fatty acids are several, but
recent studies report that their most profound effects may be on
arrhythmogenesis as well as inflammation. The GISSI study reported
a substantial decrease in cardiovascular events as a result of fish
oil supplementation. I believe the study results, although impressive,
would have been even more dramatic had the investigation used omega-6
fatty acids as well. In refractory cases of elevated lipids, which
have failed to respond to the above regimen, consider the combination
of methionine, inositol and choline in doses of 200-400 mg of each
taken 3 times daily. Lipoprotein a (Lpa) is an apolipoprotein, i.e.
an LDL particle, to which an additional protein is attached. Because
of Lpa's similarity with plasminogen, it interferes with fibrinolysis,
and of course ultimately speeds up clot formation. Several substances
as shown Table 3 can be helpful. Coenzyme Q10 for example, can inhibit
the Lpa receptor expression.
Homocysteine Reduction
There are many published studies supporting homocysteine as a risk
factor for vascular disease. Homocysteine has also been considered
a good marker for B6, B12 and folic acid deficiency. Even Raloxefen's
benefit as seen in the Ruth Study "Raloxefen use for heart
study" suggested this drug's action on coronary artery disease,
may in part be due to its homocysteine-lowering qualities. Regular
supplementation with the three B vitamins (B6, B12 and folate) will
control a great majority of elevated homocysteine levels. A simple
blood test confirming the patient's level of homocysteine should
be performed with their annual routine exam. Although laboratories
suggest that a level below 15 is normal, a level of less than 10
is ideal and less than 7 is considered optimal.
Insulin Resistance Reduction
Receptor sensitivity for insulin decreases and the body compensates
by secreting increased amounts of insulin. This is known as "insulin
resistance". Increased insulin levels promote lipogenesis,
increased thrombosis from increase in plaminogen activator/inhibitor,
and decreases through a hepatic mechanism, which will decrease HDL
while increasing triglyceride production. One of the most devastating
effects is the glycosylation process, whereby circulating glucose
attaches to proteins. Eventually this leads to advanced glycosylation
end products (AGE), which can be a precursor to microvascular disease.
The abnormal glucose/insulin metabolism augments formation of free
radicals. Of course, oxidative stress is often responsible for many
of the factors contributing to coronary artery disease. Other than
the substances noted in Table 5, caloric restriction is an excellent
way to decrease free radical formation and improve insulin sensitivity.
Equally as important is a regular exercise program given that insulin
receptors are located within muscle tissue. In addition, repletion
with antioxidants is also imperative (see Table 6).
Antioxidants and Biological Enzymes
There are many studies that support the importance of adequate antioxidant
levels and the occurrence of coronary artery disease. In several
instances, it has been postulated that antioxidant use is more important
than the control of lipid levels. It is well known that cholesterol
in itself is not problematic, but the exposure of cholesterol to
the oxidation process certainly can generate plaque. Grapeseed extract,
vitamin E and vitamin C are important components of antioxidant
therapy. Grapeseed extract alone has been shown to reduce plaque
size. Since most diets have poor consumption of antioxidants and
flavanoids, supplementation with larger doses than usual for coronary
artery disease (C.A.D.) patients may be helpful.
Bromelain has been shown to have numerous therapeutic benefits,
including effects on cytokines such as TNF-alpha, IL-1beta, IL-6
and IL-8. Studies also give evidence that bromelain may inhibit
platelet aggregation, an important cardioprotective property. Some
have claimed that bromelain can not be effective orally, but this
has since been refuted.
Researchers report that soluble fibers have a positive effect on
hypertension as well as serum-fasting insulin. Patients should be
regularly tested for glycosylated hemoglobin, fasting blood sugar
and fasting insulin levels.
Inflammation and Infection
Presently, most recognize that there are several infectious agents
that are associated with coronary vascular disease. Human herpes
virus 6, nanobacteria, chlamydia and cytomegalo virus all have been
implicated as part of the epigenesis of heart disease. Studies have
even shown 89% of patients have chlamydia in their hearts at the
time of bypass surgery. Most investigators agree that, although
these infectious organisms may not be the primary cause of heart
disease, they significantly contribute to a hypercoagulable state.
The use of low-dose broad-spectrum antibiotics such as tetracycline
has been suggested along with aggressive enzyme usage. It seems
that this combination affords the best result of reducing infection
and inflammation. Several studies have shown the overall effectiveness
of enzyme use is greater than the non-steroidal anti-inflammatories.
Sympathetic Tone
The sympathetic nervous system (flight or fight) plays an important
role in C.A.D. Greater than usual sympathetic tone will increase
heart rate and elevate blood pressure. Increased sympathetic activity
has often been demonstrated in patients with C.A.D. Increased levels
of adrenal medulla hormones, i.e., norepinephrine and epinephrine
damage the arterial lining, increase platelet aggregation and increase
oxidized cholesterol, all which lead to a faster generation of arthrogenesis.
Remember, calcium stimulates sympathetic discharge, whereas, magnesium
has antagonistic properties. Therefore, appropriate levels of magnesium
and melatonin help to control an imbalanced sympathetic nervous
system.
Researchers have demonstrated that patients with C.A.D. have nighttime
melatonin levels that are 1/5 lower than healthy controls. Explanatory
physiology is likely to be related to increased nighttime sympathetic
discharge and the subsequent increase in epinephrine/norepinephrine.
Also, melatonin levels could possibly explain why the majority of
heart attacks occur in the early morning hours. Melatonin has also
been found to inhibit platelet aggregation. Saliva melatonin sampling
can be obtained from several laboratories throughout the country.
Table 9 depicts several substances with either ionotropic (increase
heart contractibility) or chronotropic (rhythm heart stabilizing)
effects on the heart. Regular use of these substances can often
augment typical conventional medications of similar nature, i.e.,
digitalis and antiarrythmics. Several studies have shown magnesium
to be an excellent preventative of dysrythmias and can be especially
useful in intravenous doses of 2-3 gm in the early stages of heart
attack and for several days thereafter. Its use can prevent the
serious rhythm disturbances that often accompany myocardial infarction.
Long-term use is also suggested since most patients are magnesium
deficient. Other studies have determined that the use of coenzyme
Q10 in dosages of 300 mg/day one week prior to cardiac surgery improves
three-fold the serum levels and tissue levels in the heart of this
nutraceutical. This improvement seems to reduce the heart failure
associated with low coenzyme Q10. Another study on the usefulness
on coenzyme Q10 in clinical cardiology demonstrated large doses
over time will reduce overall cardiac medication requirements significantly.
(See graphic) Taurine, an amino acid has likewise been shown to
have positive cardiac effects and diuretic properties. Hawthorne
berry has been used for years by western herbologists as a good
ionotropic natural agent.
Summary
A multiangle assertive approach seems to be appropriate when treating
the coronary artery disease patient. Hormonal issues should also
be examined and a saliva profile may prove efficacious in determining
DHEA, estrogen, progesterone, and testosterone levels. Recently,
much has been written about hormones and their inverse relationship
with coronary artery disease. By routinely screening with these
saliva and blood tests, you will be able to note lipid levels, coagulability,
glucose/insulin levels, melatonin level, hormone levels, inflammatory
status, and homocysteine levels. A practitioner could then choose,
from the tables provided, those nutritional supplements that would
address areas of concern revealed by the test results. Abnormal
tests would be noted and repeated after an appropriate length of
treatment and adjustment of the treatment plan, by either increasing
doses of already-prescribed nutraceuticals, with or without the
addition of new agents. Further adjustment in the program would
be necessary when the patient is taking concurrent medicine(s).
Drugs that have similar properties to those nutraceuticals, that
your patient is already taking, would require appropriate adjustment.
For example, patients taking anti-coagulants would require lower
doses of those supplements mentioned in Table 1. However, other
patients, taking lipid-lowering drugs, may require increased doses
of CoQ10. Remember, many coronary-related medications cause other
nutritional deficiencies and I suggest that you refer to a text
describing drug-herbal and drug-nutrient interactions.
Final thoughts:
The use of EDTA, although it is considered by the conventional medical
community as controversial, has revealed in many studies to have
a significant place in the treatment of coronary artery disease
along side the nutraceuticals presented in this paper. Heavy metals
do play a role in artherogenesis and should be studied further.
Don't forget, in the midst of this complex array of nutraceuticals,
water itself may improve the outcomes of coronary events. Simply
drinking 4 or more glasses of pure water each day, can decrease
myocardial infarction by more than 50%.
References
Arsenio, L., et al. Effectiveness of Long-Term Treatment with Pantethine
in Patients with Dyslipidemias. Clin Ther, 1986; 8: 537-545.
Baggio, E., et al. Italian Multicenter Study on the Safety and Efficacy
of Coenzyme-Q-10 as Adjunctive Therapy in Heart Failure. Co-Q-10
Drug Surveillance Investigators. Mol Aspects Med, 1994; 15 Suppl:
s287-294.
Broughton, D.L., Taylor, R.L. Review: Deterioration of Glucose Tolerance
with Age: The Role of Insulin Resistance: Age and Aging, 1991; 20:
221-225.
Brugger, P., et al. Impaired Nocturnal Secretion of Melatonin in
Coronary Artery Disease. Lancet, 1995; 345: 1408.
Cantin, B., et al. Lipoprotein (a) An Independent Risk Factor for
Ischemic Heart Disease in Men? The Quebec Cardiovascular Study.
J Am Cardiol, 1998; 31:519-525.
Cardinali, D.P., Del Zar, M.M., Vacas, M.I. The Effects of Melatonin
in Human Platelets. Acta Physiol Pharmacol Ther Latinoam, 1993;
43: 1-13.
Chappell, L.T., Stahl, J.P. The Correlation Between EDTA Chelation
Therapy and Improvement in Cardiovascular Function: A Meta-Analysis.
J Adv Med, 1993; 6: 139-160.
Dabbs, J.M. Savory Testosterone Measurements: Collecting, Storing
and Mailing Saliva Samples. Physiology and Behavior, 1991; 49: 815-817.
El-Enein Ama, et al. The Role of Nicotinic Acid and Inositol Hexanicotinate
as Anti-Cholesterolemic and Anti-lipemic Agents. Nutr Rep Intl,
1983; 28: 899-911.
Folsom, A. Homocysteine: Not a Risk Factor. Circulation 98, 1998;
196-199, 204-210.
Fox, M. More Evidence that Infections Cause Heart Disease. Science
News, Sept 18, 2000.
Fukagawa, N.K., Anderson, J.W., et al. High-Carbohydrate, High Fiver
Diets Increase Peripheral Insulin Sensitivity in Healthy Young and
Old Adults. Am J Clin Nutr, 1990; 52: 524-528.
Ghen, M.J., et al. The Advanced Guide to Longevity Medicine. 2001,
Landrum, South Carolina, pp. 193-201, 239-246.
Graham, I.M., et al. Plasma Homocysteine as a Risk Factor for Vascular
Disease: The European Concerted Action Project. JAMA, 1997; 277;
1775-1781.
Hancke, C., Flytlie, K. Benefits of EDTA Chelation Therapy in Arteriosclerosis:
A Retrospective Study of 47- Patients. Journal of Advancement in
Medicine, 1993; 6(3); 161-172.
Langsjoen, H., et al. Usefulness of Coenzyme-Q-10 in Clinical
Cardiology: A Long Term Study. Mol Aspects Med, 1994; 15 Suppl:
s165-175.
Lipson, S.F., Ellison, P.T. Development of Protocols for the Application
of Salivary Steroid Analysis to Field Conditions. American Journal
of Human Biology, 1989; 1:249-255.
Lukaczer, Dan. Nutritional Support for Insulin Resistance. Applied
Nutritional Science Reports, July 2001; pp. 1-6.
Maurer HR. Bromelain: biochemistry, pharmacology and medical use.
Cell Mol Life Sci 2001;58:1234-45.
Merghioli, Robert, et al. Dietary Supplementation with N-3 Polyunsaturated
Fatty Acids and Vitamin E After Myocardial Infarction: Results
of the GISSI-PREVENZIONE Trial. The Lancet, Volume 234, Aug 7,
1999; pp 447-495.
Mori, T.A., et al. Interactions Between Dietary Fat, Fish, and
Fish Oils and their Effects on Platelet Function Men at Risk with
Cardiovascular Disease. Arterioscler Throm Vasc Biol, 1997; 17:279-286.
Phillips, R., Lemon, F., Kuzma, J. Coronary Heart Disease, Mortality
Among Seventh Day Adventists with Differing Dietary Habits. Am
J Clin Nutr, 1978 Oct 31;(10 Suppl): 5191-5198.
Rosenfeldt, Franklin, et al. Experience with Coenzyme-Q-10 in
Cardiac Surgery Patients. 2nd Conference of the International
Co-Q-10 Association. Frankfurt, Germany, December 1-3, 2000.
Watson, P.S., Scalia, G.M., et al. Lack of effect of Coenzyme-Q-10
on Left Ventricular Function in Patients with Congestive Heart
Failure. J Am Coll Cardiol, 1999, May; 33(6):1549-1552.
Weiss, Decker. Part One: Cardiovascular Disease Risk Factors and
Fundamental Nutrition. Applied Nutritional Science Reports, Feb
2000, pp. 1-6.
Welsh, A.L, Edede, M. Inositol Hexanicotinate for Improved Nicotinic
Acid Therapy. Int Record Med, 1961; 174:9-15.
Weiss, Decker. Part Two: Cardiovascular Disease Nutrtional Management
of Clinical Markers. Applied Nutritional Science Reports, Feb
2000, pp. 1-6.
|