This interview offers

an introduc- tion to Dr. Philip Miller’s natural anticoagulant regimen.

For a more detailed and compre- hensive four-part tutorial on this subject of prevention of heart at- tacks and strokes (with numer- ous visually enhanced diagrams) please visit his website at www. antiaging.com, with accompanying blog posts at blog.antiaging.com.

Focus:

On the website for your clinic, you offer a four-part, very detailed and fascinating description of a regimen you have developed to help prevent heart disease and stroke. What inspired you to craft

this regimen?

Miller:

About 1.5 million heart attacks and strokes occur every year inthe United States, andoneinevery three deaths is due to cardiovascular

disease.1 Cardiovascular disease is the number one cause of death globally.2 Everybody worries about a heart attack or stroke, especially if they’re over sixty. People worry that they’re at risk. I developed this comprehensive approach over many years, and it is empirically derived, based on a good, fundamental knowledge of all the pathways in the body that contribute to a catastrophic vascular event. My approach relies on a novel combination of anti- fibrin and anti-platelet modalities. It is a rational approach that

addresses the entire coagulation cascade, from beginning to end. This includes platelet aggregation, fibrin deposition, markers of inflammation, and even the properties of red blood cells and why and how they stick together.

My one emphatic caveat is that this regimen must be carried out under the care of a skilled and knowledgeable physician. You cannot self-treat, and nobody should abruptly stop a conventional anticoagulant routine. And let me emphasize, this proprietary anti-coagulation routine is prescribed only after starting our core program of select micro- nutrients and nutritional advice. We use CoQ10, taurine, d-ribose and carnitine in high doses to support heart and brain function. It’s all part of an integrative approach.

During the twenty years I’ve offered this regimen, I can’t remember more than 8-10 patients who have suffered a major stroke or heart attack. This is out of thousands of patients, many of them older, with significant cardiovascular risk factors.

I monitor my patients regularly, and adjust the protocol when indicated. I also follow this approach myself, because I do not want to ever have a stroke.

Focus:

What is your opinion of the conventional approach to coagulation?

Miller:

It is certainly an interesting time in the treatment of stroke and heart attack. In the last few years, the FDA has a new class of oral anticoagulant

drugs. Although their safety profile appears better than the old standby – Coumadin (warfarin) – all three of the new medicines are blood thinners that can cause excessive bleeding, and are to be used with caution in patients with kidney disease. Two of these new medicines lack an antidote in the event of a severe bleeding episode, which is of concern.3 An antidote has recently been approved for the third (dabigatran etexilate).4

Even with these advances in anticoagulant treatment, I still find the conventional, mainstream approach to stroke and heart attack to be too guideline driven. Some guidelines emphasize the prevention of platelet aggregation. Other guidelines emphasize the long-term use of anti-fibrin drugs. What is the best strategy? In this scenario it depends on the guidelines. These evolving guidelines are determined by age, associated risk factors, and preceding conditions. The guidelines were originally developed to make decision- making simple, uniform and coherent. But guidelines eventually become bloated and incoherent. They can read much like IRS tax code.5

Focus:

Give us a quick précis of the conventional approach to preventing hypercoagulation.

Miller:

The conventional approach to stroke and heart attack prevention starts by preventing platelets from clumping. Both aspirin and Clopidogrel (Plavix) are drugs of choice. Aspirin is

probably the safest conventional drug to help prevent heart attack and stroke. Clopidogrel is the second line of defense

vitamin K reserves. There are seven vitamin K-dependent blood clotting (‘coagulation’) factors, and they are each important in the coagulation cascade that helps form a clot.8 Patients on warfarin are advised not to ingest any extra vitamin K and maintain a moderate, constant level of intake.9

Vitamin K is important for building bone.10,11,12 It helps regulate cellular growth, cell division and both the

ratio seems questionable, especially if there are other, safer options.

Finally, there is a new class of anticoagulant drugs, called factor Xa drugs, which target the thrombin cascade. Thrombin is an enzyme that helps clots form. One molecule of factor Xa can cleave over 1000 molecules of

prothrombin to thrombin.18 By cleaving prothrombin, factor Xa

drugs can slow conversion to thrombin, and reduce clots.

in antiplatelet therapy. It works by breaking down into metabolites, one of which binds irreversibly to a receptor on platelets. This prevents the platelets from

Every stroke or heart attack starts with a blood clot, which is essentially the eye of the hurricane. The blood clot is our body’s universal mechanism for healing injury.

These newer drugs do not need frequent monitoring. They do not block Vitamin K. Excessive bleeding is still their big risk, and one downside to direct factor Xa inhibitors is that, in

aggregating and lasts

the entire 7 to 10 day life of a platelet.

Then there are the standard anticoagulant drugs. Coumadin is the best known. Bleeding is the major adverse effect of warfarin. Hemorrhage may occur at virtually any site in the body.6,7 My biggest concern with warfarin is its mechanism of action. It depletes

developing and aging nervous

system.13,14 Vitamin K is essential for matrix GLA protein activity, which prevents reverse calcium flow from bones into your arteries and heart valves.

Warfarin, by blocking Vitamin K, can accelerate osteoporosis and arterial calcification.15,16,17 Healthy doses of vitamin K are vital to many functions. So, to me, the risk-benefit

most cases, there are no antidotes to unintentional overdose and a bleed. Taking Vitamin K is a simple antidote to warfarin.

In addition, because these drugs are so new, we may eventually discover other long term consequences that are not apparent yet.

Focus:

What causes a stroke or heart attack?

Biography:

Dr. Philip Lee Miller combines 40 years of medical experience with a variety of interests. He is a pioneering anti-aging physician, a well-known author and avid semiprofessional photographer.

Dr. Miller graduated from UC Berkeley in 1968 with a degree in biochemistry. He graduated from UC San Diego in 1972 with an M.D. degree.

He was a close associate of Dr. Julian Whitaker for one year at Dr. Whitaker’s Wellness Institute in the early 1990s. He is a diplomat of the American board of anti-aging medicine,

formerly board certified in emergency medicine and has specialty training in neurology.

Dr. Miller has been practicing anti-aging and age management medicine since 1996, with broad emphasis on diagnosis, problem-solving through nutritional medicine, integrative medicine, functional medicine and practical knowledge of all aspects of endocrinology.

He is the author of Life Extension Revolution with the Life Extension Foundation. He also regularly writes blog posts at blog.antiaging.com.

Miller:

It all starts with the blood clot, which is essentially the eye of the hurricane. The blood clot is our body’s universal mechanism for healing injury, and it usually results from injury. In the case of stroke or heart attack, it is an injury

to the wall of a vein or artery. Take atherosclerosis, a condition where plaque builds up in the arteries over many years. Eventually, an area of plaque can rupture inside of an artery. The body attempts to repair that injury by forming a blood clot on the plaque’s surface.

up to the clot?

Miller:

Picture the blood vessel—a flexible tube through which your lifeblood is rushing at the astounding speed of three feet a minute the moment it leaves

the heart.23 Every blood vessel is lined with endothelial cells, which form a protective lining called the endothelium. The endothelium secretes substances that stop those cascading blood cells from sticking to it.

pathway is initiated. This pathway involves the body’s fibrin cascade. At first, thrombin is released. Thrombin is an enzyme in blood plasma that causes the clotting of blood. Thrombin converts fibrinogen, a soluble protein, to strong and insoluble fibrin molecules at the place of the wound. Shaped like long threads, the fibrin molecules interlace and crosslink with each other to form a kind of polymer mesh over the clot and stabilize it.

It is a remarkable feat.

If the clot becomes large enough, it can mostly or completely block blood flow, depriving tissues of oxygen (ischemia),

and leading to stroke

In both atherosclerosis and atrial fibrillation, the ‘healing’ clot proves to be a problem.

Under normal circumstances, your body has highly sensitive feedback systems to balance bleeding and

(cerebral infarction) or heart attack (myocardial infarction).

Atrial fibrillation, a heart arrhythmia, can also lead to a clot. In this case, the abnormal firing of electrical impulses causes the atria (the top chambers in the heart) to quiver. Blood flow slows down, and there is turbulence,19 which may lead to the formation of a clot. This type of arrhythmia is the most common type of irregular heartbeat and is found in 5% of those over the age of 65 and 10% of those over

80.20 Untreated atrial fibrillation increases the risk of a stroke by five-fold.21 Or alternatively, other research shows about 2% stroke incidence annually, in untreated atrial fibrillation.22

In both atherosclerosis and atrial fibrillation, the ‘healing’ clot may prove to be a problem.

Focus:

So the body’s effort to heal an injury can sometimes backfire. What pathways and what cascade of reactions and interactions leads

But when it is injured or damaged, the endothelium sends out distress signals. Those distress signals are picked up by platelets, tiny blood cells that help your body form clots. The platelets rush to the site of damage, ready to clump together (aggregate) and stick to the exposed wound and help form a clot. During and after aggregation, platelets continue to release substances that trigger further platelet accumulation and activation, as well as constrict veins and help form clots. Platelets are also involved in the inflammatory response and produce proinflammatory chemicals.24

Platelets are significant in both atherosclerosis and in the development of stroke and heart attack. Aggregating platelets form the center of the growing clot.25,26 The clot in individuals who have died of a heart attack has a layered appearance, suggesting it has grown episodically, over time.27

Once the initial platelet plug has formed, a second important

clotting. Your body produces plasmin, an enzyme that degrades fibrin clots. And, to balance that dissolving process, you also produce inhibitors of plasmin.

So, to sum it up: injury or stasis, platelet plug, fibrin mesh, successful clot—but over time, potential infarction.

Focus:

You’ve compiled a natural anticoagulation regimen that addresses all these pathways. Which natural molecules do you use and why?

Miller:

I combine four simple but powerful constituents. They are:

• Nattokinase

• Ginkgo biloba

• High dose fish oils

• Vitamin E isomers

And, I emphasize adequate hydration — which means many glasses of pure water daily. Studies have shown that water can actually

stop red blood cells from clumping as aggressively.

All of the above, when combined in proper doses by a physician, can be both gentle and potent. Every surgeon is now medically and legally required to ask, “What vitamins and herbs are you taking?” Every surgeon knows that each and all of these agents I have discussed clearly have anticoagulant effects, but via different mechanisms.

Nattokinase

Nattokinase is a well-known fibri- nolytic agent.28 As you may recall,

for cardiovascular disease, and patients undergoing dialysis. Two months of nattokinase reduced fi- brinogen, as well as two clotting factors known as factor VII and fac- tor VIII.41 And a 2014 study in Na- ture found that a single oral dose of nattokinase improved fibrinolysis and blood flow.29

Studies have consistently shown that nattokinase possesses strong fibrinolytic activity.30,31 Nattoki- nase reduces plasminogen activa- tor inhibitor I (PAI-1), which as you may recall, is important in the clotting cascade.32 Nattokinase also

Gingko biloba

Ginkgo biloba is a time-honored and venerated Chinese herb with many potent constituents, including flavonol and flavone glycosides, lactone derivatives (ginkgolides), and bilobalide.36,37 I use a standardized 26% ginkgo extract.

Ginkgo biloba exerts its action primarily as an anti-platelet and anticoagulant. It inhibits platelet aggregating factor.38 Ginkgo has many other uses. It is an antioxidant, may have vasodilatory

effects, and has been

our goal is to prevent fi- brinogen from converting to fibrin. In a 2009, an open label study of three groups of patients—healthy vol-

unteers, patients at risk

I find that my recommended regimen, when fully implemented, treats all pathways of coagulation

used for cognitive enhancement. I find it much more effective as a cardiac protective herb.

stimulates the conversion of plas- minogen to plasmin.33 Nattokinase shows thrombolytic (clot dissolv- ing) activity.45 The thrombolytic power of nattokinase may be stron- ger than plasmin.43

I have treated thousands of cases with nattokinase to help prevent recurrent thrombophlebitis, strokes and heart attacks. It is essential that you source NSK-SD® nattokinase, which is proven highly effective and standardized.

There are alternatives to natto- kinase. Lumbrokinase is a simi- lar fibrinolytic derived from the earthworm. By the manufacturer’s claims, it is even more potent. Ser- rapeptase, an enzyme derived from silkworms, has similar but not identical properties; and is often used to combat inflammation and swelling.34,35 I do use serrapeptase to treat arterial plaques.

Ginkgo is potent. A high dose can cause excess blood thinning and bleeding. Because of its action, Ginkgo biloba should not be combined with aspirin or non- steroidal anti-inflammatory drugs (NSAIDs). It will have an unwanted synergistic effect.

High Potency Fish Oils

High-dose fish oils have a “rheological” effect. That is, they prevent aggregation of red blood cells, which as you may recall, is part of the coagulation cascade.39,40 An image I find effective in describing fish oils to my patients is that they act like Teflon to prevent this aggregating effect. The dose that I recommend in my protocol is aggressive: one tablespoon daily. You will rarely achieve these doses with oral capsules. I rely on fish oils in liquid form.

Fish oils contain EPA (eicosapen- taenoic acid) and DHA (docosa- hexaenoic acid). One tablespoon of high potency fish oil will yield this high dose of 4300 mg EPA, approxi- mately 3000 mg of DHA, and 1000 mg of other Omega 3’s. You will not achieve these doses with fish oil capsules.

Fish oils, in addition to their anticoagulant effect, may have multiple ancillary benefits:

• Enhance brain function – cognitive enhancement41

• Prevent cardiovascular events42

• Antidepressant43

• Improve skin elasticity44

• Lower blood pressure45

Vitamin E isomers

Like fish oil, vitamin E has rheological properties. It prevents red blood cell aggregation and lowers blood viscosity, or stickiness.46 Vitamin E exists as a family of tocopherols and tocotrienols, and I recommend mixed tocopherols, an isomeric mix of natural tocopherols including the alpha, beta, gamma and delta forms of vitamin E. There is a difference between “natural” vitamin E and “synthetic” natural vitamin E. Synthetic vitamin E is a tocopheryl not tocopherol.

Water, Elixir of Life

And last but not least, hydration. Keep well hydrated. Hydration will also prevent red blood cell and platelet aggregation.47 It will improve skin elasticity. I recommend filtered water in glass

bottles, not plastic bottles. We all should avoid plasticizers. The softer the plastic bottle the higher the plasticizer content.

Focus:

When a patient comes to you seeking an anticoagulation protocol, what do you do?

Miller:

I run a series of tests. First, I look at typical lab work—a complete blood count (CBC), chemistries (liver and kidney function), lipids, vitamin D, thyroid and adrenal. I also look at inflammatory markers such as C-reactive protein (CRP),

erythrocyte sedimentation rate (ESR), and fibrinogen levels. With more sophisticated testing we can test arachidonic acid/EPA ratios. These are obtained through one of a number of specialty labs.

I routinely measure fibrinogen levels on every one of my patients. I am aggressive about reducing fibrinogen levels. If levels are above 350 mg/dl. I recommend nattokinase, despite most labs using an upper level for high fibrinogen > 450 mg/dl, I look at the patient’s clinical picture: age, risk factors such as hypertension, cardiovascular issues, and family history. It’s always a combination of lab values, family history, and the clinical picture.

I find that my recommended regimen, when fully implemented, treats all pathways of coagulation. Empirically and rationally there is good evidence this approach has the ability to effectively prevent heart attacks, strokes and recurrent thrombophlebitis. It is a comprehensive approach to anticoagulant therapy that, for my patients and me, has stood

the test of time.

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Fibrin synthesis cascade

Injury.

A blood vessel is severed. Blood and blood components (e.g., erythr ocytes, white blood cells,

White blood cells

etc.) are leaking out of the breaks.

Platelets

Erythrocytes

Smooth muscle contracts

V a s c u l a r spasm.

The smooth muscle in the vessel wall contract near the injury point, reducing blood loss.

Smooth muscle contracts

complex complex

Initial platelets are activated by chemicals

Forming

Platelet plug f o r m a t i o n .

Platelets are

activated by c h e m i c a l s released from the injury site and by contact with underlying collagen. The platelets become spiked and stick to each other and the wound site.

Coagulation.

In coagulation, fibrinogen is

converted to fibrin (see part b), which forms a mesh that traps more platelets and erythrocytes, producing a clot.

Bound platelets release chemicals that activate

and attract other platelets.

Platelets move toward source of chemical signals and bind. Platelet plug grows in size.

1. The general steps of clotting (b) Fibrin synthesis cascade