Vitamin E, Heart Disease, and Mortality

[Guest guest]

Vitami. MedicalConspiracies@googlegron E, Heart Disease, and Mortality

 

 

Vitamin E, Heart Disease, and Mortality

http://www.thenhf.com/articles_61.htm

by Michael T. Murray N.D.

 

December 2004

 

 

 

In 2003, during a keynote address to the dietary-supplement industry titled

" Challenges, Solutions, & Inspirations, " I spoke on how the results from

clinical studies will be used to adversely affect the public's appreciation for

natural products.

 

The two primary examples that I gave were studies with echinacea using less than

ideal preparations and studies on the effect of Vitamin E in cardiovascular

disease.

 

The recent proclamation by a set of researchers at Johns Hopkins University that

Vitamin E may actually increase the risk of mortality and the resulting media

fervor reporting this story is not surprising to me at all. In fact, I predicted

it and based upon the research it is easy to understand how this conclusion

could be made.

 

 

Although many experts and organization will be focusing on the shortcoming in

the methodology in the recent Vitamin-E meta-analysis, my feeling is that time

is better spent trying to understand the results instead of trying to discredit

them.

 

The results simply reflect some inherent defects in the manner in which research

is conducted with antioxidant nutrients.

 

Nonetheless, it is important to point out that the interpretation of the data is

based upon an analysis of 19 earlier published Vitamin E studies with a built-in

bias toward the risk of harm rather than potential benefit.

 

Focusing on the impact on the all-cause mortality outcome seems inappropriate

given that none of the 19 studies analyzed were designed with this as the

primary endpoint; the studies chosen represented quite a diversity of subjects,

disease conditions, treatments, and durations of intervention; and the follow-up

time was relatively short, ranging from 1.4 years to 8.2 years.

 

 

 

It is also important to point out that while these studies were not designed to

evaluate all-cause mortality statistics as the primary outcome, many of the

studies used in the meta-analysis showed positive results on the primary

outcomes they were designed to measure.

 

These include outcomes such as reduced progression of advanced age-related

macular degeneration and cataracts, reduced incidence of heart attacks, as well

as slowed progression of atherosclerosis and Alzheimer's Disease.

 

 

The Beta-Carotene Analogy

 

 

The results from this analysis of Vitamin E research are quite similar to those

of synthetic beta-carotene in cancer prevention. In case you missed this line of

research with beta-carotene, studies indicated that synthetic beta-carotene

supplementation contributed to earlier death in high-risk groups for cancer and

cardiovascular disease.

 

These studies did not invalidate the hundreds of studies showing the preventive

effect of a diet rich in carotenes and nutritional antioxidants against cancer

and cardiovascular disease.

 

These results seem to indicate the need for a diet high in carotenes and, if

carotene supplementation is desired, people should not smoke, natural forms

should be used, and the beta-carotene needs to be protected against the

formation of toxic derivatives by taking extra Vitamins C and E, and selenium.

 

 

It is important to realize that not all antioxidants are created equal. When it

comes to quenching free radicals, antioxidant compounds exert different (and

usually very narrow) ranges of activity.

 

For example, beta-carotene is an effective quencher of a free radical known as

singlet oxygen, but is virtually powerless against the dozens of other types of

free radicals.

 

As a result, it has a very narrow range of benefit and is very susceptible to

being damaged itself and forming a free radical without additional antioxidant

support.

 

 

Most antioxidants require some sort of " partner " antioxidant that allows it to

work more efficiently.

 

And scientists have discovered that beta-carotene itself can become damaged if

it is used alone (that is, without its partner antioxidants Vitamin C, Vitamin

E, and selenium).

 

For example, while studies showed that synthetic beta-carotene supplements given

alone actually increased the risk of cancer in smokers, when beta-carotene was

given along with Vitamin E and selenium it reduced cancer deaths by a

significant 13 percent.

Damaged beta-carotene is extremely toxic to the liver, the lining of the

arteries, and the lungs. This fact alone may explain some of the disappointing

results from the recent beta-carotene studies.

 

Undoubtedly, there will be similar discoveries about the importance of other

antioxidant nutrients in the support of Vitamin E's antioxidant benefit.

 

 

The Importance of Synergy

 

 

While the scientific research is quite clear that diets high in antioxidants are

protective against many diseases, the data is not as solid with antioxidant

supplements.

 

There are three main points to keep in mind when looking at research with

antioxidant supplements:

 

The antioxidant system of the body relies on a complex interplay of many

different dietary antioxidants.

 

Taking any single antioxidant nutrient is not enough. A total program is

necessary.

 

 

Although dietary supplements are important, they cannot replace the importance

of consuming a diet rich in antioxidants.

 

A shortcoming of many of the intervention studies with antioxidant nutrients is

that researchers often focus on the effects of just one factor.

 

In a way, this is like judging an entire symphony by listening to a single

trombone.

 

Such research has its value, but it is not complete and often raises more

questions than it answers.

 

Antioxidants and Heart Disease

 

 

The research is quite clear that dietary antioxidant nutrients like Vitamin E,

lycopene, lutein, selenium, and Vitamin C offer significant protection against

the development of cardiovascular disease.

 

Fats and cholesterol are particularly susceptible to free-radical damage.

 

When damaged, fats and cholesterol form lipid peroxides and oxidized cholesterol

that can then damage the artery walls as well as accelerate the progression of

atherosclerosis (hardening of the arteries).

 

Antioxidants block the formation of these damaging compounds.

 

 

 

While diets rich in antioxidant nutrients have consistently shown tremendous

protection against cardiovascular disease, clinical trials using antioxidant

vitamins and minerals have produced inconsistent results.

 

This failure may be due to several factors, most importantly the fact that the

human antioxidant system represents a complex scenario of interacting

components.

 

It is unlikely that any single antioxidant would be proven to be effective

especially in the absence of a supporting cast.

 

 

 

Most antioxidants require some sort of " partner " antioxidant that allows it to

work more efficiently.

 

The most salient example of this point is the partnership between the two

primary antioxidants in the human body - Vitamin C and Vitamin E.

 

Vitamin C is an " aqueous phase " antioxidant while Vitamin E is a " lipid phase "

antioxidant.

 

Although some studies have shown that supplementation with these nutrients

reduces atherosclerotic lesions more protection is likely required to insure

optimal effect.

 

 

 

In addition to Vitamin C, Vitamin E also requires selenium and Coenzyme Q10 to

work efficiently (as discussed in more detail below). Further adding to the

shortcoming of many of the studies on antioxidant nutrients is the lack of

consideration on the importance of phytochemicals and plant derived antioxidants

that in addition to exerting benefit on their own are well-known to potentiate

the activities of vitamin and mineral antioxidants.

 

The support of non-antioxidant vitamins and minerals may also be important in

assisting the effectiveness of antioxidants. Taking a multiple

vitamin-and-mineral supplement seems appropriate.

 

 

The Research on Vitamin E

 

 

Although clinical studies have shown inconsistent effects, it is clear that

Vitamin E does play a role in the protection against the oxidation of LDL

cholesterol because of its ability to be easily incorporated into the LDL

molecule.

 

Vitamin E may offer additional benefit in protecting against heart disease and

strokes by its ability to:

 

Reduce LDL cholesterol peroxidation and increase plasma LDL breakdown

 

Inhibit excessive platelet aggregation

 

Increase HDL cholesterol levels

 

Increase fibrinolytic activity

 

Reduce C-reactive protein levels

 

Improve endothelial cell function

 

Improve insulin sensitivity

 

Two early large-scale studies with relatively low dosages of Vitamin E

supplements demonstrated a significant reduction in the risk of dying of a heart

attack or a stroke.

 

The Nurses Health Study of 87,245 nurses concluded that those who took 100 IUs

of Vitamin E daily for more than 2 years had a 41% lower risk of heart disease

compared with non-users of Vitamin E supplements.

 

In the Physicians Health Study of 39,910 male health-care professionals, similar

results were found:

 

A 37% lower risk of heart disease with the intake of more than 30 IUs of

supplemental Vitamin E daily. Subsequent studies have been equivocal.

 

 

Large-scale studies examining the impact of Vitamin E supplementation

in patients with existing heart disease have also shown somewhat conflicting

results.

 

Some the disappointing results may have been the choice of synthetic Vitamin E

(D,L-alpha tocopherol) versus the more active natural form (D-alpha tocopherol).

 

There is also the problem with interference by statin drugs of Vitamin E and

Coenzyme Q10 metabolism - thereby increasing the needs for both compounds.

 

In fact, one of the reasons why more recent studies with vitamin E have not

shown the same benefit as earlier studies may turn out to be that higher dosages

of vitamin E alone and in combination with CoQ10 are required to compensate for

the detrimental effects of the now extremely popular statin drugs have on their

metabolism.

 

 

Vitamin E and CoQ10 work synergistically and each is required for the

regeneration of the other.

 

For example, CoQ10 is present in the blood in both oxidized (inactive) and

reduced (active) form.

 

During times of increased oxidative stress or low Vitamin E levels, more CoQ10

will be converted to its oxidized (inactive form). Thus, by providing higher

levels of Vitamin E, the biological activity and function of CoQ10 is enhanced

and vice versa.

 

Several studies in humans and animals have shown that the combination of Vitamin

E and CoQ10 work better than either alone.

 

For example, in a study in baboons, while supplementation with Vitamin E alone

reduced C-reactive protein (CRP) levels, co-supplementation with CoQ10, however,

significantly enhanced this effect of Vitamin E.

 

Similar results have been seen in other animal studies on other aspects

associated with atherosclerosis including LDL oxidation and lipid peroxide

content within the aorta.

 

It appears that taking 50 mg of CoQ10 for every 400 IUs of Vitamin E offers a

rational approach to supporting the antioxidant activities of both nutrients.

 

In addition to CoQ10, Vitamin E also requires adequate selenium status for

optimal antioxidant effects.

 

Selenium functions primarily as a component of the antioxidant enzyme

glutathione peroxidase.

 

This enzyme works closely with Vitamin E to prevent free-radical damage to cell

membranes.

 

Studies looking only at Vitamin E's ability to reduce cancer and heart disease

are often faulty because they fail to factor in the critical partnership between

selenium and Vitamin E, not to mention the interrelationship between Vitamin E

and Coenzyme Q10.

 

Several studies have clearly demonstrated that low selenium status is

significantly associated with coronary artery disease.

 

Failure to co-supplement with selenium as well as Vitamin C and CoQ10, may be a

major reason for the inconsistent results in intervention trials with Vitamin E

supplementation alone. A dosage of 100 to 200 mcg of selenium per day is all

that is usually required.

 

 

The " Take Home " Message

 

 

In regards to supplementation with Vitamin E at higher dosages (e.g., >400 IUs

daily), I will continue to make this recommendation to people with heart

disease, diabetes, etc., and will do so in the same manner that I have

consistently done over the past 20 years.

 

I have repeatedly written and stated that the use of any single antioxidant

nutrient at higher dosages must be made within the context of a truly

comprehensive approach that focuses on a diet rich in antioxidant nutrients

(i.e., vegetables, fruits, raw nuts, seeds, and legumes) and a strong foundation

of nutritional supplementation.

 

The three key dietary supplements that I recommend to provide a strong

foundation for a proper nutritional supplement plan are: (1) A high-potency

multiple vitamin and mineral formula; (2) A " greens " drink product; and (3) A

pharmaceutical grade fish-oil supplement.

 

 

The dietary recommendations and foundational supplements work synergistically

and in harmony with each other because of the key roles they each play in

promoting vibrant health.

 

 

 

 

 

Michael T. Murray, N.D., is widely regarded as one of the world's leading

authorities on natural medicine. He is a graduate, faculty member, and serves on

the Board of Regents of Bastyr University in Seattle, Washington. Dr. Murray is of Product Development and Education for Natural Factors Nutritional

Products

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Posted: Mon Aug 01, 2005 2:12 pm

Post subject: Inflammation and Heart Disease

 

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Inflammation and Heart Disease --Soothing the Burning Heart

 

Doctors increasingly consider inflammation as the cause of heart

disease. Here’s why – and what you can do about it…

http://www.willner.com/article.aspx?artid=33

©2004 By Jack Challem

 

Over just the past several years, researchers and physicians have been

redefining the cause of coronary artery (heart) disease. The old view

was that high-fat diets led to cholesterol deposits in arteries, choking

off the blood supply and eventually causing a heart attack.

 

The new view is that heart disease begins as an inflammatory disorder of the

blood vessels, with " cholesterol-laden " lesions

forming after the " initial damage " to arteries.

 

This is a fundamentally different way of explaining the leading cause of

death among Americans.

Some 60 million people have coronary heart disease, resulting in approximately

725,000 deaths each year. As you

might imagine, new thinking on the cause heart disease leads to

different strategies for prevention.

 

LDL Cholesterol and Inflammation

 

About 15 years ago, researchers began piecing together exactly how the

“bad” low-density lipoprotein (LDL) form of cholesterol was related to

inflammation and heart disease.

 

In a series of human and cell studies, Ishwarlal “Kenny” Jialal, M.D., then with

the University of Texas Southwestern Medical Center, Dallas, discovered that

normal LDL did not

promote heart disease. LDL caused heart disease only when it became

“oxidized,” or damaged by harmful molecules known as free radicals.

 

Jialal’s studies found that the immune system responded to oxidized LDL

much the way it did to bacteria.

 

White blood cells would attack and engulf globules of oxidized LDL, but they

would ignore normal LDL.

 

After capturing oxidized LDL, the white blood cells would then become lodged

in the walls of arteries, creating the initial lesions that most people

call “cholesterol deposits.” Jialal also found that vitamin E, an

antioxidant, prevented LDL oxidation and reduced the activity of white

blood cells against LDL.

 

C-Reactive Protein and Inflammation

 

Still, it was not until 2000 that the role of inflammation in heart

disease gained momentum. Paul Ridker, M.D., of the Harvard Medical

School, developed a new blood test, known as high-sensitivity C-reactive

protein (CRP), to measure inflammation.

 

He reported in the New England Journal of Medicine that people with elevated

blood levels of CRP were

four times more likely to suffer a heart attack, compared with people

who had normal CRP levels.1

 

CRP is both an indicator and a promoter of inflammation. It is part of a

family of molecules called cytokines, which cells use to communicate

with each other.

 

CRP, interleukin-6 (IL-6), and many other cytokines

tell immune cells to mount an " inflammatory response " .

 

Other types of cytokines let cells know when it is time to reduce inflammation.

 

Some researchers believe that inflammation, stimulated in part by CRP

and white blood cells, directly " damages " blood vessel walls.

Another view is that inflammation *destabilizes* " cholesterol deposits " ,

prompting them to break apart and block a blood vessel.

 

 

A Pro-Inflammatory Diet

 

Although the research points to a strong cause-and-effect relationship

between inflammation and heart disease, a crucial question remains:

 

What causes this chronic inflammation?

 

The answer may lie in our eatinghabits.

 

Two of the body’s principal arbiters of inflammation are the omega-6 and

omega-3 families of fats, and the building blocks of these fats are

found in foods.

 

The omega-6 family of fats generally promotes inflammation, whereas the omega-3

family reduces inflammation.

 

Ancient human diets contained relatively equal portions of these fats.

However, modern processed foods—convenience foods and fast foods—have tilted

this ratio to about 30:1 in favor of pro-inflammatory omega-6

fats.

 

These fats are found in common cooking oils (such as corn, safflower, peanut,

and soybean oils), as well as in salad dressings,

potato chips, fries, and baked goods.

 

Many of these foods also contain trans fats, which interfere with the body’s

" processing " of anti-inflammatory omega-3 fats.

 

Furthermore, research by Simin Liu, M.D., Sc.D., of the Harvard Medical

School, has shown that sugars, refined carbohydrates and other

" high-glycemic " foods increase CRP levels.

 

Diets high in sugars and refined starches also " displace " more nutritious

antioxidant-rich vegetables, which can reduce LDL oxidation and CRP

levels.

 

 

Adopting an Anti-Inflammatory Diet

 

To restore a balance between pro- and anti-inflammatory fats, it is

important to emphasize coldwater fish (such as alaskan salmon, fresh tuna, and

herring), which contain substantial amounts of anti-inflammatory omega-3 fats.

 

Chicken and beef from free-range (NOT " grain fed " ) animals also have

large amounts of omega-3 fats with relatively small amounts of saturated

fat.

 

In addition, opt for cooking oils that contain large amounts of

anti-inflammatory omega-9 fats.

These oils include extra-virgin olive oil and macadamia nut oil.

 

Also, eat nonstarchy vegetables (such as salads, broccoli, cauliflower,

and green beans) and nonstarchy fruits (such as blueberries,

raspberries, and kiwi).

 

These foods are rich in antioxidants, which " curtail " inflammation.

 

Meanwhile, reduce your consumption of foods with sugars and refined starches,

and avoid all foods with trans fats (found in partially hydrogenated vegetable

oils).

 

Taking Anti-Inflammatory Supplements

 

Several supplements have a pronounced anti-inflammatory effect and, not

surprisingly, have been found to reduce the risk of heart disease.

 

• Vitamin E. Vitamin E has been used since the 1940s to prevent and

treat heart disease. Several clinical studies have found that

natural-source vitamin E can lower CRP levels by 30 to 50 percent.4,5

Its anti-inflammatory effect has also been corroborated in two studies

of patients with rheumatoid arthritis.6,7 Try 400 IU daily.

 

• Fish oil supplements. Fish oil supplements provide a concentrated

source of anti-inflammatory omega-3 fats. These fats reduce the risk of

blood clots and heart-rhythm abnormalities.8,9 Try 1,000 to 3,000 mg

daily.

 

• Other antioxidants. Vitamin C, alpha-lipoic acid, mixed carotenoids

(beta-carotene, lutein, and lycopene), and flavonoids (such as

Pycnogenol and grape-seed extract) may also reduce inflammation and CRP levels.

 

Finally, you can reduce CRP levels by losing weight. Fat cells,

particularly those that form around the belly, produce their own

CRP—which may be why obesity is a risk factor for heart disease.

 

Jack Challem is the author of The Inflammation Syndrome (John Wiley &

Sons, 2003). This article was originally published in GreatLife magazine

and is reprinted with permission of the author. © Jack Challem. For

additional information, visit www.inflammationsyndrome.com

 

 

References:

1. Ridker PM, Hennekens CH, Buring JE, et al. C-reactive protein and

other markers of inflammation in the prediction of cardiovascular

disease in women. New England Journal of Medicine, 2000;342: 836-843.

2. Buffon A, Biasucci LM, Liuzzo G, et al. Widespread coronary

inflammation in unstable angina. New England Journal of Medicine,

2002;347:5-12.

2. Liu S, Manson JE, Buring HE, et al. Relation between a diet with a

high glycemic load and plasma concentrations of high-sensitivity

C-reactive protein in middle-aged women. American Journal of Clinical

Nutrition, 2002;75:492-498.

4. Upritchard JE, Sutherland WHF, Mann JI. Effect of supplementation

with tomato juice, vitamin E, and vitamin C on LDL oxidation and

products of inflammatory activity in type 2 diabetes. Diabetes Care,

2000, 23:733-738.

5. Devaraj S, Jialal I. Alpha tocopherol supplementation decreases serum

C-reactive protein and monocyte interleukin-6 levels in normal

volunteers and type 2 diabetic patients. Free Radical Biology &

Medicine, 2000; 29:790-792.

6. Edmonds SE, Yinyard PG, Guo R, et al. Putative analgesic activity of

repeated oral doses of vitamin E in the treatment of rheumatoid

arthritis. Results of a prospective placebo controlled double blind

trial. Annals of the Rheumatic Diseases, 1997;56:649-655.

7. Helmy M, Shohayeb M, Helmy MH, et al. Antioxidants as adjuvant

therapy in rheumatoid disease—a preliminary study.

Arzneimittel-Forschung/Drug Research, 2001;51:293-298.

8. Dwyer JH, Allayee H, Dwyer KM, et al. Arachidonate 5-lipoxygenase

promoter genotype, dietary arachidonic acid, and atherosclerosis. New

England Journal of Medicine, 2004;350:29-37.

9. Ernst E, Saradeth T, Achhammer G. n-3 fatty acids and acute-phase

proteins. European Journal of Clinical Investigation

 

Disclaimer

 

The information provided on this site, or linked sites, is provided for

informational purposes only, and should not be used as a substitute for

advice from your physician or other health care professional. Product

information contained herein has not necessarily been evaluated or

approved by the U.S. Food and Drug Administration, and is not intended

to diagnose, treat, cure or prevent disease.

=============================================

 

Post subject: Serrapeptase: Silkworm Enzyme

 

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Heard about Serrapeptase, the proteolytic enzyme sometimes known as

serrapeptase? Chances are you haven’t, until now. For over 30 years serrapeptase

has been gaining wide acceptance in Europe and Asia as a potent analgesic and

anti-inflammatory drug.

 

 

 

Serrapeptase has been used to promote wound healing and surgical recovery.

Recent Japanese patents even suggest that oral serrapeptase may help treat or

prevent such viral diseases as AIDS and hepatitis B and C.

 

But perhaps its most spectacular application is in reversing cardiovascular

disease. In fact, serrapeptase appears so effective in unblocking carotid

arteries that one researcher—Dr. Hans Nieper, the late, eminent internist from

Hannover, Germany—called it a “miracle” enzyme.

 

Does this all sound a little too miraculous to be true? Read on. There’s a solid

scientific rationale for each of these heath benefits, and they all have to do

with the fact that serrapeptase is “proteolytic” (literally,

protein-dissolving).

 

Proteolytic enzymes (also known as proteinases or peptidases) are ubiquitous in

nature, being found in animals, plants, bacteria, and fungi.

 

Human beings produce such well known peptidases as trypsin and chymotrypsin to

help digest our food, but we also generate countless others to control virtually

every regulatory mechanism in our bodies.

 

For example, various peptidases are involved in initiating blood clotting

(thrombogenesis) and also in dissolving clots (fibrinolysis);

in evoking an immune response and quelling it; and in both promoting and halting

inflammation.

 

The mechanism in each case is the ability of the enzyme to cut or cleave a

protein target into two or more pieces, usually at very specific cleavage sites.

The same mechanism makes it possible for peptidases to inactivate HIV, the

AIDS-associated virus, by pruning the viral proteins necessary for infectivity.

 

The medical use of enzymes as anti-inflammatory agents goes back many years. In

the early 1950s it was discovered that intravenous trypsin could unexpectedly

relieve the symptoms of many different inflammatory conditions, including

rheumatoid arthritis, ulcerative colitis, and atypical viral pneumonia.

 

Subsequently intramuscular enzyme injections were found to be beneficial in

counteracting post-surgical swelling (edema), treating thrombophlebitis and

lower back strain, and rapidly healing bruises caused by sports injuries.

 

At that time the mechanism of the anti-inflammatory effect remained obscure.

Today it is believed to involve degradation of inflammatory mediators,

suppression of edema, activation of fibrinolysis, reduction of immune complexes

(antibody-antigen conglomerates), and proteolytic modification of cell-surface

adhesion molecules which guide inflammatory cells to their targets.

(Such adhesion molecules are known to play an important role in the development

of arthritis and other autoimmune diseases.)

 

It’s also thought that the analgesic effect of proteolytic enzymes is due to

their cleavage of bradykinin, a messenger molecule involved in pain signalling.

 

However, according to another theory, peptidases such as trypsin may be acting

not as anti-inflammatory agents but rather as accelerants of the inflammatory

process, thereby shortening its duration.

 

Whatever the mechanism, many studies of proteolytic enzymes over the years have

demonstrated their effectiveness in relieving pain and inflammation

independently of steroids or nonsteroidal anti-inflammatory drugs (NSAIDs).

 

Fortunately we don’t need to rely on intramuscular injections any more to enjoy

the benefits of proteolytic enzymes. Around 35 years ago researchers showed that

enterically-coated enzymes such as trypsin, chymotrypsin, or bromelain were

orally active.

 

Oral proteolytic enzymes have been used successfully ever since for inflammatory

conditions.

 

Recently the intestinal absorption of orally administered serrapeptase has also

been demonstrated.16 To achieve an ideal therapeutic effect, however, it is

essential that any enzyme preparation be properly enterically coated so as to

release the enzymes in the intestines (where they can be absorbed) and not in

the stomach

(where they can be digested).

 

The proteolytic enzymes in common use today derive from bacteria (serrapeptase

grown from Serratia marcescens cultures), plants (bromelain from pineapple stem

and papain from papaya), and animal sources (trypsin and chymotrypsin from hogs

or cattle).

 

They’re all generally useful, but for many applications serrapeptase appears to

be the most useful of them all.

 

In one study serrapeptase was compared to trypsin, chymotrypsin, and pronase

(another microbial peptidase) in a rat model of scalding, which is known to

induce abnormal activation of fibrinolysis.

 

Serrapeptase was far more effective than any other enzyme in repressing

fibrinolysis in this model, in agreement with its documented clinical efficacy

as an anti-inflammatory agent.

 

By the way, in case you’ve got a good memory for details, you might have noticed

that a few paragraphs back I said the activation of fibrinolysis, not its

repression, is one of the likely anti-inflammatory mechanisms of serrapeptase.

The truth is that serrapeptase, like other peptidases, can have seemingly

contradictory effects at different times under different circumstances. The

essential point of the study just cited is that serrapeptase and the other

peptidases " inhibited " abnormal activation of fibrinolysis, and that this was a

sign of their anti-inflammatory activity.

 

In other circumstances serrapeptase is definitely fibrinolytic, i.e.,

clot-busting, and it is this property that makes it so useful in treating

cardiovascular disease.

 

According to Dr. Hans Nieper, only three 5 mg tablets of serrapeptase daily for

12 to 18 months are sufficient to remove fibrous blockages from constricted

coronary arteries, as confirmed in many of his patients by ultrasound

examination.

 

But that’s still not the whole story—serrapeptase may well offer additional

cardiovascular benefits not considered by Nieper.

 

In particular, researchers have recently proposed that inflammation contributes

to the development of arterial blockage.

 

In one study, subjects with higher levels of CRP (C-reactive protein, a marker

for systemic inflammation) were found to have a greater risk of future heart

attack and stroke, independently of other risk factors such as smoking, high

blood pressure, or cholesterol levels.

 

Serrapeptase is both anti-inflammatory and anticlotting; unlike aspirin,

serrapeptase can melt through existing fibrous deposits.

 

Serrapeptase also lacks the serious gastrointestinal side effects associated

with chronic use of NSAIDs such as aspirin. This combination of properties makes

serrapeptase just about the perfect remedy for warding off cardiovascular

disease, better even than the proverbial aspirin a day.

 

It’s beginning to look more and more as though Dr. Nieper was right—serrapeptase

is indeed a “miracle” enzyme.

 

For optimal results in unclogging arteries Nieper suggests combining

serrapeptase with other nutritional factors, including bromelain, magnesium

orotate, carnitine, and selenium; see the information packet obtainable from the

Brewer Library for more details.

 

To avoid possible pulmonary and ileal irritation, Nieper also recommends not

exceeding a dose of about three tablets per day for long-term continuous use.

 

The Japanese company that first developed serrapeptase, recommends up to six 5

mg tablets per day—two tablets three times a day, between meals—for short-term

treatment of acute inflammation due to surgery, wound healing, sinusitis,

cystitis, bronchial asthma, bronchitis, and breast engorgement in lactating

women.

-----

 

A preliminary trial of serrapeptase

in patients with carpal tunnel syndrome.

 

Panagariya A, Sharma AK

 

Dept. of Neurology, SMS Medical College and Hospital, Jaipur.

J Assoc Physicians India 1999 Dec;47(12):1170-2

 

 

OBJECTIVES: This study was planned to assess the response of serrapeptase in

patients with carpal tunnel syndrome (CTS).

 

METHODS: Twenty patients with CTS were evaluated clinically. After baseline

electrophysiological studies, these patients were given serrapetase10 mg twice

daily with initial short course of nimesulide. Clinical and electrophysiological

reassessment was done after 6 weeks.

 

RESULTS: Mean age was 43.9 years with male to female ratio of 1:2.33. Sixty five

percent cases showed significant clinical improvement which was supported by

significant improvement in electrophysiological parameters. Recurrence was

reported in four cases. No significant side effect was observed.

 

CONCLUSIONS: serrapeptase therapy may proved to be a useful alternative mode of

conservative treatment. Larger study may be further helpful to establish the

role of serrapeptase in CTS.

 

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Proteolytic enzymes: a new treatment strategy for prosthetic infections?

 

by Selan L, Berlutti F, Passariello C, Comodi-Ballanti MR, Thaller MC

 

Istituto di Microbiologia, Facolta di Farmacia, Universita La Sapienza, Rome,

Italy.

Antimicrob Agents Chemother 1993 Dec;37(12):2618-21

 

Among the different mechanisms of bacterial resistance to antimicrobial agents

that have been studied, biofilm formation is one of the most widespread. This

mechanism is frequently the cause of failure in the treatment of prosthetic

device infections, and several attempts have been made to develop molecules and

protocols that are able to inhibit biofilm-embedded bacteria. We present data

suggesting the possibility that proteolytic enzymes could significantly enhance

the activities of antibiotics against biofilms.

 

Antibiotic susceptibility tests on both planktonic and sessile cultures, studies

on the dynamics of colonization of 10 biofilm-forming isolates, and then

bioluminescence and scanning electron microscopy under seven different

experimental conditions showed that serrapetase greatly enhances the activity of

ofloxacin on sessile cultures and can inhibit biofilm formation.

 

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A New Method for Evaluating Mucolytic Expectorant Activity and its Application

 

II. Application to two proteolytic enzymes, serrapeptase and seaprose*

 

By Y. Kase, H. Seo, Y. Oyama, M. Sakata, K. Tomoda, K. Takahama, T. Hitoshi, Y.

Okano, and T. Miyata

 

Arzneim.-Forsch. / Drug Res. 32 (1), Nr. 4 (1982)

 

From the Department of Chemico-Pharmacology. Faculty of Pharmaceutical Sciences,

Kumamoto University, Kumamoto (Japan)

 

Summary: Using our new method described in a preceding paper, in vivo effects of

two proteolytic enzymes such as serrapeptase and seaprose (SAP) on sputa

collected from bronchitis rabbits were examined. Serrapeptase (20 mg/kg) and SAP

(30 mg/kg) significantly reduced the viscosity of sputum (P < 0.05) at the 1-3-h

periods and the 4-6-h periods, respectively, after intraduodenal administration.

50 mg/kg of serrapeptase also significantly decreased not only viscosity (P <

0.001) but also amount of freeze-dried substance (P < 0.05) of sputum at the

1-3-h periods, but SAP did not affect the amount of dried substance. Both

enzymes significantly increased the volume of sputum, probably as the result of

liquefaction. Thus, mucolytic expectorant activity of both enzymes can be

demonstrated first by the reduction in viscosity and next by the increase in

volume of sputa. However, the decrease in amount of freeze-dried substance is

not always in accord with the reduction in viscosity.

 

Key words: Bromhexine • Bronchitis • Mucolytic expectorants • Proteolytic

enzymes • Seaprose • serrapeptase

 

1. Introduction

 

In this previous paper [1], we reported a new method which seems to be

applicable to examine the in vivo effect of mucolytic expectorants. By the use

of this method, the expectorant effect of a drug can be evaluated from the

changes in both quantity and quality of sputa, which were quantitatively

collected from the rabbits suffering from subacute bronchitis caused by

long-term exposure to SO2 gas. The purpose of the present study is to ascertain

whether this method is well applicable to the evaluation of mucolytic

expectorant effect of the reference drugs as was expected, whose clinical

efficacy was already well established. Two proteolytic enzymes, serrapeptase and

seaprose, were chosen for such a purpose. Though their chemical properties

differ, both enzymes have so far been used as the effective mucolytics in the

treatment of various disorders related to viscous sputum or pus, and their

efficacies have been war-ranted to be more potent and reliable than those of

a-chymotrypsin and

others. Therefore, they have widely been used not only in Japan but also in.

some other countries. Nevertheless, the pharmacological evidence which

sub-stantiates their clinical efficacies, in particular, mucolytic expectorant

effect, is insufficient, though they exhibit potent mucolytic activity in in

vitro experiments [2, 3]. Bromhexine, a representative of the expectorants, was

used as a control drug, because its mechanism of action is quite different from

that of proteolytic enzyme, that is, it does not exhibit in vitro mucolytic

activity and its main effect is known only by the increase in the volume of

respiratory tract fluid (RTF) when it was examined by Perry and Boyd's method

[4-7] using normal healthy rabbits. Further pharmacological study, for instance,

the acting mechanism of mucolytic expectorant effect of intraduodenally

administered enzymes will be described in the subsequent paper.

 

2. Materials and methods

 

2.1. Animals and drugs

 

Male rabbits of New Zealand White-strain, weighing 1.8 to 2.5 kg, were used.

Serrapeptase (Danzen*, hereafter abbreviated as SER), a proteolytic enzyme

(endopeptidase) prepared from the culture broth of. genus Serratia sp. E-15 (one

of enteric bacilli in silkworm) which comes as grayish powder, was provided

 

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Evaluation of Serratia Peptidase in Acute or Chronic Inflammation of

Otorhinolaryngology Pathology: a Multicentre, Double-blind, Randomized Trial

versus Placebo

 

A. Mazzone1, M. Catalan2, M. Costanzo3, A. Drusian4, A. Mandol5, S. Russo6, E.

Guarini7 and G. Vesperini8

 

 

1Institute of Clinical Otorhinolaryngology, University of Naples, Naples, Italy;

2Ear, Nose and Throat Department, 'Gradenigo' Hospital, Turin, Italy;

3Ear, Nose and Throat Department, 'Villa Sofia' Hospital, Palermo, Italy;

4Ear Nose and Throat Department, Treviso Regional Hospital, Treviso, Italy;

5Ear, Nose and Throat Department, 'E. Fornaroli' Hospital, Magenta, Italy;

6Ear, Nose and Throat Department, Lucca Hospital, Lucca, Italy;

7Ear, Nose and Throat Department, Civil Hospital, Lecce, Italy;

8Ear, Nose and Throat Department, 'Madonna del Soccorso' Hospital, San Benedetto

del Tronto, Italy

 

 

The efficacy and tolerability of Serratia peptidase were evaluated in a

multi-centre, double-blind, placebo-controlled study of 193 subjects suffering

from acute or chronic ear, nose or throat disorders. Treatment lasted 7 - 8

days, with the drug or placebo being administered at a rate of two tablets three

times a day. After 3-4 days' treatment, significant symptom regression was

observed in peptidase-treated patients. There was also a significant reduction

in symptoms after 7 -8 days for patients in both treatment groups but the

response was more marked in those patients receiving the active drug.

Statistical comparison between the two groups confirmed the greater efficacy and

rapid action of the peptidase against all the symptoms examined at both stages.

Tolerance was found to be very good and similar for both groups. It is concluded

that Serratia peptidase has anti-inflapimatory, anti-edemic and fibrinolytic

activity and acts rapidly on localized inflammation.

 

Received for publication 2 January 1990; accepted 16 January 1990.

 

Address for correspondence: A. Mazzone, MD, Institute of Clinical

Otorhinolaryngology, University of Naples, Via Pansini 5, 80131 Naples, Italy.

 

 

INTRODUCTION

The use of enzymes with fibrinolytic, I proteolytic and anti-edemic activities

has gained increasing support in recent years for the treatment of inflammatory

ear, nose and throat (ENT) conditions1. Included among these enzymes is the

Serratia peptidase (Danzen® ), a protease obtained from non-pathogenic

enterobacteria of the genus Serratia. This proteolytic enzyme, which is

available in tablet form to enable it to be absorbed from the intestinal lumen,

has been shown lo induce intense fibrinolytic. anti-inflammatory, and

anti-edemic activity in a number of tissues and results suggest that its

anti-inflammatory activity may be of particular use for the treatment of

localized or 'closed' forms of inflammation, such as those frequently found in

ENT pathologies.' ^ Another important feature of Serratia peptidase is its

effect on pain, the enzyme acting by inhibiting the release of pain-inducing

amines, such as bradykinin, from inflammed tissue.1.7

 

This peptidase induces fragmentation offibrinose aggregates and reduces the

viscosity of exudates, " ^ thus facilitating the drainage of these products of the

inflammatory response and thereby promoting the tissue repair process, and

clinical trials have confirmed that the use of Serratia peptidase resulted in

fast resolution of the inflammatory process. " ~ '° The aim of the present

placebo-controlled multicentre study was to evaluate the efficacy and

tolerability of the Serratia peptidase in the treatment of ENT inflammatory

conditions.

 

PATIENTS AND METHODS

 

Patients

 

Patients, who were recruited from ENT clinics throughout Italy, were all

suffering from inherent acute or chronic inflammatory conditions. Any patients

with serious concomitant conditions, such as severe renal and/or hepatic

impairments, or who required additional drugs were excluded from the tnal, as

this could interfere with evaluation of the parameters under examination, and

the use of steroids, non-steroidal anti-inflammatory drugs and/or

anti-inflammatory/analgesic agents was prohibited. Antibiotics were permitted

when deemed necessary.

 

Treatment

 

Indistinguishable tablets containing 5 mg Serratia peptidase or a placebo were

provided in blister packs and patients were randomly assigned to receive two

tablets of either drug, which they were instructed to take three times daily

after meals for 7 -8 days.

 

Evaluation of treatment

Clinical signs and symptoms were assessed on days 0, 3-4 and 7-8 of treatment on

a scale of O-3 (0, absence of the symptoms: 3, maximum severity). Clinical

parameters recorded were as follows: pain; quantity of secretion; difficulty in

swallowing; nasal obstruction; anosmia; and body temperature. The appearance of

the secretion was also recorded on a scale ofO-3 (0, normal; I, mucoid; 2,

mucopurulent: 3, purulent). All evaluations were performed by an ENT specialist

unaware of the treatment given.

 

Evaluation of tolerability

Tolerability of Serralia peptidase was evaluated on the basis of the presence,

absence or severity of side-effects, recorded on the patients' data-collecting

forms.

 

Statistical analysis

All data were analysed by the most appropriate statistical tests (^-test and

Student's f-test).

 

RESULTS

 

A total of 193 subjects (96 males, 97 females), aged between 12 and 77 years

(mean ± SD 38 ± 15.7 years), with acute or chronic ENT pathologies were

recruited to the trial. Of these 193 cases, 97 (43 males, 54 females; mean ± SD

37.3 ± 15.2 years) were placed in group A and 96 (53

 

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The treatment of breast engorgement with Serrapeptase (Danzen): a randomised

double-blind controlled trial.

 

Kee WH, Tan SL, Lee V, Salmon YM.

 

Singapore Med J 1989 Feb;30(1):48-54

 

We evaluated an anti-inflammatory enzyme drug Danzen (Serrapeptase: Takeda

Chemical Industries, Ltd.) on 70 patients complaining of breast engorgement.

These patients were randomly divided into 2 groups, a treatment group and a

placebo group. A single observer, unaware of the group the patients were in,

assessed the severity of each of the symptoms and signs of breast engorgement

before treatment was commenced, and daily for 3 days, during which therapy was

administered. Danzen (Serrapeptase) was noted to be superior to placebo for

improvement of breast pain, breast swelling and induration and while 85.7% of

the patients receiving Danzen (Serrapeptase) had " Moderate to Marked "

improvement, only 60.0% of the patients receiving placebo had a similar degree

of improvement. " Marked " improvement was found in 22.9% of the treatment group

and 2.9% of the placebo group. These differences were statistically significant

(P less than 0.05). No adverse reactions were reported with the use of

Danzen (Serrapeptase). Danzen (Serrapeptase) is a safe and effective method for

the treatment of breast engorgement.

 

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A multi-centre, double-blind study of serrapeptase versus placebo in

post-antrotomy buccal swelling.

 

Tachibana M, Mizukoshi O, Harada Y, Kawamoto K, Nakai Y.

 

Pharmatherapeutica 1984;3(:526-30

 

A multi-centre, double-blind, placebo-controlled trial was carried out to

investigate the clinical efficacy of the anti-inflammatory enzyme serrapeptase

in a total of 174 patients who underwent Caldwell-Luc antrotomy for chronic

empyema. Eighty-eight patients received 10 mg serrapeptase 3 times on the day

before operation, once on the night of the operation and 3 times daily for 5

days after operation; the other 86 received placebo. Changes in buccal swelling

after operation were observed as a parameter of the response to treatment. The

degree of swelling in the serrapeptase-treated patients was significantly less

than that in the placebo-treated patients at every point of observation after

operation up to the 5th day (p less than 0.01 to p less than 0.05). Maximal

swelling throughout all the post-operative points of observation was also

significantly smaller in size in the serrapeptase-treated group than in the

placebo-treated group. No side-effects were reported.