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Allergy Research Group® Newsletter April 2003 L o n g - t e rm , L ow-intensity Warfarin (Coumadin) T h e ra pyHighly Effective Method of Preventing Recurrent Ve n o u s T h r o m b o e m b o l i s m : Can Nattokinase Play a Role? See page 2New England Journal of Medicine, April 10th, 2003. In This Issue
NEJM: Low-Dose Warfarin
Dr. Ralph Holsworth on the use of Coumadin & (Coumadin) Therapy Highly EffectiveMethod of Preventing RecurrentVenous Thromboembolism: Can Nattokinase with Practical Protocols See page 3 Nattokinase Play a Role? . . . . . . . 2 D r. Ralph Holsworth on the use ofNattokinase in Combination with New Nattokinase Case Histories from Dr. Martin Milner, N.D.
N a t t o k i n a s e : Case Histories fromD r. Martin Milner, N. D. . . . . . . . . . . 3 Green Tea Components Stand Out for Enhancing in Integrative Cancer CareL u ke G. Huber, N. D. . . . . . . . . . . . . .4 Chemotherapy and Protecting Healthy Cells See page 4 Folkman’s New Research:Anti-Angiogenic Agents Treat Obesity . . 7 Plasma VEGF in Cancer PatientsDaniel Rubin, N.D. . . . . . . . . . . . . . 8 Bindweed Extract & MPGC* Reduce Plasma VEGF** in Double-Blind Placebo ControlledStudy; Evidence of Improvement Demonstrated . . . . . . . . . . . . . . . . 9 *Muramyl Polysaccharide-Glycan Complex **Vascular endothelial growth factors Abstract: Green Tea ExtractPolyphenol May Have A Protective Rye Grass Extract & Asthma: Double-Blind, Placebo Controlled Study Demonstrates Dramatic ImprovementSee page 9 Allergy Research Group®
30806 Santana Street, Hayward, CA 94544
Phone: 800-545-9960
Dr. Freidrich Douwes, M.D. on the use of MPGC for Fax: 510-487-8682
www.AllergyResearchGroup.com
Long-term, Low-intensity Warfarin (Coumadin) Therapy
Highly Effective Method of Preventing Recurrent Venous
Thromboembolism
New England Journal of Medicine, April 10, 2003
The National Institute of Health recently discontinued what was Canada, and Switzerland had been enrolled and followed for two to be a 5-year trial on the use of long-term, low-dose warfarin years on average, with some patients followed for up to four years.
(Coumadin) therapy for the prevention of Recurrent Ve n o u s According to per -protocol and as-treated analyses, the reduction
Thromboembolism (VTE). The “PREVENT” trial was stopped in the risk of recurrent venous thromboembolism was between
almost two years early, according to a recent report in the April 76 and 81 percent .
10th issue of the New England Journal of Medicine (see abstractbelow) because such strong benefits were observed that the study’s Recurrent DVT or pulmonary embolism occurred in 37 of 253 independent Data and Safety Monitoring Board concluded that it patients assigned to placebo (7.2 per 100 person-years) and in 14 of was unnecessary to continue. "This is an important finding for the
255 patients assigned to low-dose warfarin with target interna- estimated half million Americans who each year experience either
tional normalized ratio of 1.5 - 2.0 (2.6 per 100 person-years; risk deep vein thrombosis (DVT) or pulmonary embolism. These results
reduction, 64%; hazard ratio, 0.36; 95% confidence interval, 0.19 - suggest that low-dose warfarin is a safe and effective way to pre - 0.67; P < .001).
vent future episodes of these potentially serious blood clotting
problems."- Claude Lenfant, M.D., NHLBI Director.

The current standard of care for idiopathic DVT and pulmonaryembolism is five to 10 days of intravenous or subcutaneous The randomized, double-blind PREVENT trial was designed to heparin followed by three to six months of full-dose warfarin.
enroll 750 patients, aged 30 years and older, with documented Often treatment is discontinued because of bleeding risk with idiopathic DVT or pulmonary embolism within the previous two long-term use of full-dose warfarin, leading to recurrent thrombo- years who had at least three uninterrupted months of treatment sis in 6% to 9% of patients annually.
"The PREVENT results strongly suggest that long-term use of
The trial began in 1998 and was scheduled for completion in 2005, low-intensity warfarin should be considered a new standard of
but instead was discontinued in December of 2002. When the study care for the management of venous thrombosis after stopping full-
was terminated early, 508 patients at 52 clinical sites in the U.S., dose warfarin therapy," Dr. Ridker.
Abstract
Results: The trial was terminated early after 508 patients had
undergone randomization and had been followed for up to 4.3
Long-Term, Low-Intensity Warfarin Therapy for the Prevention years (mean, 2.1). Of 253 patients assigned to placebo, 37 had recurrent venous thromboembolism (7.2 per 100 person-years), New England Journal of Medicine, April 10th, 2003.
as compared with 14 of 255 patients assigned to low-intensitywarfarin (2.6 per 100 person-years), a risk reduction of 64 percent Paul M Ridker, M.D., Samuel Z. Goldhaber, M.D., Ellie Danielson, M.I.A., Yves (hazard ratio, 0.36 [95 percent confidence interval, 0.19 to 0.67]; Rosenberg, M.D., Charles S. Eby, M.D., Steven R. Deitcher, M.D., Mary Cushman,M.D., Stephan Moll, M.D., Craig M. Kessler, M.D., C. Gregory Elliott, M.D., Rolf P<0.001). Risk reductions were similar for all subgroups, includ- Paulson, M.D., Turnly Wong, M.D., Kenneth A. Bauer, M.D., Bruce A. Schwartz, ing those with and those without inherited thrombophilia. Major M.D., Joseph P. Miletich, M.D., Henri Bounameaux, M.D., Robert J. Glynn, Sc.D., for hemorrhage occurred in two patients assigned to placebo and five assigned to low-intensity warfarin (P=0.25). Eight patients in B a c k g r o u n d : S t a n d a rd therapy to prevent re c u r rent venous
the placebo group and four in the group assigned to low-intensi- thromboembolism includes 3 to 12 months of treatment with full- ty warfarin died (P=0.26). Low-intensity warfarin was thus asso- dose warfarin with a target international normalized ratio (INR) ciated with a 48 percent reduction in the composite end point of between 2.0 and 3.0. However, for long-term management, no re c u r rent venous thromboembolism, major hemorrhage, or therapeutic agent has shown an acceptable benefit-to-risk ratio.
death. According to per-protocol and as-treated analyses, thereduction in the risk of recurrent venous thromboembolism was M e t h o d s : Patients with idiopathic venous thromboembolism who
had received full-dose anticoagulation therapy for a median of 6.5months were randomly assigned to placebo or low-intensity war- Conclusions: Long-term, low-intensity warfarin therapy is a
farin (target INR, 1.5 to 2.0). Participants were followed for re c u r- highly effective method of preventing recurrent venous throm- rent venous thromboembolism, major hemorrhage, and death.
Focus April 2003
Leading Nattokinase Researcher
Dr. Ralph Holsworth on the Use of Nattokinase
in Combination with Low-Dose Warfarin
“New studies are indicating lower doses of warfarin (Coumadin). I believe a physician should use warfarin and nat-
tokinase together and titrate the warfarin downward to maintain a prothrombin time of 18-20 seconds. This protocol
will decrease the harmful effects of warfarin, while maintaining a safer level of blood anticoagulation with the positive
effects of nattokinase. I suggest this protocol for physicians who are uncomfortable with eliminating warfarin com-
pletely, but who are interested in minimizing the negative effects of warfarin, and achieving the positive effects of nat-
tokinase. This protocol could save thousands of patients from the harmful effects of warfarin.”

See Dr. Holsworth’s Protocol on page 10.
Nattokinase:
Case Histories from Dr. Martin Milner, N.D.
Case 1 – Peripheral Vascular Disease
Case 3 – Fibromyalgia with Headaches
Case 1 is a female patient with an array of health problems including Case 3 is a female with a long standing history of chronic fatigue, advanced peripheral vascular arterial disease. Her iliac artery was f i b romyalgia, persistent leg cramps, varicose veins, hypothyro i d i s m , bypassed surgically due to full occlusion in 1999 with current occlu- c h ronic migraines, GERD, colitis, mild osteoporosis, some degenerative sion of her popliteal artery. As a result, she was experiencing severe disk disease (L 4-5), osteoarthritis in one knee, obesity, hypertension, alu- intermittent claudicating bilateral calf and thigh pain, worse at night minum and arsenic toxicity, severe adrenal insufficiency and food aller- and with exertion. She experienced cramps and pains throughout the gies. She has taken supplements extensively for many years. She began night disrupting her sleep for years. Many therapies were unsuccess - taking nattokinase in January 2003 2 caps 2x daily on an empty stomach, ful in resolving her debilitating pain. She has a long history of using and then increased to 3 caps 2x daily in April 2003. After starting nattok- intravenous EDTA once monthly for five years and then once weekly inase her energy improved with complete resolution of her headaches for the last year without improvement. She is an avid and conscien- and improved varicose veins. This are extraord i n a ry a patient who has tious consumer of health supplements, having taken for many years attempted a wide array of headache medications with no re s p o n s e .
an array of nutrients, none of which, in combination with intravenous Case 4 – COPD, Shortness of Breath, Pulmonary Micro e m b o l i z a t i o n
EDTA improved her intermittent claudication. She began taking nat- with Pulmonary Hypertension, Essential Hypert e n s i o n
tokinase in July of 2002, taking 2 caps 2x daily on an empty stomach.
Within two weeks she reported that the heaviness and achiness on Case 4 is a 49 year-old female with chronic fatigue, shortness of exertion in her left leg had improved 50-70%. Her muscles in her breath and stress-related illness. Patient is obese with a variety of calves began to reduce in achiness and within 1-2 weeks she was cardiovascular conditions including heart palpitations, high blood sleeping through the night with no pain. After taking nattokinase for pressure, Type IV Hyperlipidemia, Syndrome X, COPD with 30% air- over 6 months, she had experienced only two episodes of waking at way obstruction, pulmonary hypertension, and reports swelling in night with leg pain. She has reported no side effects throughout the feet. After taking nattokinase 2 caps 2x daily for 2.5 weeks, patient’s course of therapy. In addition, with her history of mild hypertension, breathing was dramatically improved as well as her fatigue. Patient is severe peripheral vascular arterial disease, left atrial enlargement she also able to walk around the block at a medium pace with no heavy probably has some pulmonary hypertension and micro embolization breathing at all. She is also now able to grocery shop, and is even in her lungs which has been helped significantly with nattokinase.
starting to walk longer distances wearing small ankle weights.
Case 2 – Pulmonary Emboli with Headaches
Case 5 – Peripheral Vascular Disease, possible TIA and DVT
Case 2 is a 64 year-old female with a history of five prior episodes of Case 5 is a 63 year-old male with possible DVT and passive emboliza- pulmonary emboli (clots in the lungs), apparently due to lower extrem- tion, who reports a sensation of tightness in his legs and felt like he ity venous thrombi that mobilized into her lungs. The last episode was was standing for hours yet wasn’t. He developed a suspected deep in 1977 with no new occurrences since vein stripping, which was per- vein thrombus (clot) on physical examination, and was also blowing formed in 1977. With her history, a possible chronic coagulation dis- out bloody granules from his nose for three days. These bloody gran- order aggravating her other conditions was suspected. Her other ules were of concern in assessing possible pulmonary microemboli.
related conditions included migraine headaches and a long-standing He also reports a history of pain in right leg, which was diagnosed as seizure-like disorder. She began taking nattokinase 2 caps 2x daily an inflamed vein, phlebitis. He also has possible transient ischemic upon rising and before bed in January of 2003. This reduced her symptom complex including cold nose, numbness around lips, cold headaches from 2-3x weekly to none for the first 30 days. When the upper extremities in paroxysms, intermittent cold tingling in his hands, first headache did occur in late February of 2003, she developed the face and feet. Reported coldness in hands, feet and back of head pre-migraine symptoms of nausea and visual changes without ever over into his face with a loss of sensation in hands, left foot slight loss of sensation. Patient began nattokinase, 2 caps 2x daily and all of theabove symptoms resolved after one week.
For more information call 800-545-9960 or e-mail: info@www.AllergyResearchGroup.com 3

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