Journal Of Holistic Medicine
Vol 5. No I. Spring/Summer 1983

Edta Chelation Therapy III: Treatment Of Peripheral Arterial Occlusion, An Alternative To Amputation

H. Richard Casdorph, MD, PhD Charles H. Farr, MD, PhD

ABSTRACT: Four patients are presented, each of whom represents end-stage occlusive peripheral arterial disease with gangrene of the involved extremity. These patients had exhausted all traditional forms of therapy and they had all been referred for surgical amputation. Instead of surgery, intravenous EDTA chelation therapy was instituted with complete success in each case. These gangrenous extremities all healed and were saved from amputation. Long-term follow-up, extending for more than a year, indicates that all four patients are continuing to do well, with their previously gangrenous extremities intact and pain free. Adjunctive therapies included vitamin and mineral supplementation and, in two case, hyperbaric oxygen therapy (HBO).

In the first two articles of this series, it was shown by objective scientific evidence that the use of intravenous ethylene diamine tetraacetic acid (EDTA) chelation therapy resulted in statistically significant, objective measurements of improvement in arteriosclerotic heart disease and in brain disorders.^1,2

In this paper, four case histories are presented, illustrating the lasting beneficial effects of intravenous EDTA chelation therapy in the treatment of occlusive peripheral arterial disease. These patients were first seen by the authors after end-stage complications of ischemia were well established. All four patients had been referred for surgical amputation of the involved extremity.

The similarities of action of EDTA with calcium channel blockers is apparent inasmuch as nifedipine and EDTA have both been reported to be dilators of the peripheral arterial tree. In addition, EDTA administered intravenously has numerous other beneficial physiological effects and has consistently been observed to result in continuing improvement long after the infusions are discontinued.

BACKGROUND INFORMATION

The earliest reported research using EDTA for removal of metastatic calcium deposits was conducted in 1946 at the University of Zurich and in 1947 and in 1948 at the University of Bern³

The fact that EDTA binds calcium and removes it from living tissue was shown by Grant.⁴ He utilized solutions of EDTA as a collyriurn for calcium removal from the eyes of patients with post-keratitis corneal opacities.

Bolick demonstrated the effectiveness of EDTA for the removal of calcium from atheromatous arterial plaques in vitro. Total calcium content of coronary vessels and the rate of calcium removal were determined.⁵ Bolick's studies indicated that coronary artery atheromatous calcifications can be as extensive as aortic lesions and that in both locations the lesions occur in two different forms. One form, which showed hematoxylin-ringed lacunae when calcium was removed, contained a form of calcium which was slowly extracted by EDTA. The other form of calcification showed no lacunae and appeared to be more diffusely dispersed. The calcium content of this second type of lesion was more rapidly extracted by EDTA.⁵

Koen used subcutaneous injections of magnesium disodium EDTA on rabbits which had been fed with a cholesterol enriched diet. Koen found that following injections of EDTA, the surface of the rabbit aortae showed diminished atheromata and a marked decrease in phospholipids. He also concluded that chelation therapy produced slower synthesis and more rapid destruction of phospholipids as well as increased turnover of phosphate.⁶

The first published studies in humans were performed by Clark, who administered EDTA intravenously to patients with various forms of advanced occlusive arterial disease. Relief of symptoms and objective signs following EDTA chelation therapy were reported to be superior to results obtained by any other method, including bypass or other forms of arterial surgery. Clark reported his best results in patients with intermittent claudication of the legs and in occlusive vascular disease affecting the brain.⁷

Studies in the Russian literature reported by Nikitina and in the Czechoslavakian literature reported by Brucknerova indicate beneficial effects following intravenous EDTA therapy on patients with cerebral, coronary and peripheral arterial occlusion. These authors concluded that chelation is a treatment of choice for occlusive peripheral arterial diseasc.^8,9

The fact that EDTA removes calcium from the arterial wall is an important point and has been conclusively shown in a study by Walker.³ In this study, New Zealand albino rabbits exhibited calcified aortic plaques with marked elevation of serum cholesterol levels to approximately 1200 mg/dL after 23 weeks on an atherogenic diet. One month after termination of this aetherogenic diet, the rabbits were treated with disodium EDTA (50 mg/kg body weight) via the marginal ear vein on alternating days for a total of 20 infusions each. Six weeks after completion of EDTA chelation therapy, the animals were sacrificed and the aortae were examined for tissue calcium; both quantitatively by direct microcomplexometric analysis, and histologically. Rabbits infused with EDTA exhibited significantly less (p = .05) aortic calcium (300 mcg/gm of tissue) when compared with chose animals treated with normal saline (635 mcg/mg of tissue), and also compared with those animals which received no infusions (778 mcg/mg of tissue). Obvious calcified plaques could be seen in non-infused animals while none were noted in those which had received EDTA. These results indicated conclusively that disodium EDTA chelation therapy can affect the removal of plaque calcium from the aortae of atherosclerotic rabbits, contributing to a reduction in both size and number of atheromatous lesions.

CASE 1

A 57-year-old white male, H.R., was first examined on April 30, 1981 for ischemia of his right foot, He was seen as an emergency inasmuch as he was scheduled that same day to be seen by a surgeon for amputation of the right lower extremity.

During the preceding two months he had developed progressive ischemia of the right foot with foot pain, particularly at rest. There was a history of intermittent claudication in both calves of several years duration. He had undergone a right femoral-to-popliteal bypass graft two years previously. The patient did well post-operatively until the bypass graft clotted, whereupon ischemia and claudication returned to the right lower extremity.

His toenails had been trimmed two months prior to the examination and as a consequence the right foot had become infected. When he was first examined on April 30, 1981, we expressed the opinion that it was possible to save his foot from amputation. At this point a complete physical examination was performed as well as initial laboratory studies. The patient was then started on intravenous chelation therapy with EDTA. Figure 1 represents a photograph of the foot, obtained on May 5, 1981, after the third infusion of EDTA. At the time, the foot was diffusely inflamed, red, swollen and painful, with an infected lesion where the toenail had been trimmed two months earlier.

FIGURE 1.

After the seventeenth EDTA infusion, it became apparent that arterial flow to the foot was improving. Hyperbaric oxygen (HBO) therapy was then instituted at Long Beach Memorial Hospital, initially as an outpatient. He was subsequently admitted to Long Beach Memorial Hospital on June 8, 1981 for intensive therapy of the foot with intravenous antibiotics and continuation of daily hyperbaric oxygen treatments in a Sechrist monoplace hyperbaric oxygen chamber.

The series of hyperbaric treatments was completed on July 27, 1981. The patient then returned to our office for further outpatient chelation therapy. During the period of in-hospital treatments, arterial perfusion to the foot continued to improve. However, a line of gangrenous demarcation developed across the second, third and fourth toes with sloughing and dry gangrene of the distal halves of those toes.

While hospitalized, the lower extremities were studied in the non-invasive vascular laboratory. The lower vaso-graphic pulse wave studies indicated severe sclerosis and occlusion of the arteries from the groin downward. Systolic pressures in the right lower extremity were quite low from groin to ankle and no Doppler arterial pulse could be detected in the right great toe. "The results of these measurements indicated, in our opinion, that the probability of healing the right foot was less than 50 percent."

The patient was readmitted to Long Beach Memorial Hospital on August 10, 1981, as a semi-emergency with the development of fever and dehydration associated with elevation of BUN, caused by toxicity from his gangrenous foot. Renal impairment was preexisting and was not affected by EDTA. The patient was treated with intravenous fluids and antibiotics for infection of the right foot. The intravenous antibiotics included Keflen® and Geocilllin®. A culture was obtained from the affected foot revealing both Klebsiella and Pseudomonas infection.

While in the hospital, on August 18. 1981, a photograph of the foot was obtained, as shown in Figure 2. That photograph depicts extensive dry gangrene of the second, third and fourth toes.

The patient again returned to our office to continue outpatient EDTA chelation therapy. Because of preexisting reduced renal function, with a creatinine clearance ranging between 20 to 45 ml/min (normal 70-130 ml/min), the dose of EDTA was maintained at a reduced level of 1.5 gm EDTA in 500 ml of Ringer's lactate, 25 mg/Kg of body weight. Creatine clearance was 32 ml/min on 9- 14-81. The patient continued chelation therapy one to three tunes per week at this reduced dosage of EDTA, as his condition would permit. He received his forty-fifth infusion of EDTA on December 28, 1981 with careful monitoring of his renal function throughout.

FIGURE 2

FIGURE 3

The patient was admitted to Long Beach Community Hospital on January 20, 1982 because of sloughing of the tips of the second, third and fourth toes. The patient was taken to surgery on January 23. 1982 for amputation and debridement of the necrotic right second, third and fourth toes, and removal of the right great toenail. This surgery removed all necrotic tissue from the foot. The procedure was well tolerated and the patient was discharged from the hospital on February 6, 1982 to be followed as an outpatient. The amputation sites appeared clean and healing at that time, and the patient was able to ambulate without pain.

Figure 3, a photograph obtained on March 1, 1982, shows complete absence of necrosis or ischemia, Chelation therapy was no longer necessary. The patient was ambulating on the affected foot without pain or ischemia. He was living a normal life with no limitations or disability. The foot was well healed.

CASE 2

Mr. A.H., who resides in West Palm Beach, Florida, was referred in July 1980 for evaluation of infection and ischemia of his right foot. This 65-year-old white male had exhausted all traditional medical facilities in his home city. He had been examined by several vascular specialists and amputation was recommended as the only possible therapy.

A.H. was a known diabetic. He had been admitted to St. Mary's Hospital in West Palm Beach on May 15, 1980. On the following day, a wire was removed from his right forefoot in the web between the first and second toes. The wire had been there for two weeks but was not discovered until cellulitis developed on the dorsum of the foot. He had been unaware of the wire because of diabetic neuropathy and reduced sensation in his feet. He was hospitalized for two weeks while intravenous antibiotics were administered and was released on May 30, 1980. Since that time, despite oral antibiotics, the ulcer between the toes gradually enlarged and amputation was advised. The patient then came to California for possible chelation therapy.

He was hospitalized at Long Beach Community Hospital from July 22, 1980 to August 15, 1980, during which time chelation therapy was instituted. Figure 4 shows the right foot on July 26, 1980, after the second infusion of EDTA. Note the deep ulcer, two centimeters across and two centimeters in depth, involving the forefoot at the lateral base of the right great toe. There was also an ulcer on the plantar surface of the second toe. X-rays showed evidence of osteomyelitis of the metatarsal bones. Note the cellulitis extending proximally on the dorsum of the foot in Figure 5.

During hospitalization cultures were obtained from the foot ulcers, revealing multiple organisms requiring intravenous antibiotics, including Geopen® and subsequently Amikacin® which was continued up to the day of hospital discharge.

While in the hospital, the patient received 13 intravenous infusions containing 3 gm EDTA in 500 ml Ringer's lactate. He was discharged from the hospital on August 15, 1980 with the following final diagnoses:

1. Diabetes rnellitus of the insulin-dependent type;

2. Traumatic and infected ischemic ulcer of the right forefoot in the web between the first and second toes, severe occlusive arterial disease and cellulitis of the forefoot. There was also an ulcerative lesion on the plantar surface of the second toe. This was associated with acute osteomyelitis, involving the right distal second metatarsal and base of the proximal phalanx, with inflammatory osteoporosis of the involved phalanges and distal metatarsals;

3. Possible ischemic heart disease with an abnormal electrocardiogram showing a right bundle branch block. His past history suggested myocardial ischemia requiring hospitalization in

1963;

4. Status post-operative bilateral carotid endarterectomies preceded by cerebral ischemic episodes in 1974;

5. Status post cholecystectomy for scones in l956.

Mr. A.H. was advised to continue chelation therapy on an outpatient basis. However, because of a recurrence of serious infection of the foot with systemic toxicity, the patient was readmitted to Long Beach Community Hospital on August 27, 1980. During this time the patient continued to receive intravenous antibiotics and chelation therapy with EDTA. EDTA treatments were administered approximately every other day and the patient received his twenty-second infusion of EDTA during hospitalization.

The foot showed progressive healing and he was transferred to Long Beach Memorial Hospital on September 4, 1980 for the addition of hyperbaric oxygen therapy to his therapeutic regimen. Following these various treatments, there was continued improvement of the foot with healing of the necrotic ulcer. Figures 6-A and 6-B are photographs obtained on September 26, 1980, after thirty-one infusions, each containing three grams of EDTA each, and after three weeks of daily hyperbaric oxygen therapy. Each hyperbaric oxygen treatment lasted an hour or more. These photographs indicate satisfactory healing of the ulcers on the plantar surface of the foot and clearing of cellulitis on the dorsum of the foot.

After discharge from the hospital, he returned to his permanent residence in Florida, where his foot has continued to heal without additional therapy. Approximately nine months later, on June 15, 1981, photographs were obtained of the dorsum and plantar surfaces of his foot, as shown in Figures 7 and 8, indicating complete healing. Figure 9 shows the patient in September, 1981, as he continues to walk on the foot without pain, able to lead an entirely normal life.

The patient returned to Long Beach, California, on March 12, 1982 for follow-up examination. At the time the lesions were completely healed and x-ray of the foot indicated complete clearing of the osteomyelitis. The patient was ambulating normally without pain.

FIGURE 4		FIGURE 5.
FIGURE 6A		FIGURE 6B
FIGURE 7		FIGURE 8.
FIGURE 9.

CASE 3

Mr. G.O., a 79-year-old Native American Indian chief, was first seen in January 1975, two days after dismissing himself against medical advice from a Veterans Administration Hospital where he had been scheduled to have his left leg amputated below the knee. Two months earlier he had undergone a right below-knee (B-K) amputation at that same hospital because of severe occlusive peripheral arterial disease. Before full recovery from his right leg amputation, he developed gangrene of the left great toe, prompting the same surgical team to schedule amputation of his left leg. The patient was brought to our office by his wife. A thorough examination revealed multiple disease problems relative to his generalized arteriosclerosis, including cardiomegaly, arteriosclerotic heart disease, severe generalized calcific atherosclerosis with arterial calcium deposits noted on x-ray, chronic atrial fibrillation and ischemic changes on his electrocardiogram.

The right amputation stump appeared to be healing well, although there was still significant tenderness and edema which prevented him from wearing a prosthesis. Gangrene was present on his remaining foot which involved approximately one half of the lateral-distal aspect of the left great toe. Peripheral areas of this gangrene were moist, and the central portion was dry and necrotic. The affected toe is shown in Figure 10, taken on January 30, 1975. Pulsations measured with a Buffington digital plethysmograph cuff, as shown in Figure 14-A, showed no digital pulse. There was evidence of diabetes but his other blood chemistries, including thyroid and serum lipids, were all within normal limits.

This patient was placed on a low-fat diet, given a broad spectrum vitamin and mineral supplement arid was started on a series of intravenous EDTA chelation infusions, each containing three grams of EDTA per 500 ml of five percent dextrose solution with 5,000 units of heparin added. Each infusion lasted three hours and was given at the rate of four per week. At the time of the second photograph, Figure 11, taken on March 18, 1975, the patient had received twenty treatments, for a total of 60 grams of EDTA. The gangrenous area on his toe had become dry, and the lateral edges were grandulating with obvious healing. The digital pulse recording at that time, Figure 14-B, was irregular with no significant pulsations. He was given ten additional EDTA treatments for a total of 30 infusions (90 grams of EDTA). The toe was then almost completely healed, as shown in Figure 12 taken on April 30. 1975. At the time pulse volume recordings of the left first toe showed well formed waves, although the amplitudes were small, as depicted in Figure 14-C.

Figure 13, taken on June 25, 1975, six months after beginning EDTA chelation therapy, shows continued healing. Normal pulse volume curves had returned to the toe, as shown in Figure 14.D, taken on September 16. 1975. Two months after the patient received his last EDTA treatment the healing process continued. Most patients who undergo intravenous EDTA chelation therapy experience continued improvement for several months following the last infusion. This patient was last seen on May 5, 1976, when examination revealed complete recovery and good pulses in the toes.

In the summer of 1976, Mr. G.O. returned to his native tribal home in North Carolina with a functional healthy leg which had been scheduled for surgical amputation eighteen months earlier. At no time during EDTA chelation therapy were any other medications required. There were no adverse reactions to chelation therapy.

Figure 10		Figure 14A
Figure 11		Figure 14B
Figure 12		Figure 14C
Figure 13		Figure 14D

CASE 4

Mr. V.A., a 67-yearold white male, was first seen on April I8, 1981, with a 20 year history of maturity-onset diabetes. His diabetes was reported to be fairly well controlled by diet and Orinase®, 250 mg, four times daily. Nine months previously, he had noticed the insidious onset of an ulcerated area on the medial aspect of the distal joint of the right great toe. This ulceration then spread to involve the medial and distal aspects of that toe. He was initially treated with potassium-permangenate soaks by his family physician. Antibiotics and proteolytie enzyme ointments were later added to the regimen. Despite vigorous traditional management, the ulcerated areas deteriorated rapidly. Mr. V.A. was then referred to a vascular surgeon who recommended amputation of the right foot. The patient, however, chose to explore a non-surgical approach. He was seen in our clinic for evaluation for EDTA chelation therapy. Blood profiles and renal function tests were essentially normal. Urinary and tissue trace element measurements indicated a fair nutritional status. Repeated fasting blood sugars ranged between 90 to 120 mg/dL. Vascular studies indicated fair to poor pulse waves in his toes. Stress hyperemic tests showed abnormally delayed filling of his right leg. His ankle/brachial Doppler systolic blood pressure ratios in both legs were below 0.23. In our experience, ischemic ulcerations frequently develop whenever this ratio falls below 0.3. Examination revealed an area of deep necrotic ulcerations on the medial and distal portions of the right great toe. The ulcerations had eroded completely through all tissue, exposing the phalangeal bones. The patient had peripheral neuropathy with decreased pain and vibratory sense in both feet. He was totally unaware that he had fractured the distal end of the proximal phalanx of his right first toe. The separated fracture line was easily visible under the necrotic area. Figures 15.A and B show the deep ulcerations prior to chelation therapy. Discoloration of the toenails was due to potassium-permangenate which the patient continued to use daily.

The patient's diet was not manipulated. However, he was given broad spectrum vitamin, mineral and trace element supplements to enhance the healing process. Intravenous EDTA chelation infusions were begun using 3 grains of EDTA per 500 ml of 2 % glucose in half normal saline. Five thousand units of heparin and 2 grams of magnesium chloride were added to each infusion, converting the disodium EDTA to magnesium disodium EDTA. He was given treatments at the rate of once each week, beginning on June 10, 1981. He had completed 30 treatments by December 2, 1981 for a total of 90 grams of EDTA. Blood sugars, taken at frequent intervals, as well as creatinine clearance and other renal studies, remained normal. Progressive healing of the ulcers was very evident after 30 chelation treatments. By June 12. 1982, one year later, the ulcerated areas were completely healed, as shown in Figure 16.

The patient's ankle/brachial Doppler systolic blood pressure ratio had risen to 1.1. Sensation had returned o his extremities. He continued doing quite well and he was very pleased to have saved his foot from amputation.

FIGURE 15A		FIGURE 15B
Figure 16

DISCUSSION

Basic science studies referred to above, indicate that EDTA binds and removes ectopic calcium deposits from arterial walls. Morever, clinical studies have consistently indicated improvement of symptoms in both large vessel arterial occlusion and in small vessel disease, with improved blood flow to ischemic areas following an adequate course of intravenous EDTA chelation therapy.

The four cases presented in this report all suffered with far advanced occlusive arterial disease involving the lower extremities. EDTA chelation therapy was the most important therapeutic factor in reversing the natural course of their disease. All four patients had been examined by vascular surgeons who had recommended amputation. All four patients had exhausted all other forms of medical and surgical therapy. Case 1 had previously undergone bypass surgery (femoral-popliteal) to the right lower extremity with only transient improvement. Case 3 had already undergone a B-K amputation of his right leg and was scheduled to have an additional amputation of his remaining leg.

All four patients experienced infection, ulceration, cellulitis, and gangrene. Chelation therapy, with other supportive modalities, was effective in saving these extremities from amputation. In Case 1, only the tips of the right second, third and fourth toes were amputated, followed by prompt healing. All four patients are alive and well today. They are free of pain and walking without limitation or handicap.

Two of the patients received a three week, in-hospital regimen of daily or twice daily hyperbaric oxygen therapy, each treatment lasting approximately one hour, in a monoplace hyperbaric chamber a 2ATA. Hyperbaric oxygen treatments had a synergistic beneficial effect in the presence of deep penetrating cellulitis, especially when infection involved anerobic organisms or bone. In Case 1, dry gangrene of several toes progressed to a pronounced demarcation with viable tissue during the course of hyperbaric oxygen therapy. It is the authors' opinion that the ultimate long-term survival of these feet was made possible by improvement of blood flow to the extremities resulting from EDTA chelation therapy. Clinical observations were supported in Case 3 by a very obvious increase in peripheral pulse wave measurements.

Historically, treatment of end-stage occlusive peripheral vascular disease in diabetic patients has been both difficult and disappointing. The application of intravenous EDTA chelation therapy, as illustrated in Case 4, can be effective and rewarding. Vascular disease in the diabetic patient is often ateriolar, involving primarily very small vessels. In this case, pulse volume measurement of the medium size vessels showed no significant change following chelation. However, complete healing occurred as a result of increased small vessel perfusion.

Clinical evidence reported here and elsewhere supports the use of intravenous EDTA chelation therapy as a safe and effective method of treatment of occlusive arterial disease of both the medium and small vessels.

Dr. H. Richard Casdorph is currently Assistant Clinical Professor of Medicine at the University of California Medical School. Irvine, California. He practices internal medicine and specializes in the treatment of cardiovascular disease at Long Beach, California. He received his training in cardiovascular diseases a. the Mayo Clinic and received his Ph.D. degree in Medicine from the University of Minnesota. More recently he has taught at U.C.L.A. Medical School and has been Chief of Medicine at Long Beach Community Hospital.

Dr. Charles H. Farr is Chairman of the American Board of Chelation Therapy and Diplomate in Chelation Therapy of the American Academy of Medical Preventics. He is currently in private practice in Oklahoma City, Oklahoma.

REFERENCES

1. 1. Casdorph HR. "EDTA chelation therapy, efficacy in arteriosclerotic heart disease." Journal of Holistic Medicine, 1981; 3:53-59.

2. 2. Casaorph HR. EDTA chelation therapy II, efficacy in brain disorders "Journal of Holistic Medicine, 1981, 3:101-117.

3. 3. Walker F. Th effects of EDTA chelation therapy on plaque, calcium and mineral metabolism in arteriosclerotic rabbits, PhD thesis. Texas State University, 1980; University Microfilm International, Ann Arbor, Ml 48016.

4. 4. Grant W. "New treatment of corneal opacities," Arch Ophthalmol. 1952, 48:6-81.

5. 5. Bolic LE. Blankenhorn DH. "A quantitative study of coronary artery calcification." Am J Path. 1961: 39:51 1-517.

6. 6. Koen A, McCann DS, Boyle AJ. "Some in vItro effects of chelation-Il animal experimentation," Journal of Chronic Diseases, 1963; 16:329-333.

7. 7. Clark NE. "Atherosclerosis, occlusive vascular disease and EDTA," Am J Cardiol, 1960; 6:233-236.

8. 8. Nikitina EK. "Treatment of atherosclerosis with Trilan B (EDTA)," Kardiologiia, 1972; 12:137.

9. 9. Brucknerova O, Tulachek J. "Chelates in the treatment of occlusive atherosclerosis," Vnitr Lck, 1972; 18:729.