CA2265926C - Method of altering plasma homocysteine levels in humans - Google Patents
Method of altering plasma homocysteine levels in humans Download PDFInfo
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- CA2265926C CA2265926C CA 2265926 CA2265926A CA2265926C CA 2265926 C CA2265926 C CA 2265926C CA 2265926 CA2265926 CA 2265926 CA 2265926 A CA2265926 A CA 2265926A CA 2265926 C CA2265926 C CA 2265926C
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/04—Sulfur, selenium or tellurium; Compounds thereof
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Abstract
Elemental sulfur is useful for altering plasma homocysteine levels in humans.
As a result, elemental sulfur is useful in treating a medical condition associated with abnormal homocysteine levels, particularly hyper-homocysteinemia.
As a result, elemental sulfur is useful in treating a medical condition associated with abnormal homocysteine levels, particularly hyper-homocysteinemia.
Description
METHOD OF ALTERING PLASMA HOMOCYST(E)INE LEVELS IN HUMANS
Field of the Invention This application relates to the use sulfur for altering plasma homocysteine levels in humans. In particular, altering plasma homocysteine levels is useful in treating a number of medical conditions associated with abnormal plasma homocysteine levels.
Background of the Invention Elevated plasma homocysteine concentration (hyper-homocysteinemia) is an independent risk factor for a number of conditions including accelerated atherosclerosis, generalized atherosclerosis, atherothrombosis, carotid atherosclerosis, atherosclerotic complications of diabetes mellitus, recurrent thromboembolism, deep vein thrombosis and pulmonary embolism, recurrent pulmonary embolism, deep vein thrombosis in cancer, venous thrombosis in cancer, cerebral atherosclerosis, atherosclerotic cerebral degeneration, recurrent cerebral embolisation, transient ischemic attacks, stroke, peripheral atherosclerosis, peripheral ischemia, coronary atherosclerosis, ischemic heart disease, coronary thrombosis, angina pectoris, myocardial infarction, ventricular arrhythmias, atrial arrhythmias, gout, Alzheimer's disease, nephrosclerosis, chronic renal failure, post-menopause, hypothyroidism, pernicious anemia, vitamin B12 deficiency, vitamin B6 deficiency, folic acid deficiency, psoriasis, leukemias, cancer (including breast, ovarian and pancreatic cancers), during therapy with methotrexate and like drugs, during therapy with nitrogen oxide and like drugs, during therapy with isoniazid and like drugs, during therapy with phenytoin and like drugs, during therapy with theophylline and like drugs, homocysteinuria syndrome, cystathionine-Beta-synthase deficiency, hypertension, age effects of atherosclerosis, cardiac nerve degeneration and ventricular arrhythmias due to atherosclerosis, cardiac nerve degeneration and atrial arrhythmias due to atherosclerosis, nerve degeneration due to atherosclerosis in diabetic neuropathy, nerve degeneration due to atherosclerosis in peripheral ischemic neuropathy, osteoporosis due to atherosclerosis, conditions where elemental sulfur is necessary as an addition to folic acid and vitamin B6 (pyridoxine), conditions where elemental sulfur is necessary as an addition to folic acid, conditions where elemental sulfur is necessary as an addition to vitamin B12 (cyanocobalamin) and vitamin B6 (pyridoxine), conditions where elemental sulfur is necessary as an addition to multi-vitamins containing cyanocobalamin (vitamin B12), folic acid and pyridoxine (vitamin B6), conditions where elemental sulfur is necessary as an addition to cyanocobalamin (vitamin B12) and folic acid, and conditions where elemental sulfur is necessary as an addition to multi-vitamins.
Sublimed sulfur is also known as Abric, Flores Sulfuris or Flowers of Sulfur.
Dried over phosphorus pentoxide for 4 hours, Sublimed Sulfur contains 99.5 to percent of sulfur. Sulfur is a fine, yellow, crystalline powder having a faint odor and taste. It is practically insoluble in water and nearly insoluble in alcohol.
One gram dissolves slowly and usually incompletely (non-volatile substances) in about 2 ml of carbon disulfide, about 150 ml of ether, or about 100 ml of olive oil. To prepare Sublimed Sulfur, vapors of sulfur are conducted into a chamber properly cooled where the vapors are condensed in the form of a crystalline powder which collects on the sides and bottom of the chamber. The yellowish powder is known as Sublimed Sulfur or Flowers of Sulfur. Ground roll sulfur is sometimes sold as flour of sulfur.
Ground roll sulfur does not have identical physical properties with official Sublimed Sulfur.
Summary of the Invention It has now been found that elemental sulfur has an altering effect on plasma homocysteine concentrations in humans.
There is provided a use of elemental sulfur for normalizing an abnormal plasma homocysteine concentration in a human subject.
There is provided a use of elemental sulfur for treating a medical condition associated with abnormal homocysteine concentrations in a human subject.
Field of the Invention This application relates to the use sulfur for altering plasma homocysteine levels in humans. In particular, altering plasma homocysteine levels is useful in treating a number of medical conditions associated with abnormal plasma homocysteine levels.
Background of the Invention Elevated plasma homocysteine concentration (hyper-homocysteinemia) is an independent risk factor for a number of conditions including accelerated atherosclerosis, generalized atherosclerosis, atherothrombosis, carotid atherosclerosis, atherosclerotic complications of diabetes mellitus, recurrent thromboembolism, deep vein thrombosis and pulmonary embolism, recurrent pulmonary embolism, deep vein thrombosis in cancer, venous thrombosis in cancer, cerebral atherosclerosis, atherosclerotic cerebral degeneration, recurrent cerebral embolisation, transient ischemic attacks, stroke, peripheral atherosclerosis, peripheral ischemia, coronary atherosclerosis, ischemic heart disease, coronary thrombosis, angina pectoris, myocardial infarction, ventricular arrhythmias, atrial arrhythmias, gout, Alzheimer's disease, nephrosclerosis, chronic renal failure, post-menopause, hypothyroidism, pernicious anemia, vitamin B12 deficiency, vitamin B6 deficiency, folic acid deficiency, psoriasis, leukemias, cancer (including breast, ovarian and pancreatic cancers), during therapy with methotrexate and like drugs, during therapy with nitrogen oxide and like drugs, during therapy with isoniazid and like drugs, during therapy with phenytoin and like drugs, during therapy with theophylline and like drugs, homocysteinuria syndrome, cystathionine-Beta-synthase deficiency, hypertension, age effects of atherosclerosis, cardiac nerve degeneration and ventricular arrhythmias due to atherosclerosis, cardiac nerve degeneration and atrial arrhythmias due to atherosclerosis, nerve degeneration due to atherosclerosis in diabetic neuropathy, nerve degeneration due to atherosclerosis in peripheral ischemic neuropathy, osteoporosis due to atherosclerosis, conditions where elemental sulfur is necessary as an addition to folic acid and vitamin B6 (pyridoxine), conditions where elemental sulfur is necessary as an addition to folic acid, conditions where elemental sulfur is necessary as an addition to vitamin B12 (cyanocobalamin) and vitamin B6 (pyridoxine), conditions where elemental sulfur is necessary as an addition to multi-vitamins containing cyanocobalamin (vitamin B12), folic acid and pyridoxine (vitamin B6), conditions where elemental sulfur is necessary as an addition to cyanocobalamin (vitamin B12) and folic acid, and conditions where elemental sulfur is necessary as an addition to multi-vitamins.
Sublimed sulfur is also known as Abric, Flores Sulfuris or Flowers of Sulfur.
Dried over phosphorus pentoxide for 4 hours, Sublimed Sulfur contains 99.5 to percent of sulfur. Sulfur is a fine, yellow, crystalline powder having a faint odor and taste. It is practically insoluble in water and nearly insoluble in alcohol.
One gram dissolves slowly and usually incompletely (non-volatile substances) in about 2 ml of carbon disulfide, about 150 ml of ether, or about 100 ml of olive oil. To prepare Sublimed Sulfur, vapors of sulfur are conducted into a chamber properly cooled where the vapors are condensed in the form of a crystalline powder which collects on the sides and bottom of the chamber. The yellowish powder is known as Sublimed Sulfur or Flowers of Sulfur. Ground roll sulfur is sometimes sold as flour of sulfur.
Ground roll sulfur does not have identical physical properties with official Sublimed Sulfur.
Summary of the Invention It has now been found that elemental sulfur has an altering effect on plasma homocysteine concentrations in humans.
There is provided a use of elemental sulfur for normalizing an abnormal plasma homocysteine concentration in a human subject.
There is provided a use of elemental sulfur for treating a medical condition associated with abnormal homocysteine concentrations in a human subject.
There is provided a commercial package comprising elemental sulfur and instructions for its use in normalizing an abnormal plasma homocysteine concentration in a human subject.
There is provided a commercial package comprising elemental sulfur and instructions for its use in treating a medical condition associated with abnormal plasma homocysteine concentration in a human subject.
There is provided a use of elemental sulfur for manufacturing a medicament for normalizing an abnormal plasma homocysteine concentration in a human subject.
There is provided a use of elemental sulfur for manufacturing a medicament for treating a medical condition associated with abnormal plasma homocysteine concentration in a human subject.
There is provided a composition comprising elemental sulfur and a pharmaceutically acceptable carrier for use in normalizing an abnormal plasma homocysteine concentration in a human subject.
There is provided a composition comprising elemental sulfur and a pharmaceutically acceptable carrier for use in treating a medical condition associated with abnormal homocysteine concentrations in a human subject.
Abnormal homocysteine concentrations are associated with certain medical conditions, for example, including accelerated atherosclerosis, generalized atherosclerosis, atherothrombosis, carotid atherosclerosis, atherosclerotic complications of diabetes mellitus, recurrent thromboembolism, deep vein thrombosis and pulmonary embolism, recurrent pulmonary embolism, deep vein thrombosis in cancer, venous thrombosis in cancer, cerebral atherosclerosis, atherosclerotic cerebral degeneration, recurrent cerebral embolisation, transient ischemic attacks, stroke, peripheral atherosclerosis, peripheral ischemia, coronary atherosclerosis, ischemic heart disease, coronary thrombosis, angina pectoris, myocardial infarction, ventricular arrhythmias, atrial arrhythmias, gout, Alzheimer's disease, nephrosclerosis, chronic renal failure, post-menopause, hypothyroidism, pernicious anemia, vitamin B12 deficiency, vitamin B6 deficiency, folic acid deficiency, psoriasis, leukemias, cancer (including breast, ovarian and pancreatic cancers), during therapy with methotrexate and like drugs, during therapy with nitrogen oxide and like drugs, during therapy with isoniazid and like drugs, during therapy with phenytoin and like drugs, during therapy with theophylline and like drugs, homocysteinuria syndrome, cystathionine-Beta-synthase deficiency, hypertension, age effects of atherosclerosis, cardiac nerve degeneration and ventricular arrhythmias due to atherosclerosis, cardiac nerve degeneration and atrial arrhythmias due to atherosclerosis, nerve degeneration due to atherosclerosis in diabetic neuropathy, nerve degeneration due to atherosclerosis in peripheral ischemic neuropathy, and osteoporosis due to atherosclerosis.
In the Periodic Table of Elements, elemental sulfur is immediately adjacent to oxygen, phosphorus, chlorine and selenium, elements that are readily absorbed from the gastrointestinal tract. Elemental sulfur is also readily absorbed from the gastrointestinal tract and retained in the body. It is believed that elemental sulfur alters the rate of metabolism of sulfur-containing essential amino acids by direct sulfuration, thereby normalizing plasma homocysteine level. Normal plasma homocysteine concentration in humans has been reported to be 4 to 15 ~mol per litre.
Elemental sulfur may be used to treat hyper-homocysteinemia or conditions associated with hyper-homocysteinemia. Elemental sulfur may also be used to raise abnormally low plasma homocysteine levels to more normal values.
Preferably, the elemental sulfur is sublimed sulfur. Preferably the elemental sulfur is 99.5 to 100 percent pure.
Preferably, the elemental sulfur is administered orally. The sulfur is preferably administered in solid form. The sulfur may be administered in any suitable form, for example, capsules, tablets, etc.
Further features of the invention will be described or will become apparent in the course of the following detailed description.
Description of Preferred Embodiments Example 5 Methods:
A male subject, age 45, with a control baseline plasma homocysteine level of 77 pmol per litre consented to be the initial test case. He received Sublimed Sulfur capsules 300 mg pc bid for 45 days. His plasma homocysteine was measured 24 hours after the last dose of Sublimed Sulfur and again 25 days and 160 days after the 45 day course of Sublimed Sulfur. He then received a 30 day course of Sublimed Sulfur 200 mg pc breakfast daily. His plasma homocysteine was measured 24 hours after the last dose of the 30-day course of Sublimed Sulfur and again 30 days later.
Additional subjects were recruited from a private internal medicine referral practice. Each subject was informed of the objective of the study and, if agreeable, was instructed in the methodology of the study. The participants were provided with laboratory requisitions for the necessary tests, and with a 30 day supply of Sublimed Sulfur capsules 200 mg, to be taken pc breakfast daily. Subjects fasted for 12 to 16 hours prior to laboratory tests.
Baseline control laboratory tests were done within the 24-hour period immediately preceding the first daily dose of Sublimed Sulfur. These included plasma homocysteine, a complete blood count, chemical urinalysis, fasting serum glucose, serum levels of vitamin B12, folic acid, total cholesterol, HDL cholesterol, calculated LDL cholesterol, cholesterol/HDL ratio, triglycerides, sodium, potassium, chloride, aspartate transaminase, urate and creatinine.
Follow-up laboratory tests, similar to those done at baseline, were repeated hours after the last dose of the 30-day course of Sublimed Sulfur.
There is provided a commercial package comprising elemental sulfur and instructions for its use in treating a medical condition associated with abnormal plasma homocysteine concentration in a human subject.
There is provided a use of elemental sulfur for manufacturing a medicament for normalizing an abnormal plasma homocysteine concentration in a human subject.
There is provided a use of elemental sulfur for manufacturing a medicament for treating a medical condition associated with abnormal plasma homocysteine concentration in a human subject.
There is provided a composition comprising elemental sulfur and a pharmaceutically acceptable carrier for use in normalizing an abnormal plasma homocysteine concentration in a human subject.
There is provided a composition comprising elemental sulfur and a pharmaceutically acceptable carrier for use in treating a medical condition associated with abnormal homocysteine concentrations in a human subject.
Abnormal homocysteine concentrations are associated with certain medical conditions, for example, including accelerated atherosclerosis, generalized atherosclerosis, atherothrombosis, carotid atherosclerosis, atherosclerotic complications of diabetes mellitus, recurrent thromboembolism, deep vein thrombosis and pulmonary embolism, recurrent pulmonary embolism, deep vein thrombosis in cancer, venous thrombosis in cancer, cerebral atherosclerosis, atherosclerotic cerebral degeneration, recurrent cerebral embolisation, transient ischemic attacks, stroke, peripheral atherosclerosis, peripheral ischemia, coronary atherosclerosis, ischemic heart disease, coronary thrombosis, angina pectoris, myocardial infarction, ventricular arrhythmias, atrial arrhythmias, gout, Alzheimer's disease, nephrosclerosis, chronic renal failure, post-menopause, hypothyroidism, pernicious anemia, vitamin B12 deficiency, vitamin B6 deficiency, folic acid deficiency, psoriasis, leukemias, cancer (including breast, ovarian and pancreatic cancers), during therapy with methotrexate and like drugs, during therapy with nitrogen oxide and like drugs, during therapy with isoniazid and like drugs, during therapy with phenytoin and like drugs, during therapy with theophylline and like drugs, homocysteinuria syndrome, cystathionine-Beta-synthase deficiency, hypertension, age effects of atherosclerosis, cardiac nerve degeneration and ventricular arrhythmias due to atherosclerosis, cardiac nerve degeneration and atrial arrhythmias due to atherosclerosis, nerve degeneration due to atherosclerosis in diabetic neuropathy, nerve degeneration due to atherosclerosis in peripheral ischemic neuropathy, and osteoporosis due to atherosclerosis.
In the Periodic Table of Elements, elemental sulfur is immediately adjacent to oxygen, phosphorus, chlorine and selenium, elements that are readily absorbed from the gastrointestinal tract. Elemental sulfur is also readily absorbed from the gastrointestinal tract and retained in the body. It is believed that elemental sulfur alters the rate of metabolism of sulfur-containing essential amino acids by direct sulfuration, thereby normalizing plasma homocysteine level. Normal plasma homocysteine concentration in humans has been reported to be 4 to 15 ~mol per litre.
Elemental sulfur may be used to treat hyper-homocysteinemia or conditions associated with hyper-homocysteinemia. Elemental sulfur may also be used to raise abnormally low plasma homocysteine levels to more normal values.
Preferably, the elemental sulfur is sublimed sulfur. Preferably the elemental sulfur is 99.5 to 100 percent pure.
Preferably, the elemental sulfur is administered orally. The sulfur is preferably administered in solid form. The sulfur may be administered in any suitable form, for example, capsules, tablets, etc.
Further features of the invention will be described or will become apparent in the course of the following detailed description.
Description of Preferred Embodiments Example 5 Methods:
A male subject, age 45, with a control baseline plasma homocysteine level of 77 pmol per litre consented to be the initial test case. He received Sublimed Sulfur capsules 300 mg pc bid for 45 days. His plasma homocysteine was measured 24 hours after the last dose of Sublimed Sulfur and again 25 days and 160 days after the 45 day course of Sublimed Sulfur. He then received a 30 day course of Sublimed Sulfur 200 mg pc breakfast daily. His plasma homocysteine was measured 24 hours after the last dose of the 30-day course of Sublimed Sulfur and again 30 days later.
Additional subjects were recruited from a private internal medicine referral practice. Each subject was informed of the objective of the study and, if agreeable, was instructed in the methodology of the study. The participants were provided with laboratory requisitions for the necessary tests, and with a 30 day supply of Sublimed Sulfur capsules 200 mg, to be taken pc breakfast daily. Subjects fasted for 12 to 16 hours prior to laboratory tests.
Baseline control laboratory tests were done within the 24-hour period immediately preceding the first daily dose of Sublimed Sulfur. These included plasma homocysteine, a complete blood count, chemical urinalysis, fasting serum glucose, serum levels of vitamin B12, folic acid, total cholesterol, HDL cholesterol, calculated LDL cholesterol, cholesterol/HDL ratio, triglycerides, sodium, potassium, chloride, aspartate transaminase, urate and creatinine.
Follow-up laboratory tests, similar to those done at baseline, were repeated hours after the last dose of the 30-day course of Sublimed Sulfur.
Follow-up laboratory tests were also subsequently obtained 30~1 days (30 days) after the last dose of Sublimed Sulfur. These included plasma homocysteine levels, and serum levels of vitamin B12, folic acid, total cholesterol, HDL
cholesterol, LDL cholesterol (calculated), cholesterol/HDL ratio and triglycerides.
Electrocardiograms or exercise stress tests were done at baseline and on completion of the course of Sublimed Sulfur.
Five of the additional subjects received a second 30-day course of Sublimed Sulfur. The following laboratory tests were done 24 hours after the last dose of the second 30-day course of Sublimed Sulfur and again 30 days after the second 30-day course of Sublimed Sulfur: plasma homocysteine; and serum levels of vitamin B12, folic acid, total cholesterol, HDL cholesterol, LDL cholesterol (calculated), cholesterol/HDL ratio and triglycerides.
All laboratory tests were done by two commercial laboratories. Plasma for the measurements of homocysteine was forwarded to The Banting Institute, Toronto, Ontario, by one commercial laboratory and the The London Health Sciences Center Laboratory, London, Ontario, by the other. With two exceptions, baseline and follow-up plasma homocysteine levels were done at The Banting Institute.
The study included 29 subjects, 18 males and 11 females, mean age, 54~20 years. Nineteen subjects had multiple medical problems. Twenty-one subjects had generalized atherosclerosis. Thirteen subjects had coronary atherosclerosis, angina pectoris and/or a positive exercise stress test. Four subjects had coronary angioplasty, coronary bypass surgery and/or a positive exercise stress test.
Fourteen subjects had hypertension. Two subjects had had a stroke. Fifteen subjects had hyperlipidemia. Eight subjects had diabetes mellitus. Two subjects had complications of peripheral vascular disease. Two subjects had vitamin B12 deficiency and a past history of cancer.
Many subjects were on multiple drugs. Twenty-four subjects were on one or more of the following medications: Enalapril, Conjugated Estrogens, Progesterone, Enteric-coated Acetylsalicic acid, Lovastatin, Atenolol, Nifedipine XL, Isosorbide, Acetaminophen with Codeine, Ramipril, Perindopril, Diamicron, Lipidil micro, Simvastatin, Diclofenac, Ranitidine, Lorazepam, calcium, Etidronate, Ibuprofen, Pravastatin, Amitriptylene, Transdermal Nitroglycerine, Methocarbamol-Acetaminophen, Ipratropium nasal spray, Vitamin C, Atorvastatin, Metoprolol, Oxycodone, Ferrous gluconate, Propanolol, Lanoxin, Piroxicam, Beta-carotene, Hydrochlorothiazide, L-Thyroxine, Allopurinol, Misoprostol, Venlafaxine, Diazepam, Flurazepam, Nabumetone and Verapamil.
Twelve subjects were on lipid-lowering drugs. With three exceptions, lipid lowering drugs were discontinued two weeks prior to starting Sublimed Sulfur.
Vitamins B1, B6, B12 and folic acid were also discontinued two weeks prior to the first dose of Sublimed Sulfur and were not taken by the subjects during the course of the study. Other medically indicated therapies were continued. New medications were not added during the course of the study.
Results:
The 45 day course of Sublimed Sulfur received by the initial test subject resulted in an 89.4 percent decrease in plasma homocysteine from a baseline of p,mol per litre to 8.2 pmol per litre. Plasma homocysteine measured 25 days after the last dose of Sublimed Sulfur was 11.6 ~,mol per litre. Plasma homocysteine measured 160 days after the last dose of Sublimed Sulfur was 7.8 pmol per litre. 161 days after completion of the first course of Sublimed Sulfur, a second course of Sublimed Sulfur 200 mg pc breakfast daily for 30 days resulted in a further decrease of plasma homocysteine to 3.9 ~mol per litre, representing a 94.9 percent reduction from the initial baseline.
The baseline homocysteine levels in the 29 additional subjects ranged from 2.4 to 22.1 ~mol per litre and averaged 9.6~1.0 ~,mol per litre (mean ~ standard error of the mean). Thirty days later, after treatment with Sublimed Sulfur, the homocysteine levels declined about 45 percent to 6.5~0.5 ~mol per litre (P<0.02, Wilcoxon T
cholesterol, LDL cholesterol (calculated), cholesterol/HDL ratio and triglycerides.
Electrocardiograms or exercise stress tests were done at baseline and on completion of the course of Sublimed Sulfur.
Five of the additional subjects received a second 30-day course of Sublimed Sulfur. The following laboratory tests were done 24 hours after the last dose of the second 30-day course of Sublimed Sulfur and again 30 days after the second 30-day course of Sublimed Sulfur: plasma homocysteine; and serum levels of vitamin B12, folic acid, total cholesterol, HDL cholesterol, LDL cholesterol (calculated), cholesterol/HDL ratio and triglycerides.
All laboratory tests were done by two commercial laboratories. Plasma for the measurements of homocysteine was forwarded to The Banting Institute, Toronto, Ontario, by one commercial laboratory and the The London Health Sciences Center Laboratory, London, Ontario, by the other. With two exceptions, baseline and follow-up plasma homocysteine levels were done at The Banting Institute.
The study included 29 subjects, 18 males and 11 females, mean age, 54~20 years. Nineteen subjects had multiple medical problems. Twenty-one subjects had generalized atherosclerosis. Thirteen subjects had coronary atherosclerosis, angina pectoris and/or a positive exercise stress test. Four subjects had coronary angioplasty, coronary bypass surgery and/or a positive exercise stress test.
Fourteen subjects had hypertension. Two subjects had had a stroke. Fifteen subjects had hyperlipidemia. Eight subjects had diabetes mellitus. Two subjects had complications of peripheral vascular disease. Two subjects had vitamin B12 deficiency and a past history of cancer.
Many subjects were on multiple drugs. Twenty-four subjects were on one or more of the following medications: Enalapril, Conjugated Estrogens, Progesterone, Enteric-coated Acetylsalicic acid, Lovastatin, Atenolol, Nifedipine XL, Isosorbide, Acetaminophen with Codeine, Ramipril, Perindopril, Diamicron, Lipidil micro, Simvastatin, Diclofenac, Ranitidine, Lorazepam, calcium, Etidronate, Ibuprofen, Pravastatin, Amitriptylene, Transdermal Nitroglycerine, Methocarbamol-Acetaminophen, Ipratropium nasal spray, Vitamin C, Atorvastatin, Metoprolol, Oxycodone, Ferrous gluconate, Propanolol, Lanoxin, Piroxicam, Beta-carotene, Hydrochlorothiazide, L-Thyroxine, Allopurinol, Misoprostol, Venlafaxine, Diazepam, Flurazepam, Nabumetone and Verapamil.
Twelve subjects were on lipid-lowering drugs. With three exceptions, lipid lowering drugs were discontinued two weeks prior to starting Sublimed Sulfur.
Vitamins B1, B6, B12 and folic acid were also discontinued two weeks prior to the first dose of Sublimed Sulfur and were not taken by the subjects during the course of the study. Other medically indicated therapies were continued. New medications were not added during the course of the study.
Results:
The 45 day course of Sublimed Sulfur received by the initial test subject resulted in an 89.4 percent decrease in plasma homocysteine from a baseline of p,mol per litre to 8.2 pmol per litre. Plasma homocysteine measured 25 days after the last dose of Sublimed Sulfur was 11.6 ~,mol per litre. Plasma homocysteine measured 160 days after the last dose of Sublimed Sulfur was 7.8 pmol per litre. 161 days after completion of the first course of Sublimed Sulfur, a second course of Sublimed Sulfur 200 mg pc breakfast daily for 30 days resulted in a further decrease of plasma homocysteine to 3.9 ~mol per litre, representing a 94.9 percent reduction from the initial baseline.
The baseline homocysteine levels in the 29 additional subjects ranged from 2.4 to 22.1 ~mol per litre and averaged 9.6~1.0 ~,mol per litre (mean ~ standard error of the mean). Thirty days later, after treatment with Sublimed Sulfur, the homocysteine levels declined about 45 percent to 6.5~0.5 ~mol per litre (P<0.02, Wilcoxon T
distribution, two-tailed). After a further 30 days with no further treatment, homocysteine levels rose slightly in 23 subjects of the group for whom data are available to a level of 7.8~0.8 pmol per litre (NS). For those 23 subjects, the 60 day homocysteine levels remained significantly lower than the baseline levels (P<0.05, Wilcoxon test).
Overall, there was significant correlation (+0.85, N=29, p<0.01 ) between the baseline level of homocysteine and the amount of the reduction produced by treatment with Sublimed Sulfur.
Six of nine subjects with baseline homocysteine levels of 7.0 p,mol per litre or less showed an actual increase in homocysteine levels after 30 days of treatment. Of subjects whose baseline levels of homocysteine exceeded 7.0 pmol per litre, only 4 showed an increase in homocysteine levels after treatment. This proportion differs significantly (p<0.05) in these two subgroups according to the X2 test. The 20 subjects whose baseline homocysteine level was above 7.0 ~mol per litre averaged 12.0~1.0 15 ~,mol per litre at baseline and 7.1~0.6 ~,mol per litre after 30 days of treatment (p<0.001, Wilcoxon test). The increase in homocysteine level in subjects who had a baseline homocysteine level of less than 7.0 ~,mol per litre was not statistically significant.
The baseline vitamin B12 level, recorded in 27 subjects, was 274.4~26.1 pmol 20 per litre. After 30 days of treatment with Sublimed Sulfur, the level was 267.7~24.7 ~mol per litre (NS). Red blood cell folate levels, recorded in 14 patients, was 728.6~51.3 ~mol per litre at baseline and 796.4~73.2 ~,mol per litre after 30 days of treatment (NS). Comparison of baseline and post treatment values revealed no systematic changes for total serum cholesterol, HDL cholesterol, LDL
cholesterol, serum triglycerides and total cholesterol/HDL ratio.
Overall, there was significant correlation (+0.85, N=29, p<0.01 ) between the baseline level of homocysteine and the amount of the reduction produced by treatment with Sublimed Sulfur.
Six of nine subjects with baseline homocysteine levels of 7.0 p,mol per litre or less showed an actual increase in homocysteine levels after 30 days of treatment. Of subjects whose baseline levels of homocysteine exceeded 7.0 pmol per litre, only 4 showed an increase in homocysteine levels after treatment. This proportion differs significantly (p<0.05) in these two subgroups according to the X2 test. The 20 subjects whose baseline homocysteine level was above 7.0 ~mol per litre averaged 12.0~1.0 15 ~,mol per litre at baseline and 7.1~0.6 ~,mol per litre after 30 days of treatment (p<0.001, Wilcoxon test). The increase in homocysteine level in subjects who had a baseline homocysteine level of less than 7.0 ~,mol per litre was not statistically significant.
The baseline vitamin B12 level, recorded in 27 subjects, was 274.4~26.1 pmol 20 per litre. After 30 days of treatment with Sublimed Sulfur, the level was 267.7~24.7 ~mol per litre (NS). Red blood cell folate levels, recorded in 14 patients, was 728.6~51.3 ~mol per litre at baseline and 796.4~73.2 ~,mol per litre after 30 days of treatment (NS). Comparison of baseline and post treatment values revealed no systematic changes for total serum cholesterol, HDL cholesterol, LDL
cholesterol, serum triglycerides and total cholesterol/HDL ratio.
Conclusions:
A 30 to 45 day course of Sublimed Sulfur effectively normalized plasma homocysteine.
A 30 to 45 day course of Sublimed Sulfur effectively resulted in persistence of normal plasma homocysteine levels 30 days after discontinuation of Sublimed Sulfur.
A second 30 day course of Sublimed Sulfur resulted in further reduction of plasma homocysteine.
The higher the initial plasma homocysteine, the greater the percentage reduction due to Sublimed Sulfur.
Correction of sulfur deficiency resulted in normalization of plasma homocysteine to less than 7.0 ~mol per litre.
In subjects with normal red blood cell folate and vitamin B12, Sublimed Sulfur reduced plasma homocysteine independently without the addition of folic acid, pyridoxine and cyanocobalamin.
There was no significant change in serum levels of folic acid, vitamin B12 and serum lipids due to ingestion of Sublimed Sulfur.
There were no adverse effects on the CBC, urinalysis, serum urate, serum glucose, hepatic function, renal function and electrocardiograms. A single subject reported transient bruising one week after starting the second course of Sublimed Sulfur. There were no other reports of adverse effects.
Other advantages which are inherent to the structure are obvious to one skilled in the art. The embodiments are described herein illustratively and are not meant to limit the scope of the invention as claimed. Variations of the foregoing embodiments will be evident to a person of ordinary skill and are intended by the inventor to be encompassed by the following claims.
A 30 to 45 day course of Sublimed Sulfur effectively normalized plasma homocysteine.
A 30 to 45 day course of Sublimed Sulfur effectively resulted in persistence of normal plasma homocysteine levels 30 days after discontinuation of Sublimed Sulfur.
A second 30 day course of Sublimed Sulfur resulted in further reduction of plasma homocysteine.
The higher the initial plasma homocysteine, the greater the percentage reduction due to Sublimed Sulfur.
Correction of sulfur deficiency resulted in normalization of plasma homocysteine to less than 7.0 ~mol per litre.
In subjects with normal red blood cell folate and vitamin B12, Sublimed Sulfur reduced plasma homocysteine independently without the addition of folic acid, pyridoxine and cyanocobalamin.
There was no significant change in serum levels of folic acid, vitamin B12 and serum lipids due to ingestion of Sublimed Sulfur.
There were no adverse effects on the CBC, urinalysis, serum urate, serum glucose, hepatic function, renal function and electrocardiograms. A single subject reported transient bruising one week after starting the second course of Sublimed Sulfur. There were no other reports of adverse effects.
Other advantages which are inherent to the structure are obvious to one skilled in the art. The embodiments are described herein illustratively and are not meant to limit the scope of the invention as claimed. Variations of the foregoing embodiments will be evident to a person of ordinary skill and are intended by the inventor to be encompassed by the following claims.
Claims (42)
1. Use of elemental sulfur for normalizing abnormal plasma homocysteine concentration in a human subject.
2. Use of elemental sulfur for treating a medical condition associated with abnormal plasma homocysteine concentrations in a human subject.
3. Use of elemental sulfur for manufacturing a medicament for normalizing abnormal plasma homocysteine concentration in a human subject.
4. Use of elemental sulfur for manufacturing a medicament for treating a medical condition associated with abnormal plasma homocysteine concentration in a human subject.
5. Use according to any one of claims 1 to 4, wherein the abnormal plasma homocysteine concentration is hyper-homocysteinemia.
6. Use according to any one of claims 1 to 4, wherein the abnormal plasma homocysteine concentration is associated with accelerated atherosclerosis, generalized atherosclerosis, atherothrombosis, carotid atherosclerosis, atherosclerotic complications of diabetes mellitus, recurrent thromboembolism, deep vein thrombosis and pulmonary embolism, recurrent pulmonary embolism, deep vein thrombosis in cancer, venous thrombosis in cancer, cerebral atherosclerosis, atherosclerotic cerebral degeneration, recurrent cerebral embolisation, transient ischemic attacks, stroke, peripheral atherosclerosis, peripheral ischemia, coronary atherosclerosis, ischemic heart disease, coronary thrombosis, angina pectoris, myocardial infarction, ventricular arrhythmias, atrial arrhythmias, gout, Alzheimer's disease, nephrosclerosis, chronic renal failure, post-menopause, hypothyroidism, pernicious anemia, vitamin B12 deficiency, vitamin B6 deficiency, folic acid deficiency, psoriasis, leukemias, breast cancer, ovarian cancer, pancreatic cancer, methotrexate therapy, nitrogen oxide therapy, isoniazid therapy, phenytoin therapy, theophylline therapy, homocysteinuria syndrome, cystathionine-Beta-synthase deficiency, hypertension, age effects of atherosclerosis, cardiac nerve degeneration and ventricular arrhythmias due to atherosclerosis, cardiac nerve degeneration and atrial arrhythmias due to atherosclerosis, nerve degeneration due to atherosclerosis in diabetic neuropathy, nerve degeneration due to atherosclerosis in peripheral ischemic neuropathy, or osteoporosis due to atherosclerosis.
7. Use according to any one of claims 1 to 4, wherein the abnormal plasma homocysteine concentration is associated with accelerated atherosclerosis, generalized atherosclerosis, carotid atherosclerosis, atherosclerotic complications of diabetes mellitus, cerebral atherosclerosis, atherosclerotic cerebral degeneration, peripheral atherosclerosis, coronary atherosclerosis, age effects of atherosclerosis, cardiac nerve degeneration and ventricular arrhythmias due to atherosclerosis, cardiac nerve degeneration and atrial arrhythmias due to atherosclerosis, nerve degeneration due to atherosclerosis in diabetic neuropathy, nerve degeneration due to atherosclerosis in peripheral ischemic neuropathy, or osteoporosis due to atherosclerosis.
8. Use according to any one of claims 1 to 4, wherein the abnormal plasma homocysteine concentration is associated with atherosclerosis.
9. Use according to any one of claims 1 to 8, wherein the elemental sulfur is 99.5 to 100 percent pure.
10. Use according to any one of claims 1 to 9, wherein the elemental sulfur is sublimed sulfur.
11. Use according to any one of claims 1 to 10, wherein the abnormal plasma homocysteine concentration is outside a range of from 4 to 15 µmol per litre.
12. Use according to any one of claims 1 to 11, wherein the elemental sulfur is used in solid form.
13. Use according to any one of claims 1 to 12, wherein the elemental sulfur is used in capsule form.
14. Use according to any one of claims 1 to 13, wherein the elemental sulfur is used in a first course of from 30 to 45 days.
15. Use according to claim 14, wherein the elemental sulfur is used in a second 30 day course after discontinuance of the first course.
16. Use according to any one of claims 1 to 15, wherein the elemental sulfur is used at a dose of from 200 mg to 300 mg daily.
17. A commercial package comprising elemental sulfur and instructions for its use in normalizing abnormal plasma homocysteine concentration in a human subject.
18. A commercial package comprising elemental sulfur and instructions for its use in treating a medical condition associated with abnormal plasma homocysteine concentration in a human subject.
19. The commercial package according to claim 17 or 18, wherein the abnormal plasma homocysteine concentration is hyper-homocysteinemia.
20. The commercial package according to claim 17 or 18, wherein the abnormal plasma homocysteine concentration is associated with accelerated atherosclerosis, generalized atherosclerosis, atherothrombosis, carotid atherosclerosis, atherosclerotic complications of diabetes mellitus, recurrent thromboembolism, deep vein thrombosis and pulmonary embolism, recurrent pulmonary embolism, deep vein thrombosis in cancer, venous thrombosis in cancer, cerebral atherosclerosis, atherosclerotic cerebral degeneration, recurrent cerebral embolisation, transient ischemic attacks, stroke, peripheral atherosclerosis, peripheral ischemia, coronary atherosclerosis, ischemic heart disease, coronary thrombosis, angina pectoris, myocardial infarction, ventricular arrhythmias, atrial arrhythmias, gout, Alzheimer's disease, nephrosclerosis, chronic renal failure, post-menopause, hypothyroidism, pernicious anemia, vitamin B12 deficiency, vitamin B6 deficiency, folic acid deficiency, psoriasis, leukemias, breast cancer, ovarian cancer, pancreatic cancer, methotrexate therapy, nitrogen oxide therapy, isoniazid therapy, phenytoin therapy, theophylline therapy, homocysteinuria syndrome, cystathionine-Beta-synthase deficiency, hypertension, age effects of atherosclerosis, cardiac nerve degeneration and ventricular arrhythmias due to atherosclerosis, cardiac nerve degeneration and atrial arrhythmias due to atherosclerosis, nerve degeneration due to atherosclerosis in diabetic neuropathy, nerve degeneration due to atherosclerosis in peripheral ischemic neuropathy, or osteoporosis due to atherosclerosis.
21. The commercial package according to claim 17 or 18, wherein the abnormal plasma homocysteine concentration is associated with accelerated atherosclerosis, generalized atherosclerosis, carotid atherosclerosis, atherosclerotic complications of diabetes mellitus, cerebral atherosclerosis, atherosclerotic cerebral degeneration, peripheral atherosclerosis, coronary atherosclerosis, age effects of atherosclerosis, cardiac nerve degeneration and ventricular arrhythmias due to atherosclerosis, cardiac nerve degeneration and atrial arrhythmias due to atherosclerosis, nerve degeneration due to atherosclerosis in diabetic neuropathy, nerve degeneration due to atherosclerosis in peripheral ischemic neuropathy, or osteoporosis due to atherosclerosis.
22. The commercial package according to claim 17 or 18, wherein the abnormal plasma homocysteine concentration is associated with atherosclerosis.
23. The commercial package according to any one of claims 17 to 22, wherein the elemental sulfur is 99.5 to 100 percent pure.
24. The commercial package according to any one of claims 17 to 23, wherein the elemental sulfur is sublimed sulfur.
25. The commercial package according to any one of claims 17 to 24, wherein the abnormal plasma homocysteine concentration is outside a range of from 4 to 15 µmol per litre.
26. The commercial package according to any one of claims 17 to 25, wherein the elemental sulfur is in solid form.
27. The commercial package according to any one of claims 17 to 26, wherein the elemental sulfur is in capsule form.
28. The commercial package according to any one of claims 17 to 27, wherein the instructions indicate that the elemental sulfur is to be used in a first course of from 30 to 45 days.
29. The commercial package according to claim 28, wherein the instructions indicate that the elemental sulfur is to be used in a second 30 day course after discontinuance of the first course.
30. The commercial package according to any one of claims 17 to 29, wherein the instructions indicate that the elemental sulfur is to be used in a dose of from 200 mg to 300 mg daily.
31. A composition comprising elemental sulfur and a pharmaceutically acceptable carrier for use in normalizing abnormal plasma homocysteine concentration in a human subject.
32. A composition comprising elemental sulfur and a pharmaceutically acceptable carrier for use in treating a medical condition associated with abnormal homocysteine concentrations in a human subject.
33. The composition according to claim 31 or 32, wherein the abnormal plasma homocysteine concentration is hyper-homocysteinemia.
34. The composition according to claim 31 or 32, wherein the abnormal plasma homocysteine concentration is associated with accelerated atherosclerosis, generalized atherosclerosis, atherothrombosis, carotid atherosclerosis, atherosclerotic complications of diabetes mellitus, recurrent thromboembolism, deep vein thrombosis and pulmonary embolism, recurrent pulmonary embolism, deep vein thrombosis in cancer, venous thrombosis in cancer, cerebral atherosclerosis, atherosclerotic cerebral degeneration, recurrent cerebral embolisation, transient ischemic attacks, stroke, peripheral atherosclerosis, peripheral ischemia, coronary atherosclerosis, ischemic heart disease, coronary thrombosis, angina pectoris, myocardial infarction, ventricular arrhythmias, atrial arrhythmias, gout, Alzheimer's disease, nephrosclerosis, chronic renal failure, post-menopause, hypothyroidism, pernicious anemia, vitamin B12 deficiency, vitamin B6 deficiency, folic acid deficiency, psoriasis, leukemias, breast cancer, ovarian cancer, pancreatic cancer, methotrexate therapy, nitrogen oxide therapy, isoniazid therapy, phenytoin therapy, theophylline therapy, homocysteinuria syndrome, cystathionine-Beta-synthase deficiency, hypertension, age effects of atherosclerosis, cardiac nerve degeneration and ventricular arrhythmias due to atherosclerosis, cardiac nerve degeneration and atrial arrhythmias due to atherosclerosis, nerve degeneration due to atherosclerosis in diabetic neuropathy, nerve degeneration due to atherosclerosis in peripheral ischemic neuropathy, or osteoporosis due to atherosclerosis.
35. The composition according to claim 31 or 32, wherein the abnormal plasma homocysteine concentration is associated with accelerated atherosclerosis, generalized atherosclerosis, carotid atherosclerosis, atherosclerotic complications of diabetes mellitus, cerebral atherosclerosis, atherosclerotic cerebral degeneration, peripheral atherosclerosis, coronary atherosclerosis, age effects of atherosclerosis, cardiac nerve degeneration and ventricular arrhythmias due to atherosclerosis, cardiac nerve degeneration and atrial arrhythmias due to atherosclerosis, nerve degeneration due to atherosclerosis in diabetic neuropathy, nerve degeneration due to atherosclerosis in peripheral ischemic neuropathy, or osteoporosis due to atherosclerosis.
36. The composition according to claim 31 or 32, wherein the abnormal plasma homocysteine concentration is associated with atherosclerosis.
37. The composition according to any one of claims 31 to 36, wherein the elemental sulfur is 99.5 to 100 percent pure.
38. The composition according to any one of claims 31 to 37, wherein the elemental sulfur is sublimed sulfur.
39. The composition according to any one of claims 31 to 38, wherein the abnormal plasma homocysteine concentration is outside a range of from 4 to 15 µmol per litre.
40. The composition according to any one of claims 31 to 39, wherein the elemental sulfur is in solid form.
41. The composition according to any one of claims 31 to 40, wherein the pharmaceutically acceptable carrier is a capsule.
42. The composition according to any one of claims 31 to 41, wherein the elemental sulfur is present in the composition in an amount of from 200 mg to 300 mg daily.
Priority Applications (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA 2265926 CA2265926C (en) | 1999-04-08 | 1999-04-08 | Method of altering plasma homocysteine levels in humans |
| AU58447/99A AU5844799A (en) | 1999-04-08 | 1999-09-27 | Composition, containing sublimed sulphur, for altering plasma homodyst(e) levelsin humans |
| PCT/CA1999/000892 WO2000061154A1 (en) | 1999-04-08 | 1999-09-27 | Composition, containing sublimed sulphur, for altering plasma homodyst(e) levels in humans |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA 2265926 CA2265926C (en) | 1999-04-08 | 1999-04-08 | Method of altering plasma homocysteine levels in humans |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2265926A1 CA2265926A1 (en) | 2000-10-08 |
| CA2265926C true CA2265926C (en) | 2007-01-02 |
Family
ID=29588566
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA 2265926 Expired - Lifetime CA2265926C (en) | 1999-04-08 | 1999-04-08 | Method of altering plasma homocysteine levels in humans |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA2265926C (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1701717A1 (en) * | 2003-12-18 | 2006-09-20 | London Health Sciences Research Centre Inc. | Method of treating elevated plasma homocysteine levels in esrd patients |
| JP2009538837A (en) * | 2006-06-02 | 2009-11-12 | ナチュラル エムエー インコーポレイテッド | Use of micron-sized sulfur for the prevention and treatment of pathogenic disorders in humans and animals |
-
1999
- 1999-04-08 CA CA 2265926 patent/CA2265926C/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| CA2265926A1 (en) | 2000-10-08 |
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