U.S. patent application number 10/750545 was filed with the patent office on 2005-06-30 for nutrient compositions and methods for enhanced effectiveness of the immune system.
Invention is credited to Kaiser, Jon D..
Application Number | 20050142124 10/750545 |
Document ID | / |
Family ID | 39733228 |
Filed Date | 2005-06-30 |
United States Patent
Application |
20050142124 |
Kind Code |
A1 |
Kaiser, Jon D. |
June 30, 2005 |
Nutrient compositions and methods for enhanced effectiveness of the
immune system
Abstract
The invention provides a nutrient composition for augmenting
immune strength or physiological detoxification. The nutrient
composition consists of an optimal combination of an effective
amount of at least one vitamin antioxidant, at least one mineral
antioxidant and a highly saturable amount of at least three high
potency antioxidants. The at least one vitamin antioxidant can be
vitamin C, bioflavonoid complex, vitamin E, vitamin B6 or
beta-carotene and the at least one mineral antioxidant can be zinc
or selenium. The at least three high potency antioxidants can be
alpha lipoic acid, acetyl L-carnitine, N-acetyl-cysteine, co-enzyme
Q10 or glutathione. Also provided is a nutrient composition for
augmenting immune strength or physiological detoxification that
consists of an optimal combination of an effective amount of at
least three vitamin antioxidants, at least two mineral antioxidants
and a highly saturable amount of at least three high potency
antioxidants. Further provided is a method of stimulating immune
system function or a method of augmenting a therapeutic treatment
of a disease. The method consists of administering to an individual
a nutrient composition of the invention one or more times a day
over a period of about 5-7 weeks, the immune system function being
stimulated to result in an increase of CD4+ cells of at least about
15% compared to pre-administration levels. A method of stimulating
a physiological detoxification function of an individual or a
method of augmenting a therapeutic treatment of a disease is also
provided. The method consists of administering to an individual a
nutrient composition of the invention one or more times a day over
a period of about 5-7 weeks, the physiological detoxification
function being stimulated to result in a decrease of one or more
free radical markers by about 20% compared to pre-administration
levels.
Inventors: |
Kaiser, Jon D.; (Mill
Valley, CA) |
Correspondence
Address: |
MCDERMOTT, WILL & EMERY
4370 LA JOLLA VILLAGE DRIVE, SUITE 700
SAN DIEGO
CA
92122
US
|
Family ID: |
39733228 |
Appl. No.: |
10/750545 |
Filed: |
December 31, 2003 |
Current U.S.
Class: |
424/94.1 ;
424/641; 424/702; 514/1.9; 514/15.1; 514/16.4; 514/16.6; 514/17.8;
514/17.9; 514/18.2; 514/19.3; 514/20.1; 514/21.9; 514/3.8; 514/3.9;
514/4.2; 514/440; 514/456; 514/458; 514/474; 514/5.5; 514/546;
514/562 |
Current CPC
Class: |
A61K 31/198 20130101;
A61P 37/04 20180101; A61K 33/30 20130101; A61K 31/385 20130101;
A61K 33/26 20130101; A61K 31/205 20130101; A23L 33/16 20160801;
A61K 33/24 20130101; A61K 45/06 20130101; A61K 33/34 20130101; A61K
31/525 20130101; A23L 33/175 20160801; A61K 33/18 20130101; A61K
31/519 20130101; A61P 39/06 20180101; A61K 33/04 20130101; A61K
31/381 20130101; A61K 31/455 20130101; A61P 3/02 20180101; A61K
31/7056 20130101; A61K 31/714 20130101; A61K 31/593 20130101; A61K
31/195 20130101; A61K 31/375 20130101; A61K 31/7076 20130101; A61K
31/352 20130101; A23L 33/11 20160801; A61K 33/06 20130101; A61K
33/00 20130101; A61K 31/4188 20130101; A61K 33/22 20130101; A61K
31/51 20130101; A61K 31/122 20130101; A61K 33/32 20130101; A23L
33/15 20160801; A61K 31/198 20130101; A61K 2300/00 20130101; A61K
31/205 20130101; A61K 2300/00 20130101; A61K 31/352 20130101; A61K
2300/00 20130101; A61K 31/375 20130101; A61K 2300/00 20130101; A61K
31/385 20130101; A61K 2300/00 20130101; A61K 33/04 20130101; A61K
2300/00 20130101; A61K 33/30 20130101; A61K 2300/00 20130101 |
Class at
Publication: |
424/094.1 ;
514/018; 514/440; 514/546; 514/562; 424/641; 424/702; 514/456;
514/458; 514/474 |
International
Class: |
A61K 038/43; A61K
038/05; A61K 031/198; A61K 031/353; A61K 031/375 |
Claims
1. A nutrient composition for augmenting immune strength or
physiological detoxification comprising an optimal combination of a
substantially pure and an effective amount of at least one vitamin
antioxidant, at least one mineral antioxidant and a highly
saturable amount of at least three high potency antioxidants.
2. The nutrient composition of claim 1, wherein said at least three
high potency antioxidants are selected from alpha lipoic acid,
acetyl L-carnitine, N-acetyl-cysteine, co-enzyme Q10 and
glutathione.
3. The nutrient composition of claim 1, wherein said at least three
high potency antioxidants comprise alpha lipoic acid, acetyl
L-carnitine and N-acetyl-cysteine.
4. The nutrient composition of claim 1, wherein said at least one
vitamin antioxidant is selected from vitamin C, bioflavonoid
complex, vitamin E, vitamin B6 and beta-carotene.
5. The nutrient composition of claim 1, wherein said at least one
vitamin antioxidant comprises vitamin C, bioflavonoid complex and
vitamin E.
6. The nutrient composition of claim 1, wherein said at least one
mineral antioxidant is selected from zinc and selenium.
7. The nutrient composition of claim 1, wherein said at least one
mineral antioxidant comprises zinc and selenium.
8. The nutrient composition of claim 1, wherein said vitamin
antioxidant, said mineral antioxidant or said high potency
antioxidant comprises a purity level of about 99% by total
weight.
9. The nutrient composition of claim 1, further comprising an
effective amount of one or more vitamins or minerals.
10. The nutrient composition of claim 8, wherein said one or more
vitamins or minerals are selected from the group consisting of
beta-carotene, vitamin A, vitamin B1, vitamin B2, niacinamide,
calcium panthothenate, choline, inositol, folic acid, biotin,
vitamin D3, vitamin B12, calcium, magnesium, iron, iodine, copper,
manganese, potassium, chromium, molybdenum, boron, betaine,
glutamic acid.
11. The nutrient composition of claim 10, wherein said one or more
vitamins or minerals comprise a purity level of about 99% by total
weight.
12. A nutrient composition for augmenting immune strength or
physiological detoxification comprising an optimal combination of a
substantially pure and an effective amount of at least three
vitamin antioxidants, at least two mineral antioxidants and a
highly saturable amount of at least three high potency
antioxidants.
13. The nutrient composition of claim 12, wherein said at least
three high potency antioxidants are selected from alpha lipoic
acid, acetyl L-carnitine, N-acetyl-cysteine, co-enzyme Q10 and
glutathione.
14. The nutrient composition of claim 12, wherein said at least
three high potency antioxidants comprise alpha lipoic acid, acetyl
L-carnitine and N-acetyl-cysteine.
15. The nutrient composition of claim 12, wherein said at least
three vitamin antioxidants are selected from vitamin C,
bioflavonoid complex, vitamin E, vitamin B6 and beta-carotene.
16. The nutrient composition of claim 12, wherein said at least
three vitamin antioxidants comprise vitamin C, bioflavonoid complex
and vitamin E.
17. The nutrient composition of claim 12, wherein said at least two
mineral antioxidants comprise zinc and selenium.
18. The nutrient composition of claim 12, wherein said vitamin
antioxidant, said mineral antioxidant or said high potency
antioxidant comprises a purity level of about 99% by total
weight.
19. The nutrient composition of claim 12, further comprising an
effective amount of one or more vitamins or minerals.
20. The nutrient composition of claim 18, wherein said one or more
vitamins or minerals are selected from the group consisting of
beta-carotene, vitamin A, vitamin B1, vitamin B2, niacinamide,
calcium panthothenate, choline inositol, folic acid, biotin,
vitamin D3, vitamin B12, calcium, magnesium, iron, iodine, copper,
manganese, potassium, chromium, molybdenum, boron, betaine,
glutamic acid.
21. The nutrient composition of claim 20, wherein said one or more
vitamins or minerals comprise a purity level of about 99% by total
weight.
22. A nutrient composition for augmenting immune strength or
physiological detoxification comprising an optimal combination of a
substantially pure and an effective amount of vitamin C,
bioflavonoid complex, vitamin E, zinc, selenium, alpha lipoic acid,
acetyl L-carnitine and N-acetyl-cysteine.
23. The nutrient composition of claim 22, further comprising an
effective amount of vitamin B6.
24. The nutrient composition of claim 22, wherein said vitamin C,
bioflavonoid complex, vitamin E, zinc, selenium, alpha lipoic acid,
acetyl L-carnitine and N-acetyl-cysteine comprise a purity level of
about 99% by total weight.
25. The nutrient composition of claim 22, further comprising an
effective amount of one or more vitamins or minerals.
26. The nutrient composition of claim 24, wherein said one or more
vitamins or minerals are selected from the group consisting of
beta-carotene, vitamin A, vitamin B1, vitamin B2, niacinamide,
calcium panthothenate, choline inositol, folic acid, biotin,
vitamin D3, vitamin B12, calcium, magnesium, iron, iodine, copper,
manganese, potassium, chromium, molybdenum, boron, betaine,
glutamic acid.
27. The nutrient composition of claim 26, wherein said one or more
vitamins or minerals comprise a purity level of about 99% by total
weight.
28. A method of stimulating immune system function comprising
administering to an individual the composition of claims 1, 12 or
22 one or more times a day over a period of about 5-7 weeks, said
immune system function being stimulated to result in an increase of
CD4.sup.+ cells of at least about 15% compared to
pre-administration levels.
29. The method of claim 28, wherein said increase of CD4.sup.+
cells further comprises an increase of greater than about 25%
compared to pre-administration levels.
30. The method of claim 28, wherein said increase of CD4.sup.+
cells further comprises an increase of about 40% compared to
pre-administration levels.
31. The method of claim 28, wherein said stimulation of said immune
system function promotes longevity and physiological healing.
32. A method of stimulating a physiological detoxification function
of an individual comprising administering to an individual the
composition of claims 1, 12 or 22 one or more times a day over a
period of about 5-7 weeks, said physiological detoxification
function being stimulated to result in a decrease of one or more
free radical markers by about 20% compared to pre-administration
levels.
33. The method of claim 32, wherein said decrease of free radical
markers comprises a decrease of greater than about 30% compared to
pre-administration levels.
34. The method of claim 32, wherein said decrease of free radical
markers comprises a decrease of greater than about 40% compared to
pre-administration levels.
35. The method of claim 32, wherein said decrease of free radical
markers comprises a decrease of about 50% compared to
pre-administration levels.
36. The method of claim 32, wherein said stimulation of a
physiological detoxification function comprises inhibition of
mitochondrial DNA polymerase gamma.
37. The method of claim 32, wherein said stimulation of a
physiological detoxification function comprises increasing a liver
detoxification function.
38. The method of claim 37, wherein said liver detoxification
function comprises an increase in energy production, an increased
ability to process toxins or a decrease in free radical
buildup.
39. A method of augmenting a therapeutic treatment of a disease
comprising administering to an individual the composition of claims
1, 12 or 22 one or more times a day over a period of about 5-7
weeks, wherein immune system function is stimulated to result in an
increase of CD4.sup.+ cells of at least about 15% compared to
pre-administration levels.
40. The method of claim 39, wherein said increase of CD4.sup.+
cells further comprises an increase of greater than about 25%
compared to pre-administration levels.
41. The method of claim 39, wherein said increase of CD4.sup.+
cells further comprises an increase of about 40% compared to
pre-administration levels.
42. The method of claim 39, wherein said disease comprises an
immune-mediated diseases, cancer, heart disease, chronic fatigue
syndrome, neurodegenerative diseases, radiation poisoning, ischemic
events or an infectious disease.
43. The method of claim 42, wherein said disease is selected from
acquired immunodeficiency syndrome (AIDS), multiple sclerosis,
lupus, rheumatoid arthritis, scleroderma, coronary artery disease,
atherosclerotic vessel disease, Madalung's disease, neoplastic
conditions, solid tumor malignancies, non-solid malignancies,
Alzheimer's disease, Parkinson's disease, neurodegenerative forms
of dementia, infectious hepatitis, toxic hepatitis, drug-induced
hepatitis, herpes and human immunodeficiency virus (HIV).
44. The method of claim 39, wherein said augmenting of said
therapeutic treatment comprises stimulation of immune system
function.
45. The method of claim 39, wherein said augmenting of said
therapeutic treatment comprises reduction in cellular toxicity
resulting from said therapeutic treatment.
46. The method of claim 45, wherein said therapeutic treatment
comprises HIV medications.
47. The method of claim 46, wherein said HIV medications comprise
reverse transcriptase inhibitors.
48. The method of claim 47, wherein said reverse transcriptase
inhibitors comprise a nucleoside inhibitor, a nucleotide inhibitor
or a non-nucleoside inhibitor.
49. The method of claim 46, wherein said HIV medications comprise
an HIV protease inhibitor.
50. The method of claim 46, wherein said therapeutic treatment
comprises administration of stavudine or didanosine.
51. A method of augmenting a therapeutic treatment of a disease
comprising administering to an individual the composition of claims
1, 12 or 22 one or more times a day over a period of about 5-7
weeks, wherein a physiological detoxification function is
stimulated to result in a decrease of one or more free radical
markers by about 20% compared to pre-administration levels.
52. The method of claim 51, wherein said decrease of free radical
markers comprises a decrease of greater than about 30% compared to
pre-administration levels.
53. The method of claim 51, wherein said decrease of free radical
markers comprises a decrease of greater than about 40% compared to
pre-administration levels.
54. The method of claim 51, wherein said decrease of free radical
markers comprises a decrease of about 50% compared to
pre-administration levels.
55. The method of claim 51, wherein said stimulation of a
physiological detoxification function comprises inhibition of
mitochondrial DNA polymerase gamma.
56. The method of claim 51, wherein said stimulation of a
physiological detoxification function comprises increasing a liver
detoxification function.
57. The method of claim 56, wherein said liver detoxification
function comprises an increase in energy production, an increased
ability to process toxins or a decrease in free radical
markers.
58. The method of claim 51, wherein said disease comprises an
immune-mediated diseases, cancer, heart disease, chronic fatigue
syndrome, neurodegenerative diseases, radiation poisoning, ischemic
events or an infectious disease.
59. The method of claim 58, wherein said disease is selected from
acquired immunodeficiency syndrome (AIDS), multiple sclerosis,
lupus, rheumatoid arthritis, scleroderma, coronary artery disease,
atherosclerotic vessel disease, Madalung's disease, neoplastic
conditions, solid tumor malignancies, non-solid malignancies,
Alzheimer's disease, Parkinson's disease, neurodegenerative forms
of dementia, infectious hepatitis, toxic hepatitis, drug-induced
hepatitis, herpes and human immunodeficiency virus (HIV).
60. The method of claim 51, wherein said augmenting of said
therapeutic treatment comprises stimulation of immune system
function.
61. The method of claim 51, wherein said augmenting of said
therapeutic treatment comprises a reduction in cellular toxicity
resulting from said therapeutic treatment.
62. The method of claim 61, wherein said therapeutic treatment
comprises HIV medications.
63. The method of claim 62, wherein said HIV medications comprise
reverse transcriptase inhibitors.
64. The method of claim 63, wherein said reverse transcriptase
inhibitors comprise a nucleoside inhibitor, a nucleotide inhibitor
or a non-nucleoside inhibitor.
65. The method of claim 62, wherein said HIV medications comprise
an HIV protease inhibitor.
66. The method of claim 62, wherein said therapeutic treatment
comprises administration of stavudine or didanosine.
Description
[0001] This invention relates generally to promoting the healing
process of physiological disorders or diseases and, more
specifically to nutrient compositions that promote the
effectiveness or efficiency of the immune system.
[0002] Physiological disorders and diseases affect millions of
individuals each year. Severity of such pathological conditions can
range from mild discomfort, to severe and permanent debilitating
state, to a life-ending terminal disease. Treatments have
continually strived to achieve cures that will restore an affected
individual to a normal physiological state. For many disorders or
diseases, medical treatments are limited to reduction in severity
of symptoms or improvement in one's quality of living. Therefore,
improvement in the efficacy of an available treatment continues to
be a area of medical concern.
[0003] The diagnosis and treatment of human diseases similarly
continues to be a major area of social concern. As long as there
continues to be diseases that affect individuals there will be an
effort to understand the cause of such diseases as well as efforts
to diagnose and treat such diseases. Preservation of life and
reducing the burden on society are two motivating factors that
encourage the time and expenditure invested into scientific
discovery and development processes. Applying the results of these
scientific process to the medical field has led to surprising
advancements in medicine which have improved both the quality of
life and the life-span of affected individuals.
[0004] However significant in both scientific and medical
contribution to their respective fields, the progression of
advancements has been slow and painstaking, generally resulting
from step-wise trial and error hypothesis-driven research.
Moreover, with each advancement there can be cumulative progression
in the overall scientific understanding of a problem but there is
no guarantee that the threshold needed to translate a discovery
into a practical medical application has been achieved.
Additionally, with the achievement of all too many advancements
comes the realization that the perceived final answer for a
complete understanding of a particular physiological or biochemical
process is, instead, just a beginning to a more complex process,
which requires further dissection and understanding. Further
complicating the progression of scientific advancements and their
practical application can result from technical limitations in the
available methodology.
[0005] In addition, even the most beneficial therapeutics available
for a particular disorder or disease can result in undesirable side
effects. For example, cancer chemotherapies and acquired immune
deficiency syndrome (AIDS) treatments cause severe toxic effects
due to their lack of specificity or to the occurrence of toxic
by-product reactions. Additionally, many times an individual will
become resistant to therapeutics during a treatment regime.
Numerous other examples of undesirable side effects resulting from
therapeutic treatment of, for example, immune-mediated diseases,
heart disease, chronic fatigue syndrome, neurodegenerative diseases
or an infectious disease also are prevalent and well known
occurrences within the medical field.
[0006] The ability to reduce undesirable side effects while
maintaining efficacy of a treatment remains an intense area of
investigation. Predictability has been hampered in part because of
the complexity of the human physiological system and the lack of a
complete understanding of physiological mechanisms. For example,
the advent of monoclonal antibodies and recombinant DNA technology,
each having been hailed as technology that would revolutionize
medicine and provide the ability to design highly specific
therapeutics for diseases, has yielded less than promising results.
Only some 30 years after the discovery of monoclonal antibodies are
antibody therapeutics becoming available for therapeutic use. This
long delay has resulted from the development of complementary
technology that renders the antibodies less toxic to the recipient.
Therefore, while beneficial in treating and controlling the impact
of physiological disorders and diseases, advances in therapeutic
medicines still fall short of providing the sought after cure or
the ability to deliver a desired treatment regime to maintain a
consistent improvement in quality of living.
[0007] Thus, there exists a need for compositions and methods that
enhance efficacy of therapeutic treatments or provide desirable
health benefits. The present invention satisfies this need and
provides related advantages as well.
SUMMARY OF THE INVENTION
[0008] The invention provides a nutrient composition for augmenting
immune strength or physiological detoxification. The nutrient
composition consists of an optimal combination of an effective
amount of at least one vitamin antioxidant, at least one mineral
antioxidant and a highly saturable amount of at least three high
potency antioxidants. The at least one vitamin antioxidant can be
vitamin C, bioflavonoid complex, vitamin E, vitamin B6 or
beta-carotene and the at least one mineral antioxidant can be zinc
or selenium. The at least three high potency antioxidants can be
alpha lipoic acid, acetyl L-carnitine, N-acetyl-cysteine, co-enzyme
Q10 or glutathione. Also provided is a nutrient composition for
augmenting immune strength or physiological detoxification that
consists of an optimal combination of an effective amount of at
least three vitamin antioxidants, at least two mineral antioxidants
and a highly saturable amount of at least three high potency
antioxidants. Further provided is a method of stimulating immune
system function or a method of augmenting a therapeutic treatment
of a disease. The method consists of administering to an individual
a nutrient composition of the invention one or more times a day
over a period of about 5-7 weeks, the immune system function being
stimulated to result in an increase of CD4+ cells of at least about
15% compared to pre-administration levels. A method of stimulating
a physiological detoxification function of an individual or a
method of augmenting a therapeutic treatment of a disease is also
provided. The method consists of administering to an individual a
nutrient composition of the invention one or more times a day over
a period of about 5-7 weeks, the physiological detoxification
function being stimulated to result in a decrease of one or more
free radical markers by about 20% compared to pre-administration
levels.
BRIEF DESCRIPTION OF THE DRAWINGS
[0009] FIG. 1 shows an exemplary optimal combination of a nutrient
composition and daily dosage for an individual weighing less than
about 60 kg.
[0010] FIG. 2 shows an exemplary optimal combination of a nutrient
composition and daily dosage for an individual weighing about 60 kg
or more.
[0011] FIG. 3 shows the nutrient composition shown in FIG. 2 and
daily dosages represented as the nutrient amount per kilogram of
body weight for an individual weighing about 70 kg.
DETAILED DESCRIPTION OF THE INVENTION
[0012] This invention is directed to nutrient formulations that
promote the effectiveness or efficiency of an immune system. The
nutrient formulations also promote the effectiveness or efficiency
of mitochondrial functions leading to enhanced energy production,
detoxification functions of detoxifying organs and decreasing free
radical generation or other oxidative processes. The nutrient
formulations have the advantage in that they can be used in
combination with other therapies to augment concurrent treatment or
they can be used alone on healthy or diseased individuals to
promote the health state or delay onset or severity of a
disease.
[0013] In one embodiment, the invention is directed to nutrient
formulations consisting of an optimal combination of about five
antioxidants obtained from about three different categories of
antioxidants. In a specific embodiment, the optimal combinations
are formulated with a total of about 33 nutrients where there are
16 vitamin nutrients, 14 mineral nutrients and three high potency
antioxidants. The nutrient formulation can be administered once or
twice a day over a twelve week treatment in doses such as those
shown in FIG. 3 to reduce the toxic effects of human
immunodeficiency virus (HIV) therapeutics. This treatment can
result in improvement of energy levels and pain scores as well as
an increase of about 15% or greater in CD4.sup.+ cell count
compared to pretreatment levels.
[0014] In another embodiment, the optimal combinations of nutrients
in the formulations of the invention can be used as an antidote to
neutralize toxic effects resulting from HIV therapeutics. Several
HIV therapeutics exhibit the adverse effect of inhibiting
mitochondrial DNA polymerase gamma, which decreases mitochondrial
function and increases oxidative stress. The optimal combinations
prevent or reverse this inhibitory effect resulting in greater
efficacy for the HIV therapeutics with less undesirable toxic side
effects.
[0015] As used herein, the term "immune strength" is intended to
mean an increase in the activity of an immune system function or an
increase in the amount of a component of the immune system. Immune
strength can include an increase in one, many or all functions of
an immune system as well as an increase in the amount of one, many
or all components of an immune system. Stimulation can occur, for
example, through enhancement of an activity such as by the
activation of a positive regulator or the repression of a negative
regulator. Alternatively, stimulation can occur, for example,
through suppression of an activity such as by the repression of a
positive regulator or the activation of a negative repressor. These
means of modulating immune system function as well as other means
well known in the art are included within the meaning of the term
as it is used herein. Activities or components of the immune system
include those within any or all of the cellular, humoral or innate
immune systems of an organism. An activity of an immune system
includes those activities exhibited or mediated by cells or
molecular components of these immune systems of an organism's
immune system. The term "stimulating immune system function" as it
is used herein is intended to be synonymous with the meaning of the
term "immune strength."
[0016] As used herein, the term "physiological detoxification" is
intended to mean a reduction of toxicity within a physiological
environment. A physiological environment includes, for example, an
organism, an organ, tissue, cell or cellular compartment.
Physiological detoxification can occur, for example, directly or
indirectly. A specific example of direct detoxification includes
the inhibition of a poisonous substance or activity. Such poisonous
substances can include, for example, reactants, products or
by-products of biochemical or enzymatic reactions. Specific
examples of indirect detoxification include causing an increase of
physiological detoxification functions such as those that occur in
the liver, boosting resistance to free radicals and other
undesirable oxidative conditions.
[0017] As used herein, the term "optimal combination" when used in
reference to immune strength is intended to mean a formulation of
two or more nutrients each in an effective amount that together
favorably stimulate immune system function. An optimal combination
includes combinations of nutrients that together yield preferable
immune stimulation results as well as combinations that produce
more favorable immune strength results compared to other
stimulatory formulations. An example of the former optimal
combination includes a beneficial stimulation of immune system
function compared to that which can be achieved with individual or
combinations of nutrients. An example of the latter optimal
combination includes stimulation of immune system function over
that which can be obtained with individual or combinations of
nutrients. The amount or degree of immune strength can be more
favorable or the most favorable compared to a reference end point.
Therefore, an optimal combination of nutrients includes a
formulation of nutrients that either beneficially stimulates immune
functions or enhances immune strength, or both, compared to results
achievable with other nutrients or combinations of nutrients.
[0018] Cellular immunity activities include, for example, T cell
functions such as effector and regulatory cell functions and can
include enhancing or modulating the inflammatory response or
augmenting the production of antibodies from B cells. Helper T
cells prepare, for example, both antibody-mediated and
cell-mediated effector cells for immune recognition and removal
while suppressor T cell down regulate these responses. CD4.sup.+
cells are a specific example of helper T cells that regulate both
cellular and humoral effector cells through recognition of antigen
in association with MHC Class II. Other activities of cellular
immunity include the functions associated with, for example,
natural killer cells, which recognize and destroy foreign cells on
contact and cytotoxic T cells, or CD8.sup.+ cells, which recognize
and destroy pathogen infected host cells.
[0019] An activity of the humoral immune system includes, for
example, those functions associated with B cells such as the
production of antibodies while an activity of the innate immune
system includes, for example, those functions associated with
macrophages, neutrophils and eosinophils and other
antibody-dependent cell cytotoxicity mediated events. Molecular
components of the immune system that can be increased include, for
example, cell signaling and complement mediated events. These
activities as well as others are well known to those skilled in the
art and can be found described in, for example, Kuby, Immunology,
3rd Edition, W.H. Freeman & Co., New York (1997) and in Paul,
W. E., Fundamental Immunology, 3.sup.rd Edition, Raven Press, New
York (1989).
[0020] As used herein, the term "nutrient" is intended to mean both
micronutrients and macronutrients that are required for biochemical
and physiological processes of an animal. Micronutrients include
organic compounds or chemical elements required in small amounts
for biochemical and physiological processes. Such organic compounds
and chemical elements include, for example, vitamins, minerals,
antioxidants, cofactors, free radical scavengers or other
biochemical compounds that are utilized in small amounts for the
maintenance, regulation or function of biochemical and
physiological processes.
[0021] The term "vitamin" as it is used herein, is intended to mean
a micronutrient that acts generally in small amounts in the
regulation of various metabolic processes but generally do not
serve as an energy source or as a building unit. Vitamins are
ordinarily ingested on a regular basis or stored in quantity in
humans due to deficiencies in biosynthetic capacity. Specific
examples of vitamin micronutrients include vitamins A, B, C, D and
E.
[0022] The term "mineral" as it is used herein, is intended to mean
a naturally occurring homogeneous or apparently homogeneous and
generally solid crystalline chemical element or compound that
results from inorganic processes of nature having a characteristic
crystal structure and chemical composition. Specific examples of
mineral and chemical element micronutrients include zinc, iron,
iodine and boron.
[0023] The term "antioxidant" as it is used herein, is intended to
mean a substance that opposes oxidation or inhibits reactions
promoted by, for example, oxygen, peroxides or free radicals.
Specific examples of antioxidant micronutrients include vitamin C,
bioflavinoid complex, vitamin E, vitamin B6 and beta-carotene.
Specific examples of cofactor micronutrients include vitamin B1,
vitamin B2 and vitamin B6.
[0024] Macronutrients include organic compounds and chemical
elements which are required in relatively large amounts for
biochemical and physiological processes of an animal. Specific
examples of macronutrients include, potassium, calcium and
magnesium. Therefore, the term "nutrient" as it is used herein is
intended to include vitamins, minerals, antioxidants, cofactors,
free radical scavengers, elements or other biochemical compounds
that are either or both micronutrient or macronutrient organic
compounds and chemical elements as they are well known in the art.
Specific examples of nutrients that are included in the optimal
combinations of the invention are shown in FIGS. 1 and 2.
[0025] As used herein, the term "high potency" when used in
reference to an antioxidant is intended to mean a non-vitamin or
non-mineral antioxidant. The chemical or medicinal strength or the
efficacy of such high potency antioxidants as they are found in the
formulations of the invention can be, for example, greater in
reducing oxidation, free radical destruction or chemical reactions
induced by these chemical species compared to other antioxidants or
compared to an amount of these same antioxidants as they are
normally found in food. The chemical efficacy of the high potency
antioxidants as they are used in the nutrient compositions of the
invention can be due to, for example, greater molar amounts of
antioxidants, enhanced antioxidant effectiveness resulting from
cooperative combinations with other antioxidants or nutrients in
the formulations of the invention. Therefore, high potency
antioxidants as they are found in the nutrient compositions of the
invention exhibit the ability or capacity to achieve more
efficacious results. Specific examples of high potency antioxidants
include alpha lipoic acid, acetyl L-carnitine, N-acetyl cysteine,
coenzyme Q10 and glutathione.
[0026] As used herein, the term "effective amount" is intended to
mean an amount of a nutrient that achieves stimulation of immune
strength. When used in reference to immune strength of a nutrient
contained within a formulation or combination of nutrients, the
term is intended to refer to an amount that achieves immune
strength of at least about a 15% increase in CD4.sup.+ cells over
an about 5-7 week course of administration. When used in reference
to detoxification functions, the term is intended to refer to an
amount that achieves a decrease in a free radical marker by at
least about 20% over an about 5-7 week course of administration.
Effective amounts of nutrients contained within the optimal
combinations of the invention can be in excess of the recommended
daily allowance (RDA), preferably in about 10-fold excess of the
RDA and more preferably in about 20-fold excess of the RDA.
Specific examples of effective amounts when used in the optimal
combinations of the invention are show in FIGS. 1 and 2. FIG. 3
shows these exemplary effective amounts in the form of dosages per
weight. Effective amounts can vary in range from these exemplary
dosages by about 25% of the shown kilogram dosages up to and
greater than about 200% of the shown kilogram dosages. Therefore,
effective amounts for dosages of one or more of the nutrients shown
in FIG. 3 can be, for example, 30, 40, 50, 60, 70, 80, 90, 110,
120, 130, 140, 150, 160, 170, 180, 190 or greater than 200% of the
amounts per kilogram of body weight shown in FIG. 3. All
percentages in between these values also are included within an
effective amount of a nutrient of the invention. Other effective
amounts can include, for example, amounts in excess of the RDA of
about 11-, 12-, 13-, 14-, 15-, 16-, 17-, 18- or 19-fold as well as
in excess of about 21-, 22-, 23-, 24-, 25- or 30-fold or more.
Similarly, all values in between these exemplary fold-excess also
are included within an effective amount of a nutrient of the
invention. Effective amounts of high potency antioxidants also
include, for example, ratios ranging from 1:1:1 to 1:4:6 in mg
amounts of, for example, alpha-lipoic acid, acetyl L-carnitine and
N-acetyl cysteine, respectively. Effective amounts other than those
exemplified above also can be used in the nutrient formulations of
the invention and will be known by those skilled in the art given
the teachings and guidance provided herein.
[0027] As used herein, the term "highly saturable amount" when used
in reference to a high potency antioxidant is intended to mean an
amount of high potency antioxidant that maintains an excess of
reduction potential during the course of treatment. Highly
saturable amounts are in excess of the RDA, preferably in about
10-fold excess of the RDA and more preferably in about 20-fold
excess of the RDA. Specific examples of highly saturable amounts
for the high potency antioxidants are shown in FIGS. 1 and 2. FIG.
3 shows these exemplary effective amounts in the form of dosages
per weight. Other effective amounts can include, for example,
amounts in excess of the RDA of about 11-, 12-, 13-, 14-, 15-, 16-,
17-, 18- or 19-fold as well as in excess of about 21-, 22-, 23-,
24-, 25- or 30-fold or more. Effective amounts other than those
exemplified above also can be used in the nutrient formulations of
the invention and will be known by those skilled in the art given
the teachings and guidance provided herein.
[0028] As used herein, the term "augmenting" is intended to mean
facilitate or enhance a referenced activity, state or treatment.
Facilitation or enhancement can occur, for example, by direct or
indirect action of a nutrient formulation of the invention. When
used in reference to immune strength or physiological
detoxification, the term is intended to refer to improving the
activity, performance or efficiency of an immune system or
physiological detoxification functions of an organism. When used in
reference to a therapeutic treatment, the term is intended to mean
an enhancement of the beneficial effect of the treatment.
Enhancement can occur by, for example, decreasing the oxidative
state or improving the oxidative health of targeted or non-targeted
cells. Enhancement also can occur by, for example, reducing the
toxicity of the therapeutic treatment. These and other means of
enhancing the therapeutic or beneficial effect of a treatment are
included within the meaning of the term.
[0029] The invention provides a nutrient composition for augmenting
immune strength or physiological detoxification. The nutrient
composition consists of an optimal combination of an effective
amount of at least one vitamin antioxidant, at least one mineral
antioxidant and a highly saturable amount of at least three high
potency antioxidants. The at least one vitamin antioxidant can be
vitamin C, bioflavonoid complex, vitamin E, vitamin B6 or
beta-carotene and the at least one mineral antioxidant can be zinc
or selenium. The at least three high potency antioxidants can be
alpha lipoic acid, acetyl L-carnitine, N-acetyl-cysteine, co-enzyme
Q10 or glutathione.
[0030] The nutrient compositions of the invention are useful in a
wide variety of applications to, for example, enhance immune
function, increase energy states of cells and tissues, promote
detoxification functions or to promote or maintain an overall
healthy or balanced physiological environment. One advantage of the
nutrient compositions of the invention is that they can
simultaneously enhance the immune system strength and accelerate
detoxification activities of a cell or organism. Further, the
nutrient compositions of the invention can achieve unanticipated
levels of immune system strength and accelerated detoxification
because they provide multiple nutrients in supernormal amounts that
together optimize the efficiency and effectiveness of enzyme
systems, such as cellular enzyme systems. The nutrient compositions
of the invention also can combine all, or substantially all, of the
components in supernormal amounts to simultaneously optimize or
enhance both primary and secondary enzyme systems. Supernormal
amounts of nutrients in the composition formulations of the
invention are beneficial because they can ensure that the activity
or regulation of enzyme systems remains uncompromised.
[0031] The above and other characteristics of the nutrient
compositions of the invention can be beneficially applied in
conjunction with other therapeutic treatments to, for example,
augment therapy, increase longevity or enhance the quality of life.
Similarly, normal or healthy individuals also can benefit from use
of the nutrient compositions to enhance or promote normal
physiological functions. The nutrient compositions of the invention
can supplement or augment intake requirements for vitamins,
minerals, cofactors and antioxidants. Routine administration can
ensure, for example, that the daily amounts required for normal
physiological processes are met, as well as ensure an ample
reservoir of such nutrients under physiological or metabolic stress
when there is a need for increased nutrient amounts. Additionally,
the nutrient compositions of the invention also can be taken based
upon need, as when abnormal symptoms begin to occur for example, to
defend against or retard the onset of a physiological disorder or
disease.
[0032] The nutrient compositions of the invention are described
herein primarily with reference to use in conjunction with a
therapeutic treatment. However, it is understood that the
beneficial effects afforded by a nutrient composition of the
invention when used to promote or augment physiological mechanisms
are equally applicable to promote or augment such physiological
mechanisms in a normal individual or healthy state. Accordingly,
the benefits and attributes accorded to the nutrient compositions
when described in reference to enhancing a function or effect of a
therapeutic treatment or a detoxification function are equally
accorded to such functions or effects under normal or healthy
states.
[0033] For example, the nutrient compositions of the invention can
enhance the function and effect of antiretroviral drugs by
elevating the mitochondrial energy output of all immune system
cells. This elevation of mitochondrial energy output improves both
mitochondrial number and function. In one study, described further
below in Example I, the CD4.sup.+ cell count for HIV patients
taking a nutrient composition of the invention increased by an
average of 26% over twelve weeks when compared to placebo.
CD4.sup.+ cells are an important marker of immune system strength.
Increasing CD4.sup.+ cell number or performance results in
beneficial physiological consequences in either the healthy or
diseased individual.
[0034] The nutrient compositions of the invention also can enhance
the energy level and healing capacity for patients with an immune
system dysfunction. Healing is a dynamic process that occurs within
the individual. It is achieved when you go from your present level
of health to one that is higher and more stable. It is an ongoing
process. This enhancement in energy level and healing capacity can
be attributed, for example, to the support of the mitochondria of
cells throughout the body, particularly those of the immune system.
Mitochondria are energy-producing organelles present in all
mammalian cells and are important to maintain optimal cellular
health, function and homeostasis of physiological systems.
[0035] The nutrient compositions of the invention also can prevent
or reduce the toxicity from nucleoside reverse transcriptase
inhibitor (nTRI) medications that are used to treat HIV infection.
The term for this type of toxicity is "mitochondrial toxicity." The
nutrient compositions of the invention contain, for example,
vitamin, mineral and high potency antioxidants. Because
mitochondria divide independently of cell division, and nRTI drugs
are toxic to the mitochondria due to their inhibition of the enzyme
mitochondrial DNA polymerase gamma, mitochondria are highly
susceptible to drug-induced mitochondrial toxicity. Therapeutics
that can induce mitochondrial toxicity include, for example, nTRI
drugs as well as other potent medications or long-term
administration regimes well known in the art. Mitochondrial
toxicities are diverse in nature and reflect individual differences
between a particular therapeutic, such as an individual nRTI, and
the sensitivity of the target tissue. Specific mitochondrial
toxicities can include, for example, hepatitis, anemia, peripheral
neuropathy, pancreatitis, cardiomyopathy, lactic acidosis,
radiation poisoning and fat redistribution. These mitochondrial
toxicities as well as others well known to those skilled in the art
are amenable to treatment with the nutrient compositions of the
invention.
[0036] The nutrient compositions of the invention also can be used
to enhance maintenance, performance or homeostasis of immunological
or other physiological processes. The nutrient compositions
described herein are formulated to contain optimal combinations of
vitamin, mineral and antioxidant nutrients required in biochemical
processes for normal physiological function. Administration of such
multinutrient compositions ensures an adequate supply of needed
nutrients to, for example, preclude nutrient availability as a rate
limiting step. Moreover, ensuring an adequate supply facilitates,
reduces or circumvents a lag phase when an immunological or other
physiological response is invoked because, for example, the
required nutrients are available or the cellular machinery is
poised for any extra required activity. Accordingly, the nutrient
compositions of the invention, when used either by an individual
suffering from a physiological disorder or disease or a normal
individual, can minimize undesirable burdens on biochemical or
physiological cellular process, resulting in a benefit to some or
all cellular or physiological systems of the individual.
[0037] Individuals that can benefit from administration of a
nutrient composition of the invention include, for example, normal
individuals, aging individuals as well as individuals infected or
afflicted with one or more disorders or diseases such as an
immune-mediated disease, cancer, heart disease, chronic fatigue
syndrome, neurodegenerative diseases, infectious diseases, ischemic
events, acute events or chronic events. Specific examples of such
disorders or diseases include multiple sclerosis, lupus, rheumatoid
arthritis, scleroderma, coronary artery disease, atherosclerotic
vessel disease, Madalung's disease, neoplastic conditions, solid
tumor malignancies, non-solid malignancies, Alzheimer's disease,
Parkinson's disease, dementia, infectious hepatitis, toxic
hepatitis, drug-induced hepatitis, herpes, human immunodeficiency
virus (HIV) infection, acquired immunodeficiency syndrome (AIDS),
stroke, radiation poisoning, toxic drug exposure or oxidative
stress occurring as part of the normal aging process.
Neurodegenerative forms of dementia include, for example,
deteriorated mentality such as that observed with ischemic events,
drug abuse, alcohol abuse or HIV/AIDS. Numerous other physiological
disorders or diseases also are applicable for treatment with the
nutrient compositions of the invention. Given the teachings and
guidance provided herein, those skilled in the art will know, or
can determine, such other abnormal physiological conditions
applicable for treatment with the nutrient compositions of the
invention.
[0038] The nutrient compositions of the invention can consist of a
multinutrient formulation containing an optimal combination of
vitamin, mineral and high potency antioxidants. The nutrient
compositions of the invention alternatively can consist of an
optimal combination of vitamin antioxidants, of mineral
antioxidants or of high potency antioxidants. The nutrient
compositions also can consist of an optimal combination of vitamin
and mineral antioxidants, vitamin and high potency antioxidants or
mineral and high potency antioxidants. The nutrient compositions
similarly can consist of various other combinations of these
antioxidants and can contain, for example, one, two, three, four or
five or more different antioxidants. Antioxidants are beneficial to
physiological processes because they augment immune strength or
physiological detoxification functions within the cells or tissues
of an individual. Moreover, multinutrient combinations are
beneficial physiologically because of their interdependence in a
variety of cellular and physiological process. For example,
mammalian mitochondria are interdependent on multiple nutrients for
healthful and efficient functioning. Ascorbate (vitamin C),
alpha-tocopherol (vitamin E), alpha-lipoic acid, and glutathione
(such as that derived from N-acetyl cysteine) are dependent upon
each other to replenish their lower valence, bio-active moieties
subsequent to oxidation by free radicals. Supplementing one or less
than all of these interdependent nutrients can result in a loss of
biochemical efficiency if the goal is to promote improved
functioning of, for example, a dysfunctional Kreb's cycle or
electron transport system. Other uses and beneficial effects of the
nutrient compositions of the invention for augmenting immune
strength or physiological detoxifications are described further
below with reference to the methods of the invention.
[0039] Antioxidants function in a wide variety of physiological
processes, including those described above and below as well as
other process well known by those skilled in the art.
Administration of multinutrient antioxidant formulations can
improve the functions dependent on such antioxidants as well as
improve the functions dependent on the interplay of antioxidants
and of antioxidants with other nutrients such as vitamins and
minerals. Optimal combinations of nutrients in the compositions of
the invention include amounts or types of nutrients that together
support the interdependent roles of two or more nutrients. A
specific example of such interdependence is described above with
reference to replenishing reduced molecular states of nutrients in
the Kreb's cycle or electron transport chain. Other optimal
combinations that support interdependence include, for example, the
ability of Vitamin C (Ascorbate) to regenerate native Vitamin E
(tocopherol) from its oxidized state as well as alpha lipoic acid
to regenerate native ascorbate from its oxidized state.
[0040] Vitamin antioxidants that can be selected for inclusion in a
nutrient composition of the invention as an optimal combination
include, for example, vitamin C, bioflavinoid complex, vitamin E,
vitamin B6 or beta-carotene. One or more of these or other vitamin
antioxidants well known in the art can be included in a nutrient
composition of the invention.
[0041] Vitamin C, or ascorbic acid or ascorbate, is a strong
reducing agent that can be reversibly oxidized to dehydroascorbic
acid. The term vitamin C, as it is used herein, is intended to
include any of several enolic lactones of keto aldonic acids that
are stereoisomers of ascorbic acid. As described above, vitamin C
functions in, for example, the Kreb's cycle and a deficiency can
lead to scurvy. Vitamin C also functions in building and
maintaining bone matrix, cartilage, dentin, collagen, and
connective tissue in general. Furthermore, Vitamin C participates
in resistance to infection by the immune system and proper adrenal
gland function in reaction or resistance to stress.
[0042] Bioflavinoid complex, or vitamin P, includes the substances
rutin, citrin, hesperidin, and quercitin. These substances exhibit
reducing and chelating properties and can be required for the
proper function of minute blood vessels. They also play a role in
modulating the inflammatory response, particularly of mast
cells.
[0043] Vitamin E, or d-alpha tocopherol, is a fat-soluble
tocopherol vitamin with powerful antioxidant properties. Vitamin E
also plays a role in protecting cellular membrane fatty acids from
oxidative damage. It is nutritionally required for mammals in which
its absence is associated with infertility, muscular dystrophy, or
abnormalities in the vascular system. The term vitamin E, as it is
used herein, is intended to include, any of the structurally
similar chemical compounds found within the tocopherol family of
organic compounds.
[0044] Vitamin B6, or pyroxidine HCl or pyridoxine, is a component
of the vitamin B complex and plays a role in the proper formation
and health of red blood cells and blood vessels, nerve function,
gums and teeth. Vitamin B6 also is involved in the amino acid
metabolism. Although not generally considered to be an antioxidant,
vitamin B6 does exhibit antioxidant properties.
[0045] Beta-carotene is a vitamin antioxidant that also is
convertible to vitamin A in the liver of animals. This class of
nutrients includes all those defined by the term "retinoids" and
includes those described as retinols. Since Vitamin A is only found
in animal foods, beta-carotene provides about two thirds of the
daily intake of retinoids in humans. Beta-carotene is converted to
Vitamin A in both the gastrointestinal tract and the liver. Vitamin
A is used by the body to enhance retinal function and night vision
and also plays a role in the formation and maintenance of healthy
epithelial tissue, which forms the body's primary barrier to
infection.
[0046] Mineral antioxidants that can be selected for inclusion in a
nutrient composition of the invention as an optimal combination
include, for example, zinc or selenium. Either or both of these
minerals as well as other vitamin antioxidants well known in the
art can be included in a nutrient composition of the invention.
[0047] Zinc, taken in the form of picolinate, carbonate, ascorbate,
or complexed to a chelated amino acid, for example, is one mineral
exhibiting antioxidant activity. Zinc also is utilized for the
metabolic activity of about 200 or more enzymes and is considered
important for cell division and the synthesis of DNA and
polypeptides. Zinc deficiency contributes to growth retardation and
even mild deficiency may limit growth in otherwise healthy
children. Zinc functions, for example, in energy metabolism as part
of the lactate dehydrogenase enzyme system. Zinc also participates
in immune function, as evidenced by its role in promoting enhanced
would healing, and serves as an antioxidant, such as part of the
superoxide dismutase enzyme system.
[0048] Selenium, taken in the form of picolinate, carbonate,
ascorbate, or complexed to a chelated amino acid for example, is
another mineral having antioxidant activity. Selenium is an
important component of the active sites of, for example, the
enzymes glutathione peroxidase, iodothyronine 5'-deiodinase and
mammalian thioredoxin reductase. It is also present in several
other mammalian selenoproteins. Both glutathione peroxidase and
thioredoxin reductase catalyze reactions involved in the protection
of cellular components against oxidative and free radical damage.
Therefore, selenium as well as zinc and other nutrients within the
compositions of the invention augment the activity of enzymes
within one or more antioxidant enzyme systems of an individual.
Selenium also plays a role as a mammalian cell's second line of
defense against damaging cell peroxides. It performs this role as
an integral part of the glutathione peroxidase enzyme system.
[0049] High potency antioxidants that can be selected for inclusion
in a nutrient composition of the invention as an optimal
combination include three or more of, for example, alpha lipoic
acid, acetyl L-carnitine, N-acetyl-cysteine, co-enzyme Q10 or
glutathione.
[0050] Alpha lipoic acid is a potent antioxidant found, for
example, in the mitochondria. It acts as a coenzyme in the
alpha-keto-dehydrogenase enzyme complex of the Kreb's cycle to
facilitate aerobic respiration as well as participates in the
metabolic pathways which regenerate de novo levels of ascorbate,
alpha-tocopherol, and glutathione. Alpha lipoic acid also functions
as a potent free radical scavenger. In addition to these
antioxidant activities, alpha-lipoic acid also can, for example,
inhibit NF-kappa B activation, HIV replication in cell cultures and
reduce the severity of peripheral neuropathy in diabetes mellitus
patients (Packer et al., Mol. Aspects of Med. 14: 229-239 (1993);
Baur et al., Klin. Wochenschr. 69: 722-724 (1991)). Alpha lipoic
acid also may to increase the number of CD4.sup.+ cells and the
CD4:CD8 ratio in HIV-infected patients (Fuchs et al.,
Arzneimittelforschung 43: 1359-1362 (1993)).
[0051] Acetyl L-carnitine is similarly a nutrient with potent
antioxidant activity because it supports antioxidant activity under
a diverse set of conditions. The acetyl moiety of the amino acid
carnitine regulates fatty acid transport across the mitochondrial
membrane. It enhances mitochondrial function and energy production
utilized in antioxidant activities by providing additional fuel
stores during times of oxidative stress. It also functions to
provide mitochondria with a fuel source that enhances its ability
to produce energy under anaerobic conditions. Anaerobic metabolism
can occur, for example, when the electron transport chain is
dysregulated due to a depletion of mitochondrial DNA. In addition
to the antioxidant and other energy functions of acetyl
L-carnitine, this nutrient also can, for example, reduce symptoms
of zidovudine (AZT)-induced mitochondrial myopathy (Campos et al.,
Muscle Nerve. 16: 150-153 (1993); Dalakas et al., Ann. Neurol. 35:
482-487 (1994)), or peripheral neuropathy in diabetes mellitus or
HIV infection (Famularo et al., J. Peripher. Nerv. Syst. 3: 227-29
(1998)). Acetyl L-carnitine deficiency has also been shown to be
present in HIV-infected individuals diagnosed with peripheral
neuropathy (Famularo e al., AIDS 11: 185 (1997)).
[0052] N-Acetyl Cysteine (NAC) is another nutrient with potent
antioxidant activity. The acetyl moiety of the amino acid cysteine
is a prevalent bioavailable oral source of glutathione. Glutathione
is a potent antioxidant and component of the glutathione peroxidase
enzyme system. In contrast, glutathione deficiency can be
associated, for example, with a poor prognosis in HIV disease
(Aukrust et al., Nutrition 15: 165-167 (1999); De Quay et al., AIDS
6: 815-819 (1992)), and that the HIV Tat protein or nRTI
medications may contribute to a reduction of glutathione levels in
HIV-infected cells (Choi et al., J. Biol. Chem. 275: 3693-3698
(2000)).
[0053] Co-enzyme Q10 (ubiquinone) is a further nutrient with potent
antioxidant activity. This antioxidant functions as an intermediary
in the electron transport system in the mitochondria of every cell
and adequate amounts of this nutrient are needed for optimal
production of ATP. Coenzyme Q10 also functions in the mitochondria
as an intracellular antioxidant and adequate levels are needed for
the healthful functioning of all human tissues and organs. Tissues,
organs, and systems that are the most metabolically active are more
dependent on adequate Coenzyme Q10 levels. Such metabolically
active tissues include, for example, heart, liver, immune system
and gastric mucosa.
[0054] Any of the nutrient antioxidants describe above as well as
others well known in the art can be included in a nutrient
composition of the invention. Additionally, other nutrients that
function, for example, in one or more of the antioxidant enzyme
systems described above or others well known in the art also can be
included or substituted for one or more vitamin, mineral or high
potency antioxidants included in a nutrient composition described
herein. For example, the nutrients selenium, alpha lipoic acid and
NAC participate in the glutathione peroxidase enzyme system or
function to regenerate reduced glutathione and result, for example,
in the protection of cellular components against oxidative and free
radical damage. Those skilled in the art will understand that
glutathione can be used, for example, as a functional equivalent
for these antioxidants and be substituted for a vitamin, mineral or
high potency antioxidant to achieve the same or similar results.
Various other antioxidant substitutions as functional equivalents
also can be included in the nutrient compositions of the invention.
Given the teachings and guidance provided herein, those skilled in
the art will know, or can determine, which other antioxidants can
be substituted without loosing physiological effect or
activity.
[0055] The nutrient compositions consist of at least one vitamin
antioxidant, at least one mineral antioxidant and at least three
high potency antioxidants. For example, one nutrient composition
can contain an effective amount of vitamin C as a vitamin
antioxidant, zinc as a mineral antioxidant and alpha lipoic acid,
acetyl L-carnitine and NAC as the three high potency antioxidants.
Another nutrient composition can contain an effective amount of,
for example, bioflavinoid complex as a vitamin antioxidant, zinc as
a mineral antioxidant and alpha lipoic acid, acetyl L-carnitine and
NAC as the three high potency antioxidants. Further, an additional
nutrient composition of the invention can contain an effective
amount of, for example, vitamin E as a vitamin antioxidant, zinc as
a mineral antioxidant and alpha lipoic acid, acetyl L-carnitine and
NAC as the three high potency antioxidants. Similarly, vitamin B6
or beta-carotene also can be substituted for the vitamin
antioxidant component of the nutrient composition. In like manner,
each of the exemplary vitamin antioxidants can be combined with
selenium in substitution for zinc as the mineral antioxidant, while
still containing alpha lipoic acid, acetyl L-carnitine and NAC as
the three high potency antioxidants. Further, co-enzyme Q10 or
glutathione or both can be substituted for one or more of the high
potency antioxidants alpha lipoic acid, acetyl L-carnitine or NAC.
All of the various combinations of the above vitamin, mineral and
high potency antioxidants are also included herein as a nutrient
composition of the invention.
[0056] The nutrient compositions also can contain, for example, two
or more vitamin antioxidants or two or more mineral antioxidants or
combinations of two or more vitamin antioxidants and at least one
mineral antioxidant or at least one vitamin antioxidant and two or
more mineral antioxidants. Nutrient compositions containing more
than one vitamin or mineral antioxidant also will contain at least
three high potency antioxidants. For example, in addition to
containing alpha lipoic acid, acetyl L-carnitine and NAC, or
substitutable equivalents such as glutathione or co-enzyme Q10, a
nutrient composition can contain two or more of vitamin C,
bioflavinoid complex, vitamin E, vitamin B6 or beta-carotene as
well as zinc, selenium or both. All of the various combinations of
these vitamin, mineral and high potency antioxidants are included
herein as a nutrient composition of the invention. An exemplary
nutrient composition containing more than one vitamin and more than
one mineral antioxidant can be, for example, a combination of
effective amounts of vitamin C, bioflavinoid complex, vitamin E,
zinc, selenium, alpha lipoic acid, acetyl L-carnitine and NAC.
Given the teachings and guidance provided herein, those skilled in
the art will know, or can determine, what other combinations of at
least one vitamin antioxidant, at least one mineral antioxidant and
at least three high potency antioxidants can be included in a
nutrient composition of the invention that will maintain activity
for augmenting immune strength and detoxification functions of a
physiological system.
[0057] The nutrient compositions of the invention also can contain
one or more additional vitamins, minerals, vitamin or mineral
antioxidants or high potency antioxidants or any combination
thereof. Vitamins and minerals can be additionally included to
further promote the immune strength or detoxification functions of
the nutrient compositions of the invention. Effective amounts of
such additional vitamins or minerals or additional antioxidants,
including high potency antioxidants, will provide additional
reservoirs of nutrients required by biochemical and physiological
process to perform their respective functions under either or both
normal or stressful conditions. As with the antioxidants described
previously, inclusion of effective amounts of one or more vitamins
or minerals can result in optimal performance of physiological
processes due to the interplay or interdependency of nutrients in
biochemical reactions.
[0058] Additional vitamins or minerals that can be included in the
nutrient compositions of the invention include those shown in FIG.
1 or 2 other than the antioxidants described previously. For
example, one or more nutrients from the vitamin category can be
additionally included. Similarly, one or more nutrients from the
mineral category can be additionally included. Alternatively, one
or more nutrients from both the vitamin and the mineral categories
can be additionally included in the antioxidant nutrient
compositions of the invention. Therefore, the nutrient compositions
can include any one or more, as well as all of the various
combinations of the following vitamins or minerals: beta-carotene,
vitamin A, vitamin B1, vitamin B2, vitamin B6, niacinamide, calcium
panthothenate, choline, inositol, folic acid, biotin, vitamin D3,
vitamin B12, calcium, magnesium, iron, iodine, copper, manganese,
potassium, chromium, molybdenum, boron, betaine, glutamic acid.
[0059] The above vitamins and minerals as well as others known in
the art function in a wide variety of metabolic, biochemical or
physiological processes. As such, they are useful to promote
efficiency of their respective processes as well as augment the
functioning of the antioxidant nutrients of the invention.
Accordingly, when included in a nutrient composition of the
invention, these vitamins or minerals similarly can augment immune
strength or detoxification functions including, for example,
reducing mitochondrial oxidative stress and/or oxidative damage.
Exemplary functions and activities of these vitamins and minerals
are described further below and can be found described in, for
example, Williams, B. R., Nutrition and Diet Therapy (6th Ed),
Times Mirror/Mosby Collage Publishing, St. Louis, Mo. (1989).
[0060] For example, thiamine (vitamin B1) is a water-soluble,
B-complex vitamin needed to metabolize proteins, carbohydrates, and
fats. It is used as a cofactor in numerous enzymes, enhances
nervous system health, and is used by cells for ATP production via
the Kreb's cycle.
[0061] Riboflavin (vitamin B2) is a water-soluble, B-complex
vitamin that is a constituent in several enzymes known as
flavoproteins. Two such riboflavin enzymes, flavin mononucleotide
(FMN) and flavin-adenine dinucleotide (FAD), operate in the
respiratory chain of cellular energy metabolism to produce ATP.
[0062] Pyridoxine (vitamin B6) is a water-soluble, B-complex
vitamin that, in its active form pyridoxalphosphate (B6-PO.sub.4),
is a coenzyme involved in many types of transamination and
decarboxylation reactions ocurring in amino acid, carbohydrate and
fat metabolism. Vitamin B6 also is a cofactor in immune system
functioning.
[0063] Niacinamide (a form of niacin) is a water-soluble, B-complex
vitamin that is a constituent of the cellular enzymes utilized in
energy metabolism and the production of ATP. Two niacin coenzymes
that operate in these reactions are nicotin-amide-adenine
dinucleotide (NAD) and nicotin-amide-adenine dinucleotide phosphate
(NADP).
[0064] Pantothenic acid is a water-soluble B-complex vitamin that
globally participates in metabolic processes due to its ability to
promote acetylation.
[0065] Choline, folic acid and vitamin B12 are nutritional factors
involved in transmethylation reactions. Choline is a component of
two phospholipids compounds made by the body: lecithin and
sphingomyelin.
[0066] Inositol can function as an antioixidant by chelating
divalent cations such as copper and iron. Chelation of divalent
cations can prevent the formation of reactive oxygen species (ROS)
responsible for cell injury and carcinogenesis.
[0067] Folic acid acts as a coenzyme which transfers single carbon
units for attachment in many conversion reactions such as in the
formation of hemoglobin. Folic acid deficiency can cause
anemia.
[0068] Biotin functions as a coenzyme with specific cell enzymes
involved in the process of carboxylation.
[0069] Vitamin D3 participates in the regulation of calcium and
magnesium metabolism and in the synthesis of bone.
[0070] Vitamin B12 is needed for the production of red blood cells
and healthy nervous system functioning.
[0071] Calcium is present in large amounts in the human body and is
needed, for example, for structural integrity, blood clotting and
nerve cell functioning.
[0072] Magnesium is needed for healthy intracellular metabolism of
macromolecules such as carbohydrates and protein. A magnesium-ATP
complex is the form of ATP used as a substrate in many biochemical
reactions.
[0073] Iron is utilized for the production of the hemoglobin
molecule of red blood cells.
[0074] Iodine functions as a precursor to the synthesis of thyroid
hormone which controls the body's basal metabolic rate.
[0075] Copper is associated with iron in several metabolic
reactions including those involved in energy production and the
formation of hemoglobin.
[0076] Manganese, found in concentrated amounts in the
mitochondria, functions as a catalytic component of several
energy-producing enzyme systems.
[0077] Intracellular potassium helps to balance the osmotic
pressure of cells by balancing extracellular sodium.
[0078] Chromium is a component of the organic complex glucose
tolerance factor (GTF), which potentiates the action of insulin by
facilitating the binding of insulin to the cell membrane.
[0079] Molybdenum functions as a catalytic component of several
enzyme systems necessary for healthy metabolism.
[0080] Boron is a trace mineral that functions along with calcium
and magnesium in formation of bone.
[0081] Glutamine (glutamic acid) is a prevalent amino acid in the
bloodstream and a readily utilized source of energy for muscle
cells and the intestinal mucosal lining.
[0082] Betaine hydrochloride is an acidic compound that facilitates
the absorption of other nutrients in the compositions of the
invention.
[0083] The nutrient compositions also can include all of the above
additional vitamins and minerals together with all of the vitamin,
mineral and high potency antioxidants described previously or any
combination of at least one vitamin antioxidant, one mineral
antioxidant and at least three high potency antioxidants. As with
the antioxidants described previously, other vitamins or minerals
well known in the art can similarly be included or substituted in
the nutrient compositions of the invention.
[0084] Optimal combinations of the above and below described
nutrient compositions include each nutrient in an effective amount.
Similarly, the combination of nutrients together yield an effective
amount for a total effect on stimulation of immune strength.
Effective amounts of nutrients in the formulations of the invention
include amounts of nutrients higher than those suggested by the
U.S. Food and Drug Administration as the recommended daily
allowances (RDA). The purpose of the RDA for vitamin and mineral
intake is to promote normal health and eliminate nutrient
deficiency diseases in otherwise healthy adults. The effective
amounts described herein achieve this purpose because on their
inclusion in a optimal combination in amounts in excess of the RDA.
The effective amounts described herein also provide the benefit of
producing an available reservoir for access under stress such as a
diseased or pathological condition. Effective amounts of the
nutrient compositions additionally poise cellular, biochemical and
physiological processes for action because there reduce
physiological burdens under depleted conditions. Therefore, by
utilizing effective amounts above the RDA, the nutrient
compositions are capable of augmenting immune strength or
physiological detoxification functions as well as capable of
preventing or reversing drug-induced toxicities. Preventing
includes delaying the onset of a physiological disorder as well as
reducing the severity of such disorders and diseases.
[0085] Effective amounts of the nutrient compositions of the
invention include, for example, those amounts shown in FIGS. 1 and
2 and the dosages shown in FIG. 3. Additionally, a effective amount
of co-enzyme Q10 can range, for example, from about 30-300 mg per
day for an individual weighing about 70 kg. Glutathione dosages can
range, for example, from about 100 mg/day to about 600 mg/day for
an individual weighing about 70 kg. Such effective amounts are
higher than the RDA for each nutrient listed as well as for all
nutrients contained within an optimal combination of the invention.
Effective amounts can vary depending on the need or availability of
a nutrient and include, for example, a dosage ranging from about
25% to about 200% of those amounts per body weight listed in FIG.
3. Effective amounts higher and lower similarly can be employed in
the optimal combinations of nutrients of the invention so long as
they are in excess of the RDA or in excess of nutritional
requirements under a particular physiological condition.
[0086] Effective amounts also can be defined as ratios of, for
example, antioxidants or high potency antioxidants. For example,
effective amounts for the high potency antioxidants alpha lipoic
acid, acetyl L-carnitine and NAC can include daily amounts of about
200 mg, 500 mg and 600 mg, respectively, for an individual weighing
less than about 70 kg. Similarly, for an individual weighing about
70 kg or more, an effective amount can include daily intake of
about twice these levels. Dosages include amounts per kilogram of
body weight of about 5.71 mg, 14.29 mg and 17.14 mg, respectively,
and can range from about 25% to about 200% of these dosages.
Whether expressed as amounts or dosages per body weight, the high
potency antioxidants are included in an optimal combination of the
invention in a ratio ranging from about 1:1:1 to about 1:4:6,
respectively. All values in between these ratios are similarly
included as an effective amount for an optimal combination of the
three high potency antioxidants alpha lipoic acid, acetyl
L-carnitine and NAC, respectively, as well as functional
equivalents thereof. Given the teachings and guidance provided
herein, those skilled in the art will know, or can determine, the
actual amounts, dosages or ratios other than those described above
and exemplified in FIGS. 1-3 and in Table 2, that will augment
immune strength or detoxification functions of a physiological
process.
[0087] Efficacy of the nutrient compositions of the invention,
including cooperative interactions between physiological processes,
promotion of immune strength or detoxification functions,
correlates with purity level of the nutrients within an optimal
combination of the invention. Higher the purity levels yield
greater activity and consequently can allow a reduction in the
amount included in one or more administrations. Nutrient
compositions having a purity level adequate for human ingestion is
sufficient for augmentation of immune strength or detoxification
functions.
[0088] The nutrients of the invention and optimal combinations in
the compositions of the invention can have a purity level greater
than about 90%, preferably greater than about 95% and more
preferably greater than about 98%. Purity levels greater than about
98% percent can also have a purity of about 99% or greater as
determined, for example, by total weight of the nutrient
composition. These higher purity levels can be obtained by, for
example, methods well known in the art. Additionally, purity levels
greater than about 98% and particularly greater than about 99% by
total weight can be obtained by omitting fillers, binders or
lubricants such as stearates or palmitates. Additionally, other
substances which are known in the art to inhibit, or known to
possibly inhibit, the absorption, bioavailability or tolerance of
compounds in individuals also can be excluded from the formulations
to achieve greater than about 98-99% purity without compromising
the activity of the nutrient compositions of the invention.
However, it should be understood that such fillers, binders,
lubricants or other substances also can be included in the nutrient
compositions of the invention when, for example, it is desirable or
an optimal efficacy is not needed to achieve a particular result.
Given the teachings and guidance provided herein, those skilled in
the art will know whether to utilize nutrient compositions less
than the purity levels described above or to include additional
substances in a formulation. Accordingly, various formulations well
known in the art for packaging and administration of nutrients or
other administrable chemical compounds can be utilized in
conjunction with the nutrient compositions of the invention.
[0089] Nutrients for use in the formulations of the invention can
be obtained from any of various sources known to those skilled in
the art. For example, individual nutrients or optimal combinations
meeting the amounts or dosages exemplified herein can be produced
by a commercial manufacturer. An exemplary commercial manufacturer
is Thorne Research (Dover Id., and which can be found at the URL
thorne.com). Additionally, nutrients of the invention can be
purified biochemically or synthesized chemically using methods well
known to those skilled in the art.
[0090] Therefore, the invention also provides a nutrient
composition for augmenting immune strength or physiological
detoxification that consists of an optimal combination of an
effective amount of at least three vitamin antioxidants, at least
two mineral antioxidants and a highly saturable amount of at least
three high potency antioxidants. The at least three vitamin
antioxidants can be three vitamins selected from vitamin C,
bioflavonoid complex, vitamin E, vitamin B6 or beta-carotene. The
at least two mineral antioxidants can be zinc and selenium and the
at least three high potency antioxidants can be three antioxidants
selected from alpha lipoic acid, acetyl L-carnitine,
N-acetyl-cysteine, co-enzyme Q10 or glutathione. Purity levels of
the nutrient compositions can be 99% or greater by total weight.
Further provided is a nutrient composition for augmenting immune
strength or physiological detoxification that consists of an
optimal combination of an effective amount of vitamin C,
bioflavonoid complex, vitamin E, zinc, selenium, alpha lipoic acid,
acetyl L-carnitine and N-aceytl-cysteine.
[0091] The invention additionally provides a method of stimulating
immune system function. The method consists of administering to an
individual a nutrient composition of the invention one or more
times a day over a period of about 5-7 weeks, the immune system
function being stimulated to result in an increase of CD4.sup.+
cells of at least about 15% compared to pre-administration
levels.
[0092] A method of stimulating a physiological detoxification
function of an individual is also provided. The method consists of
administering to an individual a nutrient composition of the
invention one or more times a day over a period of about 5-7 weeks,
the physiological detoxification function being stimulated to
result in a decrease of one or more free radical markers by about
20% compared to pre-administration levels.
[0093] The antioxidant nutrients compositions of the invention can
be used alone or in combination with additional vitamin or mineral
nutrients to augment immune strength or detoxification functions of
physiological processes. In addition to promoting specific
physiological processes such as energy production, detoxification
functions of cells and tissues, reduction in mitochondrial
oxidative stress or a reduction in oxidative damage, the nutrient
compositions of the invention exhibit measurable differences in
indicators of immune system strength. For example, routine intake
of a nutrient composition of the invention can result in a
significant increase in the amount of CD4.sup.+ cells within the
immune system. Because CD4.sup.+ cells are effector lymphocytes
that promote and regulate other immune system cells, an increase in
these cells also can result in enhanced function of the entire
immune system. Therefore, routine intake of a nutrient composition
of the invention also can result in increased amounts or
performance of a wide variety of other immune system cells. Such
immune system cells can be derived from the cellular, humoral or
innate immunity components of the immune system and cells can
include, for example, other helper T cells, natural killer cells,
cytotoxic T cells, B cells, macrophages, neutrophils, eosinophils
or other cells participating in antibody-dependent cell
cytotoxicity. The levels or performance of immune system cells well
known in the art other than those described above also can be
enhanced with the nutrient compositions of the invention.
[0094] With reference to the specific example of CD4.sup.+ cells,
the nutrient compositions can result in an increase in CD4.sup.+
cells by at least about 15% compared to CD4.sup.+ cell levels or
percentages prior to administration. Increases of CD4.sup.+ cells
substantially greater than about 15% compared to pre-administration
levels also can be obtained as an indicator of immune strength. For
example, administration of the nutrient compositions can result in
a CD4.sup.+ cells increase greater than about 25%, 30%, 35% or 40%
or greater compared to pre-administration levels. As a measure of
immune strength, higher levels or greater percentages of increase
in CD4.sup.+ cells indicates a commensurate increase in immune
system strength. Such immune strength includes, for example,
increases in immune system function, performance, efficiency or
capacity as well as combinations thereof. Immune system cells other
than CD4.sup.+ cells also can be increased by comparable amounts
and in approximate proportion to their normal physiological
distribution within the an immune system. Additionally, augmenting
immune strength also can occur by ensuring sustaining amounts of
nutrients for optimal performance. The nutrient compositions of the
invention achieve such sustaining amounts.
[0095] In addition to promoting immune strength, detoxification
functions, reduced mitochondrial oxidative stress or reduced
oxidative damage as well as other physiological process described
herein, the nutrient compositions of the invention also exhibit
measurable differences in indicators of physiological
detoxification functions. For example, routine intake of a nutrient
composition of the invention can result in a significant decrease
in free radical markers. Reduction of free radical markers
indicates a commensurate and proportional reduction in deleterious
free oxygen species. Because free oxygen species are reduced, the
detoxifying functions of cells and organelles are available to
efficiently scavenger nascent free radicals and can result in an
enhancement of the effectiveness or efficiency of immune strength,
energy producing process or further detoxification functions.
Therefore, routine intake of a nutrient composition of the
invention also can result in increased performance or efficiency of
a wide variety biochemical reactions or physiological processes.
Accordingly, the performance or efficiency of detoxification
functions well known to those skilled in the art other than those
described herein also can be enhanced with a nutrient composition
of the invention.
[0096] Particular clinical or laboratory free radical markers
include, for example, plasma malondialdehyde (MDA), plasma lipid
peroxides, reduced lipid peroxidation or plasma levels of
glutathione (GSH). Methods for measuring these and other free
radical markers are well know in the art. For example, diagnostic
levels of MDA can be determined by
high-performance-liquid-chromatography (HPLC) as well as other
chromatographic methods well known in the art. Levels of reduced
lipid peroxidation can be determined by, for example, breath
pentane output. The above markers and their use as indicators of
free oxygen species levels can be found described in, for example,
Allard et al., AIDS 12: 1653-1659 (1998). Various other indicators
of free oxygen species well known in the art similarly can be
utilized as a detoxification marker of the invention.
[0097] Exemplary detoxification functions augmented by a nutrient
composition of the invention include detoxification processes of
the liver, enhancement of hepatocyte functions, enhancement of
energy production or increased efficiency of toxin processing due
to a decrease in free radical buildup, for example. Additionally,
detoxification functions utilized for reducing the severity of
drug-induced toxicities such as nRTI-induced mitochondrial toxicity
as well as others well known in the art also are augmented by a
nutrient composition of the invention. These and other
detoxification functions are exemplified further below.
[0098] The nutrient compositions of the invention can result in a
decrease of one or more free radical markers by about 20% compared
to the same marker prior to administration. Decreases in free
radical markers substantially greater than about 20% compared to
pre-administration levels also can be obtained as an indicator of
detoxification function. For example, administration of the
nutrient compositions can result in a free radical marker decrease
of about 25%, 30%, 35%, 40%, 45% or 50% or greater compared to
pre-administration levels. As a measure of detoxification function,
reduced levels or a greater percent reduction in one or more free
radical markers indicates a commensurate increase in one or more
detoxification functions including, for example, increases in
detoxification performance, efficiency or capacity as well as
combinations thereof. Increased detoxification function includes,
for example, increases in energy state and resources. As with
augmenting immune strength, increasing detoxification functions
also can occur by ensuring sustaining amounts of nutrients for
optimal performance under normal or diseased conditions.
[0099] The nutrient compositions of the invention can be
administered over both short and long periods of time.
Effectiveness of the nutrient compositions is linked, for example,
to availability of the nutrient components of the formulations.
Accordingly, administration regimes can vary significantly so long
as in vivo levels of the nutrients are maintained at substantially
the same or similar levels as those achieved by the effective
amounts provided herein for oral administration. Such levels are
sufficient to maintain sustainable amounts in excess for optimal or
enhanced performance of physiological processes under normal or
stress conditions. Similarly, such in vivo amounts derivable from
the oral administrations described previously include, for example,
kinetics for nutrient uptake, clearance and half-life. Therefore,
administration regimes can include dosing intervals shorter or
longer than one or more times daily.
[0100] For example, depending on the weight of the recipient,
effective amounts can be administered once or twice daily for
orally administered nutrient compositions of the invention.
However, the nutrients can alternatively be produced, for example,
in time released formulations that allow for a reduced
administration schedule. Similarly, intravenous, subcutaneous or
other like administrations also can be utilized with the nutrient
compositions of the invention and administration schedule reduced
or increased depending on the concentration of the nutrient
formulation and amount given per administration. These and other
formulations and modes of administration are well known to those
skilled in the art. Durations that are particularly efficacious in
augmenting immune strength or detoxifying functions include, for
example, routine administrations between about 2-15 weeks,
preferable between about 3-12 weeks and more preferably between
about 5-7 weeks. Using the oral formulations described previously,
such routine administrations can occur about one to four times
daily over a course of about 6, 7, 8, 9, 10, 11, or 12 or more
weeks, for example.
[0101] As described previously, the antioxidant nutrient
compositions of the invention employed alone or in combination with
additional vitamin or mineral nutrients can be used to augment
immune strength or detoxification functions of physiological
processes within an individual. As such, the nutrient compositions
of the invention are applicable for facilitating the health
maintenance of normal individuals, promoting healing of individuals
with physiological disorders or diseases as well as to enhance the
therapeutic benefit of patients with a wide variety of disorders or
diseases. The exemplary indicators described previously as measures
of immune strength and detoxification function are similarly
applicable as indicators of health maintenance, healing as well as
improvement of disorders or diseases conditions. Therefore,
augmentation of a therapeutic treatment through combined treatment
with a nutrient composition of the invention also can be measured
with the previously describe indicators.
[0102] Exemplary physiological disorders or diseases applicable for
augmentation of a therapeutic treatment by combining the treatment
with administration of a nutrient composition of the invention
include immune-mediated diseases, cancer, heart disease, chronic
fatigue syndrome, neurodegenerative diseases or an infectious
disease. Specific examples of such disorders or diseases include
multiple sclerosis, lupus, rheumatoid arthritis, scleroderma,
coronary artery disease, atherosclerotic vessel disease, Madalung's
disease, neoplastic conditions, solid tumor malignancies, non-solid
malignancies, Alzheimer's disease, Parkinson's disease, infectious
hepatitis, toxic hepatitis, drug-induced hepatitis, herpes, human
immunodeficiency virus (HIV) infection or acquired immunodeficiency
syndrome (AIDS). Numerous other physiological disorders or diseases
also are applicable for treatment with the nutrient compositions of
the invention. Further, the nutrient compositions of the invention
also can be used to promote longevity in normal or diseased
individuals alike. Specific examples illustrating the applicability
of combined administration of the nutrient compositions of the
invention with ongoing drug therapy are described further below.
Given the teachings and guidance provided herein, those skilled in
the art will know, or can readily determine, those physiological
disorders or diseases that can be augmented when combined with
administration of a nutrient composition of the invention.
[0103] For example, as a class, the antioxidants described herein
individually enhance T and B lymphocyte proliferation, decrease the
release of lactic acid into the bloodstream, and enhance
mitochondrial energy production (Kalebic et al., Proc. Natl. Acad.
Sci. USA 88: 986-990 (1991)). These effects also can be beneficial
for preventing cell apoptosis, which occurs secondary to the
increased oxidative stress found during HIV infection irrespective
of whether infected individuals are undergoing nRTI therapy (Butte
et al., Immunol. Today 15: 7-10 (1994); Sato et al., J. Immunol.
154: 3194-3203 (1995)). Combining effective amounts of at least one
vitamin antioxidant, one mineral antioxidant and at least three
high potency antioxidants results in, for example, cooperation
between interdependent systems as well as performance of individual
nutrient targets that leads to optimal tuning of immune strength
and detoxification functions.
[0104] In addition, nucleoside reverse transcriptase inhibitors are
known to inhibit mitochondrial DNA-polymerase gamma (Parker et al.,
J. NIH Res. 6: 57-61 (1994); Chen et al., J. Biol. Chem. 264:
11934-11937 (1989)). The resultant depletion of mitochondrial DNA
contributes to a dysregulation of the cytochrome energy system of
the electron transport chain. This functional uncoupling of
oxidative metabolism creates a backup of acetyl Co-enzyme A, as
well as lactic acid, both intracellularly and extracellularly.
Release of these compounds into the blood leads to an increase in
gluconeogenesis in the liver thereby producing increased serum
insulin levels and concomitant hyperlipidemia (Khouri et al.,
Infec. Med. 17: 547-554 (2000)). These physiologic effects
contribute to an increase in truncal fat accumulation in
HIV-infected patients. This process is commonly described as
HIV-associated lipodystrophy syndrome.
[0105] Other disorders or diseases attributable to drug-induced
mitochondrial toxicity such as that caused by nRTI include, for
example, fat redistribution, hepatitis, anemia, pancreatitis, and
peripheral neuropathy. This pathogenic mechanism is also linked to
the development of life threatening lactic acidosis. While
previously rare, lactic acidosis can be more common at present due
to, for example, the large number of drugs currently used in
combination, prolonged drug therapy, improved survival or
combinations of these reasons.
[0106] The development of lactic acidosis also reflects a process
of progressive hepatotoxicity, because lactic acid is normally
converted into glucose by the liver, thereby lessening the amount
in circulation. As such, lactic acidosis is a sign of mitochondrial
toxicity or dysfunction because the mitochondria are the site of
oxidative phosphorylation, which converts lactate into pyruvate,
and pyruvate into carbon dioxide, water and ATP, in the electron
transport chain. By inhibiting this process, drugs such as nRTI
cause more pyruvate to back up with subsequent conversion in the
cytoplasm into lactate. Inhibition of oxidative phosphorylation
also inhibits the liver from clearing excess lactic acid in the
serum.
[0107] The link between drug-induced mitochondrial toxicities and
treatment with the nutrient compositions of the invention can be
exemplified with reference to nRTI-induced toxicity. Mitochondria
divide independently of cell division and are highly susceptible to
nRTI-induced toxicity due to their inhibition of mitochondrial DNA
polymerase gamma. The nutrient compositions of the invention
function to inhibit this toxicity, reduce deleterious free radical
buildup, promote liver detoxification functions and enhance energy
production, all of which promote reduced toxicity within the
mitochondria.
[0108] Similarly, mitochondrial toxicity also is linked to
peripheral neuropathy (PN). PN is a disease or degenerative state
of the peripheral nerves in which motor, sensory, or vasomotor
nerve fibers may be affected and which is marked by muscle weakness
and atrophy, pain, and numbness. PN occurs in about 10% or more of
patients beginning antiretroviral therapy with either stavudine
(D4T) or didanosine (DDI) containing antiviral regimens (Simpson et
el., Ann. Intern. Med. 121: 769-785 (1994)). Stavudine and
didanosine inhibit the production of mitochondrial DNA in
peripheral neurons, which leads to a buildup of free oxygen species
that can be toxic and lead to mitochondrial dysfunction. Buildup of
free oxygen species can be one factor for drug-induced peripheral
neuropathy such as that caused by nRTI medications (Chen et al.,
Mol. Pharmacol. 39: 625-628 (1991)).
[0109] As described previously, healthy mitochondrial functioning
is dependent, in part, on nutrients. Acetyl L-carnitine is utilized
to ferry fatty acids across the mitochondrial membrane for fuel.
N-acetyl-cysteine (NAC) and alpha-lipoic acid are utilized to
neutralize the oxidation byproducts of energy metabolism such as
those caused by free radicals. Vitamins C, E, and selenium are
similarly utilized for the neutralization of free radicals. If some
or all of these nutrient-dependent pathways becomes depleted,
increased mitochondrial toxicity leading to programmed cell death
is more likely to occur (Butte et al., Immunol. Today 15: 7-10
(1994)).
[0110] Furthermore, dietary supplementation with alpha-lipoic acid
or acetyl L-carnitine can possibly decrease the extent of
peripheral neuropathy occurring in diabetes mellitus or HIV
infection (Ziegler et al. Exp. Clin. Endocrinol. Diabetes 107:
421-30 (1999); Ziegler et al., Diabetes 46 Suppl 2: S62-66 (1997);
Scarpini et al., J. Peripher. Nerv. Syst. 2: 250-52 (1997);
Famularo et al., J. Peripher. Nerv. Syst. 3: 227-29 (1998)).
Vitamin B6 has also been studied as an treatment intervention for
carpal tunnel syndrome, which also is a form of neuropathy
(Bernstein et al., J. Am. Coll. Nutr. 12: 73-76 (1993)). Combining
effective amounts of at least one vitamin antioxidant, one mineral
antioxidant and at least three high potency antioxidants results
in, for example, cooperation enhancement of immune strength or
detoxification functions that leads to optimal performance of these
systems for enhanced treatment or reduction in the severity of
mitochondrial toxicities such as PN.
[0111] Other drug-induced mitochondrial toxicities include, for
example, hepatitis, anemia, peripheral neuropathy, pancreatitis,
cardiomyopathy, HIV protease inhibitor oxidative stress, oxidative
stress secondary to other HIV therapeutics and fat redistribution,
all of which are applicable for treatment with a nutrient
composition of the invention. Nutrient treatment for these and
other diseases can be administered alone or in combination with
another therapeutic drug regimen.
[0112] Mitochondrial toxicity induced by other insults or
conditions also can be treated with the nutrient compositions of
the invention. Administering a nutrient composition alone or in
combination with an applicable therapy will augment the immune
strength or detoxification functions of the recipient individual
including, for example, reducing mitochondrial oxidative stress,
oxidative damage or increasing energy production. Exemplary insults
or conditions other than drug induced processes that can result in
mitochondrial toxicity include, for example, radiation poisoning,
ischemic events, other acute events or chronic events. All of such
insults or conditions can result in, for example, mitochondrial
shock, oxidative stress or oxidative damage. Augmentation of immune
strength, detoxification functions or both can reduce the severity
of symptoms resulting from these occurrences by, for example,
increasing energy levels, promoting a balanced physiological state
or reducing free radical buildup.
[0113] Therefore, the invention provides a method of augmenting a
therapeutic treatment of a disease. The method consists of
administering to an individual a nutrient composition of the
invention one or more times a day over a period of about 5-7 weeks,
wherein immune system function is stimulated to result in an
increase of CD4.sup.+ cells of at least about 15% compared to
pre-administration levels.
[0114] The invention also provides a method of augmenting a
therapeutic treatment of a disease comprising administering to an
individual a composition of the invention one or more times a day
over a period of about 5-7 weeks, wherein a physiological
detoxification function is stimulated to result in a decrease of
one or more free radical markers by about 20% compared to
pre-administration levels.
[0115] The nutrient compositions useful in the methods of the
invention include an optimal combination of an effective amount of
at least one vitamin antioxidant, at least one mineral antioxidant
and a highly saturable amount of at least three high potency
antioxidants. The at least one vitamin antioxidant can be vitamin
C, bioflavonoid complex, vitamin E, vitamin B6 or beta-carotene and
the at least one mineral antioxidant can be zinc or selenium. The
at least three high potency antioxidants can be alpha lipoic acid,
acetyl L-carnitine, N-aceytl-cysteine, co-enzyme Q10 or
glutathione. Nutrient compositions useful in the methods of the
invention also include an optimal combination of an effective
amount of at least three vitamin antioxidants, at least two mineral
antioxidants and a highly saturable amount of at least three high
potency antioxidants. The at least three vitamin antioxidants can
be three vitamins selected from vitamin C, bioflavonoid complex,
vitamin E, vitamin B6 or beta-carotene. The at least two mineral
antioxidant can be zinc and selenium and the at least three high
potency antioxidants can be three antioxidants selected from alpha
lipoic acid, acetyl L-carnitine, N-aceytl-cysteine, co-enzyme Q10
or glutathione. Purity levels of the nutrient compositions can be
99% or greater by total weight. Further provided is a nutrient
composition useful in the methods of the invention that consists of
an optimal combination of an effective amount of vitamin C,
bioflavonoid complex, vitamin E, zinc, selenium, alpha lipoic acid,
acetyl L-carnitine and N-aceytl-cysteine.
[0116] Augmentation of therapeutic treatment provided by the
invention include treatments for immune-mediated disease, cancer,
heart disease, chronic fatigue syndrome, neurodegenerative diseases
or an infectious disease. Specific examples of such disorders or
diseases include multiple sclerosis, lupus, rheumatoid arthritis,
scleroderma, coronary artery disease, atherosclerotic vessel
disease, Madalung's disease, neoplastic conditions, solid tumor
malignancies, non-solid malignancies, Alzheimer's disease,
Parkinson's disease, infectious hepatitis, toxic hepatitis,
drug-induced hepatitis, herpes, human immunodeficiency virus (HIV)
infection or acquired immunodeficiency syndrome (AIDS) as well as
for the promotion of longevity in normal or diseased
individuals.
[0117] It is understood that modifications which do not
substantially affect the activity of the various embodiments of
this invention are also included within the definition of the
invention provided herein. Accordingly, the following examples are
intended to illustrate but not limit the present invention.
EXAMPLE I
Nutrient Supplementation Treatment in Patients with Peripheral
Neuropathy Induced by Stavudine or Didanosine Antiviral Therapy
[0118] This Example shows the effectiveness and non-toxicity of a
broad-spectrum, nutrient treatment for medication-induced
peripheral neuropathy in HIV-infected patients.
[0119] A clinical study was performed to assess the beneficial
effects of an antioxidant, multinutrient formula designed to lessen
the systemic clinical effects of mitochondrial toxicity, including
symptoms of PN, in HIV-infected individuals undergoing a stable,
D-drug-containing highly active antiretroviral therapy (HAART). The
design of the study consisted of a randomized, double-blind,
placebo-controlled, clinical trial to assess the use of nutrient
supplementation compared to a placebo in the treatment of stavudine
and/or didanosine-induced peripheral neuropathy in patients with
HIV infection. A 1:1 randomized patient to placebo ratio was
analyzed using a total of 40 patients that were enrolled in the
study.
[0120] HIV-infected patients enrolled in the study were required to
meet several inclusion criteria. In contrast, a number of exclusion
criteria prevented HIV-infected individuals from enrolling in the
clinical study. There were seven inclusion criteria for selecting
individuals for enrollment. These inclusion criteria required
enrollees to have: (1) an active HIV infection, where positive
diagnosis of HIV was based on the medical history, clinical signs
and symptoms, or results of laboratory testing; (2) a CD4.sup.+
cell count greater or equal to 100 cells/mm.sup.3; (3) the presence
of lower extremity peripheral neuropathy, based on history and
physical exam since starting to take stavudine and/or didanosine;
(4) receiving current treatment with the antiviral therapeutics
stavudine (D4T), didanosine (DDI) or both; (5) at least 18 years of
age; (6) women of child bearing potential were required to have a
negative pregnancy test within two weeks prior to randomization and
agree to practice barrier method birth control during the study
period, and (7) willingness and ability to sign an informed consent
statement and to comply with the protocol.
[0121] There were 11 exclusion criteria that prevented HIV-infected
individuals from enrollment in the clinical study. These exclusion
criteria removed potential enrollees from consideration where the
individual: (1) had a known allergy or intolerance to any nutrient
supplements contained in the nutrient composition; (2) was
pregnant; (3) was undergoing active treatment for an acute
opportunistic infection or malignancy, except for non-systemic
treatment of Kaposi's Sarcoma; (4) had a CD4.sup.+ cell count of
less than 100 cells/mm.sup.3; (5) exhibited vitamin B12 deficiency;
(6) exhibited an alanine aminotransferase (ALT) greater than
10.times. the normal range; (7) had serum creatinine greater than
or equal to 2.0 mg/dL; (8) was receiving recombinant human growth
hormone therapy during the previous week, during the period of the
clinical study or those on prior therapy unable to "wash out"
during the period between the screening and baseline visits; (9)
was receiving any pharmacologic treatment for peripheral neuropathy
during the previous week or unable to "wash out" prior to baseline
measurements, including both prescription and
non-prescription-strength non-steroidal anti-inflammatory drugs
(NSAIDS), narcotic and non-narcotic analgesics, tricyclic
antidepressants, and anticonvulsant medications such as gabapentin
(Neurontin); (10) was receiving acupuncture and/or massage therapy,
specifically to treat peripheral neuropathy symptoms, during the
previous four weeks, and (11) was receiving current nutrient or
herbal supplements greater than one multivitamin pill per day.
[0122] Patients enrolled in the study received one nutrient packet
twice daily at the beginning of a meal. Each nutrient packet
included: (1) a multivitamin composition; (2) a multimineral
composition; (3) vitamin B6 at 130 mg; (4) acetyl L-carnitine at
500 mg; (5) alpha-lipoic acid at 200 mg; (6) N-acetyl cysteine at
600 mg. Each placebo nutrient packet included an identical
appearing packet of placebo capsules.
[0123] Several quantitative and qualitative criteria were evaluated
to assess the efficacy of the nutrient compositions following
administration. Briefly, changes in pain intensity at 4, 8, and 12
weeks of treatment were assessed by the Neuropathy Inventory Linear
Analog Scale (NILAS). Changes in quality of life at 4, 8, and 12
weeks of treatment were assessed by both the Linear Analog Scale
Assessment (LASA) and the Medical Outcomes HIV Health Survey
(MOS-HIV). Similarly, changes in the neurological examination at 4,
8, and 12 weeks of treatment were assessed by the Neurologic
Examination Assessment Tool (NEAT). The percentage of patients in
each group able to continue their original antiviral medications at
4, 8, and 12 weeks of treatment was another criteria evaluated as
was the percentage of patients in each group able to avoid taking
prescription strength pain medications at each of these time
periods. Finally, changes in metabolic and immunologic measurements
including, for example, CD4.sup.+ cell count, HIV RNA, fasting
plasma lactate, fasting lipid panel, fasting insulin level, fasting
glucose level, and liver function tests in each group also were
measured at 4, 8, and 12 week intervals following initiation of
treatment.
[0124] Forty (40) patients were actually enrolled in the study. All
patients exhibited symptomatic peripheral neuropathy and were
undergoing either stavudine or didanosine therapy. This group was
randomly assigned to ingest either a nutrient composition as
described below or a placebo packet twice daily. The duration of
nutrient treatment lasted 12 weeks in double blinded fashion at
four research centers in the US. The baseline or nutrient
pretreatment characteristics of the patients taking either the
nutrient composition or a placebo are shown below in Table 1. A
description of the test parameters and methods are described
further below in conjunction with the results of the study.
1TABLE 1 Baseline Demographics and Clinical Characteristics Placebo
Nutrients Composition Variable (n = 22) (n = 18) Mean age 46.6 45.6
Mean CD4 count (cells) 467 357 Viral load (log10) 2.4 2.3 On
Stavudine (D4T) (%) 54% 66% On Didanosine (DDI) (%) 23% 17% On Both
(D4T and DDI) (%) 23% 17% Neuropathy Score (0 to 100) {NILAS} 57 52
(100 = severe neuropathy symptoms) QOL Score (0 to 100) {LASA} 42
48 (100 = ideal energy & QOL)
[0125] Implementation of the study required patients to continue
therapy with a stable HAART regimen and also not to consume any
nutrients other than those administered in excess of one low-dose
multivitamin pill per day. The nutrient composition tested included
substantial daily dosages of 3 potent antioxidants. These potent
antioxidants were acetyl L-carnitine at 1,000 mg/day, N-acetyl
cysteine at 1,200 mg/day and alpha lipoic acid at 400 mg/day. The
composition also contained a variety of other vitamins and minerals
all in excess of the suggested RDA requirements. The complete
formulation and total daily dose of the nutrient composition is
shown below in Table 2.
[0126] The nutrient compositions were manufactured according to the
dry weights specified in FIG. 1. Manufacturing fillers, binders or
lubricants, such as stearates, palmitates or other substances which
can be inhibitory to absorption, bioavailability or tolerance of
compounds in individuals, were omitted from the nutrient
compositions. Purity levels of the nutrient compositions were about
99 percent of total weight of the formulation.
[0127] Patients were assessed over a 12 week treatment for the
quantitative and qualitative indicators described previously.
Measurements or observations occurred at four-week intervals
throughout the course of the study. Statistical analyses were
executed using two sided t-tests with an alpha level of 0.05. No
adjustments were made for multiple comparisons and missing values
were imputed using a last-observation-carried-forward method.
2TABLE 2 Nutrient Composition (Total Daily Dosages)
Multivitamin/Multimineral Beta Carotene 20,000 i.u. Calcium 800 mg
Vitamin C 600 mg Iron 18 mg Vitamin D 400 i.u. Iodine 150 mcg
Vitamin E 800 i.u. Magnesium 400 mg Vitamin B1 60 mg Zinc 30 mg
Vitamin B2 60 mg Selenium 200 mcg Vitamin B6 260 mg Copper 2.0 mg
Niacinamide 60 mg Manganese 10 mg Folic acid 800 mcg Chromium 100
mcg Vitamin B12 2.5 mg Molybdenum 300 mcg Biotin 50 mcg Choline 60
mg Inositol 60 mg Glutamic acid 100 mg Pantothenic acid 60 mg Boron
2.0 mg Potassium 99 mg Betaine HCL 150 mg Vitamin A 8,000 i.u.
Bioflavinoid complex 300 mg Additional Antioxidants Alpha lipoic
Acid 400 mg N-acetyl cysteine 1200 mg (NAC) Acetyl L-camitine 1000
mg
[0128] Results obtained for the primary and secondary endpoint
measurements are described below. Briefly, the effect of nutrient
treatment on Neuropathy Inventory Linear Analog Scale (NILAS) was
assessed. The NILAS tool assesses pain intensity on a visual analog
scale. The responses to each of three questions were transformed to
a 0-100 scale such that a higher score indicates more pain. Each
question was reported individually and the mean of the three
questions was calculated to form an overall score. The results from
this study indicate that the invention diminished the overall
symptoms of peripheral neuropathy (pain, numbness, paresthesias) by
41.5% from baseline (on-treatment analysis).
[0129] Also assessed was the effect of nutrient treatment on
quality of life using Linear Analog Scale Assessment (LASA). The
LASA tool assesses quality of life as measured on a visual analog
scale. The responses to each of three questions were transformed to
a 0-100 scale such that a higher score indicates a higher quality
of life. Each question was reported individually and the mean of
the three questions was calculated to form an overall score. The
results from this study indicate that the invention improved the
overall quality of life (energy level, daily activities, overall
quality of life) by 29% from baseline (on-treatment analysis). The
results indicate that HIV-infected individuals with long standing
PN showed substantial improvements in both linear pain scale and
quality of life measurements (41.5% and 29%, respectively) during
twelve weeks of taking this micronutrient formula. A statistically
significant difference from placebo was not revealed, possibly due
to a small sample size.
[0130] The effect nutrient treatment on HIV viral load as
determined by HIV RNA measurements was also assessed. Viral RNA was
measured by a commercial diagnostic service (Immunodiagnostic
Laboratories (San Leandro, Calif.)). Table 3 shows the mean change
in HIV RNA at the measured time points compared to pretreatment
measurements. The patients receiving treatment with the nutrient
composition showed a trend toward decreasing HIV RNA over twelve
weeks of taking this nutrient formula. Specifically, patients
taking the nutrient composition experienced a decline of about
4,755 copies in HIV RNA viral load compared to an increase of about
7,412 copies in HIV RNA viral load in patients taking the placebo.
A statistically significant difference from placebo was not
revealed, possibly due to a small sample size.
3TABLE 3 Effect of Nutrient Composition on HIV RNA Viral Load On
Treatment Day 1 Week 4 Week 8 Week 12 Mean Change in HIV RNA 0 8494
7389 7412 (placebo) Mean Change in HIV RNA 0 -5135 -477 -4755
(nutrients)
[0131] The effect of nutrient treatment on CD4.sup.+ cell count was
also assessed. One CD4.sup.+ cell measurement determined the change
in total number of CD4.sup.+ cells at the indicated treatment
points compared to CD4.sup.+ cell numbers prior to treatment.
Briefly, the total CD4.sup.+ cell count was determined by
immunoaffinity binding performed by a commercial service
(Immunodiagnostic Laboratories (San Leandro, Calif.)). Table 4
shows the results of these measurements and indicate that the
patients taking the nutrient composition sustained a 64 cell rise
in absolute CD4.sup.+ cell counts when compared to a 13 cell rise
in patients taking the placebo.
4TABLE 4 Effect of Nutrient Composition on Absolute CD4.sup.+ Cell
Counts On Treatment Day 1 Week 4 Week 8 Week 12 Mean Change in CD4
Count 0 -15 -5 13 (placebo) Mean Change in CD4 Count 0 44 68 64
(nutrients)
[0132] Another CD4.sup.+ cell assessment calculated the percent
change in CD4.sup.+ cells compared to pretreatment values.
CD4.sup.+ cells were determined as described above for FIG. 7.
Results showing a mean change percentage of CD4.sup.+ cell compared
to baseline levels are shown in Table 5 below. The nutrient treated
group showed a steady and statistically significant rise in CD4
counts over twelve weeks. Patients taking this nutrient composition
had an average increase of 26% in their CD4.sup.+ cell counts
compared to 2% in those taking a placebo (p<0.03 OT).
5TABLE 5 Mean Change from Baseline in CD4 (%) CD4 increase from
baseline (%) Time Point Placebo Nutrient Composition Baseline -- --
Week 4 <1 14 Week 8 <1 20 Week 12 2 26 (p < 0.05)
[0133] The effects of nutrient treatment on fasting lipids,
glucose, serum lactate and ALT levels were also assessed. Each of
these tests represent direct and indirect measurements of metabolic
toxicities which can be seen as a result of either HIV disease,
antiretroviral therapy, or both. In this study, they were measured
to identify a potentially positive or negative effect of the
invention on each parameter. The study results indicated that all
of these parameters (fasting lipids, insulin, glucose, serum
lactate and ALT) were not adversely affected in patients taking the
nutrient composition.
[0134] The overall tolerability of the nutrient compositions
described above was also determined. The results indicate that
daily administration of the nutrient composition over a 12 week
course of treatment is safe for HIV-infected patients who are
taking D4T, DDI or both antiretroviral therapeutics. There were two
adverse events reported which occurred in the treatment group.
These events were bacterial pneumonia and a cystic lithiasis.
However, both were judged unrelated to the nutrient treatment and
both patients recovered uneventfully. Of note was that there were
no reported gastrointestinal (GI) side effects from the group
taking either the placebo or nutrient compositions.
[0135] Throughout this application various publications have been
referenced within parentheses. The disclosures of these
publications in their entireties are hereby incorporated by
reference in this application in order to more fully describe the
state of the art to which this invention pertains.
[0136] Although the invention has been described with reference to
the disclosed embodiments, those skilled in the art will readily
appreciate that the specific examples and studies detailed above
are only illustrative of the invention. It should be understood
that various modifications can be made without departing from the
spirit of the invention. Accordingly, the invention is limited only
by the following claims.
* * * * *