U.S. patent application number 17/148448 was filed with the patent office on 2021-07-15 for compositions and methods for activating cellular signaling pathways.
This patent application is currently assigned to LifeVantage Corporation. The applicant listed for this patent is LifeVantage Corporation. Invention is credited to Christina Beer, Brian Dixon, Qiana Martinez.
Application Number | 20210213095 17/148448 |
Document ID | / |
Family ID | 1000005383746 |
Filed Date | 2021-07-15 |
United States Patent
Application |
20210213095 |
Kind Code |
A1 |
Dixon; Brian ; et
al. |
July 15, 2021 |
COMPOSITIONS AND METHODS FOR ACTIVATING CELLULAR SIGNALING
PATHWAYS
Abstract
Compositions and methods for increasing stress response and
improving health and slowing the aging process in a user. A
composition includes one or more of a first group consisting of
milk thistle, ashwagandha, green tea, bacopa monnieri, and
turmeric. The composition includes one or more of a second group
consisting of acetyl-L-carnitine, quercetin, lipoic acid, coenzyme
Q10, cysteine, and grape. The composition includes one or more of a
third group consisting of capsaicin, wasabi, olive leaf extract,
nicotinic acid, and copper gluconate.
Inventors: |
Dixon; Brian; (Sandy,
UT) ; Beer; Christina; (Sandy, UT) ; Martinez;
Qiana; (Sandy, UT) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
LifeVantage Corporation |
Sandy |
UT |
US |
|
|
Assignee: |
LifeVantage Corporation
Sandy
UT
|
Family ID: |
1000005383746 |
Appl. No.: |
17/148448 |
Filed: |
January 13, 2021 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
62960571 |
Jan 13, 2020 |
|
|
|
Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61K 2236/53 20130101;
A61K 9/0019 20130101; A61K 36/28 20130101; A61K 31/198 20130101;
A61K 31/05 20130101; A61K 31/221 20130101; A61K 31/465 20130101;
A61K 9/20 20130101; A61K 33/34 20130101; A61K 36/82 20130101; A61K
36/31 20130101; A61K 31/352 20130101; A61K 36/9062 20130101; A61K
31/122 20130101; A61K 31/385 20130101; A61K 36/53 20130101; A61K
31/353 20130101; A61K 9/48 20130101; A61K 36/81 20130101; A61K
31/165 20130101; A61K 36/63 20130101; A61K 36/9066 20130101; A61P
39/06 20180101; A61K 36/87 20130101 |
International
Class: |
A61K 36/9066 20060101
A61K036/9066; A61K 36/28 20060101 A61K036/28; A61K 36/81 20060101
A61K036/81; A61K 36/82 20060101 A61K036/82; A61K 36/53 20060101
A61K036/53; A61K 36/87 20060101 A61K036/87; A61K 36/63 20060101
A61K036/63; A61K 36/31 20060101 A61K036/31; A61K 31/221 20060101
A61K031/221; A61K 31/352 20060101 A61K031/352; A61K 31/385 20060101
A61K031/385; A61K 31/122 20060101 A61K031/122; A61K 31/198 20060101
A61K031/198; A61K 31/165 20060101 A61K031/165; A61K 31/465 20060101
A61K031/465; A61K 33/34 20060101 A61K033/34; A61K 31/05 20060101
A61K031/05; A61K 36/9062 20060101 A61K036/9062; A61K 31/353
20060101 A61K031/353; A61K 9/48 20060101 A61K009/48; A61P 39/06
20060101 A61P039/06; A61K 9/20 20060101 A61K009/20; A61K 9/00
20060101 A61K009/00 |
Claims
1. A composition comprising: one or more of a first group
consisting of milk thistle, ashwagandha, green tea, bacopa
monnieri, and turmeric; one or more of a second group consisting of
acetyl-1-carnitine, quercetin, lipoic acid, coenzyme Q10, cysteine,
and grape; and one or more of a third group consisting of
capsaicin, wasabi, olive leaf extract, nicotinic acid, and copper
gluconate.
2. The composition of claim 1, wherein one or more of: the milk
thistle extract is screened milk thistle extract; the ashwagandha
extract is screened ashwagandha extract, the green tea extract is
screened green tea extract; the bacopa monnieri extract is screened
bacopa monnieri extract, or the turmeric extract is screened
turmeric extract.
3. The composition of claim 1, wherein one or more of: the
quercetin has greater than or equal to 90% purity; the lipoic acid
has greater than or equal to 98% purity the coenzyme Q10 has
greater than or equal to 95% purity; or the grape extract is
screened grape.
4. The composition of claim 1, wherein the composition comprises
from 5 wt % to 10 % the ashwagandha and further comprises from 15
wt % to 35 wt % the acetyl-1-carnitine and further comprises from 2
wt % to 15 wt % the capsaicin.
5. The composition of claim 1, wherein the composition comprises
olive leaf extract, and wherein the olive leaf extract comprises
from 5 wt % to 20 wt % hydroxtyrosol.
6. The composition of claim 1, wherein the composition comprises an
effective amount of the one or more of the first group for
increasing activation of an Nrf2 pathway in a body.
7. The composition of claim 1, wherein the composition comprises an
effective amount of the one or more of the second group for
increasing activation of an NRF1 pathway in a body.
8. The composition of claim 1, wherein the composition comprises an
effective amount of the one or more of the third group for
increasing activation of an NAD pathway in a body.
9. The composition of claim 1, wherein the composition comprises
each component of the first group, and wherein the first group is
present in the composition in an effective amount for increasing
expression of each of an NQO1 gene in a body and a HMOX1 gene in
the body.
10. The composition of claim 1, wherein the composition comprises
each component of the second group, and wherein the second group is
present in the composition in an effective amount for increasing
expression of each of an Nrf1 gene in a body and a PCG1-alpha gene
in the body.
11. The composition of claim 1, wherein the composition comprises
each component of the third group, and wherein the third group is
present in the composition in an effective amount for increasing
expression of each of an NMNAT1 gene in a body and an NAMPT gene in
the body.
12. The composition of claim 1, wherein the composition comprises
an effective amount of the one or more of the first group for
reducing oxidative stress and increasing detoxification in a
body.
13. The composition of claim 1, wherein the composition comprises
multiple doses to be provided to a user, and wherein each of the
first group, the second group, and the third group comprises an
independent dose to be taken simultaneously or in succession by the
user.
14. The composition of claim 1, wherein the first group is an Nrf2
group for increasing activity of an Nrf2 pathway in a body, and
wherein the composition comprises: an effective amount of the milk
thistle; an effective amount of the ashwagandha; an effective
amount of the green tea; an effective amount of the bacopa
monnieri; and an effective amount of the turmeric for increasing
activity of the Nrf2 pathway in the body.
15. The composition of claim 14, wherein the composition comprises
an effective amount of the first group for increasing expression of
an NQO1 gene in the body and a HMOX1 gene in the body.
16. The composition of claim 1, wherein the second group is an NRF1
group for increasing activity of an NRF1 pathway in a body, and
wherein the composition comprises: an effective amount of the
acetyl-1-carnitine; an effective amount of the quercetin; an
effective amount of the lipoic acid; an effective amount of the
coenzyme Q10; an effective amount of the cysteine; and an effective
amount of the grape for increasing activity of the NRF1 pathway in
the body.
17. The composition of claim 16, wherein the composition comprises
an effective amount of the second group for increasing expression
of an Nrfl gene in the body and a PCG1-alpha gene in the body.
18. The composition of claim 1, wherein the third group is an NAD
group for increasing activity of an NAD pathway in the body, and
wherein the composition comprises: an effective amount of the
alpinia galanga; an effective amount of the wasabi; an effective
amount of the olive leaf extract; an effective amount of the
nicotinic acid; and effective amount of the copper gluconate for
increasing activity of the NAD pathway in the body.
19. The composition of claim 18, wherein the composition comprises
an effective amount of the third group for increasing expression of
an NMNAT1 gene in the body and an NAMPT gene in the body.
20. The composition of claim 1, wherein the composition comprises
the milk thistle, and wherein the milk thistle is screened milk
thistle extract 80 wt % silymarin.
21. The composition of claim 1, wherein the composition comprises
the green tea, and wherein the green tea is screened green tea
extract 45% epigallocatechin gallate (EGCG).
22. The composition of claim 1, wherein the composition comprises
the turmeric, and wherein the turmeric is screened turmeric
extract.
23. The composition of claim 1, wherein the composition comprise
one or more independent compositions each encapsulated in a
capsule.
24. The composition of claim 23, wherein the composition comprises
three or more independent capsules comprising a first capsule
comprising the one or more of the first group, a second capsule
comprising the one or more of the second group, and a third capsule
comprising the one or more of the third group.
25. The composition of claim 1, wherein the composition is prepared
for oral administration as a tablet.
26. The composition of claim 1, wherein the composition is prepared
for intravenous administration.
27. The composition of claim 1, wherein the composition is prepared
for intramuscular administration.
28. A method for slowing the effects of aging in a user by
improving stress response, the method comprising: providing a
composition to the user, wherein the composition comprises: one or
more of a first group consisting of milk thistle, ashwagandha,
green tea, bacopa monnieri, and turmeric; one or more of a second
group consisting of acetyl-1-carnitine, quercetin, lipoic acid,
coenzyme Q10, cysteine, and grape; and one or more of a third group
consisting of capsaicin, wasabi, olive leaf extract, nicotinic
acid, and copper gluconate.
29. The method of claim 28, wherein one or more of: the composition
comprises each component of the first group, and wherein the first
group is present in the composition in an effective amount for
increasing expression of each of an NQO1 gene in a body and a HMOX1
gene in the body; the composition comprises each component of the
second group, and wherein the second group is present in the
composition in an effective amount for increasing expression of
each of an Nrf1 gene in a body and a PCG1-alpha gene in the body;
or the composition comprises each component of the third group, and
wherein the third group is present in the composition in an
effective amount for increasing expression of each of an NMNAT1
gene in a body and an NAMPT gene in the body.
30. A composition comprising: an effective amount of a first group
for increasing expression of each of an NQO1 gene in a body and a
HMOX1 gene in the body, wherein the first group comprises milk
thistle, ashwagandha, green tea, bacopa monnieri, and turmeric; an
effective amount of a second group for increasing expression of an
Nrf1 gene in the body and a PCG1-alpha gene in the body, wherein
the second group comprises acetyl-1-carnitine, quercetin, lipoic
acid, coenzyme Q10, cysteine, and grape leaf extract; and an
effective amount of a third group for increasing expression of an
NMNAT1 gene in the body and an NAMPT gene in the body, wherein the
third group comprises capsaicin, wasabi, olive leaf extract,
nicotinic acid, and copper gluconate.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority to U.S. Provisional Patent
Application Ser. No. 62/960,571 filed Jan. 13, 2020 titled
"COMPOSITIONS AND METHODS FOR ACTIVATING CELLULAR SIGNALING
PATHWAYS," which is incorporated herein by reference in its
entirety, including but not limited to those portions that
specifically appear hereinafter, the incorporation by reference
being made with the following exception: In the event that any
portion of the above-referenced application is inconsistent with
this application, this application supersedes the above-referenced
application.
TECHNICAL FIELD
[0002] The disclosure relates generally to compositions of matter
and particularly relates to compositions for activating cellular
signaling pathways.
BACKGROUND
[0003] Stress response is the collection of cellular and
physiological changes that occur in response to exposure to a
stressor. A stressor can be broadly defined as a chemical,
biological, environmental, mental, or other internal or external
stimuli with the potential to cause a threat to an organism' s
homeostasis, well-being, and long-term survival.
[0004] Stressors can be direct, indirect, or perceived. Examples of
direct stressors include: cold, heat, toxins, biological agents,
oxygen deprivation, physical damage/wounds, compromised cellular
function, abnormal physiology (e.g., high/low blood pressure,
abnormal blood glucose, hormone fluctuations, cholesterol levels,
pH, redox status, etc.), exercise, smoking, tobacco, alcohol,
drugs, medications, being underweight, being overweight, noise,
light, dark, overcrowding, sustained physical or mental exertion,
illness, oxidative stress, cellular damage, mutated DNA, and low
cellular energy status. Examples of indirect stressors include past
traumatic events, major life changes, environmental factors,
unpredictable events, workload, social situations,
personal/societal beliefs, psychological factors, and financial,
divorce, bereavement, unhappiness, and dangerous situations.
Examples of perceived stressors include worry or anticipatory
stress, fear, lack of control, insecurity, uncertainty, perception,
and expectations.
[0005] Exposure to any stressor can manifest itself beyond its
direct effects. For example, mammals are known to experience
headache, fatigue, disturbed sleep, difficulty concentrating,
disrupted digestion, and irritability in response to short-term
stress. Long-term exposure to stress can lead to depression, high
blood pressure, abnormal heartbeat, atherosclerosis, heart disease,
heartburn, ulcers, irritable bowel syndrome, upset stomach, cramps,
constipation, diarrhea, weight gain or weight loss, altered sex
drive, fertility issues, asthma, arthritis, and skin problems such
as acne, eczema, psoriasis, and other chronic degenerative
diseases.
[0006] Because adequately responding to stressors of all types is
essential to maintain health, combat disease, and ultimately
maintain homeostasis for healthy longevity, organisms have
developed extensive networks of biological processes to return to,
and maintain, homeostasis. The essential character of these
biological processes are conserved evolutionarily from prokaryotes
to all eukaryotes including mammals and humans. Collectively, these
biological processes are known as an organism's stress response.
This stress response can result in the release of hormones, altered
physiology, and the activation of so-called "survival genes." The
ultimate goal of a stress response is to alleviate the stressor and
return the organism to homeostasis.
[0007] Cellular signaling pathways are at the core of the body's
stress responses. Cells, tissues, and organs are in a constant
state of communication. Communication can be facilitated by direct
connections via nerves or indirect connections by signaling
pathways. Signaling within the cell, or throughout the body, can be
carried out by hormones and other signaling molecules that travel
the body by way of an intricate network of internal cellular
pathways. In some instances, these cellular signaling pathways can
be triggered or upregulated by certain compositions and methods.
This, in turn, activates the stress response pathways in a user to
promote health and slow the effects of aging.
[0008] In light of the foregoing, disclosed herein are compositions
and methods for activating stress response pathways in a user to
promote health and slow the effects of aging.
BRIEF DESCRIPTION OF THE DRAWINGS
[0009] Non-limiting and non-exhaustive implementations of the
present disclosure are described with reference to the following
figures, wherein like reference numerals refer to like parts
throughout the various views unless otherwise specified. Advantages
of the present disclosure will become better understood with regard
to the following description and accompanying drawings where:
[0010] FIG. 1 is a diagram of the Nrf2 pathway for inducing gene
expression to generate antioxidants and/or detoxification
enzymes;
[0011] FIG. 2 is a diagram of the NRF1 pathway for inducing gene
expression of the Nrf1 gene and/or the PGC1 gene to regulate
metabolic activity;
[0012] FIG. 3 is a diagram of the NAD biosynthetic and salvage
pathways for regulating the production of NAD and the NAD+/NADH
ratio;
[0013] FIG. 4A is a bar graph illustrating the percent increase in
expression of the NQO1 gene three hours after administration of the
Nrf2 composition and the combination composition as disclosed
herein;
[0014] FIG. 4B is a bar graph illustrating the percent increase in
expression of the HMOX1 gene three hours after administration of
the Nrf2 composition and the combination composition as disclosed
herein;
[0015] FIG. 5A is a bar graph illustrating the percent increase in
expression of the Nrf1 gene three hours after administration of the
NRF1 composition and the combination composition as disclosed
herein;
[0016] FIG. 5B is a bar graph illustrating the percent increase in
expression of the hPGC1-alpha gene three hours after administration
of the NRF1 composition and the combination composition as
disclosed herein;
[0017] FIG. 6A is a bar graph illustrating the percent increase in
expression of the NMNAT1 gene three hours after administration of
the NAD composition and the combination composition as disclosed
herein;
[0018] FIG. 6B is a bar graph illustrating the percent increase in
expression of the NAMPT gene three hours after administration of
the NAD composition and the combination composition as disclosed
herein;
[0019] FIG. 7A is a bar graph illustrating the percent increase in
expression of the NQO1 gene 24 hours after administration of the
Nrf2 composition and the combination composition as disclosed
herein;
[0020] FIG. 7B is a bar graph illustrating the percent increase in
expression of the HMOX1 gene 24 hours after administration of the
Nrf2 composition and the combination composition as disclosed
herein;
[0021] FIG. 8A is a bar graph illustrating the percent increase in
expression of the Nrf1 gene 24 hours after administration of the
NRF1 composition and the combination composition as disclosed
herein;
[0022] FIG. 8B is a bar graph illustrating the percent increase in
expression of the hPGC1-alpha gene 24 hours after administration of
the NRF1 composition and the combination composition as disclosed
herein;
[0023] FIG. 9A is a bar graph illustrating the percent increase in
expression of the NMNAT1 gene 24 hours after administration of the
NAD composition and the combination composition as disclosed
herein;
[0024] FIG. 9B is a bar graph illustrating the percent increase in
expression of the NAMPT gene 24 hours after administration of the
NAD composition and the combination composition as disclosed
herein;
[0025] FIG. 10 is a bar graph illustrating expression of the
hPGC1-alpha gene three hours and 24 hours after administration of a
control, an NRF1 composition, a theacrine combination composition,
an alpinia galanga combination composition, a capsaicin combination
composition, and a mango leaf extract combination composition as
disclosed herein;
[0026] FIG. 11 is a bar graph illustrating expression of the hHMOX1
gene three hours and 24 hours after administration of a control, an
Nrf2 composition, a theacrine combination composition, an alpinia
galanga combination composition, a capsaicin combination
composition, and a mango leaf extract combination composition as
disclosed herein;
[0027] FIG. 12 is a bar graph illustrating expression of the
hNMNAT1 gene three hours and 24 hours after administration of a
control, a theacrine NAD composition, a theacrine combination
composition, an alpinia galanga combination composition, a
capsaicin combination composition, and a mango leaf extract
combination composition as disclosed herein;
[0028] FIG. 13 is a bar graph illustrating expression of the hNAMPT
gene three hours and 24 hours after administration of a control, a
theacrine NAD composition, a theacrine combination composition, an
alpinia galanga combination composition, a capsaicin combination
composition, and a mango leaf extract combination composition as
disclosed herein;
[0029] FIG. 14 is a bar graph illustrating expression of the
hNMNST1 gene three hours and 24 hours after administration of a
control, a theacrine NAD composition, a theacrine combination
composition, an alpinia galanga combination composition, a
capsaicin combination composition, and a mango leaf extract
combination composition as disclosed herein; and
[0030] FIG. 15 is a bar graph illustrating expression of the hNQO1
gene three hours and 24 hours after administration of a control, an
Nrf2 composition, a theacrine combination composition, an alpinia
galanga combination composition, a capsaicin combination
composition, and a mango leaf extract combination composition as
disclosed herein.
DETAILED DESCRIPTION
[0031] Disclosed herein are compositions and methods for activating
cellular signaling pathways to maintain health and ameliorate the
effects of aging. Embodiments of the disclosure are particularly
useful for activating the Nrf2 (nuclear factor erythroid 2-related
factor 2) pathway, the NRF1 (nuclear factor erythroid 2-related
factor 1) pathway, and the NAD (nicotinamide adenine dinucleotide)
pathway in a body. These pathways are associated with stress
response processes in a body and can be activated to ameliorate the
effects of environmental and physiological stressors.
[0032] Stress response is the collection of cellular and
physiological changes that occur in response to exposure to a
stressor. A stressor can be broadly defined as a chemical,
biological, environmental, mental, or other internal or external
stimuli with the potential to cause a threat to an organism' s
homeostasis, well-being, and long-term survival.
[0033] Stressors can be direct, indirect, or perceived. Examples of
direct stressors include: cold, heat, toxins, biological agents,
oxygen deprivation, physical damage/wounds, compromised cellular
function, abnormal physiology (e.g., high/low blood pressure,
abnormal blood glucose, hormone fluctuations, cholesterol levels,
pH, redox status, etc.), exercise, smoking, tobacco, alcohol,
drugs, medications, being underweight, being overweight, noise,
light, dark, overcrowding, sustained physical or mental exertion,
illness, oxidative stress, cellular damage, mutated DNA, and low
cellular energy status. Examples of indirect stressors include past
traumatic events, major life changes, environmental factors,
unpredictable events, workload, social situations,
personal/societal beliefs, psychological factors, and financial,
divorce, bereavement, unhappiness, and dangerous situations.
Examples of perceived stressors include worry or anticipatory
stress, fear, lack of control, insecurity, uncertainty, perception,
and expectations.
[0034] Exposure to any stressor can manifest itself beyond its
direct effects. For example, mammals are known to experience
headache, fatigue, disturbed sleep, difficulty concentrating,
disrupted digestion, and irritability in response to short-term
stress. Long-term exposure to stress can lead to depression, high
blood pressure, abnormal heartbeat, atherosclerosis, heart disease,
heartburn, ulcers, irritable bowel syndrome, upset stomach, cramps,
constipation, diarrhea, weight gain or weight loss, altered sex
drive, fertility issues, asthma, arthritis, and skin problems such
as acne, eczema, psoriasis, and other chronic degenerative
diseases.
[0035] Because adequately responding to stressors of all types is
essential to maintain health, combat disease, and ultimately
maintain homeostasis for healthy longevity, organisms have
developed extensive networks of biological processes to return to,
and maintain, homeostasis. The essential character of these
biological processes are conserved evolutionarily from prokaryotes
to all eukaryotes including mammals and humans. Collectively, these
biological processes are known as an organism's stress response.
This stress response can result in the release of hormones, altered
physiology, and the activation of so-called "survival genes." The
ultimate goal of a stress response is to alleviate the stressor and
return the organism to homeostasis.
[0036] A robust stress response is essential to maintain health,
combat disease, and for healthy aging. For many organisms, a loss
of stress response and/or the aging process can be a painful and
uncomfortable process and may be undesirable. Therefore, there is a
desire to effectively maintain a robust stress response through
biological, chemical, and nutritional intervention.
[0037] Cellular signaling pathways are at the core of the body's
stress responses. Cells, tissues, and organs are in a constant
state of communication. Communication can be facilitated by direct
connections via nerves or indirect connections by signaling
pathways. Signaling within the cell, or throughout the body, can be
carried out by hormones and other signaling molecules that travel
the body by way of an intricate network of internal cellular
pathways.
[0038] Signaling within a cell begins when a certain signaling
molecule comes in contact with a corresponding receptor. To
facilitate understanding, the signaling molecule can be analogized
to a key and the receptor molecule can be analogized to a lock. The
signaling molecule and the receptor molecule may physically pair
with one another, and this causes the receptor molecule to be
activated. The act of activating the receptor molecule may be
analogized to turning the key (the signaling molecule) within the
lock (the receptor molecule). An activated receptor molecule begins
a chain of signaling events within the cell. The end result of the
chain of signaling events is a response to the initial signaling
molecule.
[0039] One purpose of cellular signaling pathways is to enable a
body to respond and adapt to its environment. This adaptive
response can happen on a micro scale within a cell. One example of
a body adapting to its environment is a body that has hyper
activated its detoxification cellular signaling pathways in
response to heavy alcohol consumption. A frequent consumer of
alcohol can likely consumer greater quantities of alcohol when
compared with a person who has never consumed alcohol. This is
because the frequent consumer of alcohol has hyper-activated
detoxification cellular signaling pathways as a result of continued
exposure to alcohol.
[0040] There are many cellular signaling pathways that are
activated or stalled in response to a cell's environmental
conditions. Examples include healing damaged tissues, triggering
cells to divide, nerve function, overall metabolism, and triggering
the body's immune response to bacteria or viruses. As a result, the
body's overall physiology is controlled through cellular signaling
pathways on the cellular level.
[0041] Cellular signaling pathways begin with activation of a first
signaling molecule. The first signaling molecule activates a second
signaling molecule after the first signaling molecule is activated
by the appropriate receptor molecule. The second signaling molecule
then activates the third signaling molecule after the second
signaling molecule is activated by the appropriate receptor
molecule. This process continues until the final signaling molecule
is activated and enters the nucleus of the cell. The nucleus of the
cell houses the DNA (deoxyribonucleic acid) of an organism. When
the final signaling molecule enters the nucleus, the final
signaling molecule can activate or deactivate specific genes within
the DNA.
[0042] Genes are instructions for the cell to generate a protein or
other molecule. For example, genes may instruct a cell to create
collagen in furtherance of holding skin together, proteins for
shuttling nutrients into the cell, proteins responsible for
generating energy, proteins for eliminating toxins, proteins for
controlling blood flow, enzymes for defending the cell, and so
forth. The cellular signaling pathways that cause proteins and
other molecules to be created are essential for the organism's
survival. In young and/or otherwise healthy organisms, these
cellular signaling pathways work efficiently and correctly and
allow for robust adaptation to environmental challenges. As the
organism falls out of optimal health and/or ages, these cellular
signaling pathways begin to work less efficiently and become less
adaptive to environmental changes.
[0043] Aging is a complex process driven by diverse changes in
genetic, molecular, biochemical, and cellular events in a body. The
process of aging is ultimately characterized by a gradual decline
in physiological functions. There are currently numerous theories
on aging and why aging occurs. Various theories hypothesize that
aging occurs due to loss of cellular communication, psychosocial
changes, biochemical changes, molecular changes, or loss of
cellular function. However, no one theory of aging can account for
all changes that are known to occur with age. It is likely that
numerous theories on aging are correct. Aging likely progresses due
to an additive effect of numerous contributing factors.
[0044] One theory of aging encompasses many of the known
biochemical, molecular, and cellular theories of aging. This theory
is referred to as the "loss of stress response theory." The loss of
stress response theory indicates that a young individual can
successfully sense and respond to stress more effectively than
older counterparts. To date, the loss of stress response theory is
the most unifying theory of aging and encompasses many of the
changes known to occur in an aging body.
[0045] There are many theories on why bodies age. Many of the
theories seem unrelated, but one common unifier is the decline in
the effectiveness of stress cellular signaling pathways. To date,
there are currently three theories of aging that have been the most
extensively studied, including the oxidative stress theory of
aging, the mitochondrial theory of aging, and the sirtuin theory of
aging. While seemingly disjoined, all three of these theories of
aging includes a cellular signaling component. As a body ages, the
body's cellular signaling pathways fail to react to respective
stimuli and signaling responses are attenuated when compared with
younger bodies.
Oxidative Stress Theory Of Disease And Aging And The Nrf2
Pathway
[0046] The oxidative stress theory of aging states that as a body
ages, the body accumulates free radicals and other oxidants. If
left unchecked, oxidative stress can have serious consequence for
the cell. Oxidative stress can ultimately lead to oxidative damage
by attacking and damaging essential biological structures in the
cell and compromising cellular function.
[0047] Antioxidants are the cell's primary defense against free
radicals and other oxidants. There are two major classes of
antioxidants, including: dietary antioxidants obtained through food
and nutritional supplements; and endogenous antioxidants produced
by the body. However, in rigorous trials of antioxidant supplements
in large numbers of people have not found that high doses of
antioxidant supplements prevent disease.
[0048] Endogenous antioxidants are created by the body and serve as
the primary line of defense against oxidative stress. In general,
endogenous antioxidants prevent free radicals and oxidants from
being formed or remove free radicals and oxidants from the body.
Endogenous antioxidants form a complex network of antioxidant
metabolites and enzymes. These networks work together through the
cell to neutralize free radicals and oxidants and protect important
biological structures from oxidative damage. While most dietary
antioxidants can only be used once, endogenous antioxidants can
neutralize numerous oxidants because they are constantly
regenerated back to their "active" or reduced state. This can be
accomplished by a redox cycle occurring within the cell.
[0049] Endogenous antioxidants can be upregulated in times of
increasing oxidative stress. The primary transcription factor
responsible for upregulating endogenous antioxidant and
detoxification pathways is Nrf2. Nrf2 is known as the nuclear
factor erythroid 2-related factor 2 or alternatively as the nuclear
factor erythroid-derived 2-like 2. Nrf2 is a transcription factor
that in humans is encoded by the NFE2L2 gene. Nrf2 is a basic
leucine zipper (bZIP) protein that regulates the expression of
antioxidant proteins that protect against oxidative damage
triggered by injury and inflammation. The Nrf2 cellular signaling
pathway triggers activation of Nrf2 and thereby triggers the
generation of endogenous antioxidant and detoxification pathways.
Under times of normal or low oxidative stress, Nrf2 is normally
found anchored to another protein in the cell membrane called KEAP1
(Kelch-like ECH-associated protein 1). During times of oxidative
stress, oxidants, and other electrophiles release Nrf2 from KEAP1.
Nrf2 then translocates to the nucleus of the cell where it binds a
promoter sequence to ultimately activate target antioxidant and
detoxification genes. As a body ages, the activity of the Nrf2
cellular signaling pathway decreases in its ability to sense
oxidative and toxicological threats and ultimately upregulate the
target genes.
Mitochondrial Theory Of Disease And Aging And The NRF1 Pathway
[0050] Another major theory of aging is the mitochondrial theory of
aging. Mitochondria are essential for cellular function. It is
estimated that about 95% of the energy a body needs to function is
produced by mitochondria. The mitochondria generate energy by
breaking down food and capturing high-energy electrons in the
process. When mitochondria are functioning properly, they harness
the energy of these electrons to produce energy for the cell. At
the end of this process, the mitochondria attach these electrons to
molecular oxygen that is ultimately detoxified to water. However,
this process is not completely efficient. Even in a young body with
healthy mitochondria, electrons can escape this process and
potentially form free radicals and other oxidants.
[0051] The mitochondrial theory of aging states that as a body
ages, the mitochondria work less efficiently. As the mitochondria
age they do not produce as much energy and release more stray
electrons that can create more free radicals and other oxidants.
The reduction in energy production comprises cellular function. The
increase in free radicals and other oxidants can damage cell
structures including the mitochondria. The mitochondrial damage
continues to further comprise mitochondrial function and leads to a
vicious downward spiral of even less mitochondrial efficiency and
the generation of more free radicals and oxidants. This ultimately
contributes to an increase in the overall cellular burden of
oxidative stress.
[0052] Numerous nutrients are known to support mitochondrial
health. Example nutrients include lipoic acid, acetyl-L-carnitine,
and coenzyme Q10. Lipoic acid is fat and water soluble and has 400
times the antioxidant power of vitamin E and vitamin C combined.
Lipoic acid is shown to neutralize oxidants that damage
mitochondria, recycle other antioxidants, and regenerate
glutathione. Acetyl-L-carnitine is an amino acid naturally produced
in the body that assists in generating energy. Coenzyme Q10 is a
fat-soluble antioxidant concentrated in the mitochondria. Coenzyme
Q10 is involved in shuttling electrons through the electron
transport chain of the mitochondria to ultimately produce
energy.
[0053] A major cellular signaling pathway involved in mitochondrial
health is NRF1. NRF1 is known as nuclear factor erythroid 2-related
factor 1. The NRF1 cellular signaling pathway directly and
indirectly regulates a number of genes involved in mitochondrial
health, turnover, and biogenesis. These include another protein
named Nrfl (nuclear respiratory factor-1). Nrfl activates the
expression of key genes involved in metabolism, cellular growth,
energy production, and mitochondrial DNA transcription and
replication. Together with Nrf2, NRF1 performs the function of
coordination gene expression between nuclear and mitochondrial
genomes. An additional protein shown to support mitochondrial
health is PGC1-alpha (peroxisome proliferator-activated receptor
gamma coactivator-1-alpha). PGC1-alpha is a transcriptional
coactivator that regulates genes involved in energy metabolism.
PGC1-alpha is the key regulator of mitochondrial biogenesis,
mitochondrial turnover, blood pressure, and cholesterol levels.
Sirtuin Theory Of Disease And Aging And The NAD Pathway
[0054] Another major theory of aging is the sirtuin theory of
aging. The sirtuin theory of aging was born of studies examining
the health benefits of caloric restriction. Caloric restriction is
the process of restricting caloric intake by as much as 40-60
percent. In numerous experimental models, animals with a
calorically restricted diet experience significant increases in
maximum lifespan by as much as 60 percent. Based on these studies,
it was ultimately determined that a family of proteins referred to
as the "sirtuins" were required to experience the increase in
lifespan brought on by caloric restriction. Numerous health
benefits are associated with caloric restriction. Humans undergoing
caloric restriction experience improvements in risk factors for
diabetes and cardiovascular disease, lower blood pressure, lower
cholesterol, weight loss, increased sexual function, better sleep,
improved cognitive function, increased autophagy, and a healthy
inflammatory response.
[0055] The enzymatic activity for many sirtuin proteins requires
the molecule NAD+. NAD is nicotinamide adenine dinucleotide and is
a cofactor that is central to metabolism. NAD exists in the cell as
a redox couple where NAD+ is the oxidized molecule while NADH is
the reduced molecule. The NAD+/NADH ratio is important for
controlling a number of cellular signaling pathways. Under normal
conditions, the cell tightly regulates the NAD+/NADH ratio.
However, changes in metabolism like long-term or short-term caloric
restriction can change this ratio. Several key enzymes, including
sirtuins, are activated by an increase in NAD caused by a change to
the NAD+/NADH ratio.
[0056] NAD+ is created in two pathways through the NAD+
biosynthetic pathway, including the de novo pathway and the salvage
pathway. In humans, de novo synthesis of NAD involves the amino
acid tryptophan. Quinolinic acid is generated directly from
tryptophan. The quinolinic acid is converted to nicotinic acid
mononucleotide (NaMN) by transfer of a phosphoribosyl moiety. An
adenylate moiety is transferred to form nicotinic acid adenine
dinucleotide (NaAD). The nicotinic acid moiety in NaAD is amidated
to nicotinamide (Nam) and ultimately forms nicotinamide adenine
dinucleotide (NAD+).
[0057] The salvage pathway in humans involves recycling individual
components of NAD+ containing a pyridine base. The three vitamin
precursors used in these salvage metabolic pathways are nicotinic
acid (NA), nicotinamide (Nam), and nicotinamide riboside (NR).
These compounds can be taken up from the diet or produced within
cells by digestion of cellular NAD+ and are termed vitamin B.sub.3
(niacin) or NR. These precursors can take up extracellular NAD+
from their surroundings. Nicotinamide and nicotinamide riboside can
be absorbed from the gut.
[0058] The salvage pathway reactions are essential in humans
despite the presence of the de novo pathway. The high requirement
for NAD+ results from the constant consumption of the NAD in
reactions such as posttranslational modifications, including those
by sirtuins. Thus, the salvage pathway is the most important for
biological function.
Nutrigenomics
[0059] Nutrigenomics is the study of how foods and individual
nutrients can affect gene expression and how genes can affect how
the body metabolizes food. Nutrigenomics demonstrates that certain
nutrients can activate cellular signaling pathways. Disclosed
herein are means for engaging cellular signaling and biochemical
pathways to unlock specific health mechanisms in cells, tissues,
and organs. Specifically, by leveraging cellular signaling and
biochemical stress response pathways known to be implicated in the
aging process, the compositions and methods disclosed herein to
reduce oxidative stress, optimize mitochondrial function, and
activate the sirtuin family of proteins.
[0060] An embodiment of the disclosure is a composition designed to
activate the Nrf2 protein irrespective of the cell's environment.
The activated Nrf2 enters the nucleus of the cell and activates
certain genes to raise the cell to a heightened state of readiness
for neutralizing free radicals and other oxidants and activate
detoxification pathways. The composition therefore reawakens Nrf2
and activates Nrf2 to its full potential to activate stress
response pathways and to slow the rate of aging.
[0061] An embodiment of the disclosure is a composition for
improving mitochondrial health by activating the NRF1 pathway. NRF1
is responsible for mitochondrial health and turnover. Poorly
performing and decayed mitochondria should be removed and replaced
with new, efficient mitochondria. NRF1 has been shown to remove
damaged mitochondria and prompt the generation of new mitochondria
within the cell. NRF1 additionally helps coordinate gene function
between mitochondria and the nucleus. The composition targets the
NRF1 protein and delivers nutrients for improving mitochondrial
health.
[0062] An embodiment of the disclosure is a composition that
targets cellular signaling pathways involved in the salvage pathway
for NAD+. The composition upregulates genes involved in the NAD+
biosynthetic pathway. The composition nutrigenomically targets the
appropriate genes to increase levels of NAD+ and thereby increase
sirtuin activity.
[0063] In the following description of the disclosure, reference is
made to the accompanying drawings, which form a part hereof, and in
which is shown by way of illustration specific implementations in
which the disclosure may be practiced. It is understood that other
implementations may be utilized, and structural changes may be made
without departing from the scope of the disclosure.
[0064] Before the structures, systems, methods, and compositions
for activating cellular stress signaling pathways are disclosed and
described, it is to be understood that this disclosure is not
limited to the particular structures, configurations, process
steps, and materials disclosed herein as such structures,
configurations, process steps, and materials may vary somewhat. It
is also to be understood that the terminology employed herein is
used for the purpose of describing particular embodiments only and
is not intended to be limiting since the scope of the disclosure
will be limited only by the appended claims and equivalents
thereof.
[0065] In describing and claiming the subject matter of the
disclosure, the following terminology will be used in accordance
with the definitions set out below.
[0066] As used herein, the terms "comprising," "including,"
"containing," "characterized by," and grammatical equivalents
thereof are inclusive or open-ended terms that do not exclude
additional, unrecited elements or method steps.
[0067] As used herein, the phrase "consisting of" and grammatical
equivalents thereof exclude any element, step, or ingredient not
specified in the claim.
[0068] As used herein, the phrase "consisting essentially of" and
grammatical equivalents thereof limit the scope of a claim to the
specified ingredients, materials, or steps and those that do not
materially affect the basic and novel characteristic or
characteristics of the claimed disclosure.
[0069] As used herein, "effective amount" means an amount of an
ingredient or a component of the product that is nontoxic, but
sufficient to provide the desired effect and performance at a
reasonable benefit/risk ratio attending any dietary supplement or
product. For example, an effective amount of a vitamin or mineral
is an amount sufficient to prevent a deficiency thereof and to
reduce the incidence of some adverse effects.
[0070] As used herein, a component or ingredient of a composition
may include any suitable form of the component or ingredient, such
as, for example, an extract, a powder, a tincture, an absolute, an
essential oil, a paste, a dehydrated form, and so forth. It should
be appreciated that any suitable form or combination of a component
or ingredient may be used unless otherwise specified.
[0071] As used herein, an extract includes any substance obtained
from a raw material. An extract may be obtained from a blossom,
fruit, root, whole plant, leaf, or other component of an
agricultural or horticultural component. An extraction may be
obtained through expression, absorption, maceration, distillation,
grinding, dehydration, and so forth. An extract may be stored in a
solvent such as ethanol or water or may be stored in a dry form
such as a powder.
[0072] Unless defined otherwise, all technical and scientific terms
used herein have the same meanings as commonly understood by one of
ordinary skill in the art to which this disclosure pertains and
belongs.
[0073] Reference will now be made in detail to the exemplary
embodiments, examples of which are illustrated in the accompanying
drawings. Wherever possible, the same reference numbers are used
throughout the drawings to refer to the same or like parts. It is
further noted that elements disclosed with respect to particular
embodiments are not restricted to only those embodiments in which
they are described. For example, an element described in reference
to one embodiment or figure, may be alternatively included in
another embodiment or figure regardless of whether or not those
elements are shown or described in another embodiment or figure. In
other words, elements in the figures may be interchangeable between
various embodiments disclosed herein, whether shown or not.
[0074] Referring now to the figures, FIG. 1 illustrates an Nrf2
pathway 100 for prompting the creation of antioxidants and
detoxification enzymes. The Nrf2 pathway 100 illustrated in FIG. 1
can prompt a body to generate enzymes for reducing levels of free
radicals, other oxidants, and toxins. Free radicals are atoms,
molecules, or ions that include an unpaired valence electron. Free
radicals are highly chemically reactive and can damage cells,
causing illness and aging. Oxidants are reactants that oxidize or
remove electrons from other reactants during a redox reaction. Free
radicals, other oxidants, and toxins are believed to contribute to
disease, cancer, and the process of aging. The body is capable of
creating antioxidants and detoxification enzymes for neutralizing
and removing free radicals, other oxidants, and toxins. In some
instances, it is beneficial to prompt the generation of additional
antioxidants. The Nrf2 pathway 100 is associated with prompting the
generation of additional antioxidants.
[0075] Nrf2 controls the basal and induced expression of an array
of antioxidant response element-dependent genes to regulate the
physiological and pathophysiological outcomes of oxidant exposure.
Nrf2 is linked to reducing oxidative stress and toxicity and
regulating antioxidant defense by the body. Reactive oxygen and
nitrogen species are constantly generated in the body from internal
metabolism and external exposure. In normal cells, reactive
oxidants are produced in a controlled manner and serve some useful
purposes. Oxidants formed in response to physiological cues act as
important signaling molecules to regulate processes such as cell
division, inflammation, immune function, autophagy, and stress
response. However, uncontrolled production of oxidants results in
oxidative stress that impairs cellular functions and contributes to
the development of chronic disease, toxicity, and aging.
[0076] Nrf2 is the primary transcription factor responsible for
upregulating endogenous antioxidant and detoxification pathways. In
humans, Nrf2 is encoded by the NFE2L2 gene. As illustrated in FIG.
1, Nrf2 is normally found anchored to another protein outside the
nucleus called KEAP1. As illustrated, Nrf2 can be released from
KEAP1 such that it can pass the wall of the nucleus and translocate
to the nucleus. Once in the nucleus, the Nrf2 binds a promotor
sequence to ultimately activate a target antioxidant gene and
prompt the gene to create antioxidants and detoxification enzymes.
In FIG. 1, the Nrf2 is bound to an antioxidant responsive element
(ARE) and a basic leucine zipper domain (bZIP). The combination of
the Nrf2, the antioxidant responsive element, and the basic leucine
zipper domain causes a gene to express and prompts the generation
of antioxidants and detoxification enzymes.
[0077] The Nrf2-ARE activation is a stress response pathway that
confers resistance to a variety of oxidative, stress-related, and
neurodegenerative insults. ARE is a regulatory element or enhancer
sequence that is found in the promoter region of several genes
encoding detoxification enzymes and cytoprotective proteins. The
core sequence of ARE includes 5'-TGACNNNGC-3'. ARE binds with Nrf2
in the nucleus of the cell to transcriptionally activate
antioxidant genes.
[0078] The basic leucine zipper domain (bZIP domain) is found in
DNA binding eukaryotic proteins. One part of the bZIP domain
includes a region that mediates sequence-specific DNA binding
properties to the ARE. The DNA binding region comprises a number of
basic amino acids such as arginine and lysine. bZIP transcription
factors are found in eukaryotes and form one of the largest
families of dimerizing transcription factors.
[0079] Disclosed herein are compositions and methods for activating
the Nrf2 pathway 100 and thereby causing antioxidants and
detoxification enzymes to be generated by a body. Therefore, the
compositions and methods disclosed herein are effective for
neutralizing free radicals and reducing oxidative stress,
toxicological burden that can damage cells, tissues, and
organs.
[0080] An embodiment of the disclosure is a composition for
activating the Nrf2 pathway. This composition is referred to herein
as the Nrf2 composition. The Nrf2 composition may include one or
more of calcium, silybum marianum extract, bacopa monnier whole
herb extract, camellia sinensis leaf extract, magnesium, silica,
medium chain triglycerides purified water, opadryl II clear,
silicon dioxide, stearic acid, calcium phosphate, hydroxypropyl
methylcellulose, oxidizable diphenols, phenylenediamines, quinones,
Michael reaction acceptors, isothiocyanates,
sulfoxylthiocarbamates, thiocarbamates, dethiolethiones, polyenes,
hydroperoxides, trivalent arsenicals, heavy metals, dimercaptans,
curcuma longo extract, proanthocyanins, resveratrol, garlic
extracts, cinnamon extracts, ferulic acid, rhubarb extract, ginger
extracts, ginseng extracts, skullcap extracts, Brazilian green
propolis, or myricetin.
[0081] FIG. 2 illustrates an exemplary NRF1 pathway 200. NRF1
functions as a transcription factor that activates the expression
of some metabolic genes for regulating cellular growth and nuclear
genes required for mitochondrial respiration. NRF1 and Nrf2 can
work together to mediate coordination between nuclear and
mitochondrial genomes by regulating the expression of
nuclear-encoded proteins.
[0082] As illustrated in FIG. 2, NRF1 is normally tethered to Hrd1
in the lumen of the endoplasmic reticulum (ER). Hrdl is a ubiquitin
ligase complex that mediates the degradation of misfolded
endoplasmic reticulum proteins. NRF1 can be untethered from Hrdl
and pass the nucleus membrane to translocate to the nucleus. In the
nucleus, NRF1 can bond with small Maf proteins. Small Maf proteins
are leucine zipper proteins associated with repressing and
activating transcription of genes. Further in the nucleus,
.beta.-TrCP serves as an adaptor for the Skp1 protein ubiquitin
ligase and promotes the degradation of NRF1 by catalyzing its
polyubiquitination. This augments the expression of NRF1 target
genes.
[0083] An embodiment of the disclosure is a composition for
activating the NRF1 pathway. This composition is referred to herein
as the NRF1 composition. The NRF1 composition may include one or
more of L-carnitine, quercetin, co-enzyme Q10, onion bulb extract,
grape extract, fruit extracts, ubiquinol, quercetin, magnesium,
proanthocyanins, cocoa extracts, or ginseng extracts.
[0084] FIG. 3 illustrates an exemplary de novo NAD pathway 300. NAD
is a cofactor that is central to metabolism. NAD is a dinucleotide
including an adenine nucleobase and a nicotinamide. NAD is involved
in redox reactions by carrying electrons from one reaction to
another. NAD may exist as an oxidizing agent or a reducing agent.
When NAD is an oxidizing agent, it accepts electrons from other
molecules and becomes reduced. When NAD is a reducing agent, it
donates electrons to other molecules. These electron transfer
reactions are the main function of NAD.
[0085] NAD coexists in cells in two forms, including the oxidized
form NAD+ and the reduced form NADH. The ratio of these two forms
(referred to as the NAD+/NADH ratio) is important for controlling
some cellular signaling pathways. As illustrated in FIG. 3, de novo
synthesis of NAD involves the amino acid tryptophan, and quinolinic
acid which is generated directly from tryptophan. The quinolinic
acid is converted to nicotinic acid mononucleotide (NaMN) by
transfer of phosphoribosyl moiety. An adenylate moiety is
transferred to form nicotinic acid adenine dinucleotide (NaAD).
[0086] An embodiment of the disclosure is a composition for
activating the NAD pathway. This composition is referred to herein
as the NAD composition. The NAD composition may include one or more
of niacin, cuprous niacin, copper, cuprous niacin, wasabi powder,
olive extract, theacrine, resveratrol, caffeine, theobromine, Yerba
mate extracts, hydroxycinnamic acid, Skullcap extracts, niacin,
nicotinic acid, nicotinamide, nicotinamide riboside, ribose vitamin
B3, nicotinamide mononucleotide, tryptophan, quinolinic acid,
beta-NAMN, and beta- NAAD, or myricetin.
[0087] In an embodiment, a composition is provided to a user for
inducing a synergistic effect to increase the activation of Nrf2,
NRF1, and NAD biosynthetic genes. The composition includes one or
more of actyl-L-carnitine, quaternary ammonium compound, coenzyme
Q10, ubiquinone, grape extract, lipoic acid, thionic acid,
quercetin, calcium, silymarin, bacopa extract, ashwagandha extract
root, green tea extract leaf, turmeric extract, lychee fruit
extract, niacin, copper, wasabi powder, olive extract, polyphenols,
flavonoids, hydroxtyrosol, theacrine, purine alkaloids,
diarylheptanoid, flavonoids, proanthocyanins, resveratrol, garlic
extracts, cinnamon extracts, ferulic acid, rhubarb extract, ginger
extracts, ginseng extracts, Skullcap extracts, Brazilian green
propolis, myricetin, cocoa extracts, caffeine, theobromine, Yerba
mate extracts, hydroxycinnamic acid, Skullcap extracts, niacin,
nicotinic acid, nicotinamide, nicotinamide riboside, ribose vitamin
B3, nicotinamide mononucleotide, tryptophan, quinolinic acid,
beta-NAMN, or beta-NAAD.
[0088] Disclosed herein are compositions and methods that provide
unexpectedly good results for activating Nrf2 genes, NRF1 genes,
and NAD genes. The compositions and methods disclosed herein are
effective for reducing oxidative stress, improving mitochondrial
activity, replacing damaged mitochondria, activating NAD
biosynthetic genes, and increasing activity of sirtuins. When
compared with compositions individually known to increase activity
of Nrf2, NRF1, or NAD genes, the compositions and methods disclosed
herein provide a synergistic effect and unexpectedly good results
for increasing activity of each of Nrf2, NRF1, and NAD genes. The
compositions and methods disclosed herein increase the activity of
Nrf2, NRF1, and NAD genes by a greater margin than other
compositions that are known to individually increase the activity
of Nrf2, NRF1, or NAD genes.
CLINICAL EXAMPLE
[0089] In one study conducted to test the effectiveness of a
composition for increasing the activation of Nrf2, NRF1, and NAD
genes as disclosed herein, the gene expression of each of Nrf2,
NRF1, and NAD genes was greatly enhanced. In the study, human HepG2
and mouse C2C12 cells were treated in a concentration gradient
(24-hour, 8-point dose-dependent curve done in quadruplicate) for
cell viability to determine if the cells are sensitive to the
ingredients in the composition, and to ascertain the optimal dosage
for gene expression studies.
[0090] In the study, the following genes were used as markers for
evaluation of treatment (see Table 1). The study included
three-hour and 24-hour timepoints done in biological triplicate.
The study included a control (untreated) sample, an NAD
composition, an NRF1 composition, an Nrf2 composition, a
combination composition with theacrine, a combination composition
with alpinia galanga, a combination composition with capsaicin, and
a combination composition with mango leaf extract. The study
measured gene expression of the NAMPT, NMNAT, PGC1-alpha, Nrf1,
NQO1, and HO1 genes.
Gene Functions Pertinent To The Study
[0091] The NAMPT (nicotinamide phosphoribosyltansferase) gene
encodes a protein that catalyzes the condensation of nicotinamide
with 5-phosphoribosyl-1-pyrophosphate to yield nicotinamide
mononucleotide (NMN). This is one step in the biosynthesis of
nicotinamide adenine dinucleotide (NAD). The protein belongs to the
nicotinic acid phosphoribosyltransferase (NAPRTase) family and is
thought to be involved in biological processes, including
metabolism, stress response, and aging.
[0092] The NMNAT 1 (nicotinamide mononucleotide
adenyltransferase-1) gene encodes an enzyme that catalyzes a step
(NMN.fwdarw.NAD+) in the biosynthesis of NAD+. The encoded enzyme
is one of several nicotinamide nucleotide adenyl transferases and
is specifically localized to the cell nucleus. Activity of this
protein leads to the activation of a nuclear deacetylase that
functions in the protection of damaged cells.
[0093] The PGC1-alpha (peroxisome proliferator-activated receptor
gamma coactivator 1-alpha) protein is transcriptional coactivator
that regulates the genes involved in energy metabolism. The
PGC1-alpha protein interacts with PAAgamma, which permits the
interaction of this protein with multiple transcription factors.
The PGC1-alpha protein can interact with and regulate the
activities of the cAMP response element binding protein (CCB and
nuclear respirator factors [NRFs]). It provides a direct link
between external physiological stimuli and the regulation of
mitochondrial biogenesis and is a major factor that regulates
muscle fiber type determination. This protein may also be involved
in controlling blood pressure, regulating cellular cholesterol
homeostasis, and the development of obesity.
[0094] The Nrfl (nuclear respirator factor-1) gene encodes a
protein that homodimerizes and functions as a transcription factor
that activates the expression of some metabolic genes for
regulating cellular grown and nuclear genes required for
respiration, heme biosynthesis, and mitochondrial DNA transcription
and replication. The protein encoded by Nrf1 has also been
associated with the regulation of neurite outgrowth.
[0095] The NQO1 (NAD(P)H quinone dehydrogenase-1) gene is a member
of the NAD(P)H dehydrogenase (quinone) family and encodes a
cytoplasmic two-electron reductase. This FAD-binding protein forms
homodimers and reduces quinones to hydroquinone. This protein's
enzymatic activity prevents the one electron reduction of quinones
that results in the production of radical species.
[0096] The HO-1 (heme oxygenase-1) enzyme is involved in heme
catabolism. The HO-1 enzyme cleaves heme to form biliverdin, which
is subsequently converted to bilirubin by biliverdin reductase, and
carbon monoxide, a putative neurotransmitter. Heme oxygenase
activity is induced by its substrate heme and by various nonheme
substances. Heme oxygenase occurs as two isozymes, an inducible
heme oxygenase-1 and a constitutive heme oxygenase-2. HMOX1 and
HMOX2 belong to the heme oxygenase family.
Gene Expression Assay
[0097] In the study, human HepG2 and mouse C212 cells were seeded
at 200,000 cells per well. After eighteen (18) hours of incubation,
the cells were treated at appropriate time points. Cells were lysed
with lysis buffer and RNA (ribonucleic acid) isolations were
conducted per manufacturer recommendations. The RNA isolations were
conducted using the PureLink Mini RNA kit (Thermo, Cat. No.
12183025). RNA was eluted with RNase free water and qualified by
spectrophotometer. Reverse transcription reactions were performed
using 1 .mu.g of RNA using the Vilo Superscript system (Thermo,
Cat. No. 11756500). A six-fold dilution was made of each cDNA in
PCR-grade water, and 2 .mu.L of this solution was carried forward
into qRT-PCR.
[0098] The reactions were carried out in 20 .mu.L total volume,
made up as follows: 2 .mu.L cDNA, 6 .mu.L PCR-grade water, 1 .mu.L
gene-of-interest primer (FAM label), 1 .mu.L GAPDH primer (VIC
label), 10 .mu.L Taqman Fast Advanced Master Mix (Thermo Fisher
Scientific, Catalog #4444963). Reactions were run on an Applied
Biosystems 7500 Fast Real-Time PCR Instrument (Thermo Fisher
Scientific) under the following conditions: 50.degree. C.-2
minutes, 95.degree. C.-20 seconds, 40 cycles of (95.degree. C.-3
seconds, 60.degree. C.-30 seconds). Threshold cycle (CT) was
determined by the instrument software. Differences in threshold
cycle between the gene of interest and GAPDH (.DELTA.CT) were
determined for each sample and used to determine fold induction of
each gene of interest, compared to untreated controls.
[0099] In the study, PCR primers, were purchased from Thermo Fisher
Scientific as follows: PPARGC1A (PGC-1 .alpha.): Hs0106724 human
Mm1208835 mouse (FAM labeled); NRF-1: Hs00602161 human Mm01135606
mouse (FAM labeled); NQO1 Hs01045993 human Mm01253561 mouse (FAM
labeled); HO1: Hs011102250 human Mm00516005 mouse (FAM labeled);
NAMPT: Hs00237184 human Mm00451938 mouse (FAM labeled); NMNAT1:
Hs00276702 human Mm01257929 mouse (FAM labeled); NMNAT3: Hs00736183
human Mm00513791 mouse (FAM labeled); and GAPDH control: 4326315E
human 4352341E mouse (VIC labeled).
[0100] In the study, the following formulas were tested for the
Nrf2 composition, the NRF1 composition, the NAD composition with
theacrine, the NAD composition with alpinia galanga, the NAD
composition with capsaicin, and the NAD composition with mango leaf
extract. The Nrf2 composition tested in the study comprised milk
thistle extract, ashwagandha extract, bacopa monnieri extract,
green tea extract, and turmeric extract. The NRF1 composition
tested in the study comprise acetyl-L-carnitine, quercetin, grape
extract, lipoic acid, and coenzyme Q10. The NAD composition with
theacrine tested in the study comprised olive extract, theacrine,
wasabi japonica powder, and cuprous niacin. The NAD composition
with alpinia galanga tested in the study comprised alpinia galanga,
wasabi powder, olive leaf extract, copper gluconate, and nicotinic
acid. The NAD composition with capsaicin tested in the study
comprised capsaicin, wasabi powder, olive leaf extract, nicotinic
acid, and copper gluconate. The NAD composition with mango leaf
extract tested in the study comprised mango leaf extract wasabi
powder, olive leaf extract, nicotinic acid, and copper
gluconate.
[0101] The study also included testing of combination compositions
and identified overall increase in gene expression when components
from the Nrf2 composition, the NRF1 composition, and one or more of
the NAD compositions are combined. The combination compositions
include (a) the theacrine combination; (b) the alpinia galanga
combination; (c) the capsaicin combination; and (d) the mango leaf
extract combination. The theacrine combination includes the
components of the Nrf2 composition, the NRF1 composition, and the
NAD composition with theacrine. The alpinia galanga combination
includes the components of the Nrf2 composition, the NRF1
composition, and the NAD composition with alpinia galanga. The
capsaicin combination includes the components of the Nrf2
composition, the NRF1 composition, and the NAD composition with
capsaicin. The mango leaf extract combination includes the
components of the Nrf2 composition, the NRF1 composition, and the
NAD composition with mango leaf extract.
[0102] In the study, the compositions for increasing activity of
the Nrf2, NRF1, and NAD genes (referred to herein as the
combination compositions) exhibited unexpectedly good results for
increasing activity of each of the Nrf2, NRF1, and NAD genes. The
combination compositions increased the activity of each of the Nrf2
genes, the NRF1 genes, and the NAD genes at a greater rate than any
of the Nrf2 composition, the NRF1 composition, or the NAD
compositions alone. Said another way, the combination composition
increased the activity of the Nrf2 target genes at a greater rate
than the Nrf2 composition alone. Further, the combination
compositions increased the activity of the NRF1 genes at a greater
rate than the NRF1 composition alone. Further, the combination
compositions increased the activity of the NAD genes at a greater
rate than the NAD composition alone. Therefore, the combination
compositions exhibited an unexpected synergistic effect for
increasing the activity of each of the Nrf2, NRF1, and NAD
genes.
[0103] FIGS. 4A-9B illustrate results of the clinical study. The
test results for the combination composition illustrated in FIGS.
4A-9B apply to the theacrine combination including the Nrf2
composition, the NRF1 composition, and the NAD composition
comprising theacrine. FIGS. 4A-4B are bar graphs indicating the
percent increase in activation of the Nrf2 pathway in response to
the Nrf2 composition and the combination composition after three
hours. FIGS. 5A-5B are bar graphs indicating the percent increase
in the activation of the NRF1 pathway in response to the NRF1
composition and the combination composition after three hours.
FIGS. 6A-6B are bar graphs indicating the percent increase in
activation of the NAD pathway in response to the NAD composition
and the combination composition after three hours. FIGS. 7A-7B are
bar graphs indicating the percent increase in activation of the
Nrf2 pathway in response to the Nrf2 composition and the
combination composition after 24 hours. FIGS. 8A-8B are bar graphs
indicating the percent increase in the activation of the NRF1
pathway in response to the NRF1 composition and the combination
composition after 24 hours. FIGS. 9A-9B are bar graphs indicating
the percent increase in activation of the NAD pathway in response
to the NAD composition and the combination composition after 24
hours.
[0104] FIGS. 4A-4B are bar graphs illustrating the comparative
percent increases to activation of the Nrf2 pathway in response to
the Nrf2 composition and the combination composition. The data
illustrated in FIGS. 4A-4B is based on HepG2 cells at 10 .mu.g/mL
for three hours. FIG. 4A illustrates the percent increase in
expression of the NQOlgene in response to the Nrf2 composition and
the combination composition. As shown, the Nrf2 composition causes
a 30.6% increase in expression of the NQO1gene over three hours.
The combination composition causes a 32.5% increase in expression
of the NQO1gene over three hours. There is a 6.2% increase in
expression of the NQO1gene by the combination composition when
compared with the Nrf2 composition. FIG. 4B illustrates the percent
increase in expression of the HMOX1 gene in response to the Nrf2
composition and the combination composition. As shown, the Nrf2
composition causes a 502.2% increase in expression of the HMOX1
gene over three hours. The combination composition causes an 867.2%
increase in expression of the HMOX1 gene over three hours. There is
a 72.7% increase in expression of the NQO1gene by the combination
composition when compared with the Nrf2 composition.
[0105] FIGS. 5A-5B are bar graphs illustrating the comparative
percent increases to activation of the NRF1 pathway in response to
the NRF1 composition and the combination composition. The data
illustrated in FIGS. 5A-5B is based on HepG2 cells at 10 .mu.g/mL
for three hours. FIG. 5A illustrates the percent increase in
expression of the Nrf1 gene in response to the NRF1 composition and
the combination composition. As shown, the NRF1 composition causes
a 31.2% increase in expression of the Nrf1 gene over three hours.
The combination composition causes a 62.3% increase in expression
of the Nrf1 gene over three hours. There is a 99.8% increase in
expression of the Nrf1 gene by the combination composition when
compared with the NRF1 composition. FIG. 5B illustrates the percent
increase in expression of the PGC1-alpha gene in response to the
NRF1 composition and the combination composition. As shown, the
NRF1 composition causes a 10.7% increase in expression of the
PGC1-alpha gene over three hours. The combination composition
causes a 43.3% increase in expression of the PGC1-alpha gene over
three hours. There is a 304.8% increase in expression of the
PGC1-alpha gene by the combination composition when compared with
the NRF1 composition.
[0106] FIGS. 6A-6B are bar graphs illustrating the comparative
percent increases to activation of the NAD pathway in response to
the NAD composition and the combination composition. The data
illustrated in FIGS. 6A-6B is based on HepG2 cells at 10 .mu.g/mL
for three hours. FIG. 6A illustrates the percent increase in
expression of the NMNAT1 gene in response to the NAD composition
and the combination composition. As shown, the NAD composition
causes a 7.5% increase in expression of the NMNAT1 gene over three
hours. The combination composition causes a 90.9% increase in
expression of the NMNAT1 gene over three hours. There is a 1104.1%
increase in expression of the NMNAT1 gene by the combination
composition when compared with the NAD composition. FIG. 6B
illustrates the percent increase in expression of the NAMPT gene in
response to the NAD composition and the combination composition. As
shown, the NAD composition causes a 1.9% increase in expression of
the NAMPT gene over three hours. The combination composition causes
a 21.1% increase in expression of the NAMPT gene over three hours.
There is a 1011.0% increase in expression of the NAMPT gene by the
combination composition when compared with the NAD composition.
[0107] FIGS. 7A-7B are bar graphs illustrating the comparative
percent increases to activation of the Nrf2 pathway in response to
the Nrf2 composition and the combination composition. The data
illustrated in FIGS. 4A-4B is based on HepG2 cells at 10 .mu.g/mL
for 24 hours. FIG. 7A illustrates the percent increase in
expression of the NQOlgene in response to the Nrf2 composition and
the combination composition. As shown, the Nrf2 composition causes
a 39.9% increase in expression of the NQO1gene over 24 hours. The
combination composition causes a 72.6% increase in expression of
the NQO1gene over 24 hours. There is an 82.1% increase in
expression of the NQO1 gene by the combination composition when
compared with the Nrf2 composition. FIG. 7B illustrates the percent
increase in expression of the HMOX1 gene in response to the Nrf2
composition and the combination composition. As shown, the Nrf2
composition causes a 49.8% increase in expression of the HMOX1 gene
over 24 hours. The combination composition causes an 838.2%
increase in expression of the HMOX1 gene over 24 hours. There is a
1582.5% increase in expression of the NQO1gene by the combination
composition when compared with the Nrf2 composition.
[0108] FIGS. 8A-8B are bar graphs illustrating the comparative
percent increases to activation of the NRF1 pathway in response to
the NRF1 composition and the combination composition. The data
illustrated in FIGS. 8A-8B is based on HepG2 cells at 10 .mu.g/mL
for 24 hours. FIG. 8A illustrates the percent increase in
expression of the Nrf1 gene in response to the NRF1 composition and
the combination composition. As shown, the NRF1 composition causes
a 60.7% increase in expression of the Nrf1 gene over 24 hours. The
combination composition causes an 84.4% increase in expression of
the Nrf1 gene over 24 hours. There is a 39.2% increase in
expression of the Nrf1 gene by the combination composition when
compared with the NRF1 composition. FIG. 8B illustrates the percent
increase in expression of the PGC1-alpha gene in response to the
NRF1 composition and the combination composition. As shown, the
NRF1 composition causes a 69.3% increase in expression of the
PGC1-alpha gene over 24 hours. The combination composition causes a
118.2% increase in expression of the PGC1-alpha gene over 24 hours.
There is a 70.7% increase in expression of the PGC1-alpha gene by
the combination composition when compared with the NRF1
composition.
[0109] FIGS. 9A-9B are bar graphs illustrating the comparative
percent increases to activation of the NAD pathway in response to
the NAD composition and the combination composition. The data
illustrated in FIGS. 9A-9B is based on HepG2 cells at 10 pg/mL for
24 hours. FIG. 9A illustrates the percent increase in expression of
the NMNAT1 gene in response to the NAD composition and the
combination composition over 24 hours. As shown, the NAD
composition causes an 11.2% increase in expression of the NMNAT1
gene over 24 hours. The combination composition causes a 225.9%
increase in expression of the NMNAT1 gene over 24 hours. There is a
1915.6% increase in expression of the NMNAT1 gene by the
combination composition when compared with the NAD composition.
FIG. 9B illustrates the percent increase in expression of the NAMPT
gene in response to the NAD composition and the combination
composition. As shown, the NAD composition causes a 11.7% increase
in expression of the NAMPT gene over 24 hours. The combination
composition causes a 126.8% increase in expression of the NAMPT
gene over 24 hours. There is a 986.8% increase in expression of the
NAMPT gene by the combination composition when compared with the
NAD composition.
[0110] FIGS. 10-15 further illustrate results of the study. The
test results illustrated in FIGS. 10-15 include results for each of
the four potential combination compositions, including the
theacrine combination, the alpinia combination, the capsaicin
combination, and the mango combination. The theacrine combination
includes the NRF1 composition, the Nrf2 composition, and the
theacrine NAD composition. The alpinia combination includes the
NRF1 composition, the Nrf2 composition, and the alpinia galanga NAD
composition. The capsaicin combination includes the NRF1
composition, the Nrf2 composition, and the capsaicin NAD
composition. The mango combination includes the NRF1 composition,
the Nrf2 composition, and the mango leaf extract NAD
composition.
[0111] FIG. 10 illustrates results for activation of hPGC1-alpha
gene expression by treating HepG2 cells with 20 .mu.g/mL for three
hours and 24 hours. As illustrated in FIG. 10, the NRF1 composition
provided some marginal increase in hPGC1-alpha gene expression when
compared with the control. However, each of the combination
compositions, including the theacrine combination, the alpinia
combination, the capsaicin combination, and the mango combination,
provided unexpectedly good results and further increase in
hPGC1-alpha gene expression when compared with the NRF1 composition
alone.
[0112] FIG. 11 illustrates results for activation of hHMOX1 gene
expression by treating HepG2 cells with 20 .mu.g/mL for three hours
and 24 hours. As illustrated in FIG. 11, the Nrf2 composition
enabled increased expression of the hHMOX1 gene when compared with
the control. However, each of the combination compositions,
including the theacrine combination, the alpinia combination, the
capsaicin combination, and the mango combination, provided
unexpectedly good results and further increase in hHMOX1 gene
expression when compared with the Nrf2 composition alone.
[0113] FIG. 12 illustrates results for activation of hNMNAT1 gene
expression by treating HepG2 cells with 20 .mu.g/mL for three hours
and 24 hours. As illustrated in FIG. 12, the NAD composition
comprising theacrine enabled increased expression of the hNMNAT1
gene when compared with the control. However, each of the
combination compositions, including the theacrine combination, the
alpinia combination, the capsaicin combination, and the mango
combination, provided unexpectedly good results and further
increase in hNMNAT1 gene expression when compared with the NAD
composition comprising theacrine alone.
[0114] FIG. 13 illustrates results for activation of hNAMPT gene
expression by treating HepG2 cells with 20 .mu.g/mL for three hours
and 24 hours. As illustrated in FIG. 13, the NAD composition
comprising theacrine enabled increased expression of the hNAMPT
gene when compared with the control. However, each of the
combination compositions, including the theacrine combination, the
alpinia combination, the capsaicin combination, and the mango
combination, provided unexpectedly good results and further
increase in hNAMPT gene expression when compared with the NAD
composition comprising theacrine alone.
[0115] FIG. 14 illustrates results for activation of hNMNST1 gene
expression by treating HepG2 cells with 20 .mu.g/mL for three hours
and 24 hours. As illustrated in FIG. 15, the NAD composition
comprising theacrine enabled increased expression of the hNMNST1
gene when compared with the control. However, each of the
combination compositions, including the theacrine combination, the
alpinia combination, the capsaicin combination, and the mango
combination, provided unexpectedly good results and further
increase in hNMNST1 gene expression when compared with the NAD
composition comprising theacrine alone.
[0116] FIG. 15 illustrates results for activation of hNQO1 gene
expression by treating HepG2 cells with 20 .mu.g/mL for three hours
and 24 hours. As illustrated in FIG. 16, the Nrf2 composition
enabled increased expression of the hNQO1 gene when compared with
the control. However, each of the combination compositions,
including the theacrine combination, the alpinia combination, the
capsaicin combination, and the mango combination, provided
unexpectedly good results and further increase in hNQO1 gene
expression when compared with the Nrf2 composition alone.
EXAMPLES
[0117] The following examples pertain to further embodiments. As
discussed in the example embodiments, the "composition" may refer
to one or more of the compositions described herein, including the
theacrine combination, the alpinia galanga combination, the
capsaicin combination, and the mango leaf extract combination.
[0118] Table 1 below shows an example embodiment of the
composition.
TABLE-US-00001 TABLE 1 Component Weight Percent in Blend
Ashwagandha extract 7.6 Bacopa monnieri extract 7.8 Green tea
extract 3.9 Turmeric extract 3.9 Acetyl-L-Carnitine 26.0 Quercetin
7.3 Grape extract 3.6 Lipoic acid 2.6 Coenzyme Q10 1.6 Olive leaf
extract 7.8 Theacrine 6.5 Wasabi japonica powder 9.6 Cuprous niacin
0.1 Milk Thistle Extract 11.7
[0119] Table 2 below shows an example embodiment of the
composition.
TABLE-US-00002 TABLE 2 Component Weight Percent Total Composition
Milk thistle extract 11.5 Ashwagandha extract 7.7 Bacopa monnieri
extract 7.7 Green tea extract 3.8 Turmeric extract 3.8
Hydroxypropyl methylcellulose 0.5 Calcium 7.9 Calcium carbonate
gran 6.1 Microcrystalline cellulose 5.1 Croscarmellose sodium 1.5
Silica 0.5 Medium chain triglycerides 0.5 Magnesium 0.7 Purified
water 3.8 Acetyl-L-carnitine 12.8 Quercetin 3.6 Lipoic acid 1.3
Coenzyme Q10 0.8 Grape extract 1.8 Wasabi rhizome powder 5.1
Theacrine 3.1 Copper niacin complex 0.1 Olive extract 3.8 Rice
flour 6.3 Syloid 0.2
[0120] Table 3 below shows an example embodiment of the
composition.
TABLE-US-00003 TABLE 3 Component Weight Percent in Blend
Acetyl-L-Carnitine 32.9 Quercetin 3.2 Grape 2.3 Lipoic acid 0.3
Coenzyme Q10 0.1 Milk Thistle 8.5 Ashwagandha 4.2 Bacopa monnieri
4.8 Green Tea 13.5 Turmeric 8.6 Wasabi japonica 8.4 Olive leaf 7.5
Theacrine 5.7 Copper Niacin Complex 0.0002
[0121] Table 4 below shows an example embodiment of the
composition.
TABLE-US-00004 TABLE 4 Component Weight Percent in Blend
Acetyl-L-Carnitine 2.2 Quercetin 0.2 Grape 0.04 Lipoic acid 0.02
Coenzyme Q10 0.008 Milk Thistle 0.5 Ashwagandha 0.2 Bacopa monnieri
0.2 Green Tea 0.05 Turmeric 0.05 Wasabi japonica 0.3 Olive leaf 0.2
Theacrine 0.1 Copper Niacin Complex 0.000008
[0122] Table 5 below shows an example embodiment of the
composition.
TABLE-US-00005 TABLE 5 Component Weight Percent in Blend
Acetyl-L-Carnitine 12.3 Quercetin 1.0 Grape 0.2 Lipoic acid 0.1
Coenzyme Q10 0.04 Milk Thistle 2.9 Ashwagandha 1.3 Bacopa monnieri
1.2 Green Tea 0.3 Turmeric 0.3 Wasabi japonica 2.8 Olive leaf 1.8
Theacrine 1.3 Copper Niacin Complex 0.00008
[0123] Table 6 below shows an example embodiment of the
composition.
TABLE-US-00006 TABLE 6 Component Weight Percent in Blend
Acetyl-L-Carnitine 15.3 Quercetin 1.2 Grape 0.3 Lipoic acid 0.2
Coenzyme Q10 0.06 Milk Thistle 3.7 Ashwagandha 1.6 Bacopa monnieri
1.6 Green Tea 0.4 Turmeric 0.4 Wasabi japonica 3.7 Olive leaf 2.4
Theacrine 1.7 Copper Niacin Complex 0.0001
[0124] Table 7 below shows an example embodiment of the
composition.
TABLE-US-00007 TABLE 7 Component Weight Percent in Blend
Acetyl-L-Carnitine 12.8 Quercetin 3.6 Grape 1.8 Lipoic acid 1.3
Coenzyme Q10 0.8 Milk Thistle 11.5 Ashwagandha 7.7 Bacopa monnieri
7.7 Green Tea 3.8 Turmeric 3.8 Wasabi japonica 5.1 Olive leaf 3.8
Theacrine 3.1 Copper Niacin Complex 0.1
[0125] Table 8 below shows an example embodiment of the
composition.
TABLE-US-00008 TABLE 8 Component Weight Percent in Blend
Ashwagandha extract 7.6 Bacopa monnieri extract 7.8 Green tea
extract 3.9 Turmeric extract 3.9 Acetyl-L-Carnitine 26.0 Quercetin
7.3 Grape extract 3.6 Lipoic acid 2.6 Coenzyme Q10 1.6 Olive leaf
extract 6.5 Alpinia galanga 9.4 Wasabi japonica powder 8.0
Nicotinic acid 0.1 Milk Thistle Extract 11.7
[0126] Table 9 below shows an example embodiment of the
composition.
TABLE-US-00009 TABLE 9 Component Weight Percent Total Composition
Milk thistle extract 11.5 Ashwagandha extract 7.7 Bacopa monnieri
extract 7.7 Green tea extract 3.8 Turmeric extract 3.8
Hydroxypropyl methylcellulose 0.5 Calcium 7.9 Calcium carbonate
gran 6.1 Microcrystalline cellulose 5.1 Croscarmellose sodium 1.5
Silica 0.5 Medium chain triglycerides 0.5 Magnesium 0.7 Purified
water 3.8 Acetyl-L-carnitine 12.8 Quercetin 3.6 Lipoic acid 1.3
Coenzyme Q10 0.8 Grape extract 1.8 Wasabi rhizome powder 5.0
Alpinia galanga 4.5 Nicotinic acid 0.1 Olive extract 2.5 Rice flour
6.3 Syloid 0.2
[0127] Table 10 below shows an example embodiment of the
composition.
TABLE-US-00010 TABLE 10 Component Weight Percent in Blend
Acetyl-L-Carnitine 32.9 Quercetin 3.2 Grape 2.3 Lipoic acid 0.3
Coenzyme Q10 0.1 Milk Thistle 8.5 Ashwagandha 4.2 Bacopa monnieri
4.8 Green Tea 13.5 Turmeric 8.6 Wasabi japonica 8.4 Olive leaf 7.5
Alpinia galanga 5.7 Nicotinic acid 0.0002
[0128] Table 11 below shows an example embodiment of the
composition.
TABLE-US-00011 TABLE 11 Component Weight Percent in Blend
Acetyl-L-Carnitine 12.2 Quercetin 0.2 Grape 0.04 Lipoic acid 0.02
Coenzyme Q10 0.008 Milk Thistle 0.5 Ashwagandha 0.2 Bacopa monnieri
0.2 Green Tea 0.05 Turmeric 0.05 Wasabi japonica 0.3 Olive leaf 0.2
Alpinia galanga 1.2 Nicotinic acid 0.000008
[0129] Table 12 below shows an example embodiment of the
composition.
TABLE-US-00012 TABLE 12 Component Weight Percent in Blend
Acetyl-L-Carnitine 12.3 Quercetin 1.0 Grape 0.2 Lipoic acid 0.1
Coenzyme Q10 0.04 Milk Thistle 2.9 Ashwagandha 1.3 Bacopa monnieri
1.2 Green Tea 5.6 Turmeric 0.3 Wasabi japonica 2.8 Olive leaf 3.5
Alpinia galanga 2.4 Nicotinic acid 0.00008
[0130] Table 13 below shows an example embodiment of the
composition.
TABLE-US-00013 TABLE 13 Component Weight Percent in Blend
Acetyl-L-Carnitine 15.3 Quercetin 1.2 Grape 0.3 Lipoic acid 0.2
Coenzyme Q10 0.06 Milk Thistle 3.7 Ashwagandha 1.6 Bacopa monnieri
1.6 Green Tea 0.4 Turmeric 0.4 Wasabi japonica 3.7 Olive leaf 2.4
Alpinia galanga 2.4 Nicotinic acid 0.0001
[0131] Table 14 below shows an example embodiment of the
composition.
TABLE-US-00014 TABLE 14 Component Weight Percent in Blend
Acetyl-L-Carnitine 12.8 Quercetin 3.6 Grape 1.8 Lipoic acid 1.3
Coenzyme Q10 0.8 Milk Thistle 11.5 Ashwagandha 7.1 Bacopa monnieri
7.7 Green Tea 3.8 Turmeric 3.8 Wasabi japonica 5.1 Olive leaf 3.8
Alpinia galanga 4.2 Nicotinic acid 0.1
[0132] Table 15 below shows an example embodiment of the
composition.
TABLE-US-00015 TABLE 15 Component Weight Percent in Blend
Ashwagandha extract 7.6 Bacopa monnieri extract 7.8 Green tea
extract 3.9 Turmeric extract 3.9 Acetyl-L-Carnitine 26.0 Quercetin
7.3 Grape extract 3.6 Lipoic acid 2.6 Coenzyme Q10 1.6 Olive leaf
extract 6.5 Capsaicin 2.3 Wasabi japonica powder 8.0 Nicotinic acid
0.1 Milk Thistle Extract 11.7 Copper gluconate 0.1
[0133] Table 16 below shows an example embodiment of the
composition.
TABLE-US-00016 TABLE 16 Component Weight Percent Total Composition
Milk thistle extract 11.5 Ashwagandha extract 7.7 Bacopa monnieri
extract 7.7 Green tea extract 3.8 Turmeric extract 3.8
Hydroxypropyl methylcellulose 0.5 Calcium 7.9 Calcium carbonate
gran 6.1 Microcrystalline cellulose 5.1 Croscarmellose sodium 1.5
Silica 0.5 Medium chain triglycerides 0.5 Magnesium 0.7 Purified
water 3.8 Acetyl-L-carnitine 12.8 Quercetin 3.6 Lipoic acid 1.3
Coenzyme Q10 0.8 Grape extract 1.8 Wasabi rhizome powder 5.0
Capsaicin 2.3 Nicotinic acid 0.1 Olive extract 2.5 Rice flour 6.3
Syloid 0.2 Copper gluconate 0.01
[0134] Table 17 below shows an example embodiment of the
composition.
TABLE-US-00017 TABLE 17 Component Weight Percent in Blend
Acetyl-L-Carnitine 32.9 Quercetin 3.2 Grape 2.3 Lipoic acid 0.3
Coenzyme Q10 0.1 Milk Thistle 8.5 Ashwagandha 4.2 Bacopa monnieri
4.8 Green Tea 13.5 Turmeric 8.6 Wasabi japonica 8.4 Olive leaf 7.5
Capsaicin 4.6 Nicotinic acid 0.0002
[0135] Table 18 below shows an example embodiment of the
composition.
TABLE-US-00018 TABLE 18 Component Weight Percent in Blend
Acetyl-L-Carnitine 12.2 Quercetin 0.2 Grape 0.04 Lipoic acid 0.02
Coenzyme Q10 0.008 Milk Thistle 0.5 Ashwagandha 0.2 Bacopa monnieri
0.2 Green Tea 0.05 Turmeric 0.05 Wasabi japonica 0.3 Olive leaf 0.2
Capsaicin 0.8 Nicotinic acid 0.000008
[0136] Table 19 below shows an example embodiment of the
composition.
TABLE-US-00019 TABLE 19 Component Weight Percent in Blend
Acetyl-L-Carnitine 12.3 Quercetin 1.0 Grape 0.2 Lipoic acid 0.1
Coenzyme Q10 0.04 Milk Thistle 2.9 Ashwagandha 1.3 Bacopa monnieri
1.2 Green Tea 5.6 Turmeric 0.3 Wasabi japonica 2.8 Olive leaf 3.5
Capsaicin 1.8 Nicotinic acid 0.00008
[0137] Table 20 below shows an example embodiment of the
composition.
TABLE-US-00020 TABLE 20 Component Weight Percent in Blend
Acetyl-L-Carnitine 15.3 Quercetin 1.2 Grape 0.3 Lipoic acid 0.2
Coenzyme Q10 0.06 Milk Thistle 3.7 Ashwagandha 1.6 Bacopa monnieri
1.6 Green Tea 0.4 Turmeric 0.4 Wasabi japonica 3.7 Olive leaf 2.4
Capsaicin 2.4 Nicotinic acid 0.0001
[0138] Table 21 below shows an example embodiment of the
composition.
TABLE-US-00021 TABLE 21 Component Weight Percent in Blend
Acetyl-L-Carnitine 12.8 Quercetin 3.6 Grape 1.8 Lipoic acid 1.3
Coenzyme Q10 0.8 Milk Thistle 11.5 Ashwagandha 7.1 Bacopa monnieri
7.7 Green Tea 3.8 Turmeric 3.8 Wasabi japonica 5.1 Olive leaf 3.8
Capsaicin 4.2 Nicotinic acid 0.1
[0139] Table 22 below shows an example embodiment of the
composition.
TABLE-US-00022 TABLE 22 Component Weight Percent in Blend
Ashwagandha extract 7.6 Bacopa monnieri extract 7.8 Green tea
extract 3.9 Turmeric extract 3.9 Acetyl-L-Carnitine 26.0 Quercetin
7.3 Grape extract 3.6 Lipoic acid 2.6 Coenzyme Q10 1.6 Olive leaf
extract 6.5 Mango leaf extract 2.3 Wasabi japonica powder 8.0
Nicotinic acid 0.1 Milk Thistle Extract 11.7 Copper gluconate
0.1
[0140] Table 23 below shows an example embodiment of the
composition.
TABLE-US-00023 TABLE 23 Component Weight Percent Total Composition
Milk thistle extract 11.5 Ashwagandha extract 7.7 Bacopa monnieri
extract 7.7 Green tea extract 3.8 Turmeric extract 3.8
Hydroxypropyl methylcellulose 0.5 Calcium 7.9 Calcium carbonate
gran 6.1 Microcrystalline cellulose 5.1 Croscarmellose sodium 1.5
Silica 0.5 Medium chain triglycerides 0.5 Magnesium 0.7 Purified
water 3.8 Acetyl-L-carnitine 12.8 Quercetin 3.6 Lipoic acid 1.3
Coenzyme Q10 0.8 Grape extract 1.8 Wasabi rhizome powder 5.0 Mango
leaf extract 2.3 Nicotinic acid 0.1 Olive extract 2.5 Rice flour
6.3 Syloid 0.2 Copper gluconate 0.01
[0141] Table 24 below shows an example embodiment of the
composition.
TABLE-US-00024 TABLE 24 Component Weight Percent in Blend
Acetyl-L-Carnitine 32.9 Quercetin 3.2 Grape 2.3 Lipoic acid 0.3
Coenzyme Q10 0.1 Milk Thistle 8.5 Ashwagandha 4.2 Bacopa monnieri
4.8 Green Tea 13.5 Turmeric 8.6 Wasabi japonica 8.4 Olive leaf 7.5
Mango leaf extract 4.6 Nicotinic acid 0.0002
[0142] Table 25 below shows an example embodiment of the
composition.
TABLE-US-00025 TABLE 25 Component Weight Percent in Blend
Acetyl-L-Carnitine 12.2 Quercetin 0.2 Grape 0.04 Lipoic acid 0.02
Coenzyme Q10 0.008 Milk Thistle 0.5 Ashwagandha 0.2 Bacopa monnieri
0.2 Green Tea 0.05 Turmeric 0.05 Wasabi japonica 0.3 Olive leaf 0.2
Mango leaf extract 0.8 Nicotinic acid 0.000008
[0143] Table 26 below shows an example embodiment of the
composition.
TABLE-US-00026 TABLE 26 Component Weight Percent in Blend
Acetyl-L-Carnitine 12.3 Quercetin 1.0 Grape 0.2 Lipoic acid 0.1
Coenzyme Q10 0.04 Milk Thistle 2.9 Ashwagandha 1.3 Bacopa monnieri
1.2 Green Tea 5.6 Turmeric 0.3 Wasabi japonica 2.8 Olive leaf 3.5
Mango leaf extract 1.8 Nicotinic acid 0.00008
[0144] Table 27 below shows an example embodiment of the
composition.
TABLE-US-00027 TABLE 27 Component Weight Percent in Blend
Acetyl-L-Carnitine 15.3 Quercetin 1.2 Grape 0.3 Lipoic acid 0.2
Coenzyme Q10 0.06 Milk Thistle 3.7 Ashwagandha 1.6 Bacopa monnieri
1.6 Green Tea 0.4 Turmeric 0.4 Wasabi japonica 3.7 Olive leaf 2.4
Mango leaf extract 2.4 Nicotinic acid 0.0001
[0145] Table 28 below shows an example embodiment of the
composition.
TABLE-US-00028 TABLE 28 Component Weight Percent in Blend
Acetyl-L-Carnitine 12.8 Quercetin 3.6 Grape 1.8 Lipoic acid 1.3
Coenzyme Q10 0.8 Milk Thistle 11.5 Ashwagandha 7.1 Bacopa monnieri
7.7 Green Tea 3.8 Turmeric 3.8 Wasabi japonica 5.1 Olive leaf 3.8
Mango leaf extract 4.2 Nicotinic acid 0.1
[0146] According to one or more embodiments of the disclosure, a
composition may include a combination of all or some, but not all,
of the following ingredients:
[0147] a. acetyl-L-carnitine;
[0148] b. coenzyme Q10;
[0149] c. grape extract;
[0150] d. lipoic acid;
[0151] e. quercetin;
[0152] f. calcium;
[0153] g. milk thistle, may include milk thistle extract;
[0154] h. alpinia galanga;
[0155] i. capsaicin;
[0156] j. mango leaf extract;
[0157] k. bacopa, may include bacopa extract;
[0158] l. ashwagandha, may include ashwagandha extract;
[0159] m. green tea, may include green tea extract;
[0160] n. onion, may include onion extract or onion powder;
[0161] o. turmeric, may include turmeric extract;
[0162] p. niacin, may specifically include cuprous niacin;
[0163] q. copper;
[0164] r. wasabi, may include wasabi powder;
[0165] s. olive leaf, may include olive leaf extract;
[0166] t. theacrine;
[0167] u. ubiquinone;
[0168] v. thionic acid;
[0169] w. flavonoids;
[0170] x. alkaline earth metals;
[0171] y. isothiocyanates;
[0172] z. grape (seed, pulp, skin);
[0173] aa. calcium;
[0174] bb. magnesium;
[0175] cc. copper niacin complex;
[0176] dd. proanthocyanins;
[0177] ee. resveratrol;
[0178] ff. garlic, may include garlic extract;
[0179] gg- cinnamon, may include cinnamon extract or ground
cinnamon powder;
[0180] hh. caffeine;
[0181] ii. theobromine;
[0182] jj. yerba mate extracts;
[0183] kk. cocoa, may include cocoa extract or ground cocoa
powder;
[0184] ll. ferulic acid;
[0185] mm. rhubarb, may include rhubarb extract;
[0186] nn. hydroxycinnamic acid;
[0187] oo. ginger, may include ginger extract;
[0188] pp. ginseng, may include ginseng extract;
[0189] qq. skullcap;
[0190] rr. Brazilian green propolis extract;
[0191] ss. myricetin;
[0192] tt. nicotinic acid;
[0193] uu. nicotinamide;
[0194] vv. nicotinamide c;
[0195] ww. ribose;
[0196] xx. vitamin B3;
[0197] yy. nicotinamide mononucleotide;
[0198] zz. tryptophan;
[0199] aaa. quinolinic acid;
[0200] bbb. beta-namn; and/or
[0201] ccc. beta-naad.
[0202] Embodiments of the composition may comprise, for example,
concentrations of acetyl-L-carnitine as follows:
[0203] a1) from about 2 wt % to about 90 wt % the total
composition;
[0204] a2) from about 5 wt % to about 90 wt % the total
composition;
[0205] a3) from about 10 wt % to about 90 wt % the total
composition;
[0206] a4) from about 15 wt % to about 90 wt % the total
composition;
[0207] a5) from about 20 wt % to about 90 wt % the total
composition;
[0208] a6) from about 25 wt % to about 90 wt % the total
composition;
[0209] a7) from about 30 wt % to about 90 wt % the total
composition;
[0210] a8) from about 2 wt % to about 85 wt % the total
composition;
[0211] a9) from about 2 wt % to about 80 wt % the total
composition;
[0212] a10) from about 2 wt % to about 75 wt % the total
composition;
[0213] a11) from about 2 wt % to about 70 wt % the total
composition;
[0214] a12) from about 2 wt % to about 65 wt % the total
composition;
[0215] a13) from about 2 wt % to about 50 wt % the total
composition;
[0216] a14) from about 2 wt % to about 45 wt % the total
composition;
[0217] a15) from about 2 wt % to about 40 wt % the total
composition;
[0218] a16) from about 2 wt % to about 35 wt % the total
composition;
[0219] a17) from about 2 wt % to about 30 wt % the total
composition;
[0220] a18) from about 2 wt % to about 25 wt % the total
composition;
[0221] a19) from about 2 wt % to about 20 wt % the total
composition;
[0222] a20) from about 2 wt % to about 15 wt % the total
composition;
[0223] a21) from about 2 wt % to about 10 wt % the total
composition;
[0224] a22) from about 20 wt % to about 30 wt % the total
composition;
[0225] a23) from about 22 wt % to about 30 wt % the total
composition;
[0226] a24) from about 24 wt % to about 30 wt % the total
composition;
[0227] a25) from about 25 wt % to about 30 wt % the total
composition;
[0228] a26) from about 26 wt % to about 30 wt % the total
composition;
[0229] a27) from about 28 wt % to about 30 wt % the total
composition;
[0230] a28) from about 20 wt % to about 28 wt % the total
composition;
[0231] a29) from about 20 wt % to about 26 wt % the total
composition;
[0232] a30) from about 20 wt % to about 24 wt % the total
composition;
[0233] a31) from about 10 wt % to about 30 wt % the total
composition;
[0234] a32) from about 5 wt % to about 15 wt % the total
composition;
[0235] a33) from about 5 wt % to about 14 wt % the total
composition;
[0236] a34) from about 5 wt % to about 16 wt % the total
composition;
[0237] a35) from about 5 wt % to about 18 wt % the total
composition;
[0238] a36) from about 5 wt % to about 20 wt % the total
composition;
[0239] a37) from about 10 wt % to about 13 wt % the total
composition;
[0240] a38) from about 10 wt % to about 15 wt % the total
composition;
[0241] a39) from about 5 wt % to about 40 wt % the total
composition;
[0242] a40) from about 5 wt % to about 50 wt % the total
composition; or
[0243] a41) from about 25 wt % to about 27 wt % the total
composition.
[0244] Embodiments of the composition may comprise, for example,
concentrations of coenzyme Q10 as follows:
[0245] b1) from about 0.005 wt % to about 50 wt % the total
composition;
[0246] b2) from about 0.005 wt % to about 45 wt % the total
composition;
[0247] b3) from about 0.005 wt % to about 40 wt % the total
composition;
[0248] b4) from about 0.005 wt % to about 35 wt % the total
composition;
[0249] b5) from about 0.005 wt % to about 30 wt % the total
composition;
[0250] b6) from about 0.005 wt % to about 25 wt % the total
composition;
[0251] b7) from about 0.005 wt % to about 20 wt % the total
composition;
[0252] b8) from about 0.005 wt % to about 15 wt % the total
composition;
[0253] b9) from about 0.005 wt % to about 10 wt % the total
composition;
[0254] b10) from about 0.005 wt % to about 5 wt % the total
composition;
[0255] b11) from about 0.005 wt % to about 4 wt % the total
composition;
[0256] b12) from about 0.005 wt % to about 3 wt % the total
composition;
[0257] b13) from about 0.005 wt % to about 2 wt % the total
composition;
[0258] b14) from about 0.005 wt % to about 1 wt % the total
composition;
[0259] b15) from about 0.005 wt % to about 0.9 wt % the total
composition;
[0260] b16) from about 0.005 wt % to about 0.8 wt % the total
composition;
[0261] b17) from about 0.005 wt % to about 0.7 wt % the total
composition;
[0262] b18) from about 0.005 wt % to about 0.6 wt % the total
composition;
[0263] b19) from about 0.005 wt % to about 0.5 wt % the total
composition;
[0264] b20) from about 0.005 wt % to about 0.4 wt % the total
composition;
[0265] b21) from about 0.005 wt % to about 0.3 wt % the total
composition;
[0266] b22) from about 0.005 wt % to about 0.2 wt % the total
composition;
[0267] b23) from about 0.005 wt % to about 0.1 wt % the total
composition;
[0268] b24) from about 0.008 wt % to about 1 wt % the total
composition;
[0269] b25) from about 0.008 wt % to about 0.9 wt % the total
composition;
[0270] b26) from about 0.008 wt % to about 0.8 wt % the total
composition;
[0271] b27) from about 0.008 wt % to about 0.7 wt % the total
composition;
[0272] b28) from about 0.008 wt % to about 0.6 wt % the total
composition;
[0273] b29) from about 0.008 wt % to about 0.5 wt % the total
composition;
[0274] b30) from about 0.008 wt % to about 0.4 wt % the total
composition;
[0275] b31) from about 0.008 wt % to about 0.3 wt % the total
composition;
[0276] b32) from about 0.5 wt % to about 5 wt % the total
composition;
[0277] b33) from about 1 wt % to about 5 wt % the total
composition;
[0278] b34) from about 2 wt % to about 5 wt % the total
composition;
[0279] b35) from about 3 wt % to about 5 wt % the total
composition;
[0280] b36) from about 4 wt % to about 5 wt % the total
composition;
[0281] b37) from about 0.5 wt % to about 4 wt % the total
composition;
[0282] b38) from about 0.5 wt % to about 3 wt % the total
composition;
[0283] b39) from about 0.5 wt % to about 2 wt % the total
composition;
[0284] b40) from about 0.5 wt % to about 6 wt % the total
composition;
[0285] b41) from about 0.5 wt % to about 7 wt % the total
composition;
[0286] b42) from about 0.5 wt % to about 8 wt % the total
composition;
[0287] b43) from about 0.5 wt % to about 9 wt % the total
composition;
[0288] b44) from about 0.5 wt % to about 10 wt % the total
composition;
[0289] b45) from about 0.2 wt % to about 1 wt % the total
composition;
[0290] b46) from about 0.3 wt % to about 1 wt % the total
composition;
[0291] b47) from about 0.4 wt % to about 1 wt % the total
composition; or
[0292] b48) from about 0.6 wt % to about 0.9 wt % the total
composition.
[0293] Embodiments of the composition may comprise, for example,
concentrations of grape extract, which may include grape leaf
extract, as follows:
[0294] c1) from about 0.04 wt % to about 20 wt % the total
composition;
[0295] c2) from about 0.04 wt % to about 15 wt % the total
composition;
[0296] c3) from about 0.04 wt % to about 10 wt % the total
composition;
[0297] c4) from about 0.04 wt % to about 9 wt % the total
composition;
[0298] c5) from about 0.04 wt % to about 8 wt % the total
composition;
[0299] c6) from about 0.04 wt % to about 7 wt % the total
composition;
[0300] c7) from about 0.04 wt % to about 6 wt % the total
composition;
[0301] c8) from about 0.04 wt % to about 5 wt % the total
composition;
[0302] c9) from about 0.04 wt % to about 4 wt % the total
composition;
[0303] c10) from about 0.04 wt % to about 3 wt % the total
composition;
[0304] c11) from about 0.04 wt % to about 2 wt % the total
composition; or
[0305] c12) from about 0.04 wt % to about 1 wt % the total
composition.
[0306] Embodiments of the composition may comprise, for example,
concentrations of lipoic acid as follows:
[0307] d1) from about 0.5 wt % to about 5 wt % the total
composition;
[0308] d2) from about 1 wt % to about 5 wt % the total
composition;
[0309] d3) from about 2 wt % to about 5 wt % the total
composition;
[0310] d4) from about 3 wt % to about 5 wt % the total
composition;
[0311] d5) from about 4 wt % to about 5 wt % the total
composition;
[0312] d6) from about 0.5 wt % to about 4 wt % the total
composition;
[0313] d7) from about 0.5 wt % to about 3 wt % the total
composition;
[0314] d8) from about 0.5 wt % to about 2 wt % the total
composition;
[0315] d9) from about 0.5 wt % to about 6 wt % the total
composition;
[0316] d10) from about 0.5 wt % to about 7 wt % the total
composition;
[0317] d11) from about 0.5 wt % to about 8 wt % the total
composition;
[0318] d12) from about 0.5 wt % to about 9 wt % the total
composition;
[0319] d13) from about 0.5 wt % to about 10 wt % the total
composition;
[0320] d14) from about 2 wt % to about 3 wt % the total
composition;
[0321] d15) from about 1 wt % to about 2 wt % the total
composition;
[0322] d16) from about 1 wt % to about 1.5 wt % the total
composition;
[0323] d17) from about 0.1 wt % to about 2 wt % the total
composition; or
[0324] d18) from about 0.1 wt % to about 4 wt % the total
composition.
[0325] Embodiments of the composition may comprise, for example,
concentrations of quercetin as follows:
[0326] e1) from about 0.1 wt % to about 40 wt % the total
composition;
[0327] e2) from about 0.1 wt % to about 35 wt % the total
composition;
[0328] e3) from about 0.1 wt % to about 30 wt % the total
composition;
[0329] e4) from about 0.1 wt % to about 25 wt % the total
composition;
[0330] e5) from about 0.1 wt % to about 20 wt % the total
composition;
[0331] e6) from about 0.1 wt % to about 15 wt % the total
composition;
[0332] e7) from about 0.1 wt % to about 10 wt % the total
composition;
[0333] e8) from about 0.1 wt % to about 9 wt % the total
composition;
[0334] e9) from about 0.1 wt % to about 8 wt % the total
composition;
[0335] e10) from about 0.1 wt % to about 7 wt % the total
composition;
[0336] e11) from about 0.1 wt % to about 6 wt % the total
composition;
[0337] e12) from about 0.2 wt % to about 7 wt % the total
composition;
[0338] e13) from about 0.3 wt % to about 7 wt % the total
composition;
[0339] e14) from about 0.4 wt % to about 7 wt % the total
composition;
[0340] e15) from about 0.5 wt % to about 7 wt % the total
composition;
[0341] e16) from about 0.6 wt % to about 7 wt % the total
composition;
[0342] e17) from about 0.7 wt % to about 7 wt % the total
composition;
[0343] e18) from about 0.8 wt % to about 7 wt % the total
composition;
[0344] e19) from about 0.9 wt % to about 7 wt % the total
composition; or
[0345] e20) from about 1 wt % to about 10 wt % the total
composition;
[0346] Embodiments of the composition may comprise, for example,
concentrations of alpinia galanga as follows:
[0347] h1) from about 0.1 wt % to about 55 wt % the total
composition;
[0348] h2) from about 0.1 wt % to about 50 wt % the total
composition;
[0349] h3) from about 0.1 wt % to about 45 wt % the total
composition;
[0350] h4) from about 0.1 wt % to about 40 wt % the total
composition;
[0351] h5) from about 0.1 wt % to about 35 wt % the total
composition;
[0352] h6) from about 0.1 wt % to about 30 wt % the total
composition;
[0353] h7) from about 0.1 wt % to about 25 wt % the total
composition;
[0354] h8) from about 0.1 wt % to about 20 wt % the total
composition;
[0355] h9) from about 0.1 wt % to about 15 wt % the total
composition;
[0356] h10) from about 0.2 wt % to about 15 wt % the total
composition;
[0357] h11) from about 0.3 wt % to about 15 wt % the total
composition;
[0358] h12) from about 0.4 wt % to about 15 wt % the total
composition;
[0359] h13) from about 0.5 wt % to about 15 wt % the total
composition;
[0360] h14) from about 0.6 wt % to about 15 wt % the total
composition;
[0361] h15) from about 0.7 wt % to about 15 wt % the total
composition;
[0362] h16) from about 0.8 wt % to about 15 wt % the total
composition;
[0363] h17) from about 0.9 wt % to about 15 wt % the total
composition;
[0364] h18) from about 1 wt % to about 15 wt % the total
composition;
[0365] h19) from about 2 wt % to about 15 wt % the total
composition;
[0366] h20) from about 3 wt % to about 15 wt % the total
composition;
[0367] h21) from about 4 wt % to about 15 wt % the total
composition;
[0368] h22) from about 5 wt % to about 15 wt % the total
composition;
[0369] h23) from about 6 wt % to about 15 wt % the total
composition;
[0370] h24) from about 7 wt % to about 15 wt % the total
composition;
[0371] h25) from about 8 wt % to about 15 wt % the total
composition;
[0372] h26) from about 9 wt % to about 15 wt % the total
composition;
[0373] h27) from about 10 wt % to about 15 wt % the total
composition;
[0374] h28) from about 0.5 wt % to about 10 wt % the total
composition;
[0375] h29) from about 1 wt % to about 10 wt % the total
composition;
[0376] h30) from about 2 wt % to about 10 wt % the total
composition;
[0377] h31) from about 3 wt % to about 10 wt % the total
composition;
[0378] h32) from about 4 wt % to about 10 wt % the total
composition;
[0379] h33) from about 5 wt % to about 10 wt % the total
composition;
[0380] h34) from about 5 wt % to about 9 wt % the total
composition;
[0381] h35) from about 5 wt % to about 8 wt % the total
composition;
[0382] h36) from about 5 wt % to about 7 wt % the total
composition;
[0383] h37) from about 5 wt % to about 6 wt % the total
composition;
[0384] h38) from about 7 wt % to about 8 wt % the total
composition;
[0385] h39) from about 6 wt % to about 9 wt % the total
composition;
[0386] h40) from about 6 wt % to about 8 wt % the total
composition;
[0387] h41) from about 5 wt % to about 15 wt % the total
composition;
[0388] h42) from about 5 wt % to about 20 wt % the total
composition;
[0389] h43) from about 2 wt % to about 4 wt % the total
composition;
[0390] h44) from about lwt % to about 5 wt % the total
composition;
[0391] h45) from about lwt % to about 8 wt % the total composition;
or
[0392] h46) from about lwt % to about 10 wt % the total
composition.
[0393] Embodiments of the composition may comprise, for example,
concentrations of capsaicin as follows:
[0394] i1) from about 0.1 wt % to about 55 wt % the total
composition;
[0395] i2) from about 0.1 wt % to about 50 wt % the total
composition;
[0396] i3) from about 0.1 wt % to about 45 wt % the total
composition;
[0397] i4) from about 0.1 wt % to about 40 wt % the total
composition;
[0398] i5) from about 0.1 wt % to about 35 wt % the total
composition;
[0399] i6) from about 0.1 wt % to about 30 wt % the total
composition;
[0400] i7) from about 0.1 wt % to about 25 wt % the total
composition;
[0401] i8) from about 0.1 wt % to about 20 wt % the total
composition;
[0402] i9) from about 0.1 wt % to about 15 wt % the total
composition;
[0403] i10) from about 0.2 wt % to about 15 wt % the total
composition;
[0404] i11) from about 0.3 wt % to about 15 wt % the total
composition;
[0405] i12) from about 0.4 wt % to about 15 wt % the total
composition;
[0406] i13) from about 0.5 wt % to about 15 wt % the total
composition;
[0407] i14) from about 0.6 wt % to about 15 wt % the total
composition;
[0408] i15) from about 0.7 wt % to about 15 wt % the total
composition;
[0409] i16) from about 0.8 wt % to about 15 wt % the total
composition;
[0410] i17) from about 0.9 wt % to about 15 wt % the total
composition;
[0411] i18) from about lwt % to about 15 wt % the total
composition;
[0412] i19) from about 2 wt % to about 15 wt % the total
composition;
[0413] i20) from about 3 wt % to about 15 wt % the total
composition;
[0414] i21) from about 4 wt % to about 15 wt % the total
composition;
[0415] i22) from about 5 wt % to about 15 wt % the total
composition;
[0416] i23) from about 6 wt % to about 15 wt % the total
composition;
[0417] i24) from about 7 wt % to about 15 wt % the total
composition;
[0418] i25) from about 8 wt % to about 15 wt % the total
composition;
[0419] i26) from about 9 wt % to about 15 wt % the total
composition;
[0420] i27) from about 10 % to about 15 wt % the total
composition;
[0421] i28) from about 0.5 wt % to about 10 % the total
composition;
[0422] i29) from about lwt % to about 10 % the total
composition;
[0423] i30) from about 2 wt % to about 10 % the total
composition;
[0424] i31) from about 3 wt % to about 10 % the total
composition;
[0425] i32) from about 4 wt % to about 10 % the total
composition;
[0426] i33) from about 5 wt % to about 10 % the total
composition;
[0427] i34) from about 5 wt % to about 9 wt % the total
composition;
[0428] i35) from about 5 wt % to about 8 wt % the total
composition;
[0429] i36) from about 5 wt % to about 7 wt % the total
composition;
[0430] i37) from about 5 wt % to about 6 wt % the total
composition;
[0431] i38) from about 7 wt % to about 8 wt % the total
composition;
[0432] i39) from about 6 wt % to about 9 wt % the total
composition;
[0433] i40) from about 6 wt % to about 8 wt % the total
composition;
[0434] i41) from about 5 wt % to about 15 wt % the total
composition;
[0435] i42) from about 5 wt % to about 20 wt % the total
composition;
[0436] i43) from about 2 wt % to about 4 wt % the total
composition;
[0437] i44) from about 1 wt % to about 5 wt % the total
composition;
[0438] i45) from about 1 wt % to about 8 wt % the total
composition; or
[0439] i46) from about 1 wt % to about 10 wt % the total
composition.
[0440] Embodiments of the composition may comprise, for example,
concentrations of mango leaf extract as follows:
[0441] j 1) from about 0.1 wt % to about 55 wt % the total
composition;
[0442] j2) from about 0.1 wt % to about 50 wt % the total
composition;
[0443] j3) from about 0.1 wt % to about 45 wt % the total
composition;
[0444] j4) from about 0.1 wt % to about 40 wt % the total
composition;
[0445] j5) from about 0.1 wt % to about 35 wt % the total
composition;
[0446] j6) from about 0.1 wt % to about 30 wt % the total
composition;
[0447] j7) from about 0.1 wt % to about 25 wt % the total
composition;
[0448] j8) from about 0.1 wt % to about 20 wt % the total
composition;
[0449] j9) from about 0.1 wt % to about 15 wt % the total
composition;
[0450] j10) from about 0.2 wt % to about 15 wt % the total
composition;
[0451] j 11) from about 0.3 wt % to about 15 wt % the total
composition;
[0452] j12) from about 0.4 wt % to about 15 wt % the total
composition;
[0453] j13) from about 0.5 wt % to about 15 wt % the total
composition;
[0454] j14) from about 0.6 wt % to about 15 wt % the total
composition;
[0455] j15) from about 0.7 wt % to about 15 wt % the total
composition;
[0456] j 16) from about 0.8 wt % to about 15 wt % the total
composition;
[0457] j17) from about 0.9 wt % to about 15 wt % the total
composition;
[0458] j18) from about lwt % to about 15 wt % the total
composition;
[0459] j19) from about 2 wt % to about 15 wt % the total
composition;
[0460] j20) from about 3 wt % to about 15 wt % the total
composition;
[0461] j21) from about 4 wt % to about 15 wt % the total
composition;
[0462] j22) from about 5 wt % to about 15 wt % the total
composition;
[0463] j23) from about 6 wt % to about 15 wt % the total
composition;
[0464] j24) from about 7 wt % to about 15 wt % the total
composition;
[0465] j25) from about 8 wt % to about 15 wt % the total
composition;
[0466] j26) from about 9 wt % to about 15 wt % the total
composition;
[0467] j27) from about 10 % to about 15 wt % the total
composition;
[0468] j28) from about 0.5 wt % to about 10 % the total
composition;
[0469] j29) from about lwt % to about 10 % the total
composition;
[0470] j30) from about 2 wt % to about 10 % the total
composition;
[0471] j31) from about 3 wt % to about 10 % the total
composition;
[0472] j32) from about 4 wt % to about 10 % the total
composition;
[0473] j33) from about 5 wt % to about 10 % the total
composition;
[0474] j34) from about 5 wt % to about 9 wt % the total
composition;
[0475] j35) from about 5 wt % to about 8 wt % the total
composition;
[0476] j36) from about 5 wt % to about 7 wt % the total
composition;
[0477] j37) from about 5 wt % to about 6 wt % the total
composition;
[0478] j38) from about 7 wt % to about 8 wt % the total
composition;
[0479] j39) from about 6 wt % to about 9 wt % the total
composition;
[0480] j40) from about 6 wt % to about 8 wt % the total
composition;
[0481] j41) from about 5 wt % to about 15 wt % the total
composition;
[0482] j42) from about 5 wt % to about 20 wt % the total
composition;
[0483] j43) from about 2 wt % to about 4 wt % the total
composition;
[0484] j44) from about lwt % to about 5 wt % the total
composition;
[0485] j45) from about lwt % to about 8 wt % the total composition;
or
[0486] j46) from about lwt % to about 10 % the total
composition.
[0487] Embodiments of the composition may comprise, for example,
concentrations of ashwagandha as follows:
[0488] l1) from about 0.2 wt % to about 60 wt % the total
composition;
[0489] l2) from about 0.2 wt % to about 55 wt % the total
composition;
[0490] l3) from about 0.2 wt % to about 50 wt % the total
composition;
[0491] l4) from about 0.2 wt % to about 45 wt % the total
composition;
[0492] l5) from about 0.2 wt % to about 40 wt % the total
composition;
[0493] l6) from about 0.2 wt % to about 35 wt % the total
composition;
[0494] l7) from about 0.2 wt % to about 30 wt % the total
composition;
[0495] l8) from about 0.2 wt % to about 25 wt % the total
composition;
[0496] l9) from about 0.2 wt % to about 20 wt % the total
composition;
[0497] l10) from about 0.2 wt % to about 15 wt % the total
composition;
[0498] l11) from about 0.2 wt % to about 10 % the total
composition;
[0499] l12) from about 0.2 wt % to about 9 wt % the total
composition;
[0500] l13) from about 0.2 wt % to about 8 wt % the total
composition;
[0501] l14) from about 0.2 wt % to about 7 wt % the total
composition;
[0502] l15) from about 0.2 wt % to about 6 wt % the total
composition;
[0503] l16) from about 0.2 wt % to about 5 wt % the total
composition;
[0504] l17) from about 0.2 wt % to about 4 wt % the total
composition;
[0505] l18) from about 0.2 wt % to about 3 wt % the total
composition;
[0506] l19) from about 0.2 wt % to about 15 wt % the total
composition;
[0507] l20) from about 0.3 wt % to about 15 wt % the total
composition;
[0508] l21) from about 0.4 wt % to about 15 wt % the total
composition;
[0509] l22) from about 0.5 wt % to about 15 wt % the total
composition;
[0510] l23) from about 0.6 wt % to about 15 wt % the total
composition;
[0511] l24) from about 0.7 wt % to about 15 wt % the total
composition;
[0512] l25) from about 0.8 wt % to about 15 wt % the total
composition;
[0513] l26) from about 0.9 wt % to about 15 wt % the total
composition;
[0514] l27) from about lwt % to about 15 wt % the total
composition;
[0515] l28) from about 2 wt % to about 15 wt % the total
composition;
[0516] l29) from about 3 wt % to about 15 wt % the total
composition;
[0517] l30) from about 4 wt % to about 15 wt % the total
composition;
[0518] l31) from about 5 wt % to about 15 wt % the total
composition;
[0519] l32) from about 6 wt % to about 15 wt % the total
composition;
[0520] l33) from about 7 wt % to about 15 wt % the total
composition;
[0521] l34) from about 8 wt % to about 15 wt % the total
composition;
[0522] l35) from about 9 wt % to about 15 wt % the total
composition;
[0523] l36) from about 10 wt % to about 15 wt % the total
composition;
[0524] l37) from about 11 wt % to about 15 wt % the total
composition;
[0525] l38) from about 0.5 wt % to about 10 % the total
composition;
[0526] l39) from about 1 wt % to about 10 % the total
composition;
[0527] l40) from about 2 wt % to about 10 % the total
composition;
[0528] l41) from about 3 wt % to about 10 % the total
composition;
[0529] l42) from about 4 wt % to about 10 % the total
composition;
[0530] l43) from about 5 wt % to about 10 % the total
composition;
[0531] l44) from about 5 wt % to about 9 wt % the total
composition;
[0532] l45) from about 5 wt % to about 8 wt % the total
composition;
[0533] l46) from about 5 wt % to about 7 wt % the total
composition;
[0534] l47) from about 5 wt % to about 6 wt % the total
composition;
[0535] l48) from about 7 wt % to about 8 wt % the total
composition;
[0536] l49) from about 6 wt % to about 9 wt % the total
composition;
[0537] l50) from about 6 wt % to about 8 wt % the total
composition;
[0538] l51) from about 5 wt % to about 15 wt % the total
composition; or
[0539] l52) from about 5 wt % to about 20 wt % the total
composition.
[0540] Other embodiments of the composition may comprise, for
example, concentrations of green tea extract as follows:
[0541] m1) from about 0.05 wt % to about 40 wt % the total
composition;
[0542] m2) from about 0.05 wt % to about 35 wt % the total
composition;
[0543] m3) from about 0.05 wt % to about 30 wt % the total
composition;
[0544] m4) from about 0.05 wt % to about 25 wt % the total
composition;
[0545] m5) from about 0.05 wt % to about 20 wt % the total
composition;
[0546] m6) from about 0.05 wt % to about 15 wt % the total
composition;
[0547] m7) from about 0.05 wt % to about 10 % the total
composition;
[0548] m8) from about 0.05 wt % to about 9 wt % the total
composition;
[0549] m9) from about 0.05 wt % to about 8 wt % the total
composition;
[0550] m10) from about 0.05 wt % to about 7 wt % the total
composition;
[0551] m11) from about 0.05 wt % to about 6 wt % the total
composition;
[0552] m12) from about 0.05 wt % to about 5 wt % the total
composition;
[0553] m13) from about 0.05 wt % to about 4 wt % the total
composition;
[0554] m14) from about 0.05 wt % to about 3 wt % the total
composition;
[0555] m15) from about 0.05 wt % to about 2.5 wt % the total
composition;
[0556] m16) from about 0.1 wt % to about 5 wt % the total
composition;
[0557] m17) from about 0.2 wt % to about 5 wt % the total
composition;
[0558] m18) from about 0.3 wt % to about 5 wt % the total
composition;
[0559] m19) from about 0.4 wt % to about 5 wt % the total
composition;
[0560] m20) from about 0.5 wt % to about 5 wt % the total
composition;
[0561] m21) from about 0.7 wt % to about 5 wt % the total
composition;
[0562] m22) from about 0.8 wt % to about 5 wt % the total
composition;
[0563] m23) from about 0.9 wt % to about 5 wt % the total
composition;
[0564] m24) from about lwt % to about 5 wt % the total
composition;
[0565] m25) from about 1.1 wt % to about 5 wt % the total
composition;
[0566] m26) from about 1.2 wt % to about 5 wt % the total
composition;
[0567] m27) from about 1.3 wt % to about 5 wt % the total
composition;
[0568] m28) from about 1.4 wt % to about 5 wt % the total
composition;
[0569] m29) from about 1.5 wt % to about 5 wt % the total
composition;
[0570] m30) from about 1.6 wt % to about 5 wt % the total
composition;
[0571] m31) from about 1 wt % to about 5 wt % the total
composition;
[0572] m32) from about 1 wt % to about 4 wt % the total
composition;
[0573] m33) from about 1 wt % to about 3 wt % the total
composition;
[0574] m34) from about 2 wt % to about 5 wt % the total
composition;
[0575] m35) from about 3 wt % to about 5 wt % the total
composition;
[0576] m36) from about 4 wt % to about 5 wt % the total
composition;
[0577] m37) from about 3 wt % to about 6 wt % the total
composition;
[0578] m38) from about 3 wt % to about 7 wt % the total
composition;
[0579] m39) from about 3 wt % to about 8 wt % the total
composition;
[0580] m40) from about 3 wt % to about 9 wt % the total
composition;
[0581] m41) from about 3 wt % to about 10 % the total
composition;
[0582] m42) from about 3 wt % to about 15 wt % the total
composition;
[0583] m43) from about 3 wt % to about 20 wt % the total
composition;
[0584] m44) from about 4 wt % to about 20 wt % the total
composition;
[0585] m45) from about 5 wt % to about 20 wt % the total
composition;
[0586] m46) from about 0.5 wt % to about 5 wt % the total
composition;
[0587] m47) from about 0.5 wt % to about 6 wt % the total
composition; or
[0588] m48) from about 0.5 wt % to about 8 wt % the total
composition.
[0589] Embodiments of the composition may comprise, for example,
concentrations of turmeric as follows:
[0590] o1) from about 2 wt % to about 5 wt % the total
composition;
[0591] o2) from about 0.05 wt % to about 40 wt % the total
composition;
[0592] o3) from about 0.05 wt % to about 35 wt % the total
composition;
[0593] o4) from about 0.05 wt % to about 30 wt % the total
composition;
[0594] o5) from about 0.05 wt % to about 25 wt % the total
composition;
[0595] o6) from about 0.05 wt % to about 20 wt % the total
composition;
[0596] o7) from about 0.05 wt % to about 15 wt % the total
composition;
[0597] o8) from about 0.05 wt % to about 10 % the total
composition;
[0598] o9) from about 0.05 wt % to about 9 wt % the total
composition;
[0599] o10) from about 0.05 wt % to about 8 wt % the total
composition;
[0600] o11) from about 0.05 wt % to about 7 wt % the total
composition;
[0601] o12) from about 0.05 wt % to about 6 wt % the total
composition;
[0602] o13) from about 0.05 wt % to about 5 wt % the total
composition;
[0603] o14) from about 0.05 wt % to about 4 wt % the total
composition;
[0604] o15) from about 0.05 wt % to about 3 wt % the total
composition;
[0605] o16) from about 0.05 wt % to about 2.5 wt % the total
composition;
[0606] o17) from about 0.1 wt % to about 5 wt % the total
composition;
[0607] o18) from about 0.2 wt % to about 5 wt % the total
composition;
[0608] o19) from about 0.3 wt % to about 5 wt % the total
composition;
[0609] o20) from about 0.4 wt % to about 5 wt % the total
composition;
[0610] o21) from about 0.5 wt % to about 5 wt % the total
composition;
[0611] o22) from about 0.7 wt % to about 5 wt % the total
composition;
[0612] o23) from about 0.8 wt % to about 5 wt % the total
composition;
[0613] o24) from about 0.9 wt % to about 5 wt % the total
composition;
[0614] o25) from about lwt % to about 5 wt % the total
composition;
[0615] o26) from about 1.1 wt % to about 5 wt % the total
composition;
[0616] o27) from about 1.2 wt % to about 5 wt % the total
composition;
[0617] o28) from about 1.3 wt % to about 5 wt % the total
composition;
[0618] o29) from about 1.4 wt % to about 5 wt % the total
composition;
[0619] o30) from about 1.5 wt % to about 5 wt % the total
composition;
[0620] o31) from about 1.6 wt % to about 5 wt % the total
composition;
[0621] o32) from about lwt % to about 5 wt % the total
composition;
[0622] o33) from about lwt % to about 4 wt % the total
composition;
[0623] o34) from about lwt % to about 3 wt % the total
composition;
[0624] o35) from about 3 wt % to about 5 wt % the total
composition;
[0625] o36) from about 4 wt % to about 5 wt % the total
composition;
[0626] o37) from about 3 wt % to about 6 wt % the total
composition;
[0627] o38) from about 3 wt % to about 7 wt % the total
composition;
[0628] o39) from about 3 wt % to about 8 wt % the total
composition;
[0629] o40) from about 3 wt % to about 9 wt % the total
composition;
[0630] o41) from about 3 wt % to about 10 % the total
composition;
[0631] o42) from about 3 wt % to about 15 wt % the total
composition;
[0632] o43) from about 3 wt % to about 20 wt % the total
composition;
[0633] o44) from about 4 wt % to about 20 wt % the total
composition;
[0634] o45) from about 5 wt % to about 20 wt % the total
composition;
[0635] o46) from about 0.5 wt % to about 5 wt % the total
composition;
[0636] o47) from about 0.5 wt % to about 6 wt % the total
composition; or
[0637] o48) from about 0.5 wt % to about 8 wt % the total
composition.
[0638] Embodiments of the disclosure may comprise, for example,
concentrations of niacin as follows:
[0639] p1) from about 0 wt % to about 5 wt % the total
composition;
[0640] p2) from about 0.0001 wt % to about 5 wt % the total
composition;
[0641] p3) from about 0.0001 wt % to about 4 wt % the total
composition;
[0642] p4) from about 0.0001 wt % to about 3 wt % the total
composition;
[0643] p5) from about 0.0001 wt % to about 2 wt % the total
composition;
[0644] p6) from about 0.0001 wt % to about lwt % the total
composition;
[0645] p7) from about 0.0001 wt % to about 0.9 wt % the total
composition;
[0646] p8) from about 0.0001 wt % to about 0.8 wt % the total
composition;
[0647] p9) from about 0.0001 wt % to about 0.7 wt % the total
composition;
[0648] p10) from about 0.0001 wt % to about 0.6 wt % the total
composition;
[0649] p11) from about 0.0001 wt % to about 0.5 wt % the total
composition;
[0650] p12) from about 0.0001 wt % to about 0.4 wt % the total
composition;
[0651] p13) from about 0.0001 wt % to about 0.3 wt % the total
composition;
[0652] p14) from about 0.0001 wt % to about 0.2 wt % the total
composition;
[0653] p15) from about 0.0001 wt % to about 0.1 wt % the total
composition; or
[0654] p16) from about 0.0001 wt % to about 0.001 wt % the total
composition.
[0655] Embodiments of the disclosure may comprise, for example,
concentrations of wasabi as follows:
[0656] r1) from about 0.3 wt % to about 70 wt % the total
composition;
[0657] r2) from about 0.3 wt % to about 65 wt % the total
composition;
[0658] r3) from about 0.3 wt % to about 60 wt % the total
composition;
[0659] r4) from about 0.3 wt % to about 55 wt % the total
composition;
[0660] r5) from about 0.3 wt % to about 55 wt % the total
composition;
[0661] r6) from about 0.3 wt % to about 40 wt % the total
composition;
[0662] r7) from about 0.3 wt % to about 35 wt % the total
composition;
[0663] r8) from about 0.4 wt % to about 35 wt % the total
composition;
[0664] r9) from about 0.5 wt % to about 35 wt % the total
composition;
[0665] r10) from about 0.6 wt % to about 35 wt % the total
composition;
[0666] r11) from about 0.7 wt % to about 35 wt % the total
composition;
[0667] r12) from about 0.8 wt % to about 35 wt % the total
composition;
[0668] r13) from about 0.9 wt % to about 35 wt % the total
composition;
[0669] r14) from about lwt % to about 35 wt % the total
composition;
[0670] r15) from about 5 wt % to about 35 wt % the total
composition;
[0671] r16) from about 10 wt % to about 35 wt % the total
composition;
[0672] r17) from about 15 wt % to about 35 wt % the total
composition;
[0673] r18) from about 0.5 wt % to about 10 wt % the total
composition;
[0674] r19) from about 1 wt % to about 10 wt % the total
composition;
[0675] r20) from about 2 wt % to about 10 wt % the total
composition;
[0676] r21) from about 3 wt % to about 10 wt % the total
composition;
[0677] r22) from about 4 wt % to about 10 wt % the total
composition;
[0678] r23) from about 5 wt % to about 10 wt % the total
composition;
[0679] r24) from about 5 wt % to about 9 wt % the total
composition;
[0680] r25) from about 5 wt % to about 8 wt % the total
composition;
[0681] r26) from about 5 wt % to about 7 wt % the total
composition;
[0682] r27) from about 5 wt % to about 6 wt % the total
composition;
[0683] r28) from about 7 wt % to about 8 wt % the total
composition;
[0684] r29) from about 6 wt % to about 9 wt % the total
composition;
[0685] r30) from about 6 wt % to about 8 wt % the total
composition; or
[0686] r31) from about 5 wt % to about 15 wt % the total
composition.
[0687] Embodiments of the composition may comprise, for example,
concentrations of olive leaf as follows:
[0688] s1) from about 0.2 wt % to about 60 wt % the total
composition;
[0689] s2) from about 0.2 wt % to about 55 wt % the total
composition;
[0690] s3) from about 0.2 wt % to about 50 wt % the total
composition;
[0691] s4) from about 0.2 wt % to about 45 wt % the total
composition;
[0692] s5) from about 0.2 wt % to about 40 wt % the total
composition;
[0693] s6) from about 0.2 wt % to about 35 wt % the total
composition;
[0694] s7) from about 0.2 wt % to about 30 wt % the total
composition;
[0695] s8) from about 0.2 wt % to about 25 wt % the total
composition;
[0696] s9) from about 0.2 wt % to about 24 wt % the total
composition;
[0697] s10) from about 0.2 wt % to about 23 wt % the total
composition;
[0698] s11) from about 0.2 wt % to about 22 wt % the total
composition;
[0699] s12) from about 0.3 wt % to about 23 wt % the total
composition;
[0700] s13) from about 0.4 wt % to about 23 wt % the total
composition;
[0701] s14) from about 0.5 wt % to about 23 wt % the total
composition;
[0702] s15) from about 0.6 wt % to about 23 wt % the total
composition;
[0703] s16) from about 0.7 wt % to about 23 wt % the total
composition;
[0704] s17) from about 0.8 wt % to about 23 wt % the total
composition;
[0705] s18) from about 0.9 wt % to about 23 wt % the total
composition;
[0706] s19) from about 1 wt % to about 23 wt % the total
composition;
[0707] s20) from about 2 wt % to about 23 wt % the total
composition;
[0708] s21) from about 3 wt % to about 23 wt % the total
composition;
[0709] s22) from about 4 wt % to about 23 wt % the total
composition;
[0710] s23) from about 5 wt % to about 23 wt % the total
composition;
[0711] s24) from about 10 % to about 23 wt % the total
composition;
[0712] s25) from about 15 wt % to about 23 wt % the total
composition;
[0713] s26) from about 0.5 wt % to about 10 % the total
composition;
[0714] s27) from about lwt % to about 10 % the total
composition;
[0715] s28) from about 2 wt % to about 10 % the total
composition;
[0716] s29) from about 3 wt % to about 10 % the total
composition;
[0717] s30) from about 4 wt % to about 10 % the total
composition;
[0718] s31) from about 5 wt % to about 10 % the total
composition;
[0719] s32) from about 5 wt % to about 9 wt % the total
composition;
[0720] s33) from about 5 wt % to about 8 wt % the total
composition;
[0721] s34) from about 5 wt % to about 7 wt % the total
composition;
[0722] s35) from about 5 wt % to about 6 wt % the total
composition;
[0723] s36) from about 7 wt % to about 8 wt % the total
composition;
[0724] s37) from about 6 wt % to about 9 wt % the total
composition;
[0725] s38) from about 6 wt % to about 8 wt % the total
composition;
[0726] s39) from about 5 wt % to about 15 wt % the total
composition;
[0727] s40) from about 5 wt % to about 20 wt % the total
composition;
[0728] s41) from about 2 wt % to about 6 wt % the total
composition;
[0729] s42) from about 1 wt % to about 6 wt % the total
composition; or
[0730] s43) from about 2 wt % to about 4 wt % the total
composition.
[0731] Embodiments of the composition may comprise, for example,
concentrations of theacrine as follows:
[0732] t1 ) from about 0.1 wt % to about 55 wt % the total
composition;
[0733] t2) from about 0.1 wt % to about 50 wt % the total
composition;
[0734] t3) from about 0.1 wt % to about 45 wt % the total
composition;
[0735] t4) from about 0.1 wt % to about 40 wt % the total
composition;
[0736] t5) from about 0.1 wt % to about 35 wt % the total
composition;
[0737] t6) from about 0.1 wt % to about 30 wt % the total
composition;
[0738] t7) from about 0.1 wt % to about 25 wt % the total
composition;
[0739] t8) from about 0.1 wt % to about 20 wt % the total
composition;
[0740] t9) from about 0.1 wt % to about 15 wt % the total
composition;
[0741] t10) from about 0.2 wt % to about 15 wt % the total
composition;
[0742] t11) from about 0.3 wt % to about 15 wt % the total
composition;
[0743] t12) from about 0.4 wt % to about 15 wt % the total
composition;
[0744] t13) from about 0.5 wt % to about 15 wt % the total
composition;
[0745] t14) from about 0.6 wt % to about 15 wt % the total
composition;
[0746] t15) from about 0.7 wt % to about 15 wt % the total
composition;
[0747] t16) from about 0.8 wt % to about 15 wt % the total
composition;
[0748] t17) from about 0.9 wt % to about 15 wt % the total
composition;
[0749] t18) from about 1 wt % to about 15 wt % the total
composition;
[0750] t19) from about 2 wt % to about 15 wt % the total
composition;
[0751] t20) from about 3 wt % to about 15 wt % the total
composition;
[0752] t21) from about 4 wt % to about 15 wt % the total
composition;
[0753] t22) from about 5 wt % to about 15 wt % the total
composition;
[0754] t23) from about 6 wt % to about 15 wt % the total
composition;
[0755] t24) from about 7 wt % to about 15 wt % the total
composition;
[0756] t25) from about 8 wt % to about 15 wt % the total
composition;
[0757] t26) from about 9 wt % to about 15 wt % the total
composition;
[0758] t27) from about 10 wt % to about 15 wt % the total
composition;
[0759] t28) from about 0.5 wt % to about 10 wt % the total
composition;
[0760] t29) from about 1 wt % to about 10 wt % the total
composition;
[0761] t30) from about 2 wt % to about 10 wt % the total
composition;
[0762] t31) from about 3 wt % to about 10 wt % the total
composition;
[0763] t32) from about 4 wt % to about 10 wt % the total
composition;
[0764] t33) from about 5 wt % to about 10 wt % the total
composition;
[0765] t34) from about 5 wt % to about 9 wt % the total
composition;
[0766] t35) from about 5 wt % to about 8 wt % the total
composition;
[0767] t36) from about 5 wt % to about 7 wt % the total
composition;
[0768] t37) from about 5 wt % to about 6 wt % the total
composition;
[0769] t38) from about 7 wt % to about 8 wt % the total
composition;
[0770] t39) from about 6 wt % to about 9 wt % the total
composition;
[0771] t40) from about 6 wt % to about 8 wt % the total
composition;
[0772] t41) from about 5 wt % to about 15 wt % the total
composition;
[0773] t42) from about 5 wt % to about 20 wt % the total
composition;
[0774] t43) from about 2 wt % to about 4 wt % the total
composition;
[0775] t44) from about 1 wt % to about 5 wt % the total
composition;
[0776] t45) from about 1 wt % to about 8 wt % the total
composition; or
[0777] t46) from about 1 wt % to about 10 % the total
composition.
[0778] The foregoing percentages, concentrations, and ratios are
presented by example only and are not intended to be exhaustive or
to limit the disclosure to the precise percentages, concentrations,
and ratios disclosed. It should be appreciated that each value that
falls within a disclosed range is disclosed as if it were
individually disclosed as set forth herein. For example, a range
indicating a weight percent from about 8% to about 14% additionally
includes ranges beginning or ending with all values within that
range, including for example a range beginning at 8.1%, 8.2%, 8.3%,
9%, 10%, 11%, 12%, and so forth.
[0779] Also, according to one or more non-limiting embodiments of
the disclosure, any of the concentrations for ingredients for a
combination of the ingredients (a) thru (jj), for example, as
listed above, may indicate the concentration for other ingredients
listed above.
[0780] Example 1 is a composition. The composition includes one or
more of a first group consisting of milk thistle, ashwagandha,
green tea, bacopa monnieri, and turmeric. The composition includes
one or more of a second group consisting of acetyl-L-carnitine,
quercetin, lipoic acid, coenzyme Q10, cysteine, and grape. The
composition includes one or more of a third group consisting of
wasabi, theacrine, copper, niacin, cysteine, and olive extract.
[0781] Example 2 is a composition as in Example 1, wherein one or
more of: the milk thistle extract is screened milk thistle extract;
the ashwagandha extract is screened ashwagandha extract; the green
tea extract is screened green tea extract; the bacopa monnieri
extract is screened bacopa monnieri extract; or the turmeric
extract is screened turmeric extract.
[0782] Example 3 is a composition as in any of Examples 1-2,
wherein one or more of: the acetyl-L-carnitine is
acetyl-L-carnitine; the quercetin has greater than or equal to 90%
purity; the lipoic acid has greater than or equal to 98% purity;
the coenzyme Q10 has greater than or equal to 95% purity; or the
grape extract is screened grape.
[0783] Example 4 is a composition as in any of Examples 1-3,
wherein one or more of: the wasabi powder is wasabi japonica; the
copper and the cuprous niacin form a copper-niacin complex
comprising from 50 wt % to 80 wt % cuprous niacin and comprising
from 10 % to 30 wt % copper; or the olive leaf extract comprises
from 5 wt % to 20 wt % hydroxytyrosol.
[0784] Example 5 is a composition as in any of Examples 1-4,
wherein: the one or more of the first group is present in the
composition in an effective amount for increasing activation of an
Nrf2 pathway in a body; the one or more of the second group is
present in the composition in an effective amount for increasing
activation of an NRF1 pathway in the body; and the one or more of
the third group is present in the composition in an effective
amount for increasing activation of an NAD pathway in the body.
[0785] Example 6 is a composition as in any of Examples 1-5,
wherein the one or more of the first group is present in the
composition in an effective amount for increasing expression of
each of an NQO1gene in a body and a HMOX1 gene in the body.
[0786] Example 7 is a composition as in any of Examples 1-6,
wherein the one or more of the second group is present in the
composition in an effective amount for increasing expression of
each of an Nrf1 gene in a body and an PCG1-alpha gene in the
body.
[0787] Example 8 is a composition as in any of Examples 1-7,
wherein the one or more of the third group is present in the
composition in an effective amount for increasing expression of
each of an NMNAT1 gene in a body and an NAMPT gene in the body.
[0788] Example 9 is a composition as in any of Examples 1-8,
wherein the one or more of the first group is present in the
composition in an effective amount for reducing oxidative stress
and increasing detoxification in a body.
[0789] Example 10 is a composition as in any of Examples 1-9,
wherein the composition comprises multiple doses to be provided to
a user, wherein the first group comprises one or more doses, the
second group comprises one or more doses, and the third group
comprises one or more doses, wherein the doses for the first group,
the second group, and the third group are independent of one
another.
[0790] Example 11 is a composition. The composition includes an
effective amount of one or more elements of an Nrf2 group for
increasing activity of an Nrf2 pathway in a body, the Nrf2 group
comprising milk thistle extract, ashwagandha extract, green tea
extract, bacopa monnieri extract, and turmeric extract. The
composition includes an effective amount of one or more elements of
an NRF1 group for increasing activity of an NRF1 pathway in the
body, the NRF1 group comprising acetyl-L-carnitine, quercetin,
lipoic acid, and coenzyme Q10. The composition includes an
effective amount of one or more elements of an NAD group for
increasing activity of an NAD pathway in the body, the NAD group
comprising wasabi powder, theacrine, copper, cuprous niacin, and
olive leaf extract.
[0791] Example 12 is a composition as in Example 11, wherein: the
milk thistle extract is screened milk thistle extract 80 wt %
silymarin; the ashwagandha extract is screened ashwagandha extract
0.35% withaferin A; the green tea extract is screened green tea
extract 45% epigallocatechin gallate (EGCG); the bacopa monnieri
extract is screened bacopa monnieri extract 45% bacosides; and the
turmeric extract is screened turmeric extract.
[0792] Example 13 is a composition as in any of Examples 11-12,
wherein: the acetyl-L-carnitine is acetyl-L-carnitine with greater
than or equal to 95% purity; the quercetin has greater than or
equal to 90% purity; the lipoic acid has greater than or equal to
98% purity; the coenzyme Q10 has greater than or equal to 95%
purity; and the grape extract is screened grape.
[0793] Example 14 is a composition as in any of Examples 11-13,
wherein: the wasabi powder is wasabi japonica; the copper and the
cuprous niacin form a copper-niacin complex comprising from 50 wt %
to 80 wt % cuprous niacin and comprising from 10 % to 30 wt %
copper; and the olive leaf extract comprises from 5 wt % to 20 wt %
hydroxytyrosol.
[0794] Example 15 is a composition as in any of Examples 11-14,
wherein the effective amount of the one or more elements of the
Nrf2 group is an effective amount for increasing expression of each
of an NQO1 gene in the body and a HMOX1 gene in the body.
[0795] Example 16 is a composition as in any of Examples 11-15,
wherein the effective amount of the one or more elements of the
NRF1 group is an effective amount for increasing expression of each
of an Nrf1 gene in the body and an PCG1-alpha gene in the body.
[0796] Example 17 is a composition as in any of Examples 11-16,
wherein the effective amount of the one or more elements of the NAD
group is an effective amount for increasing expression of each of
an NMNAT1 gene in the body and an NAMPT gene in the body.
[0797] Example 18 is a composition as in any of Examples 11-17,
wherein the composition comprises one or more independent
compositions each encapsulated in a capsule.
[0798] Example 19 is a composition as in any of Examples 11-18,
wherein the composition is prepared for one or more of: oral
administration as a capsule; oral administration as a tablet;
intravenous administration; or intramuscular administration.
[0799] Example 20 is a method for slowing the effects of aging in a
user by improving overall stress response. The method includes
providing a composition to the user. The composition includes one
or more of a first group consisting of milk thistle extract,
ashwagandha extract, green tea extract, bacopa monnieri extract,
and turmeric extract. The composition includes one or more of a
second group consisting of acetyl-L-carnitine, quercetin, lipoic
acid, coenzyme Q10, and grape extract. The composition includes one
or more of a third group consisting of wasabi powder, theacrine,
copper, cuprous niacin, and olive leaf extract.
[0800] Example 21 is a method as in Example 20, wherein one or more
of: the milk thistle extract is screened milk thistle extract 80 wt
% silymarin; the ashwagandha extract is screened ashwagandha
extract 0.35% withaferin A; the green tea extract is screened green
tea extract 45% epigallocatechin gallate (EGCG); the bacopa
monnieri extract is screened bacopa monnieri extract 45% bacosides;
or the turmeric extract is screened turmeric extract.
[0801] Example 22 is a method as in any of Examples 20-21, wherein
one or more of: the acetyl-L-carnitine is acetyl-L-carnitine with
greater than or equal to 95% purity; the quercetin has greater than
or equal to 90% purity; the lipoic acid has greater than or equal
to 98% purity; the coenzyme Q10 has greater than or equal to 95%
purity; or the grape extract is screened grape.
[0802] Example 23 is a method as in any of Examples 20-22, wherein
one or more of: the wasabi powder is wasabi japonica; the copper
and the cuprous niacin form a copper-niacin complex comprising from
50 wt % to 80 wt % cuprous niacin and comprising from 10 % to 30 wt
% copper; or the olive leaf extract comprises from 5 wt % to 20 wt
% hydroxytyrosol.
[0803] Example 24 is a method as in any of Examples 20-23, wherein:
the one or more of the first group is present in the composition in
an effective amount for increasing activation of an Nrf2 pathway in
the user; the one or more of the second group is present in the
composition in an effective amount for increasing activation of an
NRF1 pathway in the user; and the one or more of the third group is
present in the composition in an effective amount for increasing
activation of an NAD pathway in the user.
[0804] Example 25 is a method as in any of Examples 20-24, wherein
the one or more of the first group is present in the composition in
an effective amount for increasing expression of each of an NQO1
gene in the user and an HMOX1 gene in the user.
[0805] Example 26 is a method as in any of Examples 20-25, wherein
the one or more of the second group is present in the composition
in an effective amount for increasing expression of each of an Nrfl
gene in the user and an PCG1-alpha gene in the user.
[0806] Example 27 is a method as in any of Examples 20-26, wherein
the one or more of the third group is present in the composition in
an effective amount for increasing expression of each of an NMNAT1
gene in the user and an NAMPT gene in the user.
[0807] Example 28 is a method as in any of Examples 20-27, wherein
providing the composition to the user comprises providing multiple
independent doses to the user, wherein the first group is provided
in a first dose, the second group is provided in a second dose, and
the third group is provided in a third dose.
[0808] Example 29 is a composition. The composition includes one or
more of a first group comprising milk thistle extract, ashwagandha
extract, green tea extract, bacopa monnieri extract, and turmeric
extract. The composition includes one or more of a second group
comprising acetyl-L-carnitine, quercetin, lipoic acid, coenzyme
Q10, and grape extract. The composition includes one or more of a
third group comprising wasabi powder, theacrine, copper, cuprous
niacin, and olive leaf extract.
[0809] Example 30 is a composition as in Example 29, wherein one or
more of: the milk thistle extract is screened milk thistle extract
80 wt % silymarin; the ashwagandha extract is screened ashwagandha
extract 0.35% withaferin A; the green tea extract is screened green
tea extract 45% epigallocatechin gallate (EGCG); the bacopa
monnieri extract is screened bacopa monnieri extract 45% bacosides;
or the turmeric extract is screened turmeric extract.
[0810] Example 31 is a composition as in any of Examples 29-30,
wherein one or more of: the acetyl-L-carnitine is
acetyl-L-carnitine with greater than or equal to 95% purity; the
quercetin has greater than or equal to 90% purity; the lipoic acid
has greater than or equal to 98% purity; the coenzyme Q10 has
greater than or equal to 95% purity; or the grape extract is
screened grape.
[0811] Example 32 is a composition as in any of Examples 29-31,
wherein one or more of: the wasabi powder is wasabi japonica; the
copper and the cuprous niacin form a copper-niacin complex
comprising from 50 wt % to 80 wt % cuprous niacin and comprising
from 10 % to 30 wt % copper; or the olive leaf extract comprises
from 5 wt % to 20 wt % hydroxytyrosol.
[0812] Example 33 is a composition as in any of Examples 29-32
wherein: the one or more of the first group is present in the
composition in an effective amount for increasing activation of an
Nrf2 pathway in a body; the one or more of the second group is
present in the composition in an effective amount for increasing
activation of an NRF1 pathway in the body; and the one or more of
the third group is present in the composition in an effective
amount for increasing activation of an NAD pathway in the body.
[0813] Example 34 is a composition as in any of Examples 29-33,
wherein the one or more of the first group is present in the
composition in an effective amount for increasing expression of
each of an NQO1 gene in a body and a HMOX1 gene in the body.
[0814] Example 35 is a composition as in any of Examples 29-34,
wherein the one or more of the second group is present in the
composition in an effective amount for increasing expression of
each of an Nrf1 gene in a body and an PCG1-alpha gene in the
body.
[0815] Example 36 is a composition as in any of Examples 29-35,
wherein the one or more of the third group is present in the
composition in an effective amount for increasing expression of
each of an NMNAT1 gene in a body and an NAMPT gene in the body.
[0816] Example 37 is a composition as in any of Examples 29-36,
wherein the one or more of the first group is present in the
composition in an effective amount for reducing oxidative stress
and increasing detoxification in a body.
[0817] Example 38 is a composition as in any of Examples 29-37,
wherein the composition comprises multiple doses to be provided to
a user, wherein the first group comprises one or more doses, the
second group comprises one or more doses, and the third group
comprises one or more doses, wherein the doses for the first group,
the second group, and the third group are independent of one
another.
[0818] Example 39 is a method for slowing the effects of aging in a
user by improving stress response. The method includes providing a
composition to the user. The composition includes one or more of a
first group comprising milk thistle extract, ashwagandha extract,
green tea extract, bacopa monnieri extract, and turmeric extract.
The composition includes one or more of a second group comprising
acetyl-L-carnitine, quercetin, lipoic acid, coenzyme Q10, and grape
extract. The composition includes one or more of a third group
comprising wasabi powder, theacrine, copper, cuprous niacin, and
olive leaf extract.
[0819] Example 40 is a method as in Example 39, wherein one or more
of: the milk thistle extract is screened milk thistle extract 80 wt
% silymarin; the ashwagandha extract is screened ashwagandha
extract 0.35% withaferin A; the green tea extract is screened green
tea extract 45% epigallocatechin gallate (EGCG); the bacopa
monnieri extract is screened bacopa monnieri extract 45% bacosides
; or the turmeric extract is screened turmeric extract.
[0820] Example 41 is a method as in any of Examples 39-40, wherein
one or more of: the acetyl-L-carnitine is acetyl-L-carnitine with
greater than or equal to 95% purity; the quercetin has greater than
or equal to 90% purity; the lipoic acid has greater than or equal
to 98% purity; the coenzyme Q10 has greater than or equal to 95%
purity; or the grape extract is screened grape.
[0821] Example 42 is a method as in any of Examples 39-41, wherein
one or more of: the wasabi powder is wasabi japonica; the copper
and the cuprous niacin form a copper-niacin complex comprising from
50 wt % to 80 wt % cuprous niacin and comprising from 10 % to 30 wt
% copper; or the olive leaf extract comprises from 5 wt % to 20 wt
% hydroxytyrosol.
[0822] Example 43 is a method as in any of Examples 39-42, wherein:
the one or more of the first group is present in the composition in
an effective amount for increasing activation of an Nrf2 pathway in
the user; the one or more of the second group is present in the
composition in an effective amount for increasing activation of an
NRF1 pathway in the user; and the one or more of the third group is
present in the composition in an effective amount for increasing
activation of an NAD pathway in the user.
[0823] Example 44 is a method as in any of Examples 39-43, wherein
the one or more of the first group is present in the composition in
an effective amount for increasing expression of each of an NQO1
gene in the user and a HMOX1 gene in the user.
[0824] Example 45 is a method as in any of Examples 39-44, wherein
the one or more of the second group is present in the composition
in an effective amount for increasing expression of each of an Nrf1
gene in the user and an PCG1-alpha gene in the user.
[0825] Example 46 is a method as in any of Examples 39-45, wherein
the one or more of the third group is present in the composition in
an effective amount for increasing expression of each of an NMNAT1
gene in the user and an NAMPT gene in the user.
[0826] Example 47 is a method as in any of Examples 39-46, wherein
providing the composition to the user comprises providing multiple
independent doses to the user, wherein the first group is provided
in a first dose, the second group is provided in a second dose, and
the third group is provided in a third dose.
[0827] Example 48 is a composition as in any of Examples 1-47,
wherein the first group comprises milk thistle, ashwagandha, green
tea, bacopa monnieri, turmeric, calcium, lychee, black pepper,
sulforaphane, isothiocyanates, cinnamon, ginger, stilbenes,
blueberry, broccoli, thioctic acids, asparagus, rosemary, carnosol,
carnosolic acid, luteolin, and sophora japonica.
[0828] Example 49 is a composition as in any of Examples 1-48,
wherein the second group comprises carnitine, acetyl-L-carnitine,
quercetin, lipoic acid, lipoamide, coenzyme Q10, ubiquinone,
ubiquinol, tetraphenylphosphonium, pyrroloquinoline quinone, grape,
ginseng, onion, and magnesium.
[0829] Example 50 is a composition as in any of Examples 1-49,
wherein the third group comprises wasabi, theacrine, copper,
niacin, cuprous niacin, nicotinic acid, nicotinamide, nicotinamide
riboside, ribose, nicotinamide mononucleotide, tryptophan,
quinolinic acid, NAMN, NAAD, olive leaf, olive, olive leaf extract,
resveratrol, rhodiola, caffeine, theobromine, paraxanthine,
theophylline, xanthines, mango, vitamin B12, and myricetin.
[0830] Example 51 is a composition as in any of Examples 1-50,
wherein the first group consists of milk thistle, ashwagandha,
green tea, bacopa monnieri, turmeric, calcium, lychee, black
pepper, sulforaphane, isothiocyanates, cinnamon, ginger, stilbenes,
blueberry, broccoli, thioctic acids, asparagus, rosemary, carnosol,
carnosolic acid, luteolin, and sophora japonica.
[0831] Example 52 is a composition as in any of Examples 1-51,
wherein the second group consists of carnitine, acetyl-L-carnitine,
quercetin, lipoic acid, lipoamide, coenzyme Q10, ubiquinone,
ubiquinol, tetraphenylphosphonium, pyrroloquinoline quinone, grape,
ginseng, onion, and magnesium.
[0832] Example 53 is a composition as in any of Examples 1-52,
wherein the third group consists of wasabi, theacrine, copper,
niacin, cuprous niacin, nicotinic acid, nicotinamide, nicotinamide
riboside, ribose, nicotinamide mononucleotide, tryptophan,
quinolinic acid, NAMN, NAAD, olive leaf, olive, olive leaf extract,
resveratrol, rhodiola, caffeine, theobromine, paraxanthine,
theophylline, xanthines, mango, vitamin B12, and myricetin.
[0833] Example 54 is a method as in any of Examples 1-53. The
method includes reducing oxidative stress in a body by increasing
activation of an Nrf2 pathway in the body through use of the
composition.
[0834] Example 55 is a method as in any of Examples 1-54. The
method includes generating enzymes capable of neutralizing more
than 1,000,000 free radicals in a body by increasing activation of
an Nrf2 pathway in the body through use of the composition.
[0835] Example 56 is a method as in any of Examples 1-55. The
method includes detoxifying genes in a body by increasing
activation of an Nrf2 pathway in the body through use of the
composition.
[0836] Example 57 is a method as in any of Examples 1-56. The
method includes enhancing cellular health in a body by increasing
activation of an NRF1 pathway in the body through use of the
composition.
[0837] Example 58 is a method as in any of Examples 1-57. The
method includes increasing a quantity of energy produced by cells
in a body by increasing activation of an NRF1 pathway in the body
through use of the composition.
[0838] Example 59 is a method as in any of Examples 1-58. The
method includes increasing mental focus and concentration for a
user by increasing activation of an NAD pathway in the user through
use of the composition.
[0839] Example 60 is a method as in any of Examples 1-59. The
method includes increasing mental energy and physical energy for a
user by increasing activation of an NAD pathway in the user through
use of the composition.
[0840] Example 61 is a method as in any of Examples 1-60. The
method includes regulating cholesterol levels in a user by
increasing activation of an NAD pathway in the user through use of
the composition.
[0841] Example 62 is a method as in any of Examples 1-61. The
method includes improving blood flow in a user by increasing
activation of an NAD pathway in the user through use of the
composition.
[0842] Example 63 is a method as in any of Examples 1-62. The
method includes ameliorating symptoms of aging in a user by
increasing activation of each of an Nrf2 pathway, an NRF1 pathway,
and an NAD pathway in the user through use of the composition.
[0843] Example 64 is a method as in any of Examples 1-63. The
method includes increasing activation of stress response processes
in a user by increasing activation of each of an Nrf2 pathway, an
NRF1 pathway, and an NAD pathway in the user through user of the
composition.
[0844] Example 65 is a composition as in any of Examples 1-64. The
composition includes one or more of a first group consisting of
milk thistle extract, ashwagandha extract, green tea extract,
bacopa monnieri extract, and turmeric extract. The composition
includes one or more of a second group consisting of
acetyl-L-carnitine, quercetin, lipoic acid, coenzyme Q10, and grape
extract. The composition includes one or more of a third group
consisting of wasabi powder, theacrine, copper, cuprous niacin, and
olive extract.
[0845] The foregoing description has been presented for purposes of
illustration. It is not exhaustive and does not limit the invention
to the precise forms or embodiments disclosed. Modifications and
adaptations will be apparent to those skilled in the art from
consideration of the specification and practice of the disclosed
embodiments. For example, components described herein may be
removed and other components added without departing from the scope
or spirit of the embodiments disclosed herein or the appended
claims.
[0846] Other embodiments will be apparent to those skilled in the
art from consideration of the specification and practice of the
disclosure disclosed herein. It is intended that the specification
and examples be considered as exemplary only, with a true scope and
spirit of the invention being indicated by the following
claims.
* * * * *