U.S. patent application number 17/176750 was filed with the patent office on 2021-06-03 for fasting mimicking and enhancing diet for treating hypertension and lipid disorders.
The applicant listed for this patent is UNIVERSITY OF SOUTHERN CALIFORNIA. Invention is credited to SEBASTIAN BRANDHORST, VALTER D. LONGO, MIN WEI.
Application Number | 20210161191 17/176750 |
Document ID | / |
Family ID | 1000005404506 |
Filed Date | 2021-06-03 |
United States Patent
Application |
20210161191 |
Kind Code |
A1 |
LONGO; VALTER D. ; et
al. |
June 3, 2021 |
FASTING MIMICKING AND ENHANCING DIET FOR TREATING HYPERTENSION AND
LIPID DISORDERS
Abstract
Methods for lowering hypertension, elevated total cholesterol,
elevated glucose and insulin, elevated IGF-1, elevated triglyceride
levels, and/or elevated CRP levels, and elevated liver fat without
negatively affecting or lowering the levels of these
markers/factors in subjects with already low levels of these
markers are provided. A method for elevating stem cells and
regeneration and anti-inflammatory agents is also provided.
Finally, a method for treating metabolic syndrome is also provided.
A hypocaloric or calorie free diet or a fasting mimicking diet is
administered for a first time period to the subject to reduce blood
pressure or the levels of the above markers/risk factors for aging
and age-related diseases.
Inventors: |
LONGO; VALTER D.; (PLAYA DEL
REY, CA) ; BRANDHORST; SEBASTIAN; (REDONDO BEACH,
CA) ; WEI; MIN; (WEST COVINA, CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
UNIVERSITY OF SOUTHERN CALIFORNIA |
Los Angeles |
CA |
US |
|
|
Family ID: |
1000005404506 |
Appl. No.: |
17/176750 |
Filed: |
February 16, 2021 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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15148251 |
May 6, 2016 |
|
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17176750 |
|
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62157602 |
May 6, 2015 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A23L 33/20 20160801;
A23L 33/30 20160801; A23L 33/40 20160801 |
International
Class: |
A23L 33/00 20160101
A23L033/00; A23L 33/20 20160101 A23L033/20 |
Claims
1-5. (canceled)
6. A method for reducing elevated cholesterol levels and/or
elevated LDL levels without lowering HDL levels, the method
comprising: a) identifying a subject having elevated cholesterol
levels and/or elevated LDL levels; and b) administering short-term
hypocaloric or calorie free diet or a fasting mimicking diet (FMD)
to the subject for a first time period to reduce elevated
cholesterol levels and/or elevated LDL levels.
7. The method of claim 6 wherein the hypocaloric or calorie free
diet or fasting mimicking diet is administered for a period of 5
days every 2-12 weeks or 1-2 days every week.
8. The method of claim 6 wherein step b) is repeated a plurality of
times at predetermined intervals.
9. The method of claim 8 wherein step b) is repeated at intervals
from one week to 6 months.
10. The method of claim 8 wherein the subject is administered a
normal diet in between repetition of step b).
11. A method for reducing elevated triglyceride levels and/or
elevated CRP levels, the method comprising: a) identifying a
subject having elevated triglyceride levels and/or elevated CPR
levels; and b) administering a hypocaloric or calorie free diet or
a fasting mimicking diet (FMD) to the subject for a first time
period to reduce elevated triglyceride levels and/or elevated CPR
levels.
12. The method of claim 11 wherein the hypocaloric or calorie free
diet or fasting mimicking diet (FMD) is administered for a period
of 5 days every 2-12 weeks or 1-2 days every week.
13. The method of claim 11 wherein step b) is repeated a plurality
of times at predetermined intervals.
14. The method of claim 13 wherein step b) is repeated at intervals
from one week to 2 months.
15. The method of claim 13 wherein the subject is administered a
normal diet in between repetition of step b).
16-20. (canceled)
21. A method for treating abdominal obesity without negatively
affecting lean body mass, the method comprising: a) identifying a
subject that is overweight; and b) administering a hypocaloric or
calorie free diet or a fasting mimicking diet (FMD) to the subject
for a first time period to reduce fat mass without affecting lean
body mass.
22. The method of claim 20 wherein the hypocaloric or calorie free
diet or fasting mimicking diet is administered for a period of 5
days every 2-12 weeks or 1-2 days every week.
23. The method of claim 20 wherein step b) is repeated a plurality
of times at predetermined intervals.
24-35. (canceled)
36. A method for reducing fatty liver, the method comprising: a)
identifying a subject having elevated hepatic fat fraction; and b)
administering a hypocaloric or calorie free diet or a fasting
mimicking diet (FMD) to the subject for a first time period to
reduce hepatic fat fraction.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims the benefit of U.S. provisional
application Ser. No. 62/157,602 filed May 6, 2015, the disclosure
of which is hereby incorporated in its entirety by reference
herein.
TECHNICAL FIELD
[0002] In at least one aspect, the present invention relates to
methods for treating hypertension, obesity, elevated total
cholesterol, elevated triglyceride levels, elevated glucose,
levels, elevated insulin levels, and/or elevated CRP levels.
BACKGROUND
[0003] Growth hormone (GH)/Insulin-like Growth Factor 1 (IGF-1)
signaling exerts a variety of physiological effects including
promotion of growth, induction of lipolysis and gluconeogenesis,
blocking lipogenesis and insulin functioning, activation of immune
cells and boosting muscle mass growth. These physiological
functions are mediated through binding of GH to the growth hormone
receptor (GHR) on the cell surface of target cells. A key function
of GH is mediated through the liver production of IGF-1.
Deficiencies in GH/insulin/IGF-1 signaling extend lifespan in
organisms ranging from yeast to mammals. Moreover, GHR deficiency
is associated with a major reduction in pro-aging signaling,
cancer, and diabetes in humans. Hypocaloric or calorie free diets
or fasting mimicking diets can enhance the protection of normal
tissues from toxins such as chemotherapy drugs, increase tissue
regeneration, promote organism healthspan, as well as augment
biomarkers associated with age-related diseases, all of which are
mediated mainly via reduction of circulating IGF-1.
[0004] Dietary/calorie restriction (DR/CR) are well known in
improving healthspan in model organisms and possibly in humans.
However, it requires a long-term (possibly life-long) commitment in
order to reap the benefits of DR/CR, which imposes significant
burden on the practitioners. Chronic DR/CR may not be feasible
(hard to maintain) but also not safe for certain practitioners due
to the significant weight loss. Prolonged fasting may also be
difficult and potentially introduce acute malnutrition.
[0005] Accordingly, there is a need for improved dietary methods
for treating certain conditions amenable to treatment by diet.
SUMMARY
[0006] Methods for treating hypertension, elevated total
cholesterol, elevated triglyceride levels, and/or elevated CRP
levels are provided. A hypocaloric, calorie free or fasting
mimicking diet is administered for a first time period to the
subject to reduce blood pressure and/or these levels of
cholesterol, triglycerides, and/or CRP.
[0007] The results provided below show that adoption of periodic
cycles of fasting mimicking diets (FMDs) can manage body weight,
reduce inflammation, modulate risk factors associated with
age-related diseases, e.g. metabolic syndrome, diabetes,
cardiovascular diseases, neurodegenerative diseases (Alzheimer's
disease, etc.), attenuate/delay changes in biomarkers associated
with aging, reduce blood pressure, and/or reduce levels of
cholesterol, triglycerides, and
[0008] CRP.
BRIEF DESCRIPTION OF THE DRAWINGS
[0009] FIGS. 1A, 1B, 1C, 1D, 1E, 1F, and 1G. Starting at 17-month
of age, female C57BL/6 mice were subjected to cycles of 5-day FMD
every 2 weeks. A) Mice fed with FMD regained body weight upon
refeeding. FMD is not associated with chronic body weight loss. B)
Cycles of FMD initiated at middle age (17 month old) extended mean
lifespan. FMD reduced blood glucose (C), IGF-1 (D) and insulin (E),
all of which recovered after refeeding of normal diet. FMD
increased white blood cell (WBC) (F) and lymphocyte (LYM) (G)
counts.
[0010] FIGS. 2A and 2B. 18-month old female C57BL/6 mice were
subjected to cycles of 2-day FMD every week. A) Body weight
recovered quickly after refeeding of normal diet. B) FMD reduced
blood glucose.
[0011] FIGS. 3A, 3B, 3C, 3D, 3E, 3F, and 3G. 18-month old female
(A) and male (B) C57BL/6 mice were subjected to 3 cycles or 1 cycle
of a rice protein-based fasting mimicking and enhancing diet
(FMED-R) for 5 days every two weeks. Rice protein-based FMD with
moderate and low protein content (R-M and R-L) significantly
lowered circulating IGF-1, comparable to short-term starvation
(STS). 18-months old male (B) C57BL/6 mice were fed with
rice-protein based FMDs with low or moderate levels of protein (R-M
and R-L, respectively): C) Body weight recovered quickly after
refeeding of normal diet. FMDs reduced blood glucose (D), and
increased ketone bodies (E). As during short-term starvation, FMD
feeding led to a drop in white blood cell (WBC) and lymphocyte
counts (G), which recovers after a week of refeeding of normal
diet.
[0012] FIGS. 4A, 4B, 4C, 4D, 4E, 4F, 4G, 4H, 4I, 4J, and 4K.
Generally healthy participants were subjected to 3 cycles of a
fasting mimicking diet (FMD) in three months and returned to their
normal diet after each cycle. The 3 cycles of the FMD reduced the
body weight (A), waist circumference (B), and abdominal fat (C) in
obese (BMI>30) and overweight (BMI>25) people after they had
returned to their normal diet for 1 week after cycle 3. FMD reduced
fasting blood sugar in people with pre-diabetes (fasting
glucose>99 mg/dL). FMD reduced circulating IGF-1 levels (E). FMD
reduced both systolic and diastolic blood pressure in people with
above normal blood pressure (>120/80 mmHg). FMD reduced total
cholesterol and LDL levels (G). FMD reduced triglycerides and CRP
levels in people with relatively high levels of triglycerides (H)
and CRP (I). FMD increased blood cortisol level (J) and circulating
mesenchymal stem/progenitor cells (MSPC) (K).
[0013] FIG. 5 provides serum IGF-1 levels in 18-month old female
mice after 3 cycles of 5-days feeding of Control (AIN93G) or FMDs
formulated with equivalent levels of casein-derived, wheat-derived,
whole grain sprouted brown rice-derived proteins or an equivalent
level of a complete amino acid mix as a protein source. (N=5).
*p<0.01, ANOVA, compared to AIN93G.
[0014] FIG. 6 provides serum IGF-1 levels of 18-month old male mice
after 5-days feeding of Control (AIN93G) or FMDs formulated with
casein-derived, or whole grain sprouted brown rice-derived protein
or complete amino acid mix as protein source. (N=5). *p<0.01,
ANOVA, compared to AIN93G.
[0015] FIGS. 7A, 7B, and 7C. Generally healthy participants were
subjected to 3 cycles of a fasting mimicking diet (FMD) in three
months. Abdominal Mill study showed that (A) FMD reduced hepatic
fat fraction (HFF) (N=15, p<0.05, paired t test, two-tailed).
This effect is more pronounced in subjects that are (B) overweight
(BMI>25, N=8, p<0.05, paired t test, two-tailed) and in those
with (C) fatty liver (defined as baseline HFF>5%, N=5,
p<0.05, paired t test, two-tailed).
DETAILED DESCRIPTION
[0016] Reference will now be made in detail to presently preferred
compositions, embodiments and methods of the present invention
which constitute the best modes of practicing the invention
presently known to the inventors. The Figures are not necessarily
to scale. However, it is to be understood that the disclosed
embodiments are merely exemplary of the invention that may be
embodied in various and alternative forms. Therefore, specific
details disclosed herein are not to be interpreted as limiting, but
merely as a representative basis for any aspect of the invention
and/or as a representative basis for teaching one skilled in the
art to variously employ the present invention.
[0017] Except in the examples, or where otherwise expressly
indicated, all numerical quantities in this description indicating
amounts of material or conditions of reaction and/or use are to be
understood as modified by the word "about" in describing the
broadest scope of the invention. Practice within the numerical
limits stated is generally preferred. Also, unless expressly stated
to the contrary: percent, "parts of," and ratio values are by
weight; the description of a group or class of materials as
suitable or preferred for a given purpose in connection with the
invention implies that mixtures of any two or more of the members
of the group or class are equally suitable or preferred;
description of constituents in chemical terms refers to the
constituents at the time of addition to any combination specified
in the description and does not necessarily preclude chemical
interactions among the constituents of a mixture once mixed; the
first definition of an acronym or other abbreviation applies to all
subsequent uses herein of the same abbreviation and applies mutatis
mutandis to normal grammatical variations of the initially defined
abbreviation; and, unless expressly stated to the contrary,
measurement of a property is determined by the same technique as
previously or later referenced for the same property.
[0018] It is also to be understood that this invention is not
limited to the specific embodiments and methods described below, as
specific components and/or conditions may, of course, vary.
Furthermore, the terminology used herein is used only for the
purpose of describing particular embodiments of the present
invention and is not intended to be limiting in any way.
[0019] It must also be noted that, as used in the specification and
the appended claims, the singular form "a," "an," and "the"
comprise plural referents unless the context clearly indicates
otherwise. For example, reference to a component in the singular is
intended to comprise a plurality of components.
[0020] Throughout this application, where publications are
referenced, the disclosures of these publications in their
entireties are hereby incorporated by reference into this
application to more fully describe the state of the art to which
this invention pertains.
Abbreviations:
[0021] As required, detailed embodiments of the present invention
are disclosed herein; however, it is to be understood that the
disclosed embodiments are merely exemplary of the invention that
may be embodied in various and alternative forms. The figures are
not necessarily to scale; some features may be exaggerated or
minimized to show details of particular components. Therefore,
specific structural and functional details disclosed herein are not
to be interpreted as limiting, but merely as a representative basis
for teaching one skilled in the art to variously employ the present
invention.
[0022] "AL" means ad libitum.
[0023] "BMI" means body mass index.
[0024] "CRP" means C-reactive protein.
[0025] "FMD" means fasting mimicking diet.
[0026] "FMED" means fasting mimicking and enhancing diet. It is a
type of FMD that also provides various supplements.
[0027] "STS" means short-term starvation.
[0028] The terms "kilocalorie" (kcal) and "Calorie" refer to the
food calorie. The term "calorie" refers to the so-called small
calorie.
[0029] The term "subject" refers to a human or animal, including
all mammals such as primates (particularly higher primates), sheep,
dog, rodents (e.g., mouse or rat), guinea pig, goat, pig, cat,
rabbit, and cow.
[0030] In an embodiment, a method for treating hypertension in a
subject is provided. The method includes a step of identifying a
subject having hypertension. A hypocaloric or calorie free diet
(e.g., STS) or a fasting mimicking diet (FMD) is administered for a
first time period to the subject to reduce systolic blood pressure
and/or diastolic blood pressure. In general, the FMD diet provides
less than about 1200 kilocalories per day when administered. In a
refinement, the FMD diet provides less than, in increasing order of
preference, 1200 kcal, 1100 kcal, 1000 kcal, 900 kcal, 700 kcal or
600 kcal per day when administered. In a further refinement, the
FMD diet provides greater than, in increasing order of preference,
200 kcal, 250 kcal, 300 kcal, 350 kcal, 400 kcal or 500 kcal per
day when administered. In another refinement, STS or a FMD is
repeated a plurality of times at predetermined intervals. In a
further refinement, the hypocaloric or calorie free diet or fasting
mimicking diet is administered for a period of 5 days every 2-24
weeks or 1-2 days every week. For example, a hypocaloric or calorie
free diet or a FMD can be repeated at intervals from one week to 6
months. Typically, the subject is administered a normal diet in
between these repetitions.
[0031] In another embodiment, a method for treating elevated
triglycerides, inflammation, and/or CRP levels in a subject is
provided. The method includes a step of identifying a subject
having elevated triglycerides and/or CRP or other inflammatory
markers levels. A hypocaloric or calorie free diet (e.g., STS) or a
fasting mimicking diet (FMD) is administered for a first time
period to the subject to reduce elevated triglycerides and/or CRP
and/or other inflammatory markers levels. In general, the FMD diet
provides less than about 1200 kilocalories per day when
administered. In a refinement, the FMD diet provides less than, in
increasing order of preference, 1200 kcal, 1100 kcal, 1000 kcal,
900 kcal, 700 kcal or 600 kcal per day when administered. In a
further refinement, the FMD diet provides greater than, in
increasing order of preference, 200 kcal, 250 kcal, 300 kcal, 350
kcal, 400 kcal or 500 kcal per day when administered. In another
refinement, a hypocaloric or calorie free diet or a FMD is repeated
a plurality of times at predetermined intervals. In a further
refinement, the hypocaloric or calorie free diet or fasting
mimicking diet is administered for a period of 5 days every 2-24
weeks or 1-2 days every week. For example, STS or a FMD can be
repeated at intervals from one week to 6 months. In a refinement,
the STS or a FMD can be repeated at intervals from one week to 2
months. Typically, the subject is administered a normal diet in
between these repetitions.
[0032] In another embodiment, a method for elevated cholesterol
and/or elevated LDL levels without lowering HDL levels in a subject
is provided. The method includes a step of identifying a subject
having elevated cholesterol and/or elevated LDL levels. A
hypocaloric or calorie free diet (e.g., STS) or a fasting mimicking
diet (FMD) is administered for a first time period to the subject
to reduce elevated cholesterol and/or elevated LDL levels. In
general, the FMD diet provides less than about 1200 kilocalories
per day when administered. In a refinement, the FMD diet provides
less than, in increasing order of preference, 1200 kcal, 1100 kcal,
1000 kcal, 900 kcal, 700 kcal or 600 kcal per day when
administered. In a further refinement, the FMD diet provides
greater than, in increasing order of preference, 200 kcal, 250
kcal, 300 kcal, 350 kcal, 400 kcal or 500 kcal per day when
administered. In a refinement, a hypocaloric or calorie free diet
or a FMD is repeated a plurality of times at predetermined
intervals. In a further refinement, the hypocaloric or calorie free
diet or fasting mimicking diet is administered for a period of 5
days every 2-24 weeks or 1-2 days every week. For example, a
hypocaloric or calorie free diet or a FMD can be repeated at
intervals from one week to 6 months. Typically, the subject is
administered a normal diet in between these repetitions.
[0033] In still another embodiment, a method for reducing elevated
insulin and/or glucose levels in a subject with elevated levels but
not in subjects with low levels of glucose and insulin is provided.
The method includes a step of identifying a subject having elevated
insulin and/or glucose levels. A hypocaloric or calorie free diet
(e.g., STS) or a fasting mimicking diet (FMD) is administered for a
first time period to the subject to reduce elevated glucose and/or
elevated insulin levels. In general, the FMD diet provides less
than about 1200 kilocalories per day when administered. In a
refinement, the FMD diet provides less than, in increasing order of
preference, 1200 kcal, 1100 kcal, 1000 kcal, 900 kcal, 700 kcal or
600 kcal per day when administered. In a further refinement, the
FMD diet provides greater than, in increasing order of preference,
200 kcal, 250 kcal, 300 kcal, 350 kcal, 400 kcal or 500 kcal per
day when administered. In a refinement, a hypocaloric or calorie
free diet or a FMD is repeated a plurality of times at
predetermined intervals. In a further refinement, the hypocaloric
or calorie free diet or fasting mimicking diet is administered for
a period of 5 days every 2-24 weeks or 1-2 days every week. For
example, a hypocaloric or calorie free diet can be repeated at
intervals from one week to 6 months. In a refinement, the STS or a
FMD can be repeated at intervals from one week to 2 months.
Typically, the subject is administered a normal diet in between
these repetitions.
[0034] In still another embodiment, a method for promoting chronic
reduction of IGF-1 in a subject with elevated levels but not in
subjects with low levels is provided. The method includes a step of
identifying a subject having elevated IGF-1 levels. A hypocaloric
or calorie free diet (e.g., STS) or a fasting mimicking diet (FMD)
is administered for a first time period to the subject to reduce
elevated IGF-1 levels. In general, the FMD diet provides less than
about 1200 kilocalories per day when administered. In a refinement,
the FMD diet provides less than, in increasing order of preference,
1200 kcal, 1100 kcal, 1000 kcal, 900 kcal, 700 kcal or 600 kcal per
day when administered. In a further refinement, the FMD diet
provides greater than, in increasing order of preference, 200 kcal,
250 kcal, 300 kcal, 350 kcal, 400 kcal or 500 kcal per day when
administered. In a refinement, a hypocaloric or calorie free diet
or a FMD is repeated a plurality of times at predetermined
intervals. In a further refinement, the hypocaloric or calorie free
diet or fasting mimicking diet is administered for a period of 5
days every 2-24 weeks or 1-2 days every week. For example, the
hypocaloric or calorie free diet can be repeated at intervals from
one week to 6 months. In a refinement, the STS or a FMD can be
repeated at intervals from one week to 2 months. Typically, the
subject is administered a normal diet in between these
repetitions.
[0035] In still another embodiment, a method for treating a subject
with elevated IGF-1 levels and promoting long-term lowering of
IGF-1 levels without further lowering IGF-1 in subjects with
already low levels is provided. The method includes a step of
identifying a subject having elevated IGF-1 levels. A protein free
normocaloric diet to the subject while providing the subject with a
rice protein dietary supplement is administered for a first time
period to the subject to reduce elevated IGF-1 levels. In a
refinement, the protein free normocaloric diet is repeated a
plurality of times at predetermined intervals. In a further
refinement, the protein free normocaloric diet is administered for
a period of 5 days every 2-24 weeks or 1-2 days every week. For
example, protein free normocaloric diet can be repeated at
intervals from one week to 6 months. In a refinement, the protein
free normocaloric diet can be repeated at intervals from one week
to 2 months. In another refinement the protein free diet in
combination with the rice protein dietary supplement is used to
replace any major meal or snack.
[0036] In another embodiment, the rice protein supplement is
applied to patients on an FMD diet to reduce further any potential
malnourishment while achieving all of the effects of the FMD on
aging, and age-related diseases or its risk factors/markers.
Typically, the subject is administered a normal diet in between
these repetitions.
[0037] In still another embodiment, a method for method for
reducing fatty liver is provided. The method includes a step of
identifying a subject having elevated hepatic fat fraction. A
hypocaloric or calorie free diet or a fasting mimicking diet (FMD)
is administered for a first time period to the subject to reduce
elevated IGF-1 levels. In general, the FMD diet provides less than
about 1200 kilocalories per day when administered. In a refinement,
the FMD diet provides less than, in increasing order of preference,
1200 kcal, 1100 kcal, 1000 kcal, 900 kcal, 700 kcal or 600 kcal per
day when administered. In a further refinement, the FMD diet
provides greater than, in increasing order of preference, 200 kcal,
250 kcal, 300 kcal, 350 kcal, 400 kcal or 500 kcal per day when
administered. In another refinement, the hypocaloric or calorie
free diet or a fasting mimicking diet is repeated a plurality of
times at predetermined intervals. In a further refinement,
hypocaloric or calorie free diet or a fasting mimicking diet is
administered for a period of 5 days every 2-24 weeks or 1-2 days
every week. For example, the hypocaloric or calorie free diet or a
fasting mimicking diet can be repeated at intervals from one week
to 6 months. In a refinement, the hypocaloric or calorie free diet
or a fasting mimicking diet can be repeated at intervals from one
week to 2 months. Typically, the subject is administered a normal
diet in between these repetitions.
[0038] In still another embodiment, a method for treating obesity
and particularly abdominal/visceral fat in a subject is provided.
The method includes a step of identifying a subject that is
overweight. A hypocaloric or calorie free diet (e.g., STS) or a
fasting mimicking diet (FMD) is administered for a first time
period to the subject to specifically reduce the subject's fat mass
without affecting the lean body mass. In general, the FMD diet
provides less than about 1200 kilocalories per day when
administered. In a refinement, the FMD diet provides less than, in
increasing order of preference, 1200 kcal, 1100 kcal, 1000 kcal,
900 kcal, 700 kcal or 600 kcal per day when administered. In a
further refinement, the FMD diet provides greater than, in
increasing order of preference, 200 kcal, 250 kcal, 300 kcal, 350
kcal, 400 kcal or 500 kcal per day when administered. In another
refinement, a hypocaloric or calorie free diet or a FMD is repeated
a plurality of times at predetermined intervals. In a further
refinement, the hypocaloric or calorie free diet or fasting
mimicking diet is administered for a period of 5 days every 2-24
weeks or 1-2 days every week. For example, a hypocaloric or calorie
free diet can be repeated at intervals from one week to 6 months.
In a refinement, the hypocaloric or calorie free diet can be
repeated at intervals from one week to 2 months. Typically, the
subject is administered a normal diet in between these
repetitions.
[0039] In still another embodiment, a method for extending life
span and healthspan in a subject is provided. The method includes a
step of administering a hypocaloric or calorie free diet (e.g.,
STS) or a fasting mimicking diet (FMD) for a first time period to
the subject to reduce the subject's weight. In general, the FMD
diet provides less than about 1200 kilocalories per day when
administered. In a refinement, the FMD diet provides less than, in
increasing order of preference, 1200 kcal, 1100 kcal, 1000 kcal,
900 kcal, 700 kcal or 600 kcal per day when administered. In a
further refinement, the FMD diet provides greater than, in
increasing order of preference, 200 kcal, 250 kcal, 300 kcal, 350
kcal, 400 kcal or 500 kcal per day when administered. In another
refinement, a hypocaloric or calorie free diet or a FMD is repeated
a plurality of times at predetermined intervals. In a further
refinement, the hypocaloric or calorie free diet or fasting
mimicking diet is administered for a period of 5 days every 2-24
weeks or 1-2 days every week. For example, a hypocaloric or calorie
free diet can be repeated at intervals from one week to 6 months.
In a refinement, the hypocaloric or calorie free diet can be
repeated at intervals from one week to 2 months. Typically, the
subject is administered a normal diet in between these
repetitions.
[0040] In still another embodiment, a method for treating or
preventing inflammation of inflammatory diseases is provided. In
this embodiment, blood cortisol is increased thereby activating
anti-inflammatory pathways. In a variation, a subject having an
inflammatory disease or in need of having inflammation prevented is
identified. A hypocaloric or calorie free diet (e.g., STS) or a
fasting mimicking diet (FMD) is administered for a first time
period to the subject to reduce the subject's weight. In general,
the FMD diet provides less than about 1200 kilocalories per day
when administered. In a refinement, the FMD diet provides less
than, in increasing order of preference, 1200 kcal, 1100 kcal, 1000
kcal, 900 kcal, 700 kcal or 600 kcal per day when administered. In
a further refinement, the FMD diet provides greater than, in
increasing order of preference, 200 kcal, 250 kcal, 300 kcal, 350
kcal, 400 kcal or 500 kcal per day when administered. In another
refinement, a hypocaloric or calorie free diet or a FMD is repeated
a plurality of times at predetermined intervals. In a further
refinement, the hypocaloric or calorie free diet or fasting
mimicking diet is administered for a period of 5 days every 2-24
weeks or 1-2 days every week. For example, a hypocaloric or calorie
free diet can be repeated at intervals from one week to 6 months.
In a refinement, the hypocaloric or calorie free diet can be
repeated at intervals from one week to 2 months. Typically, the
subject is administered a normal diet in between these
repetitions.
[0041] In yet another embodiment, a method for increasing
regeneration is provided. In this embodiment, levels of stem or
embryonic like stem cells including circulating mesenchymal
stem/progenitor cells (MSPC) are increased. In a variation, a
subject in need of regeneration is identified. A hypocaloric or
calorie free diet (e.g., STS) or a fasting mimicking diet (FMD) is
administered for a first time period to the subject to reduce the
subject's weight. In general, the FMD diet provides less than about
1200 kilocalories per day when administered. In a refinement, the
FMD diet provides less than, in increasing order of preference,
1200 kcal, 1100 kcal, 1000 kcal, 900 kcal, 700 kcal or 600 kcal per
day when administered. In a further refinement, the FMD diet
provides greater than, in increasing order of preference, 200 kcal,
250 kcal, 300 kcal, 350 kcal, 400 kcal or 500 kcal per day when
administered. In another refinement, a hypocaloric or calorie free
diet or a FMD is repeated a plurality of times at predetermined
intervals. In a further refinement, the hypocaloric or calorie free
diet or fasting mimicking diet is administered for a period of 5
days every 2-24 weeks or 1-2 days every week. For example, a
hypocaloric or calorie free diet can be repeated at intervals from
one week to 6 months. In a refinement, the hypocaloric or calorie
free diet can be repeated at intervals from one week to 2 months.
Typically, the subject is administered a normal diet in between
these repetitions.
[0042] In each of the embodiments set forth herein, treatment of
the subject can be extended over a period of years. For example,
cycles of the hypocaloric or calorie free diet or a fasting
mimicking diet (FMD) can be administered for 1 to 5 or more years.
It should be appreciated that a normal diet is provided between
cycles of the hypocaloric or calorie free diet or a FMD.
[0043] Examples of hypocaloric fasting mimicking diet or calorie
free diet protocols are found in U.S. pat. appl. Ser. Nos.
12/430,058 and 13/488,590; the entire disclosures of which are
hereby incorporated by reference. The hypocaloric diet contains
dietary materials capable of providing nutrition to a human subject
while providing no more than 813-957 kcal (e.g., no more than 700,
500, 300, or 100 kcal, or 0 kcal) total energy, and no more than
30-36 g (e.g., no more than 20, 10, or 5 g, or 0 g) protein. If
carbohydrates are present in the dietary materials, no more than
half of the energy is in the carbohydrates. In a refinement, the
hypocaloric/calorie free diet/FMD diet may be administered to the
subject for 2-10 consecutive days. In an alternative method the
diet can be administered for only 1 day with a frequency of at
least 1 day/week every week of the month.
[0044] In another variation, the hypocaloric or calorie free diet
provides nutrition while providing no more than 11 kcal (e.g., no
more than 8, 5, or 2 kcal, or 0 kcal) energy per kilogram body
weight of the subject per day and no more than 0.4 g (e.g., 0.3,
0.2, or 0.1 g or 0 g) protein per kilogram body weight of the
animal or human per day. If carbohydrates are present in the diet,
no more than half of the energy is in the carbohydrates. In some
embodiments, the diet is capable of providing no more than 800 kcal
(e.g., 600, 400, or 200 kcal or 0 kcal) total energy per day. The
diet may be administered to animals or humans for 3-10 consecutive
days. In an alternative method the diet can be administered for
only 1 day with a frequency of at least 1 day/week every week of
the month.
[0045] As set forth above, a subject is administered a normal diet
i.e., re-feeding period) in between repetitions of the FMD for each
of the variations and embodiments of the invention. In this
context, a normal diet is a diet of sufficient caloric intake to
maintain the patient weight. In a refinement, the normal caloric
intake provides the subject with 1500 to 2500 kcal or 1800 to 2300
kcal, or 1800 to 2000 kcal.
[0046] Examples of FMD diets are found in U.S. Pat. Appl. Nos.
14,060,494 and 14,178,953 and WIPO Pub. No. WO2011/050302 and WIPO
Pub. No. WO2011/050302; the entire disclosures of which are hereby
incorporated by reference. Typically, in the FMD protocol a
subject's diet is substituted for a predetermined number of days
(i.e. 5 days). During this period, subjects consume plenty of
water. For healthy subjects of normal weight (Body Mass Index or
BMI between 18.5-25), the diet is consumed once a month (5 days on
the diet and 25-26 days on their normal diet) for the first 3
months and every 3 months thereafter (5 days every 3 months). The
weight of the subject is measured and the subject must regain at
least 95% of the weight lost during the diet before the next cycle
is begun unless weight loss is advised by a physician or healthcare
professional. Subjects with BMI of less than 18.5 should not
undertake the FMD unless recommended and supervised by a physician.
The same regimen (once every month for 3 months followed by once
every 3 months thereafter) can be adopted for the treatment, or in
support of the treatment, of all of the conditions presented in the
patent applications. U.S. pat. appl. Ser. No. 14,178,953 provides a
low protein version of the FMD diet. In an alternative method the
diet can be administered for only 1 day with a frequency of at
least 1 day/week every week of the month.
[0047] In one variation, the FMD set forth in U.S. pat. appl. Ser.
No. 12/430,058 is used in the methods set forth above. This diet
includes nutrition facts relative to calories, macronutrients and
micronutrients. Calories are consumed according to the user's body
weight. Total calorie consumption is 4.5-7 kcal per pound (or 10-16
kcal per kilogram) for day 1 and 3-5 kcal per pound (or 7-11 kcal
per kilogram) for day 2 to 5. FIGS. 12-14 provides listings of the
nutrients for day one through day five. In addition to the
macronutrients, the diet should contain less than 30 g of sugar on
day 1 and less than 20 g of sugar on days 2-5. The diet should
contain less than 28 g of proteins on day 1 and less than 18 g of
proteins on days 2-5. The diet should contain between 20 and 30
grams of monounsaturated fats on day 1 and 10-15 grams of
monounsaturated fats on days 2-5. The diet should contain between 6
and 10 grams of polyunsaturated fats on day 1 and 3-5 grams of
polyunsaturated fats on days 2-5. The diet should contain less than
12 g of saturated fats on day 1 and less than 6 grams of saturated
fats on days 2-5. Typically, the fats on all days are derived from
a combination of the following: Almonds, Macadamia Nuts, Pecans,
Coconut, Coconut oil, Olive Oil and Flaxseed. In a refinement, the
FMD diet includes over 50% of the recommended daily value of
dietary fiber on all days. In the further refinement, the amount of
dietary fiber is greater than 15 grams per day on all five days.
The diet can contain 12-25 grams of glycerol per day on days 2-5.
In a refinement, glycerol is provided at 0.1 grams per pound body
weight/day.
[0048] In a refinement, the FMD includes the following
micronutrients (at least 95% non-animal based): over 5,000 IU of
vitamin A per day (days 1-5); 60-240 mg of vitamin C per day (days
1-5); 400-800 mg of Calcium per day (days 1-5); 7.2-14.4 mg of Iron
per day (days 1-5); 200-400 mg of Magnesium per day (days 1-5); 1-2
mg of copper per day (days 1-5); 1-2 mg of Manganese per day (days
1-5); 3.5-7 mcg of Selenium per day (days 1-5); 2-4 mg of Vitamin
B1 per day (days 1-5); 2-4 mg of Vitamin B2 per day (days 1-5);
20-30 mg of Vitamin B3 per day (days 1-5); 1-1.5 mg of Vitamin B5
per day (days 1-5); 2-4 mg of Vitamin B6 per day (days 1-5);
240-480 mcg of Vitamin B9 per day (days 1-5); 600-1000 IU of
Vitamin D per day (days 1-5); 14-30 mg of Vitamin E per day (days
1-5); over 80 mcg of Vitamin K per day (days 1-5); 16-25 mcg
Vitamin B12 are provided during the entire 5-day period; 600 mg of
Docosahexaenoic acid (DHA, algae-derived) are provided during the
entire 5-day period. The FMD diet provides high micronutrient
content mostly (i.e., greater than 50 percent by weight) from
natural sources including: Kale, Cashews, Yellow Bell Pepper,
Onion, Lemon Juice, Yeast, Turmeric. Mushroom, Carrot, Olive Oil,
Beet Juice, Spinach, Tomato, Collard, Nettle, Thyme, Salt, Pepper,
Vitamin B12 (Cyanocobalamin), Beets, Butternut Squash, Collard,
Tomato, Oregano, Tomato Juice, Orange Juice, Celery, Romaine
Lettuce, Spinach, Cumin, Orange Rind, Citric Acid, Nutmeg, Cloves,
and combinations thereof. Table 1 provides an example of additional
micronutrient supplementation that can be provided in the FMD
diet:
TABLE-US-00001 TABLE 1 Micronutrient Supplementation Supplement
Formula Amount Amount Range Unit Vit A 1250 IU 900-1600 IU Vit C
Ascorbic Acid C.sub.6H.sub.8O.sub.6 15.0000 10-20 mg Ca Calcium
Carbonate CaCO.sub.3 80.0000 60-100 mg Fe Ferrous Fumarate
C.sub.4H.sub.2FeO.sub.4 4.5000 3-6 mg Vit D3 Cholecalciferol
C.sub.27H.sub.44O 0.0025 0.001-0.005 mg Vit E dl-Alpha Tocopheryl
Acetate C.sub.29H.sub.50O.sub.2 5.0000 3-7 mg Vit K Phytonadione
0.0200 0.1-0.04 mg Vit B1 Thiamine Mononitrate
C.sub.12H.sub.17N.sub.5O.sub.4S 0.3750 0.15-0.5 mg Vit B2
Riboflavin E101 C.sub.17H.sub.20N.sub.4O.sub.6 0.4250 0.2-0.6 mg
Vit B3 Niacinamide C.sub.6H.sub.6N.sub.2O 5.0000 3-7 mg Vit B5
Calcium Pantothenate C.sub.18H.sub.32CaN.sub.2O.sub.10 2.5000
1.5-4.0 mg Vit B6 Pyridoxine Hydrochloride
C.sub.8H.sub.11NO.sub.3.cndot.HCl 0.5000 0.3-0.7 mg Vit B7 Biotin
C.sub.10H.sub.16N.sub.2O.sub.3S 0.0150 0.01-0.02 mg Vit B9 Folic
Acid C.sub.19H.sub.19N.sub.7O.sub.6 0.1000 0.07-0.14 mg Vit B12
Cyanocobalamin C.sub.63H.sub.88CoN.sub.14O.sub.14P 0.0015
0.001-0.002 mg Cr Chromium Picolinate
Cr(C.sub.6H.sub.4NO.sub.2).sub.3 0.0174 0.014-0.022 mg Cu Cupric
Sulfate CuSO.sub.4 0.2500 0.18-0.32 mg I Potassium Iodide KI 0.0375
0.03-0.045 mg Mg Magnesium Oxide MgO 26.0000 20-32 mg Mn Manganese
Sulfate MnSO.sub.4 0.5000 0.3-0.7 mg Mo Sodium Molybdate
Na.sub.2MoO.sub.4 0.0188 0.014-0.023 mg Se Sodium Selenate
Na.sub.2O.sub.4Se 0.0175 0.014-0.023 mg Zn Zinc Oxide ZnO 3.7500
3-5 mg
[0049] In another embodiment, a diet package for implemented the
method forth above is provided.
[0050] The diet package includes a first set of rations for a first
diet to be administered for a first time period to a subject, the
first diet providing from 4.5 to 7 kilocalories per pound of
subject for a first day and 3 to 5 kilocalories per pound of
subject per day for a second to fifth day of the first diet. The
diet package includes rations that provide less than 30 g of sugar
on the first day; less than 20 g of sugar on the second to fifth
days; less than 28 g of proteins on the first day; less than 18 g
of proteins on the second to fifth days; 20 to 30 grams of
monounsaturated fats on the first day; 10 to15 grams of
monounsaturated fats on the second to fifth days; between 6 and 10
grams of polyunsaturated fats on the first day; 3 to 5 grams of
polyunsaturated fats on the second to fifth days; less than 12 g of
saturated fats on the first day; less than 6 grams of saturated
fats on the second to fifth days; and 12 to 25 grams of glycerol
per day on the second to fifth days. In a refinement, the diet
package further includes sufficient rations to provide the
micronutrients set forth above. In a further refinement, the diet
package provides instructions providing details of the methods set
forth above.
[0051] In refinement of the embodiments set forth above, a 5-day
supply of diet includes:
[0052] soups/broths, soft drinks, nut bars and supplements. The
diet is administered as follows: 1) on the first day a 1000-1200
kcal diet with high micronutrient nourishment as set forth above is
provided; 2) for the next 4 days a daily diet of 650-800 kcal plus
a drink containing a glucose substitution carbon source providing
between 60-120 kcal are provided.
[0053] In another refinement of the embodiments set forth above, a
6-day low-protein diet protocol includes: soups/broths, soft
drinks, nut bars, and supplements. The diet is administered as
follows: 1) on the first day a 1000-1200 kcal diet plus with high
micronutrient nourishment is provided; 2) for the next 3 days a
daily diet of less than 200 kcal plus a drink containing a glucose
substitution carbon source providing between 60 and 120 kcal. This
substitution carbon source does not interfere with the effect of
fasting on stem cell activation; 3) on the 5th day the subject
consumes a normal diet; and 4) on day 6 an additional replenishment
foods consisting of a high fat source of 300 kcal and a
micronutrient nourishment mix on day 6 replenishment foods
consisting of a high fat source of 300 kcal and a micronutrient
nourishment mix are provided in addition to normal diet.
[0054] In still another refinement, a diet protocol includes: 6-day
supply of low-protein diet includes: soups/broths, soft drinks, nut
bars, and supplements. 1) on the first day a 1000-1200 kcal diet
with high micronutrient nourishment is provided; 2) for the next 3
days a daily diet of 600 to 800 kcal which contains less than 10
grams of protein and less than 200 kcal from sugars; 3) on the 5th
day the subject receives a normal diet; and 4) on day 6 an
additional replenishment foods consisting of a high fat source of
300 kcal and a micronutrient nourishment mix on day 6 replenishment
foods consisting of a high fat source of 300 kcal and a
micronutrient nourishment mix are provided in addition to normal
diet.
[0055] Although the FMD diet encompasses virtually any source of
fat, sources high in unsaturated fat, including monounsaturated and
polyunsaturated fat sources, are particularly useful (e.g.,
omega-3/6 essential fatty acids). Suitable examples of
monounsaturated food sources include, but are not limited to,
peanut butter, olives, nuts (e.g., almonds, pecans, pistachios,
cashews), avocado, seeds (e.g., sesame), oils (e.g., olive, sesame,
peanut, canola), etc. Suitable examples of polyunsaturated food
sources include, but are not limited to, walnuts, seeds (e.g.,
pumpkin, sunflower), flaxseed, fish (e.g., salmon, tuna, mackerel),
oils (e.g., safflower, soybean, corn). The first diet also includes
a component selected from the group consisting of vegetable
extracts, minerals, omega-3/6 essential fatty acids, and
combinations thereof. In one refinement, such a vegetable extract
provides the equivalent of 5 recommended daily servings of
vegetables. Suitable sources for the vegetable extract include, but
are not limited to, bokchoy, kale, lettuce, asparagus, carrot,
butternut squash, alfalfa, green peas, tomato, cabbage,
cauliflower, beets. Suitable sources for the omega-3/6 essential
fatty acids include fish such as salmon, tuna, mackerel, bluefish,
swordfish, and the like.
[0056] The following examples are intended to illustrate, but not
to limit, the scope of the invention. While such examples are
typical of those that might be used, other procedures known to
those skilled in the art may alternatively be utilized. Indeed,
those of ordinary skill in the art can readily envision and produce
further embodiments, based on the teachings herein, without undue
experimentation.
[0057] The following FMDs and FMD regimens effectively manage body
weight, risk factors associated with aging and age-related diseases
in humans. They were developed based on animal studies as well as
based on the results of ongoing clinical trials. It is shown that
cycles of the FMD decrease fasting blood glucose and IGF-1 levels.
The reduction of serum IGF-1 level may be responsible for the
regeneration of stem and progenitor cells. The FMD regimens do not
require chronic reduction of calorie intake, nor changes in the
diet in between cycles, nor do they cause chronic weight loss.
[0058] The FMD is comprised of a variety of food items including,
but not limited to, energy bars, soups, vegetable chips, vegetable
and fruit snacks, energy drinks, supplements for minerals, vitamins
and essential fatty acids. All food items were developed to reach a
profile of macronutrients and calorie content that will mimic the
benefit of short-term starvation while providing certain levels of
support for micronutrients. In some variations, FMDs are formulated
with rice-derived protein at low to moderate protein levels (5%40%
total calorie derived from protein) as a method to reduce IGF-1
levels (see FIGS. 3-6) and maximize fasting mimicking effects.
[0059] Diet 1: the FMD will substitute a subject's normal diet for
a period of 5 days every 2-12 weeks depending on the need of the
subject in terms of body weight and disease risk factor management.
For day 1, the FMD will provide 4.5-7 kcal per pound of body weight
(or 10-16 kcal per kilogram body weight). For days 2-5, the FMD
will provide 3-5 kcal per pound of body weight (or 7-11 kcal per
kilogram body weight). The day 1 diet should contain less than 30
grams of sugar, less than 28 grams of protein, 20-30 grams of
monounsaturated fats, 6-10 grams of polyunsaturated fats and 2-12
grams of saturated fats. The Day 2-5 diets should contain less than
20 grams of sugar, less than 18 grams of protein, 10-15 grams of
monounsaturated fats, 3-5 grams of polyunsaturated fats and 1-6
grams of saturated fats. The diet will also provide micronutrients
at greater than 25% of the Daily Value (DV). In an alternative
method the diet can be administered for only 1 day with a frequency
of at least 1 day/week every week of the month. Proteins can be of
any source but plant based proteins and particularly rice-derived
can enhance the fasting mimicking effects.
[0060] Diet 2: the FMD will substitute a subject's normal diet for
a period of 2 days every week. The FMD will provide 3-5 kcal per
pound of body weight (or 7-11 kcal per kilogram body weight). The
day 1 diet should contain less than 30 grams of sugar, less than 28
grams of protein, 20-30 grams of monounsaturated fats, 6-10 grams
of polyunsaturated fats and 2-12 grams of saturated fats. The day 2
diet should contain less than 20 grams of sugar, less than 18 grams
of protein, 10-15 grams of monounsaturated fats, 3-5 grams of
polyunsaturated fats and 1-6 grams of saturated fats. The diet will
also provide micronutrients at greater than 25% of the Daily Value
(DV).
[0061] FIG. 1. Starting at 17-month of age, female C57BL/6 mice
were subjected to cycles of 5-day FMD every 2 weeks. A) Mice fed
with FMD regained body weight upon refeeding. FMD is not associated
with chronic body weight loss. B) Cycles of FMD initiated at middle
age (17 month old) extended mean lifespan. FMD reduced blood
glucose (C), IGF-1 (D) and insulin (E), all of which recovered
after refeeding of normal diet. FMD increased white blood cell
(WBC) (F) and lymphocyte (LYM) (G) counts.
[0062] FIG. 2. 18-month old female C57BL/6 mice were subjected to
cycles of 2-day FMD every week. A) Body weight recovered quickly
after refeeding of normal diet. B) FMD reduced blood glucose.
[0063] FIG. 3. 18-month old female (A) and male (B) C57BL/6 mice
were subjected to 3 cycles or 1 cycle of a rice protein-based
fasting mimicking and enhancing diet (FMED-R) for 5 days every two
weeks. Rice protein-based FMD with moderate and low protein content
(R-M and R-L) significantly lowered circulating IGF-1, comparable
to short-term starvation (STS). 18-months old male (B) C57BL/6 mice
were fed with rice-protein based FMDs with low or moderate levels
of protein (R-M and R-L, respectively): C) Body weight recovered
quickly after refeeding of normal diet. FMDs reduced blood glucose
(D), and increased ketone bodies (E). As during short-term
starvation, FMD feeding led to a drop in white blood cell (WBC) and
lymphocyte counts, which recovers after a week of refeeding of
normal diet.
[0064] FIG. 4. Generally healthy participants were subjected to 3
cycles of a fasting mimicking diet (FMD) in three months. FMD
reduced the body weight (A), waist circumference (B), and abdominal
fat (C) in obese (BMI>30) and overweight (BMI>25) people. FMD
reduced fasting blood sugar in people with prediabetes (fasting
glucose>99 mg/dL). FMD reduced circulating IGF-1 levels (E). FMD
reduced both systolic and diastolic blood pressure in people with
above normal blood pressure (>120/80 mmHg). FMD reduced total
cholesterol and LDL levels (G). FMD reduced triglycerides and CRP
levels in people with relatively high levels of triglycerides (H)
and CRP (I). FMD increased blood cortisol level (J) and circulating
mesenchymal stem/progenitor cells (MSPC) (K).
[0065] Based on these results, FMD is an effective all natural
plant-based dietary intervention to reduce abdominal adiposity and
to reduce common biomarkers/risk factors for age-related diseases.
In addition, it can promotes protective, anti-inflammatory,
regenerative, and rejuvenating effects while providing high
nourishment and allowing subjects to consume a relatively normal
diet.
FMD Composition
[0066] Fasting Mimicking Diet (FMD) is all natural plant-based
dietary intervention to manage body weight, to reduce circulating
Insulin-like Growth Factor 1 (IGF-1) and to augment common
markers/risk factors for age-related diseases. In addition, it may
promote protective, anti-inflammatory, regenerative, and
rejuvenating effects while providing high nourishment and allowing
practitioners to enjoy a relatively normal diet.
[0067] The following FMD and FMD regimens will be required to
effectively manage body weight, augment risk factors associated
with aging and age-related diseases in humans. They were developed
by extrapolating from the mouse diets and diet regimens as well as
based on the results of ongoing clinical trials.
[0068] It has been shown that the FMD, intermittent use of FMD, and
cycles of FMD decreases fasting blood glucose and IGF-1 levels. The
reduction of serum IGF-1 level has been shown to be one of the key
biomarkers that is associated with regeneration of the
hematopoietic stem and progenitor cells (HSPCs).
[0069] The FMD is comprised of a variety of food items including,
but not limited to, energy bars, soups, vegetable chips, vegetable
and fruit snacks, energy drinks, teas, and supplements for
minerals, vitamins and essential fatty acids. All food items were
developed to reach a profile of macro nutrients and calorie content
that will mimicking the benefit of short-term fasting while
providing certain levels of support for micronutrients.
ProLon Diet
[0070] Diet 1: the FMD will substitute a subject's normal diet for
a period of 5 days every 2-4 weeks depending on the need of the
subject in terms of body weight and disease risk factor management.
For day 1, the FMD will provide 4-8 kcal per pound of body weight
(or 9-18 kcal per kilogram body weight). For day 2-5, the FMD will
provide 3-6 kcal per pound of body weight (or 6-13 kcal per
kilogram body weight). The day 1 diet should contain less than 40
grams of sugar, less than 28 grams of protein, 12-25 grams of
monounsaturated fats, 4.5-10 grams of polyunsaturated fats and
4.5-10 grams of saturated fats. The Day 2-5 diets should contain
less than 25 grams of sugar, less than 18 grams of protein, 9-18
grams of monounsaturated fats, 3-6 grams of polyunsaturated fats
and 4-8 grams of saturated fats. The diet will also provide
micronutrients at great than 50% of
Rice-Protein Based Mix to Reduce IGF-1 Levels
[0071] We have identified a formulation that can replace other
common protein sources to reduce circulating IGF-1 levels. The mix
is composed of vitamins, minerals, essential fatty acids and
enzymatically processed rice protein from whole grain, sprouted
brown rice. This supplement mix will provide 17-35 gram of protein
per day and micronutrients at great than 25% of the Daily Value
(DV).
[0072] FIG. 5 provides serum IGF-1 levels in 18-month old female
mice after 3 cycles of 5-days feeding of Control (AIN93G) or FMDs
formulated with equivalent levels of casein-derived, wheat-derived
derived, whole grain sprouted brown rice-derived proteins or an
equivalent level of a complete amino acid mix as a protein source.
(N=5). *p<0.01, ANOVA, compared to AIN93G.
[0073] FIG. 6 provides serum IGF-1 levels of 18-month old male mice
after 5-days feeding of Control (AIN93G) or FMDs formulated with
casein-derived, or whole grain sprouted brown rice-derived protein
or complete amino acid mix as protein source. (N=5). *p<0.01,
ANOVA, compared to AIN93G.
[0074] While exemplary embodiments are described above, it is not
intended that these embodiments describe all possible forms of the
invention. Rather, the words used in the specification are words of
description rather than limitation, and it is understood that
various changes may be made without departing from the spirit and
scope of the invention. Additionally, the features of various
implementing embodiments may be combined to form further
embodiments of the invention.
* * * * *