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PERIODICAL
FASTING AND CALORIC RESTRICTION FOR LIFE EXTENSION,
DISEASE TREATMENT AND CREATIVITY.
(clinical and experimental data)
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FASTING AND CALORIC RESTRICTION PRODUCE VARIOUS BIOLOGICAL
EFFECTS |
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IMMUNITY
AND AUTOIMMUNITY AND FASTING |
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2004
Department of Hygiene, Hirosaki
University School of Medicine, Aomori, Japan.
AIM: A preliminary study to
investigate the combined effects of dietary restriction
and weight reduction through exercise on markers of
immune function in college judoists before and after
a single competition. METHODS: Forty-nine judoists
participated in the study. Thirty-eight athletes combined
exercise and dietary restriction (WR group), and 11
athletes did not require dietary restriction (EX group).
Changes in anthropometric parameters, energy intake,
concentrations of serum immunoglobulins and complements,
and white blood cell counts were assessed at 4 time
points: 20 days (pre-values), 4 days and 1 day before
the competition, and 7 days after the competition.
RESULTS: Compared with pre-values, the WR group exhibited
significant decreases in body weight (-2.8 kg at 1
day before) and fat free mass (-1.7 kg at 1 day before);
there were no changes in these variables in the EX
group. The WR group exhibited significant decreases
in IgG, IgM and C3 at 7 days after the competition
(all p<0.01). In the EX group, significant decreases
in IgM and C3 (both p<0.05) were observed at 7
days after the competition, though to a lesser degree
than in the WR group. CONCLUSIONS: Energy restriction
seemed to exacerbate alterations in immune markers
such as immunoglobulin and complement induced by vigorous
exercise at 7 days after a competition. Although the
changed values were still within normal limits, we
hypothesize that the potential cumulative effect of
these changes over many competitions in 1 year might
well induce abnormal levels with a possibly harmful
clinical effect on judoists.
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Division of Nutritional Sciences,
The University of Texas at Austin, Austin, TX 78712,
USA.
Dietary restriction is beneficial
in preventing a multitude of diseases, many of which
may involve the immune system in their etiology. Recent
reports examining dietary restriction focused on T
lymphocytes and macrophages. Dietary restriction delays
the onset of T-lymphocyte-dependent autoimmune disease;
this may be attributed to improved antioxidant defense
mechanisms, blunting shifts in T-lymphocyte subset
proportions and preventing DNA mutation frequencies.
The beneficial effects of dietary restriction were
shown in both the CD4 and CD8 T-lymphocyte subsets
as well as in various immune compartments such as
the spleen, mesenteric lymph nodes, peripheral blood,
thymus, and salivary glands. In contrast, dietary
restriction may have negative effects on macrophage
function because recent evidence showed that dietary
restriction rendered mice more susceptible to peritonitis
and stimulated macrophages produced lower amounts
of cytokines. The application of dietary restriction
regimens to humans would be difficult; however, understanding
the biochemical and molecular targets of dietary restriction
in the immune system may lead to the development of
new dietary strategies to delay or prevent the onset
of aging, cancer, and autoimmune disease.
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Department of Physiology and
Nutrition, University of Navarra, 31008 Pamplona,
Spain.
Impaired immune function linked
to obesity has been shown in both human and animal
studies. The purpose of this work was to evaluate
the effects of a 4-week energy restriction (50% of
total energy intake) on immune function in previously
diet-induced (cafeteria) overweight rats. Flow cytometric
analysis revealed that the number of spleen T helper
cells were significantly (P < 0.05) elevated in
control and overweight energy-restricted rats as compared
with groups fed ad libitum groups. The proliferative
response of splenocytes to phytohaemaglutinin and
concanavalin A from overweight rats after energy restriction
was significantly (P < 0.05) higher compared to
overweight nonrestricted rats. The cytotoxic activity
of natural killer cells tended to be lower in overweight
rats compared to controls. Finally, control rats under
the dietary deprivation period presented higher levels
of uncoupling protein 2 mRNA and lower levels of leptin
receptor mRNA compared with the reference control
group. These results suggest that energy restriction
is able to restore, at least in part, the impaired
immune response commonly observed in overweight animals.
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1998
Nutritional Immunology Laboratory,
Jean Mayer USDA Human Nutrition Research Center on
Aging, Tufts University, 711 Washington Street, Boston,
MA 02111, USA.
OBJECTIVE: The immunologic effects
of isocaloric reduced- and low-fat diets and a voluntary
calorie-restricted low-fat diet resulting in weight
loss were compared to the immunologic effects of an
average American diet in hyperlipidemic individuals.
METHODS: Ten hyperlipidemic subjects were studied
during three six-week weight maintenance phases: baseline
(BL) [35% fat [14% saturated fat (SFA), 13% monounsaturated
fat (MUFA), 8% polyunsaturated fat (PUFA)] and 147
mg cholesterol (C)/1000 kcal], reduced-fat (RF) [26%
fat (4% SFA, 11% MUFA, 11% PUFA) and 45 mg C/1000
kcal], and low-fat (LF) [15% fat (5% SFA, 5% MUFA,
3% PUFA) and 35 mg C/1000 kcal] diets followed by
12-week, low-fat calorie reduced phase (LFCR). RESULTS:
During the last phase, the subjects' weight significantly
decreased (p = 0.005). Cholesterol levels were significantly
reduced during all phases, compared to BL diet (p
< 0.05). Delayed-type hypersensitivity (DTH) was
assessed using Multi-test CMI. Maximum induration
diameters were 22.7, 25.4, 30.5, 34.5 mm for BL, RF,
LF and LFCR diets, respectively. Subjects on the LFCR
diets had significantly higher DTH compared to the
BL diet (p = 0.005). No significant effect of diet
was observed on lymphocyte proliferation or interleukin
(IL)-1, IL-2 and prostaglandin (PG) E(2) production.
CONCLUSIONS: These data suggest that low-fat diets
(15% energy), under conditions which result in weight
loss, do not compromise and may enhance the immune
response of middle-aged and elderly hyperlipidemic
subjects. The results of this study provide support
for the hypothesis that moderate caloric restriction
in humans may have a beneficial effect on cell-mediated
immunity such as those reported in calorie-restricted
rodents.
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1998
Jackson Laboratory, Bar Harbor,
Maine, USA.
Age-related changes in peripheral
blood, spleen, and thymus of ad libitum (AL)-fed and
dietary restricted (DR) C57BL/6J x CBA/CaH-T6/J F1
(B6CBAT6 F1) mice at young (3 mo), middle (16 mo),
and old (30 mo) ages were studied to define how dietary
restriction retards immune aging. Dietary restriction
at 25% AL intake level initiated at weaning significantly
reduced the rates of age-related declines in peripheral
blood T helper cells, naive T helper cells, and naive
cytotoxic T lymphocytes (CTLs). As a result, concentrations
of these cell types in old DR mice were equivalent
to 161%, 176%, and 250% of those in old AL controls.
Dietary restriction also abolished age-related splenomegaly
and decreased total splenocyte numbers in old DR mice.
Dietary restriction did not prevent age-related decline
in thymus size, but preserved thymus cellularity in
old mice. Old DR mice had twice as many total thymocytes
and 2.6 times as many CD4+CD8+ immature thymocytes
as old AL controls. The correlations between total
immature thymocytes and concentrations of circulating
naive T helper cells and naive CTLs increase with
age and become significant in old mice. Thus, dietary
restriction preserves immature T-cell precursors in
the thymus during aging to maintain higher concentrations
of circulating T helper and naive T cells in peripheral
blood.
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1997
Department of Psychosomatic Medicine,
Faculty of Medicine, Kyushu University, Fukuoka, Japan.
We investigated changes in
the immunoendocrine system during fasting. Ten hospitalized
patients aged 14-46 y with psychosomatic disorders
fasted for 7 or 10 d. Blood samples were collected
before and on days 3 and 7 of the 7-d fasts. When
fasting continued to 10 d, an additional sample was
taken on day 10. We measured blood cellularity (white
blood cells and total lymphocytes), the total number
and percentage of lymphocyte subsets (CD2, CD3, CD4,
CD8, and CD19), natural killer (NK) cell activity,
cytokines (interleukin 1 beta, interleukin 2, interleukin
6, granulocyte-macrophage colony stimulating factor,
tumor necrosis factor alpha, and interferon gamma),
and soluble interleukin 2 receptors. Corticotropin,
cortisol, and dehydroepiandrosterone sulfate (DHEAS)
concentrations were also determined. Although the
total number of lymphocytes decreased during fasting,
NK cell activity increased significantly. Plasma cortisol
and DHEAS concentrations also increased significantly
whereas changes in corticotropin concentrations were
not significant. The total number and percentage of
CD4 cells decreased significantly during fasting but
no other lymphocyte subsets changed significantly.
The percentage of CD4 cells was negatively correlated
with cortisol concentrations during fasting. No detectable
changes occurred in cytokines or soluble interleukin
2 receptors during the study. All measured immunoendocrine
values that changed during fasting returned to prefasting
values during the refeeding period. These findings
indicate that fasting affects immune variables such
as T cell subsets and NK cell activity at least in
part through changes in adrenal gland-related hormones.
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1992
Faculty of Medicine, Kyushu University,
Fukuoka, Japan.
Chronic energy intake restriction
(CEIR) prolonged the median life span and inhibited
autoimmunity and development of autoimmune disease
in BXSB mice, as has been established for mice of
several other autoimmune-prone, short-lived strains.
Whether imposed just after weaning or delayed until
manifestations of disease had appeared, CEIR inhibited
or reversed development of autoimmunity and immune
complex-based renal disease in male BXSB mice. CEIR
also prevented the formation of anti-DNA antibodies
and prevented the increase in circulating immune complex
levels that is typically observed in male mice of
this strain. Moreover, CEIR inhibited development
of splenomegaly and prevented the normal age-associated
decline of a number of immunological functions, including
interleukin 2 production, cell-mediated cytotoxic
responses, and mixed lymphocyte reactivity. The observed
improvement in cell-mediated immune responses was
attributed largely to the capacity of CEIR to inhibit
development of the splenomegaly that occurs concomitant
with expansion of a non-T, non-B lymphoid cell population.
These findings emphasize that CEIR, even when imposed
relatively late in life in BXSB mice, can influence
_expression of autoimmunities and autoimmune diseases
of different genetic origins and presumed pathogenetic
bases.
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Department of Veterinary Pathobiology,
University of Illinois, 2001 S. Lincoln Avenue, Urbana,
IL 61802, USA.
Vet Immunol Immunopathol 2001
Sep 28;82(1-2):57-71 While aging studies employing
a cross-sectional design have been informative in
documenting many age-related alterations in immune
function between different age cohorts within a population,
longitudinal studies are invaluable for verifying
changes at the level of the individual and for defining
the precise periods of life during which particular
changes occur. In the present study, a battery of
immunological parameters were evaluated in a group
of Labrador Retrievers as part of a comprehensive
longitudinal aging study. Twenty-three dogs (14 females,
9 males; from 4 to 11 years of age) were evaluated
annually for total WBC counts, lymphocyte subset distributions,
natural killer cell activity and neutrophil phagocytic
activity, and biannually for lymphoproliferative activity.
An age-related decline in absolute numbers of lymphocytes,
T-cells, CD4-cells and CD8-cells was observed in both
genders. The distribution of lymphocyte subsets shifted
with age, most dramatically in the females; percentages
of B-cells declined while those of T-cells increased.
Changes in percentages of CD4- and CD8-cells over
the 8-year period were not dramatic; in females, percentages
of CD8-cells increased significantly in early- to
mid-life and then stabilized. Lymphoproliferative
responses to mitogens declined over time in both genders.
Males demonstrated higher levels of NK cytolytic activity
than females; a marginal decline in activity with
age was observed. No significant age-related changes
in the phagocytic capacity of PMN were observed. These
longitudinal findings help to discriminate between
those immune parameters which change most dramatically
in early-life versus those which either change more
dramatically later in life or change gradually over
the entire span of life. In addition they identify
significant gender differences in several parameters
and corroborate our previously published cross-sectional
aging data in the same specie.
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1984
Mice of the autoimmune, lymphoproliferative
strain MRL/lpr and the congenic, nonlymphoproliferative
strain MRL/n were fed one of six diets from weaning
on-ward. These mice were sacrificed at 3 or 5 months
of age. Low fat diets resulted in lower cholesterol
and higher triglyceride levels than did cholesterol-containing
high-fat diets. Caloric restriction of MRL/lpr mice
was associated with an increased plaque-forming cell
response to trinitrophenylated polyacrylamide beads,
less lymphoproliferation, and less severe glomerulonephritis.
Diet did not affect the incidence of autoimmune vasculitis
in MRL/lpr mice sacrificed at 5 months. MRL/lpr mice
fed a low-fat, calorically restricted diet from 5
months of age to death lived longer than mice which
were fed ad libitum a cholesterol-containing, high-fat
diet. At death, MRL/lpr mice fed the former diet had
the autoimmune vasculitis which had been evident in
mice killed at 5 months, whereas mice fed the latter
diet, in addition to the vasculitis, had a high incidence
of atherosclerotic lesions of intrarenal and aortic
branch arteries.
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1978
NZB X NZW F1 mice initiated
on calorie restriction at weaning or at 4 to 5 months
of age or initiated on moderate protein restriction
at weaning, were afforded significant protection from
the development of immune nephritis. Whereas animals
on normal calorie intake demonstrated deposition of
immune reactants in glomerular basement membrane-oriented
pattern, those on either protein or calorie restriction
exhibited mesangial confinement of immunoglobulins
and complement. Associated with these divergent patterns
of immune deposition, mice on normal calorie intake
evidence extensive cellular proliferation and glomerular
sclerosis while dietary restricted mice demonstrated
virtually no hyalinization and only mild cellular
proliferation. Autoantibody formation of calorie-restricted
animals was significantly decreased compared to mice
fed a normal diet. Thus, moderate dietary restriction
may serve as either a prophylactic or effective therapeutic
approach to ongoing autoimmune disease.
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