(clinical and experimental data)
Adverse effects of energy restriction on changes in immunoglobulins and complements during weight reduction in judoists.
Dietary restriction and immune function.
Energy restriction restores the impaired immune response in overweight (cafeteria) rats.
Immunological effects of low-fat diets with and without weight loss.
Delayed immune aging in diet-restricted B6CBAT6 F1 mice is associated with preservation of naive T cells.
Alterations in lymphocyte subsets and pituitary-adrenal gland-related hormones during fasting.
The effects of dietary restriction on immune function and development of autoimmune disease in BXSB mice.
The influence of age and gender on the immune system: a longitudinal study in Labrador Retriever dogs.
Effects of nutrition on disease and life span. I. Immune responses, cardiovascular pathology, and life span in MRL mice.
Dietary restrictions early and late: effects on the nephropathy of the NZB X NZW mouse.


J Sports Med Phys Fitness. 2004 Sep;44(3):328-34.
Adverse effects of energy restriction on changes in immunoglobulins and complements during weight reduction in judoists.
Umeda T, Nakaji S, Shimoyama T, Kojima A, Yamamoto Y, Sugawara K.
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.


J Nutr. 2004 Aug;134(8):1853-6.
Dietary restriction and immune function.
Jolly CA.
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.


J Nutr Biochem. 2004 Jul;15(7):418-25.
Energy restriction restores the impaired immune response in overweight (cafeteria) rats.
Lamas O, Martinez JA, Marti A.
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.



J Am Coll Nutr. 2003 Apr;22(2):174-82.
Immunological effects of low-fat diets with and without weight loss.
Santos MS, Lichtenstein AH, Leka LS, Goldin B, Schaefer EJ, Meydani SN.
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.



J Gerontol A Biol Sci Med Sci 1998 Sep;53(5):B330-7; discussion B338-9.
Delayed immune aging in diet-restricted B6CBAT6 F1 mice is associated with preservation of naive T cells.
Chen J, Astle CM, Harrison DE.
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.



Am J Clin Nutr 1997 Jul;66(1):147-52.
Alterations in lymphocyte subsets and pituitary-adrenal gland-related hormones during fasting.
Komaki G; Kanazawa F; Sogawa H; Mine K; Tamai H; Okamura S; Kubo C.
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.



Proc Natl Acad Sci U S A 1992 Apr 1;89(7):3145-9.
The effects of dietary restriction on immune function and development of autoimmune disease in BXSB mice.
Kubo C, Gajar A, Johnson BC, Good RA.
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.


The influence of age and gender on the immune system: a longitudinal study in Labrador Retriever dogs.
Greeley EH, Ballam JM, Harrison JM, Kealy RD, Lawler DF, Segre M.
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.



Am J Pathol 1984 Oct;117(1):110-24.
Effects of nutrition on disease and life span. I. Immune responses, cardiovascular pathology, and life span in MRL mice.
Mark DA, Alonso DR, Quimby F, Thaler HT, Kim YT, Fernandes G, Good RA, Weksler ME.

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.



Lab Invest 1978 Jun;38(6):629-32.
Dietary restrictions early and late: effects on the nephropathy of the NZB X NZW mouse.
Friend PS, Fernandes G, Good RA, Michael AF, Yunis EJ.

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.

on the Adriatic Coast
The Anti-Aging Fasting Program consists of a 7-28 days program (including 3 - 14 fasting days). 7-28-day low-calorie diet program is also available .
More information
    The anti-aging story (summary)
Introduction. Statistical review. Your personal aging curve
  Aging and Anti-aging. Why do we age?
    2.1  Aging forces (forces that cause aging
Internal (free radicals, glycosylation, chelation etc.) 
External (Unhealthy diet, lifestyle, wrong habits, environmental pollution, stress, poverty-change "poverty zones", or take it easy. etc.) 
    2.2 Anti-aging forces
Internal (apoptosis, boosting your immune system, DNA repair, longevity genes) 
External (wellness, changing your environment; achieving comfortable social atmosphere in your life, regular intake of anti-aging drugs, use of replacement organs, high-tech medicine, exercise)
    2.3 Aging versus anti-aging: how to tip the balance in your favour!
    3.1 Caloric restriction and fasting extend lifespan and decrease all-cause mortality (Evidence)
      Human studies
Monkey studies
Mouse and rat studies
Other animal studies
    3.2 Fasting and caloric restriction prevent and cure diseases (Evidence)
Hypertension and Stroke
Skin disorders
Mental disorders
Neurogical disorders
Asthmatic bronchitis, Bronchial asthma
Bones (osteoporosis) and fasting
Arteriosclerosis and Heart Disease
Cancer and caloric restriction
Cancer and fasting - a matter of controversy
Eye diseases
Chronic fatigue syndrome
Sleeping disorders
Rheumatoid arthritis
Gastrointestinal diseases
    3.3 Fasting and caloric restriction produce various
      biological effects. Effects on:
        Energy metabolism
Lipids metabolism
Protein metabolism and protein quality
Neuroendocrine and hormonal system
Immune system
Physiological functions
Reproductive function
Cognitive and behavioral functions
Biomarkers of aging
    3.4 Mechanisms: how does calorie restriction retard aging and boost health?
        Diminishing of aging forces
  Lowering of the rate of gene damage
  Reduction of free-radical production
  Reduction of metabolic rate (i.e. rate of aging)
  Lowering of body temperature
  Lowering of protein glycation
Increase of anti-aging forces
  Enhancement of gene reparation
  Enhancement of free radical neutralisation
  Enhancement of protein turnover (protein regeneration)
  Enhancement of immune response
  Activation of mono-oxygenase systems
  Enhance elimination of damaged cells
  Optimisation of neuroendocrine functions
    3.5 Practical implementation: your anti-aging dieting
        Fasting period.
Re-feeding period.
Safety of fasting and low-calorie dieting. Precautions.
      3.6 What can help you make the transition to the low-calorie life style?
        Social, psychological and religious support - crucial factors for a successful transition.
Drugs to ease the transition to caloric restriction and to overcome food cravings (use of adaptogenic herbs)
Food composition
Finding the right physician
    3.7Fasting centers and fasting programs.
  Food to eat. Dishes and menus.
    What to eat on non-fasting days. Dishes and menus. Healthy nutrition. Relation between foodstuffs and diseases. Functional foods. Glycemic index. Diet plan: practical summary. "Dr. Atkins", "Hollywood" and other fad diets versus medical science

Bread, cereals, pasta, fiber
Glycemic index
Meat and poultry
Sugar and sweet
Fats and oils
Dairy and eggs
Nuts and seeds
Food composition

  Anti-aging drugs and supplements
    5.1 Drugs that are highly recommended
      (for inclusion in your supplementation anti-aging program)
        Vitamin E
Vitamin C
Co-enzyme Q10
Lipoic acid
Folic acid
Flavonoids, carotenes
Vitamin B
Vinpocetine (Cavinton)
Deprenyl (Eldepryl)
    5.2 Drugs with controversial or unproven anti-aging effect, or awaiting other evaluation (side-effects)
        Phyto-medicines, Herbs
      5.3 Drugs for treatment and prevention of specific diseases of aging. High-tech modern pharmacology.
        Alzheimer's disease and Dementia
Immune decline
Infections, bacterial
Infections, fungal
Memory loss
Muscle weakness
Parkinson's disease
Prostate hyperplasia
Sexual disorders
Stroke risk
Weight gaining
    5.4 The place of anti-aging drugs in the whole
      program - a realistic evaluation
    6.1 Early diagnosis of disease - key factor to successful treatment.
      Alzheimer's disease and Dementia
Cataracts and Glaucoma
Genetic disorders
Heart attacks
Immune decline
Infectious diseases
Memory loss
Muscle weakness
Parkinson's disease
Prostate hyperplasia
Stroke risk
Weight gaining
    6.2 Biomarkers of aging and specific diseases
    6.3 Stem cell therapy and therapeutic cloning
    6.4 Gene manipulation
    6.5 Prosthetic body-parts, artificial organs
Bones, limbs, joints etc.
Heart & heart devices
    6.6 Obesity reduction by ultrasonic treatment
  Physical activity and aging. Experimental and clinical data.
        Aerobic exercises
Weight-lifting - body-building
Professional sport: negative aspects
  Conclusion: the whole anti-aging program
    9.1 Modifying your personal aging curve
      Average life span increment. Expert evaluation.
Periodic fasting and caloric restriction can add 40 - 50 years to your lifespan
Regular intake of anti-aging drugs can add 20-30 years to your lifespan
Good nutrition (well balanced, healthy food, individually tailord diet) can add 15-25 years to your lifespan
High-tech bio-medicine service can add 15-25 years to your lifespan
Quality of life (prosperity, relaxation, regular vocations) can add 15-25 years to your lifespan
Regular exercise and moderate physical activity can add 10-20 years to your lifespan
These approaches taken together can add 60-80 years to your lifespan, if you start young (say at age 20). But even if you only start later (say at 45-50), you can still gain 30-40 years

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    9.2 The whole anti-aging life style - brief summary 
    References eXTReMe Tracker
        The whole anti-aging program: overview

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