The effect on health of alternate day calorie restriction: Eating less and more than needed on alternate days prolongs life
James B. Johnsona, Corresponding Author Contact Information, E-mail The Corresponding Author, Donald R. Laubb and Sujit Johnc
aDepartment of Surgery, Louisiana State University Medical Center, 2547A Lyon Street, 2nd Floor, San Francisco, CA 94123, United States
bDepartment of Surgery, Stanford Medical School, Stanford, CA, United States
cDepartment of Mathematics, University of New Orleans, New Orleans, LA, United States
Received 9 January 2006;
accepted 16 January 2006.
Available online 10 March 2006.
Restricting caloric intake to 60–70% of normal adult weight maintenance requirement prolongs lifespan 30–50% and confers near perfect health across a broad range of species. Every other day feeding produces similar effects in rodents, and profound beneficial physiologic changes have been demonstrated in the absence of weight loss in ob/ob mice. Since May 2003 we have experimented with alternate day calorie restriction, one day consuming 20–50% of estimated daily caloric requirement and the next day ad lib eating, and have observed health benefits starting in as little as two weeks, in insulin resistance, asthma, seasonal allergies, infectious diseases of viral, bacterial and fungal origin (viral URI, recurrent bacterial tonsillitis, chronic sinusitis, periodontal disease), autoimmune disorder (rheumatoid arthritis), osteoarthritis, symptoms due to CNS inflammatory lesions (Tourette’s, Meniere’s) cardiac arrhythmias (PVCs, atrial fibrillation), menopause related hot flashes. We hypothesize that other many conditions would be delayed, prevented or improved, including Alzheimer’s, Parkinson’s, multiple sclerosis, brain injury due to thrombotic stroke atherosclerosis, NIDDM, congestive heart failure.
Our hypothesis is supported by an article from 1957 in the Spanish medical literature which due to a translation error has been construed by several authors to be the only existing example of calorie restriction with good nutrition. We contend for reasons cited that there was no reduction in calories overall, but that the subjects were eating, on alternate days, either 900 calories or 2300 calories, averaging 1600, and that body weight was maintained. Thus they consumed either 56% or 144% of daily caloric requirement. The subjects were in a residence for old people, and all were in perfect health and over 65. Over three years, there were 6 deaths among 60 study subjects and 13 deaths among 60 ad lib-fed controls, non-significant difference. Study subjects were in hospital 123 days, controls 219, highly significant difference. We believe widespread use of this pattern of eating could impact influenza epidemics and other communicable diseases by improving resistance to infection. In addition to the health effects, this pattern of eating has proven to be a good method of weight control, and we are continuing to study the process in conjunction with the NIH.Alternate day fasting impacts the brain insulin-signaling pathway of young adult male C57BL/6 mice.
Lu J, E L, Wang W, Frontera J, Zhu H, Wang WT, Lee P, Choi IY, Brooks WM, Burns JM, Aires D, Swerdlow RH.
Department of Neurology, University of Kansas Medical Center, Kansas City, Kansas, USA.
Dietary restriction (DR) has recognized health benefits that may extend to brain. We examined how DR affects bioenergetics-relevant enzymes and signaling pathways in the brains of C57BL/6 mice. Five-month-old male mice were placed in ad libitum or one of two repeated fasting and refeeding (RFR) groups, an alternate day (intermittent fed; IF) or alternate day plus antioxidants (blueberry, pomegranate, and green tea extracts) (IF + AO) fed group. During the 24-h fast blood glucose levels initially fell but stabilized within 6 h of starting the fast, thus avoiding frank hypoglycemia. DR in general appeared to enhance insulin sensitivity. After six weeks brain AKT and glycogen synthase kinase 3 beta phosphorylation were lower in the RFR mice, suggesting RFR reduced brain insulin-signaling pathway activity. Pathways that mediate mitochondrial biogenesis were not activated; AMP kinase phosphorylation, silent information regulator 2 phosphorylation, peroxisomal proliferator-activated receptor-gamma coactivator 1 alpha levels, and cytochrome oxidase subunit 4 levels did not change. ATP levels also did not decline, which suggests the RFR protocols did not directly impact brain bioenergetics. Antioxidant supplementation did not affect the brain parameters we evaluated. Our data indicate in young adult male C57BL/6 mice, RFR primarily affects brain energy metabolism by reducing brain insulin signaling, which potentially results indirectly as a consequence of reduced peripheral insulin production.Insulin and aging.
Department of Internal Medicine and Department of Physiology, Southern Illinois University School of Medicine, Springfield, Illinois 62794-9628, USA. email@example.com
In invertebrates, signaling pathways homologous to mammalian insulin and insulin-like growth factor (IGF-1) signal transduction have a major role in the control of longevity. There are numerous indications that these pathways also influence aging in mammals, but separating the role of insulin from the effects of IGF-1 and growth hormone (GH) is difficult. In mice, selective disruption of the insulin receptor in the adipose tissue extends longevity. Increases in lifespan were also reported in mice with deletion of insulin receptor substrate 1 (IRS1) in whole body or IRS2 only in the brain. GH deficiency or resistance in mutant mice leads to hypoinsulinemia and enhanced insulin sensitivity along with remarkably extended longevity. These characteristics resemble animals subjected to calorie restriction. Studies of physiological characteristics and polymorphisms of insulin-related genes in exceptionally long-lived people suggest a role of insulin signaling in the control of human aging.The effects of intermittent or continuous energy restriction on weight loss and metabolic disease risk markers: a randomized trial in young overweight women.
Harvie MN, Pegington M, Mattson MP, Frystyk J, Dillon B, Evans G, Cuzick J, Jebb SA, Martin B, Cutler RG, Son TG, Maudsley S, Carlson OD, Egan JM, Flyvbjerg A, Howell A.
Genesis Prevention Centre, University Hospital of South Manchester NHS Foundation Trust, Manchester, UK.
Background:The problems of adherence to energy restriction in humans are well known.Objective:To compare the feasibility and effectiveness of intermittent continuous energy (IER) with continuous energy restriction (CER) for weight loss, insulin sensitivity and other metabolic disease risk markers.Design:Randomized comparison of a 25% energy restriction as IER (∼2710 kJ/day for 2 days/week) or CER (∼6276 kJ/day for 7 days/week) in 107 overweight or obese (mean (±s.d.) body mass index 30.6 (±5.1) kg m(-2)) premenopausal women observed over a period of 6 months. Weight, anthropometry, biomarkers for breast cancer, diabetes, cardiovascular disease and dementia risk; insulin resistance (HOMA), oxidative stress markers, leptin, adiponectin, insulin-like growth factor (IGF)-1 and IGF binding proteins 1 and 2, androgens, prolactin, inflammatory markers (high sensitivity C-reactive protein and sialic acid), lipids, blood pressure and brain-derived neurotrophic factor were assessed at baseline and after 1, 3 and 6 months.Results:Last observation carried forward analysis showed that IER and CER are equally effective for weight loss: mean (95% confidence interval ) weight change for IER was -6.4 (-7.9 to -4.8) kg vs -5.6 (-6.9 to -4.4) kg for CER (P-value for difference between groups=0.4). Both groups experienced comparable reductions in leptin, free androgen index, high-sensitivity C-reactive protein, total and LDL cholesterol, triglycerides, blood pressure and increases in sex hormone binding globulin, IGF binding proteins 1 and 2. Reductions in fasting insulin and insulin resistance were modest in both groups, but greater with IER than with CER; difference between groups for fasting insulin was -1.2 (-1.4 to -1.0) μU ml(-1) and for insulin resistance was -1.2 (-1.5 to -1.0) μU mmol(-1) l(-1) (both P=0.04).Conclusion:IER is as effective as CER with regard to weight loss, insulin sensitivity and other health biomarkers, and may be offered as an alternative equivalent to CER for weight loss and reducing disease risk.International Journal of Obesity advance online publication, 5 October 2010; doi:10.1038/ijo.2010.171.Improvements in LDL particle size and distribution by short-term alternate day modified fasting in obese adults.
Varady KA, Bhutani S, Klempel MC, Lamarche B.
Department of Kinesiology and Nutrition, University of Illinois at Chicago, 1919 West Taylor Street, Room 506F, Chicago, IL 60612, USA. firstname.lastname@example.org
Alternate day modified fasting (ADMF) beneficially modulates several indicators of CHD risk, but its effects on LDL particle size have never been tested. Accordingly, we examined the effects of ADMF on LDL particle size and distribution in obese adults. Sixteen obese subjects participated in a 10-week trial with three consecutive phases: (1) 2-week control phase; (2) 4-week ADMF controlled feeding phase; (3) 4-week ADMF self-selected feeding phase. After 8 weeks of diet, body weight and waist circumference were reduced (P < 0·05) by 5·6 (sem 0·9) kg and 4·0 (sem 0·9) cm, respectively. LDL-cholesterol and TAG concentrations decreased (P < 0·05) by 25 (sem 10) % and 32 (sem 6) %, respectively. Peak LDL particle size increased (P < 0·05) from 266 (sem 1) to 268 (sem 1) Å. Additionally, the proportion of small LDL particles decreased (P < 0·05) from 13 (sem 2) % to 9 (sem 3) %, while the proportion of large LDL particles increased (P < 0·05) from 68 (sem 4) % to 76 (sem 4) % post-treatment. These findings suggest that ADMF is an effective diet strategy for increasing LDL particle size and decreasing the proportion of small, dense LDL particles in obese adultsModified alternate-day fasting regimens reduce cell proliferation rates to a similar extent as daily calorie restriction in mice.
Varady KA, Roohk DJ, McEvoy-Hein BK, Gaylinn BD, Thorner MO, Hellerstein MK.
Department of Nutritional Sciences and Toxicology, University of California at Berkeley, Morgan Hall, Rm. 308, Berkeley, California, 94720-3104, USA. email@example.com
Calorie restriction (CR) and alternate-day fasting (ADF) reduce cancer risk and reduce cell proliferation rates. Whether modified ADF regimens (i.e., allowing a portion of energy needs to be consumed on the fast day) work, as well as true ADF or CR to reduce global cell proliferation rates, remains unresolved. Here, we measured the effects of true ADF, modified ADF, and daily CR on cell proliferation rates in mice. Thirty female C57BL/6J mice were randomized to one of five interventions for 4 wk: 1) CR-25% (25% reduction in daily energy intake), 2) ADF-75% (75% reduction on fast day), 3) ADF-85% (85% reduction on fast day), 4) ADF-100% (100% reduction on fast day), and 5) control (ad libitum intake). Body weights of the ADF groups did not differ from controls, whereas the CR-25% group weighed less than all other groups posttreatment. Epidermal cell proliferation decreased (P<0.01) by 29, 20, and 31% in the CR-25%, ADF-85% and ADF-100% groups, respectively, relative to controls. Proliferation rates of splenic T cells were reduced (P<0.01) by 37, 32, and 31% in the CR-25%, ADF-85%, and ADF-100% groups, respectively, and mammary epithelial cell proliferation was 70, 65, and 62% lower (P<0.01), compared with controls. Insulin-like growth factor-1 levels were reduced (P<0.05) in the CR-25% and ADF-100% groups only. In summary, modified ADF, allowing the consumption of 15% of energy needs on the restricted intake day, decreases global cell proliferation similarly as true ADF and daily CR without reducing body weight.FULL TEXT HERE Alternate-day fasting and chronic disease prevention: a review of human and animal trialsAlternate-day fasting and chronic disease prevention: a review of human and animal trials1,2,3
Krista A Varady and Marc K Hellerstein
1 From the Department of Nutritional Sciences and Toxicology, University of California at Berkeley, Berkeley, CA
2 Supported by the Natural Science and Engineering Research Council of Canada.
3 Reprints not available. Address correspondence to KA Varady, Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Morgan Hall, Room 308, Berkeley, CA 94720-3104. E-mail: firstname.lastname@example.org.
Calorie restriction (CR) and alternate-day fasting (ADF) represent 2 different forms of dietary restriction. Although the effects of CR on chronic disease prevention were reviewed previously, the effects of ADF on chronic disease risk have yet to be summarized. Accordingly, we review here animal and human evidence concerning ADF and the risk of certain chronic diseases, such as type 2 diabetes, cardiovascular disease, and cancer. We also compare the magnitude of risk reduction resulting from ADF with that resulting from CR. In terms of diabetes risk, animal studies of ADF find lower diabetes incidence and lower fasting glucose and insulin concentrations, effects that are comparable to those of CR. Human trials to date have reported greater insulin-mediated glucose uptake but no effect on fasting glucose or insulin concentrations. In terms of cardiovascular disease risk, animal ADF data show lower total cholesterol and triacylglycerol concentrations, a lower heart rate, improved cardiac response to myocardial infarction, and lower blood pressure. The limited human evidence suggests higher HDL-cholesterol concentrations and lower triacylglycerol concentrations but no effect on blood pressure. In terms of cancer risk, there is no human evidence to date, yet animal studies found decreases in lymphoma incidence, longer survival after tumor inoculation, and lower rates of proliferation of several cell types. The findings in animals suggest that ADF may effectively modulate several risk factors, thereby preventing chronic disease, and that ADF may modulate disease risk to an extent similar to that of CR. More research is required to establish definitively the consequences of ADF.
A LINK TO ANOTHER FULL STUDY ON ADF http://jn.nutrition.org/content/31/3/363.full.pdf