Intermittent Fasting
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Intermittent Fasting, Hormesis, and Delayed Aging by Mark Force, DC Long-lived peoples characteristically eat in moderation and fast periodically. These forms of caloric restriction have been studied extensively in lab animals and the results are very convincing: lab animals on caloric-restricted diets or those that intermittently fasted lived longer and exhibited fewer degenerative diseases as they aged. I began my studies in health and healing with The Miracle of Fasting by Paul Bragg, ND. Dr. Bragg overcame tuberculosis as a kid with fasting, whole and natural foods and exercise. He fasted one day every week and up to a couple of weeks four times a year. He was vital and strong until the day he died in a surfing accident at 93. For him, fasting, above all else, restored his health and kept him vigorous. I recommend Dr. Braggs book for guidance and inspiration when fasting. It has helped me immensely. At one time, Dr. Bragg had popularized the practice of fasting one day a week among many people. I’ve had the pleasure of working with some of Dr. Braggs’ disciples over the years and have been impressed with their overall health, vitality, looks, and strength relative to their age. I am convinced, both through my own experience and observing others, that this regular and longterm regimen of fasting works. Feasting and Fasting - Our Genetic Heritage Caloric restriction (CR) is well-researched and well-known to extend life-span, retard age-related health decline (senescence), and decrease the development of chronic degenerative diseases in a large number of species. 1 Intermittent fasting (IF) has been shown to have similar effects as CR, even without overall reduction in caloric intake. 2 It appears that we are adapted genetically to feast/famine and physical activity/rest cycles which modulate metabolic processes and without these cycles we become prone to metabolic derangements such as obesity and Type 2 diabetes. 3 The benefits of IF are available even when the method is initiated later in life. 4 What The Heck Is Hormesis? We are made to adapt to our environment and moderating the stressors that we adapt to seems to improve our health. Hormesis is the concept that small and usually intermittent exposures to stressors (chemical, physical, mental, thermal) will cause a beneficial or stimulatory effect where a much higher exposure of the same stressor will cause an adverse or inhibitory effect on our metabolism. Examples can include exercise, dietary restrictions, and exposure to small amounts of irritant phytochemicals. The benefits seem to be mediated molecular enzyme responses triggered by the stressor. 5 , 6 The Elements of Health… …functional & natural healthcare Scottsdale, Arizona, USA theelementsofhealth.com
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Intermittent Fasting
Transcript of Intermittent Fasting
Intermittent Fasting, Hormesis, and Delayed Agingby Mark Force, DC
Long-lived peoples characteristically eat in moderation and fast periodically. These forms of caloric restriction have been studied extensively in lab animals and the results are very convincing: lab animals on caloric-restricted diets or those that intermittently fasted lived longer and exhibited fewer degenerative diseases as they aged.
I began my studies in health and healing with The Miracle of Fasting by Paul Bragg, ND. Dr. Bragg overcame tuberculosis as a kid with fasting, whole and natural foods and exercise. He fasted one day every week and up to a couple of weeks four times a year. He was vital and strong until the day he died in a surfing accident at 93. For him, fasting, above all else, restored his health and kept him vigorous.
I recommend Dr. Braggs book for guidance and inspiration when fasting. It has helped me immensely.
At one time, Dr. Bragg had popularized the practice of fasting one day a week among many people. I’ve had the pleasure of working with some of Dr. Braggs’ disciples over the years and have been impressed with their overall health, vitality, looks, and strength relative to their age. I am convinced, both through my own experience and observing others, that this regular and longterm regimen of fasting works.
Feasting and Fasting - Our Genetic HeritageCaloric restriction (CR) is well-researched and well-known to extend life-span, retard age-related health decline (senescence), and decrease the development of chronic degenerative diseases in a large number of species.1 Intermittent fasting (IF) has been shown to have similar effects as CR, even without overall reduction in caloric intake.2
It appears that we are adapted genetically to feast/famine and physical activity/rest cycles which modulate metabolic processes and without these cycles we become prone to metabolic derangements such as obesity and Type 2 diabetes.3
The benefits of IF are available even when the method is initiated later in life.4
What The Heck Is Hormesis?We are made to adapt to our environment and moderating the stressors that we adapt to seems to improve our health. Hormesis is the concept that small and usually intermittent exposures to stressors (chemical, physical, mental, thermal) will cause a beneficial or stimulatory effect where a much higher exposure of the same stressor will cause an adverse or inhibitory effect on our metabolism. Examples can include exercise, dietary restrictions, and exposure to small amounts of irritant phytochemicals. The benefits seem to be mediated molecular enzyme responses triggered by the stressor.5,6
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Many phytochemicals, such as capsaicin from cayenne, curcumin from tumeric, allicin from garlic, and resveratrol from wine stimulate the production of cytoprotective proteins such as antioxidant enzymes, growth factors, neurotrophic factors, sirtuins,and mitochondrial proteins through their hormetic stimulation.7,8
Fasting Stimulates AntioxidantsFree radical are unstable molecules in the body produced by normal metabolism and antioxidants are the molecules produced by your body to protect you from the damage that free radicals cause (oxidative stress). Aging has been extensively associated chronic damage from oxidative stress.9
After eight weeks of intermittent fasting, antioxidant control of oxidative stress was significantly improved. This was measured through increased sirtuin levels, a group of compounds being extensively researched currently and associated with the nutrient resveratrol. What is significant is that sirtuin levels were increased without dietary supplementation.10 IF increased mitochondrial superoxide dismutase, a primary cellular antioxidant.11
Fasting Protects You From ToxinsIF appears to protect against environmental and metabolic toxins.12,13,14
Fasting, Diabetes, Cholesterol, and Heart DiseaseIntermittent fasting lowers serum glucose, increase insulin sensitivity, increases HDL levels, improves the cholesterol/HDL ratio (a heart disease risk factor), lowers homocysteine levels (a marker for systemic inflammation and stroke or heart attack risk), prevents hypoglycemia, and reduces diabetes.15,16,17,18,19,20
Adiponectin is a protein hormone that regulates blood sugar and blood fat metabolism and controls body fat that has been found to be increased with intermittent fasting.21
Intermittent fasting also improves protein metabolism, controls blood pressure, and protects the heart and cardiovascular system.22,23,24,25
Fasting Prevents Cancer?Intermittent fasting of even 1 day a week suppressed carcinogenesis in mice and this effect was even present when started late in life in mice predisposed genetically.26
Fasting, Chronic Pain, and MoodIF was found to result in control of inflammation and pain through down-regulation of NF-kappaB a primary moderator of these processes.27
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Fasting has been associated with increased brain availability of serotonin, endogenous opioids, and endocannabinoids, all of which have been associated with improved control of pain.28 Mice subjected to an intermittent fasting display markedly reduced responses to thermal and visceral pain.29
Fasting and Your HormonesDiminished cycling of hormones in relation to the time of day and lower growth hormone (GH) and IGF1 levels with increased age have been associated with degenerative changes of aging.
IF has been shown to increase GH and IGF1 with one study showing a 4-fold increase in GH. 30,31 Some of the benefits of IF may be had through improved IGF1 signaling/receptor mechanisms.32
IF seems to improve circadian rhythm (day-night cycling) of hormones through improved modulation of the hypothalamus, a part of the brain that controls internal body functions.33
Fasting and Your BrainIF has been postulated by researchers to protect against neurodegenerative disorders such as Alzheimer's and Parkinson's diseases through neurotrophic factors and antioxidant enzymes34,35 IF protects against age related cognitive decline and protects the brain from metabolic stress and injury.36,37,38,39,40
Intermittent fasting even enhances brain function as evidenced by improved memory, learning, and consolidation processes through long-term changes in synaptic efficiency and plasticity.41,42
Is Your Autonomic Nervous System Working For You?IF has been shown to decrease stress as evidenced by decreased tone of the sympathetic nervous system and improve function of the nervous systems’ regulation of the internal organs as evidenced by increased tone of the parasympathetic nervous system.43,44
How Is Your Brain Derived Neurotrophic Factor?Intermittent fasting increases production of brain-derived neurotrophic factor (BDNF). This factor increases the resistance of brain neurons to dysfunction and degeneration and may also improve glucose regulation and cardiovascular function.45,46
Fasting and AgingMethylglyoxal (MG) is a highly toxic glycating agent that is associated with impaired energy production, oxidative stress, and abnormal gene expression and cell signaling. IF has been proposed to suppress MG formation and increase sirtuins.47 It is proposed that periods of fasting might be a more acceptable approach than permanent undernutrition in our attempts to slow human aging.48
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How To FastOne-Day FastA weekly fast of 24-36 hours is an ideal health maintenance measure, as are periodic fasts (usually once a season) from three days to a week. This type of regular food restriction has been shown in research to produce very significant health benefits. This is probably due to the cellular and metabolic responses to the hormetic stimulation that fasting provides rather than only the adaptation to decreased caloric intake.
Weekly fasting makes a huge difference in my health when I have the discipline to do it. I have more energy, strength, endurance, and mental clarity. The 24-hour fast is from dinner to the next dinner. If you want to fast for 36 hours, fast from dinner on one day, through the next day, and until breakfast on the third day.
Best results, in the long run, are when you fast on water only or on water with fresh lemon. Please note that fasting is not appropriate while pregnant or nursing.
If you have difficulty fasting on water only, usually due to a drop in your blood sugar, you can add a little honey or maple syrup to the lemon, or you can use fruit and/or vegetable juices or and herb teas. Juices are preferably freshly made, but if this is not possible then glass-bottled, unpasteurized, unfiltered is a good second. Freshly made juices are much different than bottled and are much more effective. This is not the ideal way to fast as it doesn’t conform to the water fasting from the research. Typically, as you fast regularly, you will find that your tolerance for fasting will improve.
For some, undiluted juices may cause a drop in blood sugar. If you have symptoms, especially problems with energy and/or concentration when using the juices undiluted, mix the juices with an equal amount of water.
When you conclude a one-day fast, its okay to make the first meal a regular meal.
Short Fasts (2-3 days)Fasts of two or three days are done the same as the one-day fast, except most people use juices in addition to water.
Blue-green algae, spirulina, or wheat, oat, barley, and rye grass juice powders (or a combination of them) can also be used a few times a day in juice to keep your energy levels up during the fast.
If you fast for two or more days, break the fast with a lighter-than-normal meal. The best first meal after you fast is fruit or a vegetable, such as salad with an oil and vinegar-based dressing. All meals after that, eat as you normally would.
Long Fasts (4-14 days)These fasts are useful for certain conditions, but their utility is probably due to the detoxification effect primarily rather than the hormetic stimulation.
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Longer fasts are outside of the scope of this paper and will be covered in another paper on the subject of detoxification.
Enhancing The Effects of FastingExerciseExercise along with IF significantly increases the benefits overall through the hormetic stimulation.49,50
ColdCold and IF act synergistically in raising basal metabolic rate and reducing body lipids.51
Dietary IrritantsDietary polyphenols present in most fruits, vegetables, and spices have strong phytochemical effects that activate body processes that are metabolically modulating and protective through their hormetic effects.52,53,54,55 In other words, eat your fruits, veggies, and spices.
Dietary FatsIncluding dietary fats along with IF results in lower overall caloric intake (less hyperphagia) and less body fat.56
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1 Martin B, Golden E, Egan JM, Mattson MP and Maudsley S (2007) Reduced energy intake: the secret to a long and healthy life? IBS J Sci 2, 35-39.
2 Hipkiss AR (2007) Dietary restriction, glycolysis, hormesis and ageing. Biogerontology 8, 221-224.
3 Halberg N, Henriksen M, Söderhamn N, Stallknecht B, Ploug T, Schjerling P and Dela F (2005) Effect of intermittent fasting and refeeding on insulin action in healthy men. J Appl Physiol 99, 2128-2136.
4 Smith ED, Kaeberlein TL, Lydum BT, Sager J, Welton KL, Kennedy BK and Kaeberlein M (2008) Age- and calorie-independent life span extension from dietary restriction by bacterial deprivation in Caenorhabditis elegans. BMC Dev Biol 8, 49.
5 Mattson MP (2008) Hormesis defined. Ageing Res Rev 7, 1-7.
6 The concepts of hormesis are presented in Wikipedia.
7 Mattson MP (2008) Dietary factors, hormesis and health. Ageing Res Rev 7, 43-48.
8 Son TG, Camandola S and Mattson MP (2008) Hormetic dietary phytochemicals. Neuromolecular Med 10, 236-246.
9 Gilca M, Stoian I, Atanasiu V and Virgolici B (2007) The oxidative hypothesis of senescence. J Postgrad Med 53, 207-213.
10 Tajes M, Gutierrez-Cuesta J, Folch J, Ortuño-Sahagun D, Verdaguer E, Jiménez A, Junyent F, Lau A, Camins A and Pallàs M (2010) Neuroprotective role of intermittent fasting in senescence-accelerated mice P8 (SAMP8). Exp Gerontol .
11 Descamps O, Riondel J, Ducros V and Roussel AM (2005) Mitochondrial production of reactive oxygen species and incidence of age-associated lymphoma in OF1 mice: effect of alternate-day fasting. Mech Ageing Dev 126, 1185-1191.
12 Steinkraus KA, Smith ED, Davis C, Carr D, Pendergrass WR, Sutphin GL, Kennedy BK and Kaeberlein M (2008) Dietary restriction suppresses proteotoxicity and enhances longevity by an hsf-1-dependent mechanism in Caenorhabditis elegans. Aging Cell 7, 394-404.
13 Hfaïedh N, Allaqui MS, Croute F, Soleilhavoup JP, Jammoussi K, Makni Ayadi F, Kammoun A and El Feki A (2005) [Interaction of intermittent fasting on the cytotoxic effects of nickel in rats at puberty]. C R Biol 328, 648-660.
14 Hfaiedh N, Allagui MS, Carreau S, Zourgui L, Feki A and Croute F (2008) Impact of dietary restriction on peroxidative effects of nickel chloride in wistar rats. Toxicol Mech Methods 18, 597-603.
15 Favier RJ and Koubi HE (1988) Metabolic and structural adaptations to exercise in chronic intermittent fasted rats. Am J Physiol 254, R877-R884.
16 Aksungar FB, Eren A, Ure S, Teskin O and Ates G (2005) Effects of intermittent fasting on serum lipid levels, coagulation status and plasma homocysteine levels. Ann Nutr Metab 49, 77-82.
17 Pedersen CR, Hagemann I, Bock T and Buschard K (1999) Intermittent feeding and fasting reduces diabetes incidence in BB rats. Autoimmunity 30, 243-250.
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18 Aksungar FB, Topkaya AE and Akyildiz M (2007) Interleukin-6, C-reactive protein and biochemical parameters during prolonged intermittent fasting. Ann Nutr Metab 51, 88-95.
19 Wan R, Camandola S and Mattson MP (2003) Intermittent fasting and dietary supplementation with 2-deoxy-D-glucose improve functional and metabolic cardiovascular risk factors in rats. FASEB J 17, 1133-1134.
20 Mulas MF, Demuro G, Mulas C, Putzolu M, Cavallini G, Donati A, Bergamini E and Dessi S (2005) Dietary restriction counteracts age-related changes in cholesterol metabolism in the rat. Mech Ageing Dev 126, 648-654.
21 Halberg N, Henriksen M, Söderhamn N, Stallknecht B, Ploug T, Schjerling P and Dela F (2005) Effect of intermittent fasting and refeeding on insulin action in healthy men. J Appl Physiol 99, 2128-2136.
22 Tikoo K, Tripathi DN, Kabra DG, Sharma V and Gaikwad AB (2007) Intermittent fasting prevents the progression of type I diabetic nephropathy in rats and changes the expression of Sir2 and p53. FEBS Lett 581, 1071-1078.
23 Katare RG, Kakinuma Y, Arikawa M, Yamasaki F and Sato T (2009) Chronic intermittent fasting improves the survival following large myocardial ischemia by activation of BDNF/VEGF/PI3K signaling pathway. J Mol Cell Cardiol 46, 405-412.
24 Mattson MP and Wan R (2005) Beneficial effects of intermittent fasting and caloric restriction on the cardiovascular and cerebrovascular systems. J Nutr Biochem 16, 129-137.
25 Wan R, Ahmet I, Brown M, Cheng A, Kamimura N, Talan M and Mattson MP (2010) Cardioprotective effect of intermittent fasting is associated with an elevation of adiponectin levels in rats. J Nutr Biochem 21, 413-417.
26 Rocha NS, Barbisan LF, de Oliveira ML and de Camargo JL (2002) Effects of fasting and intermittent fasting on rat hepatocarcinogenesis induced by diethylnitrosamine. Teratog Carcinog Mutagen 22, 129-138.
27Castello L, Froio T, Maina M, Cavallini G, Biasi F, Leonarduzzi G, Donati A, Bergamini E, Poli G and Chiarpotto E (2010) Alternate-day fasting protects the rat heart against age-induced inflammation and fibrosis by inhibiting oxidative damage and NF-kB activation. Free Radic Biol Med 48, 47-54.
28 Michalsen A (2010) Prolonged fasting as a method of mood enhancement in chronic pain syndromes: a review of clinical evidence and mechanisms. Curr Pain Headache Rep 14, 80-87.
29de los Santos-Arteaga M, Sierra-Domínguez SA, Fontanella GH, Delgado-García JM and Carrión AM (2003) Analgesia induced by dietary restriction is mediated by the kappa-opioid system. J Neurosci 23, 11120-11126.
30 Ayson FG, de Jesus-Ayson EG and Takemura A (2007) mRNA expression patterns for GH, PRL, SL, IGF-I and IGF-II during altered feeding status in rabbitfish, Siganus guttatus. Gen Comp Endocrinol 150, 196-204.
31Sakharova AA, Horowitz JF, Surya S, Goldenberg N, Harber MP, Symons K and Barkan A (2008) Role of growth hormone in regulating lipolysis, proteolysis, and hepatic glucose production during fasting. J Clin Endocrinol Metab 93, 2755-2759.
32 Honjoh S, Yamamoto T, Uno M and Nishida E (2009) Signalling through RHEB-1 mediates intermittent fasting-induced longevity in C. elegans. Nature 457, 726-730.
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33 Froy O and Miskin R (2010) Effect of feeding regimens on circadian rhythms: implications for aging and longevity. Aging (Albany NY) 2, 7-27.
34 Martin B, Mattson MP and Maudsley S (2006) Caloric restriction and intermittent fasting: two potential diets for successful brain aging. Ageing Res Rev 5, 332-353.
35 Arumugam TV, Phillips TM, Cheng A, Morrell CH, Mattson MP and Wan R (2010) Age and energy intake interact to modify cell stress pathways and stroke outcome. Ann Neurol 67, 41-52.
36 Halagappa VK, Guo Z, Pearson M, Matsuoka Y, Cutler RG, Laferla FM and Mattson MP (2007) Intermittent fasting and caloric restriction ameliorate age-related behavioral deficits in the triple-transgenic mouse model of Alzheimer's disease. Neurobiol Dis 26, 212-220.
37 Mattson MP (2003) Gene-diet interactions in brain aging and neurodegenerative disorders. Ann Intern Med 139, 441-444.
38 Lee J, Kim SJ, Son TG, Chan SL and Mattson MP (2006) Interferon-gamma is up-regulated in the hippocampus in response to intermittent fasting and protects hippocampal neurons against excitotoxicity. J Neurosci Res 83, 1552-1557.
39Fontán-Lozano A, López-Lluch G, Delgado-García JM, Navas P and Carrión AM (2008) Molecular bases of caloric restriction regulation of neuronal synaptic plasticity. Mol Neurobiol 38, 167-177.
40 Hyun DH, Emerson SS, Jo DG, Mattson MP and de Cabo R (2006) Calorie restriction up-regulates the plasma membrane redox system in brain cells and suppresses oxidative stress during aging. Proc Natl Acad Sci U S A 103, 19908-19912.
41 Fontán-Lozano A, Sáez-Cassanelli JL, Inda MC, de los Santos-Arteaga M, Sierra-Domínguez SA, López-Lluch G, Delgado-García JM and Carrión AM (2007) Caloric restriction increases learning consolidation and facilitates synaptic plasticity through mechanisms dependent on NR2B subunits of the NMDA receptor. J Neurosci 27, 10185-10195.
42 Witte AV, Fobker M, Gellner R, Knecht S and Flöel A (2009) Caloric restriction improves memory in elderly humans. Proc Natl Acad Sci U S A 106, 1255-1260.
43 Mager DE, Wan R, Brown M, Cheng A, Wareski P, Abernethy DR and Mattson MP (2006) Caloric restriction and intermittent fasting alter spectral measures of heart rate and blood pressure variability in rats. FASEB J 20, 631-637.
44 For better understanding of the sympathetic and parasympathetic nervous systems, see my article on the autonomic nervous system from The Elements of Health website articles page.
45 Mattson MP (2005) Energy intake, meal frequency, and health: a neurobiological perspective. Annu Rev Nutr 25, 237-260.
46 Duan W, Guo Z, Jiang H, Ware M and Mattson MP (2003) Reversal of behavioral and metabolic abnormalities, and insulin resistance syndrome, by dietary restriction in mice deficient in brain-derived neurotrophic factor. Endocrinology 144, 2446-2453.
47 Hipkiss AR (2008) Energy metabolism, altered proteins, sirtuins and ageing: converging mechanisms? Biogerontology 9, 49-55.
48 Hipkiss AR (2007) Dietary restriction, glycolysis, hormesis and ageing. Biogerontology 8, 221-224.
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49 Mattson MP and Wan R (2005) Beneficial effects of intermittent fasting and caloric restriction on the cardiovascular and cerebrovascular systems. J Nutr Biochem 16, 129-137.
50 Bahadori B, McCarty MF, Barroso-Aranda J, Gustin JC and Contreras F (2009) A "mini-fast with exercise" protocol for fat loss. Med Hypotheses 73, 619-622
51 Simek V (1980) Effect of intermittent fasting followed by cold on growth, formation of reserves and energy metabolism in the golden hamster. Physiol Bohemoslov 29, 167-172.
52 Calabrese V, Cornelius C, Trovato A, Cavallaro M, Mancuso C, Di Rienzo L, Condorelli D, De Lorenzo A and Calabrese EJ (2010) The hormetic role of dietary antioxidants in free radical-related diseases. Curr Pharm Des 16, 877-883.
53 Calabrese V, Cornelius C, Mancuso C, Pennisi G, Calafato S, Bellia F, Bates TE, Giuffrida Stella AM, Schapira T, et al. (2008) Cellular stress response: a novel target for chemoprevention and nutritional neuroprotection in aging, neurodegenerative disorders and longevity. Neurochem Res 33, 2444-2471.
54 Son TG, Camandola S and Mattson MP (2008) Hormetic dietary phytochemicals. Neuromolecular Med 10, 236-246.
55 Surh YJ, Kundu JK and Na HK (2008) Nrf2 as a master redox switch in turning on the cellular signaling involved in the induction of cytoprotective genes by some chemopreventive phytochemicals. Planta Med 74, 1526-1539.
56 Krízová E and Simek V (1996) Influence of intermittent fasting and high-fat diet on morphological changes of the digestive system and on changes of lipid metabolism in the laboratory mouse. Physiol Res 45, 145-151.
