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{{short description|Dietary regime}}
'''Calorie restriction''' or '''Caloric restriction''' (CR) is the practice of limiting dietary energy intake in the hope that it will improve health and retard [[Senescence|aging]]. In human subjects, CR has been shown to lower [[cholesterol]], fasting glucose, and [[blood pressure]]. Some consider these to be [[biomarker]]s of aging, since there is a correlation between these markers and risk of diseases associated with aging. Except for houseflies ([[Calorie_restriction#Objections_to_Calorie_Restriction|below]]), animal species tested with CR so far, including [[primate]]s, [[rat]]s, [[mice]], [[spider]]s, [[C. elegans]] and [[rotifer]]s, have shown lifespan extension. CR is the only known dietary measure capable of extending [[maximum lifespan]], as opposed to [[average lifespan]]. In CR energy intake is minimized, but sufficient quantities of [[vitamin]]s, [[mineral]]s and other important [[nutrient]]s must be eaten. To emphasize the difference between CR and mere "FR" (food restriction), CR is often referred to by a plethora of other names such as CRON or CRAN (calorie restriction with optimal/adequate nutrition), or the "high-low diet" (high in all nutrients aside from calories, in which it is "low"). Other names for the diet emphasize the goal of the diet, such as CRL (calorie restriction for [[longevity]]), or simply The Longevity Diet, as in a recently published book by that name. Martin Brookes, writing in Fly - The Unsung Hero of Twentieth-Century Science (2001, CCCO, p145) said "Over three hundred different theories of aging have been proposed over the years, and the biology of aging remains littered with discarded and sometimes conflicting ideas. But one thing now seems clear: it is extremely unlikely that aging has a single cause."
{{For|caloric restriction for the purpose of weight loss|dieting}}
'''Calorie restriction''' (also known as '''caloric restriction''' or '''energy restriction''') is a [[Diet (nutrition)|dietary regimen]] that [[Calorie deficit|reduces the energy intake]] from foods and beverages without incurring [[malnutrition]].<ref name="lee">{{cite journal | vauthors = Lee MB, Hill CM, Bitto A, Kaeberlein M | title = Antiaging diets: Separating fact from fiction | journal = Science | volume = 374 | issue = 6570 | pages = eabe7365 | date = November 2021 | pmid = 34793210 | pmc = 8841109 | doi = 10.1126/science.abe7365 }}</ref><ref>{{cite journal | vauthors = Flanagan EW, Most J, Mey JT, Redman LM | title = Calorie Restriction and Aging in Humans | journal = Annual Review of Nutrition | volume = 40 | pages = 105–133 | date = September 2020 | pmid = 32559388 | pmc = 9042193 | doi = 10.1146/annurev-nutr-122319-034601 }}</ref> The possible effect of calorie restriction on [[Human body weight|body weight management]], [[diet and longevity|longevity]], and [[aging-associated disease]]s has been an active area of research.<ref name=lee/>


{{TOC limit|3}}
==Research history==
In [[1934]], Clive McCay and Mary Crowell of [[Cornell University]] observed that laboratory rats fed a severely reduced calorie diet while maintaining vital nutrient levels resulted in life spans of up to twice as long as otherwise expected. These findings were explored in detail by a series of rigid experiments with mice conducted by [[Roy Walford]] and his student [[Richard Weindruch]]. In [[1986]], Weindruch reported that restricting the calorie intake of laboratory mice proportionally increased their lifespan compared to a group of mice with a normal diet. The calorie-restricted mice also maintained youthful appearances and activity levels longer, and showed delays in age-related diseases. The results of the many experiments by Walford and Weindruch were summarized in their book ''The Retardation of Aging and Disease by Dietary Restriction'' (1988) (ISBN 0398054967).


==Dietary guidelines==
The findings have since been accepted, and generalized to a range of other animals. Researchers are investigating the possibility of parallel physiological links in humans (see Roth ''et al'' below). In the meantime, many people have independently adopted the practice of calorie restriction in some form, hoping to achieve the expected benefits themselves. Among the most notable are the members of the [[Calorie Restriction Society]].


Caloric intake control, and reduction for [[obesity|overweight]] individuals, is recommended by US dietary guidelines and science-based societies.<ref name="USDietaryGuidelines2015">{{cite web |author1=US Department of Health and Human Services. |title=2015–2020 Dietary Guidelines for Americans - health.gov |url=https://health.gov/dietaryguidelines/2015/ |website=health.gov |publisher=Skyhorse Publishing Inc. |access-date=30 September 2019 |date=2017}}</ref><ref name="AACAHA2019">{{cite journal | vauthors = Arnett DK, Blumenthal RS, Albert MA, Buroker AB, Goldberger ZD, Hahn EJ, Himmelfarb CD, Khera A, Lloyd-Jones D, McEvoy JW, Michos ED, Miedema MD, Muñoz D, Smith SC, Virani SS, Williams KA, Yeboah J, Ziaeian B | display-authors = 6 | title = 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines | journal = Circulation | volume = 140 | issue = 11 | pages = e596–e646 | date = September 2019 | pmid = 30879355 | pmc = 7734661 | doi = 10.1161/CIR.0000000000000678 | doi-access = free }}</ref><ref name="NICE2019-obesity">{{cite web |title=Obesity: maintaining a healthy weight and preventing excess weight gain |url=https://pathways.nice.org.uk/pathways/obesity/obesity-maintaining-a-healthy-weight-and-preventing-excess-weight-gain#content=view-node%3Anodes-diet |website=pathways.nice.org.uk}}</ref><ref name="USGuidelines2013">{{cite journal | vauthors = Jensen MD, Ryan DH, Apovian CM, Ard JD, Comuzzie AG, Donato KA, Hu FB, Hubbard VS, Jakicic JM, Kushner RF, Loria CM, Millen BE, Nonas CA, Pi-Sunyer FX, Stevens J, Stevens VJ, Wadden TA, Wolfe BM, Yanovski SZ, Jordan HS, Kendall KA, Lux LJ, Mentor-Marcel R, Morgan LC, Trisolini MG, Wnek J, Anderson JL, Halperin JL, Albert NM, Bozkurt B, Brindis RG, Curtis LH, DeMets D, Hochman JS, Kovacs RJ, Ohman EM, Pressler SJ, Sellke FW, Shen WK, Smith SC, Tomaselli GF | display-authors = 6 | title = 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society | journal = Circulation | volume = 129 | issue = 25 Suppl 2 | pages = S102–S138 | date = June 2014 | pmid = 24222017 | pmc = 5819889 | doi = 10.1161/01.cir.0000437739.71477.ee }}</ref><ref name="NICE2019">{{cite web |title=Diet - NICE Pathways |url=https://pathways.nice.org.uk/pathways/diet#path=view%3A/pathways/diet/dietary-interventions-and-advice-for-adults.xml&content=view-node%3Anodes-reducing-calorie-intake |website=pathways.nice.org.uk}}</ref><ref name="Garvey2016">{{cite journal | vauthors = Garvey WT, Mechanick JI, Brett EM, Garber AJ, Hurley DL, Jastreboff AM, Nadolsky K, Pessah-Pollack R, Plodkowski R | display-authors = 6 | title = American Association of Clinical Endocrinologists and American College of Endocrinology Comprehensive Clinical Practice Guidelines for Medical Care of Patients with Obesity | journal = Endocrine Practice | volume = 22 | pages = 1–203 | date = July 2016 | issue = Suppl 3 | pmid = 27219496 | doi = 10.4158/EP161365.GL | doi-access = free }}</ref>
[[Washington University in St. Louis|Washington University]] trials were set up in 2002 and involved about 30 participants. Dr. Luigi Fontana, clinical investigator, says CR practitioners seem to be ageing more slowly than the rest of us. “Take [[systolic blood pressure]],” he says. “Usually, that rises with age reliably, partly because the [[arteriosclerosis|arteries are hardening]]. In my group, mean age is 55, and mean systolic blood pressure is 110: that’s at the level of a 20-year-old.


Calorie restriction is recommended for people with [[diabetes]]<ref name="ADA2019">{{cite journal | title = 5. Lifestyle Management: ''Standards of Medical Care in Diabetes-2019'' | journal = Diabetes Care | volume = 42 | issue = Suppl 1 | pages = S46–S60 | date = January 2019 | pmid = 30559231 | doi = 10.2337/dc19-S005 | doi-access = free | author1 = American Diabetes Association }}</ref><ref name="ADA2018">{{cite journal | vauthors = Evert AB, Dennison M, Gardner CD, Garvey WT, Lau KH, MacLeod J, Mitri J, Pereira RF, Rawlings K, Robinson S, Saslow L, Uelmen S, Urbanski PB, Yancy WS | display-authors = 6 | title = Nutrition Therapy for Adults With Diabetes or Prediabetes: A Consensus Report | journal = Diabetes Care | volume = 42 | issue = 5 | pages = 731–754 | date = May 2019 | pmid = 31000505 | pmc = 7011201 | doi = 10.2337/dci19-0014 | type = Professional society guidelines | doi-access = free }}</ref> and prediabetes,<ref name="ADA2018" /> in combination with physical exercise and a weight loss goal of 5-15% for diabetes and 7-10% for prediabetes to prevent progression to diabetes.<ref name="ADA2018" /> Mild calorie restriction may be beneficial for pregnant women to reduce weight gain (without weight loss) and reduce perinatal risks for both the mother and child.<ref name="Glazier2018">{{cite journal | vauthors = Glazier JD, Hayes DJ, Hussain S, D'Souza SW, Whitcombe J, Heazell AE, Ashton N | title = The effect of Ramadan fasting during pregnancy on perinatal outcomes: a systematic review and meta-analysis | journal = BMC Pregnancy and Childbirth | volume = 18 | issue = 1 | pages = 421 | date = October 2018 | pmid = 30359228 | pmc = 6202808 | doi = 10.1186/s12884-018-2048-y | doi-access = free }}</ref><ref name="Than2012">{{cite journal | vauthors = Thangaratinam S, Rogozinska E, Jolly K, Glinkowski S, Roseboom T, Tomlinson JW, Kunz R, Mol BW, Coomarasamy A, Khan KS | display-authors = 6 | title = Effects of interventions in pregnancy on maternal weight and obstetric outcomes: meta-analysis of randomised evidence | journal = BMJ | volume = 344 | pages = e2088 | date = May 2012 | pmid = 22596383 | pmc = 3355191 | doi = 10.1136/bmj.e2088 }}</ref> For [[management of obesity|overweight or obese]] individuals, calorie restriction may improve health through weight loss, although a gradual weight regain of {{convert|1|-|2|kg|abbr=on}} per year may occur.<ref name="AACAHA2019" /><ref name="USGuidelines2013" />
“Of course, I can’t tell you if my subjects will live to 130. So many uncontrollable factors affect length of life. I don’t have enough evidence to prove these people are ageing more slowly, but it looks like it.”


===Risks of malnutrition===
==Effects of CR on different organisms==
The term "calorie restriction" as used in [[gerontology|the study of aging]] refers to dietary regimens that reduce calorie intake without incurring [[malnutrition]].<ref name=lee/> If a restricted diet is not designed to include essential nutrients, malnutrition may result in serious deleterious effects, as shown in the [[Minnesota Starvation Experiment]].<ref name="Keys A 1950" /> This study was conducted during [[World War II]] on a group of lean men, who restricted their calorie intake by 45%<ref>Keys A 1950, p. 114.</ref> for six months and composed roughly 77% of their diet with carbohydrates.<ref name="Keys A 1950">Keys A, Brozek J, Henschels A & Mickelsen O & Taylor H. The Biology of Human Starvation, 1950. University of Minnesota Press, Minneapolis</ref> As expected, this malnutrition resulted in [[Starvation response|metabolic adaptations]], such as decreased body fat, improved lipid profile, and decreased resting heart rate. The experiment also caused negative effects, such as [[anemia]], [[edema]], [[Muscle atrophy|muscle wasting]], [[weakness]], [[dizziness]], [[irritability]], [[lethargy]], and depression.<ref name="Keys A 1950" />


Typical low-calorie diets may not supply sufficient nutrient intake that is typically included in a calorie restriction diet.<ref name='St. Jeor et al, 2001'>{{cite journal | vauthors = St Jeor ST, Howard BV, Prewitt TE, Bovee V, Bazzarre T, Eckel RH | title = Dietary protein and weight reduction: a statement for healthcare professionals from the Nutrition Committee of the Council on Nutrition, Physical Activity, and Metabolism of the American Heart Association | journal = Circulation | volume = 104 | issue = 15 | pages = 1869–1874 | date = October 2001 | pmid = 11591629 | doi = 10.1161/hc4001.096152 | doi-access = free }}</ref><ref name='de Souza et al, 2008'>{{cite journal | vauthors = de Souza RJ, Swain JF, Appel LJ, Sacks FM | title = Alternatives for macronutrient intake and chronic disease: a comparison of the OmniHeart diets with popular diets and with dietary recommendations | journal = The American Journal of Clinical Nutrition | volume = 88 | issue = 1 | pages = 1–11 | date = July 2008 | pmid = 18614716 | pmc = 2674146 | doi = 10.1093/ajcn/88.1.1 }}</ref><ref name='Ma et al, 2007'>{{cite journal | vauthors = Ma Y, Pagoto SL, Griffith JA, Merriam PA, Ockene IS, Hafner AR, Olendzki BC | title = A dietary quality comparison of popular weight-loss plans | journal = Journal of the American Dietetic Association | volume = 107 | issue = 10 | pages = 1786–1791 | date = October 2007 | pmid = 17904938 | pmc = 2040023 | doi = 10.1016/j.jada.2007.07.013 }}</ref>
===Primates===


===Possible side effects===
{{section-stub}}
People losing weight during calorie restriction risk developing [[side effect]]s, such as [[cold sensitivity]], [[menstrual irregularities]], [[infertility]], or hormonal changes.<ref>{{cite journal | vauthors = Marzetti E, Wohlgemuth SE, Anton SD, Bernabei R, Carter CS, Leeuwenburgh C | title = Cellular mechanisms of cardioprotection by calorie restriction: state of the science and future perspectives | journal = Clinics in Geriatric Medicine | volume = 25 | issue = 4 | pages = 715–32, ix | date = November 2009 | pmid = 19944269 | pmc = 2786899 | doi = 10.1016/j.cger.2009.07.002 }}</ref>


===Rats===
==Research==


===Humans===
{{section-stub}}
Decreasing [[Food energy#Recommended daily intake|caloric intake]] by 20-30%, while fulfilling nutrient requirements, has been found to remedy diseases of aging, including cancer, cardiovascular disease, dementia, and diabetes in humans, and result in an average loss of {{convert|7.9|kg|lbs}} in body weight, but because of the long lifespan of humans, evidence that calorie restriction could prevent age-related disease in humans remains under preliminary research.<ref name=lee/><ref>{{cite journal | vauthors = Caristia S, Vito M, Sarro A, Leone A, Pecere A, Zibetti A, Filigheddu N, Zeppegno P, Prodam F, Faggiano F, Marzullo P | display-authors = 6 | title = Is Caloric Restriction Associated with Better Healthy Aging Outcomes? A Systematic Review and Meta-Analysis of Randomized Controlled Trials | journal = Nutrients | volume = 12 | issue = 8 | page = 2290 | date = July 2020 | pmid = 32751664 | pmc = 7468870 | doi = 10.3390/nu12082290 | doi-access = free }}</ref> While calorie restriction leads to weight and fat loss, the precise amount of calorie intake and associated fat mass for optimal health in humans is not known.<ref name=lee/> Moderate amounts of calorie restriction may have harmful effects on certain population groups, such as lean people with low body fat.<ref name=lee/>


===Mice===
===Life extension===
As of 2021, [[intermittent fasting]] and calorie restriction remain under preliminary research to assess the possible effects on disease burden and increased lifespan during aging, although the relative risks associated with long-term fasting or calorie restriction remain undetermined.<ref name=lee/>


Intermittent fasting refers to periods with intervals during which no food but only clear fluids are ingested – such as a period of daily time-restricted eating with a window of 8 to 12 hours for any caloric intake – and could be combined with overall calorie restriction and variants of the [[Mediterranean diet]] which may contribute to long-term cardiovascular health and longevity.<ref>{{cite journal | vauthors = O'Keefe JH, Torres-Acosta N, O'Keefe EL, Saeed IM, Lavie CJ, Smith SE, Ros E | title = A pesco-Mediterranean diet with intermittent fasting: JACC Review Topic of the Week | journal = Journal of the American College of Cardiology | volume = 76 | issue = 12 | pages = 1484–1493 | date = September 2020 | pmid = 32943166 | doi = 10.1016/j.jacc.2020.07.049 | s2cid = 221787788 | doi-access = free }}</ref>
Studies in female mice have shown that [[estrogen receptor]]-alpha declines in the pre-optic [[hypothalamus]] as they grow old. The female mice that were given a [[calorically restricted]] diet during the majority of their lives, maintained higher levels of ER&alpha; in the pre-optic hypothalamus than their non-calorically restricted counterparts<ref>Yaghmaie F, Saeed O, Garan SA, Freitag W, Timiras PS, Sternberg H., 2005. Caloric restriction reduces cell loss and maintains estrogen receptor-alpha immunoreactivity in the pre-optic hypothalamus of female B6D2F1 mice. Neuro Endocrinol Lett. 2005 Jun;26(3):197-203.[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15990721 PubMed]</ref>.


===Minnesota Starvation Experiment===
The [[Minnesota Starvation Experiment]] examined the physical and psychological effects of extreme calorie restriction on 32 young and lean 24-year-old men during a 40% reduction in energy intake for 6 months. The study was designed to mimic dietary conditions during World War II. Participants could only eat 1800 kcal per day, but were required to walk 5 km per day and expend 3000 [[calorie]]s.<ref name=":1">{{cite journal | vauthors = Most J, Tosti V, Redman LM, Fontana L | title = Calorie restriction in humans: An update | journal = Ageing Research Reviews | volume = 39 | pages = 36–45 | date = October 2017 | pmid = 27544442 | doi = 10.1016/j.arr.2016.08.005 | series = Nutritional interventions modulating aging and age-associated diseases | pmc = 5315691 }}</ref> The men lost about 25% of their body weight of which 67% was fat mass and 17% fat-free mass.<ref name=":1" /> The quality of the diet was insufficient to accurately represent the diet during war due to the inadequate consumption of protein, and a lack of fruits and vegetables. Despite the extreme calorie restriction, the experiment was not representative of true calorie-restrictive diets, which adhere to intake guidelines for [[macronutrient]]s and [[micronutrient]]s.<ref name=":1" /> Chronic weakness, decreased aerobic capacity, and painful lower limb edema was caused by the malnourished calorie restrictive diet.<ref name=":1" /><ref>{{Cite book | vauthors = Keys A, Brožek J, Henschel A, Mickelsen O, Taylor HL |title=The biology of human starvation (2 vols). |publisher=Univ. of Minnesota Press |year=1950}}</ref> Emotional distress, confusion, [[apathy]], depression, [[hysteria]], [[hypochondriasis]], suicidal thoughts, and loss of sex drive were among the abnormal psychological behaviors that occurred within six weeks.<ref name=":1" />


===Intensive care===
{{Asof|2019}}, current clinical guidelines recommend that hospitals ensure that the patients get fed with 80–100% of energy expenditure, the normocaloric feeding. A systematic review investigated whether people in [[intensive care unit]]s have different outcomes with normocaloric feeding or hypocaloric feeding, and found no difference.<ref>{{cite journal | vauthors = Marik PE, Hooper MH | title = Normocaloric versus hypocaloric feeding on the outcomes of ICU patients: a systematic review and meta-analysis | journal = Intensive Care Medicine | volume = 42 | issue = 3 | pages = 316–323 | date = March 2016 | pmid = 26556615 | doi = 10.1007/s00134-015-4131-4 | s2cid = 37653149 }}</ref> However, a comment criticized the inadequate control of protein intake, and raised concerns that hypocaloric feeding safety should be further assessed with underweight critically ill people.<ref>{{cite journal | vauthors = Bitzani M | title = Comments on Marik and Hooper: Normocaloric versus hypocaloric feeding on the outcomes of ICU patients: a systematic review and meta-analysis | journal = Intensive Care Medicine | volume = 42 | issue = 4 | pages = 628–629 | date = April 2016 | pmid = 26880090 | doi = 10.1007/s00134-016-4248-0 | s2cid = 34072936 }}</ref>


===Spider===
===Non-human primates===
A calorie restriction study started in 1987 by the [[National Institute on Aging]] showed that calorie restriction did not extend years of life or reduce age-related deaths in non-obese [[rhesus macaque]]s.<ref name="NIA2012">{{cite web |url=https://www.nih.gov/news-events/news-releases/nih-study-finds-calorie-restriction-does-not-affect-survival |title=NIH study finds calorie restriction does not affect survival |newspaper= |date=2012-08-29 |author=[[National Institutes of Health]] |access-date= May 17, 2016}}</ref> It did improve certain measures of health, however.<ref name="NYTimes2014">{{cite web |url=https://www.nytimes.com/2014/04/02/science/a-new-salvo-in-debate-over-caloric-restrictions-and-longevity.html |title=Diet's Link to Longevity: After 2 Studies Diverge, a Search for Consensus |newspaper=The New York Times |date= April 1, 2014 |author=Nicholas Wade |access-date= May 17, 2016}}</ref> These results were publicized as being different from the Wisconsin rhesus macaque calorie restriction study, which also started in 1987 and showed an increase in the lifespan of rhesus macaques following calorie restriction.<ref name="NIA2012" />


In a 2017 report on rhesus monkeys, caloric restriction in the presence of adequate nutrition was effective in delaying the effects of aging.<ref name="Mattison2017">{{cite journal | vauthors = Mattison JA, Colman RJ, Beasley TM, Allison DB, Kemnitz JW, Roth GS, Ingram DK, Weindruch R, de Cabo R, Anderson RM | display-authors = 6 | title = Caloric restriction improves health and survival of rhesus monkeys | journal = Nature Communications | volume = 8 | issue = 1 | pages = 14063 | date = January 2017 | pmid = 28094793 | pmc = 5247583 | doi = 10.1038/ncomms14063 | bibcode = 2017NatCo...814063M }}</ref><ref name="sd">{{cite web|url=https://www.sciencedaily.com/releases/2017/01/170117140105.htm|title=Calorie restriction lets monkeys live long and prosper|publisher=ScienceDirect|date=17 January 2017|access-date=15 February 2017}}</ref> Older age of onset, female sex, lower body weight and fat mass, reduced food intake, diet quality, and lower [[fasting]] [[blood glucose]] levels were factors associated with fewer disorders of aging and with improved survival rates.<ref name=Mattison2017/> Specifically, reduced food intake was beneficial in adult and older primates, but not in younger monkeys.<ref name=Mattison2017/> The study indicated that caloric restriction provided health benefits with fewer age-related disorders in elderly monkeys and, because rhesus monkeys are genetically similar to humans, the benefits and mechanisms of caloric restriction may apply to human health during aging.<ref name="Mattison">{{cite journal | vauthors = Mattison JA, Roth GS, Beasley TM, Tilmont EM, Handy AM, Herbert RL, Longo DL, Allison DB, Young JE, Bryant M, Barnard D, Ward WF, Qi W, Ingram DK, de Cabo R | display-authors = 6 | title = Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study | journal = Nature | volume = 489 | issue = 7415 | pages = 318–321 | date = September 2012 | pmid = 22932268 | pmc = 3832985 | doi = 10.1038/nature11432 | bibcode = 2012Natur.489..318M }}</ref><ref name="Vaughan">{{cite journal | vauthors = Vaughan KL, Kaiser T, Peaden R, Anson RM, de Cabo R, Mattison JA | title = Caloric Restriction Study Design Limitations in Rodent and Nonhuman Primate Studies | journal = The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences | volume = 73 | issue = 1 | pages = 48–53 | date = December 2017 | pmid = 28977341 | pmc = 5861872 | doi = 10.1093/gerona/glx088 }}</ref>
{{section-stub}}


===C. elegans===
===Activity levels===
Calorie restriction preserves muscle tissue in nonhuman primates<ref name=McKiernan2012>{{cite journal | vauthors = McKiernan SH, Colman RJ, Aiken E, Evans TD, Beasley TM, Aiken JM, Weindruch R, Anderson RM | display-authors = 6 | title = Cellular adaptation contributes to calorie restriction-induced preservation of skeletal muscle in aged rhesus monkeys | journal = Experimental Gerontology | volume = 47 | issue = 3 | pages = 229–236 | date = March 2012 | pmid = 22226624 | pmc = 3321729 | doi = 10.1016/j.exger.2011.12.009 }}</ref><ref name=ColmanSarco2008>{{cite journal | vauthors = Colman RJ, Beasley TM, Allison DB, Weindruch R | title = Attenuation of sarcopenia by dietary restriction in rhesus monkeys | journal = The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences | volume = 63 | issue = 6 | pages = 556–559 | date = June 2008 | pmid = 18559628 | pmc = 2812805 | doi = 10.1093/gerona/63.6.556 }}</ref> and rodents.<ref name=DirksNaylor>{{cite journal | vauthors = Dirks Naylor AJ, Leeuwenburgh C | title = Sarcopenia: the role of apoptosis and modulation by caloric restriction | journal = Exercise and Sport Sciences Reviews | volume = 36 | issue = 1 | pages = 19–24 | date = January 2008 | pmid = 18156949 | doi = 10.1097/jes.0b013e31815ddd9d | url = https://journals.lww.com/acsm-essr/Fulltext/2008/01000/Sarcopenia__The_Role_of_poptosis_and_Modulation_by.5.aspx | s2cid = 4596744 | doi-access = free | archive-url = https://web.archive.org/web/20211202203828/https://journals.lww.com/acsm-essr/Fulltext/2008/01000/Sarcopenia__The_Role_of_poptosis_and_Modulation_by.5.aspx | archive-date = 2021-12-02 }}</ref> Muscle tissue grows when stimulated, so it has been suggested that the calorie-restricted test animals exercised more than their companions on higher calories, perhaps because animals enter a foraging state during calorie restriction. However, studies show that overall activity levels are no higher in calorie restriction than [[ad libitum]] animals in youth.<ref name=Faulks2006>{{cite journal | vauthors = Faulks SC, Turner N, Else PL, Hulbert AJ | title = Calorie restriction in mice: effects on body composition, daily activity, metabolic rate, mitochondrial reactive oxygen species production, and membrane fatty acid composition | journal = The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences | volume = 61 | issue = 8 | pages = 781–794 | date = August 2006 | pmid = 16912094 | doi = 10.1093/gerona/61.8.781 | doi-access = free }}</ref>


=== Sirtuin-mediated mechanism ===
{{section-stub}}


{{Main|Caloric restriction mimetic}}
===Rotifer===


Preliminary research indicates that [[sirtuin]]s are activated by fasting and serve as "energy sensors" during [[metabolism]].<ref>{{cite journal | vauthors = Chang HC, Guarente L | title = SIRT1 and other sirtuins in metabolism | journal = Trends in Endocrinology and Metabolism | volume = 25 | issue = 3 | pages = 138–145 | date = March 2014 | pmid = 24388149 | pmc = 3943707 | doi = 10.1016/j.tem.2013.12.001 | hdl = 1721.1/104067 }}</ref> Sirtuins, specifically Sir2 (found in yeast) have been implicated in the aging of yeast,<ref name="cshs">{{cite journal | vauthors = Guarente L | title = Sirtuins in aging and disease | journal = Cold Spring Harbor Symposia on Quantitative Biology | volume = 72 | pages = 483–488 | date = 2007 | pmid = 18419308 | doi = 10.1101/sqb.2007.72.024 | doi-access = free }}</ref> and are a class of [[Conserved sequence|highly conserved]], NAD<sup>+</sup>-dependent [[histone deacetylase]] [[enzyme]]s.<ref name="Lin 12–16">{{cite journal | vauthors = Lin SJ, Ford E, Haigis M, Liszt G, Guarente L | title = Calorie restriction extends yeast life span by lowering the level of NADH | journal = Genes & Development | volume = 18 | issue = 1 | pages = 12–16 | date = January 2004 | pmid = 14724176 | pmc = 314267 | doi = 10.1101/gad.1164804 }}</ref> Sir2 homologs have been identified in a wide range of organisms from bacteria to humans.<ref name=cshs/><ref name="Kaeberlein, M. 1999">{{cite journal | vauthors = Kaeberlein M, McVey M, Guarente L | title = The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms | journal = Genes & Development | volume = 13 | issue = 19 | pages = 2570–2580 | date = October 1999 | pmid = 10521401 | pmc = 317077 | doi = 10.1101/gad.13.19.2570 }}</ref>
{{section-stub}}


== See also ==
==Why might CR increase longevity?==
* [[Calorie deficit]]
There have been many theories as to how CR works, and many of them have fallen out of favor or been disproved. These include reduced [[basal metabolic rate]], developmental delay, the control animals being [[wiktionary:glutton|glutton]]s, and decreased [[glucocorticoid]] production.
* [[CR Society International]]
* [[Fasting]]
* [[Intermittent fasting]]
* [[List of diets]]
* [[Okinawa diet]]
* [[Very low calorie diet]]


== References ==
===Hormesis hypothesis===
{{reflist}}
A small, but rapidly growing number of researchers in the CR field are now proponents of a new theory known as the "Hormesis Hypothesis of CR". In the early 1940s, Southam & Ehrlich, 1943 reported that a bark extract that was known to inhibit fungal growth, actually stimulated growth when given at very low concentrations. They coined the term "[[hormesis]]" to describe such beneficial actions resulting from the response of an organism to a low-intensity biological stressor. The word "hormesis" is derived from the Greek word "hormaein" which means "to excite". The [[Hormesis Hypothesis of CR]] proposes that the diet imposes a low-intensity biological stress on the organism, which elicits a defense response that helps protect it against the causes of aging. In other words, CR places the organism in a defensive state so that it can survive adversity, and this results in improved health and longer life. This switch to a defensive state may be controlled by [[longevity genes]] (see below).


== Further reading ==
Recent research has suggested (see [[Matthias Bluher]], [[C. Ronald Kahn]], [[Barbara B. Kahn]], et al.) that it is not reduced intake which influences longevity. This was done by studying animals which have their metabolism changed to reduce [[insulin]] uptake, consequently retaining the leanness of animals in the earlier studies. It was observed that these animals can have a normal dietary intake, but have a similarly increased lifespan. This suggests that lifespan is increased for an organism if it can remain lean and if it can avoid any excess accumulation of [[adipose tissue]]: if this can be done while not diminishing dietary intake (as in some minority eating patterns, see e.g. [[Living foods diet]] or [[Joel Fuhrman]]) then the 'starvation diet' anticipated as an impossible requirement by earlier researchers is no longer a precondition of increased longevity.
{{refbegin}}
* {{cite book| vauthors = Everitt AV, Heilbronn LK, Le Couteur DG | veditors = Everitt AV, Rattan SI, Le Couteur DG, de Cabo R |title=Calorie Restriction, Aging and Longevity|publisher=Springer|location=New York|isbn=978-90-481-8555-9|year=2010|chapter=Food Intake, Life Style, Aging and Human Longevity}}
* {{cite book|title=The Biology of Human Starvation|volume=I|year=1950|author-link=Ancel Keys| vauthors = Keys A, Brozek J, Henschel A, Mickelsen O, Taylor HL |publisher=University of Minnesota Press|isbn=978-0-8166-7234-9}}
{{refend}}


{{Diets}}
The extent to which these findings may apply to human [[nutrition]] and [[longevity]] is as noted above under investigation. A paper in the [[Proceedings of the National Academy of Sciences]], U.S.A. in 2004 showed that practitioners of a CR diet had significantly better cardiovascular health (PMID 15096581). Also in progress are the development of [[CR mimetic]] interventions.
{{Longevity}}


{{DEFAULTSORT:Calorie Restriction}}
===Sir2===
Recent discoveries have suggested that the [[gene]] [[Sir2]] might underlie the effect of CR. In [[baker's yeast]] the Sir2 enzyme is activated by CR, which leads to a 30% lifespan extension in test subjects. David Sinclair {{fact}} showed that in test mammals the Sir2 equivalent gene known as [[SIRT1]] is turned on by a CR diet, and this protects cells from dying under stress. An article in the June 2004 issue of the magazine [[Nature (magazine)|Nature]] showed that SIRT1 releases fat from storage cells.
<ref>Picard F, Kurtev M, Chung N, et. al. ''Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-gamma.'' Nature. 2004 Jun 17;429(6993):771-6. PMID 15175761. Letter in [http://www.nature.com/nature/journal/v429/n6993/abs/nature02583.html ''Nature'']</ref>
See also [http://www.ensembl.org/Mus_musculus/geneview?gene=ENSMUSG00000020063 SIRT1 in the Ensembl genome browser]. Sinclair's lab reported that they have found small molecules (e.g. [[resveratrol]]) that activate Sir2 and can extend the lifespan of yeast. {{fact}}

More recent discoveries at the [[University of Washington]] have demonstrated that CR may not act through Sir2. This research discredits Sinclair's work with resveratrol by suggesting that the findings in Sinclair's Nature paper are an artifact of the Biomol Fluor de Lys assay.
<ref>Kaeberlein M, McDonagh T, Heltweg B, et. al. ''Substrate-specific activation of sirtuins by resveratrol.'' J Biol Chem. 2005 Apr 29;280(17):17038-45. PMID 15684413</ref>

===DHEA===
While calorie restriction has been shown to increase [[DHEA]] in primates (PMID 12543259), it has not been shown to increase [[DHEA]] in post-pubescent primates (PMID 15247063).
===Free radicals and glycation===
Two very prominent theories of aging are the [[Free-radical theory|free radical theory]] and the [[glycation]] theory, both of which can explain how CR could work. With high amounts of energy available, [[mitochondria]] do not operate very efficiently and generate more [[superoxide]]. With CR, energy is conserved and there is less free radical generation. A CR organism will be less fat and require less energy to support the weight, which also means that there does not need to be so much glucose in the bloodstream. Less blood glucose means less [[glycation]] of adjacent proteins and less fat to oxidize in the bloodstream to cause sticky blocks resulting in atherosclerosis. Type II [[Diabetes mellitus|Diabetics]] are people with insulin insensitivity caused by long-term exposure to high blood glucose. Obesity leads to type&nbsp;2 diabetes. Type&nbsp;2 diabetes and uncontrolled type&nbsp;1 diabetes are much like "accelerated aging", due to the above effects. There may even be a continuum between CR and the [[metabolic syndrome]].

In examining Calorie Restriction with Optimal Nutrition, it is observed that with less food, and equal nutritional value, there is a higher ratio of nutrients to calories. This may lead to more ideal essential and beneficial nutrient levels in the body. Many nutrients can exist in excess to their need, without side effects as long as they are in balance and not beyond the body's ability to store and circulate them. Many nutrients serve protective effects as [[antioxidants]], and will be at higher levels in the body as there will be lower levels of free radicals due to the lower food intake.

Calorie Restriction with Optimal Nutrition has not been tested in comparison to Calorie Excess with Optimal Nutrition. It may be that with extra calories, nutrition must be similarly increased to ratios comparable to that of Calorie Restriction to provide similar antiaging benefits.

Stated levels of calorie needs may be biased towards sedentary individuals. Calorie restriction may be more of adapting the diet to the body's needs.

Although aging can be conceptualized as the accumulation of damage, the more recent determination that free radicals participate in intracellular signaling has made the categorical equation of their effects with "damage" more problematic than was commonly appreciated in years past.

===Papers on CR in yeast: dismissing increased respiration===
In late 2005 [[Matt Kaeberlein]] and [[Brian Kennedy]] published two important papers on calorie restriction in yeast. In a paper published in [http://genetics.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pgen.0010069.eor PLoS Genetics] they show that Lenny Guarente's model for calorie restriction increasing respiration is wrong. In a potentially much more important paper published in [http://www.sciencemag.org/cgi/content/abstract/310/5751/1193 Science] they tell us what might actually be happening with calorie restriction - decreased TOR activity. TOR is a nutrient-responsive signaling protein already known to regulate aging in worms and flies, and this paper is the first to directly link TOR to calorie restriction.

==Objections to Calorie Restriction==
===No benefit to houseflies===
One of the most significant oppositions to caloric restriction comes from Michael Cooper, who has shown that caloric restriction has no benefit in the [[housefly]] [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15319362&query_hl=22&itool=pubmed_docsum PMID: 15319362]. Michael Cooper claims that the widely purported effects of calorie restriction may be because a diet containing more calories can increase [[bacteria]]l proliferation, or that the type of high calorie diets used in past experiments have a stickiness, general composition, or texture that reduces longevity.

===Catabolic damage===
A major conflict with calorie restriction is that a calorie excess is needed to prevent catabolizing the body's tissues. A body in a [[catabolic]] state promotes the degeneration of muscle tissue, including the heart. It also makes gaining muscle tissue difficult. Loss of muscle tissue is a strong indicator of aging.

===Physical activity testing biases===
While some tests of calorie restriction have shown increased muscle tissue in the calorie-restricted test subjects, how this has occurred is unknown. Muscle tissue grows when stimulated, so it is possible that the calorie-restricted test animals exercised more than their companions on higher calories. The reasons behind this may be irrelevant, as in any case it would be a bias in testing. Such tests need to be monitored to make sure that levels of physical activity are equal between groups.

===Insufficient calories and amino acids for exercise===
Exercise has also been shown to increase health and lifespan and lower the incidence of several diseases. Calorie restriction comes into conflict with the high calorie needs of [[athlete]]s, and may not provide them adequate levels of energy or sufficient amino acids for repair.

===Benefits only the young===
There is evidence to suggest that the benefit of CR in rats might only be reaped in early years. A study on rats which were gradually introduced to a CR lifestyle at 18 months showed no improvement over the average lifespan of the [[Ad libitum]] group.
<ref>Lipman RD, Smith DE, Bronson RT, Blumberg J. ''Is late-life caloric restriction beneficial?'' Aging (Milano). 1995 Apr;7(2):136-9. PMID 7548264</ref>

===Possible contraindications===
'''ALS''': Both animal and human research suggest CR may be contraindicated for people with [[amyotrophic lateral sclerosis]] (ALS). Research on a [[Genetically modified organism|transgenic]] mouse model of ALS demonstrates that CR may hasten the onset of death in ALS. Hamadeh ''et al'' therefore concluded: "These results suggest that CR diet is not a protective strategy for patients with amyotrophic lateral sclerosis (ALS) and hence is contraindicated." <ref>Hamadeh MJ, Rodriguez MC, Kaczor JJ, Tarnopolsky MA. ''Caloric restriction transiently improves motor performance but hastens clinical onset of disease in the Cu/Zn-superoxide dismutase mutant G93A mouse.'' Muscle Nerve. 2005 Feb;31(2):214-20. PMID 15625688.</ref> Hamadeh ''et al'' also note two human studies:

:"''Our data may also provide support for the findings by others that low energy intake correlates with death in people with ALS. In patients with ALS, decreases in body fat, lean body mass, muscle power, and nitrogen balance correlated with death,''<ref> Kasarskis EJ, Berryman S, Vanderleest JG, Schneider AR, McClain CJ. ''Nutritional status of patients with amyotrophic lateral sclerosis: relation to the proximity of death.'' Am J Clin Nutr. 1996 Jan;63(1):130-7. PMID 8604660.</ref>'' and nutritional support improved prognosis.''<ref>Slowie LA, Paige MS, Antel JP. ''Nutritional considerations in the management of patients with amyotrophic lateral sclerosis (ALS).'' J Am Diet Assoc. 1983 Jul;83(1):44-7. PMID 6863783</ref> "

In the first human study that Hamadeh ''et al'' cite, Slowie, Paige, and Antel state: "We conclude that ALS patients have a chronically deficient intake of energy and recommended augmentation of energy intake." (PMID 8604660) Previously Pedersen and Mattson also found that in the ALS mouse model, CR "accelerates the clinical course" of the disease and had no benefits. <ref> Pedersen WA, Mattson MP. ''No benefit of dietary restriction on disease onset or progression in amyotrophic lateral sclerosis Cu/Zn-superoxide dismutase mutant mice.'' Brain Res. 1999 Jun 26;833(1):117-20. PMID 10375685. </ref> Suggesting that a calorically dense diet may slow ALS, a [[ketogenic diet]] in the ALS mouse model has been shown to slow the progress of ALS. <ref>Zhao Z, Lange DJ , Voustianiouk A, et. al. ''A ketogenic diet as a potential novel therapeutic intervention in amyotrophic lateral sclerosis.'' [http://www.biomedcentral.com/1471-2202/7/29 BMC Neuroscience 2006, 7:29.] (PMID 16584562). [http://www.sciencedaily.com/releases/2006/04/060417104324.htm Media report on Zhao ''et al''].</ref>

===Negligible effect on larger organisms===
Another objection to CR as a lifestyle would be that the effect is small to negligible in larger organisms. A review of CR suggests that the situation is vastly oversimplified when applied to larger mammals.
<ref>Phelan JP, Rose MR. ''Why dietary restriction substantially increases longevity in animal models but won't in humans.'' Ageing Res Rev. 2005 Aug;4(3):339-50. PMID 16046282</ref>

==Note on Terminology: Calorie Restriction vs. Caloric Restriction==

Most believe that "calorie restriction" is the best term for this diet. The adjective "caloric" is inappropriate for the same reason that the theory of music is not called "musical theory," but rather "music theory." A musical theory is a theory of a musical nature, not a theory of or about music. The CR diet is not a "restriction of a caloric nature." Likewise, the restriction of protein in the diet is referred to as "protein restriction," not "proteinic restriction." Nonetheless, many researchers still say "caloric restriction."

==Intermittent fasting as an alternative approach==
Studies by Mark P. Mattson, PhD, chief of the [[National Institute on Aging]]'s (NIA) Laboratory of Neurosciences, and colleagues have found that intermittent fasting and calorie restriction affect the progression of diseases similar to [[Huntington's disease]], [[Parkinson's disease]], and [[Alzheimer's disease]] in mice (PMID 11119686). In one study, rats and mice ate a low-calorie diet or were deprived of food for 24 hours every other day (PMID 12724520). Both methods improved glucose metabolism, increased [[insulin sensitivity]], and increased [[Stress (medicine)|stress]] resistance. Researchers have long been aware that calorie restriction extends lifespan, but this study showed that improved glucose metabolism also protects [[neurons]] in experimental models of Parkinson's and [[stroke]].

Another NIA study found that intermittent fasting and calorie restriction delays the onset of Huntington's disease-like symptoms in mice and prolongs their lives (PMID 12589027). Huntington's disease (HD), a [[genetic disorder]], results from neuronal degeneration in the [[striatum]]. This neurodegeneration results in difficulties with movements that include walking, speaking, eating, and swallowing. People with Huntington's also exhibit an abnormal, diabetes-like metabolism that causes them to lose weight progressively.

This NIA study compared adult HD mice who ate as much as they wanted to HD mice who were kept on an intermittent fasting diet during adulthood. HD mice possess the abnormal human gene huntingtin and exhibit clinical signs of the disease, including abnormal metabolism and neurodegeneration in the striatum. The mice on the fasting program developed clinical signs of the disease about 12 days later and lived 10 to 15% longer than the free-fed mice. The brains of the fasting mice also showed less degeneration. Those on the fasting program also regulated their glucose levels better and did not lose weight as quickly as the other mice. Researchers found that fasting mice had higher [[brain-derived neurotrophic factor]] (BDNF) levels. BDNF protects neurons and stimulates their growth. Fasting mice also had high levels of heat-shock protein-70 ([[Hsp70]], which increases cellular resistance to stress.

Another NIA study indicates that intermittent fasting may be more beneficial than cutting calorie intake. The researchers fed one group of mice 40% of the calories given to a control group. A third group was fasted for 24 hours, then permitted to free-feed. According to an Associated Press article (29 April 2003), the fasting mice "didn't cut total calories because they ate twice as much on days they weren't fasting. Both the fasting mice and those on a restricted diet had significantly lower blood sugar and insulin levels than the free-fed controls. A toxin that damages hippocampal cells was injected in all of the mice. Hippocampal damage is associated with Alzheimer's. Interestingly, the scientists found less damage in the brains of the fasting mice than in those that ate either a restricted or a normal diet. The NIA is planning a human study that will compare a group eating three meals a day with a group eating the same diet and amount of food within four hours and then fasting 20 hours."

==References==
<div style="font-size: 90%;">
<references/>
</div>
* ''Genes & Development'' ; Koubova,J; 17(3):313-321 (2003) [http://www.genesdev.org/cgi/content/full/17/3/313 Review of maximum life span extension by calorie restriction]

* ''The Retardation of Aging and Disease by Dietary Restriction'' Richard Weindruch, Roy L. Walford (1988). ISBN 0398054967

* Ageless Quest. Lenny Guarente, Cold Spring Harbor Press, NY. 2003. ISBN 0879696524.

*''The retardation of aging in mice by dietary restriction: longevity, cancer, immunity and lifetime energy intake.'' Journal of Nutrition, 116(4), pages 641-54.Weindruch R, et al.,April, 1986. PMID 3958810.

*''Caloric Restriction and Aging'' Richard Weindruch in Scientific American, Vol. 274, No. 1, pages 46--52; January 1996.

*'' 2-Deoxy-D-Glucose Feeding in Rats Mimics Physiological Effects of Caloric Restriction.'' Mark A. Lane, George S. Roth and Donald K. Ingram in Journal of Anti-Aging Medicine, Vol. 1, No. 4, pages 327--337; Winter 1998.

*''Biomarkers of caloric restriction may predict longevity in humans.'' Roth GS, Lane MA, Ingram DK, Mattison JA, Elahi D, Tobin JD, Muller D, Metter EJ.: 297: 811, Science 2002. PMID 12161648.

*''Eat more, weigh less, live longer'', New Scientist, January 2003. http://www.newscientist.com/article.ns?id=dn3303

*''Extended longevity in mice lacking the insulin receptor in adipose tissue.'' Bluher, Khan BP, Kahn CR, Science 299(5606): 572-4, [[24 January]] [[2003]]. PMID 12543978.

*Interview,' 'I want to live forever'', Cynthia Kenyon Professor of Biochemistry and Biophysics at the University of California, San Francisco, by James Kingsland. New Scientist online, [[20 October]] [[2003]]. http://www.newscientist.com/channel/opinion/mg18024175.300

*''Sir2-independent life span extension by calorie restriction in yeast'', Kaeberlein, M., K.T. Kirkland, S. Fields, and B.K. Kennedy. 2004. PLoS Biol 2: E296. PMID 15328540.

*''Substrate-specific Activation of Sirtuins by Resveratrol'', Kaeberlein, M., T. McDonagh, B. Heltweg, J. Hixon, E.A. Westman, S.D. Caldwell, A. Napper, R. Curtis, P.S. Distefano, S. Fields, A. Bedalov, and B.K. Kennedy. 2005. J Biol Chem 280: 17038-45. PMID 15684413.

*Interview, ''Longevity and Genetics'', Matt Kaeberlein, Brian Kennedy. [http://www.sagecrossroads.com/Default.aspx?tabid=171 SAGE Crossroads]

*''Increased Life Span due to Calorie Restriction in Respiratory-Deficient Yeast'', Kaeberlein M, Hu D, Kerr EO, Tsuchiya M, Westman EA, Dang N, Fields S, Kennedy BK. PLoS Genet. [[25 November]] [[2005]];1(5):e69

*''Regulation of yeast replicative life span by TOR and Sch9 in response to nutrients'', Kaeberlein M, Powers RW 3rd, Steffen KK, Westman EA, Hu D, Dang N, Kerr EO, Kirkland KT, Fields S, Kennedy BK. Science. [[18 November]] [[2005]];310(5751):1193-6.

==See also==
* [[Alzheimer's disease]]
* [[Calorie Restriction Society]]
* [[Fasting]]
* [[Huntington's disease]]
* [[Life extension]]
* [[Resveratrol]]
* [[Starvation]]

==Articles==
* [http://www.medpagetoday.com/Cardiology/Prevention/tb/2483 Calorie Restricters Seem Young at Heart]
* [http://www.americanscientist.org/template/AssetDetail/assetid/28346?fulltext=true&print=yes American Scientist Online, "Aging: A Biological Perspective" retrieved September 29, 2005]
* [http://www.scienceboard.net/community/perspectives.144.html Life Extension, Caloric Restriction and Scientific Philanthropy]
* [http://www.iangoddard.net/cr.htm Eat Less Live More]

==External links==
* [http://www.calorierestriction.org/ Calorie Restriction Society]
* [http://www.scientificpsychic.com/health/cron1.html Caloric Restriction Calculator]
* [http://www.thedoctorslounge.net/centers/nutrition/weight_loss/index.htm Weight loss methods and classification of caloric restriction diets.]
* [http://www.okinawaprogram.com/ A study of the high rate of centenarians in Okinawa.]
* [http://www.cron-web.org/ Calorie Restriction with Optimum Nutrition Web site.]
* [http://www.benbest.com/lifeext/aging.html Mechanisms of Aging.]
* [http://www.optimal.org/peter/cronindex.htm Practical CRON tips.]
*[http://www.senescence.info/antiaging.html senescence.info] Informational website related to aging research that includes a discussion of caloric restriction and its mechanisms.
*[http://www.modeldietplan.com/caloriereduction.htm Pros and Cons of Calorie Restriction]
*[http://www.walford.com Dr. Walford's web site ]
[[Category:Diets]]
[[Category:Diets]]
[[Category:Eating behaviors]]
[[Category:Eating behaviors]]
[[Category:Gerontology]]
[[Category:Life extension]]
[[Category:Senescence]]

[[ja:カロリー制限]]

Latest revision as of 17:01, 18 June 2024

For caloric restriction for the purpose of weight loss, see dieting.

Calorie restriction (also known as caloric restriction or energy restriction) is a dietary regimen that reduces the energy intake from foods and beverages without incurring malnutrition.[1][2] The possible effect of calorie restriction on body weight management, longevity, and aging-associated diseases has been an active area of research.[1]

Dietary guidelines[edit]

Caloric intake control, and reduction for overweight individuals, is recommended by US dietary guidelines and science-based societies.[3][4][5][6][7][8]

Calorie restriction is recommended for people with diabetes[9][10] and prediabetes,[10] in combination with physical exercise and a weight loss goal of 5-15% for diabetes and 7-10% for prediabetes to prevent progression to diabetes.[10] Mild calorie restriction may be beneficial for pregnant women to reduce weight gain (without weight loss) and reduce perinatal risks for both the mother and child.[11][12] For overweight or obese individuals, calorie restriction may improve health through weight loss, although a gradual weight regain of 1–2 kg (2.2–4.4 lb) per year may occur.[4][6]

Risks of malnutrition[edit]

The term "calorie restriction" as used in the study of aging refers to dietary regimens that reduce calorie intake without incurring malnutrition.[1] If a restricted diet is not designed to include essential nutrients, malnutrition may result in serious deleterious effects, as shown in the Minnesota Starvation Experiment.[13] This study was conducted during World War II on a group of lean men, who restricted their calorie intake by 45%[14] for six months and composed roughly 77% of their diet with carbohydrates.[13] As expected, this malnutrition resulted in metabolic adaptations, such as decreased body fat, improved lipid profile, and decreased resting heart rate. The experiment also caused negative effects, such as anemia, edema, muscle wasting, weakness, dizziness, irritability, lethargy, and depression.[13]

Typical low-calorie diets may not supply sufficient nutrient intake that is typically included in a calorie restriction diet.[15][16][17]

Possible side effects[edit]

People losing weight during calorie restriction risk developing side effects, such as cold sensitivity, menstrual irregularities, infertility, or hormonal changes.[18]

Research[edit]

Humans[edit]

Decreasing caloric intake by 20-30%, while fulfilling nutrient requirements, has been found to remedy diseases of aging, including cancer, cardiovascular disease, dementia, and diabetes in humans, and result in an average loss of 7.9 kilograms (17 lb) in body weight, but because of the long lifespan of humans, evidence that calorie restriction could prevent age-related disease in humans remains under preliminary research.[1][19] While calorie restriction leads to weight and fat loss, the precise amount of calorie intake and associated fat mass for optimal health in humans is not known.[1] Moderate amounts of calorie restriction may have harmful effects on certain population groups, such as lean people with low body fat.[1]

Life extension[edit]

As of 2021, intermittent fasting and calorie restriction remain under preliminary research to assess the possible effects on disease burden and increased lifespan during aging, although the relative risks associated with long-term fasting or calorie restriction remain undetermined.[1]

Intermittent fasting refers to periods with intervals during which no food but only clear fluids are ingested – such as a period of daily time-restricted eating with a window of 8 to 12 hours for any caloric intake – and could be combined with overall calorie restriction and variants of the Mediterranean diet which may contribute to long-term cardiovascular health and longevity.[20]

Minnesota Starvation Experiment[edit]

The Minnesota Starvation Experiment examined the physical and psychological effects of extreme calorie restriction on 32 young and lean 24-year-old men during a 40% reduction in energy intake for 6 months. The study was designed to mimic dietary conditions during World War II. Participants could only eat 1800 kcal per day, but were required to walk 5 km per day and expend 3000 calories.[21] The men lost about 25% of their body weight of which 67% was fat mass and 17% fat-free mass.[21] The quality of the diet was insufficient to accurately represent the diet during war due to the inadequate consumption of protein, and a lack of fruits and vegetables. Despite the extreme calorie restriction, the experiment was not representative of true calorie-restrictive diets, which adhere to intake guidelines for macronutrients and micronutrients.[21] Chronic weakness, decreased aerobic capacity, and painful lower limb edema was caused by the malnourished calorie restrictive diet.[21][22] Emotional distress, confusion, apathy, depression, hysteria, hypochondriasis, suicidal thoughts, and loss of sex drive were among the abnormal psychological behaviors that occurred within six weeks.[21]

Intensive care[edit]

As of 2019, current clinical guidelines recommend that hospitals ensure that the patients get fed with 80–100% of energy expenditure, the normocaloric feeding. A systematic review investigated whether people in intensive care units have different outcomes with normocaloric feeding or hypocaloric feeding, and found no difference.[23] However, a comment criticized the inadequate control of protein intake, and raised concerns that hypocaloric feeding safety should be further assessed with underweight critically ill people.[24]

Non-human primates[edit]

A calorie restriction study started in 1987 by the National Institute on Aging showed that calorie restriction did not extend years of life or reduce age-related deaths in non-obese rhesus macaques.[25] It did improve certain measures of health, however.[26] These results were publicized as being different from the Wisconsin rhesus macaque calorie restriction study, which also started in 1987 and showed an increase in the lifespan of rhesus macaques following calorie restriction.[25]

In a 2017 report on rhesus monkeys, caloric restriction in the presence of adequate nutrition was effective in delaying the effects of aging.[27][28] Older age of onset, female sex, lower body weight and fat mass, reduced food intake, diet quality, and lower fasting blood glucose levels were factors associated with fewer disorders of aging and with improved survival rates.[27] Specifically, reduced food intake was beneficial in adult and older primates, but not in younger monkeys.[27] The study indicated that caloric restriction provided health benefits with fewer age-related disorders in elderly monkeys and, because rhesus monkeys are genetically similar to humans, the benefits and mechanisms of caloric restriction may apply to human health during aging.[29][30]

Activity levels[edit]

Calorie restriction preserves muscle tissue in nonhuman primates[31][32] and rodents.[33] Muscle tissue grows when stimulated, so it has been suggested that the calorie-restricted test animals exercised more than their companions on higher calories, perhaps because animals enter a foraging state during calorie restriction. However, studies show that overall activity levels are no higher in calorie restriction than ad libitum animals in youth.[34]

Sirtuin-mediated mechanism[edit]

Main article: Caloric restriction mimetic

Preliminary research indicates that sirtuins are activated by fasting and serve as "energy sensors" during metabolism.[35] Sirtuins, specifically Sir2 (found in yeast) have been implicated in the aging of yeast,[36] and are a class of highly conserved, NAD+-dependent histone deacetylase enzymes.[37] Sir2 homologs have been identified in a wide range of organisms from bacteria to humans.[36][38]

See also[edit]

References[edit]

  1. ^ a b c d e f g Lee MB, Hill CM, Bitto A, Kaeberlein M (November 2021). "Antiaging diets: Separating fact from fiction". Science. 374 (6570): eabe7365. doi:10.1126/science.abe7365. PMC 8841109. PMID 34793210.
  2. ^ Flanagan EW, Most J, Mey JT, Redman LM (September 2020). "Calorie Restriction and Aging in Humans". Annual Review of Nutrition. 40: 105–133. doi:10.1146/annurev-nutr-122319-034601. PMC 9042193. PMID 32559388.
  3. ^ US Department of Health and Human Services. (2017). "2015–2020 Dietary Guidelines for Americans - health.gov". health.gov. Skyhorse Publishing Inc. Retrieved 30 September 2019.
  4. ^ a b Arnett DK, Blumenthal RS, Albert MA, Buroker AB, Goldberger ZD, Hahn EJ, et al. (September 2019). "2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines". Circulation. 140 (11): e596–e646. doi:10.1161/CIR.0000000000000678. PMC 7734661. PMID 30879355.
  5. ^ "Obesity: maintaining a healthy weight and preventing excess weight gain". pathways.nice.org.uk.
  6. ^ a b Jensen MD, Ryan DH, Apovian CM, Ard JD, Comuzzie AG, Donato KA, et al. (June 2014). "2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society". Circulation. 129 (25 Suppl 2): S102–S138. doi:10.1161/01.cir.0000437739.71477.ee. PMC 5819889. PMID 24222017.
  7. ^ "Diet - NICE Pathways". pathways.nice.org.uk.
  8. ^ Garvey WT, Mechanick JI, Brett EM, Garber AJ, Hurley DL, Jastreboff AM, et al. (July 2016). "American Association of Clinical Endocrinologists and American College of Endocrinology Comprehensive Clinical Practice Guidelines for Medical Care of Patients with Obesity". Endocrine Practice. 22 (Suppl 3): 1–203. doi:10.4158/EP161365.GL. PMID 27219496.
  9. ^ American Diabetes Association (January 2019). "5. Lifestyle Management: Standards of Medical Care in Diabetes-2019". Diabetes Care. 42 (Suppl 1): S46–S60. doi:10.2337/dc19-S005. PMID 30559231.
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Further reading[edit]

  • Everitt AV, Heilbronn LK, Le Couteur DG (2010). "Food Intake, Life Style, Aging and Human Longevity". In Everitt AV, Rattan SI, Le Couteur DG, de Cabo R (eds.). Calorie Restriction, Aging and Longevity. New York: Springer. ISBN 978-90-481-8555-9.
  • Keys A, Brozek J, Henschel A, Mickelsen O, Taylor HL (1950). The Biology of Human Starvation. Vol. I. University of Minnesota Press. ISBN 978-0-8166-7234-9.
source: https://en.wikipedia.org/w/index.php?title=Calorie_restriction&diff=1229772314&oldid=70761229

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