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			{{short description\|Dietary regime}}
	'''Calorie restriction''' or '''Caloric restriction''' (CR) is the practice of limiting dietary energy intake to improve health and retard ]. In human subjects, CR has been shown to lower ] and ]. Some consider these to be ]s of aging, as related diseases are more frequent with increasing age. Except for houseflies (]), animal species tested with CR so far, including ]s, ]s, ], ]s, ] and ]s, have shown lifespan extension. CR is the only known dietary measure capable of extending ], as opposed to ]. Energy intake must be minimized, but sufficient quantities of ]s, ]s and other important ]s must still be ingested. To emphasize this, 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.
			{{For\|caloric restriction for the purpose of weight loss\|dieting}}
			'''Calorie restriction''' (also known as '''caloric restriction''' or '''energy restriction''') is a ] that ] from foods and beverages without incurring ].<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 ], ], and ]s has been an active area of research.<ref name=lee/>

			{{TOC limit\|3}}
	==Research history==
	In ], Clive McCay and Mary Crowell of ] 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 ] and his student ]. In ], 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 Caloric Restriction society.

			Caloric intake control, and reduction for ] 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>
	] 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 ],” he says. “Usually, that rises with age reliably, partly because the ]. 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 ]<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 ] 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===
			The term "calorie restriction" as used in ] refers to dietary regimens that reduce calorie intake without incurring ].<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 ].<ref name="Keys A 1950" /> This study was conducted during ] 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 ], such as decreased body fat, improved lipid profile, and decreased resting heart rate. The experiment also caused negative effects, such as ], ], ], ], ], ], ], 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>
	==Effects of CR different organisms==

			===Possible side effects===
	===Primates==
			People losing weight during calorie restriction risk developing ]s, such as ], ], ], 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===
	===Mice===
	===Spider===
	===C. elegans===
	===rotifer===

			==Research==

			===Humans===
	==Why might CR increase longevity?==
			Decreasing ] 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/>
	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 ], developmental delay, the control animals being ]s, and decreased ] production.

	===~~Hormesis~~ ~~hypothesis~~===		===Life extension===
			As of 2021, ] 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/>
	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 "]" 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 ] proposes that the diet imposes a low-intensity biological stress on the organism, which elicits a defense response that helps protects 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 ] (see below).

			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 ] 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>
	Recent research has suggested (see ], ], ], et al.) that it is not reduced intake which influences longevity. This was done by studying animals which have their metabolism changed to reduce ] 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 ]: if this can be done while not diminishing dietary intake (as in some minority eating patterns, see e.g. ] or ]) then the 'starvation diet' anticipated as an impossible requirement by earlier researchers is no longer a precondition of increased longevity.

			===Minnesota Starvation Experiment===
	The extent to which these findings may apply to human ] and ] is as noted above under investigation. A paper in the ], 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 ] interventions.
			The ] 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 ]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 ]s and ]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, ], depression, ], ], 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 ]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>
	Recent discoveries have suggested that the ] Sir2 might underlie the effect of CR. In ] the Sir2 enzyme is activated by CR, which leads to a 30% lifespan extension in test subjects. David Sinclair showed that in test mammals the Sir2 equivalent gene known as ] is turned on by a CR diet, and this protects cells from dying under stress. Leonard Guarente showed that SIRT1 releases fat from storage cells. This work was published in the June 2004 issues of the magazines ] and ] (PMID 15175761). See also for information on SIRT1. Sinclair's lab reported that they have found small molecules (e.g. ]) that activate Sir2 and can extend the lifespan of yeast.

			===Non-human primates===
	More recent discoveries by ] and ] at the have demonstrated that CR may not act through Sir2. Kaeberlein and Kennedy have also largely discredited Sinclair's work with resveratrol, demonstrating that the findings in Sinclair's Nature paper are an artifact of the Fluor de Lys assay (PMID 15684413).
			A calorie restriction study started in 1987 by the ] showed that calorie restriction did not extend years of life or reduce age-related deaths in non-obese ]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=] \|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 press release \|title=Calorie restriction lets monkeys live long and prosper \|url=https://www.sciencedaily.com/releases/2017/01/170117140105.htm \|work=ScienceDaily \|publisher=University of Wisconsin-Madison \|date=17 January 2017 }}</ref> Older age of onset, female sex, lower body weight and fat mass, reduced food intake, diet quality, and lower ] ] 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>
	===DHEA===
	While calorie restriction has been shown to increase ] in primates (PMID 12543259), it has not been shown to increase ] in post-pubescent primates (PMID 15247063).

	===Free radicals and glycation===
	Two very prominent theories of aging are the ] and the ] theory, both of which can explain how CR could work. With high amounts of energy available, ] do not operate very efficiently and generate more ]. 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 ] of adjacent proteins and less fat to oxidize in the bloodstream to cause sticky blocks resulting in atherosclerosis. Type II ] are people with insulin insensitivity caused by long-term exposure to high blood glucose. Obesity leads to type 2 diabetes. Type 2 diabetes and uncontrolled type 1 diabetes are much like "accelerated aging", due to the above effects. There may even be a continuum between CR and the ].

			===Activity levels===
	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 ], 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 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 }}</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 ] 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 ===
	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.

			{{Main\|Caloric restriction mimetic}}
	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.

			Preliminary research indicates that ]s are activated by fasting and serve as "energy sensors" during ].<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 ], NAD<sup>+</sup>-dependent ] ]s.<ref name="Lin 12–16">{{cite journal \| vauthors = Lin SJ, Ford E, ], 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>
	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.

			== See also ==
	===Papers on CR in yeast: dismissing increased respiration===
			* ]
	In late 2005 ] and ] published two important papers on calorie restriction in yeast. In a paper published in they show that Lenny Guarente's model for calorie restriction increasing respiration is wrong. In a potentially much more important paper published in 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 ] . Michael Cooper claims that the widely purported effects of caloric restriction may be because a diet containing more calories can increase ]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 ] 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 ]s, and may not provide them adequate levels of energy or sufficient amino acids for repair.

	===Benefits only the young===
	Furthermore there is evidence to suggest that this benefit can only be reaped in early years. Lipman, Smith, Bronson and Blumberg published a study on Long Evans rats which were gradually introduced to a CR lifestyle at 18 months. This population showed no improvement over the median lifespan of ] group.

	===Negligible effect on larger organisms===
	Another objection to CR as a lifestyle would be that the effect is small to negligible in larger organisms. John Phelan published an article postulating that the CR case is vastly oversimplified when applied to larger mammals.

	==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 ]'s (NIA) Laboratory of Neurosciences, and colleagues have found that intermittent fasting and calorie restriction affect the progression of diseases similar to ], ], and ] 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 ], and increased ] resistance. Researchers have long been aware that calorie restriction extends lifespan, but this study showed that improved glucose metabolism also protects ] in experimental models of Parkinson's and ].

	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 ], results from neuronal degeneration in the ]. 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 ] (BDNF) levels. BDNF protects neurons and stimulates their growth. Fasting mice also had high levels of heat-shock protein-70 (], 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==
	* ''Genes & Development'' ; Koubova,J; 17(3):313-321 (2003)

	* ''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, ] ]. 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, ] ]. 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.

	*''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. ] ];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. ] ];310(5751):1193-6.

	==See also==
	* ]		* ]
	* ]		* ]
	* ]		* ]
			* ]
			* ]

	==~~Articles~~==		== References ==
			{{reflist}}
	*
	*
	*
	*

			== Further reading ==
	==External links==
			{{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}}
	*
	*
	*
	*
	* Informational website related to aging research that includes a discussion of caloric restriction and its mechanisms.

			{{Diets}}
			{{Longevity}}

			{{DEFAULTSORT:Calorie Restriction}}
	]		]
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Latest revision as of 05:43, 30 December 2024

Dietary regime 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. The possible effect of calorie restriction on body weight management, longevity, and aging-associated diseases has been an active area of research.

Dietary guidelines

Caloric intake control, and reduction for overweight individuals, is recommended by US dietary guidelines and science-based societies.

Calorie restriction is recommended for people with diabetes and prediabetes, 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. 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. 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.

Risks of malnutrition

The term "calorie restriction" as used in the study of aging refers to dietary regimens that reduce calorie intake without incurring malnutrition. 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. This study was conducted during World War II on a group of lean men, who restricted their calorie intake by 45% for six months and composed roughly 77% of their diet with carbohydrates. 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.

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

Possible side effects

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

Research

Humans

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. 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. Moderate amounts of calorie restriction may have harmful effects on certain population groups, such as lean people with low body fat.

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.

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.

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 calories. The men lost about 25% of their body weight of which 67% was fat mass and 17% fat-free mass. 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. Chronic weakness, decreased aerobic capacity, and painful lower limb edema was caused by the malnourished calorie restrictive diet. 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.

Intensive care

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. 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.

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 macaques. It did improve certain measures of health, however. 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.

In a 2017 report on rhesus monkeys, caloric restriction in the presence of adequate nutrition was effective in delaying the effects of aging. 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. Specifically, reduced food intake was beneficial in adult and older primates, but not in younger monkeys. 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.

Activity levels

Calorie restriction preserves muscle tissue in nonhuman primates and rodents. 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.

Sirtuin-mediated mechanism

Main article: Caloric restriction mimetic

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

References

^ 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.
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.
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.
^ 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.
"Obesity: maintaining a healthy weight and preventing excess weight gain". pathways.nice.org.uk.
^ 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.
"Diet - NICE Pathways". pathways.nice.org.uk.
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.
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.
^ Evert AB, Dennison M, Gardner CD, Garvey WT, Lau KH, MacLeod J, et al. (May 2019). "Nutrition Therapy for Adults With Diabetes or Prediabetes: A Consensus Report". Diabetes Care (Professional society guidelines). 42 (5): 731–754. doi:10.2337/dci19-0014. PMC 7011201. PMID 31000505.
Glazier JD, Hayes DJ, Hussain S, D'Souza SW, Whitcombe J, Heazell AE, Ashton N (October 2018). "The effect of Ramadan fasting during pregnancy on perinatal outcomes: a systematic review and meta-analysis". BMC Pregnancy and Childbirth. 18 (1): 421. doi:10.1186/s12884-018-2048-y. PMC 6202808. PMID 30359228.
Thangaratinam S, Rogozinska E, Jolly K, Glinkowski S, Roseboom T, Tomlinson JW, et al. (May 2012). "Effects of interventions in pregnancy on maternal weight and obstetric outcomes: meta-analysis of randomised evidence". BMJ. 344: e2088. doi:10.1136/bmj.e2088. PMC 3355191. PMID 22596383.
^ Keys A, Brozek J, Henschels A & Mickelsen O & Taylor H. The Biology of Human Starvation, 1950. University of Minnesota Press, Minneapolis
Keys A 1950, p. 114.
St Jeor ST, Howard BV, Prewitt TE, Bovee V, Bazzarre T, Eckel RH (October 2001). "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". Circulation. 104 (15): 1869–1874. doi:10.1161/hc4001.096152. PMID 11591629.
de Souza RJ, Swain JF, Appel LJ, Sacks FM (July 2008). "Alternatives for macronutrient intake and chronic disease: a comparison of the OmniHeart diets with popular diets and with dietary recommendations". The American Journal of Clinical Nutrition. 88 (1): 1–11. doi:10.1093/ajcn/88.1.1. PMC 2674146. PMID 18614716.
Ma Y, Pagoto SL, Griffith JA, Merriam PA, Ockene IS, Hafner AR, Olendzki BC (October 2007). "A dietary quality comparison of popular weight-loss plans". Journal of the American Dietetic Association. 107 (10): 1786–1791. doi:10.1016/j.jada.2007.07.013. PMC 2040023. PMID 17904938.
Marzetti E, Wohlgemuth SE, Anton SD, Bernabei R, Carter CS, Leeuwenburgh C (November 2009). "Cellular mechanisms of cardioprotection by calorie restriction: state of the science and future perspectives". Clinics in Geriatric Medicine. 25 (4): 715–32, ix. doi:10.1016/j.cger.2009.07.002. PMC 2786899. PMID 19944269.
Caristia S, Vito M, Sarro A, Leone A, Pecere A, Zibetti A, et al. (July 2020). "Is Caloric Restriction Associated with Better Healthy Aging Outcomes? A Systematic Review and Meta-Analysis of Randomized Controlled Trials". Nutrients. 12 (8): 2290. doi:10.3390/nu12082290. PMC 7468870. PMID 32751664.
O'Keefe JH, Torres-Acosta N, O'Keefe EL, Saeed IM, Lavie CJ, Smith SE, Ros E (September 2020). "A pesco-Mediterranean diet with intermittent fasting: JACC Review Topic of the Week". Journal of the American College of Cardiology. 76 (12): 1484–1493. doi:10.1016/j.jacc.2020.07.049. PMID 32943166. S2CID 221787788.
^ Most J, Tosti V, Redman LM, Fontana L (October 2017). "Calorie restriction in humans: An update". Ageing Research Reviews. Nutritional interventions modulating aging and age-associated diseases. 39: 36–45. doi:10.1016/j.arr.2016.08.005. PMC 5315691. PMID 27544442.
Keys A, Brožek J, Henschel A, Mickelsen O, Taylor HL (1950). The biology of human starvation (2 vols). Univ. of Minnesota Press.
Marik PE, Hooper MH (March 2016). "Normocaloric versus hypocaloric feeding on the outcomes of ICU patients: a systematic review and meta-analysis". Intensive Care Medicine. 42 (3): 316–323. doi:10.1007/s00134-015-4131-4. PMID 26556615. S2CID 37653149.
Bitzani M (April 2016). "Comments on Marik and Hooper: Normocaloric versus hypocaloric feeding on the outcomes of ICU patients: a systematic review and meta-analysis". Intensive Care Medicine. 42 (4): 628–629. doi:10.1007/s00134-016-4248-0. PMID 26880090. S2CID 34072936.
^ National Institutes of Health (2012-08-29). "NIH study finds calorie restriction does not affect survival". Retrieved May 17, 2016.
Nicholas Wade (April 1, 2014). "Diet's Link to Longevity: After 2 Studies Diverge, a Search for Consensus". The New York Times. Retrieved May 17, 2016.
^ Mattison JA, Colman RJ, Beasley TM, Allison DB, Kemnitz JW, Roth GS, et al. (January 2017). "Caloric restriction improves health and survival of rhesus monkeys". Nature Communications. 8 (1): 14063. Bibcode:2017NatCo...814063M. doi:10.1038/ncomms14063. PMC 5247583. PMID 28094793.
"Calorie restriction lets monkeys live long and prosper". ScienceDaily (Press release). University of Wisconsin-Madison. 17 January 2017.
Mattison JA, Roth GS, Beasley TM, Tilmont EM, Handy AM, Herbert RL, et al. (September 2012). "Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study". Nature. 489 (7415): 318–321. Bibcode:2012Natur.489..318M. doi:10.1038/nature11432. PMC 3832985. PMID 22932268.
Vaughan KL, Kaiser T, Peaden R, Anson RM, de Cabo R, Mattison JA (December 2017). "Caloric Restriction Study Design Limitations in Rodent and Nonhuman Primate Studies". The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 73 (1): 48–53. doi:10.1093/gerona/glx088. PMC 5861872. PMID 28977341.
McKiernan SH, Colman RJ, Aiken E, Evans TD, Beasley TM, Aiken JM, et al. (March 2012). "Cellular adaptation contributes to calorie restriction-induced preservation of skeletal muscle in aged rhesus monkeys". Experimental Gerontology. 47 (3): 229–236. doi:10.1016/j.exger.2011.12.009. PMC 3321729. PMID 22226624.
Colman RJ, Beasley TM, Allison DB, Weindruch R (June 2008). "Attenuation of sarcopenia by dietary restriction in rhesus monkeys". The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 63 (6): 556–559. doi:10.1093/gerona/63.6.556. PMC 2812805. PMID 18559628.
Dirks Naylor AJ, Leeuwenburgh C (January 2008). "Sarcopenia: the role of apoptosis and modulation by caloric restriction". Exercise and Sport Sciences Reviews. 36 (1): 19–24. doi:10.1097/jes.0b013e31815ddd9d. PMID 18156949.
Faulks SC, Turner N, Else PL, Hulbert AJ (August 2006). "Calorie restriction in mice: effects on body composition, daily activity, metabolic rate, mitochondrial reactive oxygen species production, and membrane fatty acid composition". The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 61 (8): 781–794. doi:10.1093/gerona/61.8.781. PMID 16912094.
Chang HC, Guarente L (March 2014). "SIRT1 and other sirtuins in metabolism". Trends in Endocrinology and Metabolism. 25 (3): 138–145. doi:10.1016/j.tem.2013.12.001. hdl:1721.1/104067. PMC 3943707. PMID 24388149.
^ Guarente L (2007). "Sirtuins in aging and disease". Cold Spring Harbor Symposia on Quantitative Biology. 72: 483–488. doi:10.1101/sqb.2007.72.024. PMID 18419308.
Lin SJ, Ford E, Haigis M, Liszt G, Guarente L (January 2004). "Calorie restriction extends yeast life span by lowering the level of NADH". Genes & Development. 18 (1): 12–16. doi:10.1101/gad.1164804. PMC 314267. PMID 14724176.
Kaeberlein M, McVey M, Guarente L (October 1999). "The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms". Genes & Development. 13 (19): 2570–2580. doi:10.1101/gad.13.19.2570. PMC 317077. PMID 10521401.