PMID- 35842755
OWN - NLM
STAT- MEDLINE
DCOM- 20220719
LR  - 20240416
IS  - 1760-4788 (Electronic)
IS  - 1279-7707 (Print)
IS  - 1279-7707 (Linking)
VI  - 26
IP  - 7
DP  - 2022
TI  - Modestly Increased Incidence of Ketosis in Caloric Restriction Does not 
      Significantly Alter the Effects of Caloric Restriction.
PG  - 657-662
LID - 10.1007/s12603-022-1815-7 [doi]
AB  - OBJECTIVES: Caloric restriction (CR) has been shown to slow the aging processes 
      in a number of preclinical studies and reduces expression of aging-associated 
      biomarkers in human trials. We hypothesized that CR would lead to increased 
      incidence of ketosis and that ketosis in CR individuals would alter the 
      aging-protective effects of CR or biomarkers thereof. 
      DESIGN/SETTING/PARTICIPANTS: We analyzed data from the "Comprehensive Assessment 
      of Long-Term Effects of Reducing Intake of Energy (CALERIE, Phase 2)" Public Use 
      Database available at calerie.duke.edu. In this study, non-obese adults between 
      the ages of 21 and 50 were randomized to 25% CR or control (ad lib) diet groups 
      and extensively monitored for two years. Given our focus on the effect of caloric 
      restriction on ketosis, individuals with detectible ketones during the baseline 
      visit (pre-randomization) and those with missing data for ketone testing were 
      excluded from the analysis, leaving 71 control and 117 CR participants. 
      MEASUREMENTS: We analyzed the incidence of ketosis as well as ketosis free 
      survival in control and CR participants and assessed the effect of ketosis on a 
      number of clinical lab values, functional assessments, and participant survey 
      data related to aging biology. RESULTS: We report that CR was associated with 
      modestly increased incidence of ketosis (4.4% in CR vs 1.9% in control), though 
      CR-associated changes in T3, VO2, SUMPT-WT (weight normalized composite strength 
      score - peak torque), physical functioning, and general health did not appear to 
      be altered by the presence or absence of ketosis. Additional observations of 
      interest include: 1) striking patterns of biomarker expression changes (MCP-1, 
      TNFalpha, TGF-beta1, GH) in both the control and CR participants between the baseline 
      visit and the 24-month post-randomization visit and 2) 
      pro-growth/anti-inflammatory baseline (pre-randomization) biomarker expression 
      profile in CR individuals that later test ketone positive relative to other CR 
      individuals. CONCLUSIONS: CR modestly increases the incidence of ketosis in 
      healthy adults, yet the increase in ketosis in CR patients did not significantly 
      affect the aging-protective effects of CR. However, given the relatively small 
      number of participants who were ketone positive, further investigation in larger 
      study cohorts is still required for definitive conclusions.
FAU - Ferguson, B S
AU  - Ferguson BS
AD  - Matthew S Stratton, Department of Physiology and Cell Biology, Davis Heart and 
      Lung Research Institute, Ohio State University Wexner Medical Center, Columbus 
      OH, 43210 USA, matthew.stratton@osumc.edu.
FAU - Sahoo, P
AU  - Sahoo P
FAU - McGrail, E
AU  - McGrail E
FAU - Francois, A
AU  - Francois A
FAU - Stratton, M S
AU  - Stratton MS
LA  - eng
GR  - K01 AG056848/AG/NIA NIH HHS/United States
GR  - P20 GM130459/GM/NIGMS NIH HHS/United States
GR  - UL1 TR002733/TR/NCATS NIH HHS/United States
GR  - R15 HL143496/HL/NHLBI NIH HHS/United States
GR  - 857280/AHA/American Heart Association-American Stroke Association/United States
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - France
TA  - J Nutr Health Aging
JT  - The journal of nutrition, health & aging
JID - 100893366
RN  - 0 (Ketones)
SB  - IM
MH  - *Aging
MH  - *Caloric Restriction
MH  - Diet
MH  - Humans
MH  - Incidence
MH  - Ketones
PMC - PMC9704061
MID - NIHMS1844248
OTO - NOTNLM
OT  - CALERIE phase 2
OT  - Caloric restriction
OT  - ketosis
COIS- The authors declare that no financial conflicts of interest exist.
EDAT- 2022/07/18 06:00
MHDA- 2022/07/20 06:00
PMCR- 2022/11/28
CRDT- 2022/07/17 01:42
PHST- 2022/07/17 01:42 [entrez]
PHST- 2022/07/18 06:00 [pubmed]
PHST- 2022/07/20 06:00 [medline]
PHST- 2022/11/28 00:00 [pmc-release]
AID - S1279-7707(23)00831-X [pii]
AID - 10.1007/s12603-022-1815-7 [doi]
PST - ppublish
SO  - J Nutr Health Aging. 2022;26(7):657-662. doi: 10.1007/s12603-022-1815-7.