Impact of Nutrition on Telomere Health: Systematic Review of Observational Cohort Studies and Randomized Clinical Trials

Serena Galiè; Silvia Canudas; Jananee Muralidharan; Jesús García-Gavilán; Mònica Bulló; Jordi Salas-Salvadó

doi:10.1093/advances/nmz107

TABLE 1
Epidemiologic studies evaluating the effect of dietary macronutrients on telomere length¹
Reference Design Population Method Factor Results
Tucker AL et al., 2018 (21) Cross-sectional 5674 healthy participants from the NHANES study PCR Dietary fibers Fiber intake per 1000 kcal was positively associated with TL (linear association)
Cassidy A et al., 2010 (12) Cross-sectional 2284 women from the Nurses' Health Study PCR Dietary fiber, fats, protein Fiber intake was positively associated with LTL, whereas protein intake was not associated to LTL. PUFA (specifically, Linoleic acid) intake were significantly inversely associated with LTL
Zhou M et al., 2016 (20) Cross-sectional Chinese population with normal glucose tolerance (n = 200), pre-diabetes (n = 197) and newly diagnosed diabetes (n= 159) PCR Dietary carbohydrate, protein and fat intake No correlation between daily carbohydrate, protein and fat intake and LTL was reported
Mirabello L et al., 2009 (24) Case-control 612 advanced prostate cancer cases and 1049 age matched cancer free controls from the PLCO Cancer Screening Trial PCR Dietary fat intake Prostate cancer cases and controls did not differ with respect to mean relative TL. Non-significant trends for fat intake related to relative TL was found
Song Y et al., 2013 (25) Case-control 4029 women from the WHI-OS with and without diabetes PCR Different types of fat intake Women with SFA intake in the lowest compared to highest quartile had significantly longer TL. MUFAs and PUFAs were not significantly associated with TL in the fully adjusted models. SMSFA had an inverse association with TL
Tiainen A-MK et al., 2012 (26) Cross-sectional 1942 Healthy subjects from the Helsinki birth cohort PCR Dietary fats In men, high total fat, SFA, and butter intake was inversely associated with LTL
Kark D J et al., 2012 (27) Prospective cohort 609 Healthy subjects from the Jerusalem LRC study SB Daily carbohydrate, protein and fat intake In men, PUFA and MUFA as a percentage of total energy showed significant inverse associations with LTL in bivariate models. This significance was maintained only in MUFAs in the multivariable backward stepwise regression
Kielcot-Glaser et al., 2013 (28) RCT 106 Healthy subjects treated with: a) 2.5 g/day n-3 PUFA; b) 1.25 g/day n-3 PUFA; c) placebo capsule constituted by a mixture of oils representative of dietary fat content in American diet for 4 months PCR; TRAP n-3 PUFA supplementation, n-6:n-3 PUFA ration No significant differences in TL between the three groups were noted. Decrease in one unit of n-6: n-3 PUFA was associated with an increase in TL by 20 bp
O’Callaghan N et al., 2014 (30) RCT 33 adults with mild cognitive impairment with supplemented either: a)n-3 PUFAs as EPA (1.67 g EPA+ 0.16 g DHA/day) b) n-3 PUFAs as DHA (1.55 g DHA+ 0.40g EPA/day) c) n-6 PUFA as linoleic acid (2.2g LA) for 6 months PCR n-3 supplementation Changes in erythrocyte DHA group were inversely significantly associated with TL. No differences between intervention groups were observed in changes of TL
Pawelczyk T et al., 2018 (31) RCT 71 Schizophrenic patients treated with: a) 2.2 g/day of n-3 PUFA (n= 36); b) Placebo (Olive oil, n= 35) for 26 weeks PCR n-3 supplementation Significant increase in the telomerase activity in both groups were observed and the increase in the n-3 PUFA group were significantly higher than placebo
Pavanello S et al., 2011 (34) Case-control 457 Healthy participants (controls = 257, cases of alcohol abusers = 200) PCR Alcohol consumption (units of drink/day, each unit = 10–12 g of alcohol) Abusive intake of alcohol was negatively associated with TL. Participants consuming >4 drink units per day compared with <4 drink units per day had a significantly shorter TL
Bekaert S et al., 2007 (35) Cross-sectional 2509 Healthy participants from Asklepios study PCR Alcohol consumption (units alcohol per week) Alcohol consumption in both men and women were inversely associated with TL

¹LTL, leukocyte telomere length; PLCOCST, Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial; TL, telomere length.

Reference	Design	Population	Method	Factor	Results
Tucker AL et al., 2018 (21)	Cross-sectional	5674 healthy participants from the NHANES study	PCR	Dietary fibers	Fiber intake per 1000 kcal was positively associated with TL (linear association)
Cassidy A et al., 2010 (12)	Cross-sectional	2284 women from the Nurses' Health Study	PCR	Dietary fiber, fats, protein	Fiber intake was positively associated with LTL, whereas protein intake was not associated to LTL. PUFA (specifically, Linoleic acid) intake were significantly inversely associated with LTL
Zhou M et al., 2016 (20)	Cross-sectional	Chinese population with normal glucose tolerance (n = 200), pre-diabetes (n = 197) and newly diagnosed diabetes (n= 159)	PCR	Dietary carbohydrate, protein and fat intake	No correlation between daily carbohydrate, protein and fat intake and LTL was reported
Mirabello L et al., 2009 (24)	Case-control	612 advanced prostate cancer cases and 1049 age matched cancer free controls from the PLCO Cancer Screening Trial	PCR	Dietary fat intake	Prostate cancer cases and controls did not differ with respect to mean relative TL. Non-significant trends for fat intake related to relative TL was found
Song Y et al., 2013 (25)	Case-control	4029 women from the WHI-OS with and without diabetes	PCR	Different types of fat intake	Women with SFA intake in the lowest compared to highest quartile had significantly longer TL. MUFAs and PUFAs were not significantly associated with TL in the fully adjusted models. SMSFA had an inverse association with TL
Tiainen A-MK et al., 2012 (26)	Cross-sectional	1942 Healthy subjects from the Helsinki birth cohort	PCR	Dietary fats	In men, high total fat, SFA, and butter intake was inversely associated with LTL
Kark D J et al., 2012 (27)	Prospective cohort	609 Healthy subjects from the Jerusalem LRC study	SB	Daily carbohydrate, protein and fat intake	In men, PUFA and MUFA as a percentage of total energy showed significant inverse associations with LTL in bivariate models. This significance was maintained only in MUFAs in the multivariable backward stepwise regression
Kielcot-Glaser et al., 2013 (28)	RCT	106 Healthy subjects treated with: a) 2.5 g/day n-3 PUFA; b) 1.25 g/day n-3 PUFA; c) placebo capsule constituted by a mixture of oils representative of dietary fat content in American diet for 4 months	PCR; TRAP	n-3 PUFA supplementation, n-6:n-3 PUFA ration	No significant differences in TL between the three groups were noted. Decrease in one unit of n-6: n-3 PUFA was associated with an increase in TL by 20 bp
O’Callaghan N et al., 2014 (30)	RCT	33 adults with mild cognitive impairment with supplemented either: a)n-3 PUFAs as EPA (1.67 g EPA+ 0.16 g DHA/day) b) n-3 PUFAs as DHA (1.55 g DHA+ 0.40g EPA/day) c) n-6 PUFA as linoleic acid (2.2g LA) for 6 months	PCR	n-3 supplementation	Changes in erythrocyte DHA group were inversely significantly associated with TL. No differences between intervention groups were observed in changes of TL
Pawelczyk T et al., 2018 (31)	RCT	71 Schizophrenic patients treated with: a) 2.2 g/day of n-3 PUFA (n= 36); b) Placebo (Olive oil, n= 35) for 26 weeks	PCR	n-3 supplementation	Significant increase in the telomerase activity in both groups were observed and the increase in the n-3 PUFA group were significantly higher than placebo
Pavanello S et al., 2011 (34)	Case-control	457 Healthy participants (controls = 257, cases of alcohol abusers = 200)	PCR	Alcohol consumption (units of drink/day, each unit = 10–12 g of alcohol)	Abusive intake of alcohol was negatively associated with TL. Participants consuming >4 drink units per day compared with <4 drink units per day had a significantly shorter TL
Bekaert S et al., 2007 (35)	Cross-sectional	2509 Healthy participants from Asklepios study	PCR	Alcohol consumption (units alcohol per week)	Alcohol consumption in both men and women were inversely associated with TL