TABLE 2

Epidemiologic studies and RCTs evaluating the effect of dietary micronutrients on telomere length¹

Reference	Design	Population	Method	Factor	Results
Borras et al. 2012 (42)	Case-control	62 hemodialysis patients, 55 sex-matched controls. 24 hemodialysis patients received vitamin D supplements for 28.8 mo	SB	Vitamin D	Hemodialysis patients had shorter TL compared with the controls. Significant associations between phosphorous concentrations, active vitamin D treatment, and LTL were observed
Mirabello et al. 2009 (24)	Case-control	612 prostate cancer cases and 1049 age-matched cancer-free controls from the PLCOCST	PCR	Vitamins and minerals	No significant baseline associations were found between the intake of vitamin E, lycopene, β-carotene, vitamin D, selenium, and LTL
Xu et al. 2009 (43)	Cross- sectional	586 participants with breast cancer from the Sisters Study	PCR	Multivitamin supplementation in diet	Multivitamin supplementation was associated with longer TL. Compared with the nonusers, daily users had an average 5.1% longer TL. With adjustment for multivitamin use, the total intake of micronutrients remained significant only for vitamins C and E
Marcon et al. 2012 (44)	Cross- sectional	56 healthy subjects	TRF	Thiamin, riboflavin, niacin, vitamin B-6, folate, vitamins A, C, D, E, and β-carotene	Vitamins A, C, E, folic acid, and β-carotene were positively correlated with LTL. After adjustments, only β-carotene show a significant correlation
Cassidy et al. 2010 (12)	Cross- sectional	2284 female participants from the Nurses’ Health Study	PCR	Vitamin D	No significant associations between vitamin D and TL were reported
Lee et al. 2017 (45)	Cross- sectional	1958 men and women from the Korean Genome Epidemiology Study	PCR	Vitamins A, C, E, thiamin, riboflavin, vitamin B6, niacin, retinol, carotene, folate, calcium, phosphorous, iron, zinc	After adjusting for potential confounders, vitamin C and potassium were significantly positively associated with LTL. Folate showed a trend for positive association
Lin et al. 2018 (46)	Cross- sectional	7324 participants from the NHANES study	PCR	Dietary copper intake	One unit of log-transformed dietary copper intake was significantly associated with longer telomeres
Zhu et al. 2012 (47)	RCT (parallel)	37 African Americans randomly assigned to: 1) experimental group (n = 19, 2000 IU vitamin D/d); 2) control group (n = 18, placebo) for 16 wk	TRAP	Vitamin D supplementation	Significant differences in changes of telomerase activity were observed between groups. A significant increase in the PBMC telomerase activity from baseline to postintervention was noted in the vitamin D-supplemented group
Balcerczyk et al. 2014 (48)	RCT (parallel)	Healthy subjects supplemented with either: 1) NucleVital Q10 Complex (n = 66 women) containing various micronutrients and ω-3 PUFA; 2) control group (n = 34 women) for 12 wk	PCR	NucleVital Q10 Complex supplementation	A significant increase in telomerase concentration but not in TL was seen in the supplementation group. However, differences in changes between intervention groups were not checked
Sharif et al. 2015 (49)	RCT (parallel)	90 elderly participants with Zn deficiency were randomly assigned to: 1) Zn supplementation group (n = 45; 20 mg/d Zn tablets); 2) placebo group (n = 45; 100% maltodextrin tablets) for 12 wk	PCR	Zinc supplementation	Telomeres were shorter in the Zn group compared with placebo after intervention; however, this difference was not significant. Significant increase in TL within groups was observed

¹LTL, leukocyte telomere length; PBMC, peripheral blood mononuclear cell; PLCOCST, Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial; RCT, randomized clinical trial; SB, Southern blotting; TL, telomere length; TRAP, telomerase repeated amplification protocol; TRF, telomere restriction fragment; Zn, zinc.