Effects of Zinc Supplementation on Serum Lipids

A Systematic Review and Meta-Analysis

Priyanga Ranasinghe; WS Wathurapatha; MH Ishara; R. Jayawardana; P. Galappatthy; P. Katulanda; GR Constantine

Nutr Metab. 2015;12(26)

Conclusions

The present meta-analysis demonstrates that Zinc supplementation has favourable effects on plasma lipid parameters. Zinc supplementation significantly reduced total cholesterol, LDL cholesterol and triglycerides. In addition to that, Zinc supplementation in non-healthy patients demonstrated a significant elevation of HDL cholesterol. Therefore it may have the potential to reduce the incidence of atherosclerosis related morbidity and mortality especially in non-healthy patients who are at risk of atherosclerosis.

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Abbreviations
FBG: Fasting blood glucose, HbA1c: Glycosylated hemoglobin, HDL-c: High density lipoprotein cholesterol, LDL-c: Low density lipoprotein cholesterol, TG: Triglycerides, TC: total cholesterol, RCT: Randomized control trial, MVM: Multi vitamin mineral

Table 1. Description of included studies
Authors^[ref] Year of Publication; Country	Study design	Duration of Zn supplementation	n control(s)/placebo, n Zn supplement(s) n Other supplements	Gender	Age	Health status	Formulation Elemental Zn dose(s)	Lipid parameters studied	Significant outcomes
Afkhami-Ardekani et al. [18] 2008; Iran	R, P	1.5 months	20 20	Both	52.67 ± 8.6	Type-2 diabetes patients	ZnSO ₄ 660 mg/day^a	TG, TC, HDL-c, LDL-c	Reduction in TG, TC and LDL
Age-Related Eye Disease Study Research Group 48] 2002; United States	R, DB, P	5 years	166 202 (Zn),168(Zn + antioxidants) 181 (antioxidants)	Both	55–80	Patients with Age-related macular degeneration	ZnO 80 mg/day	TG, TC, HDL-c, LDL-c	Lipid profile not significantly affected by long-term supplementation with Zinc
Black et al. 36] 1988; United States	R, DB, P	3 months	9 13,9	Males	19–29	Healthy	Zn gluconate 50 mg/day (n = 13) 75 mg/day (n = 9)	TG, TC, HDL-c, LDL-c, VLDL	Serum TC, VLDL, LDL-c, TG not affected. Both Zn groups had significantly lower HDL than placebo group and lower than baseline
Bogden et al. 37] 1988; United States	R, DB, P	3 months	36 36, 31	Both	60–89	Healthy	Zn acetate 15 mg/day (n = 36) 100 mg/day (n = 31)	TC, HLD-c,	Serum TC and HDL-c was not altered significantly by Zinc
Boukaïba et al. 35] 1993; France	R, DB, C	2 months	23, 21	Both	73–106	Healthy 2 groups Reference- BMI >24 kg/m² (n = 23)	Zn gluconate 20 mg/day	TG, TC, HDL-c, LDL-c	Reduced TC in both Lean and Reference groups than placebo. Reduced HDL in Reference group. Higher TG in Lean group. No effect on TG in Reference group. Ratio of LDL-c to HDL-c not affected.
			23, 21			Healthy 2 groups Reference- BMI >24 kg/m² (n = 23)
			23, 21			Lean – BMI < 21 kg/m² (n = 21)
Brewer et al. [49] 1991; United States	O	1–5 years	No controls	Both	NM	Wilson's disease	NM	TG, TC, HDL-c,	HDL level reduced in males only. TC reduced in both genders.
			No controls					LDL-c, TC/HDL-c
			11(F), 13(M)					LDL-c, TC/HDL-c
Chevalier et al. 38] 2002; United States	R, DB, P	3 months	10	Both	23–80	End-Stage Renal	ZnSO ₄	TC, HDL-c,	TC and LDL-c increased. No change in HDL-c
			10			Disease on Haemodialysis	50 mg/day	LDL-c
			10			Disease on Haemodialysis	50 mg/day	LDL-c
Crouse et al. 39] 1984; United States	R, DB, P	2 months	10,11	Males	20–55	Healthy	ZnSO ₄	TG, TC, HDL-c,	No significant change in lipid parameters in both groups
			10,11			2 groups	28.7 mg/day	LDL-c
			11,12			Endurance trained
						(n = 21)
						Sedentary (n = 23)
Farvid et al. 34] 2004; Iran	R, DB, P	3 months	18	Both	30–69	Type-2	ZnSO ₄	TG, TC, HDL-c,	Co-supplementation of Mg, Zn, Vitamins C and E significantly increases HDL-c. TG, TC, LDL-c not altered
			18			Diabetes patients	30 mg/day	LDL-c
			16 (Zn + Mg), 17(Zn + Mg + Vit.C + Vit.E) 18 (Vit C+ Vit.E)			Diabetes patients	30 mg/day	LDL-c
Federico et al. 45] 2001; Italy	R, CC	2 months	30	Both	46–61	Gut cancer patients	NM	TC	No Significant reduction in TC
			30				21 mg/day
			30 (Zn + Se)				21 mg/day
Feillet-Coudray et al. 40] 2006; France	R, DB, P	6 months	16 (F),16 (M), 16 (F), 16 (M)	Both	55–70	Healthy	Zn gluconate	TG, TC, HDL-c,	No significant change in lipid parameters
			16 (F), 16 (M), 15 (F), 16 (M)					TG, TC, HDL-c,
								LDL-c
							15 mg/day(n = 32)
							30 mg/day(n = 31)
Foster et al. 33] 2013; Australia	R, DB, P	3 months	10	Females	65.0 ± 7.8	Type-2	Zn sulphate	TG, TC, HDL-c,	No significant change in lipid parameters
			10			Diabetes patients	40 mg/day	LDL-c
			12 (Zn), 11 (Zn + ALA)
			10 (ALA)
Freeland-Graves et al. 50] 1982; United States	R, DB, P	2 months	8	Females	18–40	Healthy	Zn Acetate	HDL-c	A transient non-dose related reduction in HDL-c
			8				15 mg/day (n = 8)
			8, 8, 8				50 mg/day (n = 8)
			8, 8, 8				100 mg/day (n = 8)
Gatto and Samman 51] 1995; Australia	R, B, C	1 month	10	Males	24.3 ± 4.2	Healthy	ZnSO₄	TG, TC,	No significant changes in TC, LDL-c or TG. HDL₂ :HDL₃ ratio increased
			10				50 mg/day	HDL-c,
			10				50 mg/day	LDL-c
Gunasekara et al. 46] 2011; Sri Lanka	R, B, P	4 months	32	Both	M-54.6 ± 7.0	Type-2	ZnSO4	TG, TC, HDL-c,	Reduced TC, LDL and TC/HDL-c ratio only in the group receiving Zinc + MVM supplementation.
			32		F- 54.9 ± 9.0	Diabetes patients	22 mg/day	LDL-c
			28 (Zn + MVM)
			26 (MVM)
Hashemipour et al. 17] 2009; Iran	R, DB, C	2 months	60	Both	6–10	Obese	ZnSO4	TG, TC, HDL-c,	TC, LDL-c and TG reduced. No change in HDL-c
			60				20 mg/day	LDL-c
			60				20 mg/day	LDL-c
Hercberg et al. 44] 2005; France	R, DB, P	7.5 years	3869 (F), 2508(M)	Both	35–60	Healthy	Multi-vitamin	TG, TC, HDL-c,	Significant reduction of HDL-c in men. No significant change in other lipid parameters
Hercberg et al. 44] 2005; France	R, DB, P	7.5 years	3844 (F), 2520(M)	Both	35–60	Healthy	(Zn 20 mg/day)	LDL-c
Hininger-Favier et al. 41] 2007; Europe	R, DB, P	6 months	130	Both	55–85	Healthy	Zn Gluconate	TG, TC, HDL-c,	No effect with Zinc 15 mg/day or 30 mg/day
			130				15 mg/day	LDL-c, LDL:HDL
			126, 131				(n = 126)
			126, 131				30 mg/day (n = 131)
Hooper et al. 52] 1980, United States	P	5 weeks	8	Males	23–35	Healthy	ZnSO4	TG, TC, HDL-c,	25 % reduction of HDL-c. TC, TG, and LDL-c no significant change.
							160 mg/day	TG, TC, HDL-c,
								LDL-c
			12					LDL-c
Kadhim et al. 20] 2006; Iraq	DB, P	3 months	15 (Metformin + Placebo)	Both	40–64	Type-2 Diabetes patients	Zn acetate	TG, TC, HDL-c,	Reduced TC, TG and LDL-c. HDL-c significantly increased.
			18 (Metformin + Melatonin + Zn)				50 mg/day^a	LDL-c
			13 (Melatonin + Zn)				50 mg/day^a	LDL-c
Khan et al. 42], 2013; India	R, P	3 months	21	Both	40–69	Type-2 Diabetes patients	ZnSO4	TG, TC, HDL-c,	Decrease in TG. HDL-c increased. No change in TC and LDL-c.
Khan et al. 42], 2013; India	R, P	3 months	23	Both	40–69	Type-2 Diabetes patients	50 mg/day	LDL-c	Decrease in TG. HDL-c increased. No change in TC and LDL-c.
Kim and Lee 21] 2012; South Korea	P	2 months	20	Females	19–28	Obese	Zn gluconate	TG, TC, HDL-c	No significant change in lipid parameters
			20				30 mg/day
			20				30 mg/day
Li et al. 28] 2010; China	R, DB, P	6.5 months	29	Females	18–55	Obese	Multi-vitamin	TG, TC, HDL-c,	Reduced TC and LDL-c and increased HDL-c in multivitamin & mineral supplemented group. No change in TG.
			29				(Zn 15 mg/day)	LDL-c
			30 (multivitamin & mineral)
			28 (Calcium)
Partida-Hernández et al. 19] 2006, Mexico	R, DB, C	3 months	27	Males	35–65	Type-2	ZnSO4	TG, TC, HDL-c,	Reduced TC, TG, VLDL-c. Increased HDL-c
			27			Diabetes patients	100 mg/day ^a	LDL-c, VLDL-c
			27			Diabetes patients	100 mg/day ^a	LDL-c, VLDL-c
Payahoo et al. 26] 2013; Iran	R, DB, P	1 month	30	Both	18–45	Obese	Zn gluconate	TG, TC, HDL-c,	TG level decreased.
			30				Zn gluconate	TG, TC, HDL-c,	TG level decreased.
			30				30 mg/day^a	LDL-c	No change in other lipid parameters
Rahimi-Ardabili et al. 27] 2012; Iran	R, DB, P	2 months	30	Both	52.8 ± 12.7	End-Stage Renal	ZnSO4	TG, TC, HDL-c,	No change in TC, TG and LDL-c.
			30			End-Stage Renal	ZnSO4	TG, TC, HDL-c,	No change in TC, TG and LDL-c.
			30			Disease on Haemodialysis	100 mg/day ^a	LDL-c	Increase in HDL
RangaRao et al. 53] 1990; India	CC	1 month	5	Males	NM	Type-1	ZnSO4	TG, TC, HDL-c	No significant change in lipid parameters
			5			Diabetes patients	660 mg/day^a
			7			Diabetes patients	660 mg/day^a
Roozbeh et al. 22] 2009; Iran	R, DB, P	1.5 months	26	Both	55.7	End-Stage Renal	ZnSO4	TG, TC, HDL-c,	Increase in TC, TG, LDL-c and HDL-c
			26			Disease on Haemodialysis	50 mg/day	LDL-c
			27			Disease on Haemodialysis	50 mg/day	LDL-c
Samman and Roberts 54] 1988; Australia	R, DB, C	1.5 months	41	Both	M-28.2 ± 2.0	Healthy	ZnSO4	TC, LDL-	No change in TC. In females LDL-C reduced. HDL2 increased and HDL 3 decreased.
			41		F- 26.8 ± 1.6		150 mg/day	c, HDL-c,
			41		F- 26.8 ± 1.6		150 mg/day	HDL2, HDL3
Seet et al. 23] 2011; Singapore	R, B, P	3 months	20	Males	NM	Type-2	Zn gluconate	TG, TC, HDL-c,	No significant change in lipid parameters
			20			Diabetes patients	240 mg/day	LDL-c
			20			Diabetes patients	240 mg/day	LDL-c
Shah et al. 43] 1988; India	R, P	1 month	10	Males	31–70	Ischaemic Heart	ZnSO4	TC, TG, α- and	Significant reduction in TC, β-lipoprotein. Increase in α-lipoprotein. No change in TG
			10			Disease patients	600 mg/day ^a	β-lipoprotein
			10			Disease patients	600 mg/day ^a	β-lipoprotein
Thurnham et al. 55] 1988; Chiina	R, DB, P	13.5 months	610 ^b	Both	35–64	Healthy	Zn gluconate	TC	No significant change
Thurnham et al. 55] 1988; Chiina	R, DB, P	13.5 months	610 ^b	Both	35–64	Healthy	50 mg/d	TC	No significant change

ALA-α-linolenic acid, B-Single blinded, C-Cross over; CC-Case-control, DB-Double Blinded, F-female, HDL-c-High Density Lipoprotein-Cholesterol, LDL-c-Low Density Lipoprotein-Cholesterol, M-male, MVM- multivitamin/mineral, NM-Not Mentioned, O- Observational, P-Parallel, R-Randomized, TC-Total Cholesterol, TG-Triglycerides, Age presented as mean ± SD in years where data were available and as age range in other studies
^aDosage of formulation,; ^bNumber of participants in each group is not mentioned

Table 2. Jaded scale
Study	Randomised	Double blind	Withdrawals and drop outs	Randomisationmethod described and appropriate	Blinding method described and appropriate	Total
Afkhami-Ardekani et al., 2008	1	0	1	0	N/A	2
Age-Related Eye Disease Study Research Group, 2002	1	1	0	0	0	2
Black et al., 1988	1	1	1	0	0	3
Bogden et al., 1988	1	1	0	1	0	3
Boukaïba et al., 1993	1	1	1	0	0	3
Brewer et al., 1991	0	0	0	0	0	0
Chevalier et al., 2002	1	1	1	0	0	3
Crouse et al., 1984	1	1	1	0	0	3
Farvid et al., 2004	1	1	1	1	0	4
Federico at al., 2001	1	0	1	0	N/A	2
Feillet-Coudray et al., 2006	1	1	1	0	0	3
Foster et al., 2013	1	1	1	1	1	5
Freeland-Graves et al., 1982	1	1	0	0	0	2
Gatto et al., 1995	1	0	1	0	N/A	2
Gunasekara et al., 2011	1	0	1	1	0	3
Hashemipour et al., 2009	1	1	1	1	0	4
Hercberg et al., 2005	1	1	1	1	1	5
Hininger-Favier et al., 2007	1	1	1	1	1	5
Hooper et al., 1980	0	0	0	0	0	0
Kadhim et al., 2006	0	1	1	N/A	0	2
Khan et al., 2013	1	0	1	0	N/A	2
Kim et al., 2012	0	0	1	0	0	1
Li et al., 2010	1	1	1	1	0	4
Partida-Hernández et al., 2006	1	1	1	0	0	3
Payahoo et al., 2013	1	1	1	1	1	5
Rahimi-Ardabili et al., 2012	1	1	0	0	0	2
RangaRao et al., 1990	0	0	1	0	0	1
Roozbeh et al., 2009	1	1	1	0	1	4
Samman et al., 1988	1	1	1	0	0	3
Seet et al., 2011	1	0	1	0	N/A	2
Shah et al., 1988	1	0	1	0	N/A	2
Thurnham et al., 1988	1	1	0	0	0	2