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

Disclosures

Nutr Metab. 2015;12(26) 

In This Article

Results

Literature Search

Literature search was done according to the above search criteria and the search strategy is summarized in Fig. 1. The number of articles identified initially from the different databases were as follows; PubMed (n = 995), Web of Science (n = 802), SciVerse Scopus (n = 549). Five additional articles were identified by manual searching the reference lists of included studies. After removal of duplicates and screening of studies by reading the title, abstract and finally the full text, 32 studies were eligible to be included in systematic review. Descriptions of included studies are presented in Table 1 . Only 24 studies were included in Meta analysis and the reasons for exclusion of 8 studies[48–55] are also mentioned in Fig. 1.

Figure 1.

Summarized search strategy

Description of the Studies and Quality Assessment

Studies that were included in the meta-analysis are English-language, human, controlled trials. Out of the total of 33 Zinc interventions included in meta-analysis, 26 interventions[17–19,21–23,26,27,33,35–43] investigated the effects of Zinc supplementation alone on plasma lipids while other 7 interventions investigated the effect of supplementation of Zinc together with other vitamins and/or minerals. Duration of Zinc supplementation ranged from 1 month to 6.5 months with the exception of one long term study in which Zinc was supplemented for 7.5 years.[44] The dose of elemental Zinc supplemented in these interventions ranged from 15–240 mg/day (average dose of elemental Zinc per intervention: 39.3 mg/day). A variety of Zinc anions were used, including sulfate,[17–19,22,27,33,34,38,39,42,43,46] gluconate[21,23,26,35,36,40,41] and acetate[20,37] or undefined.[28,44,45]

In total, 14,515 participants were assigned to a Zinc intervention or control group. The age range of participants was 19–106 years except one study which was done in children aged 6–10 years. Out of 24 studies, 7 studies (16 interventions) involved healthy participants. Of the remaining trials, 8 studies were undertaken in those with type 2 Diabetes, 4 studies in obese individuals, 3 studies in subjects with end stage renal failure undergoing haemodialysis, 1 study in gut cancer patients and 1 study in patients with Ischemic heart disease. The mean jaded scale score for all trials included in meta-analysis was 3.13, out of a maximum score of 5 and 16 out of 24 studies scored ≥ 3 marks ( Table 2 ). Two studies that scored zero points were excluded from the meta-analysis due to poor methodological quality (Fig. 1).[49,52]

Effect Zinc Supplementation on Total Cholesterol

Effect of Zinc supplementation on total cholesterol concentration was studied in all 24 studies (33 interventions, n = 14515)[17–23,26–28,33–46] included in the meta-analysis. There was a statistically significant reduction in TC concentration in the Zinc supplemented group. The pooled mean difference for TC between Zinc supplemented and placebo groups from random effects analysis was −10.92 mg/dl (95 % CI: −15.33, − 6.52; p < 0.0001). However statistical heterogeneity as indicated by I 2 = 83 % (p < 0.05) of the data prevents the evaluation of a pooled estimate for TC (Fig. 2 (I)). In the subgroup-analyses, the group of interventions (26 interventions, n = 1528) in which Zinc was supplemented alone demonstrated a similar, statistically significant reduction in TC concentration in comparison to control groups. The pooled mean difference for TC between Zinc supplemented and placebo groups from random effect analysis was −10.72 mg/dl (95 % CI: −19.01, −1.32; p <0.05) (Fig. 3(I)) and statistical heterogeneity as indicated by I 2 = 80 % (p < 0.05). When studies were grouped by health status, reduction in TC in comparison to control groups was statistically significant and was greater in magnitude (−17.02 mg/dl [95 % CI: −30.52, −3.52; p < 0.05,I 2 = 87, p < 0.05]) among non-healthy participants (18 interventions, n = 866) (Fig. 4 (I)). Zinc supplementation among healthy participants (15 interventions, n = 13,650) demonstrated minor but statistically significant reduction in TC (−1.22 mg/dl [95 % CI: −2.17, −0.26; p < 0.05,I 2 = 0, p >0.05]) (Fig. 5(I)).

Figure 2 (I).

Forest plots showing effect of Zinc supplementation on; (I) Total cholesterol, (II) HDL cholesterol, (III) LDL cholesterol, (IV) Triglycerides. a- female, (b)- male, (c)- Zinc supplementation 15 mg/day, (d)- Zinc supplementation 30 mg/day, (e)- Zinc supplementation 50 mg/day, (f)- Zinc supplementation 75 mg/day, (g)- Zinc supplementation 100 mg/day, (h)- reference group, (i)- Lean group, (j)- Sedentary males, (k)- Trained malesFig. 3. Forest plots showing effect of Zinc supplementation alone (sub-analysis) on; (I) Total cholesterol, (II) HDL cholesterol, (III) LDL cholesterol, IV Triglycerides. (a)- female, (b)- male, (c)- Zinc supplementation 15 mg/day, (d)- Zinc supplementation 30 mg/day, (e)- Zinc supplementation 50 mg/day, (f)- Zinc supplementation 75 mg/day, (g)- Zinc supplementation 100 mg/day, (h)- reference group, (i)- Lean group, (j)- Sedentary males, (k)- Trained malesFig. 4. Forest plots showing effect of Zinc supplementation in non-healthy participants on; (I) Total cholesterol, (II) HDL cholesterol, (III) LDL cholesterol, (IV) TriglyceridesFig. 5. Forest plots showing effect of Zinc supplementation in healthy participants on; (I) Total cholesterol, (II) HDL cholesterol, (III) LDL cholesterol, (IV) Triglycerides

Figure 2 (II).

Forest plots showing effect of Zinc supplementation on; (I) Total cholesterol, (II) HDL cholesterol, (III) LDL cholesterol, (IV) Triglycerides. a- female, (b)- male, (c)- Zinc supplementation 15 mg/day, (d)- Zinc supplementation 30 mg/day, (e)- Zinc supplementation 50 mg/day, (f)- Zinc supplementation 75 mg/day, (g)- Zinc supplementation 100 mg/day, (h)- reference group, (i)- Lean group, (j)- Sedentary males, (k)- Trained malesFig. 3. Forest plots showing effect of Zinc supplementation alone (sub-analysis) on; (I) Total cholesterol, (II) HDL cholesterol, (III) LDL cholesterol, IV Triglycerides. (a)- female, (b)- male, (c)- Zinc supplementation 15 mg/day, (d)- Zinc supplementation 30 mg/day, (e)- Zinc supplementation 50 mg/day, (f)- Zinc supplementation 75 mg/day, (g)- Zinc supplementation 100 mg/day, (h)- reference group, (i)- Lean group, (j)- Sedentary males, (k)- Trained malesFig. 4. Forest plots showing effect of Zinc supplementation in non-healthy participants on; (I) Total cholesterol, (II) HDL cholesterol, (III) LDL cholesterol, (IV) TriglyceridesFig. 5. Forest plots showing effect of Zinc supplementation in healthy participants on; (I) Total cholesterol, (II) HDL cholesterol, (III) LDL cholesterol, (IV) Triglycerides

Figure 2 (III).

Forest plots showing effect of Zinc supplementation on; (I) Total cholesterol, (II) HDL cholesterol, (III) LDL cholesterol, (IV) Triglycerides. a- female, (b)- male, (c)- Zinc supplementation 15 mg/day, (d)- Zinc supplementation 30 mg/day, (e)- Zinc supplementation 50 mg/day, (f)- Zinc supplementation 75 mg/day, (g)- Zinc supplementation 100 mg/day, (h)- reference group, (i)- Lean group, (j)- Sedentary males, (k)- Trained malesFig. 3. Forest plots showing effect of Zinc supplementation alone (sub-analysis) on; (I) Total cholesterol, (II) HDL cholesterol, (III) LDL cholesterol, IV Triglycerides. (a)- female, (b)- male, (c)- Zinc supplementation 15 mg/day, (d)- Zinc supplementation 30 mg/day, (e)- Zinc supplementation 50 mg/day, (f)- Zinc supplementation 75 mg/day, (g)- Zinc supplementation 100 mg/day, (h)- reference group, (i)- Lean group, (j)- Sedentary males, (k)- Trained malesFig. 4. Forest plots showing effect of Zinc supplementation in non-healthy participants on; (I) Total cholesterol, (II) HDL cholesterol, (III) LDL cholesterol, (IV) TriglyceridesFig. 5. Forest plots showing effect of Zinc supplementation in healthy participants on; (I) Total cholesterol, (II) HDL cholesterol, (III) LDL cholesterol, (IV) Triglycerides

Figure 2 (IV).

Forest plots showing effect of Zinc supplementation on; (I) Total cholesterol, (II) HDL cholesterol, (III) LDL cholesterol, (IV) Triglycerides. a- female, (b)- male, (c)- Zinc supplementation 15 mg/day, (d)- Zinc supplementation 30 mg/day, (e)- Zinc supplementation 50 mg/day, (f)- Zinc supplementation 75 mg/day, (g)- Zinc supplementation 100 mg/day, (h)- reference group, (i)- Lean group, (j)- Sedentary males, (k)- Trained malesFig. 3. Forest plots showing effect of Zinc supplementation alone (sub-analysis) on; (I) Total cholesterol, (II) HDL cholesterol, (III) LDL cholesterol, IV Triglycerides. (a)- female, (b)- male, (c)- Zinc supplementation 15 mg/day, (d)- Zinc supplementation 30 mg/day, (e)- Zinc supplementation 50 mg/day, (f)- Zinc supplementation 75 mg/day, (g)- Zinc supplementation 100 mg/day, (h)- reference group, (i)- Lean group, (j)- Sedentary males, (k)- Trained malesFig. 4. Forest plots showing effect of Zinc supplementation in non-healthy participants on; (I) Total cholesterol, (II) HDL cholesterol, (III) LDL cholesterol, (IV) TriglyceridesFig. 5. Forest plots showing effect of Zinc supplementation in healthy participants on; (I) Total cholesterol, (II) HDL cholesterol, (III) LDL cholesterol, (IV) Triglycerides

Figure 3 (I).

Forest plots showing effect of Zinc supplementation alone (sub-analysis) on; (I) Total cholesterol, (II) HDL cholesterol, (III) LDL cholesterol, IV Triglycerides. (a)- female, (b)- male, (c)- Zinc supplementation 15 mg/day, (d)- Zinc supplementation 30 mg/day, (e)- Zinc supplementation 50 mg/day, (f)- Zinc supplementation 75 mg/day, (g)- Zinc supplementation 100 mg/day, (h)- reference group, (i)- Lean group, (j)- Sedentary males, (k)- Trained males

Figure 3 (II).

Forest plots showing effect of Zinc supplementation alone (sub-analysis) on; (I) Total cholesterol, (II) HDL cholesterol, (III) LDL cholesterol, IV Triglycerides. (a)- female, (b)- male, (c)- Zinc supplementation 15 mg/day, (d)- Zinc supplementation 30 mg/day, (e)- Zinc supplementation 50 mg/day, (f)- Zinc supplementation 75 mg/day, (g)- Zinc supplementation 100 mg/day, (h)- reference group, (i)- Lean group, (j)- Sedentary males, (k)- Trained males

Figure 3 (III).

Forest plots showing effect of Zinc supplementation alone (sub-analysis) on; (I) Total cholesterol, (II) HDL cholesterol, (III) LDL cholesterol, IV Triglycerides. (a)- female, (b)- male, (c)- Zinc supplementation 15 mg/day, (d)- Zinc supplementation 30 mg/day, (e)- Zinc supplementation 50 mg/day, (f)- Zinc supplementation 75 mg/day, (g)- Zinc supplementation 100 mg/day, (h)- reference group, (i)- Lean group, (j)- Sedentary males, (k)- Trained males

Figure 3 (IV).

Forest plots showing effect of Zinc supplementation alone (sub-analysis) on; (I) Total cholesterol, (II) HDL cholesterol, (III) LDL cholesterol, IV Triglycerides. (a)- female, (b)- male, (c)- Zinc supplementation 15 mg/day, (d)- Zinc supplementation 30 mg/day, (e)- Zinc supplementation 50 mg/day, (f)- Zinc supplementation 75 mg/day, (g)- Zinc supplementation 100 mg/day, (h)- reference group, (i)- Lean group, (j)- Sedentary males, (k)- Trained males

Figure 4 (I).

Forest plots showing effect of Zinc supplementation in non-healthy participants on; (I) Total cholesterol, (II) HDL cholesterol, (III) LDL cholesterol, (IV) Triglycerides

Figure 4 (II).

Forest plots showing effect of Zinc supplementation in non-healthy participants on; (I) Total cholesterol, (II) HDL cholesterol, (III) LDL cholesterol, (IV) Triglycerides

Figure 4 (III).

Forest plots showing effect of Zinc supplementation in non-healthy participants on; (I) Total cholesterol, (II) HDL cholesterol, (III) LDL cholesterol, (IV) Triglycerides

Figure 4 (IV).

Forest plots showing effect of Zinc supplementation in non-healthy participants on; (I) Total cholesterol, (II) HDL cholesterol, (III) LDL cholesterol, (IV) Triglycerides

Figure 5 (I).

Forest plots showing effect of Zinc supplementation in healthy participants on; (I) Total cholesterol, (II) HDL cholesterol, (III) LDL cholesterol, (IV) Triglycerides

Figure 5 (II).

Forest plots showing effect of Zinc supplementation in healthy participants on; (I) Total cholesterol, (II) HDL cholesterol, (III) LDL cholesterol, (IV) Triglycerides

Figure 5 (III).

Forest plots showing effect of Zinc supplementation in healthy participants on; (I) Total cholesterol, (II) HDL cholesterol, (III) LDL cholesterol, (IV) Triglycerides

Figure 5 (IV).

Forest plots showing effect of Zinc supplementation in healthy participants on; (I) Total cholesterol, (II) HDL cholesterol, (III) LDL cholesterol, (IV) Triglycerides

Effect of Zinc Supplementation on HDL Cholesterol

Twenty one studies (29 interventions, n = 1,694)[17–23,26–28,33–42,46] explored the effect of Zinc supplementation on HDL cholesterol. The forest plot for overall analysis of HDL cholesterol (Fig. 2(II)) shows the pooled mean difference for HDL cholesterol between Zinc supplemented and placebo groups from random effect analysis was 2.12 mg/dl (95 % CI: −0.74, 4.98; p = 0.15) and statistical heterogeneity as indicated by I 2 = 83 % (p < 0.05). Also the group of interventions (25 interventions, n = 1,508) employing Zinc supplementation alone did not demonstrate a statistically significant increase in HDL-c levels (+0.73 mg/dl, 95 % CI: −2.30, 3.75, p = 0.64) in subgroup-analysis (Fig. 3(II)). However, as Fig. 4(II) illustrates Zinc supplementation among non-healthy participants (16 interventions, n = 785) demonstrated a considerable and statistically significant increase in HDL-c (+6.15 mg/dl [95 % CI: 2.38, 9.92; p < 0.05,I 2 = 85, p < 0.05]). In contrast to this Zinc supplementation in healthy participants (13 interventions, n = 909) demonstrated a significant reduction in HDL-c (−3 mg/dl [95 % CI: −5.91, 0.10; p < 0.05,I 2 = 45, p < 0.05]) (Fig. 5 (II)).

Effect of Zinc Supplementation on LDL Cholesterol

There were 17 studies[17–20,22,23,26–28,33–35,39–42,46] (23 interventions, n = 1,455) in which the effect of Zinc supplementation on LDL cholesterol was studied. Forest plot for LDL-c (Fig. 2(III)) shows there is a statistically significant reduction in LDL-c in Zinc supplemented group. The pooled mean difference for LDL-c between Zinc supplemented and placebo group from random effect analysis was −6.87 mg/dl (95 % CI: −11.16, −2.58; p < 0.001) and the statistical heterogeneity of the data as indicated by I 2 = 31 was insignificant (p = 0.08). Forest plot for subgroup analysis (Fig. 3(III)) of LDL-c shows the pooled mean difference for LDL-c between Zinc alone supplemented group and placebo groups from random effect analysis was −4.78 mg/dl (95 % CI: −9.14, −0.43; p < 0.05) and the statistically heterogeneity was I 2 = 24 (p = 0.17). When the interventions done in non- healthy participants (14 interventions, n = 725) were grouped together, Zinc supplementation demonstrated a significant reduction in LDL-c (−11.25 mg/dl [95 % CI: −16.06, −6.44; p < 0.05,I 2 = 15, p > 0.05]) and the magnitude of reduction was greater than that in overall ungrouped analysis (Fig. 4 (III)). In contrast to this, Zinc supplementation in healthy participants (9 interventions, n = 730) demonstrated a smaller and insignificant increase in LDL-c (+1.12 mg/dl [95 % CI: −3.93, 6.16; p > 0.05,I 2 = 0, p > 0.05]) (Fig. 5 (III)).

Effect of Zinc Supplementation on Triglycerides

Effect of Zinc supplementation on Triglyceride concentration was studied in 19 studies (25 interventions, n = 1,503)[17–23,26–28,33–35,39–43,46] included in meta analysis. There was a statistically significant reduction in triglyceride concentration in Zinc supplemented group. The pooled mean difference for triglyceride between Zinc supplemented and placebo groups from random effects analysis was −10.92 mg/dl (95 % CI: −18.56, − 3.28; p < 0.01) in the presence of statistical heterogeneity of the data as indicated by I 2 = 69 % (p < 0.0001) (Fig. 2(IV)). Also sub-analysis of the group of interventions in which Zinc was supplemented alone (21 interventions, n = 1,317) demonstrated statistically significant reduction in TG levels in Zinc supplemented groups in comparison to their controls (−8.73 mg/dl, 95 % CI: −16.29,-1.17, p < 0.05) and statistical heterogeneity as indicated by I 2 = 64 % (p < 0.0001) (Fig. 3 (IV)). As Fig. 4 (IV) illustrates Zinc supplementation in non-healthy participants (16 interventions, n = 773) demonstrated a significant reduction in TG levels which was greater in magnitude than that in ungrouped analysis (−17.59 mg/dl [95 % CI: −28.80, −6.39; p < 0.05,I 2 = 77, p < 0.05]). However, Zinc supplementation in healthy participants (9 interventions, n = 730) did not demonstrate a significant reduction in TG levels (−2.97 mg/dl [95 % CI: −9.75, 3.81; p > 0.05,I 2 = 0, p > 0.05]) (Fig. 5 (IV)).

Other Significant Effects

Gunasekara, et al. reported a significant reduction in Total cholesterol/HDL ratio from 3.39 to 3.21 (p < 0.05) after Zinc supplementation.[46] Although not statistically significant, a study carried out by Brewer, et al. also reported reduction of this ratio after Zn supplementation in newly diagnosed female patients with Wilson's disease and patients who had received anti copper therapy (both genders).[49] Zinc supplementation has shown significant reduction in VLDL cholesterol concentration in few studies.[19,36] Studies have shown Zinc supplementation results in cholesterol to shift from HDL3 to HDL2 causing an increase in HDL2/HDL3 ratio.[51,54]

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