Elevated circulating magnesium levels in patients with Parkinson’s disease: a meta-analysis

Figures & data

Figure 1 Meta-analysis flow diagram of the study search strategy.

Table 1 Characteristics of the included studies in this meta-analysis (arranged by publication time)

First author	Year	Country	Analysis method	Sample size		Magnesium concentration (mg/L)		Age (years)		Gender (% female)		Duration of disease
				PD	HC	PD	HC	PD	HC	PD	HC	PD
Serum
Schwab RS^Citation28	1964	USA	Colorimetry	75	34	20.9±2.8	20.7±1.9	NR	NR	NR	NR	NR
Luo PY^Citation50	1987	China	AAS	30	20	35.6±3.5	34.1±34.3	61.5±8.4	NR	30.0	NR	NR
Forte G^Citation24	2004	Italy	ICP-AES	26	13	19.2±1.8*	17.5±1.3	64.9±10.8	63.8±13.7	7.7	53.8	4.8±3.8
Hegde ML^Citation51	2004	India	ICP-AES	52	25	25.5±2.2	21.9±2.2	58.2±4.7	55.4±6.4	46.2	48.0	4.8±2.5
Forte G^Citation25	2005	Italy	ICP-AES	71	44	19.0±3.3*	17.2±1.8	65.5±9.4	51.9±4.0	25.4	25.0	4.6±4.5
Sanjay Pande MB^Citation52	2005	India	ICP-AES	50	25	25.5±2.2	21.8±2.2	NR	NR	NR	NR	NR
Bocca B^Citation26	2006	Italy	ICP-AES	91	18	31.7±4.7*	26.5±4.8	65.5±9.7	63.3±13.8	29.7	44.4	4.6±4.1
Alimonti A^Citation23	2007	Italy	ICP-AES	71	124	17.4±1.9	18.9±3.2	65.5±9.4	44.8±12.7	25.4	34.7	4.6±4.5
Gellein K^Citation22	2008	Norway	ICP-MS	19	99	20.7±2.5	21.4±3.0	61.9±9.5	NR	52.6	51.5	7.7±2.3
Ahmed SS^Citation53	2010	India	ICP-AES	45	42	20.1±0.4*	17.5±0.2	57.6±9.1	55.6±3.3	42.2	40.5	NR
Ogunrin AO^Citation54	2013	Nigeria	AAS	68	60	41.3±15.8*	25.0±11.2	65.7±7.3	61.5±8.3	32.4	36.7	NR
Sanyal J^Citation29	2016	India	AAS	250	280	20.4±1.2*	19.9±1.5	57.9±12.1	56.4±9.7	35.2	34.6	4.9±3.0
Blood
Barbeau A^Citation21	1963	USA	Colorimetry	28	20	15.8±2.2	22.5±4.9	NR	NR	NR	NR	NR
Forte G^Citation24	2004	Italy	ICP-AES	26	13	27.9±7.0*	24.0±2.4	64.9±10.8	63.8±13.7	7.7	53.8	4.8±3.8
Forte G^Citation25	2005	Italy	ICP-AES	71	44	31.4±4.7	40.2±5.0	65.5±9.4	51.9±4.0	25.4	25.0	4.6±4.5
Feng J^Citation55	2012	China	AAS	50	50	46.2±6.8	46.4±8.5	62.7±14.1	61.4±11.8	40.0	40.0	NR
CSF
Forte G^Citation24	2004	Italy	ICP-AES	26	13	20.9±2.0	21.2±3.2	64.9±10.8	63.8±13.7	7.7	53.8	4.8±3.8
Alimonti A^Citation56	2007	Italy	ICP-AES	42	20	23.7±4.3	21.9±3.5	64.5±10.7	66.2±14.7	14.3	15.0	4.9±4.3
Hozumi I^Citation57	2011	Japan	ICP-MS	20	15	31.6±3.6	29.6±6.5	NR	NR	55.0	60.0	NR
Sanyal J^Citation29	2016	India	AAS	50	60	25.3±3.4*	22.7±2.4	58.7±12.4	60.1±10.4	32.0	30.0	3.8±2.3
Maass F^Citation27	2018	Germany	ICP-OES	36	42	22.0±1.3*	21.0±1.2	67.0±11.0	65.5±13.1	50.0	42.9	5.0±5.5

Notes: P-value <0.05 was considered as statistical significance, mean ± SD.

* P<0.05.

Abbreviations: AAS, atomic absorption spectrometry; CSF, cerebrospinal fluid; HC, healthy control; ICP-AES, inductively coupled plasma-atomic emission spectrometer; ICP-MS, inductively coupled plasma-mass spectrometry; ICP-OES, inductively coupled plasma optical emission spectrometry; NR, not reported; PD, Parkinson’s disease.

Table 2 The subgroup analysis of studies reporting serum Mg levels in PD

Subgroup	No of studies	SMD (95% CI)	Test of SMD =0		Heterogeneity
			Z	P for Z	I^2 (%)	P for I^2
All studies	12	1.09 (0.52, 1.66)	3.76	0.000	95.6	0.000
Location
Asia	5	2.22 (0.82, 3.63)	3.10	0.002	97.6	0.000
Europe	5	0.37 (−0.32, 1.06)	1.06	0.289	91.6	0.000
America	1	0.08 (−0.33, 0.48)	0.38	0.705	–	–
Africa	1	1.18 (0.80, 1.55)	6.13	0.000	–	–
Analysis method
ICP-MS/ICP-AES	8	1.55 (0.54, 2.57)	2.99	0.003	97.0	0.000
AAS	3	0.55 (−0.04, 1.14)	1.84	0.066	88.2	0.000
Colorimetry	1	0.08 (−0.33, 0.48)	0.38	0.705	–	–

Abbreviations: AAS, atomic absorption spectrometry; ICP-AES, inductively coupled plasma-atomic emission spectrometer; ICP-MS, inductively coupled plasma-mass spectrometry; PD, Parkinson’s disease; SMD, standardized mean difference.

Figure 2 Forest plot of serum Mg levels between PD patients and HC subjects.

Notes: The horizontal lines represent 95% CI. The sizes of the shaded squares are proportional to study weight. Weights are from random-effects analysis.
Abbreviations: HC, healthy control; PD, Parkinson’s disease; SMD, standardized mean difference.

Table 3 The meta-regression of studies reporting serum Mg levels in PD

Covariates	Coefficients	95% CI	Std. Err.	P-value	Adj I^2 (%)
Duration (years)-PD	−0.28	−1.00, 0.43	0.28	0.357	−0.84
Mean age (years)-PD	−0.33	−0.83, 0.17	0.22	0.168	12.6
Female (%)-PD	0.04	−0.11, 0.20	2.31	0.530	−7.9

Abbreviations: PD, Parkinson’s disease; Std. Err., standard error.

Figure 3 Forest plot of peripheral blood Mg levels between PD patients and HC subjects.

Notes: The horizontal lines represent 95% CI. The sizes of the shaded squares are proportional to study weight. Weights are from random-effects analysis.
Abbreviations: HC, healthy control; PD, Parkinson’s disease; SMD, standardized mean difference.

Table 4 The subgroup analysis of studies reporting peripheral blood Mg levels in PD

Subgroup	No of studies	SMD (95% CI)	Test of SMD =0		Heterogeneity
			Z	P for Z	I^2 (%)	P for I^2
All studies	16	0.64 (0.10, 1.19)	2.32	0.020	96.2	0.000
Location
Asia	6	1.78 (0.70, 2.86)	3.25	0.001	97.2	0.000
Europe	8	−0.14 (−0.89, 0.62)	0.35	0.724	94.9	0.000
America	1	0.08 (−0.33, 0.48)	0.38	0.705	–	–
Africa	1	1.18 (0.80, 1.55)	6.13	0.000	–	–
Analysis method
ICP-MS/ICP-AES	10	1.13 (0.17, 2.09)	2.30	0.021	97.3	0.000
AAS	4	0.41 (−0.06, 0.89)	1.70	0.090	86.6	0.000
Colorimetry	2	−0.08 (−2.79, 1.04)	0.90	0.369	95.6	0.000

Abbreviations: AAS, atomic absorption spectrometry; ICP-AES, inductively coupled plasma-atomic emission spectrometer; ICP-MS, inductively coupled plasma-mass spectrometry; PD, Parkinson’s disease; SMD, standardized mean difference.

Table 5 The meta-regression of studies reporting peripheral blood Mg levels in PD

Covariates	Coefficients	95% CI	Std. Err.	P-value	Adj I^2 (%)
Duration (years)-PD	−0.15	−1.07, 0.78	0.39	0.717	−12.9
Mean age (years)-PD	−0.37	−0.78, 0.04	0.19	0.073	20.3
Female (%)-PD	0.04	−0.07, 0.15	0.05	0.466	−4.6

Abbreviations: PD, Parkinson’s disease; Std. Err., standard error.

Figure 4 Forest plot of CSF Mg levels between PD patients and HC subjects.

Notes: The horizontal lines represent 95% CI. The sizes of the shaded squares are proportional to study weight. Weights are from random-effects analysis.
Abbreviations: CSF, cerebrospinal fluid; HC, healthy control; PD, Parkinson’s disease; SMD, standardized mean difference.

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