Reaction products of sodium glucoheptonate with zinc sulfate and sodium hydroxide

Exposure related observations in humans: other data

Administrative data

Endpoint:

exposure-related observations in humans: other data

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

2000

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

Changes in dietary zinc and copper affect zinc-status indicators of postmenopausal women, notably, extracellular superoxide dismutase and amyloid precursor proteins

Author:

Davis, C. D., Milne, D. B., and Nielsen, F. H.

Year:

2000

Bibliographic source:

Am J Clin Nutr 2000;71:781–8.

Materials and methods

Endpoint addressed:

repeated dose toxicity: oral

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Indicators of zinc status were measured in 25 healthy postmenopausal women aged 64.9 ± 6.7 y. After a 10-d equilibration period, volunteers consumed a diet with either a low (1 mg/d; n = 12) or a high (3 mg/d; n = 13) copper content based on a total energy content of 8.4 MJ. They received the same amount of copper throughout the study. Both groups were fed the basal diet (3 mg Zn/d) with no zinc supplement for one 90-d period, and the diet supplemented with 50 mg Zn/d for another 90-d period.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Bis(D-gluconato-O1,O2)zinc

EC Number:

224-736-9

EC Name:

Bis(D-gluconato-O1,O2)zinc

Cas Number:

4468-02-4

Molecular formula:

C12H22O14Zn

IUPAC Name:

zinc bis(2,3,4,5,6-pentahydroxyhexanoate) (non-preferred name)

Method

Ethical approval:

not specified

Details on study design:

Indicators of zinc status were measured in 25 healthy postmenopausal women aged 64.9 ± 6.7 y. After a 10-d equilibration period, volunteers consumed a diet with either a low (1 mg/d; n = 12) or a high (3 mg/d; n = 13) copper content based on a total energy content of 8.4 MJ. They received the same amount of copper throughout the study. Both groups were fed the basal diet (3 mg Zn/d) with no zinc supplement for one 90-d period, and the diet supplemented with 50 mg Zn/d for another 90-d period.

Details on exposure:

Subjects were fed a constant weighed basal diet of conventional foods that was low in copper (0.6 mg, 0.61 ± 0.07 mg by analysis) and zinc (3 mg, 2.96 ± 0.24 mg by analysis), based on an energy content of 8.4 MJ. The diet was supplemented with 492 mg Ca (as calcium carbonate), 23 mg Fe (as ferrous sulfate), 180 mg Mg (as magnesium gluconate), and 10 mg cholecalciferol. Iron was supplemented to compensate for losses through phlebotomy. The diet was adequate in all other known nutrients. The subjects participated in an equilibration period of 10 d in which they received the basal diet supplemented with 1.4 mg Cu (2 mg total) and 6 mg Zn (9 mg total). The women were then randomly divided into 2 groups: 1 group (n = 12) was fed the basal diet supplemented with 0.4 mg Cu and the other group (n = 13) was fed the basal diet supplemented with an additional 2.4 mg Cu/d. The remaining 190 d was divided into two 90-d dietary periods for both groups: the basal diet with no zinc supplement was fed for one 90-d period and the basal diet supplemented with 50 mg Zn/d was fed for the other 90-d period. All of the women were fed the low-zinc diet first. The two 90-d periods were separated by a second equilibration period of 10d, during which the basal diet supplemented with 1.4 mg Cu/d and 6 mg Zn/d was fed. Zinc was supplemented as zinc gluconate and copper was supplemented as cupric sulfate in beverages served at breakfast, lunch, and dinner. All other aspects of the diet remained constant throughout the study. All food was weighed and provided by the research center. Foods were weighed to an accuracy of 1% during preparation in the metabolic kitchen and eaten quantitatively by the subjects.

Results and discussion

Any other information on results incl. tables

Tab. 1: Effect of dietary zinc and copper on zinc-status indicator ¹

	equili-bration diet (n=23)	Low-copper diet (n=10)*		high-copper diet (n=12)
		Low zinc	High zinc	Low zinc	High zinc
		(3 mg)	(53 mg)	(3 mg)	(53 mg)	Pooled SD	P^2
Zinc concentrations
Plasma ((xmol/L)	13.1	13.4	18.1	14.8	18.0	1.66	0.0001
Platelet (nmol/10^9)	3.53	3.97	4.37	3.91	4.41	0.52	0.08
Erythrocyte ((xmol/L)	172	182	173	176	168	5.40	NS
Erythrocyte membrane (mmol/mg protein)	3.43	3.19	2.99	3.52	3.23	0.51	NS
Alkaline phosphatase
Plasma ((xkat/L)	1.57	1.56	1.65	1.54	1.63	0.09	NS
Bone specific ((xkat/L)	0.32	0.34	0.40	0.33	0.39	0.09	0.014
Erythrocyte membrane ([xkat/[xg protein)	2.30	1.29	2.36	2.45	1.99	0.44	NS
5' Nucleotidase
Plasma (U/L)	6.1	5.4	3.9	7.3	5.2	0.90	0.0001
Mononuclear (U/L)^3	18.7	12.4	13.0	11.9	22.9	7.27	0.015
Erythrocyte membrane (U/L)	13.2	15.2	16.3	15.1	14.5	3.37	NS
Superoxide dismutase
Extracellular (1000 U/L)^4	27.3	25.8	31.3	28.8	31.2	1.82	0.0001
Erythrocyte Cu/Zn (U/mg protein)	61.1	59.3	57.5	62.7	59.3	4.71	NS
Thyroid status
Free triiodothyronine (pmol/L)	4.71	4.17	4.56	4.27	4.56	0.61	0.07
Free thyroxine (pmol/L)	13.91	12.28	13.29	12.91	13.78	0.84	0.002
Thyroid stimulating hormone (mU/L)	2.44	2.33	2.22	2.16	1.97	0.26	0.07

^* Two of the volunteers fed low-copper diets were supplemented before the end of the 90-d dietary periods with dietary copper because of significant changes detected by the Holter electrocardiograph; these volunteers were not included in this statistical analysis

¹Values are the mean of 2 blood samples collected during the last month of each dietary period, except for plasma zinc, for which the values are the mean of 3 blood samples collected during the last month of each dietary zinc period. Equilibration diet (2.0 mg Cu and 9 mg Zn); low-copper diet (1 mg Cu); highcopper diet (3 mg Cu); low-zinc diet (3 mg Zn); high-zinc diet (53 mg Zn).

²Indicates differences between low and high dietary zinc by two-way ANOVA. No significant independent effects of copper were observed.

³ Significant zinc 3 copper interaction, P < 0.03.

4 Significant zinc 3 copper interaction, P < 0.01.

Applicant's summary and conclusion

Conclusions:

Zinc supplementation (50 mg zinc / day) significantly increased extracellular but not erythrocyte superoxide dismutase activity. This increase was more apparent when subjects were fed the low copper diet. Zinc supplementation in combination with the low copper diet significantly decreased amyloid precursor protein expression in platelets. Other indicators of zinc status that were significantly elevated after zinc supplementation were as follows: plasma zinc and free thyroxine concentrations and mononuclear 59-nucleotidase activity.

Executive summary:

Indicators of zinc status were measured in 25 healthy postmenopausal women aged 64.9 ± 6.7 y. After a 10-d equilibration period, volunteers consumed a diet with either a low (1 mg/d; n = 12) or a high (3 mg/d; n = 13) copper content based on a total energy content of 8.4 MJ. They received the same amount of copper throughout the study. Both groups were fed the basal diet (3 mg Zn/d) with no zinc supplement for one 90-d period, and the diet supplemented with 50 mg Zn/d for another 90-d period. Zinc supplementation (50 mg zinc / day) significantly increased extracellular but not erythrocyte superoxide dismutase activity. This increase was more apparent when subjects were fed the low copper diet. Zinc supplementation in combination with the low copper diet significantly decreased amyloid precursor protein expression in platelets. Other indicators of zinc status that were significantly elevated after zinc supplementation were as follows: plasma zinc and free thyroxine concentrations and mononuclear 59-nucleotidase activity.