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This report is designed to re-examine the use of our presently accepted normal laboratory levels for human serum zinc and copper and to suggest a technique, previously unreported in the literature, to more precisely understand the relationship of serum zinc and copper in health and disease. Data from a patient population of 95 and a healthy population of 115 who met certain criteria are compared.
A score or more published reports deal with the normal range for serum zinc and copper.
Table I summarizes available reports of normal serum zinc levels. The sample sizes range from as few as 6 subjects to a high of 200. The mean scores range from 84 to 120 mcg/dl and the spread about the mean, the standard deviation, from 2 to 22. The overall mean and standard deviation for the 547 reported subjects is approximately 104 ± 15 mcg/dl.
Table I–Reported “Normal” Serum Zinc Values
Table II outlines the available reports for normal serum copper. The sample sizes are in the same range as the zinc studies. The mean scores vary from 98 to 144 mcg/dl with standard deviation of 2 to 26. For the entire sample of 711 subjects, the mean and standard deviation is 117 ± 18 mcg/dl.
Table II–Reported “Normal” Serum Copper Values
Of significance in past studies is what appears to be rather imprecise and arbitrary methods for the selection of “normal” subjects.
Finally, as far as we can ascertain, there is not one published study purporting to investigate the optimal copper/zinc ratio.
Materials and Methods
Two hundred and ten persons participated in this present study. One group of subjects consisted of 95 patients who appeared in a private medical practice for the treatment of a variety of complaints ordinarily considered to be psychosomatic. They are referred to in this report as the “patient population.” Each patient completed an extensive medical history including a review of systems which consisted of 37 questions requiring a positive or negative response. The questions were so structured that a positive response could be medically significant. Each patient, after a 10 to 14-hour fast, also underwent a comprehensive battery of biochemical tests. Included in this series of tests were serum copper and zinc determinations.
The other group of participants consisted of 115 persons who were recruited by means of brief newspaper articles, television news coverage and by word of mouth. The criteria used were to: (1) be within 10% of ideal body weight (Metropolitan Life Insurance Tables), (2) have not smoked cigarettes in the past three years, (3) consume less than three ounces of alcohol per week, (4) engage in an exercise program involving some form of active body movement for at least 20 minutes three times per week, (5) eat three meals per day in a regular pattern including breakfast, (6) sleep six to eight hours in each 24-hour period, (7) not have seen a physician for the purpose of treating an illness within the prior 12 months, (8) not have taken any form of medication, including antibiotics, birth control pills or hormones for one year, or antihistamines for two weeks. This group is referred to in this report as the “healthy people population.” Each healthy person completed the same medical history, including review of systems, as did the patient population. After a 10 to 14-hour fast, each healthy person underwent the same battery of biochemical tests as did the patients.
All healthy participants in the time period were processed in a similar manner to the patients in regard to testing, time of fast, body position and use of tourniquet. Serum copper and zinc were determined. These tests were performed at the Bio Center Laboratory, Wichita, Kansas, which is certified by HHS. Statistical tools employed in the evaluation of data include student’s t-test and the F-distribution.17
As a result of these studies, the following three questions will be considered:
- Were there significant differences in the serum copper and/or zinc values in the “patient” versus the “healthy people” populations?
- Were there significant differences in the copper/zinc ratios in these two groups of subjects?
- Can philosophic or practical conclusions be drawn from these subsets of data on serum copper, zinc and their ratios?
A number of points deserve special mention. First, the evidence is clear that there were no significant differences between the mean ages (P>0.5000) and variances (P>0.2300) of the patient sample (43.4 years) and the mean age of the healthy people group (44.3 years), (Table III).
Table III–Relationship of Clinical State (Review of Systems) Versus Biochemical State (Blood Copper) in Patient Versus Healthy People Population
* statistically significant difference
The number of patient “complaints” on the review of systems (ROS) are more than twice (11.7 versus 5.2) those of the healthy people group. In this instance, (Table III), there exists not only statistically significant differences of the means (P<0.0010), but also of the variances (P<0.0050).
Finally, and most importantly, the serum copper levels are significantly higher on statistical analyses in the patient population than in the healthy people population (137 versus 110 mcg/dl, P<0.0010). It is important to emphasize that the variance is also significantly different (P<0.0005) in these two groups (43 versus 25 mcq/dl).
Table IV–Relationship of Clinical State (Review of Systems) Versus Biochemical State (Blood Zinc) in Patient Versus Healthy People Populations
* statistically significant difference
Serum zinc levels, (Table IV), show the same findings for the age and the review of systems. However, the mean serum zinc levels are not significantly different (P>0.5000) while the variances are (P<0.0100).
Finally, Table V summarizes the relationships of the serum copper/zinc ratio. Means (1.46 versus 1.12) are highly significant (P<0.0010) as are the variances (0.56 versus 0.24).
Table V–Relationship of Clinical State (Review of Systems) Versus Biochemical State (Copper/Zinc Ratio) in Patient Versus Healthy People Populations
* statistically significant difference
Question One: Are there significant differences in the serum copper and zinc values in the “patient” versus the “healthy people” samples? Three points can be made: First, utilizing the review of systems as a measure of clinical health, the evidence is clear that the number of “complaints” in the “healthy people” population is approximately one-half that observed in the patient sample. Also, there are differences in the serum zinc and copper between the two groups. Specifically, both the means and the variances are higher with respect to copper while only the variances are different with respect to zinc.
Question Two: Are there significant differences in the serum copper and zinc ratios in the “patient” versus the “healthy people” samples? Table V summarizes the ratio data. Two points are evident. First, there is a statistically significant difference of the mean (1.46 versus 1.12, P<0.0010) and of the variances (0.56 versus 0.24, P<0.0005). Second, a comparison of these differences in ratio versus those for copper and zinc independently indicates that the patient and healthy people groups are more sharply delineated in the ratio value.
Question Three: Can philosophic or practical conclusions be drawn from these subsets of data on serum copper, zinc and their ratios? Three points warrant special consideration. The general body of information (Table I) shows that utilizing imprecise techniques for selecting normal subjects, a serum zinc level of 104 ± 15 mcg/dl was found. Our studies, utilizing what we believe to be less arbitrary specifications, reveal a result of 100 ± 20 mcg/dl. When one considers the problem of quality control, there seems to be little difference between our observations and those generally reported by others.
The literature consensus for normal serum copper (Table II) is 117 ± 18 mcg/dl; our findings (Table III) 110 ± 25 mcg/dl. Once again, in light of expected laboratory differences, the findings are strikingly similar.
There are several reports suggesting the possible diagnostic utility, and even preference, of copper/zinc ratio versus absolute copper and zinc scores in disease states particularly in malignant syndromes12,13,14,18 and in cardiovascular disorders.19,20 As far as we have been able to determine, no one has offered.a ratio or even a range for a ratio specific for any particular disease state or group of syndromes. No one has suggested an “ideal” copper/zinc ratio. According to our findings, the serum copper/zinc ratio is approximately 1.46 ± 0.56 in nonspecific disease states and approximately 1.12 ± 0.24 in nonpatients meeting specific criteria for health.
These findings suggest a possible direction for future research in the realm of trace mineral metabolism.
Within the limits of this study, it is clear that, utilizing a less arbitrary method of establishing normality (meaning healthy and not average) that the optimal limits for fasting serum zinc and copper and their ratio is more restricted than generally held.
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