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| Name | Class |
|---|---|
| DePuy Orthopaedics | INDUSTRY |
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The purpose of this study is to investigate steady-state cobalt levels following dietary supplementation for 90 days with 1 mg cobalt/day (as cobalt chloride in solution) in healthy adult volunteers.
Over the counter cobalt (Co) dietary supplements are available for sale in the United States, but little is known regarding their clinical effects and biokinetic distribution and body burden with long-term use. This study assessed blood kinetics, steady-state levels, biochemical responses, and clinical effects in five adult males and five adult females who voluntarily ingested approximately 1.0 mg Co/day of a commercially available Co supplement over a three month period. Volunteers were instructed to take the Co-dietary supplement in the morning according to the manufacturer's label. Blood samples were collected and analyzed for a number of biochemical parameters before, during, and after dosing. Hearing, vision, cardiac, and neurological functions were also assessed in volunteers before, during, and after dosing.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Study Volunteers | Volunteers (males and females) were instructed to take the cobalt dietary supplement in the morning according to the manufacturer's label, which suggested a serving of 1 mg cobalt (~2 mL) daily "in water or juice as maintenance." Dietary supplementation lasted for approximately three months. |
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| Measure | Description | Time Frame |
|---|---|---|
| Cobalt Whole Blood Concentrations | The cobalt concentration in whole blood and serum was determined one to two weeks pre-dosing and on the day of the first day of dosing before taking the supplement. Samples were also analyzed during the dosing period as follows: Day 4/5, Day 8/9, Day 14/16, Day 22/23, Day 29/30, Day 43/44, Day 57/58, Day 71/72, and Day 88/90. Cobalt concentration in whole blood and serum was also determined at one, two, six, ten and 16 weeks post-dosing. | Before, during and after cobalt supplementation |
| Cobalt Serum Concentrations | The cobalt concentration in whole blood and serum was determined one to two weeks pre-dosing and on the day of the first day of dosing before taking the supplement. Samples were also analyzed during the dosing period as follows: Day 4/5, Day 8/9, Day 14/16, Day 22/23, Day 29/30, Day 43/44, Day 57/58, Day 71/72, and Day 88/90. Cobalt concentration in whole blood and serum was also determined at one, two, six, ten and 16 weeks post-dosing. | Before, during and after cobalt supplementation |
| Measure | Description | Time Frame |
|---|---|---|
| Albumin Bound Cobalt Fraction in Serum | The fraction of albumin bound cobalt in serum was determined one to two weeks pre-dosing and on the day of the first dose before taking the supplement. Samples were also analyzed during the dosing period as follows: Day 4/5, Day 8/9, Day 14/16, Day 22/23, Day 29/30, Day 43/44, Day 57/58, Day 71/72, Day 88/90 and the fraction of albumin bound cobalt in serum was also determined at one and two weeks post-dosing. |
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Inclusion Criteria:
Exclusion Criteria:
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Healthy adult volunteers from work site and off work site
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| Name | Affiliation | Role |
|---|---|---|
| David Galbraith, MD | Cardno ChemRisk | Principal Investigator |
| David Galbraith, MD | Cardno ChemRisk | Study Director |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24500148 | Derived | Tvermoes BE, Unice KM, Paustenbach DJ, Finley BL, Otani JM, Galbraith DA. Effects and blood concentrations of cobalt after ingestion of 1 mg/d by human volunteers for 90 d. Am J Clin Nutr. 2014 Mar;99(3):632-46. doi: 10.3945/ajcn.113.071449. Epub 2014 Feb 5. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Study Volunteers | Volunteers (males and females) were instructed to take the cobalt dietary supplement in the morning according to the manufacturer's label, which suggested a serving of 1 mg cobalt (~2 mL) daily "in water or juice as maintenance." Dietary supplementation lasted for approximately three months. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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Our pair-wise comparisons had a power of 80% to detect a mean increase in RBC count of 0.34 million (sgma =0.2 million; n=5) and a mean increase of Hgb of 0.85 g/dL (sigma =0.5 g/dL; n=5), which are less than the minimum increases detected in the males that experienced polycythemia in Davis and Fields (1958).
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| ID | Title | Description |
|---|---|---|
| BG000 | Study Volunteers | Volunteers (males and females) were instructed to take the cobalt dietary supplement in the morning according to the manufacturer's label, which suggested a serving of 1 mg cobalt (~2 mL) daily "in water or juice as maintenance." Dietary supplementation lasted for approximately three months. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Secondary | Albumin Bound Cobalt Fraction in Serum | The fraction of albumin bound cobalt in serum was determined one to two weeks pre-dosing and on the day of the first dose before taking the supplement. Samples were also analyzed during the dosing period as follows: Day 4/5, Day 8/9, Day 14/16, Day 22/23, Day 29/30, Day 43/44, Day 57/58, Day 71/72, Day 88/90 and the fraction of albumin bound cobalt in serum was also determined at one and two weeks post-dosing. | Analysis was carried out on the first 12 participants of the study | Mean | Standard Deviation | percentage of total blood cobalt | Study volunteers will be followed for the duration of the study, an average of about 8 months for most volunteers |
|
During the study: 7-8 months (approximate length of the study)
Summary of self-reported adverse events
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Study Volunteers | Study volunteers (males and females) were instructed to take the cobalt dietary supplement in the morning according to the manufacturer's label, which suggested a serving of 1 mg cobalt (~2 mL) daily "in water or juice as maintenance." Dietary supplementation lasted for approximately three months. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Ear pain and tinnitus associated with sinusitis | General disorders | Non-systematic Assessment | The tinnitus persisted in the right ear throughout the remainder of the study and post-dosing period, but did not impact daily activities. At two months post-dosing, the volunteer still reported mild tinnitus on the side of his prior infection. |
The primary limitation of our study was its small sample size. We believe the study was sufficiently robust because we evaluated effects on hematologic and thyroid variables, both of which have been identified as sensitive markers of cobalt exposure.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. David Galbraith | Cardno | 415-618-3211 | david.galbraith@cardno.com |
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| ID | Term |
|---|---|
| D013959 | Thyroid Diseases |
| ID | Term |
|---|---|
| D004700 | Endocrine System Diseases |
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whole blood, serum and urine
| Study volunteers will be followed for the duration of the study, an average of about 8 months for most volunteers |
| Effects on the Immune System | Sensitivity to metals before and after cobalt supplementation was assessed by an in vitro lymphocyte transformation test (LTT) performed at week 0 and after three months of cobalt supplementation. The average proliferation rate for each metal treatment was normalized to individual proliferation rates of untreated control cells which generated a stimulation index (SI). According to the manufacture, the SI ranges from 0-15, with an SI from 2 to 4 indicated mild reactivity, from 5 to 8 indicated moderate reactivity, and >8 indicated high reactivity to the metal. The data is presented as the averaged normalized lymphocyte transformation response to each metal in men and women combined (n = 10). | 0 weeks and three months |
| Hemoglobin Levels After 1, 2 and 3 Months of Dosing | Blood chemistries assessed during the study included a lipid panel, comprehensive metabolic panel, creatine kinase-myocardial band, thyroid stimulating hormone, free thyroxine, and complete blood count with differential, total iron, and ferritin. Blood chemistries were assessed at one or two week pre-dose, pre-dose/ Day 1 before taking the supplement, Day 29/30, Day 57/58, Day 88/90 and one and two weeks post-dose. | Study volunteers were assessed before, during and after cobalt supplementation (2 wk post) |
| Changes in Audiological Function | Audiologic assessments including pure tone threshold determination at frequencies ranging from 250 to 16000 Hz were performed with volunteers serving as their own baseline controls for receptive changes during the study (i.e., week 0, ~day 45, ~day 90). Audiologic assessments including a pure-tone threshold determination at frequencies that ranged from 250 to 16000 Hz were performed with volunteers serving as their own baseline controls for receptive changes during the study. Decreases in hearing were considered clinically significant when one of the following 3 American Speech-Language-Hearing Association criteria were met: 1) a ≥20-dB decrease in the pure-tone threshold at one test frequency, 2) a ≥10-dB decrease at 2 adjacent test frequencies, or 3) the loss of 3 consecutive test frequencies where responses were previously obtained. | Baseline, at the study midpoint, and at the study completion |
| Changes in Cardiac Function | Two-dimensional and Doppler echocardiographic examinations were used to assess cardiac anatomy, structure, and function during the study with volunteers serving as their own baseline controls for changes during the study (i.e., week 0, ~day 45, ~day 90). | Baseline, at the study midpoint, and at the study completion |
| Changes in Visual Function | Ophthalmology studies included an assessment of visual acuity, slit lamp evaluations, and visual field testing. Retinal nerve fiber layer (RNFL) thickness and optic nerve head (ONH) were assessed using optical coherence tomography (OCT). Volunteers served as their own baseline controls for changes during the study (i.e., week 0, ~day 45, ~day 90). | Baseline, at the study midpoint, and at the study completion |
| Changes in Neurological Function (Peroneal Motor Amplitude) | Values of the sural sensory and peroneal motor variables. Volunteers served as their own baseline controls for changes during the study (i.e., week 0, ~day 45, ~day 90, and ~4-6 post-weeks). | Baseline, at the study midpoint, and at the study completion |
| White Blood Cell (WBC) Levels After 1, 2 and 3 Months of Cobalt Dietary Supplementation | Blood chemistries assessed during the study included a lipid panel, comprehensive metabolic panel, creatine kinase-myocardial band, thyroid stimulating hormone, free thyroxine, and complete blood count with differential, total iron, and ferritin. Blood chemistries were assessed at one or two week pre-dose, pre-dose/ Day 1 before taking the supplement, Day 29/30, Day 57/58, Day 88/90 and one and two weeks post-dose. | Study volunteers were assessed before, during and after cobalt supplementation (2 wk post) |
| Red Blood Cell (RBC) Levels After 1, 2 and 3 Months of Dosing | Blood chemistries assessed during the study included a lipid panel, comprehensive metabolic panel, creatine kinase-myocardial band, thyroid stimulating hormone, free thyroxine, and complete blood count with differential, total iron, and ferritin. Blood chemistries were assessed at one or two week pre-dose, pre-dose/ Day 1 before taking the supplement, Day 29/30, Day 57/58, Day 88/90 and one and two weeks post-dose. | Study volunteers were assessed before, during and after cobalt supplementation (2 wk post) |
| Hematocrit Levels After 1, 2 and 3 Months of Dosing | Blood chemistries assessed during the study included a lipid panel, comprehensive metabolic panel, creatine kinase-myocardial band, thyroid stimulating hormone, free thyroxine, and complete blood count with differential, total iron, and ferritin. Blood chemistries were assessed at one or two week pre-dose, pre-dose/ Day 1 before taking the supplement, Day 29/30, Day 57/58, Day 88/90 and one and two weeks post-dose. | Study volunteers were assessed before, during and after cobalt supplementation (2 wk post) |
| Protein Levels After 1, 2 and 3 Months of Dosing | Blood chemistries assessed during the study included a lipid panel, comprehensive metabolic panel, creatine kinase-myocardial band, thyroid stimulating hormone, free thyroxine, and complete blood count with differential, total iron, and ferritin. Blood chemistries were assessed at one or two week pre-dose, pre-dose/ Day 1 before taking the supplement, Day 29/30, Day 57/58, Day 88/90 and one and two weeks post-dose. | Study volunteers were assessed before, during and after cobalt supplementation (2 wk post) |
| Albumin Levels After 1, 2 and 3 Months of Dosing | Blood chemistries assessed during the study included a lipid panel, comprehensive metabolic panel, creatine kinase-myocardial band, thyroid stimulating hormone, free thyroxine, and complete blood count with differential, total iron, and ferritin. Blood chemistries were assessed at one or two week pre-dose, pre-dose/ Day 1 before taking the supplement, Day 29/30, Day 57/58, Day 88/90 and one and two weeks post-dose. | Study volunteers were assessed before, during and after cobalt supplementation (2 wk post) |
| Thyroid-Stimulating Hormone (TSH) Levels After 1, 2 and 3 Months of Dosing | Blood chemistries assessed during the study included a lipid panel, comprehensive metabolic panel, creatine kinase-myocardial band, thyroid stimulating hormone, free thyroxine, and complete blood count with differential, total iron, and ferritin. Blood chemistries were assessed at one or two week pre-dose, pre-dose/ Day 1 before taking the supplement, Day 29/30, Day 57/58, Day 88/90 and one and two weeks post-dose. | Study volunteers were assessed before, during and after cobalt supplementation (2 wk post) |
| T4 Levels After 1, 2 and 3 Months of Dosing | Blood chemistries assessed during the study included a lipid panel, comprehensive metabolic panel, creatine kinase-myocardial band, thyroid stimulating hormone, free thyroxine, and complete blood count with differential, total iron, and ferritin. Blood chemistries were assessed at one or two week pre-dose, pre-dose/ Day 1 before taking the supplement, Day 29/30, Day 57/58, Day 88/90 and one and two weeks post-dose. | Study volunteers were assessed before, during and after cobalt supplementation (2 wk post) |
| Total Iron Levels After 1, 2 and 3 Months of Dosing | Blood chemistries assessed during the study included a lipid panel, comprehensive metabolic panel, creatine kinase-myocardial band, thyroid stimulating hormone, free thyroxine, and complete blood count with differential, total iron, and ferritin. Blood chemistries were assessed at one or two week pre-dose, pre-dose/ Day 1 before taking the supplement, Day 29/30, Day 57/58, Day 88/90 and one and two weeks post-dose. | Study volunteers were assessed before, during and after cobalt supplementation (2 wk post) |
| Ferritin Levels After 1, 2 and 3 Months of Dosing | Blood chemistries assessed during the study included a lipid panel, comprehensive metabolic panel, creatine kinase-myocardial band, thyroid stimulating hormone, free thyroxine, and complete blood count with differential, total iron, and ferritin. Blood chemistries were assessed at one or two week pre-dose, pre-dose/ Day 1 before taking the supplement, Day 29/30, Day 57/58, Day 88/90 and one and two weeks post-dose. | Study volunteers were assessed before, during and after cobalt supplementation (2 wk post) |
| Creatine Creatine Kinase-Myocardial Band (CK-MB) Levels After 1, 2 and 3 Months of Dosing | Blood chemistries assessed during the study included a lipid panel, comprehensive metabolic panel, creatine kinase-myocardial band, thyroid stimulating hormone, free thyroxine, and complete blood count with differential, total iron, and ferritin. Blood chemistries were assessed at one or two week pre-dose, pre-dose/ Day 1 before taking the supplement, Day 29/30, Day 57/58, Day 88/90 and one and two weeks post-dose. | Study volunteers were assessed before, during and after cobalt supplementation (2 wk post) |
| Creatinine Levels After 1, 2 and 3 Months of Dosing | Blood chemistries assessed during the study included a lipid panel, comprehensive metabolic panel, creatine kinase-myocardial band, thyroid stimulating hormone, free thyroxine, and complete blood count with differential, total iron, and ferritin. Blood chemistries were assessed at one or two week pre-dose, pre-dose/ Day 1 before taking the supplement, Day 29/30, Day 57/58, Day 88/90 and one and two weeks post-dose. | Study volunteers were assessed before, during and after cobalt supplementation (2 wk post) |
| Alanine Aminotransferase (ALT) Levels After 1, 2 and 3 Months of Dosing | Blood chemistries assessed during the study included a lipid panel, comprehensive metabolic panel, creatine kinase-myocardial band, thyroid stimulating hormone, free thyroxine, and complete blood count with differential, total iron, and ferritin. Blood chemistries were assessed at one or two week pre-dose, pre-dose/ Day 1 before taking the supplement, Day 29/30, Day 57/58, Day 88/90 and one and two weeks post-dose. | Study volunteers were assessed before, during and after cobalt supplementation (2 wk post) |
| Aspartate Aminotransferase (AST) Levels After 1, 2 and 3 Months of Dosing | Blood chemistries assessed during the study included a lipid panel, comprehensive metabolic panel, creatine kinase-myocardial band, thyroid stimulating hormone, free thyroxine, and complete blood count with differential, total iron, and ferritin. Blood chemistries were assessed at one or two week pre-dose, pre-dose/ Day 1 before taking the supplement, Day 29/30, Day 57/58, Day 88/90 and one and two weeks post-dose. | Study volunteers were assessed before, during and after cobalt supplementation (2 wk post) |
| HDL Cholesterol Levels After 3 Months of Cobalt Supplementation | Blood chemistries assessed during the study included a lipid panel, comprehensive metabolic panel, creatine kinase-myocardial band, thyroid stimulating hormone, free thyroxine, and complete blood count with differential, total iron, and ferritin. HDL cholesterol levels were assessed before cobalt dietary supplementation and after three months of supplementation. | Study volunteers were assessed before and at the end of cobalt supplementation |
| Total Cholesterol Levels After 3 Months of Cobalt Supplementation | Blood chemistries assessed during the study included a lipid panel, comprehensive metabolic panel, creatine kinase-myocardial band, thyroid stimulating hormone, free thyroxine, and complete blood count with differential, total iron, and ferritin. Total cholesterol levels were assessed before cobalt dietary supplementation and after three months of supplementation. | Study volunteers were assessed before and at the end of cobalt supplementation |
| Triglyceride Levels After 3 Months of Cobalt Supplementation | Blood chemistries assessed during the study included a lipid panel, comprehensive metabolic panel, creatine kinase-myocardial band, thyroid stimulating hormone, free thyroxine, and complete blood count with differential, total iron, and ferritin. Triglyceride levels were assessed before cobalt dietary supplementation and after three months of supplementation. | Study volunteers were assessed before and at the end of cobalt supplementation |
| Glucose Levels After 1, 2 and 3 Months of Dosing | Blood chemistries assessed during the study included a lipid panel, comprehensive metabolic panel, creatine kinase-myocardial band, thyroid stimulating hormone, free thyroxine, and complete blood count with differential, total iron, and ferritin. Blood chemistries were assessed at one or two week pre-dose, pre-dose/ Day 1 before taking the supplement, Day 29/30, Day 57/58, Day 88/90 and one and two weeks post-dose. | Study volunteers were assessed before, during and after cobalt supplementation (2 wk post) |
| Cobalt Urine Concentrations | A 24 hr urine collection for cobalt analysis was performed at Day 14/16, Day 43/44 and Day 88/90. | During cobalt supplementation |
| Cobalt Urine Concentrations After Cessation of Cobalt Supplementation | A 24 hr urine collection for cobalt analysis was performed on three volunteers (two females and one male) at one, two, six and ten weeks post-dosing. The one male volunteer provided three consecutive 24-hr urine samples at the one and two week post-dosing time points; data for individual urine collections were averaged together to give an average one and two week post-dosing data concentration. | After cobalt supplementation |
| Changes in Cardiac Function (LVEF) | Two-dimensional and Doppler echocardiographic examinations were used to assess cardiac anatomy, structure, and function during the study with volunteers serving as their own baseline controls for changes during the study (i.e., week 0, ~day 45, ~day 90). | Baseline, at the study midpoint, and at the study completion |
| Changes in Cardiac Function (LA Volume Index) | Two-dimensional and Doppler echocardiographic examinations were used to assess cardiac anatomy, structure, and function during the study with volunteers serving as their own baseline controls for changes during the study (i.e., week 0, ~day 45, ~day 90). | Baseline, at the study midpoint, and at the study completion |
| Changes in Visual Function (Average RNFL Thickness) | Ophthalmology studies included an assessment of visual acuity, slit lamp evaluations, and visual field testing. Retinal nerve fiber layer (RNFL) thickness and optic nerve head (ONH) were assessed using optical coherence tomography (OCT). Volunteers served as their own baseline controls for changes during the study (i.e., week 0, ~day 45, ~day 90). | Baseline, at the study midpoint, and at the study completion |
| Changes in Visual Function (Average C:D Ratio) | Ophthalmology studies included an assessment of visual acuity, slit lamp evaluations, and visual field testing. Retinal nerve fiber layer (RNFL) thickness and optic nerve head (ONH) were assessed using optical coherence tomography (OCT). Volunteers served as their own baseline controls for changes during the study (i.e., week 0, ~day 45, ~day 90). | Baseline, at the study midpoint, and at the study completion |
| Changes in Visual Function (Cup Volume) | Ophthalmology studies included an assessment of visual acuity, slit lamp evaluations, and visual field testing. Retinal nerve fiber layer (RNFL) thickness and optic nerve head (ONH) were assessed using optical coherence tomography (OCT). Volunteers served as their own baseline controls for changes during the study (i.e., week 0, ~day 45, ~day 90). | Baseline, at the study midpoint, and at the study completion |
| Changes in Visual Function (VFI) | Ophthalmology studies included an assessment of visual acuity, slit lamp evaluations, and visual field testing. Retinal nerve fiber layer (RNFL) thickness and optic nerve head (ONH) were assessed using optical coherence tomography (OCT). Volunteers served as their own baseline controls for changes during the study (i.e., week 0, ~day 45, ~day 90). | Baseline, at the study midpoint, and at the study completion |
| Changes in Visual Function (Mean Deviation and PSD) | Ophthalmology studies included an assessment of visual acuity, slit lamp evaluations, and visual field testing. Retinal nerve fiber layer (RNFL) thickness and optic nerve head (ONH) were assessed using optical coherence tomography (OCT). Volunteers served as their own baseline controls for changes during the study (i.e., week 0, ~day 45, ~day 90). | Baseline, at the study midpoint, and at the study completion |
| Changes in Neurological Function (Sural Sensory Amplitude) | Values of the sural sensory and peroneal motor variables. Volunteers served as their own baseline controls for changes during the study (i.e., week 0, ~day 45, ~day 90, and ~4-6 post-weeks). | Baseline, at the study midpoint, and at the study completion |
| Changes in Neurological Function (Velocity) | Values of the sural sensory and peroneal motor variables. Volunteers served as their own baseline controls for changes during the study (i.e., week 0, ~day 45, ~day 90, and ~4-6 post-weeks). | Baseline, at the study midpoint, and at the study completion |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Weight | Mean | Standard Deviation | pounds (lbs) |
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| Secondary | Effects on the Immune System | Sensitivity to metals before and after cobalt supplementation was assessed by an in vitro lymphocyte transformation test (LTT) performed at week 0 and after three months of cobalt supplementation. The average proliferation rate for each metal treatment was normalized to individual proliferation rates of untreated control cells which generated a stimulation index (SI). According to the manufacture, the SI ranges from 0-15, with an SI from 2 to 4 indicated mild reactivity, from 5 to 8 indicated moderate reactivity, and >8 indicated high reactivity to the metal. The data is presented as the averaged normalized lymphocyte transformation response to each metal in men and women combined (n = 10). | Participants that completed three months of cobalt supplementation | Mean | Standard Deviation | units on a scale: stimulation index (SI) | 0 weeks and three months |
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| Secondary | Hemoglobin Levels After 1, 2 and 3 Months of Dosing | Blood chemistries assessed during the study included a lipid panel, comprehensive metabolic panel, creatine kinase-myocardial band, thyroid stimulating hormone, free thyroxine, and complete blood count with differential, total iron, and ferritin. Blood chemistries were assessed at one or two week pre-dose, pre-dose/ Day 1 before taking the supplement, Day 29/30, Day 57/58, Day 88/90 and one and two weeks post-dose. | Participants that completed three months of cobalt supplementation. Individual baseline values for the 1-wk predose draw and the day 1 (predose) draw were averaged together to give one baseline value. | Mean | Standard Deviation | g/dL | Study volunteers were assessed before, during and after cobalt supplementation (2 wk post) |
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| Secondary | Changes in Audiological Function | Audiologic assessments including pure tone threshold determination at frequencies ranging from 250 to 16000 Hz were performed with volunteers serving as their own baseline controls for receptive changes during the study (i.e., week 0, ~day 45, ~day 90). Audiologic assessments including a pure-tone threshold determination at frequencies that ranged from 250 to 16000 Hz were performed with volunteers serving as their own baseline controls for receptive changes during the study. Decreases in hearing were considered clinically significant when one of the following 3 American Speech-Language-Hearing Association criteria were met: 1) a ≥20-dB decrease in the pure-tone threshold at one test frequency, 2) a ≥10-dB decrease at 2 adjacent test frequencies, or 3) the loss of 3 consecutive test frequencies where responses were previously obtained. | Participants that completed three months of cobalt supplementation | Mean | Standard Deviation | dB | Baseline, at the study midpoint, and at the study completion |
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| Secondary | Changes in Cardiac Function | Two-dimensional and Doppler echocardiographic examinations were used to assess cardiac anatomy, structure, and function during the study with volunteers serving as their own baseline controls for changes during the study (i.e., week 0, ~day 45, ~day 90). | Participants that completed three months of cobalt supplementation | Mean | Standard Deviation | cm | Baseline, at the study midpoint, and at the study completion |
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| Secondary | Changes in Visual Function | Ophthalmology studies included an assessment of visual acuity, slit lamp evaluations, and visual field testing. Retinal nerve fiber layer (RNFL) thickness and optic nerve head (ONH) were assessed using optical coherence tomography (OCT). Volunteers served as their own baseline controls for changes during the study (i.e., week 0, ~day 45, ~day 90). | Participants that completed three months of cobalt supplementation | Mean | Standard Deviation | mm^2 | Baseline, at the study midpoint, and at the study completion |
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| Secondary | Changes in Neurological Function (Peroneal Motor Amplitude) | Values of the sural sensory and peroneal motor variables. Volunteers served as their own baseline controls for changes during the study (i.e., week 0, ~day 45, ~day 90, and ~4-6 post-weeks). | Participants that completed three months of cobalt supplementation | Mean | Standard Deviation | Peroneal Motor Amplitude (mV) | Baseline, at the study midpoint, and at the study completion |
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| Primary | Cobalt Whole Blood Concentrations | The cobalt concentration in whole blood and serum was determined one to two weeks pre-dosing and on the day of the first day of dosing before taking the supplement. Samples were also analyzed during the dosing period as follows: Day 4/5, Day 8/9, Day 14/16, Day 22/23, Day 29/30, Day 43/44, Day 57/58, Day 71/72, and Day 88/90. Cobalt concentration in whole blood and serum was also determined at one, two, six, ten and 16 weeks post-dosing. | Participants that completed three months of cobalt supplementation | Mean | Standard Deviation | µg Co/L | Before, during and after cobalt supplementation |
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| Secondary | White Blood Cell (WBC) Levels After 1, 2 and 3 Months of Cobalt Dietary Supplementation | Blood chemistries assessed during the study included a lipid panel, comprehensive metabolic panel, creatine kinase-myocardial band, thyroid stimulating hormone, free thyroxine, and complete blood count with differential, total iron, and ferritin. Blood chemistries were assessed at one or two week pre-dose, pre-dose/ Day 1 before taking the supplement, Day 29/30, Day 57/58, Day 88/90 and one and two weeks post-dose. | Participants that completed three months of cobalt supplementation. Individual baseline values for the 1-wk predose draw and the day 1 (predose) draw were averaged together to give one baseline value. | Mean | Standard Deviation | thousand cells/µL | Study volunteers were assessed before, during and after cobalt supplementation (2 wk post) |
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| Secondary | Red Blood Cell (RBC) Levels After 1, 2 and 3 Months of Dosing | Blood chemistries assessed during the study included a lipid panel, comprehensive metabolic panel, creatine kinase-myocardial band, thyroid stimulating hormone, free thyroxine, and complete blood count with differential, total iron, and ferritin. Blood chemistries were assessed at one or two week pre-dose, pre-dose/ Day 1 before taking the supplement, Day 29/30, Day 57/58, Day 88/90 and one and two weeks post-dose. | Participants that completed three months of cobalt supplementation. Individual male baseline values for the 1-wk predose draw and the day 1 (predose) draw were averaged together. For females, the average baseline is the 1-wk predose data only because there was a significant difference between the 1-wk predose draw and the day 1 (predose) draw. | Mean | Standard Deviation | million cells/µL | Study volunteers were assessed before, during and after cobalt supplementation (2 wk post) |
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| Secondary | Hematocrit Levels After 1, 2 and 3 Months of Dosing | Blood chemistries assessed during the study included a lipid panel, comprehensive metabolic panel, creatine kinase-myocardial band, thyroid stimulating hormone, free thyroxine, and complete blood count with differential, total iron, and ferritin. Blood chemistries were assessed at one or two week pre-dose, pre-dose/ Day 1 before taking the supplement, Day 29/30, Day 57/58, Day 88/90 and one and two weeks post-dose. | Participants that completed three months of cobalt supplementation. Individual baseline values for the 1-wk predose draw and the day 1 (predose) draw were averaged together to give one baseline value. | Mean | Standard Deviation | Percentage | Study volunteers were assessed before, during and after cobalt supplementation (2 wk post) |
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| Secondary | Protein Levels After 1, 2 and 3 Months of Dosing | Blood chemistries assessed during the study included a lipid panel, comprehensive metabolic panel, creatine kinase-myocardial band, thyroid stimulating hormone, free thyroxine, and complete blood count with differential, total iron, and ferritin. Blood chemistries were assessed at one or two week pre-dose, pre-dose/ Day 1 before taking the supplement, Day 29/30, Day 57/58, Day 88/90 and one and two weeks post-dose. | Participants that completed three months of cobalt supplementation. Individual baseline values for the 1-wk predose draw and the day 1 (predose) draw were averaged together to give one baseline value. | Mean | Standard Deviation | g/dL | Study volunteers were assessed before, during and after cobalt supplementation (2 wk post) |
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| Secondary | Albumin Levels After 1, 2 and 3 Months of Dosing | Blood chemistries assessed during the study included a lipid panel, comprehensive metabolic panel, creatine kinase-myocardial band, thyroid stimulating hormone, free thyroxine, and complete blood count with differential, total iron, and ferritin. Blood chemistries were assessed at one or two week pre-dose, pre-dose/ Day 1 before taking the supplement, Day 29/30, Day 57/58, Day 88/90 and one and two weeks post-dose. | Participants that completed three months of cobalt supplementation. Individual baseline values for the 1-wk predose draw and the day 1 (predose) draw were averaged together to give one baseline value. | Mean | Standard Deviation | g/dL | Study volunteers were assessed before, during and after cobalt supplementation (2 wk post) |
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| Secondary | Thyroid-Stimulating Hormone (TSH) Levels After 1, 2 and 3 Months of Dosing | Blood chemistries assessed during the study included a lipid panel, comprehensive metabolic panel, creatine kinase-myocardial band, thyroid stimulating hormone, free thyroxine, and complete blood count with differential, total iron, and ferritin. Blood chemistries were assessed at one or two week pre-dose, pre-dose/ Day 1 before taking the supplement, Day 29/30, Day 57/58, Day 88/90 and one and two weeks post-dose. | Participants that completed three months of cobalt supplementation. Individual baseline values for the 1-wk predose draw and the day 1 (predose) draw were averaged together to give one baseline value. | Mean | Standard Deviation | mIU/L | Study volunteers were assessed before, during and after cobalt supplementation (2 wk post) |
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| Secondary | T4 Levels After 1, 2 and 3 Months of Dosing | Blood chemistries assessed during the study included a lipid panel, comprehensive metabolic panel, creatine kinase-myocardial band, thyroid stimulating hormone, free thyroxine, and complete blood count with differential, total iron, and ferritin. Blood chemistries were assessed at one or two week pre-dose, pre-dose/ Day 1 before taking the supplement, Day 29/30, Day 57/58, Day 88/90 and one and two weeks post-dose. | Participants that completed three months of cobalt supplementation.Individual baseline values for the 1-wk predose draw and the day 1 (predose) draw were averaged together to give one baseline value. | Mean | Standard Deviation | ng/dL | Study volunteers were assessed before, during and after cobalt supplementation (2 wk post) |
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| Secondary | Total Iron Levels After 1, 2 and 3 Months of Dosing | Blood chemistries assessed during the study included a lipid panel, comprehensive metabolic panel, creatine kinase-myocardial band, thyroid stimulating hormone, free thyroxine, and complete blood count with differential, total iron, and ferritin. Blood chemistries were assessed at one or two week pre-dose, pre-dose/ Day 1 before taking the supplement, Day 29/30, Day 57/58, Day 88/90 and one and two weeks post-dose. | Participants that completed three months of cobalt supplementation. Individual baseline values for the 1-wk predose draw and the day 1 (predose) draw were averaged together to give one baseline value. | Mean | Standard Deviation | µg/dL | Study volunteers were assessed before, during and after cobalt supplementation (2 wk post) |
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| Secondary | Ferritin Levels After 1, 2 and 3 Months of Dosing | Blood chemistries assessed during the study included a lipid panel, comprehensive metabolic panel, creatine kinase-myocardial band, thyroid stimulating hormone, free thyroxine, and complete blood count with differential, total iron, and ferritin. Blood chemistries were assessed at one or two week pre-dose, pre-dose/ Day 1 before taking the supplement, Day 29/30, Day 57/58, Day 88/90 and one and two weeks post-dose. | Participants that completed three months of cobalt supplementation. Individual female baseline values for the 1-wk predose draw and the day 1 (predose) draw were averaged together. For males, the average baseline is the 1-wk predose data only because there was a significant difference between the 1-wk predose draw and the day 1 (predose) draw. | Mean | Standard Deviation | ng/mL | Study volunteers were assessed before, during and after cobalt supplementation (2 wk post) |
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| Secondary | Creatine Creatine Kinase-Myocardial Band (CK-MB) Levels After 1, 2 and 3 Months of Dosing | Blood chemistries assessed during the study included a lipid panel, comprehensive metabolic panel, creatine kinase-myocardial band, thyroid stimulating hormone, free thyroxine, and complete blood count with differential, total iron, and ferritin. Blood chemistries were assessed at one or two week pre-dose, pre-dose/ Day 1 before taking the supplement, Day 29/30, Day 57/58, Day 88/90 and one and two weeks post-dose. | Participants that completed three months of cobalt supplementation. Individual female baseline values for the 1-wk predose draw and the day 1 (predose) draw were averaged together. For males, the average baseline is the 1-wk predose data only because there was a significant difference between the 1-wk predose draw and the day 1 (predose) draw. | Mean | Standard Deviation | ng/mL | Study volunteers were assessed before, during and after cobalt supplementation (2 wk post) |
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| Secondary | Creatinine Levels After 1, 2 and 3 Months of Dosing | Blood chemistries assessed during the study included a lipid panel, comprehensive metabolic panel, creatine kinase-myocardial band, thyroid stimulating hormone, free thyroxine, and complete blood count with differential, total iron, and ferritin. Blood chemistries were assessed at one or two week pre-dose, pre-dose/ Day 1 before taking the supplement, Day 29/30, Day 57/58, Day 88/90 and one and two weeks post-dose. | Participants that completed three months of cobalt supplementation. Individual baseline values for the 1-wk predose draw and the day 1 (predose) draw were averaged together to give one baseline value. | Mean | Standard Deviation | mg/dL | Study volunteers were assessed before, during and after cobalt supplementation (2 wk post) |
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| Secondary | Alanine Aminotransferase (ALT) Levels After 1, 2 and 3 Months of Dosing | Blood chemistries assessed during the study included a lipid panel, comprehensive metabolic panel, creatine kinase-myocardial band, thyroid stimulating hormone, free thyroxine, and complete blood count with differential, total iron, and ferritin. Blood chemistries were assessed at one or two week pre-dose, pre-dose/ Day 1 before taking the supplement, Day 29/30, Day 57/58, Day 88/90 and one and two weeks post-dose. | Participants that completed three months of cobalt supplementation. Individual baseline values for the 1-wk predose draw and the day 1 (predose) draw were averaged together to give one baseline value. | Mean | Standard Deviation | U/L | Study volunteers were assessed before, during and after cobalt supplementation (2 wk post) |
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| Secondary | Aspartate Aminotransferase (AST) Levels After 1, 2 and 3 Months of Dosing | Blood chemistries assessed during the study included a lipid panel, comprehensive metabolic panel, creatine kinase-myocardial band, thyroid stimulating hormone, free thyroxine, and complete blood count with differential, total iron, and ferritin. Blood chemistries were assessed at one or two week pre-dose, pre-dose/ Day 1 before taking the supplement, Day 29/30, Day 57/58, Day 88/90 and one and two weeks post-dose. | Participants that completed three months of cobalt supplementation. Individual baseline values for the 1-wk predose draw and the day 1 (predose) draw were averaged together to give one baseline value. | Mean | Standard Deviation | U/L | Study volunteers were assessed before, during and after cobalt supplementation (2 wk post) |
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| Secondary | HDL Cholesterol Levels After 3 Months of Cobalt Supplementation | Blood chemistries assessed during the study included a lipid panel, comprehensive metabolic panel, creatine kinase-myocardial band, thyroid stimulating hormone, free thyroxine, and complete blood count with differential, total iron, and ferritin. HDL cholesterol levels were assessed before cobalt dietary supplementation and after three months of supplementation. | Participants that completed three months of cobalt supplementation | Mean | Standard Deviation | mg/dL | Study volunteers were assessed before and at the end of cobalt supplementation |
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| Secondary | Total Cholesterol Levels After 3 Months of Cobalt Supplementation | Blood chemistries assessed during the study included a lipid panel, comprehensive metabolic panel, creatine kinase-myocardial band, thyroid stimulating hormone, free thyroxine, and complete blood count with differential, total iron, and ferritin. Total cholesterol levels were assessed before cobalt dietary supplementation and after three months of supplementation. | Participants that completed three months of cobalt supplementation | Mean | Standard Deviation | mg/dL | Study volunteers were assessed before and at the end of cobalt supplementation |
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| Secondary | Triglyceride Levels After 3 Months of Cobalt Supplementation | Blood chemistries assessed during the study included a lipid panel, comprehensive metabolic panel, creatine kinase-myocardial band, thyroid stimulating hormone, free thyroxine, and complete blood count with differential, total iron, and ferritin. Triglyceride levels were assessed before cobalt dietary supplementation and after three months of supplementation. | Participants that completed three months of cobalt supplementation | Mean | Standard Deviation | mg/dL | Study volunteers were assessed before and at the end of cobalt supplementation |
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| Secondary | Glucose Levels After 1, 2 and 3 Months of Dosing | Blood chemistries assessed during the study included a lipid panel, comprehensive metabolic panel, creatine kinase-myocardial band, thyroid stimulating hormone, free thyroxine, and complete blood count with differential, total iron, and ferritin. Blood chemistries were assessed at one or two week pre-dose, pre-dose/ Day 1 before taking the supplement, Day 29/30, Day 57/58, Day 88/90 and one and two weeks post-dose. | Participants that completed three months of cobalt supplementation. Individual male baseline values for the 1-wk predose draw and the day 1 (predose) draw were averaged together. For females, the average baseline is the 1-wk predose data only because there was a significant difference between the 1-wk predose draw and the day 1 (predose) draw. | Mean | Standard Deviation | mg/dL | Study volunteers were assessed before, during and after cobalt supplementation (2 wk post) |
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| Secondary | Cobalt Urine Concentrations | A 24 hr urine collection for cobalt analysis was performed at Day 14/16, Day 43/44 and Day 88/90. | Participants that completed three months of cobalt supplementation | Mean | Standard Deviation | µg/L | During cobalt supplementation |
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| Secondary | Cobalt Urine Concentrations After Cessation of Cobalt Supplementation | A 24 hr urine collection for cobalt analysis was performed on three volunteers (two females and one male) at one, two, six and ten weeks post-dosing. The one male volunteer provided three consecutive 24-hr urine samples at the one and two week post-dosing time points; data for individual urine collections were averaged together to give an average one and two week post-dosing data concentration. | Participants that completed three months of cobalt supplementation and volunteered to do additional urine collections after stopping cobalt supplementation. "n" represents the number of urine samples analyzd at each time point. | Mean | Standard Deviation | µg/L | After cobalt supplementation |
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| Primary | Cobalt Serum Concentrations | The cobalt concentration in whole blood and serum was determined one to two weeks pre-dosing and on the day of the first day of dosing before taking the supplement. Samples were also analyzed during the dosing period as follows: Day 4/5, Day 8/9, Day 14/16, Day 22/23, Day 29/30, Day 43/44, Day 57/58, Day 71/72, and Day 88/90. Cobalt concentration in whole blood and serum was also determined at one, two, six, ten and 16 weeks post-dosing. | Participants that completed three months of cobalt supplementation | Mean | Standard Deviation | µg Co/L | Before, during and after cobalt supplementation |
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| Secondary | Changes in Cardiac Function (LVEF) | Two-dimensional and Doppler echocardiographic examinations were used to assess cardiac anatomy, structure, and function during the study with volunteers serving as their own baseline controls for changes during the study (i.e., week 0, ~day 45, ~day 90). | Participants that completed three months of cobalt supplementation | Mean | Standard Deviation | LVEF (2D est) (%) | Baseline, at the study midpoint, and at the study completion |
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| Secondary | Changes in Cardiac Function (LA Volume Index) | Two-dimensional and Doppler echocardiographic examinations were used to assess cardiac anatomy, structure, and function during the study with volunteers serving as their own baseline controls for changes during the study (i.e., week 0, ~day 45, ~day 90). | Participants that completed three months of cobalt supplementation | Mean | Standard Deviation | LA volume index (mL/m^2) | Baseline, at the study midpoint, and at the study completion |
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| Secondary | Changes in Visual Function (Average RNFL Thickness) | Ophthalmology studies included an assessment of visual acuity, slit lamp evaluations, and visual field testing. Retinal nerve fiber layer (RNFL) thickness and optic nerve head (ONH) were assessed using optical coherence tomography (OCT). Volunteers served as their own baseline controls for changes during the study (i.e., week 0, ~day 45, ~day 90). | Participants that completed three months of cobalt supplementation | Mean | Standard Deviation | Average RNFL thickness (µm) | Baseline, at the study midpoint, and at the study completion |
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| Secondary | Changes in Visual Function (Average C:D Ratio) | Ophthalmology studies included an assessment of visual acuity, slit lamp evaluations, and visual field testing. Retinal nerve fiber layer (RNFL) thickness and optic nerve head (ONH) were assessed using optical coherence tomography (OCT). Volunteers served as their own baseline controls for changes during the study (i.e., week 0, ~day 45, ~day 90). | Participants that completed three months of cobalt supplementation | Mean | Standard Deviation | ratio | Baseline, at the study midpoint, and at the study completion |
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| Secondary | Changes in Visual Function (Cup Volume) | Ophthalmology studies included an assessment of visual acuity, slit lamp evaluations, and visual field testing. Retinal nerve fiber layer (RNFL) thickness and optic nerve head (ONH) were assessed using optical coherence tomography (OCT). Volunteers served as their own baseline controls for changes during the study (i.e., week 0, ~day 45, ~day 90). | Mean | Standard Deviation | mm^3 | Baseline, at the study midpoint, and at the study completion |
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| Secondary | Changes in Visual Function (VFI) | Ophthalmology studies included an assessment of visual acuity, slit lamp evaluations, and visual field testing. Retinal nerve fiber layer (RNFL) thickness and optic nerve head (ONH) were assessed using optical coherence tomography (OCT). Volunteers served as their own baseline controls for changes during the study (i.e., week 0, ~day 45, ~day 90). | Mean | Standard Deviation | VFI (%) | Baseline, at the study midpoint, and at the study completion |
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| Secondary | Changes in Visual Function (Mean Deviation and PSD) | Ophthalmology studies included an assessment of visual acuity, slit lamp evaluations, and visual field testing. Retinal nerve fiber layer (RNFL) thickness and optic nerve head (ONH) were assessed using optical coherence tomography (OCT). Volunteers served as their own baseline controls for changes during the study (i.e., week 0, ~day 45, ~day 90). | Mean | Standard Deviation | dB | Baseline, at the study midpoint, and at the study completion |
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| Secondary | Changes in Neurological Function (Sural Sensory Amplitude) | Values of the sural sensory and peroneal motor variables. Volunteers served as their own baseline controls for changes during the study (i.e., week 0, ~day 45, ~day 90, and ~4-6 post-weeks). | Participants that completed three months of cobalt supplementation | Mean | Standard Deviation | Sural Sensory Amplitude (µV) | Baseline, at the study midpoint, and at the study completion |
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| Secondary | Changes in Neurological Function (Velocity) | Values of the sural sensory and peroneal motor variables. Volunteers served as their own baseline controls for changes during the study (i.e., week 0, ~day 45, ~day 90, and ~4-6 post-weeks). | Participants that completed three months of cobalt supplementation | Mean | Standard Deviation | m/s | Baseline, at the study midpoint, and at the study completion |
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| 0 |
| 13 |
| 4 |
| 13 |
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| Migraine headaches with prior history of headache | General disorders | Non-systematic Assessment | The volunteer had a history of migraine headaches, and developed worsening headaches one week after starting to take the Co dietary supplement. |
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| Vesicular rash following vaccination | General disorders | Non-systematic Assessment | The volunteer had recently received a tetanus vaccination, as well as other vaccinations for yellow fever and typhoid near the time of the rash development |
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| Rash on face, neck, upper trunk, and back with peeling skin on palms of hands on both sides | General disorders | Non-systematic Assessment | Study leaders were notified approximately 72 hours after the rash first developed, and some of her symptoms had resolved by the time she was assessed by the study director. Her skin changes gradually resolved about a month after she stopped taking Co |
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Not provided
Not provided
Not provided
| Normalized lymphocyte transformation response: Cr |
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| Normalized lymphocyte transformation response: Mo |
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| Normalized lymphocyte transformation response: Ni |
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| Normalized lymphocyte transformation response: V |
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| Normalized lymphocyte transformation response: Zr |
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| Normalized lymphocyte transformation response: Fe |
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| Days 57 and 58 (n = 5, 5) |
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| Days 88 and 90 (n = 5, 5) |
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| 1 wk postdose (n = 5, 5) |
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| 2 wk postdose (n = 5, 5) |
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| 500 Hz |
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| 1000 Hz |
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| 2000 Hz |
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| 3000 Hz |
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| 4000 Hz |
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| 6000 Hz |
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| 8000 Hz |
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| 12,000 Hz |
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| 16,000 Hz |
|
|
| RVID (ed) (cm) |
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| Ao Root (ed) (cm) |
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| IVS (ed) (cm) |
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| IVS (es) (cm) |
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| LVPWs (ed) (cm) |
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| LVPWs (es) (cm) |
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| LA (es) (cm) |
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| Disc Area (mm^2) |
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| Day 14/16 |
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| Day 22/23 |
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| Day 29/30 |
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| Day 43/44 |
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| Day 57/58 |
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| Day 71/72 |
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| Day 88/90 |
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| 1 wk post |
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| 2 wk post |
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| 6 wk post |
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| 10 wk post |
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| 16 wk post |
|
| Days 57 and 58 (n = 5, 5) |
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| Days 88 and 90 (n = 5, 5) |
|
| 1 wk postdose (n = 5, 5) |
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| 2 wk postdose (n = 5, 5) |
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| Days 57 and 58 (n = 5, 5) |
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| Days 88 and 90 (n = 5, 5) |
|
| 1 wk postdose (n = 5, 5) |
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| 2 wk postdose (n = 5, 5) |
|
| Days 57 and 58 (n = 5, 5) |
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| Days 88 and 90 (n = 5, 5) |
|
| 1 wk postdose (n = 5, 5) |
|
| 2 wk postdose (n = 5, 5) |
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| Days 57 and 58 (n = 5, 5) |
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| Days 88 and 90 (n = 5, 5) |
|
| 1 wk postdose (n = 5, 5) |
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| 2 wk postdose (n =5, 5) |
|
| Days 57 and 58 (n = 5, 5) |
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| Days 88 and 90 (n = 5, 5) |
|
| 1 wk postdose (n = 5, 5) |
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| 2 wk postdose (n = 5, 5) |
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| Days 57 and 58 (n = 5, 5) |
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| Days 88 and 90 (n = 5, 5) |
|
| 1 wk postdose (n = 5, 5) |
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| 2 wk postdose (n = 5, 5) |
|
| Days 57 and 58 (n = 5, 5) |
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| Days 88 and 90 (n = 5, 5) |
|
| 1 wk postdose (n = 5, 5) |
|
| 2 wk postdose (n = 5, 5) |
|
| Days 57 and 58 (n = 5, 5) |
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| Days 88 and 90 (n = 5, 5) |
|
| 1 wk postdose (n = 5, 5) |
|
| 2 wk postdose (n = 5, 5) |
|
| Days 57 and 58 (n = 5, 5) |
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| Days 88 and 90 (n = 5, 5) |
|
| 1 wk postdose (n = 5, 5) |
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| 2 wk postdose (n = 5, 5) |
|
| Days 57 and 58 (n = 5, 5) |
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| Days 88 and 90 (n = 5, 5) |
|
| 1 wk postdose (n = 5, 5) |
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| 2 wk postdose (n = 5, 5) |
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| Days 57 and 58 (n = 5, 5) |
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| Days 88 and 90 (n = 5, 5) |
|
| 1 wk postdose (n = 5, 5) |
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| 2 wk postdose (n = 5, 5) |
|
| Days 57 and 58 (n = 5, 5) |
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| Days 88 and 90 (n = 5, 5) |
|
| 1 wk postdose (n = 5, 5) |
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| 2 wk postdose (n = 5, 5) |
|
| Days 57 and 58 (n = 5, 5) |
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| Days 88 and 90 (n = 5, 5) |
|
| 1 wk postdose (n = 5, 5) |
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| 2 wk postdose (n = 5, 5) |
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| Days 57 and 58 (n = 5, 5) |
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| Days 88 and 90 (n = 5, 5) |
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| 1 wk postdose (n = 5, 5) |
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| 2 wk postdose (n = 5, 5) |
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| Day 88/90 |
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| 6 wk postdose (n = 2, 1) |
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| 10 wk postdose (n = 2, 1) |
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| Day 14/16 |
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| Day 22/24 |
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| Day 29/30 |
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| Day 43/44 |
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| Day 57/58 |
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| Day 71/72 |
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| Day 88/90 |
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| 1 wk post |
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| 2 wk post |
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| 6 wk post |
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| 10 wk post |
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| 4 month post |
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| Vertical C:D ratio |
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| PSD (dB) |
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| Peroneal Motor Velocity |
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