Vitamin C-Lipid Metabolites: Uptake and Retention and Effect On Plasma C-Reactive Protein and Oxidized LDL Levels in Healthy Volunteers
Vitamin C-Lipid Metabolites: Uptake and Retention and Effect On Plasma C-Reactive Protein and Oxidized LDL Levels in Healthy Volunteers
Vitamin C-Lipid Metabolites: Uptake and Retention and Effect On Plasma C-Reactive Protein and Oxidized LDL Levels in Healthy Volunteers
COM
PMID: 18971870 Clinical Research
Received: 2008.01.25
Accepted: 2008.03.11 Vitamin C-lipid metabolites: Uptake and retention and CR
Published: 2008.11.01
effect on plasma C-reactive protein and oxidized LDL
levels in healthy volunteers
Authors’ Contribution:
A Study Design Dario Pancorbo1 ABCDEFG, Carlos Vazquez1 ABDEF, Mary Ann Fletcher2 BDEF
B Data Collection
C Statistical Analysis 1
Comprehensive HealthCare of Miami, LLC, Miami, FL, U.S.A.
D Data Interpretation 2
Director of Clinical Immunology Laboratory University of Miami School of Medicine, Miami, FL, U.S.A.
E Manuscript Preparation
F Literature Search Source of support: Departmental sources
G Funds Collection
Summary
Background: Previously, a novel formulation of vitamin C-lipid metabolites (PureWay-C®) was shown to be more
rapidly taken-up by human T-lymphocytes and more rapidly stimulate neurite outgrowth, fibro-
blast adhesion and inhibition of xenobiotic-induced T-cell hyperactivation. Here, PureWay-C® se-
rum levels were measured in healthy volunteers after oral supplementation. Plasma C-reactive pro-
tein and oxidized low density lipoprotein levels (LDL) were also measured.
Material/Methods: Healthy volunteers maintained a low vitamin C diet for 14 days and, following an overnight fast,
received a single oral dose of (vitamin C) 1000 mg of either ascorbic acid (AA), calcium ascorbate
(CaA), vitamin C-lipid metabolites (PureWay-C®), or calcium ascorbate-calcium threonate-dehy-
droascorbate (Ester-C®). Blood samples were collected immediately prior to the oral dose admin-
istration and at various times post ingestion. Twenty-four-hour urine collections were saved for ox-
alate and uric acid assays.
Results: PureWay-C® supplementation leads to the highest absolute serum vitamin C levels when com-
pared to AA, CaA and Ester-C®. PureWay-C® provides a statistically significant greater serum level
than calcium ascorbate at 1, 2, 4, and 6 hours post oral supplementation whereas Ester-C® shows a
less but slightly statistically significant increase at only 1 and 4 hours. Oral supplementation with
PureWay-C® also led to a greater reduction in plasma C-reactive protein and oxidized LDL levels
compared to the other vitamin C formulations.
Conclusions: PureWay-C® is more rapidly absorbed and leads to higher serum vitamin C levels and greater re-
duction of plasma levels of inflammatory and oxidative stress markers than other forms of vitamin
C, including Ester-C®.
key words: vitamin C • lipid metabolites • absorption • serum levels • inflammation • oxidative stress
Author’s address: Dario Pancorbo, Comprehensive HealthCare of Miami, LLC, 7650 W. Flagler St., Miami, FL 33174, U.S.A.,
e-mail: Innteam@aol.com
Current Contents/Clinical Medicine • IF(2007)=1.607 • Index Medicus/MEDLINE • EMBASE/Excerpta Medica • Chemical Abstracts CR547
Clinical Research Med Sci Monit, 2008; 14(11): CR547-551
CR548
Med Sci Monit, 2008; 14(11): CR547-551 Pancorbo1 D et al – Vitamin C-lipid metabolites: Uptake and retention and effect…
Results
AA The rate of vitamin C absorption in serum after oral admin-
2.0 CaA istration was compared between several different vitamin C
Serum VItamin C (mg/dl)
PWC
EC formulations. We found significantly different rates of up-
take depending on the formulation of vitamin C. Prior to
vitamin C supplementation the groups of ten healthy vol-
CR
unteers did not show a significant difference in serum vita-
1.0 min C levels between or within groups. One hour after vi-
tamin C administration, PureWay-C® showed the greatest
serum absorption levels with a mean mg/dl concentration
of 1.3 while Ester C showed a mean of 1.22 mg/dl and cal-
0.0 cium ascorbate showed a mean of only 0.88 mg/dl (Figure
0 6 12 18 24 1). For both PureWay-C and Ester-C, this difference was
Hours statistically significant with p values of 0.0026 and 0.497 re-
spectively. Two hours post administration, PureWay-C® again
Figure 1. Serum vitamin C levels at various times post-supplementation. showed the highest absorption into serum at 2.17 mg/dl,
Volunteers were placed in groups of ten and supplemented which was statistically significantly higher than ascorbic acid
with ascorbic acid (AA), calcium ascorbate (CaA), PureWay-C (AA) at 1.64 mg/dl (p=0.05) and calcium ascorbate (CaA) at
(PWC) or Ester-C (EC) and serum vitamin C concentrations were 1.12 mg/dl (p=0.009). PureWay-C® also showed statistically
determined immediately prior (0 hours) and at hours 1, 2, 4, significantly higher levels than CaA at four hours (p=0.028)
6 and 24 post-supplementation as described in the materials and six hours (p=0.047). Indeed, PureWay-C® demonstrated
and methods section. The data represent the mean + the the highest serum vitamin C absorption levels at all times
S.E.M. Statistically different results were obtained between tested throughout the 24 hour period, including the 24 time
PWC and CaA at hours, 1, 2, 4, and 6 with p values of 0.0026, point (Figure 1, Table1). In contrast, Ester-C failed to show
0.0009, 0.0278 and 0.0470 respectively. EC also showed a statistically significant increase in absorption when com-
statistically significant differences from CaA at hours 1 and 4 pared to all vitamin C formulation, with the exception of
with p values 0.049 and 0.0477 respectively. Confidence of CaA at one hour (p=0.049) and four hours (p=0.047). All vi-
statistical significance was determined using the paired T-test. tamin C formulations showed peak absorption levels at two
hours post administration with only slightly elevated levels
twenty-four hours post administration. However, it is worth
were collected at baseline, 0 hr (before-treatment), 1 hr, 2 noting that PureWay-C® maintains the highest serum level
hr, 4 hr, 6 hr and 24 hr (after-treatment): medical history, of 0.85 mg/dl vitamin C at 24 hours post treatment, which
brief physical, weight, body mass index (BMI) and blood is nearly statistically significant compared to the 0.59 mg/ml
pressure, patient symptom checklist, fasting C-reactive pro- observed with CaA at 24 hours (p=0.057). To a statistically
tein, CBC, basic metabolic panel, TSH and b-HCG (baseline significant extent, these data demonstrate that PureWay-C™
only); and for safety reasons, also creatinine, AST/ALT, CK is better absorbed by the human body than Ascorbic Acid
and blood glucose, oxidized low-density lipoproteins, serum and Calcium Ascorbate, and that this increased absorption
levels of ascorbic acid, plasma levels of C-reactive protein is greater than that observed with Ester-C.
and oxidized low density lipoprotein, urine uric acid (at 24
hr only), and urine oxalate (at 24 hr only). In addition to the greatest absorption rates, PureWay-C®
supplementation lead to the greatest drop in volunteer
Measurement of serum, plasma and urine markers plasma C-reactive protein levels. While the drop in plasma
C-reactive protein of 22.7 ng/ml was greater than that for
Serum vitamin C levels were determined as previously de- AA (12 ng/ml), CaA (8.3 ng/ml) and Ester-C (20.6 ng/ml),
scribed [21]. Briefly, blood was drawn in a chilled tube and the differences between these formulations was not statis-
immediately centrifuged to collect serum. The serum sam- tically significant (Figure 2, Table1). Plasma oxidized low
ples were frozen and protected from light. Vitamin C levels density lipoprotein levels (oxLDL) were also most greatly
were then determined by high pressure liquid chromatogra- reduced by PureWay-C® compared to AA, CaA and Ester-
phy (HPLC) with electrochemical detection (EC). C (Figure 3). PureWay-C® supplementation resulted in a
3.8U/ml drop in oxLDL which is a statistically significant-
Plasma C-reactive protein levels were measured according ly greater drop than that observed with AA (p=0.045) and
to the manufacturer’s guidelines by instant ELISA from again a greater and more beneficial effect that what was ob-
Bender MedSystems, Vienna, Austria. served with CaA and Ester C.
Plasma levels of oxidized LDL was measured according to Taken together, these data show that PureWay-C® is ab-
manufacturer’s guidelines, using a solid phase two site oxi- sorbed into the human body after oral supplementation to
dized LDL ELISA kit from Mercodia, Uppsala, Sweden, which a greater extent than is Ester-C and that, once absorbed, it
is designed for use in measuring plasma oxidized LDL in ar- persists longer in the body, providing better health bene-
bitrary units (presented as U/ml in the results section. fits with regard to circulating inflammatory markers. Urine
uric acid and oxalate levels were not significantly elevated
Urine uric acid was measured by uricase as previously de- during this study, demonstrating that the increase activity
scribed [22] and urine oxalate levels were measured enzymat- of PureWay-C® is not associated with any of the adverse ef-
ically using the Cobas Fara as previously described [23]. fects associated with mega doses of vitamin C.
CR549
Clinical Research Med Sci Monit, 2008; 14(11): CR547-551
AA 80 AA
Plasma C-reactive protein (ng/ml)
CaA CaA
PWC PWC
1.7
200 EC EC
2.9
3.8
8.3
20.6
3.3
40
22.7
12
100
0 0
0 24 0 24
Hours Hours
Figure 2. Plasma C-reactive protein levels before and after Figure 3. Plasma oxidized low density lipoprotein (oxLDL) levels
vitamin C supplementation. Volunteers were placed before and after vitamin C supplementation. Volunteers
in groups of ten and supplemented with ascorbic acid were placed in groups of ten and supplemented with
(AA), calcium ascorbate (CaA), PureWay-C (PWC) or ascorbic acid (AA), calcium ascorbate (CaA), PureWay-
Ester-C (EC) and plasma C-reactive protein levels were C (PWC) or Ester-C (EC) and plasma oxLDL levels were
determined immediately prior (0 hours) and 24 hour post- determined immediately prior (0 hours) and 24 hour
supplementation as described in the materials and methods post-supplementation as described in the materials and
section. The numbers in the bars at 24 hours are the change methods section. The numbers in the bars at 24 hours are
(decrease) in plasma C-reactive protein levels after vitamin the change (decrease) in plasma oxLDL levels after vitamin
C supplementation. These are the same data shown in Table C supplementation. These are the same data shown in Table
1, although the numbers shown for the change in C-reactive 1, although the numbers shown for the change oxLDL were
protein were rounded-off here to fit in the bar space. rounded-off here to fit in the bar space.
Table 1. Summary of the clinical data showing serum vitamin C levels, plasma C-reactive protein and oxidized LDL levels and urine uric acid and
oxalate levels.
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Med Sci Monit, 2008; 14(11): CR547-551 Pancorbo1 D et al – Vitamin C-lipid metabolites: Uptake and retention and effect…
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