Su-Lin Lim, Evan J.C. Lee, Cho-Cho Myint, Kae-Tee Ong, Meng-Eng Tay, Nor Yusuf,
Choon-Nam Ong1
From: Division of Nephrology, Department of Medicine, National University Hospital,
and 1Department of Community, Occupational and Family Medicine, National University
of Singapore, Singapore.
Ascorbic acid is involved in the formation and repair of collagen, in the development
of bones and teeth, in amino acid metabolism, in the synthesis of hormones,
and in wound healing (1). It facilitates iron absorption and utilization. Ascorbic
acid is also an important plasma antioxidant. Patients undergoing continuous
ambulatory peritoneal dialysis (CAPD) are at great risk to become deficient
in ascorbic acid because of inadequate dietary intake (due to nausea and loss
of appetite), altered metabolism in uremia, and loss into dialysate (2). Oxidative
stress may possibly increase the requirement for ascorbic acid to maintain normal
serum levels.
Serum levels of ascorbic acid have been reported to be low in some studies of
dialysis patients (3,4). Supplementation with ascorbic acid has been recommended,
but an optimum dose has yet to be determined, as excessive intake of ascorbic
acid may cause hyperoxalemia in dialysis patients (2). We therefore conducted
a cross-sectional study on clinically stable CAPD patients to determine the
relationship between serum ascorbic acid and daily oral ascorbic acid intake.
For the study, we selected 50 patients aged 18 years and above who had been on peritoneal dialysis for at least 3 months (mean: 22 ± 26 months, Table I). Exclusion criteria were current peritonitis or peritonitis within the preceding 4 weeks, a history of renal calculous disease, or a history of smoking.
Measurement of serum ascorbic acid
Venous blood samples from patients were analyzed for serum ascorbic acid (SAA)
by high-performance liquid chromatography (HPLC) with ultraviolet detection
at 245 nm according to the procedure of Liau et al, 1993 (5).
Oral ascorbic acid intake
Patients were given a 3-day food diary chart with appropriate instructions.
On the fourth day, patients were interviewed about their food diaries. Food
items and amounts were verified using food models. Dietary ascorbic acid intake
was calculated using the NutriGenie Total Nutrition software, version 4.8
(Stanford University, Stanford, CA, U.S.A.). Data for local foods not listed
in the software were entered based on nutrient analyses from Singapore Food
Facts 1999 and Nutrient Composition of Malaysian Food, 4th edition (6). All
supplements containing ascorbic acid were taken into account. Total ascorbic
acid intake was then determined for each patient by totaling the dietary intake
and oral supplementation.
Statistical methods
Data was analyzed using SPSS 10.0 for Windows (SPSS Inc., Chicago, IL,
U.S.A.). The bivariate correlation coefficient was calculated between SAA and
oral ascorbic acid intake. A p value less than 0.05 was considered significant.
Ascorbic acid obtained from diet in our CAPD patients ranged from 7 mg
to 215 mg daily (mean: 67 ± 51 mg daily, Table II).
Of the studied patients, 36% did not consume even 1 serving of fruit daily;
42% consumed just 1 serving of fruit; only 22% ate 2 servings of fruit
daily (Figure 1). All but 5 patients were taking ascorbic acid supplements
of 50 – 360 mg daily (Figure 2). The total oral ascorbic
acid intake (diet + supplements) ranged from 28 mg to 412 mg
daily (Table II). Only one patient had a total oral intake below 60 mg
daily.
The patients’ SAA levels ranged from 1.00 mg/L to 36.17 mg/L.
Although a strong correlation was seen between intake and SAA (p < 0.001,
R2 = 0.47), the variation in SAA at any given intake level was wide (Figure 3).
Of the studied patients, 62% had an SAA < 8.7 mg/L, 40% had an
SAA < 5.1 mg/L (below the level of healthy Singapore adults), and
12% had levels below 2 mg/L (scorbutic). However, none of the patients
demonstrated clinical signs or symptoms of scurvy.
 |
figure 1 Daily fruit consumption among continuous ambulatory peritoneal dialysis patients. |
 |
figure 2 Ascorbic acid supplements in continuous ambulatory peritoneal dialysis patients. |
 |
figure 3 Scatter plot and correlation of serum levels with daily oral intake of ascorbic acid. |
Ascorbic acid has been shown to be essential for health. It is an important
antioxidant in humans (7). It is not synthesized, but must be obtained from
dietary intake (8). It is water-soluble [removed through dialysate (9)], and
serum levels have been shown to be low in several populations of CAPD patients
(3,10).
The U.S. recommended dietary allowance (RDA) for ascorbic acid is 60 mg
daily for healthy, nonsmoking adults (11). This amount prevents the development
of scurvy for about 1 month on a diet lacking in ascorbic acid (12). Smokers
need at least 100 mg daily (1). Our study excluded patients who were smokers.
The requirement for ascorbic acid is increased in many situations (such as wound
healing) and its efficacy is reduced by many drugs (for example, tobacco and
aspirin) (13).
Ascorbic acid obtained from diet in our CAPD patients ranged from 7 mg
to 215 mg daily (mean: 67 mg). Of our patients, 56% had a dietary
ascorbic acid intake below the U.S. RDA. Most of our patients have a relatively
low intake of fresh fruit, which is the main dietary source of ascorbic acid.
Thirty-six percent did not consume even 1 serving of fruit daily (Figure 1).
However the total oral intake of ascorbic acid inclusive of supplements exceeded
60 mg daily for almost all of our patients.
The optimum daily intake needed to prevent ascorbic acid deficiency in CAPD
patients is still controversial, as large doses of ascorbic acid may lead to
hyperoxalemia (14). Healthy, nonsmoking adults in Singapore have SAA levels
ranging from 5.1 mg/L to 8.7 mg/L (12). The range for normal, healthy
adults in the U.S. is 4 – 15 mg/L (15). Our results show that
a large portion of our CAPD population have low SAA levels (< 5.1 mg/L)
as compared with a culturally comparable population without renal failure (16).
Possible reasons are
• reduced intake owing to renal failure (loss of appetite, nausea, and
easy satiety) and inadequate or inappropriate diet preparation. In addition,
some patients may continue to follow pre-dialysis advice to restrict potassium
(which indirectly limits foods that tend to be high in ascorbic acid) and to
boil vegetables (which destroys ascorbic acid).
• increased loss into dialysate. Dialysate removal of ascorbic acid rises
with intake (3,17) and can reach as high as 10.5 mg/L of dialysate (3).
Estimates place the loss of ascorbic acid into the dialysate at 62% of plasma
concentration (3).
Of our patients, 12% had SAA levels below scorbutic level (< 2 mg/L).
The finding that none of the patients had signs of scurvy despite a low serum
ascorbic acid level suggests that scorbutic signs may manifest only late in
a deficiency state—perhaps because the body normally stores about 1500 mg
of vitamin C, and clinical signs of deficiency occur only when the body
pool falls below 300 mg, which may take several weeks (1). Our data confirm
that deficiency of ascorbic acid can be detected earlier with SAA measurements.
Studies in normal populations in the United States have shown that serum ascorbic
acid level and oral intake correlate well until dietary intake reaches 100 –
150 mg daily. At that point, the serum level reaches a plateau of 14 mmol/L
(18). In our study, serum levels did not reach a plateau with dietary intake
of 100 – 150 mg daily. On the contrary, we found that patients
ingesting a higher amount of ascorbic acid continued to show a higher SAA. The
data also showed a strong correlation between oral intake and SAA (p <
0.001, R2 = 0.47). However the variation in SAA at any given intake level
was very wide. This observation may be due to lack of precision in our methods
of estimating overall intake, or it may suggest that oral intake is not the
only factor influencing SAA.
All of our patients except one had a total oral ascorbic acid intake estimated to be above the U.S. RDA of 60 mg daily. Despite these intakes, 40% of our CAPD patients had an SAA level below 5.1 mg/L. This finding suggests that the daily oral ascorbic acid requirement in CAPD patients to maintain an SAA levels comparable to normal healthy adults should be more than 60 mg daily. From our data, we conclude that this oral ascorbic acid intake level should be 90 – 140 mg daily (Figure 3).
Evan J.C. Lee, md, Division of Nephrology, Department of Medicine, National
University Hospital, 5 Lower Kent Ridge Road, Singapore 119074.